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New Concepts in Underwriting Diabetes September 2002 - Manila, Philippines By Dr. Philip Smalley MD FRCPC Vice President and Medical Director RGA International Toronto Objectives Diabetes definitions and epidemiology Discuss diabetic complications Demonstrate new therapies in diabetes Diabetes mortality and prognostic indicators Underwriting diabetes: • How to place the good risks and avoid the early death claims. Diabetes Classifications Type 1 Diabetes (10 – 15% of all diabetics) Type 2 Diabetes Maturity-onset Diabetes of Youth (MODY) Maternally Inherited Diabetes and Deafness Secondary Diabetes • Pancreatic disease • Hemochromatosis • Medication Induced Impaired Glucose Tolerance Gestational Diabetes Global Prevalence of Diabetes 135 million diabetics in the world 300 million by year 2025 • More diabetics in developed countries • More increase in diabetes prevalence in under-developed countries Impaired Glucose Tolerance more common 1/3 – 1/2 of diabetics are undiagnosed H. King et al, Diabetes Care 1998 Sep;21(9):1414-31 H. King et al, Diabetes Care 1993 Jan;16(1):157-77 Ali O et al, Diabetes Care 1993 Jan;16(1):68-75 Diabetes Across the Globe Population World US Whites Mortality Rate per 100,000 Prevalence Male DM Female DM *******1.5% *****19% US Japanese Japan Japanese **9.9% Philippines *9.8% Both Sexes DM 4% 12% 14% 20% 16% 5% 4% ****7.8% ******10.9% ***4% Asian Indians in Tanzania 40% Africans 0.3% Philippine Health Statistics – Department of Health, 1995; SEAMIC Health Statistics 1999 – http://www.seamic-imfj.or.jp/PDF/1999SHS/1-3.pdf SEAMIC Health Statistics 1999 - http://www.seamic-imfj.or.jp/PDF/1999SHS/1-3.pdf Fernando RE, Indian J Pediatr 1989 Nov – Dec;56 Suppl 1:S67-70 National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics fact sheet: general information and national estimates on diabetes in the United States, 2000. Bethesda, MD: U.S. Department of Health and Human Services, National Institutes of Health, 2002. http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#7 ***** World Health Organization: Themes and Focuses http://www.wpro.who.int/themes_focuses/ Theme2/focus4/t2f4pub_50dia.asp ****** Diabetes.com http://www.niddk.nih.gov/health/diabetes/pubs/dmstats/dmstats.htm#12 ******* WHO: The Global Burden of Disease 2000 project: aims, methods and data sources. Global Programme on Evidence for Health Policy Discussion Paper No. Annex Table 8 summarizes GBD 2000 Version 1 estimates of death by cause, age and sex… http://www3.who.int/whosis/burden/papers/Discussion%20Paper%2036%20Revised.doc * ** *** **** New Criteria for Diagnosis of DM Canadian and American Diabetes Association’s NEW Definition of Diabetes 1998 • FBS >125 mg/dl (7.0 mmol/l) • In past, diagnosis with glucose > 140 mg/dl (7.8 mmol/l) • Random glucose >200 mg/dl (11.1 mmol/l) and symptoms • IGT FBS 110 - 124 mg/dl • Normal FBS < 100 mg/dl Oral Glucose Tolerance Tests Glycosuria is poor marker of diabetes • Poor sensitivity and specificity The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus,, Diabetes Care Volume 22 Supplement 1, American Diabetes Association: Clinical Practice Recommendations 1999. Measures of Control Urine dipstick (poor indicator) Blood glucometer readings Hb A1c (reflects 12 - 15 weeks of control) Fructosamine (reflects 2 week control) Diabetes is a Serious Disease Acute onset ketoacidosis or hyperosmotic coma can be lethal Treatment induced hypoglycemia can be lethal Microvascular Complications • nephropathy, retinopathy, and neuropathy Macrovascular Complications • heart disease, stroke, peripheral vascular disease, diabetic ulcers Premature Death • Diabetics live about 8 years less than non-diabetics Yearly mortality in diabetics is 2.9% in meta-analysis of 27 international studies Kanters SD et al, Vasc Med 1999; 4(2): 67-75 Type 2 Versus Heart Disease Mortality Non DM, no MI DM but no MI Non DM with MI DM with MI Figure 1: Kaplan-Meier Estimates of the Probability of Death from Coronary Heart Disease in 1059 Subjects with Type 2 Diabetes and 1378 Nondiabetic Subjects with and without Prior Myocardial Infarction. Figure from Haffner SM et al, NEJM July 23, 1998 Vol. 339, No. 4 Determinants of All Cause Mortality in Diabetics Type 1 higher rates than Type 2 • Type 1 Risk Ratios of 3 to 15 • Type 2 Risk Ratios of 1.4 to 3.7 Effect of Gender Standardized mortality ratios higher for women than men in both Type 1 and Type 2 • 21,447 diabetics followed for 26 years • Male Standardized Mortality Ratio 1.44 - 1.74 • Female Standardized Mortality Ratio 1.73 - 2.42 Diabetes causes the loss of the usual protective effect of female hormones on the heart Kessler II, Am J Med 1971 Dec;51(6):715-24 Mortality Ratio Falls with Age of Patient Type 1 M Type 2 F M F Figure from Muller WA,, J Insur Med 1998;30(1):17-27, Published erratum appears in J Insur Med 1998;30(2):129. Effect of Duration of Diabetes Type 1 Type 2 Risk of nephropathy declines if no proteinuria after 15 years of diabetes history Figure from Muller WA,, J Insur Med 1998;30(1):17-27, Published erratum appears in J Insur Med 1998;30(2):129. Complications of Diabetes Heart Disease Major cause of death in diabetics Krolewski reported 2 fold risk of CAD mortality in males and 4 fold in females Occurs at younger ages than non-diabetics More atypical presentations of CHD Prognosis is worse in CHD with underlying diabetes Autonomic Neuropathy 72% five year survival with autonomic neuropathy 92% five year survival without neuropathy Figure from Muller WA,, J Insur Med 1998;30(1):17-27, Published erratum appears in J Insur Med 1998;30(2):129. Nephropathy Prevalence • 30 - 40% of Type 1 DM • 20% of Type 2 DM Proteinuria to renal failure in 5 to 23 years Improved prognosis of nephropathy recently with more BP therapy, better DM control and ACE Inhibitor therapy Nephropathy in Type 1 ____ Solid line 1971 ……. Fine dot 1983 . . . . . Dotted 1985 - - - - Slashed 1989 Also improved end stage kidney disease therapies and transplant mortality Figure from Muller WA,, J Insur Med 1998;30(1):17-27, Published erratum appears in J Insur Med 1998;30(2):129. Microalbuminuria (MAU) Confusing Name • “Small amounts of proteinuria” • 0.03 - 0.3 g/ day (30 - 200 ug / min) Use microalbumin / urine creatinine ratio Best to have repeated results Less MAU if diastolic BP is below 75 mmHg Becoming standard of care to check MAU yearly and treat with ACE Inhibitor to lower MAU Microalbuminuria (MAU) Marker of nephropathy in Type 1 diabetics Marker of heart disease in Type 2 diabetics Dinneen SF 1997 • Analyzed 11 studies of Type 2 and MAU • 20% to 36% of Type 2 had MAU • Odds ratio for death was 2.4 Dinneen SF, et al Arch Intern Med 1997 Jul 14;157(13):1413-8 Stroke Diabetics have 4 times more strokes than non-diabetics Treatment of Diabetes 12 year follow up of 6956 men with glucose intolerance Diet and exercise improved mortality • 6.5 / 1000 person-years with intervention • 14.0 / 1000 person-years without the intervention • 6.2 / 1000 person-yrs in normal glucose tolerance controls Eriksson KF et al, Diabetologia 1998 Sep;41(9):1010-6 Inhaled Insulin Cefalu WT et al, Inhaled Human Insulin Treatment in Patients with Type 2 Diabetes Mellitus, Annals of Internal Medicine 6 February 2001;134: 203-207 Newer Diabetes Therapies Combination therapies Agents to increase insulin sensitivity Drugs to delay glucose load from bowel Inhaled Insulin Pancreatic cell transplants Gene therapy 30 http://www.unos.org/Newsroom/critdata_main.htm 31 Gene Therapy for Diabetes Insert gene for insulin into intestine cells Diabetic mice have normal glucose levels http://news.bbc.co.uk/hi/english/sci/tech/newsid_1059000/1059925.stm Control of Diabetes Diabetes Control and Complication Trial • • • • • • 10 year study of 1,441 Type 1 DM Intensive group had better control 76% less retinopathy 60% less neuropathy 56% less nephropathy 3 times more hypoglycemia The DCCT Research Group, NEJM Sept 30, 1993 Vol. 329, No. 14 UK Prospective Diabetes Study (UKPDS) Multi-center study of Type 2 diabetics 3055 Type 2 patients with median follow up of 7.9 years Turner RC et al, BMJ 1998; 316:823-828 (14 March) Baldeweg SE et al, Prim Care 1999 Dec;26(4):809-27 Nasr CE et al, Cleve Clin J Med 1999 Apr;66(4):247-53 Turner RC, Diabetes Care 1998 Dec;21 Suppl 3:C35-8 Turner RC et al, BMJ 1998; 316:823-828 (14 March) What to look for in Underwriting Diagnosis Duration Treatment Control Follow up Complications Other cardiac risk factor profile Case 1 35 year old Type 1 Diabetic for 15 years on: 1) 30 units of insulin once per day or 2) 10 units of insulin 4 times per day with rare mild hypoglycemic episodes following glucometer readings carefully Case 2 55 year old Type 2 Diabetic 1) On oral pills glyberide 10 mg bid and metformin 1g tid with HbA1c 11.5 or 2) On insulin 10 units daily with HbA1c 5.5 Case 3 55 year old male Type 2 diabetic HbA1c 7.2 BP 150/90 Cholesterol 7.0 Ex-smoker for 5 yrs 55 year old male Type 2 diabetic HbA1c 9.2 BP 120/80 Cholesterol 4.9 Never smoked Case 4 22 year old Type 1 diabetic for 12 years. Urine microalbumin/urine Cr ratio is elevated. Proliferative retinopathy and BP is 170/95 Case 5 62 year old male with increased BMI at 28. Sees his MD frequently and had a normal blood tests 1 year ago. His stress test is normal. • a) Family Doctor recently found and started treatment for a FBS of 170 mg/dl (9.4 mmol/l) and HbA1c elevated to 7.0 • b) Insurance blood profile currently shows FBS of 170 mg/dl (9.4 mmol/l) and HbA1c is elevated at 7.0 Summary of Diabetes High risk if other risk factors or end organ damage especially Type 1 Diabetics Improved trends in therapy and case fatality rate Better risk in older ages Credit for cardiac work up, good control and follow up Urine microalbumin can stratify risks but has marketing issues Look at full risk factor profile Thank you !