1. What… ? The SAUDI DIABETES Why do we have more Diabetes…? Genetic,… Nutritional,… Cultural,… Clues The 1 st Arab-Iranian Congress of Endocrinology and Diabetes

2. What… ? The RED ZONE WHO report (2000) More prevalence Less population Less prevalence More population Genetic: Ethnicity Family history Nutritional: Diet change Calorie intake Cultural: Physical activity 50% of the total Diabetic patients (~ 100 millions) Type 2 Diabetes Prevalence

3. What… ? Genetic in Diabetes Type 2 Diabetes Mellitus Genes Environment Higher concordance in monozygotic than dizygotic twins. Clustering in families. Higher prevalence in certain ethnic group. Higher concordance in monozygotic than dizygotic twins. Clustering in families. Higher prevalence in certain ethnic group. Links to life-style and diet. Different incidence in genetically similar population living in different area. Type 2 diabetes secondary to other conditions. Links to life-style and diet. Different incidence in genetically similar population living in different area. Type 2 diabetes secondary to other conditions. Genetic risk: will be the result of the following factor/s: Ethnicity: Arab, black, Hispanic,……. Tribe: Pima Indians Familial factor: Different studies. Twin: Identical & non-identical. Environmental Risk: The result of change in life style. Genetic Risk Enviro- nmental Risk Diabetes Joslin’s Diabetes Mellitus, 14 edition, 2005

4. What… ? Birmingham Study A random sample of 4886 birth. Comparison between the most valid data:2432North European babies 956British Pakistani babies Couple family relation in the two group:0.4%North European 69%British Pakistani Prevalence of congenital and genetic disorders:4.3%North European 7.9%British Pakistani Genetic Scin. 48, 446 2002

5. What… ? Genetic Factors in Type 2 Diabetes Strong family history of diabetes add to other factors like obesity. Ethnicity and family history show the genetic factor in type 2 diabetes. Controls Offspring of type 2 diabetes subjects Impact of diabetogenes on obesity induced insulin resistance

6. What… ? Genetic Factors in Type 2 Diabetes Ethnicity EffectFamilial Effect Diabetes Care, 23, 589-594. 2000

7. What… ? Ethnicity as a risk factor Arab Americans study Metabolic syndrome study: The Adult Treatment Panel (APT III) : Increase in prevalence with time. Prevalence is the same for both men and women but higher in women aged  50 years. Diabetes Care, Vol. 27, 2004

8. What… ? Saudi Genetic study Common disease. Behave Genetically. Extended families. Known tribes. Family 1 Family 2Family 3 187 74118 Number 93/94 33/4167/51 Male/Female 56 5547 Age (mean) 82% 48.6%7% Diabetes + IGT SAUDI DIABETES GENOME

9. What… ? One Saudi Family 90’s 70’s 50’s 30’s <30 Age group All are type 2 diabetic patients. Five level study. Intermarriage. Gene mixture. High diabetes prevalence AGE (years). Mean 23 Range15-31 SexMalesFemalesTotal Total 33 41 74 Affected 20 16 36 % 60.6 39 48.6 Affected female Affected male Non-affected female Non-affected male SAUDI DIABETES GENOME

10. What… ? Diabetes susceptibility loci Chromosome 2 Chromosome 5Chromosome 6Chromosome 10 IDDM10 IDDM17 IDDM1 IDDM15 IDDM5 IDDM8 IDDM18 IDDM7 IDDM12 IDDM13 Chromosome 11 Chromosome 14Chromosome 15Chromosome 18 IDDM17 IDDM3 IDDM11 IDDM2 IDDM4 18 regions of the genome have been linked with influencing type 2 diabetes risk

11. What… ? DNA analysis Central genetic lab. DNA samples stored in tissue bank. DNA analyzed with the same team.

12. What… ? Study Results HypothesisResultConclusion 1.Association of KCNJ11 E/E 529 (71%)Support association gene E23K polymorphisE/K 190 (26%)in susceptibility or K/K 23 (3%)pathogenesis. 2.Association of CAPN10111/111 haplotype Compared with that gene haplotypescombination observedseen in other population and other combinations 3.Association of PPARG very high incidence ofMore relevant gene P12Athe P12 allele (95%)

13. What… ? Genetic Role in the Prevalence Community tolerance to glucose metabolism differ in different communities and affect the prevalence of both diabetes and IGT. Acta Diabetol, 1999Chronic disease in SA 1999 Age effect Genetic effect

14. What… ? Diabetes Prevalence in Saudis Types of diabetes: Type 2 start earlier than before. Type 1 dominate population <18 years of age. Gestational diabetes in the reproductive age is found in 3.6% pregnant and non- pregnant subjects. Diabetes Type Age group adjusted prevalence rate 0-67-1819-4546-65>65 Type 1087.517.45.610 Type 21006.2578.994.490 Unpublished data (80,000 subjects)

15. Brazil 1974-1997 3.6% Brazil 1974-1997 3.6% Chile 1985-1995 1.6% Chile 1985-1995 1.6% Haiti 1978-1995 3.5% Haiti 1978-1995 3.5% Costa Rica 1982-1996 2.7% Costa Rica 1982-1996 2.7% USA 1973-1999 2.3% USA 1973-1999 2.3% Ghana 1988-1994 3.8% Ghana 1988-1994 3.8% England 1984-1994 2.4% England 1984-1994 2.4% Australia 1985-1995 4% Australia 1985-1995 4% China 1991-1997 1.1% China 1991-1997 1.1% Japan 1970-1996 2.5% Japan 1970-1996 2.5% Morocco 1987-1992 2.5% Morocco 1987-1992 2.5% Egypt 1978-1996 3.9% Egypt 1978-1996 3.9% Global prevalence of childhood obesity- predictor of type 2 diabetes in youth Lancet 2002; 360:476

16. What… ? Diabetes Prevalence Which type make the difference? Type 2 increase steadily with different age cut-offs demonstrating age effect. Type 1 demonstrate miner change demonstrating no age effect. Unpublished data (80,000 subjects)

17. What… ? Gene at larger scale Genetic factor: Genetic factor start earlier. It has more effect than other risk factors. It work independent to other risk factor. Positive family history of diabetes in Diabetic and Non- diabetic subjects 19.7 years

18. What… ? Obesity as risk factor Obesity as a risk factor: It has a major effect earlier in life (before 50 years of age) Older population (>65 years of age) obesity did not demonstrate any effect. Obesity effect

19. What… ? Physical activity as a risk factor Physical activity assessment: Physical activity duration or frequency did not demonstrate any effect. But the Met score show clear reduction with age without a significant difference between diabetic and none diabetic group. This could be explained by the narrow physical activity range. The magnitude of risk contributed by obesity is much greater than that imparted by lack of physical activity. Diabetes Care. 2007 Jan;30(1):53-8.

20. What… ? Physical Activity TV Watching (2h/d) Sitting At work (2h/d) Other sitting (2h/d) Standing At work (2h/d) Standing At home (2h/d) Brisk Walkin g (1h/d) % Change in Risk Percentage Changes in Risk of Developing type 2 Diabetes Among Non-diabetic Women Associated With Television (TV) Watching, Other Sedentary Behaviors, and Walking. Adjusted for age, smoking, alcohol consumption, family history of diabetes, and dietary covariates. All sedentary behavior variables are included simultaneously in the model. Other sitting includes reading, mealtime, and at desk. Error bars indicate 95% confidence intervals. JAMA. 2003;289:1785-1791.

21. What… ? Activity Diabetes/Mortality Leisure-time physical activity and age-adjusted CHD mortality rates in normoglycaemic men (n=6056) and men with IGT/diabetes (n=352) in the Whitehall study Leisure-time physical activity and age-adjusted CHD mortality rates in normoglycaemic men (n=6056) and men with IGT/diabetes (n=352) in the Whitehall study Clin. Sci. (2006) 110, 409-425

22. Vegetable protein Vegetable fat Animal fat Carbohydrate Animal protein 10000 7300 6300 4500 2700 2200 1700 1300 1000 700 400 200 Annual per capita national income (USD) Sweeteners What… ? Annual income and diet as a risk for type 2 diabetes: Relationship between the proportion of energy from each food source and gross national product per capita with the population residing in urban areas Fat 20% Carbohydrate 75% Protein 15% Fat 35% Carbohydrate 50% Protein 15% Increase Of fat by 40 gm/day Type 2 Diabetes risk increase by 3.4 fold Increase Of fat by 40 gm/day Type 2 Diabetes risk increase by 3.4 fold Diabetes care(17) 1994 Food balance data (FAOUN), GNP data from the world bank

23. What… ? Dietary change Diet change in SAUDI ARABIA: There has been an increase in the total calorie in-take from 1900 to 3000 cal. This increase is associated with low fiber diet.

24. What… ? Diet and Exercise Incidence of type 2 diabetes at or before the six year follow-up in the Da Qing study The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537-544.

25. What… ? Prevention Cumulative incidence of type 2 diabetes with: placebo, metformin and lifestyle intervention Diabetes is a reversible pathological condition that can be done with: Exercise Diet Drugs N Engl J Med 2002; 346: 393-403.

26. What… ? FINALLY Is it the Globalization ?