MSc in Diabetes A population approach

1. UniS MSc in DiabetesA population approach Impaired glucose tolerance and undiagnosed diabetes Ross Lawrenson Postgraduate Medical School University of Surrey

2. Metabolic syndrome • Impaired glucose tolerance • Undiagnosed Type 2 diabetes

3. Theories on the aetiology of Type 2 diabetes • Barker hypothesis • Reaven Syndrome • Thrifty genotype

4. Barker hypothesis • The thrifty phenotype

5. Odds ratio of NIDDM and IGT related to birth weight Odds Ratio Birth Weight in pounds

6. Barker hypothesis • Malnutrition in the prenatal and early infant years. (Hales and Barker) • Beta cells increase of 130 times between 12 th intra-uterine week and 5 th post natal month. • Malnutrition. • Obesity in later life.

7. Reaven syndrome • First described by Himsworth in 1936 • Described in New Zealand by Ian Prior in 1966 in Maori (obesity, hypertension diabetes and gout) • Syndrome X sometimes called Reaven syndrome after Gerry Reaven

8. Relationship between glucose uptake and fasting plasma glucose Reaven G. Diabetes 1988

9. Reaven syndrome • Reaven syndrome or Syndrome X • Resistance to insulin-stimulated glucose uptake • Hyperinsulinaemia or glucose intolerance • Hypertension • Decreased HDL • Increased VLDL • Central obesity

10. Thrifty genotype • Thrifty genotype • Ability to lay down fat • Survive times of hardship • Alternative metabolic pathway in high protein diet

11. Age adjusted prevalence of NIDDM and IGT in adults aged over 20 years Simmons D. The Coventry Diabetes Study. Quarterly Journal of Medicine. 1991; 81: 1021-1030

12. Prevalence of undiagnosed NIDDM with age in New Zealand adults aged over 20 years. The overall crude rate was 56/3896 (1.4%).

13. Prevalence of undiagnosed NIDDM per 1000 people screened by BMI.

14. Mean BMI of men and women by ethnic origin.

15. Variables associated with the presence of undiagnosed diabetes in people 40 years.

16. Significant factors associated with undiagnosed diabetes in Europeans over the age of 40 years. 95% Confidence interval Variable Adjusted OR Age 1.07 1.04 - 1.10 BMI 1.13 1.06 - 1.21 Family history 2.34 1.16 - 4.71

17. Study using the General Practice Research Database - characteristics of subjects Type 1Type 2 Mean age in 199233.4 63.6 Mean age at diagnosis (yrs) 18.0 56.7 Mean duration to 1992 (yrs) 16.2 7.1 Mean period of follow-up (yrs) 5.3 5.1 Total of 5528 type 1 and 25707 type 2 patients

18. Impaired glucose tolerance • This group are asymptomatic and do not have diabetes • Do not suffer the microvascular complications • The diagnosis is important because: • High rate of macrovascular disease • A number will eventually become diabetic • Secondary prevention in this group may reduce morbidity and mortality

19. Prevalence

20. Progression to diabetes

21. Impaired glucose tolerance • After 10 years between 15 and 45% will have diabetes • After 10 years about 1/3 will be normal • If OGTT is repeated within 3 months approximately 50% will have a normal GTT • Tukitonga showed that those with IGT in Niue who progressed to diabetes were more likely to be sedentary whilst those who were active were more likely to return to normal • Tuomilheto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P et al. Prevention of Type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New England Journal of Medicine 2001; 344(18) 1343-9

22. Summary • Type 2 diabetes is increasing • Intervention strategies are needed to reduce incidence • Identifying undiagnosed patients with type 2 diabetes may reduce onset of complications • Identifying and treating IGT has proved worthwhile