Published on

Published in: Health & Medicine
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide


  1. 1. Postprandial Hyperglycemia [email_address]
  2. 2. Outline <ul><li>Diabetic Explosion in India </li></ul><ul><li>Indian Lifestyle – Changing Scenario </li></ul><ul><li>Post-Prandial Hyperglycemia – The dark face! </li></ul><ul><li>Management of Post-Prandial Hyperglycemia </li></ul><ul><li>Summary </li></ul>[email_address]
  3. 3. “ DIABETIC EXPLOSION” [email_address]
  4. 4. <ul><li>“ 70 million diabetics in India by ’15: A Study” </li></ul><ul><li>‘ Diabetic Explosion ‘ Due to Changing Lifestyle </li></ul><ul><li>Aren't we aware of it ??? </li></ul><ul><li>Then ??? </li></ul>[email_address]
  5. 5. Diabetes – An Epidemic… <ul><li>According to Diabetes Atlas published in 2007, there are 246 million diabetics across the world, with 80% of them in developing and underdeveloped countries. </li></ul><ul><li>India has 40.9 million diabetics with a prediction of 69.9 million by 2015. </li></ul><ul><li>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. </li></ul><ul><li>This shift according to Endocrine Diagnostic Centre & Diabetes Care is due to Changing Lifestyle and Genetic factors!!! </li></ul>[email_address]
  6. 6. Along with it… <ul><li>“ The global prevalence of diabetes is set to double over the next 25 years. </li></ul><ul><li>Developing countries like India, already top of the diabetes league, are expected to shoulder much of this burden. </li></ul><ul><li>Epidemiological studies show that the prevalence of diabetes is particularly high in urban areas in India. </li></ul><ul><li>Cities are also home to a large pool of people with a great risk of developing diabetes in the future.” </li></ul>[email_address]
  7. 7. What is driving Diabetes Epidemic in INDIA??? OR [email_address]
  8. 8. What are appropriate goals? <ul><li>HbA1c </li></ul><ul><li>FPG </li></ul><ul><li>2 hr PPG </li></ul><ul><li>Normalization of Glycemia </li></ul>[email_address]
  9. 9. Glycemic Targets in Clinical Practice: Postprandial vs Preprandial and Fasting? [email_address]
  11. 11. Have a look at this… <ul><li>Mr. Sunil Agarwal, software engineer of age 32 years is a resident of Delhi </li></ul><ul><li>Family Details – </li></ul><ul><ul><li>Married, a son of 3 years </li></ul></ul><ul><ul><li>Father – Diabetic Patient </li></ul></ul><ul><ul><li>Mother – Died due to Heart Attack </li></ul></ul><ul><li>Personal Details – </li></ul><ul><ul><li>Weight – 82 kgs </li></ul></ul><ul><ul><li>Smoker (5-7 cigarettes/day) </li></ul></ul><ul><ul><li>Drinks occasionally </li></ul></ul><ul><ul><li>Diet pattern – Nonvegetarian, but irregular meal pattern </li></ul></ul>[email_address]
  12. 12. Case Contd… <ul><li>On the World Heart Day, his software firm was having free BP and Blood Glucose check up camp. </li></ul><ul><li>His report revealed – </li></ul><ul><ul><li>BP – 124/82 mmHg </li></ul></ul><ul><ul><li>FPG – 117 mg/dl </li></ul></ul><ul><ul><li>PPBG – 276 mg/dl </li></ul></ul><ul><li>He was shocked with the reports and he decided to visit his family physician. </li></ul><ul><li>His family physician confirmed him as patient of IGT with Postprandial Hyperglycemia </li></ul>[email_address]
  13. 13. Post Prandial Hyperglycemia <ul><li>Independent risk factor for cardiovascular disease </li></ul><ul><li>Increases earlier and faster than plasma glucose levels </li></ul><ul><li>Contributes more to HbA1c than to fasting glucose at A1c levels below 8.5% </li></ul><ul><li>Rate limiting factor for achieving adequate glycemic control </li></ul><ul><li>Harmful acute effects </li></ul><ul><ul><li>Endothelial dysfunction </li></ul></ul><ul><ul><li>Increase in oxidative stress </li></ul></ul><ul><ul><li>Increases the inflammatory milieu </li></ul></ul><ul><ul><li>Increase in protein glycosylation </li></ul></ul><ul><ul><li>Coagulation affected </li></ul></ul>[email_address]
  14. 14. Post Prandial Glucose Disposal in Type 2 Diabetes <ul><li>Lack of appropriate suppression of endogenous glucose release </li></ul><ul><ul><li>Both gluconeogenesis & glycogenolysis </li></ul></ul><ul><li>Normal total tissue glucose uptake </li></ul><ul><li>Decreased tissue glucose clearance </li></ul><ul><li>Decreased glucose oxidation </li></ul><ul><li>Increased nonoxidative glycolysis </li></ul><ul><li>Increased glycogen cycling </li></ul><ul><li>Increased glucose uptake by alternative tissues </li></ul>[email_address]
  15. 15. Patients With Type 2 Diabetes May Spend More Than 12 Hours per Day in the Postprandial State 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 [email_address]
  16. 16. Correlation between plasma glucose levels after OGTT and standard mixed meal Wolever TMS et al. Diabetes Care 1998;21:336–40 [email_address] r=0.97
  17. 17. Changes in Postprandial Glucose Metabolism in Type 2 DM <ul><li>Use triple isotope technique and indirect calorimetry </li></ul><ul><li>DM pts had: </li></ul><ul><ul><li>increased overall glucose release </li></ul></ul><ul><ul><li>Increased gluconeogenesis and glycogenolysis </li></ul></ul><ul><ul><li>~90% of the increased glucose release occurred in the first 90 min post-prandial </li></ul></ul><ul><ul><li>In DM glucose clearance and oxidation were reduced </li></ul></ul><ul><ul><li>Non-oxidative glycolysis was increased </li></ul></ul><ul><ul><li>Net splanchnic glucose storage was reduced ~ 45% d.t. increased glycogen cycling </li></ul></ul>Woerle HJ et al Am J Physiol Endocrinol Metab 2006 [email_address]
  18. 18. Relationship between HbA1C, FPG and 2 h. PPG Van Haeften T et al Metabolism 2000 [email_address]
  19. 19. As Patients Get Closer to A1C Goal, the Need to Successfully Manage PPG Significantly Increases 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. [email_address]
  20. 20. Post-Prandial Hyperglycemia Antecedes Fasting Hyperglycemia Monnier L et al Diabetes Care 30:263-269, 2007 [email_address]
  21. 21. PPG, but not FPG distinguishes patients with HbA1C Between 6.0-7.0% <ul><li>Characteristics </li></ul><ul><ul><li># of patients </li></ul></ul><ul><ul><li>Gender </li></ul></ul><ul><ul><li>Age </li></ul></ul><ul><ul><li>BMI </li></ul></ul><ul><ul><li>FPG </li></ul></ul><ul><ul><li>2hPPG </li></ul></ul><ul><ul><li>Mean HbA1C </li></ul></ul><ul><li>6.0-6.5 6.6-7.0 </li></ul><ul><ul><li>37 16 </li></ul></ul><ul><ul><li>14/23 8/8 </li></ul></ul><ul><ul><li>54.6 49.6 </li></ul></ul><ul><ul><li>27.8 27.9 </li></ul></ul><ul><ul><li>111 113 (p=0.88) </li></ul></ul><ul><ul><li>198 226 (p=0.03) </li></ul></ul><ul><ul><li>6.26 6.73 </li></ul></ul>HbA1C Group (%) Woerle HJ et al Arch Intern Med.  2004;164:1627-1632. [email_address]
  22. 22. Relative risk for death increases with 2-hour blood glucose irrespective of the FPG level <6.1 6.1–6.9  7.0  11.1 7.8–11.0 <7.8 Fasting plasma glucose (mmol/l) 2-hour plasma glucose (mmol/l) 2.5 2.0 1.5 1.0 0.5 0.0 Hazard ratio Adjusted for age, center, sex DECODE Study Group. Lancet 1999;354:617–621 [email_address]
  23. 23. Relationship Between HbA 1c , FPG and PPG in Treated T2DM Patients <ul><li> Major </li></ul><ul><li>HbA 1c (%) FPG (mM) PPG (mM) Problem </li></ul><ul><li>5 5.1 7.0 - </li></ul><ul><li>6 6.3 8.4 PPG </li></ul><ul><li>7 7.5 9.8 PPG </li></ul><ul><li>8 8.7 11.2 FPG+PPG </li></ul><ul><li>9 9.9 12.6 FPG+PPG </li></ul><ul><li>10 11.1 14.0 FPG </li></ul>Woerle et al., 2006. [email_address]
  24. 24. Long-Term Problems Source: Kidney Intl. 1987; 32 (supp 22): S53-S56 [email_address] Post-prandial glucose Range Time to onset of proteinuria Persistent <200 110-198 23 yrs Intermittent >200 118-228 19 yrs Persistent > 200 201 + 14 yrs
  25. 25. Long-Term Problems 22-yr CVD Mortality Risk by Baseline post-challenge glucose Source: Chicago Heart Study, Lowe et al, Diabetes Care, 1997; 20: 163-170. [email_address]
  26. 26. Effects of Reducing PPHG [email_address] Risk of progression to diabetes Risk of cardiovascular events Risk of development of new cases of hypertension
  27. 27. Post Prandial Hyperglycemia <ul><li>Rationale for treating PPHG : </li></ul><ul><li>Postprandial blood glucose better predictor of glycaemic control than FPG </li></ul><ul><li>PPHG associated with microvascular complications e.g. Retinopathy, Nephropathy etc. </li></ul><ul><li>Recognized risk factor for CAD e.g. MI, death </li></ul>[email_address]
  28. 28. Postprandial Hyperglycemia (PPHG) : Management <ul><li>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. </li></ul><ul><li>Similarly, the higher the fasting hyperglycemia in the morning, the higher postprandial hyperglycemia will be during the day. </li></ul><ul><li>Thus, maneuvers that primarily target fasting hyperglycemia might not be successful in normalizing fasting plasma glucose levels and achieving satisfactory HbA 1c levels if postprandial hyperglycemia persists. </li></ul>General Considerations John E. Gerich, MD. Arch Intern Med.  2003;163:1306-1316. [email_address]
  29. 29. Non pharmacologic Interventions <ul><li>In individuals with IGT and in those with type 2 diabetes with suboptimal, but not awful, glycemic control (eg, HbA 1c 7.0%-8.0%), simple lifestyle modifications such as exercise, weight reduction, or change in diet composition can be particularly helpful. </li></ul><ul><li>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. </li></ul><ul><li>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. </li></ul>John E. Gerich, MD. Arch Intern Med.  2003;163:1306-1316. [email_address]
  30. 30. Approaches/Agents That Address Postprandial Hyperglycemia <ul><li>Meglitinides </li></ul><ul><li>Alpha-Glucosidase Inhibitors </li></ul><ul><li>Prandial Insulin </li></ul><ul><li>GLP-1 analogues </li></ul><ul><li>DPP-IV inhibitors </li></ul><ul><li>Pramlintide </li></ul><ul><li>Glycemic Index/Load </li></ul>[email_address]
  31. 31. <ul><li>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. </li></ul><ul><li>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. </li></ul>[email_address]
  32. 32. Results & Conclusion Voglibose, in addition to lifestyle modification, can reduce the development of type 2 diabetes in high-risk individuals with impaired glucose tolerance. [email_address]
  33. 33. Br J Clin Pharmacol / 66:2 / 318–319 [email_address]
  34. 34. Results & Conclusion <ul><li>Voglibose treatment prevented the increase of body weight induced by Pioglitazone in Type 2 diabetes patients. </li></ul><ul><li>Thus, Voglibose may be a potentially useful drug for increasing the benefit of Pioglitazone treatment by controlling body weight. </li></ul>Br J Clin Pharmacol / 66:2 / 318–319 [email_address]
  35. 35. Conclusions <ul><li>Hyperglycemia is an important risk factor for both microvascular and macrovascular complications of diabetes. </li></ul><ul><li>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. </li></ul><ul><li>The key factor responsible for postprandial hyperglycemia is impaired early insulin secretion. </li></ul><ul><li>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). </li></ul>John E. Gerich, MD. Arch Intern Med.  2003;163:1306-1316. [email_address]
  36. 36. <ul><li>Thank You </li></ul>[email_address]