Introduction

IMPAIRED FASTING GLUCOSE AND IMPAIRED GLUCOSE TOLERANCE IN OVERWEIGHT AND OBESE INDIVIDUALS AND THE ROLE OF EXERCISE AND WEIGHT REDUCTION TO IMPROVE GLYCEMIC CONTROL

Submitted by

Dr.NAGESWARA RAO ADAPALA MBBS, DNB

Admission number 9277/DFID/2011

A PROJECT REPORT SUBMITTED FOR THE DISTANCE

FELLOWSHIP IN DIABETOLOGY

CHRISTIAN MEDICAL COLLEGE

VELLORE-632004 TAMIL NADU, INDIA

DECLARATION

I hereby declare that this project report entitled “Impaired fasting glucose and impaired glucose tolerance in overweight and obese individuals and the role of exercise and weight reduction to improve glycemic control” has been prepared by me in partial fulfillment of the regulations governing the award of Distance Fellowship in Diabetology (DFID) .

Place : hyderAbad

Date :

Dr .Nageswara rao adapala Mbbs,DNB

Adm no: 9277/DFID/2011

ACKNOWLEDGEMENT

I am extremely fortunate to have Dr. Lakshmi and Dr.Sai Ram as my collegues . I express a deep

sense of gratitude for their advice and help throughout the period of study.

I am grateful to Microsoft office 2007 which made my work easier .

Above all I thank the patients who have co-operated with me in all respects while being

subjected to the study.

INDEX

1.INTRODUCTION – BACK GROUND -01

2.AIMS & OBJECTIVES -27

3.MATERIALS & METHODS -28

4.TERMS USED IN MASTER SHEET AND RESULTS -29

5.RESULTS -30

6.DISCUSSION -37

7.CONCLUSIONS -39

8.BIBLIOGRAPHY -40

9.MASTER SHEET

INTRODUCTION

Diabetes mellitus (DM) refers to a group of common metabolic disorders that share the

phenotype of hyperglycemia. Several distinct types of DM are caused by a complex interaction

of genetics and environmental factors. Depending on the etiology of the DM, factors

contributing to hyperglycemia include reduced insulin secretion, decreased glucose utilization,

and increased glucose production. The metabolic dysregulation associated with DM causes

secondary pathophysiologic changes in multiple organ systems that impose a tremendous burden

on the individual with diabetes and on the health care system.

DM predisposes to end-stage renal disease (ESRD), nontraumatic lower extremity amputations,

adult blindness,cardiovascular diseases. With an increasing incidence worldwide, DM will be a

leading cause of morbidity and mortality for the foreseeable future.

CLASSIFICATION

DM is classified on the basis of the pathogenic process that leads to hyperglycemia, as opposed

to earlier criteria such as age of onset or type of therapy. The two broad categories of DM are

designated type 1 and type 2. Type 2 DM is preceded by a period of abnormal glucose

homeostasis classified as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).

Table -1 Etiologic Classification of Diabetes Mellitus

I. Type 1 diabetes (beta cell destruction, usually leading to absolute insulin deficiency)

A. Immune-mediated

B. Idiopathic

II. Type 2 diabetes (may range from predominantly insulin resistance with relative insulin

deficiency to a predominantly insulin secretory defect with insulin resistance)

III. Other specific types of diabetes

A. Genetic defects of beta cell function characterized by mutations in:

1. Hepatocyte nuclear transcription factor (HNF) 4 (MODY 1)

2. Glucokinase (MODY 2)

3. HNF-1 (MODY 3)

4. Insulin promoter factor-1 (IPF-1; MODY 4)

5. HNF-1 (MODY 5)

6. NeuroD1 (MODY 6)

7. Mitochondrial DNA

8. Subunits of ATP-sensitive potassium channel

9. Proinsulin or insulin

B. Genetic defects in insulin action

1. Type A insulin resistance

2. Leprechaunism

3. Rabson-Mendenhall syndrome

4. Lipodystrophy syndromes

C. Diseases of the exocrine pancreas—pancreatitis, pancreatectomy, neoplasia, cystic fibrosis,

hemochromatosis, fibrocalculous pancreatopathy, mutations in carboxyl ester lipase

D. Endocrinopathies—acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma,

hyperthyroidism, somatostatinoma, aldosteronoma

E. Drug- or chemical-induced—glucocorticoids, vacor (a rodenticide), pentamidine, nicotinic

acid, diazoxide, -adrenergic agonists, thiazides, hydantoins, asparaginase, -interferon, protease

inhibitors, antipsychotics (atypicals and others), epinephrine

F. Infections—congenital rubella, cytomegalovirus, coxsackievirus

G. Uncommon forms of immune-mediated diabetes— "stiff-person" syndrome, anti-insulin

receptor antibodies

H. Other genetic syndromes sometimes associated with diabetes— Wolfram's syndrome, Down's

syndrome, Klinefelter's syndrome, Turner's syndrome, Friedreich's ataxia, Huntington's chorea,

Laurence-Moon-Biedl syndrome, myotonic dystrophy, porphyria, Prader-Willi syndrome

IV. Gestational diabetes mellitus (GDM)

Abbreviation: MODY, maturity-onset diabetes of the young.

Source: Adapted from American Diabetes Association, 2011

EPIDEMIOLOGY

The worldwide prevalence of DM has risen dramatically over the past two decades, from an

estimated 30 million cases in 1985 to 285 million in 2010. Based on current trends, the

International Diabetes Federation projects that 438 million individuals will have diabetes by the

year 2030. Although the prevalence of both type 1 and type 2 DM is increasing worldwide, the

prevalence of type 2 DM is rising much more rapidly, presumably because of increasing obesity,

reduced activity levels as countries become more industrialized, and the aging of the population

In 2010, the prevalence of diabetes ranged from 11.6 to 30.9% in the 10 countries with the

highest prevalence (Naurua, United Arab Emigrates, Saudi Arabia, Mauritius, Bahrain, Reunion,

Kuwait, Oman, Tonga, Malaysia—in descending prevalence; There is considerable geographic

variation in the incidence of both type 1 and type 2 DM. Scandinavia has the highest incidence of

type 1 DM (e.g., in Finland, the incidence is 57.4/100,000 per year). The Pacific Rim has a much

lower rate of type 1 DM (in Japan and China, the incidence is 0.6–2.4/100,000 per year);

Northern Europe and the United States have an intermediate rate (8–20/100,000 per year).

Top Ten Countries for Estimated Number of Adults with Diabetes in

Millions

Country 1995 Country 20251 India 19.4 India 57.22 China 16.0 China 37.63 U.S 13.9 U.S 21.94 Russian Federation 8.9 Pakistan 14.55 Japan 6.3 Indonesia 12.46 Brazil 4.9 Russian Federation 12.27 Indonesia 4.5 Mexico 11.78. Pakistan 4.3 Brazil 11.69 Mexico 3.8 Egypt

10 Ukraine 3.6 Japan 8.5All other Countries 49.7 103.6

Total 135.3 300.0

Much of the increased risk of type 1 DM is believed to reflect the frequency of highrisk human

leukocyte antigen (HLA) alleles among ethnic groups in different geographic locations. The

prevalence of type 2 DM and its harbinger, IGT, is highest in certain Pacific islands and the

Middle East and intermediate in countries such as India and the United States. This variability is

likely due to genetic, behavioral, and environmental factors. DM prevalence also varies among

different ethnic populations within a given country.

The global burden due to diabetes is mostly contributed by type 2 diabetes which constitutes 80-

95% total diabetic population.nearly 70% of the people with diabetes live in developing

countries.

The largest number of diabetes are in the 40-59 age groups (132 million in 2010 ) which is

expected to rise further .By 2030 there will be more diabetic people in the 60-70 age groups (196

million)

Type 2 DM in children is becoming common in many countries ,especially so among asian

populations.

PREVALENCE OF DIABETES IN INDIA

The prevalence of diabes in India in 1970’s was 2.3% in urban and 1.55 in rural areas, as shown

by multicentric study by the Indian Council Of Medical Research (ICMR). In 2000s the

prevalence has risen to 12-19% in urban areas and to 4% to 9% in rural areas. A study from rural

Andhra Pradesh reported a prevalence of 13.2%

India which has a large pool of pre –diabetic subjects ( IGT and IFG) shows a rapid conversion

of these high risk subjects to diabtes.the Indian diabetes prevention programme -1 (IDPP-1) has

shown an annual incidence of approximately 18% among subjects with IGT.

Studies of the Prevalence of Niddm in India.*

Year Author (s) Ref PlacePrevalence (%)DM -IGT / IFG

1971 Tripathy et al Cuttack 1.2 ( U)1972 Ahuja et al 17 New Delhi 2.3 (U )1979 Johnson et al Madurai 0.5 ( U)1979 Gupta et al Multicentre 3.0 (U)1984 Murthy et al Tenall 4.7 ( U)1986 Patel Bhadran 3.8 ( R)1988 Ramachandran et al Kudremukh 5.0 ( U)1989 Kodali et al Gangavathi 2.2 ( R)1989 Rao et al Eluru 1.6 ( Rl)1989 Ramachandran et al 3 Madras 8.3 ( U) 8.3 (U)1992 Ramachandran et al 9 Madras 8.2 (U) 8.7 (U)

2.4 (R) 7.8 (R )1995 Ramachandran et al 3 Madras 11.6 (U) 9.1(U)2001 Ramachandran et al 20 NUDS 13.9 (U) 14.4 (U)

2001Indian Task Force on Diabetes

13 PODIS 9.6 (U) 9.71(U)

4.26(R ) 7.49(R )*Ramaiya et al, 1990 - Unless specified otherwise.U URBAN,R RURAL

National studies on diabetes complications are sparse in India. A few population based studies

indicate the prevalence of retinopathy to be 18% to 27%, and overt nephropathy to be about

2.2% with a large percentage (27%) having microalbuminuria.

Peripheral vascular disease is prevalent in 6.3% , peripheral neuropathy in 26% , and coronary

artery disease (CAD) is detected in 21%.

The major contributory factors for the high prevalence of the complications are, delayed

diagnosis of diabetes , inadequate control of glycemia, hypertension and lack of awareness about

the disease among majority of public.

ECONOMIC BURDEN DUE TO DIABETES

The cost of diabetes care is high and escalating world wide.it is estimated by WHO that global

expenditure for diabetes care would increase form 234 billions in 2007 to 411 billions in the next

20 years .over the next 10 years ,lost national income in billions of USD will amount to 555.7 in

China, 303.2 in Russian federation , 336.6 in India , 49.2 in Brazil, and 2.5 in Tanzania

In Asia, the prevalence of diabetes is increasing rapidly and the diabetes phenotype appears to be

different from that in the United States and Europe —onset at a lower BMI and younger age,

greater visceral adiposity, and reduced insulin secretory capacity. Diabetes is a major cause of

mortality

Annual economic burden of Diabetes direct and indirect. Apportioned at individual, Family and Societal Level. *

TABLE 14.Level of Burden

Direct Costs (INR)Indirect Costs (INR)

Total Costs (INR)

RoutineMoni & Lab

Hospital Total

Personal 1882.40 291.10 2551.10 4724.80 1850.50 4024.20Family 4076.80 531.30 6127.50 10735.60 1722.00 5330.10Society 1112.80 124.90 67.50 1305.20 15376.30 16614.00Total 7072.00 947.40 8746.10 16,765.50 18948.80 35714.30* Rayappa PH et al Int.J.Diab.Dev Countries July - Sept 1999.

Table 2 Criteria for the Diagnosis of Diabetes Mellitus

Symptoms of diabetes plus random blood glucose concentration 11.1 mmol/L (200 mg/dL)or

Fasting plasma glucose 7.0 mmol/L (126 mg/dL)or

A1C > 6.5%or

Two-hour plasma glucose 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test

Abnormal glucose homeostasis is defined as

1.FPG = 5.6–6.9 mmol/L (100–125 mg/dL), which is defined as IFG (note that the World Health

Organization uses an FPG of 6.1–6.9 mmol/L (110 125 mg/dL);

2.Plasma glucose levels between 7.8 and 11 mmol/L (140 and 199 mg/dL) following an oral

glucose challenge, which is termed impaired glucose tolerance (IGT);

3.A1C of 5.7–6.4%.

A1C of 5.7–6.4%. IFG, and IGT do not identify the same individuals, but individuals in all three

groups are at greater risk of progressing to type 2 diabetes and have an increased risk of

cardiovascular disease. Some use the term "prediabetes," "increased risk of diabetes" (ADA), or

"intermediate hyperglycemia" (WHO) for this category.

The current criteria for the diagnosis of DM emphasize that the A1C or the FPG as the most

reliable and convenient tests for identifying DM in asymptomatic individuals.

The global burden due to diabetes is mostly contributed by type 2 diabetes which constitutes 80-

95% total diabetic population.nearly 70% of the people with diabetes live in developing

countries.

The largest number of diabetes are in the 40-59 age groups (132 million in 2010 ) which is

expected to rise further .By 2030 there will be more diabetic people in the 60-70 age groups (196

million)

Risk Factors for Type 2 Diabetes Mellitus

1 Family history of diabetes (i.e., parent or sibling with type 2 diabetes)

2.Obesity (BMI 25 kg/m2),apple shaped figure

3.Physical inactivity,

4.Race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific

Islander)

5.Previously identified with IFG, IGT, or an A1C of 5.7–6.4%

6.History of GDM or delivery of baby >4 kg (9 lb),

7.Hypertension (blood pressure 140/90 mmHg)

8.HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82

mmol/L)

9.Polycystic ovary syndrome or acanthosis nigricans

10.History of cardiovascular disease

11.age > 45 years

12.low birth weight – greater propensity for DM later in life

Abbreviations: BMI, body mass index; GDM, gestational diabetes mellitus; HDL, high-density

lipoprotein; IFG, impaired fasting glucose; IGT, impaired glucose tolerance. Source: Adapted

from American Diabetes Association, 2011.

Screening

Widespread use of the FPG or the A1C as a screening test for type 2 DM is recommended

because (1) a large number of individuals who meet the current criteria for DM are

asymptomatic and unaware that they have the disorder, (2) epidemiologic studies suggest that

type 2 DM may be present for up to a decade before diagnosis, (3) some individuals with type 2

DM have one or more diabetes-specific complications at the time of their diagnosis, and (4)

treatment of type 2 DM may favorably alter the natural history of DM.

INSULIN BIOSYNTHESIS, SECRETION, AND ACTION

Insulin is produced in the beta cells of the pancreatic islets. It is initially synthesized as a single-

chain 86-amino-acid precursor polypeptide, preproinsulin. Subsequent proteolytic processing

removes the amino-terminal signal peptide, giving rise to proinsulin. Proinsulin is structurally

related to insulin-like growth factors I and II, which bind weakly to the insulin receptor.

Cleavage of an internal 31-residue fragment from proinsulin generates the C peptide and the A

(21 amino acids) and B (30 amino acids) chains of insulin, which are connected by disulfide

bonds.

Secretion

Glucose is the key regulator of insulin secretion by the pancreatic beta cell, although amino

acids, ketones, various nutrients, gastrointestinal peptides, and neurotransmitters also influence

insulin secretion.

Glucose levels >3.9 mmol/L (70 mg/dL) stimulate insulin synthesis, primarily by enhancing

protein translation and processing.

Glucose stimulation of insulin secretion begins with its transport into the beta cell by a

facilitative glucose transporter.Glucose phosphorylation by glucokinase is the rate-limiting step

that controls glucose-regulated insulin secretion. Further metabolism of glucose-6- phosphate via

glycolysis generates ATP, which inhibits the activity of an ATP-sensitive K+ channel.

This channel consists of two separate proteins: one is the binding site for certain oral

hypoglycemics (e.g., sulfonyl-ureas, meglitinides); the other is an inwardly rectifying K+

channel protein (Kir6.2). Inhibition of this K+ channel induces beta cell membrane

depolarization, which opens voltage-dependent calcium channels (leading to an influx of

calcium), and stimulates insulin secretion.

Insulin secretory profiles reveal a pulsatile pattern of hormone release, with small secretory

bursts occurring about every 10 min, superimposed upon greater amplitude oscillations of about

80–150 min.

Incretins are released from neuroendocrine cells of the gastrointestinal tract following food

ingestion and amplify glucose-stimulated insulin secretion and suppress glucagon secretion.

Glucagon-like peptide 1 (GLP-1), the most potent incretin, is released from L cells in the small

intestine and stimulates insulin secretion only when the blood glucose is above the fasting level.

Incretin analogues, are used to enhance endogenous insulin secretion .

Action Once insulin is secreted into the portal venous system, 50% is removed and degraded by

the liver. Unextracted insulin enters the systemic circulation where it binds to receptors in target

sites.

Insulin binding to its receptor stimulates intrinsic tyrosine kinase activity, leading to receptor

autophosphorylation and the recruitment of intracellular signaling molecules, such as insulin

receptor substrates (IRS). IRS and other adaptor proteins initiate a complex cascade of

phosphorylation and dephosphorylation reactions, resulting in the widespread metabolic and

mitogenic effects of insulin.

As an example, activation of the phosphatidylinositol-3′-kinase (PI-3-kinase) pathway stimulates

translocation of a facilitative glucose transporter (e.g., GLUT4) to the cell surface, an event that

is crucial for glucose uptake by skeletal muscle and fat.

Activation of other insulin receptor signaling pathways induces glycogen synthesis, protein

synthesis, lipogenesis, and regulation of various genes in insulin-responsive cells.

Glucose homeostasis reflects a balance between hepatic glucose production and peripheral

glucose uptake and utilization.

Insulin is the most important regulator of this metabolic equilibrium, but neural input, metabolic

signals, and other hormones (e.g., glucagon) result in integrated control of glucose supply and

utilization.

In the fasting state, low insulin levels increase glucose production by promoting hepatic

gluconeogenesis and glycogenolysis and reduce glucose uptake in insulin-sensitive tissues

(skeletal muscle and fat), thereby promoting mobilization of stored precursors such as amino

acids and free fatty acids (lipolysis). Glucagon, secreted by pancreatic alpha cells when blood

glucose or insulin levels are low, stimulates glycogenolysis and gluconeogenesis by the liver and

renal medulla. Postprandially, the glucose load elicits a rise in insulin and fall in glucagon,

leading to a reversal of these processes. Insulin, an anabolic hormone, promotes the storage of

carbohydrate and fat and protein synthesis.

The major portion of postprandial glucose is utilized by skeletal muscle, an effect of insulin-

stimulated glucose uptake. Other tissues, most notably the brain, utilize glucose in an insulin-

independent fashion.

PATHOGENESIS of TYPE 2 DIABETES MELLITUS

Insulin resistance and abnormal insulin secretion are central to the development of type 2 DM.

Insulin resistance precedes an insulin secretory defect but that diabetes develops only when

insulin secretion becomes inadequate.

Genetic Considerations Type 2 DM has a strong genetic component. The concordance of type 2

DM in identical twins is between 70 and 90%.

Individuals with a parent with type 2 DM have an increased risk of diabetes; if both parents have

type 2 DM, the risk approaches 40%.

Insulin resistance, as demonstrated by reduced glucose utilization in skeletal muscle, is present in

many nondiabetic, firstdegree relatives of individuals with type 2 DM.

The disease is polygenic and multifactorial, since in addition to genetic susceptibility,

environmental factors (such as obesity, nutrition, and physical activity) modulate the phenotype.

The genes that predispose to type 2 DM are incompletely identified, but recent genome-wide

association studies have identified a large number of genes that convey a relatively small risk for

type 2 DM (>20 genes, each with a relative risk of 1.06–1.5). Most prominent is a variant of the

transcription factor 7–like 2 gene that has been associated with type 2 diabetes in several

populations and with impaired glucose tolerance in one population at high risk for diabetes.

Genetic polymorphisms associated with type 2 diabetes have also been found in the genes

encoding the peroxisome proliferators–activated receptor- , inward rectifying potassium channel,

zinc transporter, IRS, and calpain 10. The mechanisms by which these genetic loci increase the

susceptibility to type 2 diabetes are not clear, but most are predicted to alter islet function or

development or insulin secretion. While the genetic susceptibility to type 2 diabetes is under

active investigation (estimation that <10% of genetic risk is determined by loci identified thus

far), it is currently not possible to use a combination of known genetic loci to predict type 2

diabetes.

PATHOPHYSIOLOGY

Type 2 DM is characterized by impaired insulin secretion, insulin resistance, excessive hepatic

glucose production, and abnormal fat metabolism.

Obesity, particularly visceral or central (as evidenced by the hip-waist ratio), is very common in

type 2 DM (80% or more are obese).

In the early stages of the disorder, glucose tolerance remains near-normal, despite insulin

resistance, because the pancreatic beta cells compensate by increasing insulin output . As insulin

resistance and compensatory hyperinsulinemia progress, the pancreatic islets in certain

individuals are unable to sustain the hyperinsulinemic state

IGT(impaired glucose tolerance ) characterized by elevations in postprandial glucose, then

develops. A further decline in insulin secretion and an increase in hepatic glucose production

lead to overt diabetes with fasting hyperglycemia. Ultimately, beta cell failure ensues.

METABOLIC ABNORMALITIES

Abnormal Muscle and Fat Metabolism

Insulin resistance, the decreased ability of insulin to act effectively on target tissues (especially

muscle, liver, and fat), is a prominent feature of type 2 DM and results from a combination of

genetic susceptibility and obesity.

Insulin resistance impairs glucose utilization by insulin-sensitive tissues and increases hepatic

glucose output; both effects contribute to the hyperglycemia. Increased hepatic glucose output

predominantly accounts for increased FPG levels, whereas decreased peripheral glucose usage

results in postprandial

hyperglycemia. In skeletal muscle, there is a greater impairment in nonoxidative glucose usage

(glycogen formation) than in

oxidative glucose metabolism through glycolysis.

Glucose metabolism in insulin-independent tissues is not altered in type 2 DM.

"Postreceptor" defects in insulin-regulated phosphorylation/dephosphorylation appear to play the

predominant role in insulin resistance.

The obesity accompanying type 2 DM, particularly in a central or visceral location, is thought to

be part of the pathogenic process. The increased adipocyte mass leads to increased levels of

circulating free fatty acids and other fat cell products

Adipocytes secrete a number of biologic products (nonesterified free fatty acids, retinol-binding

protein4, leptin, TNF- , resistin, and adiponectin).

In addition to regulating body weight, appetite, and energy expenditure, adipokines also

modulate insulin sensitivity. The increased production of free fatty acids and some adipokines

may cause insulin resistance in skeletal muscle and liver.

Free fatty acids impair glucose utilization in skeletal muscle, promote glucose production by the

liver, and impair beta cell function. In contrast, the production by adipocytes of adiponectin, an

insulinsensitizing peptide, is reduced in obesity, and this may contribute to hepatic insulin

resistance.

Adipocyte products and adipokines also produce an inflammatory state and may explain why

markers of inflammation such as IL-6 and C-reactive protein are often elevated in type 2 DM.

Inflammatory cells have been found infiltrating adipose tissue. Inhibition of inflammatory

signaling pathways such as the nuclear factor B (NF- B) pathway appears to reduce insulin

resistance and improve hyper-glycemia in animal models.

Impaired Insulin Secretion

Insulin secretion and sensitivity are interrelated .In type 2 DM, insulin secretion initially

increases in response to insulin resistance to maintain normal glucose tolerance. Initially, the

insulin secretory defect is mild and selectively involves glucose-stimulated insulin secretion. The

response to other nonglucose secretagogues, such as arginine, is preserved.

Eventually, the insulin secretory defect progresses to a state of inadequate insulin secretion.

The reason(s) for the decline in insulin secretory capacity in type 2 DM is unclear. The

assumption is that a second genetic defect—superimposed upon insulin resistance—leads to beta

cell failure. Beta cell mass is decreased by approximately 50% in individuals with long-standing

type 2 diabetes. Islet amyloid polypeptide or amylin is co-secreted by the beta cell and forms the

amyloid fibrillar deposit found in the islets of individuals with long-standing type 2 DM.

Whether such islet amyloid deposits are a primary or secondary event is not known.

The metabolic environment of diabetes may also negatively impact islet function, chronic

hyperglycemia paradoxically impairs islet function ("glucose toxicity") and leads to a worsening

of hyperglycemia. Improvement in glycemic control is often associated with improved islet

function. In addition, elevation of free fatty acid levels ("lipotoxicity") and dietary fat may also

worsen islet function.

Increased Hepatic Glucose and Lipid Production

In type 2 DM, insulin resistance in the liver reflects the failure of hyperinsulinemia to suppress

gluconeogenesis, which results in fasting hyperglycemia and decreased glycogen storage by the

liver in the postprandial state.

Increased hepatic glucose production occurs early in the course of diabetes, though likely after

the onset of insulin secretory abnormalities and insulin resistance in skeletal muscle.

As a result of insulin resistance in adipose tissue, lipolysis and free fatty acid flux from

adipocytes are increased, leading to increased lipid [very low density lipoprotein (VLDL) and

triglyceride] synthesis in hepatocytes. This lipid storage or steatosis in the liver may lead to

nonalcoholic fatty liver disease and abnormal liver function tests.

This is also responsible for the dyslipidemia found in type 2 DM [elevated triglycerides, reduced

high-density lipoprotein (HDL), and increased small dense low-density lipoprotein (LDL)

particles].

INSULIN RESISTANCE SYNDROMES

The insulin resistance condition comprises a spectrum of disorders, with hyperglycemia

representing one of the most readily diagnosed features. The metabolic syndrome, the insulin

resistance syndrome, or syndrome X are terms used to describe a constellation of metabolic

derangements that includes insulin resistance, hypertension, dyslipidemia (decreased HDL and

elevated triglycerides), central or visceral obesity, type 2 diabetes or IGT/IFG, and accelerated

cardiovascular disease.

Clinical Identification of the Metabolic Syndrome—Any Three Risk Factors

Risk Factor Defining Level

Abdominal obesity Men (waist circumference) >102 cm, Women >88 cm

Triglycerides >1.7 mmol/L (>150 mg/dL)

HDL cho-lesterol Men <1 mmol/L (<40 mg/dL) Women <1.3 mmol/L (<50 mg/dL)

Blood pressure 130/ 85 mmHg

Fasting glucose >6.1 mmol/L (>110 mg/dL)

Overweight and obesity are associated with insulin resistance and the metabolic syndrome.

However, the presence of abdominal obesity is more highly correlated with the metabolic risk

factors than is an elevated body mass index (BMI). Therefore, the simple measure of waist

circumference is recommended to identify the BMI component of the metabolic syndrome.

Two distinct syndromes of severe insulin resistance have been described in adults

Type A, which affects young women and is characterized by severe hyperinsulinemia, obesity,

and features of hyperandrogenism-- have an undefined defect in the insulin-signaling pathway.

Type B, which affects middleaged women and is characterized by severe hyperinsulinemia,

features of hyperandrogenism, and autoimmune disorders --have autoantibodies directed at the

insulin receptor. These receptor autoantibodies may block insulin binding or may stimulate the

insulin receptor, leading to intermittent hypoglycemia.

Polycystic ovary syndrome (PCOS) is a common disorder that affects premenopausal women

and is characterized by chronic anovulation and hyperandrogenism. Insulin resistance is seen in a

significant subset of women with PCOS, and the disorder substantially increases the risk for type

2 DM, independent of the effects of obesity.

ACUTE COMPLICATIONS OF DM

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute

complications of diabetes.

DKA was formerly considered a hallmark of type 1 DM, but also occurs in individuals who lack

immunologic features of type 1 DM and who can sometimes subsequently be treated with oral

glucose-lowering agents. The initial management of DKA is similar.

HHS is primarily seen in individuals with type 2 DM.

Both disorders are associated with absolute or relative insulin deficiency, volume depletion, and

acid-base abnormalities.

Chronic Complications of Diabetes Mellitus

Microvascular

Eye disease

Retinopathy (nonproliferative/proliferative)

Macular edema

Neuropathy

Sensory and motor (mono- and polyneuropathy)

Autonomic

Nephropathy

Macrovascular

Coronary heart disease

Peripheral arterial disease

Cerebrovascular disease

Other

Gastrointestinal (gastroparesis, diarrhea)

Genitourinary (uropathy/sexual dysfunction)

Dermatologic

Infectious

Cataracts

Glaucoma

Periodontal disease

Hearing loss

The risk of chronic complications increases as a function of the duration and degree of

hyperglycemia; they usually do not become apparent until the second decade of hyperglycemia.

Since type 2 DM often has a long asymptomatic period of hyperglycemia, many individuals with

type 2 DM have complications at the time of diagnosis.

The microvascular complications of both type 1 and type 2 DM result from chronic

hyperglycemia. Large, randomized clinical trials of individuals with type 1 or type 2 DM have

conclusively demonstrated that a reduction in chronic hyperglycemia prevents or delays

retinopathy, neuropathy, and nephropathy. Other incompletely defined factors may modulate the

development of complications. For example, despite long-standing DM, some individuals never

develop nephropathy or retinopathy. Many of these patients have glycemic control that is

indistinguishable from those who develop microvascular complications, suggesting that there is a

genetic susceptibility for developing particular complications.

Evidence implicating a causative role for chronic hyperglycemia in the development of

macrovascular complications is less conclusive.

Coronary heart disease events and mortality rate are two to four times greater in patients with

type 2 DM. These events correlate with fasting and postprandial plasma glucose levels as well as

with the A1C. Dyslipidemia and hypertension also play important roles in macrovascular

complications.

Mechanisms of Complications

Although chronic hyperglycemia is an important etiologic factor leading to complications of

DM, the mechanism(s) by which it leads to such diverse cellular and organ dysfunction is

unknown.

At least four prominent theories, which are not mutually exclusive, have been proposed . An

emerging

hypothesis is that hyperglycemia leads to epigenetic changes in the affected cells

.

One theory is that increased intracellular glucose leads to the formation of advanced

glycosylation end products (AGEs), which bind to a cell surface receptor, via the nonenzymatic

glycosylation of intra- and extracellular proteins. Nonenzymatic glycosylation results from the

interaction of glucose with amino groups on proteins. AGEs have been shown to cross-link

proteins (e.g., collagen, extracellular matrix proteins), accelerate atherosclerosis, promote

glomerular dysfunction, reduce nitric oxide synthesis, induce endothelial dysfunction, and alter

extracellular matrix composition and structure.

The serum level of AGEs correlates with the level of glycemia, and these products accumulate as

the glomerular filtration rate (GFR) declines.

A second theory is based on the observation that hyperglycemia increases glucose metabolism

via the sorbitol pathway. Intracellular glucose is predominantly metabolized by phosphorylation

and subsequent glycolysis, but when increased, some glucose is converted to sorbitol by the

enzyme aldose reductase. Increased sorbitol concentration alters redox potential, increases

cellular osmolality, generates reactive oxygen species, and likely leads to other types of cellular

dysfunction.Testing of this theory in humans, using aldose reductase inhibitors, has not

demonstrated significant beneficial effects on clinical endpoints of retinopathy, neuropathy, or

nephropathy.

A third hypothesis proposes that hyperglycemia increases the formation of diacylglycerol

leading to activation of protein kinase C (PKC). PKC alters the transcription of genes for

fibronectin, type IV collagen, contractile proteins, and extracellular matrix proteins in endothelial

cells and neurons. Inhibitors of PKC are being studied in clinical trials.

A fourth theory proposes that hyperglycemia increases the flux through the hexosamine

pathway, which generates fructose-6- phosphate, a substrate for O-linked glycosylation and

proteoglycan production. The hexosamine pathway may alter function by glycosylation of

proteins such as endothelial nitric oxide synthase or by changes in gene expression of

transforming growth factor (TGF- ) or plasminogen activator inhibitor-1 (PAI-1).

Individuals with DM are 25 times more likely to become legally blind than individuals without

DM.

Blindness is primarily the result of progressive diabetic retinopathy and clinically significant

macular edema.

Diabetic nephropathy is the leading cause of ESRD and a leading cause of DM-related morbidity

and mortality. Both microalbuminuria and macroalbuminuria in individuals with DM are

associated with increased risk of cardiovascular disease. Individuals with diabetic nephropathy

commonly have diabetic retinopathy.

Neuropathy and Diabetes Mellitus

Diabetic neuropathy occurs in 50% of individuals with long-standing type 1 and type 2 DM. It

may manifest as polyneuropathy, mononeuropathy, and/or autonomic neuropathy.The

development of neuropathy correlates with the duration of diabetes and glycemic control.

Additional risk factors are BMI (the greater the BMI, the greater the risk of neurop-athy) and

smoking. The presence of cardiovascular disease, elevated triglycerides, and hypertension is also

associated with diabetic peripheral neuropathy. Both myelinated and unmyelinated nerve fibers

are lost.

Gastrointestinal/Genitourinary Dysfunction

Long-standing type 1 and 2 DM may affect the motility and function of gastrointestinal (GI) and

genitourinary systems. The most prominent GI symptoms are delayed gastric emptying

(gastroparesis) and altered small- and large-bowel motility (constipation or diarrhea).

Diabetic autonomic neuropathy may lead to genitourinary dysfunction including cystopathy,

erectile dysfunction, and female sexual dysfunction (reduced sexual desire, dyspareunia, reduced

vaginal lubrication). Symptoms of diabetic cystopathy begin with an inability to sense a full

bladder and a failure to void completely.

Cardiovascular Morbidity and Mortality

Cardiovascular disease is increased in individuals with type 1 or type 2 DM. The Framingham

Heart Study revealed a marked increase in PAD, CHF, CHD, MI, and sudden death (risk

increase from one- to fivefold) in DM.

The American Heart Association has designated DM as a "CHD risk equivalent." Type 2

diabetes patients without a prior MI have a similar risk for coronary artery –related events as

nondiabetic individuals who have had a prior MI

PREVENTION

Impaired glucose tolerance and impaired fasting glucose form an intermediate stage in the natural

history of diabetes mellitus.Impaired glucose tolerance is defined as two-hour glucose levels of

140 to 199 mg per dL (7.8 to 11.0 mmol) on the 75-g oral glucose tolerance test, and impaired

fasting glucose is defined as glucose levels of 100 to 125 mg per dL (5.6 to 6.9 mmol per L) in

fasting patients.

Classification of glucose tolerance state

State FPG level (mg/dl)2-h plasma glucose in OGTT (mg/dl)*

IFG 100–125 <200

        Isolated IFG

100–125 <140

IGT <126 140–199

        Isolated IGT

<100 140–199

Combined IFG/IGT 100–125 140–199

State FPG level (mg/dl)2-h plasma glucose in OGTT (mg/dl)*

NGT <100 <140

These glucose levels are above normal but below the level that is diagnostic for diabetes. Patients

with impaired glucose tolerance or impaired fasting glucose have a significant risk of developing

diabetes and thus are an important target group for primary prevention

In an analysis of six prospective studies,6 the risk of developing diabetes was found to be approximately

3.6 to 8.7 percent per year in patients with IGT. During the pre-diabetic state, the risk of a CVD

event is modestly increased (11–22)

IFG and IGT frequently are associated with metabolic syndrome. It is important for family physicians to

identify patients with metabolic syndrome and to intervene aggressively to reduce the risk of diabetes

and macrovascular disease.

People with isolated IFG predominantly have hepatic insulin resistance and normal muscle

insulin sensitivity, whereas individuals with isolated IGT have normal to slightly reduced

hepatic insulin sensitivity and moderate to severe muscle insulin resistance.

People with isolated IFG have a decrease in first-phase (0–10 min) insulin secretory

response to intravenous glucose and a reduced earlyphase (first 30 min) insulin response to

oral glucose. However, the late-phase (60–120 min) plasma insulin response during the

OGTT is normal in isolated IFG. Isolated IGT also has a defect in early-phase insulin

secretion in response to an oral glucose load and in addition has a severe deficit in

latephase insulin secretion.

In IFG the impairment in early insulin response in combination with hepatic insulin resistance

results in the excessive early rise of plasma glucose in the 1st hour of the OGTT. However, the

preservation of late insulin secretion combined with normal muscle insulin sensitivity allows

glucose levels to return to the preload value in isolated IFG.

In contrast, in isolated IGT the defective late insulin secretion, combined with muscle and

hepatic insulin resistance, results in prolonged hyperglycemia after a glucose load.

The majority of people with IFG/IGT will develop progressive hyperglycemia and eventually

meet criteria for diabetes.

A wide variety of interventions have been shown to alter the natural history of IFG/IGT

progression to diabetes.

The prevention or delay of diabetes should lead to a decrease in duration-dependent

diabetesrelated microvascular complications; however, direct data are not available to determine

whether this occurs. Published trials have not been sufficiently powered to show a reduction in

these hard outcomes.

One of the other major reasons to recommend therapeutic interventions for individuals with

IFG/IGT is the potential

to reduce the long-term increased risk of CVD associated with diabetes.

The epidemic increase in diabetes and its serious long-term consequences strongly support

efforts to prevent its occurrence, with the expectation that morbidity and mortality will be

decreased.

The strong association between diabetes and obesity suggests that our first priority is

maintenance of healthy weight

and obesity prevention. All individuals who are overweight or obese, regardless of their blood

glucose value, should be intensively counseled to lose weight and to exercise. lifestyle

modification therapy emphasizing modest weight loss (5–10% of body wt) and moderate-

intensity physical activity (_30 min daily) is the treatment of choice for individuals with

IFG/IGT. it seems very likely that lifestyle modification would benefit all people with IFG/IGT

The population to be screened for IFG/IGT should be the same as currently recommended for

screening for diabetes.

At present, FPG and 2-h OGTT are the tests of choice to identify all states of hyperglycemia

Type 2 DM is preceded by a period of IGT or IFG, and a number of lifestyle modifications and

pharmacologic agents prevent or delay the onset of DM.

The Diabetes Prevention Program (DPP) demonstrated that intensive changes in lifestyle (diet

and exercise for 30 min/d five times/week) in individuals with IGT prevented or delayed the

development of type 2 DM by 58% compared to placebo.

This effect was seen in individuals regardless of age, sex, or ethnic group.

In the same study, metformin prevented or delayed diabetes by 31% compared to placebo.

The lifestyle intervention group lost 5–7% of their body weight during the 3 years of the study.

Studies in Finnish and Chinese populations noted similar efficacy of diet and exercise in

preventing or delaying type 2 DM; -glucosidase inhibitors, metformin, thiazolidinediones, and

orlistat prevent or delay type 2 DM but are not approved for this purpose.

Individuals with a strong family history of type 2 DM and individuals with IFG or IGT should be

strongly encouraged to maintain a normal BMI and engage in regular physical activity.

Pharmacologic therapy for individuals with prediabetes is currently controversial because its

cost-effectiveness and safety profile are not known.

The ADA has suggested that metformin be considered in individuals with both IFG and IGT who

are at very high risk for progression to diabetes (age <60 years, BMI 35 kg/m2, family history of

diabetes in first-degree relative, elevated triglycerides, reduced HDL, hypertension, or A1C

>6.0%).

Individuals with IFG, IGT, or an A1C of 5.7–6.4% should be monitored annually to determine if

diagnostic criteria for diabetes are present.

Author/date Aim of study Type of the study

Main findings/conclusion

Strengths and limitations

Knowler et al., (2002)

To assess the effectiveness of intensive lifestyle intervention (The US diabetes prevention program) in prevention of diabetes

Randomized control trial

Significantly lower incidence of diabetes cases and higher leisure time physical activity in the intervention group after an average of 2.8 years follow up. There was a significant

reduction in fasting

plasma glucose in the

intervention group

during 2.8 years follow

up.

Representative sample Good sample size (3234) Partly blinded study Unclear process of follow up including the number of participants who dropped out Exercises were

assessed by self-

reported

questionnaire.

Diabetes Prevention Program Research Group et al., (2009)

To assess the effectiveness of intensive lifestyle intervention (The US diabetes prevention program) against general lifestyle recommendations in prevention of diabetes

Cohort study After 10 years follow up, the incidence rate did not differ significantly between the lifestyle intervention and the control group. However, the cumulative incidence rate (overall new diabetes cases over 10 years) of diabetes was the least in lifestyle intervention

This study was designed similar to (Knowler et al., 2002), but the follow up period was extended to 10 years. Possibility of other

confounding factors

as a result of long

follow up period

Allen et al., (2008)

To evaluate lifestyle intervention to prevent type 2 diabetes among American Indian

Randomized control trial

The mean change of fasting blood glucose was significantly reduced among participants after

Small sample size (42) Less prone to selection bias Exercise were

women with impaired glucose tolerance

6, 12 and 18 months follow up.

assessed by self-

reported

questionnaire

Thompson et al., (2008)

To evaluate lifestyle intervention to prevent type 2 diabetes among American Indian women with impaired glucose tolerance

Randomized control trial

No significant change in the mean of fasting blood glucose among participants during 6, 12 and 18 months follow up

A sample size of 200 Participants were randomized by tow computer generated lists Less prone to

selection bias

Yates et al., (2009)

To evaluate the effectiveness of (PREPARE) program, which promote walking activity with or without pedometer, in improving impaired glucose tolerance

Randomized control trial

A structured education program with pedometer use (PREPARE) is effective in reducing fasting plasma glucose and 2 h glucose after one year follow up.

Small sample size (87) More men than women participated Partly blinded study Short follow up period Clear process of

randomization

Tuomilehto et al., (2001)

To assess the effect of exercise and dietary life style intervention (The Finnish diabetes prevention program) in preventing type 2 diabetes for people who are at risk.

Randomized control trial

The Finnish diabetes prevention program showed significant reduction in fasting plasma glucose and 2 h plasma glucose among the intervention group after one year follow up

Sample size of (523) Clear process of randomization Partly blinded study Exercise was assessed only by self-reported questionnaire

Ramachandran et al., (2006)

To assess the effectiveness of lifestyle intervention in reducing diabetes cases among Asian Indians with

Randomized control trial

The cumulative incidence of diabetes was significantly lower in the intervention groups

Sample size of (531) Unclear process of randomization Blinding was not achieved More men (412)

than women (110)

impaired glucose tolerance.

participated in the

study

AIMS AND OBJECTIVES

Improvement in glycemic control in patients with IFG and IGT in overweight (BMI> 25) and obese individuals with weight reduction and exercise

MATERIALS AND METHODS

This study was conducted in outpatient based clinic in Hyderabad during the period from

December 2011 to may 2012 over a period of 6 months ,consecutive patients present with

impaired fasting glucose were enrolled for the study with their prior permission after explaining

the details fully.

METHODOLOGY

A)INCLUSION CRITERIA

1)people with BMI> 25

2)Age > 30yrs

3)Fasting plasma glucose > 100mg/dl and <126mg/dl

4)2-hr plasma glucose >140mg/dl and <200mg/dl in OGTT-oral glucose tolerance test

B)EXCLUSION CRITERIA

1)Prior history of diabetes mellitus

2)Who on metformin theraphy for other reasons

CLINICAL DATA –around 25 individuals enrolled in this study with prior permission from

them . In all of them I measured body weight, height ,BMI, checked Blood pressure. Regular

plasma fasting glucose, fasting lipids measured. OGTT performed and 2hr plasma glucose

recorded. I advised them regular exercise of 30-45mts a day for minimum five days a week.

Fasting glucose measured after minimum of 8 hours fast

OGTT performed with 75 gms of oral glucose and 2 hr post bood glucose recorded

LIPID PROFILE measured after minimum of 12 hours fast

Statistical analysis For quantitative data , mean , standard deviation used to compare two

groups, responders, progressors.,obese, overweight. Z-test was applied to compare two

proportions.chisquare test or fisher’ test to compare outcomes between two groups.

Abbreviations used

HT - height in cms

WT -1 - weight in kilograms base line reading.

WT -2 - weight in kilograms after 6 months

BMI - body mass index kg/cm2

W.C.-1 waist circumference in cms base line reading

W.C.-2 waist circumference in cms after 6 months

SYS BP-1 systolic blood pressure in mm hg base line reading

SYS BP-2 systolic blood pressure in mm hg after 6 months

DIA BP-1 diastolic blood pressure in mm hg base line reading

DIA BP -2 - diastolic blood pressure in mm hg after 6 months

FG-1 - fasting glucose in mg/dl base line reading

FG-2 fasting glucose in mg/dl after 6 months

OGTT-1 oral glucose tolerance test in mg/dl base line reading

OGTT-2 oral glucose tolerance test in mg/dl after six months.

HDL-1 - high density lipoproteins in mg/dl base line reading

HDL-2 – high density lipoproteins in mg/dl after 6 months

LDL-1 – low density lipoproteins in mg/dl base line reading

LDL-2 – low density lipoproteins in mg/dl after 6 months

TG-1 - triglycerides in mg/dl base line reading

TG-2 - triglycerides in mg/dl after 6 months

Responders – who responded positively after 6 months whose blood sugars reduced

Progressors - who do not responded positively after 6 months , whose blood sugars continue to

raise.

RESULTS

The study was conducted in 25 patients over a period of 6 months.

Total no of patients - 25

Total no of males - 15

Total no of females - 10

No of persons with Impaired Fasting glucose (IFG) – 25

No of persons with Impaired Glucose Tolerance (IGT)- 20

No of overweight persons - 19 (76%)

No of obese persons -6 (24%)

No of persons who improved glucose control with exercise and wt reduction -19 (76%)

No of persons who progressed with increasing glucose levels -6 (24%)

No of obese persons who showed positive response 2 out of 6----- 33.33%

No of overweight persons who showed positive response 16 out of 19---84%

No of persons who reduced their weight is -21

No of persons who maintained or increased their weight is -- 04

Mean weight initially is 75.67 kg

Mean weight after 6 months is 72.28 kg a change of 4.41%

Mean weight in overweight persons is 73.20 kg after 6 months 69.89 kg a change of 4.5%

Mean weight in obese persons is 83.5 kg after 6 months 80.00 kg cnahge of 4.1 %

Mean weight in responders is 75.04 kg after 6 months 71 kg decrease by 5.3 %

Mean weight in progressors is 77.66 kg after 6 months 76.33 kg decrease by 1.71 %

1 out of 4 persons who doesnot lost weight responded positively.

Mean waist circumference in males – 89.46 cms

After 6 months -- 86.66 cms - 3.12% change

Mean waist circumference in females—84.2 cms

After 6 months --- 81.4 cms -3.32 % change

Mean Fasting Glucose -1in all the patients is ---114.56

Mean Fasting Glucose -2 in all the patients is ---108.4---change of 5.37 %

Mean OGTT-1 all the patients is --- 160.32

Mean OGTT -2 in all the patients is--- 150.64---- CHANGE of 6.03%

Mean fasting glucose in responders is – 114.05—after 6 months - 102.20 decreased by (10.39%)

Mean fasting glucose in progressors is – 116.16- after 6 months - 128.00 increased by (10.19%)

Mean OGTT values in responders is -158.94 after 6 months - 140.63 decreased by (11.52%)

Mean OGTT values in progressors is 164.66 after 6 months 182.33 increased by ( 10.73 %)

No of persons with normal BP -05

No of persons with prehypertension -13

No of persons with stage 1 hypertension -07

No of persons stage 11 hypertension -00

Systolic BP reduced in 3 out of 19 responders significantly with exercise.

No change in BP observed in 15 out of 19 responders.

1 out of 6 obese persons showed decreased systolic BP after exercise.

2 out of 19 over weight persons showed improvement in systolic BP.

Systolic BP increased in 1 out of 19 responders.

Systolic BP- no significant change observed in progressors.

16 out of 19 reponders showed mild increase in HDL levels after exercise.

6 out of 6 progressors showed moderate increase in HDL level after exercise.

10 out of 19 responders showed a significant decrese in LDL level after exercise.

7 out of 19 responders showed almost no change in LDL level after exercise.

2 out of 19 responders showed increase in LDL level after exercise.

3 out of 6 progressors showed a significant decrease in LDL level after exercise.remaining 3 showed

almost the same values.

12 out of 19 responders showed a moderate decrease in TG level after exercise.remaing have almost the

same values.

3 out of 6 progressors showed moderate decrease in the TG values after exercise. 2 showed no

significant difference .1 out of 6 showed a moderate increase in TG levels.

AGE DISTRIBUTION OF PATIENTS

AGE in Yrs MALE FEMALE RESPONDERS PROGRESSORS TOTAL

31-40 08 06 14 00 14

41-50 06 03 04 05 09

51-60 01 01 01 01 02

TypeMean wt-1 KG

MeanWt-2KG

Mean W.C.-1cms

MeanW.C.-2cms

MeanFG-1Mg/dl

MeanFG-2Mg/dl

Mean OGTT-1Mg/dl

Mean OGTT-2Mg/dl

Mean BMIKg/m2

Responders

75.04 71.00 86.89 84.47 114.05 102.21 158.94 140.63 28.05

Progressors 77.66 76.33 88.83 84.83 116.16 126.83 164.66 182.33 28.95

total

male

female

overw

eight

obese

responders

progre

ssors

weight r

educed

weight n

ot red

uced0

5

10

15

20

25

3025

15

10

19

6

19

6

21

4

Series1

Gender distribution of patients

total responders progressors0

2

4

6

8

10

12

14

16

malesfemales

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

FG-1

106

110

109

120

109

122

120

111

108

115

120

115

109

107

114

118

120

115

119

FG-2

101

105

100

101

98 100

121

100

96 99 105

102

105

97 104

97 108

98 105

10

30

50

70

90

110

130

FG changes in responders

glu

cose

mg/

dl

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

OGTT-1

155

160

136

145

178

165

134

156

178

180

167

154

139

136

178

169

166

154

170

OGTT-2

140

150

123

135

160

135

132

138

139

144

140

145

123

130

151

142

146

138

161

10

50

90

130

170

OGTT values in responders G

luco

se m

g/d

l

Weight changes in responders

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

WT in kg I

71 66.3

77 75 88 82 75 76 61.5

84.5

79 85 62 74 73 74 73 67 82.5

WT in KG 2

67 67 73 71 83 77 71 72 57 79 75 80 58 70 69 71 70 61 78

525456585

weight changes in responders

weig

ht

in k

gs

1 2 3 4 5 6

Series1 69 63 81 74 90 89

Series2 66 65 81 70 90 86

5152535455565758595

weight changes in progressorsw

eigh

t in

kgs

1 2 3 4 5 6

FG-1 111 105 118 124 117 122

FG-2 128 122 130 130 127 131

10

30

50

70

90

110

130

FG changes in progressors

bloo

d gl

ucos

e m

g/dl

1 2 3 4 5 6

OGTT-1 180 148 154 133 188 185

OGTT-2 200 156 206 130 198 204

25

75

125

175

225

OGTT changes in progressorsb

llod

glu

cose

mg/

dl

DISCUSSION

Out of the 25 cases of Impaired Fasting glucose and Impaired Glucose Tolerance studied at

outpatient based clinic during the period from December 2011 to may 2012 , most of the

recognized risk factors were seen.

The study showed that IFG & IGT improve with exercise and weight gain.

The mean age in our study is 41.04 yrs.

The p value between different age groups in relation to glucose improvement is variable,

significant between 31-40yrs & 41-50 yrs , but not significant when 31-40 yrs& and 51-60 yrs

groups compared.

The males and females ratio is 3:2 – 15 and 10

12 out of 15 males responded positively and 7 out of 10 females responded positively. Sex

difference has no significant impact on the improvement in IFG & IGT status ( p value 0.65)

Over weight patients are 19 out of which 17 responded positively.

Obese patients are 06 out of which 02 responded positively.

There a significant relation between overweight and obese patients in reducing glucose levels.

IFG and IGT improve more in Overweight patients compared to obese patients ( p value 0.015)

Out of 25 patients 21 patients loose weight after 6 months and 4 patients not loose weight.

Those who lost weight showed a significant improvement in glycemic status compared to those

who did not loose weight. ( p value 0.03)

FACTORS INFLUENCING OUTCOME IN RESPONDERS AND PROGRESSORS

Characteristic Total Glucose reduced Glucose not reduced

P value

Sex

Male

Female

15

10

12

07

03

03

0.65

NOT SIGNIFICANT

Weight

Overweight

Obese

19

6

17

02

02

04

0.015

SIGNIFICANT

Weight

Wt reduced

Wt not reduced

21

4

18

01

03

03

0.03

SIGNIFICANT

Glucose

IFG

IFG& IGT

25

20

19

15

06

05

1

NOT SIGNIFICANT

Age in yrs

31-40

41-50

31-40

14

09

14

14

04

14

00

05

00

0.003

Significant

0.12

51-60 02 01 01 Not significant

CONCLUSIONS

1.There is a significant reduction in blood glucose values with exercise and weight reduction in patients with Impaired Fasting Glucose and Impaired Glucose tolerance.

2.Exercise and weight reduction a minimum of 5% is advised to patients with Impaired Fasting Glucose and Impaired Glucose Tolerance to prevent or to delay progression to Type 2 Diabetes Mellitus.

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