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Outline Diabetic Explosion in India Indian Lifestyle – Changing Scenario Post-Prandial Hyperglycemia – The dark face! Management of Post-Prandial Hyperglycemia Summary
“70 million diabetics in India by ’15: A Study”‘Diabetic Explosion ‘ Due to Changing
Lifestyle
Aren't we aware of it ???
Then ???
Diabetes – An Epidemic… According to Diabetes Atlas published in 2007, there are 246
million diabetics across the world, with 80% of them in developing and underdeveloped countries.
India has 40.9 million diabetics with a prediction of 69.9 million by 2015.
An observation reveals that, there is 40% increase in prevalence in urban areas in 6 years whereas, 49% increase in merely 3 years in rural areas.
This shift according to Endocrine Diagnostic Centre & Diabetes Care is due to Changing Lifestyle and Genetic factors!!!
Along with it…
“The global prevalence of diabetes is set to double over the next 25 years.
Developing countries like India, already top of the diabetes league, are expected to shoulder much of this burden.
Epidemiological studies show that the prevalence of diabetes is particularly high in urban areas in India.
Cities are also home to a large pool of people with a great risk of developing diabetes in the future.”
Have a look at this… Mr. Sunil Agarwal, software engineer of age 32 years is
a resident of Delhi
Family Details – Married, a son of 3 years Father – Diabetic Patient Mother – Died due to Heart Attack
Personal Details – Weight – 82 kgs Smoker (5-7 cigarettes/day) Drinks occasionally Diet pattern – Nonvegetarian, but irregular meal pattern
Case Contd… On the World Heart Day, his software firm was
having free BP and Blood Glucose check up camp. His report revealed –
BP – 124/82 mmHg FPG – 117 mg/dl PPBG – 276 mg/dl
He was shocked with the reports and he decided to visit his family physician.
His family physician confirmed him as patient of IGT with Postprandial Hyperglycemia
Post Prandial Hyperglycemia Independent risk factor for cardiovascular disease
Increases earlier and faster than plasma glucose levels
Contributes more to HbA1c than to fasting glucose at A1c levels below 8.5%
Rate limiting factor for achieving adequate glycemic control
Harmful acute effects Endothelial dysfunction Increase in oxidative stress Increases the inflammatory milieu Increase in protein glycosylation Coagulation affected
Post Prandial Glucose Disposal in Type 2 Diabetes
Lack of appropriate suppression of endogenous glucose release Both gluconeogenesis & glycogenolysis
Normal total tissue glucose uptake Decreased tissue glucose clearance Decreased glucose oxidation Increased nonoxidative glycolysis Increased glycogen cycling Increased glucose uptake by alternative tissues
Adapted from Monnier L. Eur J Clin Invest. 2000;30(suppl 2):3-11.
Duration of postprandial state
Breakfast Lunch Dinner Midnight 4 AM Breakfast
8 AM 11 AM 2 PM 5 PM
Postprandial Postabsorptive Fasting
Patients With Type 2 Diabetes May Spend More Than 12 Hours per Day in the Postprandial State
0
2
4
6
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10
12
14
16
0 5 10 15 20 25
2 hr af ter OGTT plasma glucose (mmol/ l)
2 h
r af
ter
SM
M p
lasm
a gl
ucos
e (m
mol
/l)
0
2
4
6
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0 5 10 15 20 25
2 hr af ter OGTT plasma glucose (mmol/ l)
2 h
r af
ter
SM
M p
lasm
a gl
ucos
e (m
mol
/l)
Correlation between plasma glucose levels after OGTT and standard mixed meal
Wolever TMS et al. Diabetes Care 1998;21:336–40
r=0.97r=0.97
Changes in Postprandial Glucose Metabolism in Type 2 DM
Use triple isotope technique and indirect calorimetry DM pts had:
increased overall glucose release Increased gluconeogenesis and glycogenolysis ~90% of the increased glucose release occurred in
the first 90 min post-prandial In DM glucose clearance and oxidation were reduced Non-oxidative glycolysis was increased Net splanchnic glucose storage was reduced ~ 45%
d.t. increased glycogen cycling
Woerle HJ et al Am J Physiol Endocrinol Metab 200617 [email protected]
Relationship between HbA1C, FPG and 2 h. PPG
Van Haeften T et al Metabolism 2000Van Haeften T et al Metabolism 200018 [email protected]
Increasing Contribution of PPG as A1C Improves
30%40% 45% 50%
70%
60% 55% 50%30%
70%
0%
20%
40%
60%
80%
100%
< 10.2 10.2 to 9.3 9.2 to 8.5 8.4 to 7.3 < 7.3
A1C Range (%)
%
Co
ntr
ibu
tio
n
FPGPPG
Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and postprandial plasnma glucose increments to the overall diurnal hyper glycemia of Type 2 diabetic patients: variations with increasing levels of HBA(1c). Diabetes Care. 2003;26:881-885.
As Patients Get Closer to A1C Goal, the Need to Successfully Manage PPG Significantly Increases
Post-Prandial Hyperglycemia Antecedes Fasting Hyperglycemia
Monnier L et al Diabetes Care 30:263-269, 200720 [email protected]
PPG, but not FPG distinguishes patients with HbA1C Between 6.0-7.0%
Characteristics # of patients Gender Age BMI FPG 2hPPG Mean HbA1C
6.0-6.5 6.6-7.0 37 16 14/23 8/8 54.6 49.6 27.8 27.9 111 113 (p=0.88) 198 226 (p=0.03) 6.26 6.73
HbA1C Group (%)
Woerle HJ et al Arch Intern Med. 2004;164:1627-1632.21 [email protected]
<6.1 6.1–6.9 7.0
11.1
7.8–11.0
<7.8
Fasting plasma glucose (mmol/l) 2-ho
ur p
lasm
a gl
ucos
e
(mm
ol/l)
2.5
2.0
1.5
1.0
0.5
0.0
Haz
ard
rat
io
Adjusted for age, center, sexDECODE Study Group. Lancet 1999;354:617–621
Relative risk for death increases with 2-hour blood glucose irrespective of the FPG level
Relationship Between HbA1c, FPG and PPG in Treated T2DM Patients
MajorHbA1c (%) FPG (mM) PPG (mM) Problem 5 5.1 7.0 - 6 6.3 8.4 PPG 7 7.5 9.8 PPG 8 8.7 11.2 FPG+PPG 9 9.9 12.6 FPG+PPG 10 11.1 14.0 FPG
Woerle et al., 2006.23 [email protected]
Long-Term Problems
Post-prandial glucose
RangeTime to onset of
proteinuria
Persistent <200 110-198 23 yrs
Intermittent >200 118-228 19 yrs
Persistent > 200 201 + 14 yrs
Source: Kidney Intl. 1987; 32 (supp 22): S53-S5624 [email protected]
22-yr CVD Mortality Risk by Baseline post-challenge glucose
Source: Chicago Heart Study, Lowe et al, Diabetes Care, 1997; 20: 163-170.25
Long-Term Problems
Effects of Reducing PPHG
-36 -34
-49-60
-50
-40
-30
-20
-10
0
% R
edu
ctio
n
Risk of progression to diabetes
Risk of cardiovascular events
Risk of development of new cases of hypertension
Post Prandial Hyperglycemia
Rationale for treating PPHG :
Postprandial blood glucose better predictor of glycaemic control than FPG
PPHG associated with microvascular complications e.g. Retinopathy, Nephropathy etc.
Recognized risk factor for CAD e.g. MI, death
Postprandial Hyperglycemia (PPHG) : Management
The higher the plasma glucose level with which a patient goes to bed as a result of postprandial hyperglycemia, the higher will be the fasting hyperglycemia in the morning.
Similarly, the higher the fasting hyperglycemia in the morning, the higher postprandial hyperglycemia will be during the day.
Thus, maneuvers that primarily target fasting hyperglycemia might not be successful in normalizing fasting plasma glucose levels and achieving satisfactory HbA1c levels if postprandial hyperglycemia persists.
28
General Considerations
John E. Gerich, MD. Arch Intern Med. 2003;163:1306-1316. [email protected]
Non pharmacologic Interventions In individuals with IGT and in those with type 2 diabetes with
suboptimal, but not awful, glycemic control (eg, HbA1c 7.0%-8.0%), simple lifestyle modifications such as exercise, weight reduction, or change in diet composition can be particularly helpful.
For example, several studies have demonstrated that weight-reducing diets and exercise can normalize glucose tolerance in individuals with IGT and reduce the risk of their developing type 2 diabetes.
Similarly, reducing the consumption of meals containing high glycemic index items (eg, rice and potatoes vs pasta) can lower postprandial plasma glucose increments as well as the average 24-hour plasma glucose concentration.
John E. Gerich, MD. Arch Intern Med. 2003;163:1306-1316. 29 [email protected]
Approaches/Agents That Address Postprandial Hyperglycemia
Meglitinides Alpha-Glucosidase Inhibitors Prandial Insulin GLP-1 analogues DPP-IV inhibitors Pramlintide Glycemic Index/Load
Objective - Voglibose, an α-glucosidase inhibitor, could prevent the development of type 2 diabetes in high-risk Japanese individuals with impaired glucose tolerance was assessed.
Trial Method - 1780 patients randomly assigned to oral Voglibose 0·2 mg three times a day (n=897) or placebo (n=883) in a multicentre, double-blind, parallel group trial.31 [email protected]
Results & Conclusion
0100200300400500600700
Voglibose Placebo
Pts achieved normoglycemia
Pts achieved normoglycemia
Voglibose, in addition to lifestyle modification, can reduce the development of type 2 diabetes in high-risk individuals with impaired glucose tolerance.32 [email protected]
Br J Clin Pharmacol / 66:2 / 318–31933 [email protected]
Results & Conclusion
Voglibose treatment prevented the increase of body weight induced by Pioglitazone in Type 2 diabetes patients.
Thus, Voglibose may be a potentially useful drug for increasing the benefit of Pioglitazone treatment by controlling body weight.
Br J Clin Pharmacol / 66:2 / 318–31934 [email protected]
Conclusions Hyperglycemia is an important risk factor for both
microvascular and macrovascular complications of diabetes.
Considerable recent evidence has accumulated, indicating that isolated postprandial hyperglycemia (ie, 2-hour postprandial levels >140 mg/dL and fasting levels <110 mg/dL) is common and is an independent clinically significant risk factor for CVD.
The key factor responsible for postprandial hyperglycemia is impaired early insulin secretion.
Fortunately, treatment modalities are now available that
specifically target postprandial hyperglycemia by improving
early postprandial plasma insulin levels (eg, meglitinides,
rapid-acting insulin analogues) and several new ones are in
development (eg, inhaled insulin and GLP-1 agonists). John E. Gerich, MD. Arch Intern Med. 2003;163:1306-1316.
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