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The SAUDI DIABETES What… ? Why do we have more Diabetes…? Genetic,… Nutritional,… Cultural,… Clues The 1st Arab-Iranian Congress of Endocrinology and Diabetes The?RED ZONE What… 50% of the total Diabetic patients (~ 100 millions) More prevalence Less population Genetic: Ethnicity Family history Nutritional: Diet change Calorie intake Cultural: Physical activity WHO report (2000) Less prevalence More population 25 Type 2 Diabetes Prevalence 20 15 10 5 0 West countries East countries Genetic in Diabetes What… ? Type 2 Diabetes Mellitus Genes • Higher concordance in monozygotic than dizygotic twins. Environment • Links to life-style and diet. • Clustering in families. • Different incidence in genetically similar population living in different area. • Higher prevalence in certain ethnic group. • 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. Joslin’s Diabetes Mellitus, 14 edition, 2005 Genetic Risk Diabetes Environmental Risk Birmingham Study What… ? A random sample of 4886 birth. Comparison between the most valid data: 2432 956 North European babies British Pakistani babies Couple family relation in the two group: 0.4% 69% North European British Pakistani Prevalence of congenital and genetic disorders: 4.3% 7.9% North European British Pakistani 80 Corrected congenital malformation 60 Disability 40 Death 1 month - 5 years Death <1 month (lethal malformation) 20 Genetic abortion 0 North European British Pakistani Genetic Scin. 48, 446 2002 Genetic ?Factors in Type 2 Diabetes What… • Strong family history of diabetes add to other factors like obesity. • Ethnicity and family history show the genetic factor in type 2 diabetes. 12 Impact of diabetogenes on obesity induced insulin resistance 11 Insulin sensivity 10 9 8 7 6 5 4 90 100 110 120 130 140 150 160 170 180 Ideal body weight (%) Genetic ?Factors in Type 2 Diabetes What… Ethnicity Effect Familial Effect 90.00% General Population 50% General Population African Descent Latin American Descent Parent or Sibling Native American Descent Identical Twin Pima Indians 10.60% 10.20% 12.20% 5.20% Diabetes Care, 23, 589-594. 2000 12.00% 5.20% Ethnicity as a risk factor What… ? 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. Plevalence %% 75 70 Male Female 52 50 45 30 28 31 25 14 8.5 10 20-29 30-39 8 0 40-49 Age group Diabetes Care, Vol. 27, 2004 50-59 >60 Genetic study What… Saudi ? • Common disease. Family 1 Family 2 Family 3 187 74 118 93/94 33/41 67/51 56 55 47 82% 48.6% 7% Number Male/Female • Behave Genetically. Age (mean) Diabetes + IGT • Extended families. 46 36 34 DM IGT • Known tribes. 11 5 Family 1 SAUDI DIABETES GENOME Family 2 2 Family 3 What… ? One Saudi Family • All are type 2 diabetic patients. • Five level study. Sex Males Females Total Total 33 41 74 Affected 20 16 36 % 60.6 39 48.6 • Intermarriage. 90’s • Gene mixture. • High diabetes prevalence 70’s 50’s Affected female Affected male 30’s Non-affected female Non-affected male <30 Mean Range AGE (years) . 23 15-31 SAUDI DIABETES GENOME Age group Diabetes susceptibility loci What… ? Chromosome 2 Chromosome 5 Chromosome 6 Chromosome 10 IDDM1 IDDM10 IDDM15 IDDM7 IDDM12 IDDM13 Chromosome 11 IDDM18 Chromosome 14 IDDM5 IDDM8 Chromosome 15 IDDM17 Chromosome 18 IDDM2 IDDM4 IDDM17 IDDM11 IDDM3 18 regions of the genome have been linked with influencing type 2 diabetes risk What… ? DNA analysis • Central genetic lab. • DNA samples stored in tissue bank. • DNA analyzed with the same team. Study Results What… ? 1. 2. Hypothesis Result Conclusion Association of KCNJ11 E/E 529 (71%) Support association gene E23K polymorphis E/K 190 (26%) in susceptibility or K/K 23 (3%) pathogenesis. Association of CAPN10 111/111 haplotype Compared with that gene haplotypes combination observed seen in other population and other combinations 3. Association of PPARG very high incidence of gene P12A the P12 allele (95%) More relevant Genetic? Role in the Prevalence What… Community tolerance to glucose metabolism differ in different communities and affect the prevalence of both diabetes and IGT. 50 SAUDI ARABIA 25 KUWAIT 25 Genetic effect Age effect 0 0 20-30 30-40 40-50 Acta Diabetol, 1999 20-30 30-40 40-50 50-60 Chronic disease in SA 1999 >60 Diabetes Prevalence in Saudis What… ? Types of diabetes: 100 Distribution pattern of Diabetes Mellitus according 100 to age group 94.4 90 87.5 Type 2 start earlier than before. 80 Type 1 dominate population <18 years of age. 60 Gestational diabetes in the reproductive age is found in 3.6% pregnant and nonpregnant subjects. 78.9 GDM Type 1 Type 2 40 20 17.4 3.6 0 6.25 00 0 5.6 0 10 0 0-6 years Diabetes Type Type 1 Type 2 Unpublished data (80,000 subjects) 7-18 years 19-45 years 46-65 years > 65 years Age group adjusted prevalence rate 0-6 7-18 19-45 46-65 >65 0 100 87.5 6.25 17.4 78.9 5.6 94.4 10 90 Global prevalence of childhood obesity- predictor of type 2 diabetes in youth USA 1973-1999 2.3% Costa Rica 1982-1996 2.7% Haiti 1978-1995 3.5% Japan 1970-1996 2.5% Chile 1985-1995 1.6% China 1991-1997 1.1% Brazil 1974-1997 3.6% England 1984-1994 2.4% Ghana 1988-1994 3.8% Morocco 1987-1992 2.5% Egypt 1978-1996 3.9% Australia 1985-1995 4% Lancet 2002; 360:476 Diabetes Prevalence What… ? 30 Which type make the difference? 25 Prevalence of DM using different age cut-offs 19.8 Type 2 increase steadily with different age cut-offs demonstrating age effect. Type 1 demonstrate miner change demonstrating no age effect. 17.8 20 15.2 15 10 12.5 Type 1 Type 2 7 5 0.8 1.2 1.4 1.5 1.6 0 Over-all Unpublished data (80,000 subjects) > 20 years > 25 years > 30 years > 35 years What… G ? ene at larger scale 80 Positive family history of diabetes in Diabetic and Nondiabetic subjects Genetic factor: Non-Diabetic Saudi Genetic factor start earlier. Diabetic Saudi 60 Diabetic American Non-Diabetic American It has more effect than other risk factors. 40 It work independent to other risk factor. 70 60 Percent (%) cases of subjects with established family history of diabetes (N = 9,055) 20 19.7 years 50 40 30 20 0 38.7% 57.7% Non-Diabetic Diabetic 10 0 0-6 7-18 19-45 46-65 >65 Obesity as risk factor What… ? 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. 60 Obesity among Diabetics and Non-Diabetics Percent (%) cases of DM according to Body Mass Index (BMI) 50 Obesity effect 40 42.4 50 33.5 40 30 30 20 Diabetic Non-Diabetic 10 24.2 20 10 0 0 7-18 19-45 46-65 >65 Normal Overweight Obese Physical activity as a risk factor What… ? Physical activity assessment: Physical activity duration or frequency did not demonstrate any effect. 6 Met Score (N) Met Score (DM) Activity hours (N) 4 Activity frequancy (N) Activity hours (DM) Activity frequancy (DM) But the Met score show clear reduction with age without a significant difference between 2 diabetic and none diabetic group. This could be explained by the narrow physical activity range. 0 7-18 19-45 46-65 >65 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. Physical Activity What… ? 30 25 20 % 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. 15 10 5 0 -5 -10 -15 -20 -25 -30 -35 -40 -45 TV Watching (2h/d) JAMA. 2003;289:1785-1791. Sitting At work (2h/d) Other sitting (2h/d) Standing At work (2h/d) Standing At home (2h/d) Brisk Walkin g (1h/d) Activity Diabetes/Mortality What… ? 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 Annual income and diet as a risk for type 2 diabetes: What… ? Relationship between the proportion of energy from each food source and gross national product per capita with the population residing in urban areas Animal Vegetable protein protein 10000 Annual per capita national income (USD) 7300 Vegetable fat Animal fat Carbohydrate Sweeteners 6300 4500 Fat 35% Carbohydrate 50% Protein 15% 2700 2200 Increase Of fat by 40 gm/day 1700 1300 1000 Type 2 Diabetes risk increase by 3.4 fold 700 400 200 Food balance data (FAOUN), GNP data from the world bank Fat 20% Carbohydrate 75% Protein 15% Diabetes care(17) 1994 change What…Dietary ? 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. 4000 3600 Total fat intake 123 3000 120 3000 2000 160 1900 80 1000 40 0 0 1970 1990 USA 33 1970 1990 What… ? Diet and Exercise Incidence of type 2 diabetes at or before the six year follow-up in the Da Qing study Incidence per 100 person 20 18 Lean Obese 16 14 12 10 8 6 4 2 0 Control Diet Exercise The Da Qing IGT and Diabetes Study. Diabetes Care 1997; 20: 537-544. Exercise+Diet Prevention What… ? 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. FINALLY What… ? Is it the Globalization ?