Adel abdel aziz.cgc 2
1 like838 views
Glycaemic targets are often not met with current diabetes treatments. While treatment aims to lower blood glucose, it can lead to weight gain and hypoglycemia. Achieving comprehensive glycaemic control requires addressing both fasting and post-prandial glucose to reduce symptoms, complications, and improve quality of life. The risk of severe hypoglycemia increases with longer duration of insulin treatment. Early and sustained glycemic control can reduce long-term complications like heart attacks and eye/kidney/nerve damage.
Adel abdel aziz.cgc 2
- 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-EGYPT 422HQ10PM039
- 2. Glycaemic targets are going unmet with current treatments 80 P<.001 Shortcomings 70 of current treatments Treatment Goal at 8 y, % 60 Patients Obtaining P=.001 50 • Glucose control is difficult 40 even with intensification of 30 therapy 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 achieve glycaemic 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 target 1. 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, et al. 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 diabetes Del Prato S, et al. Int J Clin Pract. 2005,59:1345-55.
- 5. Early achievement and maintenance of glycaemic control reduces the incidence of long-term complications UKPDS: Early intensive therapy in newly diagnosed type 2 diabetes significantly reduces 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 randomisation No. At Risk Conventional therapy 1138 1013 857 578 221 20 1138 1018 844 508 172 13 Sulphonylurea- insulin 2729 2488 2097 1459 577 66 2729 2465 2076 1368 488 53 Holman R, et al. N Engl J Med. 2008;359:1577-89.
- 6. Achieving comprehensive glycaemic control requires 1 an action on both FPG and PPG HbA1c= Fasting Glucose + Postprandial Glucose Relative contributions of postprandial and fasting hyperglycemia (%) to the overall diurnal hyperglycemia FPG PPG 100 80 Contribution (%) 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 control 2 Excessive fluctuations in daily glucose levels contribute to symptoms, complications and impaired QoL glucose level Daily plasma 1. 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 and CV 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 episodes increases 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 mechanism for 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 events2 1. DCCT Research Group. Diabetes Care 1988;11:567-73. 2. Russell-Jones D, Khan R. Diabetes Obes Metab. 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) 6 Change 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 effect on HbA1c and weight change Weight loss Metformin DPP-4 Inhibitors HbA1c increase HbA1c decrease TZDs Weight gain Sulphonylureas
- 13. Injectable anti hyperglycaemic drugs and their effect 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