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JOURNAL OF INTERNAL MEDICINE OF INDIA � APR - JUNE 2018 � VOL. 12 � NO. 2 � RNI No. 69152/98

© JIMI � APR - JUNE 2018 � VOL. 12 1

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2

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© JIMI � APR - JUNE 2018 � VOL. 12

Editorial

Dear all, It is a great pleasure to inform you that the Journal of Internal Medicine of India-UP Chapter has now been indexed with Copernicus. Our endeavour should be to maintain the standards of the Journal at International level to provide you with upgraded knowledge and help in meeting a uniform standard for all our members. We have already achieved many great initiatives covering various areas of internal medicine, prevention, epidemiology, statistics, health economics and plan to develop and implement authoritative guidelines and standards of care as a part of professional education for the benefit of our members.

3

Gestational diabetes which affects approximately 10% of a l l pregnant women i s assoc ia ted wi th h igh cardiovascular risk. Women with diabetes are 2.5 times more likely to develop CVD, 2.2 times more likely to die from CVD than non diabetic women. Obese women with diabetes also have a greater lifetime risk of CVD than non obese women. Prevalence of diabetes is higher in women than men more than 60 years of age. Sex specific guidelines for stroke prevention in women were recently released outlining the importance of gestational diabetes and pre-eclampsia as sex specific risk factor. The LOOK-AHEAD trial which included 60% women failed to demonstrate reduction in CVD event among men or women randomised to intensive lifestyle intervention for sustain weight loss.

Non communicable disease form a major cause of mortality and morbidity in India. Diabetes Mellitus as number one health epidemic world is facing deserves a lot of attention from healthcare professionals, researchers, Industry leaders, policy makers and people suffering from the disease. This year world diabetes day campaign was dedicated to women and diabetes and our right to a healthy future. The right of women to have access to diabetes prevention and care equates to healthier generation and brighter future. It is imperative that women take a lead role in the fight against diabetes. Women with diabetes experience a number of challenges in today's world. Power dynamics, gender roles, and socioeconomic inequalities that inuence vulnerability including factors like poor diet, nutrition and physical inactivities. Highlighting women and diabetes this year meant a great deal since women take on the bulk of the

1weight dealing with diabetes for the entire family.

Type 2 Diabetes and Cardiovascular Risk in WomenDiabetes Mellitus increases the risk of cardiovascular disease by three to four times in women and two to three times in men after adjusting for other risk factors. Due to population growth and ageing there is steep rise in incidence of diabetes and its associated complications. There is also mounting evidence of clinically important sex and gender differences. Men usually have more visceral fat and higher degree of insulin resistance compare to women of similar age and BMI. Waist hip ratio is a better predictor of diabetes and cardiovascular disease. Women with early menarche, irregular cycles and

2-3PCOS were shown to be at a higher risk. Lower mood scores and a higher prevalence of depression are reported

Prediabetes and womenThe prevalence of diabetes differs between sexes which gives rise to clinical implications. Men more often develop impaired fasting glucose whereas women more often show IGT. IGT may better predict progression to diabetes and mortality risk and relates more strongly to an increase

4CVD risk.

“Women pay more attention to the health of the men and children in the family, having with them less time to devote to their own wellbeing”. Time has now come to give credit to all the efforts women do for prevention of diabetes and its complications.

ReferencesIDF Diabetes Atlas Eighth Edition 2017Alexandra Kautzky-Willer, Giovannella Baggio, Type 2 Diabetes and Cardiovascular Risk in Women: International Journal of Endocrinology Volume 2017,ID 6905697.Dawn R. Witt, MPH, Jackie L. Boucher: The Problem of Diabetes and Cardiovascular Disease: Diabetes Spectrum Volume 26, Number 3, 2013.A. Kautzky-Willer, J. Harreiter, and G. Pacini, “Sex and gender differences in risk, pathophysiology and complications of type 2 diabetes mellitus,” Endocrine Reviews, vol. 37, no. 3, pp. 278–316, 2016.

1.2.

3.

4.

by women than by men with diabetes. Thus, depression has been implicated as an independent risk factor for CHD in women with diabetes.


© JIMI � APR - JUNE 2018 � VOL. 12

Contents

ORIGINAL ARTICLE

REVIEW ARTICLE


© JIMI � APR - JUNE 2018 � VOL. 12 4

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2.

3.

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Conventional Lipids And Lipoprotein (A) In Pregnant Mothers andCord Blood: South Asian Experience

Shridhar Dwivedi, Amitesh Aggarwal, Sameer Khanna, Mukul P Agarwal,Amita Suneja, Suman B. Sharma,

Clinico-physiological Profile of Patients of Cured PulmonaryTuberculosis Attending A Tertiary Health CentreAntriksh Srivastava, Devendra Kumar Singh, Vinisha Chandra, Saurabh Srivastava

Study to Evaluate The Efficacy of Cranberry Supplementation In TheManagement of Complicated and Recurrent Urinary Tract Infection In Either Sex

Waleem Ahmad, Anjum Mirza Chughtai

Study of Serum Ferritin in Type 2 Diabetes Mellitus andIts Relation With Microvascular Complications

Ajeet Kumar Chaurasia, Manoj Kumar Mathur, Poonam Gupta, Vatsal Singh

To study the prevalence of subclinical hypothyroidism inpatients with type 2 diabetes mellitus (T2DM)

5.

Raj K Singh, Amit Singh, Aradhana Singh, Mahim Mittal, Ajay Kumar

Fibromyalgia: A Chronic Condition that Remains Underdiagnosed.Saxena V, MS, Verma Vijay Deepak, MD, Babu Suresh, MD

6.

An Epidemiological Study of Hepatitis C Infection In Patients AttendingTertiary Care Hospital In North India

7.

DavidLalrutsanga , Verma.V, Singh.M, Himanshu Dandu, Ajay Kumar,Rohin Saini(Corresponding Author)

5

11

15

20

26

32

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Tuberous Xanthoma, Xanthelesma with GlutealXanthoma: Uncommon manifestation of common diseaseAmitesh Aggarwal, MD

Pharmacogenetics of Type 2 Diabetes: A Systematic ReviewDr. Anshu Nanda, Savera Gulati, A.K. Shukla, Meenakshi Jain

Pharmacoeconomic Analysis of EffectivenessVersus Efficacy- A Clinicians Must Know Perspective R.K. Dixit, Divya Singh, Suchi Jain

Recent Advances in AntiAlzheimer's DrugsR.K.Dixit, Shireen Barua1, Garima Adhaulia

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9.

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MANUSCRIPT

The Editorial Process12. 62

Conventional Lipids And Lipoprotein (A) In PregnantMothers and Cord Blood: South Asian Experience

Original Article

1 2 3Shridhar Dwivedi , Amitesh Aggarwal , Sameer Khanna ,

4 5 6Mukul P Agarwal , Amita Suneja , Suman B. Sharma ,

AbstractBackground: Maternal lipids have been studied extensively in normal and pre-eclamptic pregnancies, demonstrating a major increase in all the lipid fractions, but little is known about the lipids and Lp(a) levels in cord blood in South Asian subjects. It is said that the seeds of atherosclerosis are sown in-utero. We, therefore, hypothesized that maternal lipid perturbations during pregnancy may have an effect on the cord blood lipid profile.

Major alterations in the maternal lipid profile and Lp(a) levels, on an average two fold increase in total cholesterol (TC) levels, a three fold increase in the triglycerides (TG) levels with an average 41% increase in high density lipoprotein cholesterol (HDL-C) levels, have been

[ 1 , 2 ]reported during uncomplicated pregnancies .Preeclmaptic women also demonstrate a marked dyslipidemia. However, studies comparing lipid values during normal pregnancy and in pre-eclampsia have found variable results. Some reports demonstrate

Introduction

1 2Department of Medicine , Obstetrics & Gynaecology 3and Biochemistry

University College of Medical Sciences, University of Delhi, GTB Hospital,Delhi, India

Objectives: (i) to compare the conventional lipids and Lp(a) of normotensive and preeclamptic mothers with non pregnant apparently healthy women and (ii) to measure the umbilical cord lipids and Lp(a) and to correlate them with maternal lipids and Lp(a).

Methods: We studied 30 normotensive and 30 preeclamptic mothers in their third trimester and 30 non-pregnant age matched healthy women acting as controls for the study. Lipid profile [total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides] and Lp(a) estimation was done for all the subjects and the cord blood collected at the time of delivery.

Results: The mean age for normotensive pregnant (24.0±3.3 years), preeclamptic mothers (25.7±3.8 years) and controls (25.4±4.0 years) were statistically similar. Maternal total cholesterol (254.5±97.6, 231.5±69.6 vs 131.4±25.0 mg/dl), LDL-C (149.3±73.3, 141.0±56.6 vs 77.9±24.1 mg/dl), HDL-C (46.3±8.5, 42.4±9.0 vs 31.2±5.9 mg/dl), TG (299.7±123.7, 241.9±106.2 vs 105.6±51.4 mg/dl) were significantly elevated in normotensive and preeclamptic mothers as compared to non-pregnant controls respectively. Lp(a) levels of mother correlated significantly with Lp(a) levels of the cord blood (r=0.453, p=0.012). However, maternal total cholesterol, LDL-C, HDL-C and TG showed no significant association with corresponding values in cord blood. The lipids and Lp(a) levels were not significantly different in the normotensive and pre-eclamptic mothers.

Conclusions: These findings indicate a state of dyslipidemia during pregnancy and a significant correlation between the maternal and cord blood Lp(a) . These findings need to be studied in a larger sample size as it raises an important question: whether and how to treat dyslipidemic pregnant mothers? Further, offsprings of hypertensive or dyslipidemic pregnant mothers need close follow-up for future cardiovascular risk.

Keywords: Pregnancy; Preeclampsia; Cord blood lipids; Lipoprotein(a).

elevated TG levels during the third trimester with a decrease in HDL-C levels while others have found no significant change in the lipid profile of preeclamptic


© JIMI � APR - JUNE 2018 � VOL. 12 5

[3-7]women as compared to normal pregnant females . Similarly, variable levels of Lp(a) during normal and pre-eclamptic pregnancies have been reported in different

[3,8-12]studies . levels.

[13,14,15]There is hardly any data regarding the levels of lipids [16,17] and Lp(a) in cord blood from South Asian countries.

There is only one study regarding the levels of fetal lipids [15]during pre-eclampsia . We hypothesized that maternal

lipid alterations during pregnancy may have an effect on the fetal lipid profile. So we performed this study to see the effect of pregnancy and preeclampsia on maternal lipids and to see the effect of maternal lipids and Lp(a) levels on the fetal lipids and Lp(a)

Materials And MethodsSubjects: The study included 30 normotensive pregnant women and 30 preeclamptic women in their third trimester. 30 non-pregnant age matched females were taken as controls for this study. Patient characteristics were recorded at the time of sampling with respect to age, gestational age, prior history of hypertension or diabetes mellitus, with a detailed obstetric and menstrual history. A comprehensive physical and cardiovascular examination of each subject was done. All the complicated pregnancies [e.g. twins or intrauterine growth retardation (IUGR)], diabetes mellitus diagnosed before pregnancy or gestational diabetes mellitus, patients of coronary artery disease, cerebrovascular disease, kidney or liver disease, any metabolic disease (like hypothyroidism), smokers and alcoholics were excluded from the study. Preeclampsia was defined according to the International Society for the study of hypertension in pregnancy criteria (BP 140/90 after 20 wks of gestation and proteinuria 300 mg/24 hrs or 1+ dipstick proteinuria in absence of renal disease or infection). The design of the study was approved by institutional ethical committee. All subjects gave written informed consent.

Collection of blood samples: Subjects were sampled during third trimester, prior to delivery. All the samples were taken after an overnight fast. 15 ml of blood was collected from antecubital fossa by venepuncture into plain vials. Fetal cord blood was collected into plain vials from the placental end of the cord, after the delivery of the baby but before the delivery of the placenta.

Lipid profile and Lipoprotein(a) estimation: The blood samples were centrifuged immediately and serum was collected into aliquots for lipid profile and Lp(a) estimation. The samples were stored at -70°C. The TC was estimated using cholesterol esterase method, triglycerides

using lipoprotein lipase method using commercially available kits, HDL-C was estimated using the method of

[18,19,20]Burstein et al and LDL-C were determined using [21]Freidwald's and Fredrickson's formula . Lipoprotein(a)

[Lp(a)] was estimated using latex immunoturbidimetric method using kits from 'DAIICHI' Japan and Hitachi 717

[22]automated analyzer. .

Statistical Analysis: Data was analyzed using SPSS software version 13.0 from SPSS Incorporation. Data are presented as mean±SD. Biochemical parameters between the three groups - normotensive and preeclamptic females and the controls were analysed using one way analysis of variance (ANOVA) followed by Tukey's test at 5%. The cord blood biochemical parameters in the normotensive group and preeclamptic group were compared using unpaired t-test and significance was taken at 5%. The correlation between maternal and fetal lipids and Lp(a) was done using Pearson's correlation coefficient and significance was taken at 5%.

Baseline characteristics of the study groups: The study comprised of 90 subjects, recruited from the Department of Obstetrics & Gynaecology, UCMS & GTB Hospital, Delhi, India. The three groups were not different from each other in respect of mean age and gravidity, gestational age or mean weight of the babies. The only significant difference was in the mean SBP, mean DBP and mean arterial pressure of the females (Table 1).

Results

Table 1: Demographic prole of study subjects

Variables Normotensive pregnant

group

(n=30)

Preeclamptic Group

(n=30)

Controls (n=30)

P-value

Mean age (yrs) 24.03±3.30

25.73±3.87

25.47±4.9

NS

Gravida

G1 15 10

-

NS

G2 8 8

-

G3 6 5

-

G>3 1 7

-

Gestational Age (wks) 38.29±1.45

38.05±1.64

-

NS

Blood pressure (mmHg)

SBP 115.07±8.81

159.73±17.25**

114.87±8.54

<0.001*

DBP 75.4±5.28

102.73±7.15**

74.60±7.13

<0.001*

Mean Arterial Pressure 88.62±6.45 121.73±10.51** 88.02±7.6 <0.001*Sex of the baby (nos.)

Male 15 18 - NSFemale 15 12 -

Weightof baby (kg)Both combined 2.66±0.38 2.55±0.50 - NSMale 2.67±0.31 2.59±0.48 -Female 2.65±0.46 2.47±0.53 -*P<0.05 – significant**Hypertensive group is significantly different from controls and normotensive group


© JIMI � APR - JUNE 2018 � VOL. 12 6

Lipid profile and Lp(a) levels of pregnant mothers and controls: The mean levels of TC, LDL-C, HDL-C and TG were significantly higher in the normotensive and preeclmaptic group as compared to non pregnant controls. Similarly TC/HDL-C and TG/HDL-C ratios were significantly higher in the normotensive and preeclamptic group. But there was no statistically significant difference in the Lp(a) levels of the three groups (Table 2).

Table 2: Comparison of serum lipid prole and Lp(a) levels of normotensive pregnant, preeclamptic mothers and controls

Variables Normotensive pregnant group

(n=30)

Preeclamptic group

(n=30)

Controls(n=30)

TC (mg/dl) 254.53±92.68

231.53±69.6

131.40±25.04LDL-C (mg/dl) 149.33±73.37

141.07±56.64

77.97±24.19HDL-C (mg/dl) 46.33±8.58

42.40±9.06

31.27±5.95TG (mg/dl) 299.77±123.72

241.97±106.23

105.67±51.44Lp(a) (mg/dl) 14.54±11.46

11.27±13.22

8.33±7.31TC/HDL-C ratio 5.45±1.55

5.48±1.27

4.26±0.77TG/HDL-C ratio 6.53±2.53

5.83±2.59

3.50±1.82

LDL-C/HDL-C ratio 3.16±1.31 3.32±1.18 2.52±0.74Normotensive vs controls : P value < 0.05 for all parameters except Lp(a) and LDL-C/HDL-c ratio.Preeclamptic gp. vs controls : P value < 0.05 for all except Lp(a).Normotensive vs preeclamotic gp : P value=not significant

Lipid profile and Lp(a) levels in the cord blood of normotensive and preeclamptic group: Mean TC and LDL-C were slightly higher in the babies of preeclamptic group with a lower HDL-C levels in the preeclmaptic group but the results were statistically insignificant. Similarly there was no statistically significant difference in the Lp(a) levels of both groups. But the TC/HDL-C and LDL-C/HDL-C ratios were significantly elevated in the babies of preeclamptic group (Table 3).

Table 3: Comparison between cord blood biochemical parameters between babies of the normotensive mothers and babies of Preeclamptic group

Variables Cord blood of the normotensive mothers

(n=30)

Cord blood of the

Preeclamptic group

(n=30)

p-value

TC (mg/dl) 83.67±21.62 85.13±22.25 NSLDL-C (mg/dl) 46.47±15.81 48.73±18.96 NSHDL-C (mg/dl) 27.13±6.46 23.53±7.570 NSTG (mg/dl) 66.77±28.62 65.03±28.09 NSLp(a) (mg/dl) 1.73±2.954 1.57±3.16 NSTC/HDL-C ratio 3.13±0.68 3.83±1.14 0.006TG/HDL-C ratio 2.57±1.19 3.17±2.08 NSLDL-C/HDL-C ratio 1.72±0.49 2.20±0.96 0.018

Correlation between maternal and fetal lipids and Lp(a) in normotensive group: There was no significant correlation between maternal and fetal TC, LDL-C, HDL-C and TG levels but the maternal Lp(a) levels correlated significantly with the fetal Lp(a) levels (r=0.453, p=0.012) (Fig. 1a and Fig. 1b).

-0.3

-0.2

-0.1

0

0.1

0.2

0.3

0.4

0.5

TC

with T

C

LD

L-C

with

LD

L-C

HD

L-C

with H

DL-

C

TG

with T

G

Lp(a

) w

ith

Lp(a

)

Co

rrela

tio

n c

oef

cie

nt

Fig.1a: Correlation between the lipid profile and Lp(a) levels of normotensive pregnant mothers and cord blood of the newborns of normotensive pregnant mothers

Fig. 1b: Correlation of mothers Lp(a) with cord blood Lp(a) in normotensive group

0

1

2

3

4

5

6

0 10 20 30 40 50

Mothers Lp(a)

Co

rd b

loo

d L

p(a

)

Lp(a) cord=0.117*Lp(a)

mother+0.035

Correlation between maternal and fetal lipids and Lp(a) levels in pre-eclamptic group: There was found to be no significant association between maternal and fetal lipids or Lp(a) in the preeclamptic group (Fig. 2).

Fig. 2: Correlation between the lipid profile and Lp(a) levels of PIH mothers and cord blood of the newborns of PIH mothers

-0.1

-0.05

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

TC

with

TC

LD

L-C

with

LD

L-C

HD

L-C

with

HD

L-C

TG

with

TG

Lp

(a)

with

Lp

(a)

Co

rrela

tio

n c

oef

cie

nt


© JIMI � APR - JUNE 2018 � VOL. 12 7

Difference between the cord blood lipids and Lp(a) levels of male and female babies: The triglyceride levels were found to be significantly higher in the male babies of normotensive group as compared to female babies, with no significant difference in the TC, LDL-C, HDL-C and Lp(a) levels. Similar findings were observed in the babies of preeclamptic group.

Difference between cord blood lipids and Lp(a) levels of low birth weight (LBW, <2.5 kg) and appropriate birth weight (2.5 kg) babies: There was a trend towards lower TC, LDL-C and higher HDL-C levels in appropriate birth weight babies as compared to low birth weight babies but the results were statistically insignificant. The TC/HDL-C ratio was found to be significantly lower in the appropriate birth weight babies when compared to low birth weight babies (p=0.037).

DiscussionThis is the first study to report the levels of fetal lipids and the effect of maternal lipids on the fetal lipids in South Asian babies. We demonstrated a major increase in all the lipid fractions and Lp(a) levels in the normal pregnant and pre-eclamptic females as compared to non-pregnant healthy controls. We also found a positive association between maternal and fetal Lp(a) in the normotensive group, with insignificant correlation between other lipid fractions. Interestingly we also noticed a significant elevation in TG levels of male babies as compared to female babies.

Studies done regarding the lipid profile during normal pregnancy have conclusively demonstrated that in the third trimester, levels of TC, HDL-C, LDL-C and TG rise to

[1,2]a great extent . Our study also had similar results with mean TC levels of 254.53±92.68 mg/dl, mean LDL-C of 149.33±73.37 mg/dl, mean HDL-C of 46.33±8.58 mg/dl and mean TG of 299.77±123.72 mg/dl in the normotensive group. These levels of lipids can be explained by an increase in estrogen levels during normal pregnancy. This increase in lipids occurs also as a result of increase in plasma progesterone levels due to placental production of progesterone, increased cortisol levels during pregnancy and a peripheral insulin resistance state during pregnancy.

A few authors have studied the changes in serum lipid profile during hypertensive pregnancies and have found

[4]variable results. Kokia et al have found that serum TG levels were significantly higher in pregnancy induced

[5]hypertension (PIH) patients than in controls. Franz et al observed elevated TG levels in case of PIH patients, but

[7] [3]DeAlavarez et al and Leung et al did not find

significant changes in the lipid profile in PIH patients. We also could not find any significant difference between the lipid profile of the normotensive and the hypertensive group.

Various studies have examined the levels of Lp(a) in [8]normal pregnancy and PIH. Zechner et al did not find

any significant difference in the Lp(a) levels in the third trimester of pregnancy as compared to the prepregnant

[9]state. In a study by Silliman et al , the mean Lp(a) was 13.7±17 mg/dl with no difference during pregnancy and postpartum state. The findings of our study are in confirmity to above observations. There was no significant difference in the Lp(a) levels during normal pregnancy as

[3]compared to controls. Leung et al studied the Lp(a) levels in the PIH patients and found lower Lp(a) levels in PIH group. These observations are similar to our findings.

The next question to be answered was the correlation between lipid levels of the pregnant mothers in third trimester and the cord blood lipids. Only two studies, one

[13] [15]by Ortega et al and another by Rodie et al , have addressed this issue but the results were variable. Only a weak correlation was found between maternal and fetal TC concentration. Our study has also found a positive correlation between the lipids of pregnant mother's and cord blood but the results were not significant.

[23]Study by Neary et al addressing the correlation of Lp(a) in pregnant mother and cord blood revealed significant positive correlation between the two. This is in consonance to our findings wherein a positive correlation between pregnant mother's Lp(a) levels and the cord blood Lp(a) levels has been clearly demonstrated. This correlation assumes significance because Lp(a) is considered to be a genetic marker of atherosclerosis. This has future cardiovascular risk implications in the offsprings whose mothers have increased Lp(a) levels.

[24]Further, Napoli et al have reported that the correlation between the maternal and fetal lipids was found to be linear only upto 6 months of gestation. After that there was found to be no significant correlation between maternal and fetal lipids. Though we measured lipids at one point of time, i.e. at 36 weeks and above, our findings are similar to those of Napoli et al. Correlation between maternal and fetal lipids were not significant. The exact cause for this weak correlation of lipids in third trimester of pregnancy is not known but it is postulated that this may be due to the growth of the placenta with advancing gestation. However, the issue of Lp(a) levels in pregnant mother and cord blood was not addressed by Napoli et al, while we have studied this point and found a


© JIMI � APR - JUNE 2018 � VOL. 12 8

An important question, which needs to be addressed, is whether we should treat hyperlipidemia during pregnancy? The answer to this question is difficult, as the rise in lipids during normal pregnancy appears to be physiological, as a result of hormonal changes and is necessary for the growth of the fetus. Animal studies by

[25,26]Napoli et al have demonstrated a decrease in size of fatty streaks in aorta when their mothers were fed low cholesterol diet or any interventions were used to decrease the serum lipids. There are no human studies in this regard uptil now. Also the drugs available for treating hyperlipidemia like statins or fibrates are teratogenic and not safe for the fetus per se

[15]Only one study by Rodie et al has compared the fetal lipids between normal and PIH pregnancies and demonstrated higher fetal TC and TG levels in PIH pregnancies. In our study a statistically insignificant elevation of TC and LDL-C has been seen and a trend towards lower HDL-C has been found in the PIH group.

The finding of lower TC, TG and LDL-C levels in higher birth weight newborns in our study corroborates with the

[14]results of previous studies in this respect done by Pardo [13]and Ortega et al . The previous studies by Aguado and

[27] [13]Perez et al , Ortega et al , Rodie et al [15] have failed to demonstrate any difference in lipid levels between male and female newborns except the study by Loughrey et al [28] who found an elevated TG level in male babies as was the finding in the present study.

When we compared the fetal lipids in the present study [13,14,15]with the studies reported in international literature ,

we found higher TC and TG levels in the newborns in our study. But the mean gestational age and birth weight was slightly lower in our study than in studies from international literature. This finding is an important observation. It implies that the future risk of CAD in newborns might be decreased by improving maternal nutrition and targeting an optimal birth weight for newborn babies.

ConclusionThis study was undertaken with the aim to have an insight into the earliest changes in serum lipids and whether maternal lipids have any effect on fetal lipids. The findings of the present study indicate significant correlation between maternal and fetal Lp(a) levels in the normotensive mothers. Besides, there exists a state of dyslipidemia in the third trimester of pregnancy. These findings need to be explored in a larger sample size. Lower lipid levels in higher birth weight babies suggest that the future incidence of CAD in the newborns might be

reduced by improving maternal nutrition. Close cardiovascular monitoring of babies whose mothers are dyslipidemic during pregnancy is desirable.

Potter JM, Nestel PJ. The hyperlipidemia of pregnancy in normal and complicated pregnancies. Am J Obstet Gynecol 1979; 133: 165-70Fahraeus L, Larsson-Cohn U, Wallentin L. Plasma lipoproteins including high density lipoprotein subfractions during normal pregnancy. Obstet Gynecol 1985; 66: 468-72Leung TN, Lam CWK, To KF, Haines CJ. Changes in concentrations of lipoprotein(a) and other lipids and lipoprotein in pregnancies complicated by PIH or IUGR. Hypertension in Pregnancy 1998; 17: 157-168.Kokia E, Barkai G, Reichman B, Segal P, Goldman B, Mashiach S. Maternal serum lipid profile in pregnancies complicated by hypertensive disorders. J Perinat Med 1990; 18: 473-8.Franz H, Wendler D. A controlled study of maternal serum concentrations of lipoproteins in pregnancy-induced hypertension. Arch Gynecol Obstet 1992; 252: 81-6Cong KJ, Wang TT, Liu GR. Lipid metabolism and pregnancy induced hypertension. Zhonghua Fu Chan Ke Za Zhi 1994; 29: 651-3, 697-8.De Alvarez RR, Bratvold GE. Serum lipids in preeclampsia-eclampsia. Am J Obstet Gynecol 1961; 81: 1140-8.Zechner R, Desoye G, Schweditsch MO, Pfeiffer KP, Kostner GM. Fluctuations of plasma lipoprotein(a) concentrations during pregnancy and post partum. Metabolism 1986; 35: 333-6.Silliman K, Shore V, Forte TM. Hypertriglyceridemia during late pregnancy is associated with the formation of small dense low-density lipoproteins and the presence of large buoyant high-density lipoproteins. Metabolism 1994; 43:1035-41.Panteghini M, Pagani F. Serum concentrations of lipoprotein(a) during normal pregnancy and postpartum. Clin Chem 1991; 37: 2009-10.Chiang AN, Yang ML, Hung JH, Chou P, Shyn SK, Ng HT. Alterations of serum lipid levels and their biological relevances during and after pregnancy. Life Sci 1995; 56: 2367-75.Mori M, Mori A, Saburi Y, Sida M, Ohta H. Levels of lipoprotein(a) in normal and compromised pregnancy. J Perinat Med 2003; 31: 23-8.Ortega RM, Gaspar MJ, Cantero M. Inuence of maternal serum lipids and maternal diet during the third trimester of pregnancy on umbilical cord blood lipids in two populations of Spanish newborns. Int J Vitam Nutr Res 1996; 66: 250-7.Pardo IM, Geloneze B, Tambascia MA, Barros-Filho AA. Atherogenic lipid profile of Brazilian near-term newborns. Braz J Med Biol Res 2005; 38: 755-60.Rodie VA, Caslake MJ, Stewart F, Sattar N, Ramsay JE, Greer IA, et al. Fetal cord plasma lipoprotein status in uncomplicated human pregnancies and in pregnancies complicated by pre-eclampsia and intrauterine growth restriction. Atherosclerosis 2004; 176: 181-7Rifai N, Heiss G, Doetsch K. Lipoprotein(a) at birth, in blacks and whites. Atherosclerosis 1992; 92: 123-9. Low PS, Heng CK, Saha N, Tay JSH. Racial variation of cord plasma lipoprotein(a) levels in relation to coronary risk level: A study in three ethnic groups in Singapore. Pediatr Res 1996; 40: 718-722.

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Werener M, Gabrieulsen DC. Estimation of serum triglycerides. Clin Chem 1981; 27: 268.Allain CC, Poon LS, Chan CS, Richmond W, Fu PC. Enzymatic estimation of cholesterol. Clin Chem 1974; 20: 470.Burstein M, Scholnick HR, Morgin R. Rapid method of isolation of lipoprotein from human serum by precipitation with polyanion. J Lipid Res 1970; 11: 1583.Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18; 499-502.Sakurabayashi I, Saito Y, Kita T, Matsuzawa Y, Goto X. Reference intervals for serum apolipoprotein A-I, A-II, B, C-II, C-III and E in healthy Japanese determined with a commercial immunoturbidimetric assay and effects of age, sex, smoking, drinking and Lp(a) levels. Clinica Chimica Acta 2001; 312: 87-95.Neary RH, Kilby MD, Kumpatula P, Game FL, Bhatnagar D, Durrington PN, et al. Fetal and maternal lipoprotein metabolism in human pregnancy. Clin Sci (Lond) 1995; 88: 311-8.

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Napoli C, D'Armianto FP, Fostiglion A, et al. Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. J Clin Invest 1997; 100: 2680-2690.Napoli C, Witztum JL, Calara F, de Nigris F, Palinski W. Maternal hypercholesterolemia enhances atherogenesis in normocholesterolemic rabbits, which is inhibited by antioxidant or lipid-lowering intervention during pregnancy. Circ Res 2000; 87: 946-952.Palinski W, D'Armiento FP, Witztum JL, de Nigris F, Casanada F, Condorelli M, et al. Maternal hypercholesterolemia and treatment during pregnancy inuence the long term progression of atherosclerosis in offspring of rabbits. Circ Res 2001; 89: 991-6.Aguado F, Perez L. Perfil lipidico en recien nacidos sanos. Rev Ebp Pediatr 1989; 45: 303-306.Loughrey CM, Rimm E, Heiss G, Rifai N. Race and gender differences in cord blood lipoproteins. Atherosclerosis 2000; 148: 57-65

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© JIMI � APR - JUNE 2018 � VOL. 12 10

Clinico-physiological Profile of Patients of Cured PulmonaryTuberculosis Attending A Tertiary Health Centre

Original Article

1 2 3 4Antriksh Srivastava , Devendra Kumar Singh , Vinisha Chandra , Saurabh Srivastava

AbstractBackground: Pulmonary tuberculosis (TB) is a unique infectious disease that more often than not results in permanent structural changes in the lung parenchyma. It is by virtue of these changes that the patients even after bacteriological cure continue to suffer the after effects of the disease.

Pulmonary TB survivors frequently experience structural1 and functional lung sequels that vary in severity that have recently been more completely

1described . Pulmonary tuberculosis (TB) can cause parenchymal destruction by up-regulation of several

2proteases and dysregulation of protease control. The histopathological abnormalities after treatment for pulmonary TB include fibrosis, bronchiectasis, and bronchial stenosis, all of which can cause pulmonary

3,4function abnormalities.

Introduction

1. Dr. Antriksh Srivastava, Senior Resident, Department of Respiratory Medicine, School of Medical Sciences & Research, Greater Noida2. Dr. Devendra Kumar Singh (Corresponding Author), Assistant Professor, Department of Respiratory Medicine, School of Medical Sciences & Research, Greater Noida. 3: Dr. Vinisha Chandra, Assistant Professor, Department of Medicine, School of Medical Sciences & Research, Greater Noida4: Dr. Saurabh Srivastava, Professor, Department of Medicine, School of Medical Sciences & Research, Greater Noida

Objective: To assess the clinico-physiological profile of patients of cured pulmonary tuberculosis attending a tertiary health centre.

Materials and Methods: From August 2017 to August 2018, i.e., over the time period of 1 year, 350 patients of cured pulmonary tuberculosis were identified and studied about their clinico-physiological profile. This profile included age, sex, category of treatment, pulmonary function test pattern, exercising capacity, exercise tolerance and quality of life.

Results: It was found that majority of the patients were males, >60 years of age and had taken Category-II treatment. Most of the patients were having an obstructive pattern on PFT, poor exercise tolerance and exercise capacity and a poor quality of life.

Conclusion: Patients of cured pulmonary TB continue to experience respiratory symptoms owing to the permanent anatomical changes in the lung conferred by the disease.

Key words: Cured Pulmonary TB

Pulmonary impairment after tuberculosis was recently 5,6,7described as a non-fatal negative health effect .

Pulmonary impairment after tuberculosis (PIAT) refers to chronic pulmonary function loss that occurs in persons who have achieved microbiologic cure of pulmonary tuberculosis. Levels of impairment were determined in previous studies via spirometry using American Medical Association's Guide to Evaluations on Permanent

8Impairment (fifth edition) .

In India, the burden of tuberculosis is very high due to a multiplicity of causes such as overcrowding, poor hygiene conditions and lack of orientation towards role of early diagnosis and treatment of the disease. Patients approach the physician very late after onset of the disease when the pulmonary impairment has established itself to a great extent. In our study, we enrolled all those patients who were adequately treated for pulmonary tuberculosis and were declared as cured but still continued having symptoms pertaining to respiratory system.


© JIMI � APR - JUNE 2018 � VOL. 12 11

Materials and MethodsFrom August 2017 to August 2018, i.e., over the time period of 1 year, 350 patients of healed pulmonary tuberculosis attending School of Medical Sciences and Research, Sharda Hospital were identified and studied about their clinico-physiological profile. This profile included age, sex, category of treatment, pulmonary function test pattern, exercising capacity, exercise tolerance and quality of life. Participants gave written informed consent, and patient anonymity was preserved using ethical committee approved protocols.

Patients enrolled in the study were either those who came to the hospital having adequately treated previously or those who were diagnosed as active pulmonary TB cases and went on to complete the treatment and declared as cured according to RNTCP guidelines. In either case, confirmation of healed pulmonary TB was done by getting sputum smear and culture bacteriologically negative. All the patients had some degree of respiratory discomfort and symptoms which were not compliant with their routine life. Patients excluded from the study were those with other significant comorbidities such as cor-pulmonale, diabetes mellitus, COPD, bronchial asthma or pulmonary impairment not as a result of TB.

Sr. no. ParameterNo. of

pa�ents Percentage

1 Age

20-39 69 19.71

40-59 138 39.43

>60 143 40.86

2 Sex

Male 211 60.29

Female

139

39.71

3

Category of Treatment

I

106

30.29

II

222

63.43

IV

22

6.29

4

PFT Pa�ern

Normal

113

32.29

Obstruc�ve

127

36.29 Restric�ve

53

15.14 Mixed

57

16.29

5 6-MWT Distance(m)

<250 59 16.86

251 to 349

238

68.00

>350

53

15.14

6

Modified Borg's Score

<4

64

18.29

4 to 7

184

52.57

>7

102

29.14

7 SGRQ Score

<10 52 14.86

10 to 15 201 57.43

>15 97 27.71

Various tools were used for calculation of parameters as described below:

PFT was done using EasyOne Pro/LAB v5.0 pulmonary system in the department of Respiratory Medicine at School of Medical Sciences and Research, Sharda Hospital.Exercising capacity was measured using the 6-minute walk test distance.Exercise tolerance was measured using the modified Borg's scale.Quality of life was measured using the validated Hindi version of the Saint George's Respiratory Questionnaire.

a½

b½

c½

d½

The study was a periodic, longitudinal and observational study aimed at assessing the overall functional status of patients of cured pulmonary TB and to understand the various limitations whether functional, social or behavioural that they face in their daily life.

ResultsTable 1 summarises all the observations of the study.

Table 1


© JIMI � APR - JUNE 2018 � VOL. 12 12

Total 350 patients were included and gave consent to participate in our study over the time period of 1 year. The majority of the patients were >60 years of age (40.86%) closely followed by age group 40-59 years (39.43%) and lastly followed by 20-39 years age group (19.71%). The majority of the patients were male (60.29%) and the remaining were female (39.71%). Category-II treatment was the most common course of anti tubercular treatment taken by the patients (63.43%) followed by Category-I (30.29%) and Category-IV (6.29%) respectively. The most common pattern of PFT observed was obstructive (36.29%) closely followed by normal (32.29%), mixed (16.29%) and restrictive (15.14%) in that order. The 6-minute walk distance of the majority of patients lied between 251-349 metres (68%). The rest were almost equally divided between <250 metres (16.86%) and >350 metres (15.14%). The majority of patients had a fair exercise tolerance as indicated by the Modified Borg's score of 4-7 in most patients (52.57%). However, a significant proportion of patients had a poor exercise tolerance (Modified Borg's score >7 in 29.14%). A few had a good Modified Borg's score of <4 (18.29%). The quality of life index was predominated by a poor quality of life as indicated by SGRQ score 10-15 (57.43%), followed by very poor quality (27.71%) and then by a fair quality of life in the minority of patients (14.86%).

Discussion:Patients with Pulmonary Tuberculosis (PTB) often develop impairment in pulmonary function due to anatomical changes secondary to the i l lness . Histopathologic findings resulting from tuberculosis include the formation of caseating granuloma, tissue

9liquefaction, and cavity formation. When these occur in the lung, many survivors experience permanent anatomical changes. These result in pulmonary sequelae that are characterized by bronchial and parenchymal structural changes, including broncho-vascular distortion, bronchiectasis, emphysematous changes, and fibrotic bands. These changes cause symptoms like breathlessness, cough with expectoration, recurrent infections and chest pain, and thus deteriorate the quality of life of the patients. While these changes remain after a microbiological cure, the further evaluation of persons

9after tuberculosis is not recommended.

Studies of pulmonary function in individuals with pulmonary tuberculosis demonstrated variable patterns

10-15and severity of impairment. Patients of PIAT also suffer from impaired pulmonary function. Pulmonary function

10-15studies can show restrictive, obstructive, or mixed patterns and range from normal to severe impairment.

16In a previous study done in South Africa by Cole G et al , it was found that FEV1, FVC and FEV1/FVC all values were decreased in patients of healed pulmonary TB. Similar results were found in our study, although different patterns were observed. Similar results were found by

17Bhola Singh et all in their study on patients of healed pulmonary TB where they found obstructive impairment to be the most prevalent.


© JIMI � APR - JUNE 2018 � VOL. 12 13

Table 2

In previous studies, it was found that patients of both active as well as healed pulmonary TB suffer a modest decline in pulmonary function, exercise capacity, exercise

18,19,20tolerance and quality of life. The great inammatory component causes major injuries that trigger fibroblastic reaction, fibrosis and chest wall retraction, compromising pulmonary expansion, which translates into a clinically and functionally moderate restrictive pattern and

21dyspnea during exercise. Involvement of lung airways and parenchyma by inammation, effusion, cavitation and fibrosis in these diseases leads to reduced compliance and increased elastic recoil , neuro-mechanical dissociation, ventilation-perfusion derangement and cardiovascular limitations. Due to continuing airway and parenchymal inammation and destruction, there is gradual increase in breathlessness on exertion and reduction in functional exercise capacity. Obliteration of the normal architecture of the lungs increases work of breathing and makes them more prone to infections. Increased secretions due to recurrent infections and ongoing inammation impair gas exchange resulting in hypoxia and free radical injury during rest and activity. Early fatigue constrains patients to go out into the community lest they get breathless which makes them socially isolated and depressed. Functional disability and repeated hospitalisations reduces their efficiency at home and at work-place and is associated with an increased expense and health care utilisation, resulting in socio-

20economic burden.

Conclusion:The patients of pulmonary TB continue to suffer from the various sequelae of the disease even after taking complete treatment. These post tubercular limitations are a source of permanent distress and social withdrawal for the patients. These issues thus should be addressed and the survivors of pulmonary TB should be kept in a regular follow-up. This can help in reducing the burden on the health services as hospital admission rates can be lowered by timely interventions to control exacerbations of pulmonary impairment.

FINANCIAL SUPPORT AND SPONSORSHIP: Nil

CONFLICTS OF INTEREST: Nil

ReferencesPasipanodya et al. BMC Public Health 2010, 10:259Dheda K, Booth H, Huggett JF, Johnson MA, Zumla A, Rook GA. Lung remodeling in pulmonary tuberculosis. J Infect Dis. 2005; 192: 1201–9, doi: 10.1086/444545Curtis JK. The significance of bronchiectasis associated with pulmonary tuberculosis. Am J Med. 1957; 22: 894–903, doi: 10.1016/0002 9343(57)90025-6.

Rosenzweig DY, Stead WW. The role of tuberculosis and other forms of bronchopulmonary necrosis in the pathogenesis of bronchiectasis. Am Rev Respir Dis. 1966; 93: 769–85.Pasipanodya JG, Miller TL, Vecino M, Munguia G, Garmon R, Bae S, Drewyer G, Weis SE: Pulmonary Impairment After Tuberculosis.Chest 2007, 131:1817-1824.Pasipanodya JG, Miller TL, Vecino M, Munguia G, Bae S, Drewyer G, Weis SE: Using the St George's Respiratory Questionnaire to ascertain health quality in persons with treated pulmonary tuberculosis.Chest 2007, 132:1591-1598.Menezes AMB, Hallal PC, Perz-Padilla R, Jardin JRB, Muino A, Lopez MV, Valdivia G, Montes de Oca M, Talamo C, Pertuze J, Victora CG for the Latin American Project for the Investigation of Obstructive Lung Disease (PLATINO) Team: Tuberculosis and airow obstruction: evidence from the PLATINO study in Latin America.EurRespir J. 2007, 30:1180-1185.Andersson GBJ, Cocchiarella L, eds: Guides to the Evaluation of Permanent Impairment. 5th edition. AMA Press. Chicago. IL; 2000:2-15. ISBN 1-57947-085-8. 87-112, 565-586Sodeman, WA, Sodeman, TM Pathologic physiology: mechanisms of disease. 7th ed.1985,467 WB Saunders. Philadelphia: PA: American Thoracic Society. Treatment of tuberculosis. MMWR Morb Moral Wkly Rep2003;52,1-77Long, R, Maycher, B, Dhar, A, et al Pulmonary tuberculosis treated with directly observed therapy: serial changes in lung structure and function. Chest1998; 113, 933-943. [PubMed] [CrossRef]Gaensler, EA, Lindgren, I Chronic bronchitis as an etiologic factor in obstructive emphysema, preliminary report. Am Rev Respir Dis1959; 80, 185-193. [PubMed]Snider, GL, Doctor, L, Demas, TA, et al Obstructive airways disease in patients with treated pulmonary tuberculosis. Am Rev Respir Dis1971; 103, 625-640. [PubMed]Wilcox, PA, Ferguson, AD Chronic obstructive airways disease following treated pulmonary tuberculosis. Respir Med1989; 83, 195-198. [PubMed]Weiner, H Changes in employment status associated with hospitalization for tuberculosis: analysis of 163 consecutively admitted males. Am Rev Respir Dis1963;87,17-22. [PubMed]Hnzido, E, Singh, T, Churchyard, G Chronic pulmonary function impairment by initial and recurrent pulmonary tuberculosis following treatment. Thorax2000;55,32-38. [PubMed]Cole G et al: Pulmonary impairment after Tuberculosis in a South African Population. South African Journal of Physiotherapy; 72(1); a307.Bhola Singh et al. Trends of Pulmonary impairment in persons with treated pulmonary tuberculosis. Int J Med Res Prof. 2015; 1(1); 8-11. Donna de GrassShamilaManie, and SeyiLadeleAmosun. Effectiveness of a home-based pulmonary rehabilitation programme in pulmonary function and health related quality of life for patients with pulmonary tuberculosis: a pilot study. Afr Health Sci. 2014 Dec; 14(4): 866–872Esther Cecilia Wilches, Julián Andrés Rivera, Ricardo Mosquera, Liliana Loaiza, LucelyObando, Psicol. Pulmonary rehabilitation in multi-drug resistant tuberculosis (TB MDR): a case report. Colomb Med. 2009; 40: 436-41.Vishal Bansal. Pulmonary Rehabilitation in Chronic Respiratory Diseases. Indian J Chest Dis Allied Sci 2014; 56:147-148.

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© JIMI � APR - JUNE 2018 � VOL. 12 14

Study to Evaluate The Efficacy of Cranberry Supplementation InThe Management of Complicated and Recurrent Urinary

Tract Infection In Either Sex

Original Article

Waleem Ahmad¹, Anjum Mirza Chughtai²

AbstractBackground: Urinary tract infections (UTIs) are the leading cause of gram-negative bacteremia in patients of all ages and are associated with a high risk of morbidity and mortality, especially in elderly and account for significant health care costs. Complicated UTI is one that occurs because of anatomic, functional factors that predispose the patients to persistant infection, recurrent infection or treatment failure. with emerging trend of development of resistant strains to beta lactam & aminoglycoside antibiotics, newer &expensive antibiotics have to be given for a long period to eradicate infection; management of which is not affordable to majority of our population. Therefore we have to find out easily available & affordable means of alternative or adjuvant therapy to standard chemotherapeutic protocol for effective & long lasting care of patients suffering from resistant, recurrent & complicated UTI.

Urinary Tract Infection (UTI) is one of the most common bacterial infections and second most common infectious disease in the community practice. UTI occurs in all populations, from the neonate to the geriatric patient, but

Introduction

1. Assistant Professor, Department of Medicine, JN Medical college , AMU, Aligarh, UP (First author)2. Associate professor, Department of Medicine, JN Medical college, AMU, Aligarh, UP (Corresponding author)

Method: In this Parallel group, Randomized Controlled Study, total 102 patients of complicated and recurrent UTI were enrolled and randomized to receive either antibiotics for recommended period as per urine culture and sensitivity pattern with cranberry capsules 300 mg twice a day (Group A, n=51) till the 6 weeks follow up or only antibiotics for recommended period as per urine culture and sensitivity pattern(Group B, n=51). Follow up was done after 6 weeks and whenever they experience a symptomatic UTI. Patients were enquired about the clinical symptoms of UTI and urine culture was repeated at the time of follow up. Appropriate statistical tests were used where ever required considering statistically significant level at p<0.05.

Results: At the end of the study, total 102 patients (Group A: 51 and Group B: 51) completed the study. Demographic and baseline disease characteristics were comparable in both groups. Efficacy was evaluated in total 102 patients. 2 out of 51(3.92%) patients in cranberry plus antibiotics group (Group A) developed symptomatic UTI whereas 7 out of 51 (13.7%) patients in antibiotic group (Group B) developed symptomatic UTI during 6 weeks follow up. Although there is difference in the occurrence of symptomatic UTI but this difference between two groups is not statistically significant, relative risk (RR) being 0.29 [95% CI 0.06-1.33, P = 0.081).

Conclusion: Cranberry supplementation is not effective in the management of complicated and recurrent UTI.

Keywords: Cranberry, Complicated and recurrent urinary tract infection

it has a particular impact on females of all ages (especially during pregnancy), males at the two extremes of life, kidney transplant recipients, and those with functional or structural abnormalities of the urinary tract. In fact, UTI is the leading cause of gram-negative bacteremia in patients of all age groups and are associated with a high risk of mortality and morbidity, especially in the elderly, and

[1]account for significant health care cost. The most important issues regarding UTI are their long-term


© JIMI � APR - JUNE 2018 � VOL. 12 15

consequences rather than the direct infectious disease morbidity and mortality of these infections. Bacteriuria may have a significant impact on children, especially in the presence of an anatomic or functional abnormality, like vasicoureteric reux. UTI causes permanent renal damage in children. Chronic pyelonephritis is a frequent cause of hypertention in children and secondary

[2]hypertension in adults. In case of pregnant women, untreated, asymptomatic bacteriuria is associated with a lot of adverse effects. Approximately half of such untreated women subsequently develop symptomatic UTI, and 25% to 30% have acute pyelonephritis. An association of bacteriuria in pregnancy with anemia, hypertension, decreased glomerular filtration rate, and decreased urinary concentration ability, which is

[3]improved by therapy, has also been noted. Untreated bacteriuria in pregnancy either symptomatic or asymptomatic is associated with a 50% increase in the risk of low birth weight and a significant increase in the risk of premature delivery, pre-eclampsia, anemia, hypertension

[4,5]and postpartum endometritis.

UTIs are classified into two groups: Uncomplicated UTI [6]and complicated UTI. Each type of UTI has different

clinical characteristics. Uncomplicated UTI refers to acute cystitis or pyelonephritis in non-pregnant outpatient w o m e n w i t h o u t a n a t o m i c a b n o r m a l i t i e s o r instrumentation of the urinary tract. Complicated UTI (cUTI) is one that occurs because of anatomic, functional or pharmacologic factors that predispose the patient to persistent infection, recurrent infection or treatment

[7]failure. The definition is basically needed for the differing line of management of cUTI and uncomplicated UTI. The uropathogens causing cUTI and their antibiotic sensitivity pattern varies considerably not only from that in acute uncomplicated UTI but also with time.

In present scenario, the essence of antimicrobial drug resistance of major uropathogens has posed a global

[8]threat. Of the various uropathogens, the most common o r g a n i s m s a r e E . C o l i , E n t e r o c o c c u s f e c a l i s , Staphylococcus aureus, Enterococci species and Klebsiella

[9]species. So newer & expensive antibiotics have to be given for a long period to eradicate infection & to preserve the kidney function so that the patient may not land up Chronic kidney disease(CKD) & End stage kidney disease (ESKD); management of which is neither accessible nor affordable to majority of our population. Therefore, the present study is to find out easily available & affordable means of alternative or adjuvant therapy to standard chemotherapeutic protocol for effective & long lasting care of patients suffering from complicated & recurrent UTI mostly due to resistant strains. The adhesion of bacteria to uroepithelial cells or urinary catheters is the

first step in the development of biofilm formation and urinary tract infections (UTIs). Previous research has suggested that consumption of cranberry juice can prevent the recurrence of UTIs by decreasing bacterial (e.g. E.coli) adhesion since isolated compounds in cranberries, known as A-type proanthocyanidins (PACs) prevent bacterial adhesion mediated via both P fimbriae & type 1 fimbriae that help attach bacteria (e.g. E.coli) to

[10,11]epithelial cell receptor. Several studies have been conducted to assess the effectiveness of cranberry products in prevention and treatment of only recurrent UTIs but present study was done to assess the efficacy of cranberry supplementation in both complicated and recurrent UTIs.

Materials and MethodsThis was a Parallel group, Randomized Controlled Study conducted in Department of Medicine, Department of Microbiology and endocrinology centre, JN Medical College and Hospital, AMU, Aligarh. The study was conducted from february, 2013 to October, 2014.

Patients of UTI of age 13 years and above who were having clinical features and bacteriological evidence of urinary tract infection (i.e urinary tract infection confirmed by positive urine culture reports) undergoing treatment in the medicine department and endocrinology centre were included in the study. The study protocol was approved by institute ethical committee and the study was conducted in accordance with the ethical standards of institutional ethics and research advisory committee of Jawaharlal Nehru Medical College, AMU, Aligarh. After patient selection, study protocol was completely explained to the patients and written informed consent was taken from each patient.

Patient selection criteriaA total of 102 patients of either sex with age 13 years and above were enrolled in the study fulfilling the following inclusion criteria: patients with diagnosis of UTI with at least one of the following features- Indwelling catheter, diabetes mellitus, functional/anatomical abnormality of urinary tract, Immunosuppression, male sex, voiding dysfunction, renal failure, urolithiasis, history of urinary tract surgery, polycystic kidneys. Patients with a history of recurrent UTI (more than 2 episodes of UTI in previous 6 months or more than 3 episodes of UTI in previous 12 months) were also included in the study. Patients with HIV ,advanced renal failure, advanced hepatic dysfunction, multiorgan failure, uncontrolled diabetes mellitus, malignancy, renal transplant, renal replacement therapy, plans to leave study within 4-6 weeks, allergy to cranberry or cranberry compounds, already on antibiotics therapy and critically ill patients were excluded from the study.


© JIMI � APR - JUNE 2018 � VOL. 12 16

Treatment protocol102 patients having symptomatic UTI fulfilling the inclusion and exclusion criteria were randomly assigned to group A and group B. Patients in Group A (Intervention group) were given antibiotics for recommended period as per urine culture and sensitivity pattern with cranberry capsules 300 mg twice a day till the 6 weeks follow up. Patients in Group B (Control group) were given only antibiotics for recommended period as per urine culture and sensitivity pattern. Participants had follow-up visits at 6 weeks, and whenever they experienced the symptoms of UTI. Participants completed questionnaire at study entry, at the time of follow up visit after 6 weeks or whenever patient experience symptoms of UTI. Urine specimens taken at each visit to test for the presence of bacteria that cause urinary tract infections.

Data for proposed study was collected in pre-designed proforma which included various parameters like age, sex, detailed history, clinical examination and investigations as per patients proforma. Patients who are having clinical feature and microbiological evidence of UTI and fulfilling the inclusion and exclusion criteria were included in the study. Follow up was done after 6 weeks and whenever they experience a symptomatic UTI. Patients were enquired about the clinical symptoms of UTI and urine culture was repeated at the time of follow up as per proforma. A detailed history and physical examination was carried out for every subject who entered in the study as per a pre-designed proforma . Examination comprised of a thorough physical examination, assessment of vital parameters, and systemic examination. Screening investigations included Hemoglobin, total leukocyte count, differential leukocyte count, general blood picture, plasma glucose, blood urea, serum creatinine, liver function test, routine urine analysis and USG abdomen.

Various culture samples including urine and Foley's urinary catheter tip were sent in appropriate culture vials using standard techniques. Urine samples collected were Midstream urine, early morning urine sample, void after 4 hours of prior voiding and rapid transportation of urine sample to laboratory was done. Suprapubic aspiration specimen was used when a bedridden patient cannot be catheterized or a sterile specimen is required. Antimicrobial susceptibility testing was done for all the isolates using Kirby Bauer disc diffusion method as recommended by Clinical and Laboratory Standards Institute (CLSI M2-A9,2012). The antibiotic panels for each group of isolates were selected according to the CLSI guidelines( M100-S22,2012) were obtained from HiMedia, India.

E�cacy criteriaChanges in signs and symptoms were monitored from day 2 to 6 weeks. Efficacy was evaluated on the basis of changes in basel ine s igns and symptoms and microbiological confirmation of UTI by urine culture and sensitivity. Primary outcome measures are the number of symptomatic UTIs in each group at the end of the treatment period of 6 weeks .

Appropriate statistical tests were used where ever required considering statistically significant level at p<0.05. The overall relative risk (RR) was used to report the relative rates of symptomatic UTI in the intervention group and control groups, with RR less than one favouring the intervention and p value <0.05 considered statistically significant.

Statistical Analysis

Observation and ResultsA total of 102 patients (52 males and 50 females) of complicated and recurrent urinary tract infections were enrolled in the study. Out of these total 51 (50%) patients were randomized to receive antibiotics for recommended period as per urine culture and sensitivity pattern with cranberry capsules 300 mg twice a day till the 6 weeks follow up (Group A) and 51 (50%) patients received antibiotics for recommended period as per urine culture and sensitivity pattern (Group B).

Table 1 shows the age distribution of all patients. Demographic and baseline characterstics were comparable in both groups. There was no significant difference in demographic parameters in both groups. The age of patients in group A ranged from 23 to 70 years with a mean age of 45.97±14.41 years and in group B, the age ranged from 15 to 80 years with mean age of 45.81±14.56 years. The disease baseline sign and symptoms were also similar in both the groups (Table 2).

Table 1: Demographic and baseline characterstics ofpatients

Parameter Group A

(n=51)

Group B

(n=51)

Males, n (%)

27 (52.94)

25 (49.01)

Female n (%) 24 (47.05) 26 (50.98)

Age (Years)

Range

23-70 15-80

Mean±SD 45.97±14.41 45.81±14.56


© JIMI � APR - JUNE 2018 � VOL. 12 17

Table 2: Disease characterstics of patients

Symptoms and

sign

Group A

(n=51)

Group B

(n=51)

Dysuria 31 (60.78%)

33 (64.70%)

Fever 21 (41.17%) 22 (43.13%)

Frequency

13 (25.49%)

11 (21.56%)

Urgency 10 (19.60%)

8 (15.68%)

Hematuria 2 (3.92%) 1 (1.96%)

Table 3: Complicating factors

Complicating

factor/Recurrent UTI

Group A

(n=51)

Group B

(n=51)

Diabetes mellitus

21

(41.17%)

19

(37.25%)

Indwelling catheter

9 (17.64%)

10

(19.60%)

Renal failure 4 (7.84%) 4 (7.84%)

History of urinary tract

surgery

1 (1.96%)

0

Urolithiasis 1 (1.96%) 1 (1.96%)

Recurrent UTI 4 (7.84%) 6 (11.76%)

E�cacy of cranberry supplementationIn our study 2 out of 51(i.e 3.92%) patients in cranberry plus antibiotics group (Group A) developed symptomatic UTI whereas 7 out of 51 (i.e 13.7%) patients in antibiotic group (Group B) developed symptomatic UTI during 6 weeks follow up. This is equal to 9.78 % reduction in absolute risk in the cranberry plus antibiotic group compared with the antibiotic group. For the 9 patients who developed a symptomatic UTI during the study, the urine culture results were as follows: E. coli, 6 (2 in the cranberry with antibiotic group and 5 in the antibiotic group); Klebsiella pneumoniae, 2 in the antibiotic group.

Although there is difference in the occurence of symptomatic UTI but this difference between two groups is not statistically significant , relative risk (RR) being 0.29 [95% CI 0.06-1.33, P = 0.081). Value of chi square =2.939 with 1 degree of freedom , p=0.086. Further the odd ratio (OR) of symptomatic UTI in antibiotic group was 3.897 (95% CI,from 0.77-19.76 , p=0.16) in the follow up as compared to cranberry with antibiotic group.

DiscussionThe present study evaluated the efficacy of cranberry supplementation in the management of complicated and recurrent UTI. A complicated UTI is a urinary infection occurring in a patient with a structural or functional abnormality of the genitourinary tract which is mainly caused by gram negative bacteria, E. coli being the single

most common organism. Maximum numbers of cases in our study were observed in males in 41-50 years age groups. Most clinicians suggest that male gender alone is

[12] criteria for being a complicated UTI. The reason for complicated UTI being more common in male is that the structural and genitourinary abnormalities are more common in male as compared to female. The major presenting symptom was dysuria followed by fever and increased frequency of micturition. Diabetes mellitus was the most common complicating factor while the most common risk factor in our study was following bladder catheterization. Major organism isolated in our study was E. coli (72.54%), others being klebsiella (14.7%) and staphylococcus (4.9%). These results are similar to that

[13,14] from worldwide review by different authers.

In our study we included patients having complicated and recurrent UTI and fulfilling the inclusion criteria. The patients were randomized into two groups and group A was given antibiotics plus cranberry capsule and group B was given antibiotics as per urine culture and sensitivity pattern. Cranberry capsules have potential advantages over juice; capsules are more convenient, and may overcome compliance issues for some individuals. The high rates of withdrawal from some previous studies suggest that cranberry juice may not be an acceptable therapy over a long period of time. In our study a total of 9 out of 102 (i.e 8.82%) patients developed symptomatic UTI during 6 weeks follow up. 2 out of 51(i.e 3.92%) patients in cranberry with antibiotics group developed symptomatic UTI whereas 7 out of 51 (i.e 13.7%) patients in antibiotic group developed symptomatic UTI. Although there is a better outcome in cranberry with antibiotic group but this difference between the two groups was not statistically significant, relative risk (RR) being 0.29. Further the odd ratio (OR) of symptomatic UTI in the 6 weeks follow up in antibiotic group was 3.897 as compared to cranberry with antibiotic group.

Other studies which evaluated efficacy of cranberry supplementation in recurrent UTI included some double

[15,16]blind, randomized placebo controlled trials. The difference in recurrence rate of UTI between cranberry group and placebo group was not statistically significant.

[17] [18]Kontoikari et al. and Ferrara et al. compared recurrence of UTI in female patients administered with cranberry-lingoberry juice vs lactobacillus GG vs control group. Again , the recurrence of UTI in each group was not statistically significant. Cochrane Database of Systematic Reviews 2012, included a total of 24 studies (six cross-over studies, 11 parallel group studies with two arms; five with three arms, and two studies with a factorial design) with a total of 4473 participants. The comparison/control arms were placebo, no treatment, water, methenamine hippurate, antibiotics, or lactobacillus. Data included in


© JIMI � APR - JUNE 2018 � VOL. 12 18

the meta-analyses showed that, compared with placebo, water or not treatment, cranberry products did not significantly reduce the occurrence of symptomatic UTI overall (RR 0.86, 95% CI 0.71 to 1.04) or for any the subgroups: women with recurrent UTIs (RR 0.74, 95% CI 0.42 to 1.31); older people (RR 0.75, 95% CI 0.39 to 1.44); pregnant women (RR 1.04, 95% CI 0.97 to 1.17); children with recurrent UTI (RR 0.48, 95% CI 0.19 to 1.22); cancer patients (RR 1.15 95% CI 0.75 to 1.77); or people with neuropathic bladder or spinal injury (RR 0.95, 95% CI: 0.75 to 1.20).

ConclusionThe results from present study suggest that, compared wi th ant ib io t i c group (Group B) , c ranberry supplementation did not significantly reduce the occurrence of symptomatic UTI ( 3.92% vs 13.7%). Further more studies of cranberry products such as tablets and capsules that contain the recommended amount of PACs (at least 36 mg/d) and are quantified using standardised and validated measures with larger sample and longer duration of follow up need to be done to evaluate the efficacy of cranberry supplementation in the management of complicated and recurrent urinary tract infection.

ReferencesStamm WE, Norrby SR. Urinary tract infections: disease panorama and challenges. J Infect Dis. 2001; 183(Suppl 1): S1-S4.Tullus K, Winberg J: Urinary tract infections in childhood. In Brumfitt W, Hamilton-Miller JMT, Bailey RR (eds): Urinary Tract Infections. London, Chapman & Hall, 1998.Millar LK, Wing DA, Paul RH, et al. Outpatient treatment of pyelonephritis in pregnancy: a randomized controlled trial. Obstet Gynecol 1995 Oct; 86(4 Pt 1):560-4.Mittendorf R, Lain KY, Williams MA, Walker CK: Preeclampsia: A nested, case-control study of risk factors and their interactions. J Reprod Med 41:491, 1996 .Rizvi M, Khan F, Shukla I, Malik A, Shaheen. Rising prevalence of antimicrobial resistance in urinary tract infections during pregnancy: Necessity for exploring newer treatment options. J Lab Physicians 2011;3:98-103.Johansen TE, Botto H, Cek M, Grabe M, Tenke P, Wagenlehner FM, et al. Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system. Int J Antimicrob Agents. 2011;38(Suppl):64–70.

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Resistance Patterns of Community-acquired Urinary Tract

Infections in J N M C Hospital Aligarh, India. Ann Clin

Microbiol Antimicrob. 2007; 6: 4.Khan AU and Zaman MS. Multiple Drug Resistance Pattern In

Urinary Tract Infection Patients In Aligarh. Biomedical

Research. 2006; 17 (3): 179-181.Howell, A. B., Reed, J. D., Krueger, C. G., Winterbottom, R.,

Cunningham, D. G. & Leahy, M. A-type cranberry

proanthocyanidins and uropathogenic bacterial anti-adhesion

activity. Phytochemistry 66, 2281-91 (2005).Foo LY, Lu Y, Howell AB, Vorsa N. The structure of cranberry

proanthocyanidins which inhibit adherence of uropathogenic

P-fimbriated Escherichia coli in vitro. Phytochemistry.

2000;54(2):173-81.F o x m a n B : E p i d e m i o l o g y o f u r i n a r y t r a c t

infections—incidence, morbidity, and economic costs. Am J

Med 113:55, 2002.Hande Arslan, O¨zlem Kurt Azap, O¨nder Ergo¨nu¨, Funda

Timurkaynak. Risk factors for ciprooxacin resistance among

Escherichia coli strains isolated from community acquired

urinary tract infections in Turkey. Journal of Antimicrobial

Chemotherapy (2005) 56, 914–918.Chen SS, Chen KK, Lin AT, Chang YH, Wu HH, Hsu TH, Chiu

AW, Chang LS. Complicated urinary tract infection: analysis of

179 patients. Zhonghua Yi Xue Za Zhi (Taipei). 1998

Nov;61(11):651-6.Barbosa-Cesnik C, Brown MB, Buxton M, Zhang L,

DeBusscher J, Foxman B. Cranberry juice fails to prevent

recurrent urinary tract infection: results from a randomized

placebo-controlled trial. Clin Infect Dis. 2011;52(1):23-30.McMurdo ME, Bissett LY, Price RJ, Phillips G, Crombie IK.

Does ingestion of cranberry juice reduce symptomatic urinary

tract infections in older people in hospital? A double-blind,

placebo-controlled trial. Age Ageing. 2005;34(3):256-61.Kontiokari T, Sundqvist K, Nuutinen M, Pokka T, Koskela M,

Uhari M. Randomised trial of cranberry-lingonberry juice and

Lactobacillus GG drink for the prevention of urinary tract

infections in women. BMJ. 2001;322(7302):1571.Ferrara P, Romaniello L, Vitelli O, Gatto A, Serva M, Cataldi L.

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© JIMI � APR - JUNE 2018 � VOL. 12 19

Study of Serum Ferritin in Type 2 Diabetes Mellitus andIts Relation With Microvascular Complications

Original Article

1 2 3 4Ajeet Kumar Chaurasia , Manoj Kumar Mathur , Poonam Gupta , Vatsal Singh

AbstractBackground: Association of diabetes with haemochromatosis is well established. This association led to studies, testing the hypothesis that iron metabolism is involved with the development of diabetes. A few studies have suggested a causal relationship between high iron stores and diabetes. Studies have also linked serum ferritin with obesity, metabolic syndrome and insulin resistance. However, no major studies, have been conducted to assess the relation of serum iron and ferritin levels with microvascular complications of diabetes.

Association of diabetes with haemochromatosis is well 1established . This association led to studies, testing the

hypothesis that iron metabolism is involved with the 2,3development of diabetes . A few studies have suggested a

causal relationship between high iron stores and

4diabetes . High dietary iron intake has been shown to be 5associated with increased risk of gestational diabetes as

6well as diabetes in postmenopausal women . Apart from diabetes, studies have also linked serum ferritin with

7,8obesity, metabolic syndrome and insulin resistance . However, no major studies, have been conducted to assess the relation of body iron levels with changes in glycemic status or associations with microvascular complications.

Introduction

1. Associate Professor, Department of Medicine , MLN medical 2College Allahabad ,Uttar Pradesh . Junior Resident ,Department of

3 4Medicine , MLN medical College Allahabad , Uttar Pradesh

Method: In this observational case control study, Adults, aged > 18 years, with T2DM as per the Diagnostic criteria by the American Diabetes Association (ADA) were included.We measured FBG, PPBG, A1C, Serum Ferritin, Serum Creatinine, Glomerular Filtration Rate (GFR) and Urine Microalbumin in all the patients. Fundus examination was also done.

Results: We enrolled 93 patients with diabetes. 63 (67.74%) were males and 30 (32.26%) were females. Mean serum ferritin of all patients was 354.22 + 22.31 ng/ml and mean A1C % of all patients was 8.41 + 0.41%. We categorized all patients into two groups- Normal(28) and High Ferritin (65) groups. The mean A1C, FBG and PPBG levels were similar in both the groups. The mean serum creatinine and GFR were also similar between both the groups. Urine Microalbumin was 172.71 + 23.57 in Normal Ferritin group while 246.65 + 17.74 in high ferritin group which was statistically significant (p= 0.019).

Conclusion: We found that serum ferritin was significantly high in patients with diabetes both males and females as compared to normal population. Serum ferritin levels correlate significantly with FBG levels. Diabetic patients with A1C>8.5% have significantly higher serum ferritin levels. Diabetics with high serum ferritin have significantly higher microalbuminuria.

Keywords: Serum Ferritin, T2DM, Microvascular complication, Microalbuminuria

Objective: To find the level of Serum ferritin in Type 2 DM and its relation with microvascular complications..

Results: We enrolled 93 patients with diabetes. 63 (67.74%) were males and 30 (32.26%) were females. Mean serum ferritin of all patients was 354.22 + 22.31 ng/ml and mean A1C % of all patients was 8.41 + 0.41%. We categorized all patients into two groups- Normal(28) and High Ferritin (65) groups. The mean A1C, FBG and PPBG levels were similar in both the groups. The mean serum creatinine and GFR were also similar between both the groups. Urine Microalbumin was 172.71 + 23.57 in Normal Ferritin group while 246.65 + 17.74 in high ferritin group which was statistically significant (p= 0.019).


© JIMI � APR - JUNE 2018 � VOL. 12 20

The patho-physiology behind this relationship is largely unknown, however, it is proposed that iron mediated free radical injury is the responsible factor. Iron can be very easily oxidised and reduced reversibly, and this property, vital for its metabolic function, also makes it potentially

9hazardous by generating oxidative stress . It has also been shown that iron causes hyperinsulinaemia by decreasing

10the insulin uptake and metabolism by hepatocytes .

Al though numerous s tudies , have supported involvement of iron in association with diabetes, the hypothesis is still not considered valid. In the recently

11published data from the EPIC-Interact study , higher serum ferritin levels were associated with higher risk of diabetes, yet the authors concluded that the relationship is more complex than simple direct correlation. Therefore, the association between iron parameters and diabetes must be further established with more prospective studies, and more studies are needed to find relation of iron parameters with microvascular complications.

AIM of Study :The aim of our study was to find the level of Serum ferritin in Type 2 DM and its relation with microvascular complications.

In this observational case control study, Adults, aged > 18 years, with T2DM as per the Diagnostic criteria12 by the American Diabetes Association (ADA) were included in

Results :

Material And Method: We enrolled 93 patients with diabetes. 63 (67.74%) were males and 30 (32.26%) were females. Mean age of all patients was 56 + 11.69 years. Mean serum ferritin of all patients was 354.22 + 22.31 ng/ml and mean A1C % of all patients was 8.41 + 0.41% (Table 1).

the study-1. Fasting blood glucose (FBG) level of 126 mg/dl (7.0 mmol/L) or higher, or2.2-hour plasma glucose level of 200 mg/dl (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or3.Random plasma glucose of 200 mg/dl (11.1 mmol/L) or higher in a patientwith classic symptoms of hyperglycemia or hyperglycemic crisis.We excluded patients with Anemia (Hb<10 g/dL), patients with illnesses that cause hyperferritinemia or affect serum ferritin level - Acute and chronic liver disease, Sepsis, Inammation, Malignancies, Iron overload (haemochromatosis, thalassemia), End-stage renal disease and patients with raised ESR (>22 mm/hr in males, >29 mm/hr in females) or CRP (>10 mg/dL)METHOD :We measured FBG, PPBG, A1C, Serum Ferritin, Serum Creatinine, Glomerular Filtration Rate (GFR) and Urine Microalbumin in all the patients. Fundus examination was also done.All data was collected into Microsoft Excel. All statistical analysis was done using Statistica-8 software. Categorical data were compared using Chi-square test. Continuous data were compared using one-way analysis of variance (ANOVA).

Table 1. Basic Characteristics (n=93)

Mean +

SE

Range

Age (years)

56 +

1.82

30 - 87

Sex: Males

Females

63 (67.74%)

30 (32.26%)

FBG (mg/dl)

154.59 +

7.76

79 - 334

PPBG (mg/dl)

232.47 +

10.33

109.00 - 454.00

A1C (%)

8.41 +

0.41

4.60 - 15.90

Serum Ferritin (ng/ml)

354.22 +

22.31

51.20 - 1149.00

Serum Creatinine (mg/dl)

1.30 +

0.11

0.45 – 3.97

Urine Micralbumin (mg/dl) 224.38 + 11.29 13.20 - 600.00

GFR (ml/min/1.73m2) 80.18 + 7.23 5.32 - 206.45

FBG= Fasting Blood Glucose, PPBG= Post Prandial Blood Glucose, GFR= Glomerular Filtration Rate, SE= Standard Error

Comparison of ferritin categories


© JIMI � APR - JUNE 2018 � VOL. 12 21

We categorized all patients into two groups- Normal and High Ferritin groups. Normal ferritin group (NF Group) included 28 (30.10%) patients with serum ferritin levels between 12 and 204 ng/ml. High ferritin group (HF group) group included 65 (69.89%) patients with serum ferritin above 204 ng/ml. The proportion of males and age were similar in both the groups (Table 2). The mean serum ferritn levels of NF and HF groups were 134.09 + 8.09 ng/ml and 49.05 + 32.73 ng/ml respectively. The mean A1C, FBG and PPBG levels were similar in both the groups. The mean serum creatinine and GFR were also similar between both the groups. Urine Microalbumin was 172.71 + 23.57 in Normal Ferritin group while 246.65 + 17.74 in high ferritin group which was statistically significant (p= 0.019)

Normal Ferritin Group (n=28) High Ferritin Group

(n=65)

p-value

Males 17 (60.71%)

46 (70.77%)

p=0.141

(χ²=0.905)

Females 11 (31.29%)

19 (29.23%)

Age + SE (years)

55.29 +

1.89

57.05 +

1.54

0.508

FBG + SE (mg/dl)

143.88 + 9.33

159.22 +

7.37

0.234

PPBG +SE (mg/dl) 231.23 + 10.76 233.02 + 8.39 0.903

A1C1 + SE (%) 8.11 + 0.37 8.55 + 0.25 0.338

Ferritin1 + SE (ng/ml)

134.09 + 8.09

449.05 + 32.73

0.001

Diabetic Retinopathy

10 (35.71%)

24 (36.92%)

p=0.743

(χ²=0.012)

Urine Micralbumin+ SE (mg/dl)

172.71 +

23.57

246.65 +

17.74

0.019

GFR + SE (ml/min/1.73m2)

91.57 +

8.67

75.28 +

5.14

0.095

Table 2. Comparison of basic characteristics between normal ferritin and high ferritin groups

Figure 1. Mean urine micralbumin and GFR in normal ferritin and high ferritin groups


© JIMI � APR - JUNE 2018 � VOL. 12 22

We also classified all subjects on the basis of their A1C levels. There were 44 (47.31%) patients with A1C levels less than 7.5%, 17 (18.28%) patients with A1C levels between 7.6 and 8.5% and 32 (34.41%) patients had A1C more than 8.5%. Those with A1C >8.5% had significantly higher serum ferritin level (435.99 + 53.45 ng/ml) in comparison to those with A1C levels between 7.6 and 8.5% (223.59 + 16.88 ng/ml) as well as than those with <7.5% (207.98 + 6.54 ng/ml).

Figure 2. Shows serum ferritin levels in groups with A1C<7.5%, A1C 7.6-8.5% and A1C>8.5%

Correlations: Correlation analysis was performed between serum ferritin and various other parameters. Significant correlation was found between serum ferritin and FBG levels (r=0.213, p=0.040, Figure 3) and serum ferritin and urinary microalbumin. Correlation was not significant between serum ferrritn and A1C level, PPBG, serum creatinine and GFR.

Figure 3. Correlation between FBG and serum ferritin

Scatterplot of FBG against FERRITIN1

Spreadsheet18 20v*100c

FBG = 138.4098+0.0457*x

0 200 400 600 800 1000 1200

FERRITIN1

60

80

100

120

140

160

180

200

220

240

260

280

300

320

340

360

FB

G

FERRITIN1:FBG: r = 0.2131, p = 0.0403

Discussion :

In this study we evaluated serum ferritin levels in T2DM patients. We found that mean serum ferritin was raised in the diabetes patients of our study (354.22 + 22.31 ng/ml). Other studies have also shown that serum ferritin is raised in diabetes, however, there is a large variation in the absolute values of serum ferritin. Jiang R et in 200413 reported that patients with diabetes had mean serum

In this study we evaluated serum ferritin levels in T2DM patients. We found that mean serum ferritin was raised in the diabetes patients of our study (354.22 + 22.31 ng/ml). Other studies have also shown that serum ferritin is raised in diabetes, however, there is a large variation in the absolute values of serum ferritin. Jiang R et in 200413 reported that patients with diabetes had mean serum


© JIMI � APR - JUNE 2018 � VOL. 12 23

We devided patients into two groups having normal ferritin (NF) and high ferritin (HF). Both groups were matched with respect to age and sex. Although the serum A1C levels of HF group was higher in comparison to NF group, the difference was not statistically significant (8.55 + 0.25 vs 8.11 + 0.37 ng/ml, p=0.338). Similarly, mean FBG and PPBG levels were also higher in HF group than NF group but the difference was statistically not significant (159.22 + 7.37 vs 143.88 + 9.33 ng/ml, p=0.234). Many studies have found an association of serum ferritin with incidence of diabetes11,15, metabolic syndrome and insulin resistance16,17. Jiang R et al reported that mean serum ferritin of 698 diabetic females was 109 ng/ml, significantly higher in comparison to healthy controls who had mean serum ferritin of 71.5 ng/ml13. Halle M et al., reported 3.26 times higher risk for developing type 2 diabetes and 2.8 times higher risk for developing metabolic syndrome for individuals with the highest serum ferritin quartile compared with those of the lowest18. But there is not enough evidence to prove that the relation is causal, that is, high iron is sufficient to cause diabetes. At the same time, it is clear that iron has a multiplicity of effects in many tissues that can be either pro- or anti-diabetic at the ends of the spectrum that runs from iron deficiency to iron excess. In a meta-analysis published in 2013 , it was found that elevated levels of ferritin may help identify individuals at high risk of type 2 diabetes. They analysed 12 published studies involving 1,85,462 participants and 11,079 incident T2DM events and showed that the pooled fully adjusted relative risk with 95% confidence interval for type 2 diabetes was 1.73 (1.35-2.22).

We studied relationship of ferritin with two micro-complications of diabetes, nephropathy and retinopathy. The mean urine albumin of patients in high serum ferritin was significantly higher in comparison to those with normal serum ferritin (246.65 + 17.74 vs 172.71 + 23.57 mg/dl, p=0.019) and this came to be statistically significant. However, serum creatinine (1.37 + 0.09 vs 1.17 + 0.12, p=0.206) and GFR (75.28 + 5.14 vs 91.57 + 8.67 mg/dl, p= 0.095) were similar in both the groups. We did not find any statistical difference in number of patients having diabetic retinopathy between high and normal ferritin groups (36.92 vs 35.71%, p=0.743). None of the the previous studies have studied the relationship of ferritin with micro-complications of diabetes.

In this study, we found a significant correlation of serum ferritin with fasting blood glucose levels (r=0.213, p=0.04) but not with post-prandial blood glucose level or A1C level (r=0.071, p=0.878 and r=0.160, p=0.125 respectively). The correlation between serum ferritin and A1C levels has been studied by a few other studies with variable results.

Kunduet al20 showed that serum ferritin levels were highest in diabetics with A1C >8% (p<0.001) but they also did not find direct correlation between ferritin and A1C. In a small study by Padwal MK et al8 high serum ferritin levels were found to be correlated to metabolic syndrome and insulin resistance.

Thus we further need to understand the effect of “normal” iron concentrations on diverse metabolic processes in tissues including liver, fat, muscle, pancreas, gut, and brain and the molecular mechanism for these effects. The patho-physiological association needs to be decoded before reliably commenting on clinical implications. Along with we need lomg term follow up studies to determine what is the impact of correction of anemia and iron level on diabetic profile of the patient and how does the duration of diabetes affect the Iron and ferritin level of body.

Conclusion We found that serum ferritin was significantly high in patients with diabetes both males and females as compared to normal population. Serum ferritin levels correlate significantly with FBG levels. Patients with diabetics with A1C>8.5% have significantly higher serum ferritin levels. Diabetics with high serum ferritin have significantly higher microalbuminuriaThe association of serum ferritin with diabetes is complex. Further studies on larger populations are required to resolve these complexities.

ReferencesT. Creighton Mitchell, and D. A. McClain, 'Diabetes and Hemochromatosis', CurrDiab Rep, 14 (2014), 488.N. G. Forouhi, A. H. Harding, M. Allison, M. S. Sandhu, A. Welch, R. Luben, S. Bingham, K. T. Khaw, and N. J. Wareham, 'Elevated Serum Ferritin Levels Predict New-Onset Type 2 Diabetes: Results from the Epic-Norfolk Prospective Study', Diabetologia, 50 (2007), 949-56.R. Jiang, J. E. Manson, J. B. Meigs, J. Ma, N. Rifai, and F. B. Hu, 'Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women', JAMA, 291 (2004), 711-7N. F. Olivieri, and G. M. Brittenham, 'Iron-Chelating Therapy and the Treatment of Thalassemia', Blood, 89 (1997), 739-61.K. Bowers, E. Yeung, M. A. Williams, L. Qi, D. K. Tobias, F. B. Hu, and C. Zhang, 'A Prospective Study of Prepregnancy Dietary Iron Intake and Risk for Gestational Diabetes Mellitus', Diabetes Care, 34 (2011), 1557-63.D. H. Lee, A. R. Folsom, and D. R. Jacobs, Jr., 'Dietary Iron Intake and Type 2 Diabetes Incidence in Postmenopausal Women: The Iowa Women's Health Study', Diabetologia, 47 (2004), 185-94V. Abril-Ulloa, G. Flores-Mateo, R. Sola-Alberich, B. Manuel-y-Keenoy, and V. Arija, 'Ferritin Levels and Risk of Metabolic Syndrome: Meta-Analysis of Observational Studies', BMC Public Health, 14 (2014), 483.M. K. Padwal, M. Murshid, P. Nirmale, and R. R. Melinkeri, 'Association of Serum Ferritin Levels with Metabolic

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Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance', J ClinDiagn Res, 9 (2015), BC11-3.S. Swaminathan, V. A. Fonseca, M. G. Alam, and S. V. Shah, 'The Role of Iron in Diabetes and Its Complications', Diabetes Care, 30 (2007), 1926-33.J. M. Fernandez-Real, A. Lopez-Bermejo, and W. Ricart, 'Cross-Talk between Iron Metabolism and Diabetes', Diabetes, 51 (2002), 2348-54.C. Podmore, K. Meidtner, M. B. Schulze, R. A. Scott, A. Ramond, A. S. Butterworth, E. Di Angelantonio, J. Danesh, L. Arriola, A. Barricarte, H. Boeing, F. Clavel-Chapelon, A. J. Cross, C. C. Dahm, G. Fagherazzi, P. W. Franks, D. Gavrila, S. Grioni, M. J. Gunter, G. Gusto, P. Jakszyn, V. Katzke, T. J. Key, T. Kuhn, A. Mattiello, P. M. Nilsson, A. Olsen, K. Overvad, D. Palli, J. R. Quiros, O. Rolandsson, C. Sacerdote, E. Sanchez-Cantalejo, N. Slimani, I. Sluijs, A. M. Spijkerman, A. Tjonneland, R. Tumino, A. Dl van der, Y. T. van der Schouw, E. J. Feskens, N. G. Forouhi, S. J. Sharp, E. Riboli, C. Langenberg, and N. J. Wareham, 'The Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The Epic-Interact Study', Diabetes Care (2016).Classification and Diagnosis of Diabetes', Diabetes Care, 40 (2017), S11-S24.R. Jiang, J. E. Manson, J. B. Meigs, J. Ma, N. Rifai, and F. B. Hu, 'Body Iron Stores in Relation to Risk of Type 2 Diabetes in Apparently Healthy Women', JAMA, 291 (2004), 711-7.Q. Tang, Z. Liu, Y. Tang, A. Tan, Y. Gao, Z. Lu, Q. Wang, Y. Chen, C. Wu, H. Zhang, X. Yang, and Z. Mo, 'High Serum Ferritin Level Is an Independent Risk Factor for

Metabolic Syndrome in a Chinese Male Cohort Population', DiabetolMetabSyndr, 7 (2015), 11.F. Zhou, Z. Zhao, L. Tian, T. Zheng, Y. Gao, T. Chen, F. Yan, and H. Tian, 'Association of Serum Ferritin Level with Risk of Incident Abnormal Glucose Metabolism in Southwestern China: A Prospective Cohort Study', Biol Trace Elem Res, 169 (2016), 27-33.F. Zhou, Z. Zhao, L. Tian, T. Zheng, Y. Gao, T. Chen, F. Yan, and H. Tian, 'Association of Serum Ferritin Level with Risk of Incident Abnormal Glucose Metabolism in Southwestern China: A Prospective Cohort Study', Biol Trace Elem Res, 169 (2016), 27-33.K. Nakamura, M. Sakurai, Y. Morikawa, S. Y. Nagasawa, K. Miura, M. Ishizaki, T. Kido, Y. Naruse, M. Nakashima, K. Nogawa, Y. Suwazono, and H. Nakagawa, 'Serum Ferritin, Insulin Resistance, and Beta-Cell Dysfunction: A Prospective Study in Normoglycemic Japanese Men', ExpClinEndocrinol Diabetes, 125 (2017), 12-20.M. Halle, D. Konig, A. Berg, J. Keul, and M. W. Baumstark, 'Relationship of Serum Ferritin Concentrations with Metabolic Cardiovascular Risk Factors in Men without Evidence for Coronary Artery Disease', Atherosclerosis, 128 (1997), 235-40.S. K. Kunutsor, T. A. Apekey, J. Walley, and K. Kain, 'Ferritin Levels and Risk of Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-Analysis of Prospective Evidence', Diabetes Metab Res Rev, 29 (2013), 308-18.D. Kundu, A. Roy, T. Mandal, U. Bandyopadhyay, E. Ghosh, and D. Ray, 'Relation of Iron Stores to Oxidative Stress in Type 2 Diabetes', Niger J ClinPract, 16 (2013), 100-3.

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© JIMI � APR - JUNE 2018 � VOL. 12 25

To study the prevalence of subclinical hypothyroidism inpatients with type 2 diabetes mellitus (T2DM)

Original Article

1 2 3 4 5Raj K Singh , Amit Singh , Aradhana Singh , Mahim Mittal , Ajay Kumar

AbstractBackground: Type 2 diabetes mellitus (T2DM) is associated with increased incidence of thyroid dysfunction (TD). The coexistence of thyroid dysfunction with T2DM patient is important barrier in an achieving treatment goal. The present study was aimed to know the prevalence of subclinical hypothyroidism (SCH) in T2DM patients of Eastern Uttar Pradesh.

Thyroid disorders have a major impact on diabetes control and its complication. Hyperthyroidism impairs glycemic control in diabetic subjects, while hypothyroidism may increase susceptibility to hypoglycemia thus complicating diabetes management. A high frequency of diabetic retinopathy and nephropathy was observed in diabetic patients even with subclinical hypothyroidism.Subcl inical hypothyroidism and even cl inical hypothyroidism is a commonly overlooked and missed diagnosis not even in T2DM patients but also in general patients without diabetes. Missing the diagnosis of SCH in T2DM patients posed a great hurdle to achieve euglycemia, weight management, lipid management and good quality of life.

Introduction

1,2,4&5 Department of Medicine, Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh, India.3. Department of Obstetrics and Gynaecology, Baba Raghav Das Medical College, Gorakhpur, Uttar Pradesh, India.

Method: Thisis an observational cross sectional study conducted at department of medicine,Baba Raghav Das medical college, Gorakhpur, Uttar Pradesh, India over a period of 1 year; to know the prevalence of subclinical hypothyroidism among 250 T2DM patients diagnosed as per American diabetes association(ADA) criteria. SCH is diagnosed on the basis of American thyroid association (ATA) criteria. All subjects underwent a detailed history, clinical examination and relevant biochemical tests.

Results: The prevalence of subclinical hypothyroidism in T2DM patients was found to be 14% in our study.

Conclusion: The prevalence of SCH was found to be higher in type 2 diabetes mellitus patients in comparison to general population as mentioned in different literature.

Keywords: Type 2 diabetes mellitus (T2DM), Subclinical hypothyroidism (SCH) thyroid dysfunction (TD), thyroid stimulating hormone (TSH)

It has been established that thyroid dysfunction is more prevalent in people with type 1diabetes (T1DM). Autoimmune thyroid disease and type 1diabetes are caused by similar mechanism of dysregulation of immune surveillance and tolerance. American Thyroid

Association / American Association of Clinical Endocrinology (ATA/AACE-2012)1and American Diabetes Association (ADA-2005)2 has given a guideline for screening of thyroid dysfunction in type 1 diabetes patients. But no such guideline exists for screening of thyroid dysfunction in T2DM patients till date.T2DM and thyroid dysfunction both are prevalent in our country and it is observed in common clinical practice that many T2DM patients also have thyroid dysfunction. Controlling hyperglycemia in the presence of underlying thyroid dysfunction poses problem even when it is subclinical. Therefore detection and management of thyroid dysfunction in T2DM patients may prove beneficial.

Numerousepidemiologicalstudies indicate the higher preva lence o f over thypothyro id ism in type 2 diabetesmellitus (T2DM) population than inthe general

3 & 4population. However, therelationship between subcl inical hypothyroidism (SCH) and T2DM iscontroversial. SCH (theslight hypothyroidism state) is asymptomatic but mildelevations inthyroid-stimulating hormone (TSH) withnormal circulating freethyroid

5hormone concentrations are observed. Numerous


© JIMI � APR - JUNE 2018 � VOL. 12 26

studies suggestthatSCH isassociated with hypertension ,highcholesterol, and abnormal homocysteine level and patients withSCH haveahigher riskof metabolic syndrome, atherosclerosis, cardiovascularevents,

6-8andmortality. Presently,controversypersists about indications for treatmentof SCHand whether individuals

9&10should be routinely screened for thisdysfunction.

The aim of present study was to determine the prevalence of subclinical hypothyroidism in T2DM patients, attending the OPD of medicine department of Baba Raghav Das Medical College which is the only tertiary care health facility for Eastern UP and bordering Bihar and Nepal.

Material And MethodThis observational cross-sectional study was conducted on already diagnosed 250 T2DM patients (as per ADA guideline) presenting to the OPD of Medicine Department, Baba RaghavDas Medical College, Gorakhpur from December 2016 to December 2017.Sample Size: Calculated using EPIINFO software version 7 with 95% confidence level and 5% confidence limit and power 80% minimum sample size required is 250.Study tools: Semi-structured questionnaire for demographic and clinical profile of patients.Data analysis: Data entry was done in MS Excel and analyzed using appropriate statistical tests.Inclusion Criteria: All already diagnosed T2DM patients (as per ADA guidelines) presenting to the OPD of Medicine Department, BRD Medical College, Gorakhpur. ADA guidelines for diagnosis of Diabetes Mellitus (DM) in adults are:-

1. A1C �6.5%. The test should be performed in a

laboratory using a method that is NGSP certified and standardized to the DCCT assay.*

2. FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.*

3. 2-h plasma glucose ≥200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.*

4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dl (11.1 mmol/l).*In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing

Exclusion Criteria:-

Non-consenting patients,

Type 1 diabetes mellitus patients,

Critically ill patients,

Diabetic nephropathy patients,

Gestational Diabetes Mellitus patients,

Patients on drug affecting thyroid function,

Patients who underwent thyroid gland surgery.

Ethical Clearance: Ethical permission was taken from the institutional ethics committee of BRD medical college.

Methods of Data CollectionA detailed clinical history such as age, sex, family history of diabetes was recorded. A thorough clinical history regarding diabetes mellitus (onset, duration, lifestyle), any history of long term illness, any previous thyroid dysfunction, previous history of hypertension, any kind of drug therapy, whether the patient was on oral hypoglycaemic agent (OHA) or insulin or both was sought. Personal history of smoking or alcohol intake was taken.

A thorough clinical examination including general physical examination, vitals (pulse, blood pressure, temperature and respiratory rate), anthropometric measurement (weight, height, BMI and waist hip ratio), and systemic examination was carried out. BMI was calculated using Quetlet's index {BMI = weight in kg / (height in meters) 2} and waist hip ratio was measured by Seca 203 Circumference Measuring Tape. .

All selected T2DM patients were then subjected to estimation of HbA1c, serum triglyceride, HDL, serum urea, serum creatinine, and urine routine microscopic. All evaluation was done in the central pathology of the Nehru Hospital, B.R.D. Medical College. HbA1c level was estimated by Ion Exchange High Performance Liquid Chromatography (HPLC) on BIO-RAD-D-10. Lipid profile by enzymatic colorimetric (CHOD-PAP) Trinder End point method on SELECTRA-PRO-M.

Then all the patients were evaluated for thyroid dysfunction by testing thyroid profile (T3, T4 and TSH). T h y r o i d h o r m o n e l e v e l s w e r e m e a s u r e d b y ChemiluminescencentMicroparticle Immunoassay (CMIA) using ARCHITECT TSH ASSAY machine.


© JIMI � APR - JUNE 2018 � VOL. 12 27

Diagnostic Critreria For Thyroid Dysfunction: According to American thyroid association1

DISORDER TSH

(mIU/mL)

Hypothyroidism

>10

Subclinical hypothyroidism 4.50 -10

Normal thyroid function

0.

0.45-4.50

Hyperthyroidism <0.45

Subclinical hypothyroidism was defined as an elevated TSH level with normal serum thyroid hormone levels.

The correlation of prevalence of thyroid disorder with gender distribution, age distribution, HbA1C, duration of diabetes, hypertension, BMI, Waist-hip ratio, usage of OHAs / insulin / both and dyslipidemia (TG & HDL) was then done. The observations and interpretations were recorded and results obtained were statistically analyzed.

Table-1: Prevalence of subclinical hypothyroidism among study subjects

Subclinical hypothyroidism

No. (n=250)

%

Present

35

14.0

Absent 215 86.0

We observed that 35 out of total 250 study subjects with type 2 diabetes had subclinical hypothyroidism. In this study prevalence of subclinical hypothyroidism was found to be 14% in patients of type 2 diabetes.

Table-2:Prevalence of subclinical hypothyroidism among study subjects according to gender

Gender No. of

patients

% Subclinical

hypothyroidism

OR (95%

CI)

p-

value1

Present

Absent

No. % No. % Male 127 50.8

12

9.4

115

90.6

0.45 (0.21-

0.95)

0.03

Female 123 49.2 23 18.7 100 81.3 1.00 (Ref.)

In this study we observed out of 127 male subjects 12 had subclinical hypothyroidism and out of 123 female subjects 23 had subclinical hypothyroidism, therefore the prevalence subclinical hypothyroidism was higher among females (18.7%) compared to males (9.4%). The prevalence of subclinical hypothyroidism was significantly lower in males in comparison to males. (OR=0.45, 95%CI=0.21-0.95, p=0.03).

Table-3: Prevalence of subclinical hypothyroidism among study subjects according to age

Age( in

years)

No. of

patients

% Subclinical hypothyroidism OR

(95%CI)

p-

value1

Present Absent

No.

%

No.

%

<30 7 3.2

0

0.0

7

100.0

-

30-60 188 75.2

24

12.8

164

87.2

0.58 (0.26-

1.28)

0.18

>60 55 21.6 11 20.0 44 80.0 1.00 (Ref.)

In our study we observed that out of 250 subjects, 7 subjects were of less than 30 years of age, and none of them had subclinical hypothyroidism, 188 subjects were between 30 to 60 years of age and out of them 24 had subclinical hypothyroidism and 55 subjects were more than 60 years and out of them 11 had subclinical hypothyroidism. Therefore prevalence of subclinical hypothyroidism was highest in age >60 years (20%) followed by >30-60(12.8%) and <30(0%) years.

Table-4: Prevalence of Subclinical hypothyroidism among study subjects according to HbA1C

HbA1C No. of

patient

% Subclinical

hypothyroidism

OR (95%CI) p-value1

Present

Absent

No.

%

No.

%

<7 105

42

9

8.6

96

91.4

0.42

(0.19-0.95)

0.03

�7 145 58 26 17.9 119 82.1 1.00 (Ref.)

In this study out of 105 patients with HbA1C <7, 9 patients had subclinical hypothyroidism; and out of 145 patients w i t h H b A 1 C > 7 , 2 6 p a t i e n t s h a d s u b c l i n i c a l hypothyroidism. Therefore, in our study we observed that prevalence of subclinical hypothyroidism was

significantly (p=0.03) higher among HbA1C�7 (17.9%)

than HbA1C<7 (8.6%).


© JIMI � APR - JUNE 2018 � VOL. 12 28

Table-5: Prevalence of Subclinical hypothyroidism among study subjects according to BMI

BMI No. of

patient

% Subclinical

hypothyroidism

OR (95%CI) p-

value1

Present

Absent

No.

%

No.

%

<22.9 88 35.2 4 4.5 84 95.5 1.00 (Ref.)

23-24.9 75 30.0

5

6.7

70

93.3

1.50

(0.38-5.80)

0.55

�25 87 34.8 26 29.9 61 70.1 8.95

(2.97-26.97)

0.0001

In this study we observed that 4 out of 88 patients in the BMI range 18-22.9, 5 out of 75 patients in the BMI range 23-24.9, 26 out of 87 patients with BMI >25 had subclinical hypothyroidism. The prevalence of subclinical

hypothyroidism was significantly higher among BMI�25 (OR=8.95, 95%CI=2.97-26.97, p=0.0001).

Table-6: Prevalence of Subclinical hypothyroidism among study subjects according to WHR

WHR No. of

patient

% Subclinical

hypothyroidism

OR (95%CI) p-

value1

Present

Absent

No.

%

No.

%

Central

obesity

93 37.2 26 28.0 67 72.0 6.38 (2.83-

14.36)

0.0001

*

No central

obesity

157 62.8 9 5.7 148 94.3 1.00 (Ref.)

In our study we observed, 26 patients out of 93 patients with central obesity had subclinical hypothyroidism; while only 9 out of 157 patients with no central obesity had subclinical hypothyroidism. Thus the prevalence of subc l in ica l hypothyroidism was found to be significantlyhigher among patients with central obesity (28%) than those with no central obesity (5.7%).(OR=6.38, CI=2.83-14.36, p-value=0.0001)

Table-7: Prevalence of Subclinical hypothyroidism among study subjects according to duration of diabetes

Duration

of diabetes

in years

No. of

patient

% Subclinical

hypothyroidism

OR (95%CI) p-

value1

Present

Absent

No.

%

No

. %

<1 76 30.4 15 19.7 61 80.3 1.65

(0.70-3.86)

0.24

1-5 89 35.6

9

10.1

80

89.9

0.75

(0.29-1.93

0.56

>5 85 34.0 11 12.9 74 87.1 1.00 (Ref.)

In our study we observed that out of 76 patients with<1 year of diabetes of which 15 patients had subclinical hypothyroidism; and out of 89 patients with 1-5 year of diabetes 9 patients hadsubclinical hypothyroidism; out of 85 patients with >5 years of diabetes 11 patients hadsubclinical hypothyroidism. Thus the prevalence of subclinical hypothyroidism among diabetic patients was not significantly (p>0.05) associated with the duration of diabetes.

Table-8: Prevalence of Subclinical hypothyroidism among study subjects according to TG

TG No. of

patients

% Subclinical

hypothyroidism

OR (95%CI) p-

value1

Present

Absent

No.

%

No.

%

High 181 72.4

33

18.2

148

81.8

7.47

(1.74-32.04)

0.002

Low 69 27.6 2 2.9 67 97.1 1.00 (Ref.)

In this study we observed that 181 patients had high TG and out o f them 33 pat ients had subc l in ica l hypothyroidism; 69 patients had low TG out of them only 2 patients hadsubclinical hypothyroidism. Thus the prevalence of subcl inical hypothyroidismwas significantly (p=0.001) higher among high TG groups (18.2%) than low TG groups (2.9%).

Table-9: Prevalence of Subclinical hypothyroidism among study subjects according to HDL

HDLNo. of

patients%

Subclinical

hypothyroidism

Odds ratiop-

value1Present

Absent

No. % No. % High 205 82.0

24

11.7

181

88.3

0.41 (0.18-0.91) 0.02

Low 45 18.0 11 24.4 34 75.6 1.00 (Ref.)

In our study we observed that 205 patients had high HDLout of which 24 patients have subclinical hypothyroidism; and 45 patients had low HDL out of which 16 patients had subclinical hypothyroidism. Thus we observedthe prevalence of subclinical hypothyroidism was significantly (p=0.02) lower among high HDL (11.7%) than low HDL groups (24.4%).


© JIMI � APR - JUNE 2018 � VOL. 12 29

DiscussionThe present institutional cross sectional observational study was conducted over patients of T2DM, who attended the OPD of the department of medicine of B.R.D. medical college Gorakhpur, from December 2016 to December 2017. Patients were selected according to inclusion and exclusion criteria. Detailed history, clinical examination and required laboratory investigations were done. All the study subjects were receiving individualized treatment, such as life style modification, medical nutrition therapy, OHA's or insulin or both.Subclinical hypothyroidism is a common endocrine disorder, but frequently underdiagnosed. SCH is diagnosed mainly based on biochemical parameters rather than clinical findings, defined by a raised serum TSH with a normal serum free T4 level, irrespective of the p r e s e n c e o r a b s e n c e o f c l i n i c a l f e a t u r e s o f hypothyroidism.

Thyroid hormones play an important role in glucose regulation by causing modifications in the circulating levels of insulin and counter-regulatory hormones, intestinal absorption, hepatic production and glucose uptake by peripheral tissues.11The effect of SCH on the glycemic control appears to be controversial. Many studies did not show a statistically significant correlation between thyroid dysfunction and glycemic control. A study done in Greek on patients with type 2 DM revealed a reduced HbA1c level in patients with coexisting hypothyroidism (7.38% compared to 7.81%) but this was not statistically significant.12

Hypothyroidism affects lipid profile in patients with Type 2 DM, but the pattern of lipid profile varies in different studies. A meta-analysis revealed that subclinical hypothyroidism does not seem to be associated with dyslipidaemia.13 A study conducted by Chubb et al did not show any significant relationship between subclinical hypothyroidism and dyslipidaemia14 but, a study conducted by Kim et al found elevated total and LDL cholesterol in diabetics with SCH compared to euthyroid patients.15

The aim of our study was to determine the prevalence of subclinical hypothyroidism among patients with type 2 diabetes mellitus. The present study was conducted on 250 with type 2 DM and found the prevalence of SCH to be 14 % in the diabetic individuals and prevalence was found to be more in females. There was insignificant correlation between the age of the individual and prevalence of SCH. Prevalence of SCH hypothyroidism was higher among patients with uncontrolled diabetes(HBA1C>7), and this was found to be statistically significant. The serum levels of HDL were significantly lower in the SCH group and

serum triglyceride levels were significantly higher in the SCH group. The prevalence of SCH was significantly higher in T2DM patients with increased BMI and central obesity.

ConclusionThis study showed a high prevalence of SCH (14%) in patients of T2DM which was further found to be more in females, elderly patients, patients with uncontrolled diabetes, i.e., HbA1C > 7, patients with BMI > 25and patients with central obesity. Thus,periodicthyroid function testing isnecessary as apart ofdiabetic care. Dyslipidemia was common in T2DM patients with SCH.Finally, whethermetformin forT2DMmay ameliorate SCHin T2DM patients should be studied and whether individualizedlevothyroxine intervention for SCH patientswithT2DM may reduce or delaydiabetic-complications are of interest andworthstudying.

ReferencesATA/AACE guidelines for hypothyroidism in adults, Endrocrpract. 2012;18(6.)Silverstein J, Klingensmith G, Copeland K, Plotnick L, Kaufman F, Laffel L, Deeb L, Grey M, Anderson B, Holzmeister LA, Clark N: Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association (ADA Statement). Diabetes Care 28: 186–212, 2005.DistillerL.A.,PolakowE.S.,JoffeB.I., Type2 diabetesme-l l i t u s a n d h y p o t h y r o i d i s m : t h e p o s s i b l e i n u e n c e ofmetformintherapy.DiabetMed.2014;31(2):172–5.HollowellJG,StaehlingNW,FlandersWD,HannonWH,GunterEW,SpencerCA,etal.SerumTSH,T (4),and thyroidantibod-iesintheUnitedStatespopulation(1988to1994):NationalHealthandNutritionExaminationSurvey(NHANESIII).JClinEndocrinolMetab.2002;87(2):489–99.TunbridgeWM,EveredDC,HallR,AppletonD,BrewisM,ClarkF,etal.Thespectrumofthyroiddiseaseinacommunity:theWhickhamsurvey.ClinEndocrinol(Oxf).1977;7(6):481–93.VanderpumpMP,TunbridgeWM,FrenchJM,AppletonD,BatesD,ClarkF,etal .Theincidenceofthyroid disordersin-thecommunity:atwenty-yearfollowupofthe Whickham Survey.ClinEndocrinol (Oxf).1995;43(1):55–68.KabadiUM.'Subclinicalhypothyroidism'Naturalcourseofthesyndromeduringaprolongedfollow-up study. ArchIntern Med.1993; 153(8):957–6. TunbridgeWM,BrewisM,FrenchJM,AppletonD,BirdT,ClarkF,etal.Naturalhistoryofautoimmune thyroiditis. BrMedJ (ClinResEd).1981;282(6260):258–62.WangC,CrapoLM.TheepidemiologyofthyroiddiseaseandimplicationsforscreeningEndocrinolMetab.Clin.North.Am.1997;26(1):189–218.HakAE,PolsHA,VisserTJ,DrexhageHA,HofmanA,WittemanJC.Subclinicalhypothyroidismisan independentriskfactorfora-therosclerosisandmyocardialinfarctioninelderlywomen:theRotterdam Study.AnnInternMed.2000;132(4):270–8.Suhail MM. Thyroid function tests of type 2 diabetic patients in Baghdad Governorate. Med J Babylon 2014;11:1.Papazafiropoulou A, Sotiropoulos A, Kokolaki A, Kardara M, Stamataki P, Pappas S. Prevalence of thyroid dysfunction among greek type 2 diabetic patients attending an outpatient clinic. Journal of clinical medicine research. 2010 Apr;2(2):75.

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Hueston WJ, Pearson WS.Subclinical hypothyroidism and the risk of hypercholesterolemia. Ann Fam Med 2004; 2(4): 351-5. Chubb SA, Davis WA, Inman Z, Davis TM. Prevalence and progression of subclinical hypothyroidism in women with type 2 diabetes: the Fremantle Diabetes Study. Clinical endocrinology. 2005 Apr 1; 62(4):480-6.

Kim BY, Kim CH, Jung CH, Mok JO, Suh KI, Kang SK. Association between subclinical hypothyroidism and severe diabetic retinopathy in Korean patients with type 2 diabetes. Endocrine journal. 2011;58(12):1065-70.

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© JIMI � APR - JUNE 2018 � VOL. 12 31

Fibromyalgia: A Chronic Conditionthat Remains Underdiagnosed.

Original Article

1 2 3Saxena V, MS , Verma Vijay Deepak, MD , Babu Suresh, MDCorresponding Author: Dr Vijay Deepak Verma

AbstractBackground: Objective: To develop simple and rational approach to patients with chronic widespread pain along with multiple somatic symptoms for diagnosis and management of fibromyalgia patients in suburban population.

Chronic low back pain is an important cause of attendance in orthopaedic, neurology and pain clinic. Most of the time chronic low back pain is associated with psychological component and has to be evaluated in detail by meticulous history, careful examination and battery of radiological and lab investigations. Although this sort of evaluation needs specialized dedicated centres but in developing country it is usually not possible not only due to lack of infrastructure but because of financial constraints of suburban population. Fibromyalgia is an important cause of chronic low backache which is prevalent more than its consideration. Fibromyalgia is characterized by widespread aching of more than three

Introduction

1. Associate Professor, Department of Orthopaedics, Government Institute of Medical Sciences, Greater Noida. 2. Assistant Professor, Department of Medicine, Government Institute of Medical Sciences, Greater Noida 3. Senior Consultant, Department of Medicine, Government Institute of Medical Sciences, Greater NoidaCorresponding Author: Dr Vijay Deepak Verma

Method: : 54 patients with chronic low back pain asked for somatic symptoms and evaluated using criteria based on widespread pain index (WPI) and symptoms severity scale (SS). Twenty Four patients with multiple somatic symptoms could be diagnosed using these criteria even in absence of tender point criteria of American college of Rheumatology (ACR) 1990.

Results: Approximately 54.1 % of patients of fibromyalgia, not satisfying the American College of Rheumatology (ACR) 1990 classification criteria could be diagnosed by criteria using Widespread Pain Index (WPI) and symptom severity (SS) scale. Revised Fibromyalgia Impact Questionnaire (FIQR) used for initial and subsequent assessment showed average improvement from 60.9 to 18.9 after 6 months of treatment with pharmacological therapy.

Conclusion: The patients with chronic widespread pain along with marked symptoms variability need consideration of Fibromyalgia for possible diagnosis especially in the absence of secondary cause for these symptoms. Revised fibromyalgia diagnostic criteria are simple and reproducible means of diagnosis of fibromyalgia which lead to better prospects of managing this crippling condition.

Keywords: Chronic widespread pain, symptom severity scale, fibromyalgia impact questionnaire.

months duration, presence of multiple tender points in 1soft tissues and disturbed sleep .

Fibromyalgia (Fibrositis) is a term currently used for patients with chronic widespread musculoskeletal pain along with psychosomatic symptoms for which no alternative cause can be identified, However, lack of finding of inammation in the connective tissues led to the change in the name of entity from Fibrositis to Fibromyalgia. Diversity of symptoms leads to visit of these individuals to different clinical sub specialities for variegated symptoms apart from orthopod for backache.American college of Rheumatology (ACR) criteria for fibromyalgia requires an individual to have both a history of chronic widespread pain and finding of 11 or more of

2possible 18 tender points on examination . The presence of multiple tender points is most specific criterion although few Authors disagree on the number of tender points required for the diagnosis of fibromyalgia. In addition to chronic widespread pain patients with fibromyalgia often reports fatigue, non-restorative sleep, cognitive


© JIMI � APR - JUNE 2018 � VOL. 12 32

3,4,5.dysfunction, stiffness and mood disturbances Wolfe et al laid down criteria for clinical diagnosis of fibromyalgia that do not require tender point examination diagnostic confirmation and depend upon presence of widespread

pain index (WPI) �7 and symptom severity (SS) scale

score �5 or WPI 3-6 and SS6 scale score �9. However,

symptoms should last for 3 months at similar level in the absence of disorder that would otherwise explain the pain7.

Research shows that there are changes in central nervous system causing the brain to process signals abnormally leading to augmented pain and sensory symptoms in these patients. One of the earliest finding in this regard was that the tenderness in fibromyalgia is not confined to

8,9.tender points, but instead extends throughout the bodyThe diversity of symptoms and lack of awareness make diagnosis of this disease difficult. Apart from this, there are limited studies over fibromyalgia in Indian subcontinent. So, it is crucial to create a framework for evaluation of patients with chronic pain along with multiple somatic symptoms as many a times fibromyalgia is co-morbid with other conditions and optimum management will require simultaneous consideration of both conditions. The present prospective study comprises 24 patients with fibromyalgia who were diagnosed by either ACR 1990 or Wolfe diagnostic criteria and managed by pharmacological and non-pharmacological means. The results were assessed by revised fibromyalgia impact

10Questionnaire (FIQR) .

Material and methodsThis study was conducted by authors to evaluate the patients presenting with chronic widespread pain, multiple tender points along with fatigue, sleep disturbance, cognitive symptoms and multiple somatic symptoms for diagnosing patient of fibromyalgia as per ACR 1990 or clinical diagnostic criteria by Wolfe et al.A total of 54 individuals with chronic backache (>3 months) were evaluated for pain and non-pain symptoms, overlapping syndromes, psychosocial history, presence of tender points followed by laboratory and radiographic assessment to exclude the patients with secondary fibromyalgia syndrome. The diagnosis of fibromyalgia was made by either ACR criteria or on clinical grounds. An informed consent was obtained from patients to be included in this study.

Pain of fibromyalgia is chronic i.e. present on most of the days for at least three months and involves muscles, joints and even skin. The pain is poorly localized, difficult to ignore, severe in nature and interfere with routine works. The Non-pain symptoms includes stiffness, fatigue, sleep disturbance, cognitive dysfunctions, anxiety and

11depression . Pain, stiffness and fatigue are often worsened by physical inactivity. Sleep disturbances include difficulty in falling asleep, staying asleep, early and un-refreshed awakening. Regional and localized syndromes that overlap with fibromyalgia are tension/ migraine headache, temporomandibular joint syndrome, oesophageal dysmotility, irritable bowel syndrome, interstitial cystitis, female urethral syndrome and vulvodynia.

Palpation of tender points is typically performed using the thumb and with a force that causes blanching from thumb nail. The criteria require 11 out of 18 tender points to elicit pain to identify patients with fibromyalgia. However, we relied on clinical diagnostic criteria where tender point criteria could not be met.

The patients with complaint of chronic widespread pain are assessed by judicious use of investigations to exclude the common entities in the differential diagnosisThe functional assessment was done by revised fibromyalgia impact questionnaire in Hindi or English as per patient's educational status (FIQR). The patients were asked to fill the FIQR form and show it to assistant for completeness and seeking help for understanding the questions in case of difficulty if any. The patients with poor educational status required more help in understanding the questionnaire and grading.

Once clinico-diagnostic evaluation is done, the patient is educated about the importance of adherence to all aspects of treatment program including medication and non-pharmacological therapies like yoga, exercise and sleep hygiene. Then patients were started on pregabalin along with tramadol with or without amitryptiline and duloxetine for symptomatic management. Dose of pregabalin was increased and duloxetine is added as per patient's response to treatment. The patients were followed up at weekly interval until 6 months and assessed at every follow up by FIQR.


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Table showing clinical profile of patients diagnosed for fibromyalgia either by ACR fibromyalgia classification or revised fibromyalgia criteria of wolfe et al. Their progress was evaluated by FIQR at 6 months.

ResultsIn our study 24 patients out of 54 patients with chronic backache could be diagnosed for fibromyalgia with either of criteria. Most of the patients were not fulfilling the tender point criteria of ACR 1990 but fibromyalgia criteria of Wolfe. Most of the patients were in 30-40 years age range (average 33 years) and were females (F:M ratio 8:1). The duration of symptoms was in range of 4months to 10 years (average 39 months) at the time of presentation. Majority of patients consulted other clinicians for their variety of symptoms at the time of presentation. 54.1 % patients who were diagnosed by fibromyalgia criteria

could met ACR 1990 criteria contrary to opposite. Backache, neck pain, sleep disturbances, cognitive dysfunction and irritable bowel symptoms were present in majority of patients. Average Widespread pain index was 13.4 while average symptom severity scale was 7.3. Majority of patients could be treated with Tramadol, Amitryptiline and Pregabalin, however few patients required addition of duloxetine for symptomatic improvement. Average functional status by FIQR was 60.9 at presentation which improved to 18.9 after 6 months of treatment.


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ResultsThe diagnosis of somatic syndromes that lack objective physical or laboratory features or well-characterized pathologic findings remains challenge for clinicians. The ACR fibromyalgia classification criteria were accepted for chronic widespread pain, which was present for more than 3 months and no other disease could be attributed for the chronic widespread pain. These ACR classification criteria performed well in specialty clinics, However, they have not been widely embraced in primary care as the tender point criteria of ACR fibromyalgia classification was difficult to execute at primary care level and that too, not always met to make diagnosis. The case definition of fibromyalgia has changed somewhat with increasing recognition of the importance of cognitive problems and somatic symptoms, factors that were not even considered in the 1990 ACR classification criteria. Wolfe et al laid down new diagnostic criteria, identified 2 variables that best defined fibromyalgia and its symptom spectrum: the WPI and the composite SS scale. The WPI, which strongly correlated with the tender point count and the SS scale, a composite variable composed of physician-rated cognitive problems, unrefreshed sleep, fatigue, and somatic symptom count to measure fibromyalgia symptom severity; best identified patients diagnosed with the ACR classification criteria6.The diagnosis of these patients with fibromyalgia becomes more difficult in the setting of primary health care and even speciality centres with sub urban or rural population, who complains of primary symptoms like chronic backache and neckache. These patients do not disclose their other symptoms as they think these irrelevant and unrelated, until asked specifically. So, every patient with chronic backache should be asked specifically for generalized widespread pain, sleep disturbance, cognitive dysfunction and multiple somatic symptoms even in the absence of tender point criteria of ACR fibromyalgia classification. These patient with fibromyalgia responds well to pregabalin and amitryptiline. Some patients, unresponsive of these drugs or with high initial FIQR may require duloxetine as well. Non-pharmacological means like sleep hygiene, moderate exercises and yoga contribute positively in the management of fibromyalgia, so should be advised appropriately.

ConclusionFibromyalgia is more prevalent than understood among Indian population. Lack of awareness, complexity and multiplicity of symptoms, unavailability of specialized rheumatology clinics make it underdiagnosed. Early and prompt suspicion about the disorder, in patients with generalized widespread pain along with sleep disturbance, cognitive dysfunction and multiple somatic symptoms, has to be undertaken for timely diagnosis.

ReferencesSmythe HA. Fibrositis and other diffuse musculoskeletal syndromes. In: Textbook of Rheumatology. WN Kelley, ED Harris Jr., S Ruddy, CB Sledge, eds. (1st ed.) Philadelphia: WB Saunders, 1981; 485-93.Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicentre criteria committee. Arthritis Rheum 1990; 33(2):160-72.Arnold LM, Crofford LJ, Mease PJ, et al. Patient perspectives on the impact of fibromyalgia. Patient Educ Couns. 2008; 73(1):114-120.Choy EH, Mease PJ. Key symptom domains to be assessed in fibromyalgia (outcome measures in rheumatoid arthritis clinical trials). Rheum Dis Clin North Am. 2009; 35(2):329-337.Arnold LM, Clauw DJ, McCarberg BH; the FibroCollaborative. Improving the recognition and diagnosis of fibromyalgia. Mayo Clin Proc. 2011; 86(5):457-464.Wolfe F, Clauw DJ, Fitzcharles MA et al. The American College of Rheumatology preliminary diagnosis criteria for fibromyalgia and measurement of symptom severity. Arthritis Care Res 2010; 62: 600-610. Bondy B, Spaeth M, Offenbaecher M, et al. The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia. Neurobiol Dis 1999; 6(5):433-439.Granges G, Littlejohn G. Pressure pain threshold in pain-free subjects, in patients with chronic regional pain syndromes, and in patients with fibromyalgia syndrome. Arthritis Rheum 1993; 36(5):642-646.Wolfe F, Ross K, Anderson J, et al. Aspects of fibromyalgia in general population: sex, pain threshold and fibromyalgia symptoms. J Rheumatol 1995; 22(1):151-156.Bennett RM, Friend R, Jones KD, Ward R, Han BK, Ross RL. The revised fibromyalgia impact questionnaire (FIQR): validation and psychometric properties. Arthritis Res Ther 2009; 11: R120.Yunus MB, Masi AT, Aldag JC. A controlled study of primary fibromyalgia syndrome: clinical features and association with other functional syndromes. J Rheum 1989; 16:62-71.

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An Epidemiological Study of Hepatitis C Infection InPatients Attending Tertiary Care Hospital In North India

Original Article

1 2 3 4 5DavidLalrutsanga , Verma.V , Singh.M , Himanshu Dandu , Ajay Kumar ,5Rohin Saini (Corresponding Author)

AbstractHepatitis C infection is a liver disease caused by the hepatitis C virus (HCV). It is one of the important risk factorfor causing chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver failure. In India reported prevalence rates vary widely in range of 0.09%-2.02%. The purpose of the study was to establish current sero-prevalence of HCV among patients attending outpatient department in tertiary care hospitals of Aizawal and Lucknow.

Hepatitis C virus (HCV) belongs to Flaviviridae family.It is known risk factor for development of chronic hepatitis, cirrhosis, and hepatocellular carcinoma and is responsible

[1]for significant morbidity and mortality. Majority of patients develop chronic disease after acute infection which depends upon factor inuencing interaction between host and the virus. HCV infection is usually asymptomatic so only few patients are diagnosed during acute phase.Spontaneous viral clearance is rare and thus the most infected individuals proceed to chronic hepatitis.Even those patients who develop chronic HCV infection often undiagnosed because the infection remains

[2]asymptomatic. Due to lack of anti-HCV screening measures in our country, HCV infection is on a rising trend courtesy of unscreened donors,intravenous drug abusers,unsafe injection practices in peripheral hospitals and unsterile techniques in the hospitals which form the

Introduction

1. Assistant Professor, Dept of Medicine, Mizoram institute of medical education and research,Falkawn,Mizoram.2. Resident, Dept of Medicine, King George medical university, lucknow3. Associate professor,Dept of medicine,King George medical university Lucknow, Uttar Pradesh

Method: : A retrospective study was carried out in patients attendingout patient department ofKing George Medical University, Lucknow and Community hospital; Aizawalfrom January 2014 to September 2018.Serum samples were collected and screened for antibody against HCV by ELISA method.The study highlighted various epidemiological aspects such as sex distribution, mode of transmission and age group predominantly involved.

Result: 1382 patients were tested positive for Anti-HCV antibodies(762 patients from community hospital, Aizawal and 620 patients from KGMC, Lucknow).Aizawal group had 80%(610) males and 20%(152) femaleswhile lucknow data revealed 57%(353) males and 47%(267) females, the most common affected age group was 31-50 years in Aizawal group and was slightly young in lucknow group 25-45 years. Both groups had most common genotype 3 followed by genotype 1.Most common mode of transmission was surgical intervention for females in both groups while parenteral(iv drug user, blood transfusion, needle stick) was the most common mode of transmission in males from Aizawal Group while roadside shave was the most common cause of transmission in males from lucknow group.

Conclusion: The present study highlights current scenario of HCV infection in North Indian tertiary care hospital and helps assess prevalence of most common genotype available and may help to detect target group for early detection and treatment in order to prevent complication and further transmission of infection.

major contributors of the disease pool. Prevention is the only cure for Hepatitis C as the medications are expensive and there are no vaccinations available. Prevalence of HCV infection is variable. Higher prevalence is found in developing countries where facilities for treatment and

[3]diagnosis are limited .Global prevalence of HCV [4]infection is upto 3% of the world's population. In India

[5-reported prevalence rates vary widely in range of 1-1.9% 6].Chronic infection with hepatitis C virus (HCV) has emerged as a major public health problem since past


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decades. Globally, an estimated 71 million people have [4,7]chronic hepatitis C infection . A significant number of

chronically infected individuals will develop cirrhosis or hepatocellular cancer. Although antiviral medicines can cure more than 95% of persons with hepatitis C infection, thereby reducing the risk of death from liver cancer and cirrhosis, access to diagnosis and treatment is low.Lack ofa vaccine against hepatitis C and carcinogenic property

[8]of virusadds further to the evolvingproblem.Most common modes of infection with Hepatitis C are usually parenteral. This can be via injection drug use, unsafe injection practices and the transfusion of blood and

[9]blood products . There is a deficiency of data related to the epidemiological aspects of HCV infection in North India and thus the present study was done/undertaken with the objective to understand and assess the prevalence of HCV patients attending the outpatient department in tertiary care hospitals in North India.

Materials and methodThis retrospective study was carried out in patients attending community hospital, Aizawal and KGMU Lucknow from January 2014 to September 2018 along. Blood samples of all patients for HCV testing were collected and sent to the department of Microbiology. Serum samples were collected and screened for anti HCV antibodies by ELISA method. The test procedure and interpretation of result was done according to standard protocol and manufacturer's instructions. The test results were noted in a proforma and subjects who tested positive for the anti-HCV screening testwere contacted for clinical evaluation.

ResultsWe found HCV antibodies positive in 762 patients from Aizawal and 620 patients from Lucknowwhich includes 610 males and 152 femalesfrom Aizawal and 420 males and 200females respectively. Seroprevalence was higher in males compared to females in both Aizawal and lucknow(80% and 53% respectively) the most common affected age group was 31-50years in Aizawal cohort while it was 25-45 years in Lucknow population positive for HCV antibodies.Most common genotype was genotype 3. The main risk factor for HCV infection is surgery (49.0%%) and the least common risk factor is sexual (2.6%) in the data obtained from KGMC while CHC Aizawal showed main risk factor as Parenteral injections and least common mode of transmission as vertical transmission, Our study revealed that, amongst females, surgical intervention (92.9%) was the main risk factor while in male, road side shave (75.6%) is the main risk factor from patients in Lucknow. In data obtained from Aizawal,both male and females acquire HCV from parenteral routes. In our study, the most frequent

genotype in north Indian population is genotype 3 followed by 3a, 1 and 4. This was concurrently established by data obtained from both hospitals.

DiscussionHepatitis C virus belongs to Flaviviridae family and is responsible for hepatitis C infection, chronic liver disease

[1-2]and hepatocellular carcinoma. Wide variation of epidemiology across various parts of globe and country emphasizes the importance of prevalence studies of this disease.It is difficult to treat HCV because of poor compliance of patients,continuation of risk factors like drugs, alcohol intake,noncompliance with medications

[9]and high risk sexual practices. Recently the number of treated cases have increased courtesy RSBY scheme since

[10] 2017. In India, the HCV infection spreads mainly due to inability to screen all blood products for viral RNA along with other means of parenteral transmission such as unsterile precautions in surgical interventions, unsafe therapeutic injections, injection drug users, unprotected sex with infected partner, and health care associated procedures. There is an urgent need of awareness among the medical care providers about safe injection and other medical or surgical procedures, especially in smaller towns and in rural settings where injectable therapies or dental procedures may be performed by untrained individuals using unsterilized syringes or equipment. In India, it is a widely held belief that intramuscular injections are more effective than oral medications thus exposing the population to the risk of unnecessary

[11]injections . HCV genotypes show differing distributions in different geographic regions.In developed countries such as United States, about 70% of cases are caused by genotype 1 followed by (20%) by genotype 2, and 1% by

[12]each of the other genotypes. Genotype 1 is also the most [13]common in South America and Europe. In India,

g e n o t y p e 3 h a s b e e n p r e d o m i n a n t i n t h e Northern,[14]while in South India, genotypes 1 and 3 have been reported in decreasing order of frequency. HCV genotype 4 and 6 have been reported exclusively from

[15,21,22]South India. Genotype 3 has also been reported to be the commonest type from the neighboring countries of Nepal and Pakistan, while in the eastern countries of Thailand, Vietnam and Japan, genotype 1 is the most

[16]prevalent type. Knowledge of regional distribution of HCV genotypes is important since this could inuence configuration of diagnostic assays as well as vaccine designs.In accordance with earlier published data from northern regions of India, we observed type 3 to be the commonest type in all risk groups followed by type 1 and 2.This was in contrast to studies done in north in earlier

[24]decade where type 3 and 2 were most prevalent. However, within genotype 3(72.9%), we observed that


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subtype 3a (8.2%), the current most prevalent type as reported in all previous reports from this region, is still the predominant subtype compared to subtype 3b (1.9%).this

[17]differed from views of other study which stated that subtype 3a is being replaced by subtype 3b. We also found a lower frequency of subtype 1b (0.6%) as compared to previous studies where it was higher (5.5-8.16%). [18]Recently, a study in Venezuela demonstrated replacement of HCV genotype 1b by genotype 2 over a 10-

[18]year period. Any change in distribution of HCV genotypes/subtypes must be monitored as this can have serious therapeutic implications.For physicians, knowing the genotype of Hepatitis C is helpful in deciding type and duration of therapy.Several clinical trials of Pegylated interferon/ribavirin therapy have revealed significant differences in response rates for

[19]the various HCV genotypes. However with shift to pangenomic direct antiviral agents these differences have less significant impact.Injectable therapy was still prevalent form of therapy in earlier years of our study(2014-2016) Individuals with genotypes 2 and 3 tend to respond better with therapy including alpha interferon or the combination therapy of alpha interferon and

[19]ribavirin than individuals with genotype 1. One probable reason for more treatment failures with HCV viral specific cause suchas efficient replication ability enabling it to establish higher viral RNA and other errors


© JIMI � APR - JUNE 2018 � VOL. 12 38

Gender NumberAizawal Number kgmc Male 610 420 Female 152 190

of human end involving poor compliance,continuation of intravenous drug use and incomplete assessment at

[20]ignition of therapy.It has earlier been reported that HCV genotype distribution varies with age. In a study from Pakistan, subtypes 1a/1b were seen more commonly in younger patients, while subtypes 2a/2b and 3a/3b were more

[16]prevalent in older patients. However in our study the Lucknow group had slightly younger but comparable population to Aizawal group and depicted that patients in North India generally are infected between 20-40 years of age. We found a higher percentage 56.5% and 72.9% of genotype 3 (3a/3b) mean age of 20-40 yr old in this study in Aizawal and Lucknow respectively. There is evidence suggesting that different types of HCV genotypes/ subtypes may be associated with different transmission routes.In this study, we didn't find any significant genotypic association with specific route of transmission. In our study surgery is the main (primary/leading) risk factor in females from Lucknow group and Aizawal group. In male patientsshaving from roadside barbers is the main risk factor in Lucknow groupwhile parenteral mode of transmission(80%intravenous drug users and blood transfusion)was the main risk factor in Aizawal group. Improvement in hand hygiene and barrier precaution methods can help reduce transmission of HCV virus.

ReferencesHanafiah KM, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of

age�specific antibody to HCV seroprevalence. Hepatology.

2013 Apr 1;57(4):1333-42.Robertson B, Myers G, Howard C, Brettin T, Bukh J, Gaschen B, Gojobori T, Maertens G, Mizokami M, Nainan O, Netesov S. Shin i T, Simmonds P, Smith D, Stuyver L, Weiner A: Classification, nomenclature, and database development for hepatitis C virus (HCV) and related viruses: proposals for standardization. International Committee on Virus Taxonomy. Arch Virol. 1998;143(12):2493-503.Preeti, B., Mindolli, Manjunath, P., Salmani. 2015. Seroprevalence of Hepatitis C Virus in a Tertiary Care Centre in Vijaypur, Karnataka, India. Int. J. Curr. Microbiol. Appl. Sci., Volume 4 Number 10: pp. 956-959Who hepatitis C fact sheet updated July, 2016.Anantharamu T, Sharma S, Sharma AK, Gupta AK, Dahiya N, Brashier DB. A review of the current anti-HCV therapy: Are we finally ready for interferon-free regimens. International Journal of Nutrition, Pharmacology, Neurological Diseases. 2014 Dec 1;4(5):6.Mukhopadhyaya, A. 2008. Hepatitis C in India. J. Biosci., 33: 465–473.Razavi H, ElKhoury AC, Elbasha E, Estes C, Pasini K, Poynard T, Kumar R.Chronic hepatitis C virus (HCV) disease burden and cost in the United States. Hepatology. 2013 Jun;57(6):2164 70.van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, Duarte-Rojo A, Heathcote EJ, Manns MP, Kuske L, Zeuzem S. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis . Jama. 2012 Dec 26;308(24):2584-93.

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Chen SL, Morgan TR. The natural history of hepatitis C virus (HCV) infection. International journal of medical sciences. 2006;3(2):47.Devadasan N, Seshadri T, Trivedi M, Criel B. Promoting universal financial protect ion: evidence from the RashtriyaSwasthyaBima Yojana (RSBY) in Gujarat, India. Health Research Policy and Systems. 2013 Dec;11(1):29.Raghuraman S, Abraham P. HCV genotyping in India-Quo Vadis? Indian J Med Res 2004;119:9-11.Wilkins T, Malcolm JK, Raina D, Schade RR. Hepatitis C: Diagnosis and treatment. Am Fam Physician 2010;81:1351-7. Rosen HR. Clinical practice. Chronic hepatitis C infection. N Engl J Med 2011;364:2429-38.Hissar SS, Goyal A, Kumar M, Pandey C, Suneetha PV, Sood A, et al. Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic l i v e r d i s e a s e . J M e d V i r o l 2 0 0 6 ; 7 8 : 4 5 2 - 8 . Valliammai T, Thyagarajan SP, Zuckelmam AJ, Harrison TJ. Diversity of genotype of hepatitis C virus in southern India. J Gen Virol1995;76:711-6. Idrees M, Riazuddin S. Frequency distribution of hepatitis C virus genotypes in different regions of Pakistan and their possible routes of transmission. BMC Infect Dis 2008;8:69. Chakravarti A, Dogra G, Verma V, Srivastava AP. Distribution pattern of HCV genotypes and its association with viral load. Indian J Med Res 2011;133:326-31. Pang PS, Planet PJ, Glenn JS. The evolution of the major hepatitis C genotypes and correlates with clinical response to interferon therapy. PLoS One 2009;4:e6579.

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Dusheiko G, Schmilovitz-Weiss H, Brown D, McOmish F, Yap PL, Sherlock S, et al. Hepatitis C virus genotypes. An investigation of type specific differences in geographic origin and disease. Hepatology 1994;19:13-8.Chakraborty A, Pramanik SB, Roy DS, Sarkar S, Chakraborty M, Nandi A. A retrospective study on the sero-prevalence of Hepatitis C infection in a Tertiary Care Hospital in Kolkata, India. Int J Curr Microbiol App Sci. 2015;4(3):115-23.Chandra M, Khaja MN, Farees N, Poduri CD, Hussain MM, Aejaz MH, Habibullah CM. Prevalence, risk factors and genotype distribution of HCV and HBV infection in the tribal population: a community based study in south India. Tropical gastroenterology: official journal of the Digestive Diseases Foundation. 2003;24(4):193-5.Gowri V, Chandraleka C, Vanaja R. The current seroprevalence of hepatitis C virus in a tertiary care centre in Vellore, Tamil Nadu. Indian journal of community medicine: official publication of Indian Association of Preventive & Social Medicine. 2012 Apr;37(2):137.Hazari, S., Panda, S.K., Gupta, S.D., Batra, Y., Singh, R., Acharya, S.K. 2004. Treatment of hepatitis C virus infection in patients of northern India. J. Gastroenterol. Hepatol., 19: 1058 65.

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ConclusionIn conclusion,we would like to say that hepatitis C is a treatable andpreventabledisease provided patients are educated about early detection,modes of communication and early treatment and compliance to medication as these methods are economical and far better in preventing chronic liver disease and hepatocellular cancer and decreasing transmission. Genotype 3 is still the predominant genotype in the northern region of India. One must press hard upon the fact prevention is always better with regard to Hepatitis C as there are no vaccinations or post exposure prophylaxis for the virusalong with paucity of symptoms in acute phase of illness which further delays its detection and treatment.It is often that difficulties too arise in treatment aspect due to difficulty in diagnosis, poorcompliance of patient s to medication along with continuation of high risk factors thereby contributing to the circulating pool of hepatitis C.

JIMIupchapterapi.com/uploaded/journalPdf/journal_pdf_7_3242.pdf · Dr. Anubha Srivastava Dr. Abha Gupta Governing Body ASSOCIATION OF PHYSICIANS OF INDIA NOIDA CHAPTER Governing Body

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