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Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
Adel abdel aziz.cgc 2
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Adel abdel aziz.cgc 2

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  • 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. 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. 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. 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. 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. 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. 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. 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. 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. ‘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. 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. 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. Injectable anti hyperglycaemic drugs and theireffect on HbA1c and weight change Weight loss GLP-1 analogues HbA1c increase HbA1c decrease Weight gain Insulin
  • 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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