Presentation on theme: "Management of Diabetes Treat to Target Approach (A1c <7%) by Professor Dr Intekhab Alam D epartment of Medicine Postgraduate Medical Institute Lady Reading."— Presentation transcript:
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 Insulin glargine Insulin discovered First sulphonylureas NPHinsulin Lente insulins Metformin Insulin pump Rapid-acting insulin UKPDS A1c DCCT 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; US FDA Center for Drug Evaluation and Research. Available at: Accessed March 18, Lantus Consumer Information. Available at: Accessed March 18, 2003.
Insulin Resistance Type 2 Diabetes -cell Dysfunction Insulin Resistance Hyperglycaemia Insulin Concentration Insulin Action Euglycaemia -cell Failure Normal IGT ± Obesity Diagnosis of type 2 diabetes Progression of type 2 diabetes Dual defect of type 2 diabetes: Treating a moving target DeFronzo et al. Diabetes Care 1992;15:318-68
Diet Metformin UKPDS Group. Lancet 1998;352: Median HbA 1C (%) Time from randomisation (years) Sulphonylurea Insulin Progressive hyperglycaemia in type 2 diabetes HbA 1C 6.5% (IDF & AACE goal value)
ADA- and AACE/ACE-Recommended Goals for Glycaemic Control: A1c, FPG, and PPG Normal 1 Goal 1 Biochemical Control 1 A1c * (%) <6.0 <7.0 <7.0 FPG (mg/dL) Average preprandial < PPG (mg/dL) <140 <180 § *Referenced to the nondiabetic range using a DCCT assay. 1 AACE/ACE recommendation: 6.5%. 2 AACE/ACE recommendation: 6.5%. 2 AACE/ACE recommendation: <110 mg/dL. 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.
A1c Reflects Overall Glucose Control u A1c is the glycated form of the abundant red blood cell protein 1 u A1c levels provide a 2- to 3-month index of glycaemic control 2 u The target A1c level for patients with diabetes is <7% 1 u Overall blood glucose control is best obtained by monitoring A1c 3 1. Pickup JC. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Boston, Mass: Blackwell Science; Clark N. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; Cefalu WT. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
Relationship of Mean Plasma Glucose and A1c MPG, mean plasma glucose. Adapted from Rohlfing CL et al. Diabetes Care. 2002;25:
DCCT, Diabetes Control and Complications Trial. 1. Adapted from Skyler JS. Endocrinol Metab Clin North Am. 1996;25: DCCT. N Engl J Med. 1993;329: DCCT. Diabetes. 1995;44: Relative Risk A1c (%) A1c and Relative Risk of Microvascular Complications: DCCT RetinopathyNephropathy Neuropathy Microalbuminuria 20
*Diet, only. Insulin or sulphonylurea + diet. UKPDS, United Kingdom Prospective Diabetes Study. Adapted from UKPDS Group. Lancet. 1998;352: Cross-sectional median values Time From Randomisation (years) Conventional Treatment* (n=1138) Intensive Treatment (n=2729) Median A1c (%) Type 2 Diabetes Is a Progressive Disease: UKPDS
Complications DCCT 1,2 Ohkubo 3 UKPDS 4 of diabetes mellitus (9% 7%) (9% 7%) (8% 7%) Retinopathy -63% -69% -21% Nephropathy -54% -70% -34% Neuropathy -60%–– Macrovascular disease -41%*– -16%* Risk reduction by decrease in A1c (%) Good Glycaemic Control Reduces Incidence of Complications *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: DCCT Research Group. Diabetes. 1995;44: Ohkubo Y et al. Diabetes Res Clin Pract. 1995;28: UKPDS Group. Lancet. 1998;352:
UKPDS, United Kingdom Prospective Diabetes Study; MI, myocardial infarction; PVD, peripheral vascular disease. Stratton IM et al. Br Med J. 2000;321: Correlation of A1c and Complication Risk: UKPDS Risk reduction in complications per each 1% reduction in mean A1c Amputation or Death From PVD Risk Reduction (%) Microvascular Any Endpoint Related to Diabetes Death Related to Diabetes Fatal and Nonfatal MI Type 2 DM
*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: Preservation of Benefit: EDIC Progression of Retinopathy EDIC (year) Cumulative Incidence (%) Conventional Treatment* Intensive Treatment Type 1 DM
Risk of Death Related to A1c Levels 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 CardiovascularDisease Ischaemic Heart Disease All Causes Relative Risk (%) A1c 5.0%-5.4% A1c 5.5%-6.9% A1c 7.0%
A Comprehensive Approach To Treat to Target *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: Steno diabetes center,Denmark. n Number at Risk/Treatment Conventional Conventional Intensive Intensive Primary Composite Endpoint* (%) Follow-up (months) P= Conventional Treatment Intensive Treatment Type 2 DM
*P=.011 sulphonylurea insulin vs insulin alone; P< 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: Patients Achieving A1c <7% at 6 Years (%)Conventional Glucose Control Insulin Alone SU ± Insulin Intensive Glucose Control (FPG < 108 mg%) Median A1c (IQR): 7.6% ( ) 7.1% ( ) 6.6% ( ) Median A1c (IQR): 7.6% ( ) 7.1% ( ) 6.6% ( ) * Insulin Helps Achieve Control Type 2 DM
DCCT, Diabetes Control and Complications Trial; UKPDS, United Kingdom Prospective Diabetes Study. Treat to Target A1c u A1c is a key marker of diabetes treatment efficacy u A1c levels correlate with a patients relative risk of death and of microvascular and macrovascular complications u The DCCT, UKPDS, and other major trialsas well as major diabetes organizationssupport treatment-to-target A1c <7%
LDL-C, low-density lipoprotein cholesterol. Treat to Target A1c u Aggressive therapy is often necessary to achieve control u Treat to target requires a comprehensive approach: control of blood pressure and control of LDL-c, bolstering a concerted attack on A1c levels u Treat to target reduces risk of complications and its associated costs
Pitfalls In HbA 1C Estimation u False high HbA 1C : –Hb F, Acetylated Hb, Cabamoylated Hb. u False low HbA 1C : –Hb S or C, Hemolytic anemias, Hemmorhage. u Reliability in diagnosing Diabetes: sensitivity 85% specificity 91%. u Fructosamine levels: nonenzymatic glycosylation of serum proteins esp Albumin 1.5-2,4 mmol/l with 5gm/dl of Albumin.
The ABC of Diabetes Management u Effective management of diabetes requires –A – Control of A1c –B – Control of Blood pressure –C – Control of Cholesterol
ADA Glycemic Targets American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 1999;22(Suppl):S32-S41. NormalGoalAction Level HbA1c (%) 8 Fasting and preprandial blood glucose (mg/dL) 140
ADA Blood Pressure Targets American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 1999;22(Suppl):S32-S41. Goal (mm Hg) Usual patient<130/85 Isolated systolic hypertension If 180<160 If 160 to 179Reduce by 20
ADA LDL-Cholesterol Targets (mg/dl) American Diabetes Association. Standards of Medical Care for Patients with Diabetes Mellitus. Diabetes Care 1999;22(Suppl):S32-S41 & S56-S59. Medical Nutrition Therapy Drug Therapy Begin RxGoal Begin Rx Goal With CV disease> > No CV disease> >
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)
European Diabetes Policy Group Desktop Guide u At each assessment –Set individual targets for blood glucose, blood lipid and blood pressure –Targets should incorporate an assessment of risk and the patients 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)
Assessment u 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 advice Failure to attempt to reach agreed targets is inadequate care European Diabetes Policy Group (1998–1999)