Thongchai Pratipanawatr Update on DM treatment Thongchai Pratipanawatr

เราทำไมต้องรักษาโรคเบาหวาน?

เราทำไมต้องรักษาโรคเบาหวาน? 1.ให้ผู้ป่วยอายุยืนยาว 2. ให้ผู้ป่วยไม่เจ็บไม่ป่วย 3. ให้ผู้ป่วยให้ผู้ป่วยมีความสุข

The impact of type 2 diabetes

50% of type 2 diabetes patients have complications at the time of diagnosis MICROVASCULAR MACROVASCULAR Retinopathy, glaucoma or cataracts Cerebrovascular disease Coronary heart disease Nephropathy In the UKPDS, 50% of patients had a diabetes-related complication at diagnosis.1 Neuropathy affects around 70% of those with diabetes at the time of diagnosis, leading to 55,000–60,000 amputations in the US each year.2 Retinopathy, glaucoma or cataracts occur in around 10% of people after 15 years of diabetes. Blindness affects around 2%.2 Nephropathy is the leading cause of end-stage renal disease.2 Coronary heart disease (CHD) affects 7.5–20% of all people with diabetes over 45 years of age in the US. The risk of CHD is two to four times higher than for those without diabetes.2 Cerebrovascular disease: the risk of stroke is two to four times higher in people with diabetes. Fifteen percent of people with type 2 diabetes die from stroke.2 The risk of peripheral vascular disease is four to eight times higher in people with type 2 diabetes.2 1. UKPDS Group. UKPDS 33. Lancet 1998; 352:837–853. 2. World Health Organization/International Diabetes Federation. The economics of diabetes and diabetes care: a report of the Diabetes Health Economics Study Group. 1999 (WHO). Peripheral vascular disease Neuropathy UKPDS Group. UKPDS 33. Lancet 1998; 352:837–853.

Thai Diabetic Registry Project: Diabetic complications J Med Assoc Thai 2006; 89(Suppl 1): S1-9

Atherosclerosis in Diabetes ~80% of all diabetic mortality 75% from coronary atherosclerosis 25% from cerebral or peripheral vascular disease >75% of all hospitalizations for diabetic complications National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995.

Causes of death in Thai diabetes pts

Current ADA treatment targets HbA1c < 7% Blood pressure < 130/80 mmHg LDL-cholesterol < 100 mg/dl (2.6 mmol/l) HDL-cholesterol Men > 40 mg/dl (1.1 mmol/l) Women > 50 mg/dl (1.3 mmol/l) Triglycerides < 150 mg/dl (1.7 mmol/l) Aspirin ASA 75-162mg/day Others American Diabetes Association. Diabetes Care 2004; 27 (Suppl. 1):S15–S35.

Thai Diabetic Registry Project: Metabolic targets 2003 J Med Assoc Thai 2006; 89(Suppl 1): S1-9

Dyslipidemia/lipid management Statin therapy should be added to lifestyle therapy, regardless of baseline lipid levels, for diabetic patients: with overt CVD (A) without CVD who are over the age of 40 and have one or more other CVD risk factors. (A) American Diabetes Association. Diabetes Care 2008; 31 (Suppl. 1):S12–S54.

Dyslipidemia/lipid management For lower-risk patients than those specified above (e.g., without overt CVD and under the age of 40). Statin therapy should be considered in addition to lifestyle therapy if LDL cholesterol remains 100 mg/dl or in those with multiple CVD risk factors (E). American Diabetes Association. Diabetes Care 2008; 31 (Suppl. 1):S12–S54.

Dyslipidemia/lipid management In individuals without overt CVD, the primary goal is an LDL cholesterol 100 mg/dl . (A) In individuals with overt CVD, a lower LDL cholesterol goal of 70 mg/dl. (E) If drug-treated patients do not reach the above targets on maximal tolerated statin therapy, a reduction in LDL cholesterol of 40% from baseline is an alternative therapeutic goal. (A) American Diabetes Association. Diabetes Care 2008; 31 (Suppl. 1):S12–S54.

Percentage of Thai diabetic patients who may need lipid lowering agents NCEP III target New 2005 ADA lipid target All Age >40 No need for lipid lowering agents 13 2.7 1.4 Need for lipid lowering agents 87 97.3 98.6

Glycemic control

Glycemic control A1C <7% Prepandial glucose 90-130 Post pandial <180

Glycemic control Diabetic diet Exercise Medication Type 1 DM Insulin Oral hypoglcemic agent

New ADA/EASD consensus 2008

Tier 1:Glucose lowering intervensions HbA1c Advantage Disadv Sulphonylurea 1-2% Rapidly effective Weight gain, Hypoglycemia Metformin Weight neutral GI side effect, C/I in renal failure Insulin 1.5-3.5% No dose limit, rapidly effect, improve lipid Lifestyle Broad benefits Insufficiency within 1st yr

Tier 2:Glucose lowering intervensions HbA1c Advantage Disadv TZDs 0.5-1.4% PIO:Improve lipid profile, decrease MI Flueid retension, CHF, Fracture, weight gain, potential increase MI (Rosi) GLP 1 0.5-2% Weight loss Two injection a day, GI side effect, long term safety not established

Other interventions Disadv HbA1c Advan Glinide 0.5-1.5% Rapidly effective Weight gain, Hypoglycemia, 3-times a day Acrabose 0.5-0.8% Weight neutral GI side effect, 3-times a day DDP IV inhibitor long term safety not established

Tier 1: Well-validated therapies Life style intervention + Metformin Add Sulfonylurea Add Basal insulin Intensive insulin treatment+metformin

Tier 2: Less well-validated therapies Life style intervention + Metformin Add Pioglitazone or GLP-1 Met+SU+Pio or Met+Basal insulin Intensive insulin treatment+metformin

Recent diabetic trials 1. UKPDS 10 yrs Follow up Glycemic control and macrovascular complication 2. ADVANCE Tight glycemic control (HbA1c<6.5) reduce complications Microvascular Macrovascular 3.ACCORD Tight glycemic control (HbA1c<6.0) reduce complications 1. N Engl J Med 2008;359:1-13 2. N Engl J Med 2008;358:2560-72. 3.N Engl J Med 2008;358:2545-59.

Summerize the studies on glycemic control and complications UKPDS1 ADVANCE2 ACCORD3 Onset Newly 8 10 Prior CVD 32 35 Target FPG(mg/%) 108vs270 HbA1c(%) 6.5 vs 7-8 6.0 vs 7-8 F/U(yr) 5 3.5 1. N Engl J Med 2008;359:1-13 2. N Engl J Med 2008;358:2560-72. 3.N Engl J Med 2008;358:2545-59.

Summerize the studies on glycemic control and complications UKPDS1 ADVANCE2 ACCORD3 HbA1c (%) 6.4 vs 7.0 6.5 vs 7.5 Microvas Better Same CVD Worst Sudden death 1. N Engl J Med 2008;359:1-13 2. N Engl J Med 2008;358:2560-72. 3.N Engl J Med 2008;358:2545-59.

Glycemic control and complications 1. UKPDS 10 yrs Follow up Microvascular(~6yrs) Yes Macrovascular Yes 2. ADVANCE (HbA1c<6.5) F/U 5 year Microvascular Yes Macrovascular No 3.ACCORD (HbA1c<6.0) F/U 3.4 yrs Macrovascular No(worst) 1. N Engl J Med 2008;359:1-13 2. N Engl J Med 2008;358:2560-72. 3.N Engl J Med 2008;358:2545-59.

A1C Goals For Clinical Practice 10.0 9.5 DISCUSSION POINTS: Although there is evidence that we have better tools to more aggressively treat diabetes, recent population data show that A1C levels are often in excess of 8 or 9%. This is far above the current AACE target goal A1C (less than 6.5) and the ADA target goal A1C (less than 7%)… Click 1: Percent of patients >8% arrow appears Recent publications based on data collected in the late 1990s through 2000 found approximately 40 to over 50% of patients with diabetes have an A1C >8%. Click 2: Percent of patients >9.5% arrow appears Approximately 20 to over 40% of patients fall well within the “red” range where patients show very poor glycemic control (A1C 9.5%). Click 3: Insulin user arrow appears Even patients with type 2 diabetes who commit to insulin therapy fail to reach glycemic goals much of the time. Approximately 30% of patients using insulin in a recent survey of patients with type 2 diabetes had an A1C less than 8%. SLIDE BACKGROUND: NHANES/BRFSS data from two US population-based cross-sectional surveys: NHANES III: National Health and Nutrition Examination Survey, 1988-1994 (total people NHANES III surveyed = 16,705) N=1026 from NHANES III participants with self-reported diagnosis of diabetes BRFSS: Behavioral Risk Factors Surveillance System, 1995 (total people BRFSS surveyed = 103,929) N=3059 from BRFSS participants with self-reported diagnosis of diabetes Subjects were aged 18-75, with a self-reported diabetes diagnosis, median A1C=7.5% Data from these two surveys were analyzed separately Ref: Saaddine_21417AnnInternMed2002_p565,568 Harmel et al study was noncomparative, multicenter, epidemiologic survey of type 2 patients from 9 community care clinics in western US (1997-1998) Subjects (N=602) were aged 35-70 years, using oral antidiabetic medications or insulin or both, mean A1C = 8.2% Ref: Harmel_21416EndocrPract2002_p185,187,189 9.0 ~70% have A1C > 7 % Thailand Diabetic Registry. A1C (%) 8.5 8.0 7.5 7.0 ADA Target < 7 ? 6.5 ADVANCE Target ADA 2006: “The HbA1c goal for the individual patient is an HbA1c as close to normal (<6%) as possible without significant hypoglycemia” < 6.5 6.0 X ACCORD Target ? 5.5

Management for type 1 diabetes

วิธีการใช้ยาฉีดอินสุลิน เบาหวานชนิดที่ 1 Multiple insulin injection ( 4 injections/ day ) Continuous insulin infusion pump เบาหวานชนิดที่ 2 Mix and split ( 2 injections/ day ) or Oral hypoglycemic agent + bedtime insulin                                                    

Hypertension control

What is BP optimal target? Answer: BP<130/80 mmHg

จะเลือกใช้ยาลดความดันอย่างไร ?

จะเลือกใช้ยาลดความดันอย่างไร ? ACE inhibitor If fail Add Thiazide diuretic

จะเลือกใช้ยาลดความดันอย่างไร ? ACE inhibitor + Thiazide diuretic If fail Add B-blocker or Ca blocker

จะเลือกใช้ยาลดความดันอย่างไร ? ไม่สามารถใช้ ACE inhibitor เช่น ไอ Thiazide diuretic or A II blocker

Management of dyslipidemia

Lipid treatment (LDL target) Without CVD Age<40 LDL <100 mg/dl Age>40 Cholesterol ≥135: Start Statin Aim 30-40% reduction and LDL<100

Lipid treatment (LDL target) With CVD Cholesterol ≥135: Start Statin Aim 30-40% reduction and LDL<70

Percentage of Thai diabetic patients who may need lipid lowering agents NCEP III target New 2005 ADA lipid target All Age >40 No need for lipid lowering agents 13 2.7 1.4 Need for lipid lowering agents 87 97.3 98.6

Other dyslipidemia TG >400 mg/dl : Fibrate HDL<40 mg/dl Primary prevention: no medication secondary prevention: Fibrate

Anti-platelet agents

ASA(75-162 mg/day) A secondary prevention A primary prevention Age>40 year or Additional risk factor F Hx, HT, smoking, dyslipidemia or albuminurea Not recommended for age<21, no data for age<30.

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