Understanding diabetes Do the recent trials help?

Transcription

1 Understanding diabetes Do the recent trials help? Dr Geoffrey Robb Consultant Physician and Diabetologist CMO RGA UK Services and Partnership Assurance AMUS 25 th March 2010 The security of experience. The power of innovation.

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5 Facts Diabetes affects > 10% of adults in developing countries Diabetics are 2 4 times more likely to develop severe cardiovascular outcome Most diabetics die from a cardiovascular cause

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7 Diabetes work to soar under HbA1c switch European authorities are considering changing the diagnostic criteria for diabetes, in a move that could almost double the number of people classed as having the disease, Pulse has learned. The American diabetes Association formally switched to diagnosis of type 2 diabetes by HbA1c testing in January, after an international consensus statement last year recommended it is used instead of the oral glucose tolerance test.

8 Diagnosis of Diabetes Fasting blood sugar (mmol/l) Up to 6.0 (WHO, IDF) Normal Impaired fasting glycaemia 7.0 or Diabetes more (US) Impaired fasting glycaemia 7.0 or Diabetes more

9 What about FBS mmol/l? 62% abnormal: 19% had diabetes 43% I.G.T

10 Mortality rate for diabetic and nondiabetic adults Rate per 1000 person years Age Diabetics Non Diabetics Data Ratio NHANES I

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12 Panzran study was: before HbA1c available before BSM before disposable syringes and needles before UKPDS before structured diabetes education

13 Differences between Type 1 and Type 2 Diabetes Type 1 Type 2 Thin Young Symptomatic Low insulin levels Quick onset Liable to ketosis Usually overweight Middle or old age May have no symptoms Insulin resistant Slow onset 12 years Not ketotic

14 Trials in Type I diabetes DCCT EDIC CSII Golden Years

15 DCCT 1441 patients with Type I Diabetes: Half standard treatment from usual physicians Half intensive treatment

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17 DCCT Did good control reduce complications? Microvascular YES Macrovascular? (too few events)

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20 CSII Continuous Subcutaneous Infusion of Insulin CSII MDI 20 patients 20 patients matched 3 year study of protein excretion

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23 Golden Years Project 50 years of Diabetes and Insulin Nabarro Medal 60 years of Diabetes and Insulin Lawrence Medal 70 years of Diabetes and Insulin Macleod Medal

24 Golden Years Project 581 subjects Common features: Normal body mass Insulin sensitive Parental longevity High HDL (Mean = 1.84 mmol/l) Moderate alcohol Low BP Poor diabetic control

25 Trials in Type II Diabetes UKPDS Blood sugar control Blood pressure control ADVANCE ACCORD VADT UK GP Database analysis

26 UKPDS Blood Glucose Control Conventional HbA1c 7.9% Intensive HbA1c 7.0% 10-year Follow-up 24% reduction in microvascular events (P = 0.001) 15% reduction in myocardial infarction (P = 0.01) Conclusion must be a legacy effect i.e. ongoing benefit from early good control

27 UKPDS Blood Pressure Control Tight control <150/85 Less tight control <180/105 Initial benefit 44% reduction in stroke NS reduction in myocardial infarction Conclusion Benefit LOST within 2 years of completion of study No legacy effect

28 ADVANCE 11,140 patients with Type II Diabetes Intensive: HbA1c aim 6.5%, actual 6.3% Conventional: HbA1c aim 7.3%, actual 7.0% Result NS reduction in CV events 21% reduction in nephropathy and microalbuminuria

29 ACCORD 10,251 patients with Type II Diabetes Poor control (average HbA1c of 8.1%) Previous CV event or other risk factors Target Intensive control HbA1c 6.0% or less (actual - 6.4%) Standard control HbA1c 7-7.9% (actual 7.4%) Result 22% increase in mortality in intensive group TRIAL STOPPED

30 VADT 1,791 patients with Type II Diabetes Uncontrolled at entry HbA1c 9.4% Target Intensive control HbA1c aim 6.0% (actual - 6.9%) Standard control HbA1c 7.5% (actual 8.5%) Result No difference in CV events

31 but Short history of DM (less than 12 years) BENEFIT from intensive treatment Long history of DM (more than 12 years) HAZARD from intensive treatment

32 UK GP Database analysis Survival Study Lancet 6th Feb ,965 intensified treatment with tablets (A) 20,005 intensified treatment with insulin (B)

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34 Table 1 Metabolic effects of conventional bariatric procedures 1 Improvement LAGB RYGB BPD Resolution of T2DM Rates of improvement (%) after surgery Resolution of hypertension Improvement of hyperlipidaemia Excess weight loss (% of excess body weight [actual weight minus ideal body weight] that is loss with surgery Abbreviations: BPD, biliopancreatic diversion; LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; T2DM, type 2 diabetes mellitus

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36 Table 1 Metabolic effects of conventional bariatric procedures 1 Improvement LAGB RYGB BPD Resolution of T2DM Rates of improvement (%) after surgery Resolution of hypertension Improvement of hyperlipidaemia Excess weight loss (% of excess body weight [actual weight minus ideal body weight] that is loss with surgery Abbreviations: BPD, biliopancreatic diversion; LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; T2DM, type 2 diabetes mellitus

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38 Table 1 Metabolic effects of conventional bariatric procedures 1 Improvement LAGB RYGB BPD Resolution of T2DM Rates of improvement (%) after surgery Resolution of hypertension Improvement of hyperlipidaemia Excess weight loss (% of excess body weight [actual weight minus ideal body weight] that is loss with surgery Abbreviations: BPD, biliopancreatic diversion; LAGB, laparoscopic adjustable gastric banding; RYGB, Roux-en-Y gastric bypass; T2DM, type 2 diabetes mellitus

39 Problem Areas HbA1c Microalbuminuria (early nephropathy) Blood pressure Lipids Retinopathy

40 HbA1c Glycated Haemoglobin Reflects average glucose levels over 2-3 month period ADA advise HbA1c level to diagnose diabetes threshold 6.5% Not point of care assay Readings unreliable with haemoglobinopathy, anaemia and renal failure

41 HbA1c for diagnosis? Logic Assay standardised Current difference between USA and WHO/IDF More accurately reflects CV risk Readings unreliable with haemoglobinopathy, anaemic and renal failure

42 Hazard ratio for CHD according to HbA1c HbA1c HR for CHD Less than Over

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44 For all cause mortality curve is J shaped

45 HbA1c Target HbA1c target is < 7.0% Except: recent onset, young age and no IHD aim lower with co-morbidities, older, long-standing DM accept higher

46 Microalbuminuria (early nephropathy) Common cause of end-stage renal disease Marker of increased CVD risk

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48 What is Microalbuminuria? Definitions and prevalence Levels of urinary albumin above the normal range, but lower than dipstick-positive proteinuria below are termed microalbuminuria Microalbuminuria is found in: 5-7% of the healthy population 12-30% of the hypertensive population Morning urine sample (mg/l) Morning urine sample Albumin to Creatinine Ratio (mg/mmol) Normal Microalbuminuria <20 Males <2.5 Females < Males Females Macroalbuminuria (proteinuria) >200 Males >25 Females >25

49 Microalbuminuria and Mortality 2138 Type 2 patients followed for 6.4 years Odds ratio for total mortality 2.4 ( ) Odds ratio for cardiovascular death and morbidity 2.0 ( ) Annual mortality rate with normoalbuminuria 2.7%, annual mortality rate with microalbuminuria 5.9%

50 Standards of Medical Care Table 15 Stages of CKD GFR Stage Description (ml/min per 1.73m 2 body surface area) 1 Kidney damage* with normal or increased GFR >90 2 Kidney damage* with mildly decreased GFR Moderately decreased GFR Severely decreased GFR Kidney failure <15 or dialysis * Kidney damage defined as abnormalities on pathologic, urine, blood or imaging tests. Adapted from ref 283.

51 Blood Pressure Target less than 130/80 Drugs 1 st choice ACE (e.g. Ramipril) or ARB (e.g. Irbesartan) 2 nd choice diuretic (USA), calcium blocker (UK) Most need 3-6 different drugs for good control

52 Lipids Target Total cholesterol less than 4 mmol/l LDL cholesterol less than 2 mmol/l (70 mg/dl) HDL cholesterol more than 1.3 mmol/l (50 mg/dl) Achieve by lifestyle advice Statin (not in pregnancy) + fibrate (?) + niacin (?)

53 Retinopathy Background risk to vision, not to life Proliferative risk to both Treatment available Good diabetic care Laser photocoagulation Anti VEGF injections

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55 Conclusion What s Important Smoking Lipid control Blood pressure Proteinuria Microalbuminuria Macroalbuminuria Gender Family history of premature death Glucose control especially in early years of condition

56 Thank you Any questions? Cases Dr Geoffrey Robb AMUS 25th March 2010 The security of experience. The power of innovation.