Adel abdel aziz.cgc 2

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Adel abdel aziz.cgc 2

  1. 1. Comprehensive Glycaemic Control Prof. ADEL A EL-SAYED MD Chair Elect Middle East and North Africa (MENA) Region International Diabetes Federation (IDF) Professor of Internal Medicine Sohag Faculty of Medicine Sohag-EGYPT422HQ10PM039
  2. 2. Glycaemic targets are going unmet with currenttreatments 80 P<.001Shortcomings 70of current treatments Treatment Goal at 8 y, % 60 Patients Obtaining P=.001 50• Glucose control is difficult 40even with intensification of 30therapy P=.06 20• Treatment related trade-offs 10 • Weight gain 0 HbA1c Systolic BP Cholesterol • Hypoglycaemia <6.5% <130 mm Hg <4.5 mmol/L Intensive (n=63) Conventional (n=67) Conventional therapy was according to 2000 revised Danish Medical Association guidelines (diet alone, oral hypoglycaemic drugs, and/or insulin); intenassive therapy added behaviour modification and pharmacologic therapy that targeted hyperglycaemia, hypertension, dyslipidaemia, and microalbuminuria, and added aspirin for secondary prevention of cardiovascular disease
  3. 3. Current management often fails to achieveglycaemic targets EUROPE LATIN AMERICA (CODE-2)1 (DEAL)2 31% HbA1c ≤6.5% 43% HbA1c ≤7% 69% 57% CANADA USA (DRIVE)3 (NHANES)4 53% 37% HbA1c ≤7% HbA1c <7% 47% 63% HbA1c above target HbA1c at or below target1. Liebl A, et al. Diabetologia. 2002;45:S23-S28. 2. Lopez Stewart G, et al. Rev Panam Salud Publica. 2007;22:12-20. 3. Braga M, etal. Presented at ADA 68th Scientific Sessions; 2008: Poster 1189-P. 4. Saydah SH, et al. JAMA. 2004;291:335-42.
  4. 4. Disease progression ultimately overwhelms current medications 10 9 HbA1c (%) 8 7 6 Duration of diabetesDel Prato S, et al. Int J Clin Pract. 2005,59:1345-55.
  5. 5. Early achievement and maintenance of glycaemic controlreduces the incidence of long-term complicationsUKPDS: Early intensive therapy in newly diagnosed type 2 diabetes significantlyreduces long-term complications Kaplan-Meier plots for cumulative incidence of clinical outcomes Myocardial infarction Microvascular Disease 1.0 1.0 Proportion with event Proportion with event P=0.01 P=0.001 0.8 0.8 0.6 0.6 Conventional Conventional therapy therapy 0.4 0.4 0.2 0.2 Sulphonylurea- Sulphonylurea- insulin insulin 0.0 0.0 0 5 10 15 20 25 0 5 10 15 20 25 Years since randomisation Years since randomisationNo. At RiskConventionaltherapy 1138 1013 857 578 221 20 1138 1018 844 508 172 13Sulphonylurea-insulin 2729 2488 2097 1459 577 66 2729 2465 2076 1368 488 53Holman R, et al. N Engl J Med. 2008;359:1577-89.
  6. 6. Achieving comprehensive glycaemic controlrequires 1 an action on both FPG and PPGHbA1c= Fasting Glucose + Postprandial GlucoseRelative contributions of postprandial and fasting hyperglycemia (%) to theoverall diurnal hyperglycemia FPG PPG 100 80Contribution (%) 60 40 20 0 <7.3 7.3-8.4 8.5-9.2 9.3-10.2 >10.2 n=58 n=58 n=58 n=58 n=58 HbA1c (%)Monnier L, et al. Diabetes Care. 2003;26:881-5.
  7. 7. Need for comprehensive glycaemic control2 Excessive fluctuations in daily glucose levels contribute to symptoms,complications and impaired QoLglucose levelDaily plasma1. Kleefstra N, et al. Neth J Med. 2005;63:215-21. 2. Monnier L, et al. JAMA. 2006;295:1681-7. 3.Cerriello A, et al. Nutr Metab Cardiovasc Dis. 2006;16:453-6. 4. Mitri J, Hamdy O. Expert Opin Drug Saf.2009;8:573-84. 5. Marrett E, et al. Diabetes Obes Metab. 2009;11:1138-44.
  8. 8. Inter-relationship between overweight/obesity, diabetes andCV risk: potential impact of treatment-related weight gain + Weight gain/ obesity Treatment- related weight + gain, and/or weight gain through Diabetes CV risk “defensive snacking” because of - hypoglycaemia Glucose- lowering therapy Increases CV risk Decreases CV risk
  9. 9. The incidence of severe hypoglycaemic episodesincreases with duration of treatment episode of severe hypoglycaemia Proportion reporting at least one Type 2 DM sulphonylureas (n= 103) 0.6 Type 2 DM <2 years insulin (n= 85) Type 2 DM >5 years insulin (n= 75) Type 1 DM <5 years (n= 46) Type 1 DM >15 years (n= 54) 0.4 Annual 0.2 Prevalence = 7% 0.0 Treated with <2 yrs >5 yrs <5 yrs >15 yrs sulphonylurea of insulin treatment of insulin treatment Type 2 diabetes Type 1 diabetes Error bars, 95% confidence interval. The proportion of patients with type 2 diabetes experiencing severe hypoglycaemia was similar for those treated with sulphonylureas or insulin for <2 years (7% in both groups)UK Hypoglycaemia Study Group. Diabetologia. 2007;50:1140-7.
  10. 10. ‘Defensive snacking’ as a potential mechanismfor weight gain in diabetes In the DCCT, insulin-treated patients with severe hypoglycaemia had a significantly (P<0.05) greater increase in weight than those without severe hypoglycaemia during the study1 Patients with severe +6.8 kg hypoglycaemia Patients without severe +4.6 kg hypoglycaemia 0 2 4 6 8 Weight gain (kg) A potential explanation for this is “defensive snacking” - an increase in a patient’s carbohydrate intake following hypoglycaemia due to their fear of further events21. DCCT Research Group. Diabetes Care 1988;11:567-73. 2. Russell-Jones D, Khan R. Diabetes ObesMetab. 2007;9:799-812.
  11. 11. Most current therapies result in weight gain over time UKPDS: up to 8 kg ADOPT: up to 4.8 kg in 12 years1 in 5 years2 8 100 Annualised slope (95% CI) Insulin (n=409) Rosiglitazone, 0.7 (0.6 to 0.8) 7 Metformin, -0.3 (-0.4 to -0.2) Glibenclamide, -0.2 (-0.3 to 0.0) 6Change in weight (kg) 96 5 Weight (kg) Glibenclamide (n=277) 4 92 3 Conventional (n=411)* 2 88 Treatment difference (95% CI) 1 Rosiglitazone vs metformin 6.9 (6.3 to 7.4); P<0.001 Metformin (n=342) Rosiglitazone vs glibenclamide, 0 2.5 (2.0 to 3.1); P<0.001 0 0 3 6 9 12 0 1 2 3 4 5 Years Years * Conventional treatment; diet initially then sulphonylureas, insulin and/or metformin if FPG >15 mmol/L (>270 mg/dL) n=at baseline 1. UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854-65. 2. Kahn SE, et al (ADOPT). N Engl J Med. 2006;355:2427-43.
  12. 12. Oral anti hyperglycaemia drugs and their effecton HbA1c and weight change Weight loss Metformin DPP-4 Inhibitors HbA1c increase HbA1c decrease TZDs Weight gain Sulphonylureas
  13. 13. Injectable anti hyperglycaemic drugs and theireffect on HbA1c and weight change Weight loss GLP-1 analogues HbA1c increase HbA1c decrease Weight gain Insulin
  14. 14. Summary• Diabetes treatment usually fails with time. So, it requires a more proactive approach• HbA1c is important but does not accurately reflect glycaemic fluctuations• Hypoglycaemia and weight gain may be barriers to tight glycaemic control• Drugs need to be chosen with a view to achieve tight glycaemic control with a low propensity for hypoglycaemia and/or weight gain

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