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

H. King et al, Diabetes Care 1998 Sep;21(9):1414-31H. King et al, Diabetes Care 1993 Jan;16(1):157-77 Ali O et al, Diabetes Care 1993 Jan;16(1):68-75

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

Diabetes Across the GlobePopulation Mortality

Rate per 100,000

Prevalence

Male DM Female DM Both Sexes DM

World *******1.5% 4%

US Whites *****19% 12% 14% ****7.8%

US Japanese 20% 16%

Japan Japanese **9.9% 5% 4% ******10.9%

Philippines *9.8% ***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 specificityThe 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

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

Non DM, no MI

DM but no MINon DM with MI

DM with MI

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

Kessler II, Am J Med 1971 Dec;51(6):715-24

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

Mortality Ratio Falls with Age of PatientType 1 Type 2

M 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

Figure from Muller WA,, J Insur Med 1998;30(1):17-27, Published erratum appears in J Insur Med 1998;30(2):129.

Risk of nephropathy declines if no proteinuria after 15 years of diabetes history

Type 1 Type 2

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

Dinneen SF, et al Arch Intern Med 1997 Jul 14;157(13):1413-8

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

Stroke

Diabetics have 4 times more strokes than non-diabetics

Eriksson KF et al, Diabetologia 1998 Sep;41(9):1010-6

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

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

http://www.unos.org/Newsroom/critdata_main.htm

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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):809-27Nasr 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 !