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Milestones in Diabetes Treatment

Management of Diabetes Treat to Target Approach (A1c <7%) by Professor Dr Intekhab Alam D epartment of Medicine Postgraduate Medical Institute Lady Reading Hospital, Peshawar. Milestones in Diabetes Treatment. 1920. 1940. 1960. 1980. 2000. Insulin glargine. DCCT. NPH insulin. A1c.

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Milestones in Diabetes Treatment

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  1. Management of DiabetesTreat to Target Approach (A1c <7%)byProfessorDr Intekhab AlamDepartment of MedicinePostgraduate Medical InstituteLady Reading Hospital, Peshawar.

  2. Milestones in Diabetes Treatment 1920 1940 1960 1980 2000 Insulin glargine DCCT NPH insulin A1c Metformin Insulin discovered First sulphonylureas UKPDS Insulin pump Lente insulins Rapid-acting insulin DCCT, Diabetes Control and Complications Trial; UKPDS, United Kingdom Prospective Diabetes Study. 1. Tattersall RB. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Boston, Mass: Blackwell Science; 2003. 2. US FDA Center for Drug Evaluation and Research. Available at: http://www.fda.gov/cder/da/ddpab96.htm. Accessed March 18, 2003. 3. Lantus Consumer Information. Available at: http://www.fda.gov/cder/consumerinfo/druginfo/lantus.htm.Accessed March 18, 2003.

  3. Dual defect of type 2 diabetes: Treating a moving target b-cell Dysfunction Insulin Resistance Type 2 Diabetes Hyperglycaemia Insulin Action b-cell Failure Insulin Concentration Insulin Resistance Euglycaemia Normal Diagnosis oftype 2 diabetes Progression oftype 2 diabetes IGT ± Obesity DeFronzo et al. Diabetes Care 1992;15:318-68

  4. Progressive hyperglycaemia in type 2 diabetes 9 Diet 8 Insulin Median HbA1C (%) Metformin 7 HbA1C 6.5% (IDF & AACE goal value) Sulphonylurea 6 0 2 4 6 8 10 Time from randomisation (years) UKPDS Group. Lancet 1998;352:854-65

  5. ADA- and AACE/ACE-Recommended Goals for Glycaemic Control: A1c, FPG, and PPG Goal1 Biochemical Control1 Normal1 A1c* (%) <6.0 <7.0† FPG (mg/dL)Average preprandial <110 90-130‡ PPG (mg/dL) <140 <180§ *Referenced to the nondiabetic range using a DCCT assay.1 †AACE/ACE recommendation: 6.5%.2 ‡AACE/ACE recommendation: <110 mg/dL.2 §AACE/ACE recommendation: <140 mg/dL.2 ADA, American Diabetes Association; AACE/ACE, American Association of Clinical Endocrinologists/American College of Endocrinology; FPG, fasting plasma glucose; PPG, postprandial glucose; DCCT, Diabetes Control and Complications Trial. 1. ADA. Diabetes Care. 2003;26(suppl 1):S33-S50. 2. AACE/ACE. Endocr Pract. 2002;8(suppl 1):40-82.

  6. A1c Reflects Overall Glucose Control • A1c is the glycated form of the abundant red blood cell protein1 • A1c levels provide a 2- to 3-month index of glycaemic control2 • The target A1c level for patients with diabetes is <7%1 • Overall blood glucose control is best obtained by monitoring A1c3 1. Pickup JC. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Boston, Mass: Blackwell Science; 2003. 2. Clark N. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002. 3. Cefalu WT. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.

  7. Relationship of Mean Plasma Glucose and A1c MPG, mean plasma glucose. Adapted from Rohlfing CL et al. Diabetes Care. 2002;25:275-278.

  8. A1c and Relative Risk of Microvascular Complications: DCCT Retinopathy Nephropathy Neuropathy Microalbuminuria 20 15 13 11 9 Relative Risk 7 5 3 1 6 7 8 9 10 11 12 A1c (%) DCCT, Diabetes Control and Complications Trial. 1. Adapted from Skyler JS. Endocrinol Metab Clin North Am. 1996;25:243-254. 2. DCCT. N Engl J Med. 1993;329:977-986. 3. DCCT. Diabetes. 1995;44:968-983.

  9. Type 2 Diabetes Is a ProgressiveDisease: UKPDS Cross-sectional median values Conventional Treatment* (n=1138) Intensive Treatment† (n=2729) 9 8 Median A1c (%) 7 6 0 0 3 6 9 12 15 Time From Randomisation (years) *Diet, only. †Insulin or sulphonylurea + diet. UKPDS, United Kingdom Prospective Diabetes Study. Adapted from UKPDS Group. Lancet. 1998;352:837-853.

  10. Good Glycaemic Control Reduces Incidence of Complications Risk reduction by decrease in A1c (%) Complications DCCT1,2 Ohkubo3 UKPDS4 of diabetes mellitus (9% 7%) (9% 7%) (8% 7%) Retinopathy -63% -69% -21% Nephropathy -54% -70% -34% Neuropathy -60% – – Macrovascular disease -41%* – -16%* *Not statistically significant. DCCT, Diabetes Control and Complications Trial; UKPDS, United Kingdom Prospective Diabetes Study. 1. DCCT Research Group. N Engl J Med. 1993;329:977-986. 2. DCCT Research Group. Diabetes. 1995;44:968-983. 3. Ohkubo Y et al. Diabetes Res Clin Pract. 1995;28:103-117. 4. UKPDS Group. Lancet. 1998;352:837-853.

  11. Correlation of A1c and Complication Risk: UKPDS Risk reduction in complications per each 1% reduction in mean A1c Type 2 DM 43 37 Risk Reduction (%) 21 21 14 Any Endpoint Related to Diabetes Death Related to Diabetes Fatal and Nonfatal MI Amputation or Death From PVD Microvascular UKPDS, United Kingdom Prospective Diabetes Study; MI, myocardial infarction; PVD, peripheral vascular disease. Stratton IM et al. Br Med J. 2000;321:405-412.

  12. Preservation of Benefit: EDIC Progression of Retinopathy Type 1 DM Conventional Treatment* Intensive Treatment† 24 22 20 18 16 14 12 Cumulative Incidence (%) 10 8 6 4 2 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 EDIC (year) *1-2 insulin injections and 1 urine/blood glucose test daily. †3 insulin injections/pump treatments daily + SMBG + diet + exercise. EDIC, Epidemiology of Diabetes Interventions and Complications trial; SMBG, self-monitored blood glucose. DCCT/EDIC Research Group. N Engl J Med. 2000;342:381-389.

  13. Risk of Death Related to A1c Levels A1c 5.0%-5.4% A1c 5.5%-6.9% 6 A1c 7.0% 4 Relative Risk (%) 2 0 Cardiovascular Disease Ischaemic Heart Disease All Causes Note: A1c <5.0% was defined as a relative risk of 1. Adapted from Khaw K-T et al. Br Med J. 2001;322:1-6. Norfolk cohort of the European Prospective Investigation of cancer and Nutrition, n-4662

  14. A Comprehensive Approach To Treat to Target Type 2 DM Conventional Treatment Intensive Treatment 60 P=.007 50 40 Primary Composite Endpoint* (%) 30 20 10 0 0 12 24 36 48 60 72 84 96 Follow-up (months) Number at Risk/Treatment Conventional Intensive 80 72 70 63 59 50 44 41 13 80 78 74 71 66 63 61 59 19 *Composite endpoint = cardiovascular death and amputation (with either therapy), and relative risk for organ damage (with intensive therapy). Gaede P et al. N Engl J Med. 2003;348:383-393. Steno diabetes center,Denmark. n 160.

  15. Insulin Helps Achieve Control Conventional Glucose Control Type 2 DM 60 * 47 50 40 35 Patients Achieving A1c <7% at 6 Years (%) 30 20 20 10 0 Insulin Alone SU ± Insulin Intensive Glucose Control (FPG < 108 mg%) Median A1c (IQR): 7.6% (6.8-8.7) 7.1% (6.2-8.0)† 6.6% (6.0-7.6)†‡ *P=.011 sulphonylurea  insulin vs insulin alone; †P<.00011 insulin or sulphonylurea  insulin vs conventional glucose control policy; ‡P=.0066 sulphonylurea  insulin vs insulin alone. SU, sulphonylurea; IQR, interquartile range. Adapted from Wright A et al. Diabetes Care. 2002;25:330-336.

  16. Treat to Target A1c • A1c is a key marker of diabetes treatment efficacy • A1c levels correlate with a patient’s relative risk of death and of microvascular and macrovascular complications • The DCCT, UKPDS, and other major trials—as well as major diabetes organizations—support treatment-to-target A1c <7% DCCT, Diabetes Control and Complications Trial; UKPDS, United Kingdom Prospective Diabetes Study.

  17. Treat to Target A1c • Aggressive therapy is often necessary to achieve control • Treat to target requires a comprehensive approach: control of blood pressure and control of LDL-c, bolstering a concerted attack on A1c levels • Treat to target reduces risk of complications and its associated costs LDL-C, low-density lipoprotein cholesterol.

  18. Pitfalls In HbA1C Estimation • False high HbA1C: • Hb F, Acetylated Hb, Cabamoylated Hb. • False low HbA1C: • Hb S or C, Hemolytic anemias, Hemmorhage. • Reliability in diagnosing Diabetes: sensitivity 85% specificity 91%. • Fructosamine levels: nonenzymatic glycosylation of serum proteins esp Albumin 1.5-2,4 mmol/l with 5gm/dl of Albumin.

  19. The ABC of Diabetes Management • Effective management of diabetes requires • A – Control of A1c • B – Control of Blood pressure • C – Control of Cholesterol

  20. ADA Glycemic Targets Normal Goal Action Level HbA1c (%) <6 <7 >8 Fasting and preprandialblood glucose (mg/dL) <110 80 to 120 >140 American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus.Diabetes Care 1999;22(Suppl):S32-S41.

  21. ADA Blood Pressure Targets Goal (mm Hg) Usual patient <130/85 Isolated systolic hypertension If ≥180 <160 If 160 to 179 Reduceby 20 American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus.Diabetes Care 1999;22(Suppl):S32-S41.

  22. ADA LDL-Cholesterol Targets (mg/dl) Medical Nutrition Therapy Drug Therapy Begin Rx Goal Begin Rx Goal With CV disease >100 ≤100 >100 ≤100 No CV disease >100 ≤100 >130 ≤100 American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus.Diabetes Care 1999;22(Suppl):S32-S41 & S56-S59.

  23. European Diabetes Policy Group Desktop Guide ‘Providing a greater emphasis on arterial risk factor management rather than just good blood glucose control’ European Diabetes Policy Group (1998–1999)

  24. European Diabetes Policy Group Desktop Guide • At each assessment • Set individual targets for blood glucose, blood lipid and blood pressure • Targets should incorporate an assessment of risk and the patient’s needs • Set realistic objectives within a time period • Evaluate individual targets at least yearly in the light of past successes and if clinical circumstances change European Diabetes Policy Group (1998–1999)

  25. Assessment • Measure • HbA1c every 2-6 months • blood lipid profile (total, LDL- and HDL-cholesterol, and triglycerides) every 2-6 months if previously above assessment levels otherwise annually • blood pressure at each consultation unless known to be below assessment levels European Diabetes Policy Group (1998–1999)

  26. European Diabetes Policy Group advice ‘Failure to attempt to reach agreed targets is inadequate care’ European Diabetes Policy Group (1998–1999)

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