difficulties in achieving

John B. Buse, MD, PhD Associate Professor of Medicine Chief, Division of General Medicine and Clinical Epidemiology Director, Diabetes Care Center University of North Carolina Chapel Hill, NC jbuse@med.unc.edu Difficulties in Achieving Target A1c Values 63% of Patients With Diabetes are Not At ADA A1C Goal <7% 37.2% >8% 63% ≥7% 7.8% 25.8% 37.0% 17.0% 12.4% % of Subjects n = 404 A1C Adults aged 20-74 years with previously diagnosed diabetes who participated in the interview and examination components of the National Health Examination Survey (NHANES), 1999-2000. Only 7% of adults with diabetes in NHANES 1999-2000 attained: • A1C level <7% • Blood pressure <130/80 mm Hg • Total cholesterol <200 mg/dL Saydah SH et al. JAMA. 2004;291:335-342. Case DATE FPG AVG A1c REGIMEN SUMMARY MONITOR 3/28 150 9.8 70/30 - 36 BID ADD MTF 500 BID I 2/d 4/11 INCREASE 70/30 - 40 BID INCREASE MTF 1000 BID I+M 2/d 4/25 8.4 INCREASE 70/30 50 BID ADD ROSIGLITAZONE 4 QD I+M+R 2/d 5/11 162 CHANGE 70/30 - 45 Q AM, 50 Q PM I+M+R 2/d 5/22 132 6.9 SWITCH INSULINS: GLARGINE 75 QHS + ASPART 10 ac TID I+M+R 4/d 6/20 89 5.6 CHANGE ASPART 1 unit/5 grams CHO CHANGE GLARGINE 70 QHS INCREASE ROSIGLITAZONE 4 BID MDI+M+R 4/d 7/18 5.8 INCREASE ASPART 1 unit/3 grams CHO MDI+M+R 4/d 8/15 73 CHANGE GLARGINE 65 QHS MDI+M+R 4/d 9/19 5.2 CHANGE GLARGINE 62 QHS MDI+M+R 4/d Difficulties in Achieving Target A1C Values  What is the appropriate A1C target  Challenges – Late diagnosis and initiation of therapy – Therapeutic inertia – Lack of effective lifestyle intervention – Secondary failure – Adverse events associated with antihyperglycemic therapies – Complexity of care – Role of postprandial glucose in failure Difficulties in Achieving Target A1C Values  What is the appropriate A1C target  Challenges – Late diagnosis and initiation of therapy – Therapeutic inertia – Lack of effective lifestyle intervention – Secondary failure – Adverse events associated with antihyperglycemic therapies – Complexity of care – Role of postprandial glucose in failure DCCT Research Group. N Engl J Med. 1993;329:977-986. Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:103-117. UKPDS 33: Lancet 1998; 352, 837-853. Slide modified from D. Kendall - International Diabetes Center, Minneapolis. HbA1c Retinopathy Nephropathy Neuropathy Cardiovascular disease DCCT 9 → 7.2% 63% 54% 60% 41% (NS) Kumamoto 9 → 7% 69% 70% Improved - UKPDS 8 → 7% 17-21% 24-33% - 16% (NS) Intensive Diabetes Therapy: Reduced Incidence of Complications Potential Adverse Effects Related to Pursuit of Stringent Glycemic Goals  Hypoglycemia  Cost  Long-term exposure to poorly studied combinations of medications  Lessened attention to other difficult to manage health care risks (e.g. BP, HDL, immunization, cancer screening)  Weight gain Risk of Progression of Complications: DCCT Study Skyler JF. Endocrinol Metab Clin North Am. 1996;25:243-254. Relative Risk HbA1c, % 7 8 9 10 11 12 Diabetic retinopathy Nephropathy Neuropathy Microalbuminuria 15 13 11 9 7 5 3 1 Rate of Severe Hypo. (per 100 patient- years) 0 20 40 60 80 100 120 Severe hypoglycemia 6 Nathan D. American Diabetes Association 2005 Scientific Sessions; June 10-14, 2005; San Diego, CA. EDIC 12-year Follow-Up of DCCT Study End point Relative risk reduction (%) (95% CI) p Cardiovascular events 42 (19-63) 0.016 Nonfatal MI, stroke, and cardiovascular death 57 (12-79) 0.018 Incidence Rate for Complications in UKPDS: Epidemiological Analysis* * Expressed for white men aged 50-54 years at diagnosis and with mean duration of diabetes of 10 years Stratton, et al. BMJ. 321:405-412, 2000 Any diabetes related endpoint Myocardial infarction Microvascular endpoints 5 6 7 8 9 10 11 5 6 7 8 9 10 11 Updated mean hemoglobin A 1c 160 140 120 100 80 60 40 20 90 60 40 20 Adjusted incidence per 1000 patient years (%) [...]... Lower A1C – Sliding scale insulin Lifestyle intervention, patient education Use metformin, glitazones, α-glucosidase inhibitors, exenatide, nateglinide, analog insulin Monitor glucose, keep logs Goal resetting and dose reduction in response to severe or asymptomatic hypoglycemia Difficulties in Achieving Target A1C Values  What is the appropriate A1C target  Challenges – Late diagnosis and initiation... TZD Therapy on β−cell Function in ZDF Rats ZDF rat model – Obese, insulin resistant – Progressive decline in β cell Obese 6 weeks Obese 12 weeks  Lean control TZD 12 weeks Obese 16 weeks TZD 16 weeks function and mass  Effect of Glitazone – Improve insulin resistance and normalize glucose – Rosiglitazone prevents decline in β cell mass and maintains normal glucose Finegood D Diabetes 50:1021–1029,... Weight Gain: Management  Inform the patient of the risk – Greatest risk of weight gain -     Young Female Shorter duration of DM Higher A1C at baseline Lifestyle intervention Use metformin, α-glucosidase inhibitors, exenatide, pramlintide – Consider weight loss medications Monitor weight Dose reduction in response to excessive weight gain Diabetes Therapy and Hypoglycemia: Management      Inform... 5.2 5.0 - * * * * * P . Medicine Chief, Division of General Medicine and Clinical Epidemiology Director, Diabetes Care Center University of North Carolina Chapel Hill, NC jbuse@med.unc.edu Difficulties in Achieving Target. GLARGINE 65 QHS MDI+M+R 4/d 9/19 5.2 CHANGE GLARGINE 62 QHS MDI+M+R 4/d Difficulties in Achieving Target A1C Values  What is the appropriate A1C target  Challenges – Late diagnosis and initiation. failure Difficulties in Achieving Target A1C Values  What is the appropriate A1C target  Challenges – Late diagnosis and initiation of therapy – Therapeutic inertia – Lack of effective lifestyle intervention – Secondary