English abstract
This study was carried out to investigate Type 2 diabetes (T2D) among Omanis. In order to investigate T2D from different angles, this study was divided into six small studies.
Study 1: This study assessed the clinical care given to T2D patients at Sultan Qaboos University Hospital (SQUH). A total of 673 T2D Omani patients were included. Using the American Diabetes Association (ADA) standards of medical care in diabetes, 22% of the patients achieved HbAlc goal, 47% achieved blood pressure goal, 48% achieved serum low density lipoprotein (LDL) cholesterol goal, 67% achieved serum triglycerides goal, 59% and 43% of the males and females achieved high density lipoprotein (HDL) cholesterol goals, respectively. Almost 60% of the patients had urinary microalbumin/creatinine ratio (ACR) within normal range. The clinical outcomes of the care that T2D patients get at SQUH were lower than those reported in Europe and North America. However, it is similar to those reported in the Arabian Gulf region.
Study 2: This study estimated the prevalence of T2D complications and associated problems among Omani patients. A total of 986 T2D Omani patients were included in this study. Half of the patients had at least one T2D complication, while 86% had a complication or associated problem. Ten percent had documented retinopathy, 15% had microalbuminuria, 31% had nephropathy, 9% had neuropathy, 2% had PVD, 20% had CAD, 5% had a stroke and 66% had hypertension. From serum lipids profile analysis, 35% had high total cholesterol, 63% had high LDL cholesterol, 38% had high triglycerides, while 50% and 48% of the males and females, respectively, had low HDL cholesterol. In addition, 36% were overweight and 51% were obese. The prevalence of diabetes complications and associated problems among Omani T2D patients was not different from other populations. However, prevalence of diabetes retinopathy and neuropathy were lower and this indicates the need for a proper assessment and documentation.
Study 3: The objective of this study was to estimate the prevalence of impaired fasting glucose (IFG) among Omani adults with no family history (FH) of diabetes; and to investigate the factors behind the risk of developing T2D, excluding FH of diabetes, among the Omani adults. A total of 1182 Omani subjects, aged > 40 years, were interviewed and asked if they had T2D or FH of T2D. Only 191 (16%) reported no personal history of T2D and had no FH of the disease. Those subjects (n=191) underwent anthropometric and biochemical investigations. Twenty-six percent of those (n=42) were found to have IFG. BMI, fasting insulin, HbAic and blood pressure (BP), were also significantly higher among IFG individuals. In addition, fasting insulin, BP and serum lipid profile were correlated with obesity indices. In spite of claiming no FH of diabetes, yet a large sector of Omani adults have a high risk of developing diabetes,
Study 4: The aim of this study was to screen Omani individuals for the familial aggregation of T2D. A random cohort of 1182 Omani individuals visiting Family Medicine Clinic at SQUH, for regular medical checkup, aged > 40 years, were sampled. Only 16% of these Omani individuals had no diabetes and no FH of diabetes. Another separate random cohort of 232 Omani T2D patients, from the Diabetes Clinic at SQUH, were interviewed and questioned about their FH of T2D. Ninety five percent of these patients had a FH of diabetes. Eighty percent had first degree relatives with diabetes and 46% had second degree relatives with diabetes. At least one parent with diabetes was reported among 55% of these diabetics. The findings of this study confirm familial aggregation of diabetes among the Omani population.
Study 5: This study investigated the association of 10 known common gene variants with susceptibility to 12D among Omani Arabs using case-control design. A total of 992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped for the following gene variants: KCNJ11 (rs5219), TCF7L2 (rs7903146), CDKALI (rs10946398), CDKN2A/B (rs10811661), FTO (139939609 & rs8050136), IGF2BP2 (rs4402960), SLC30A8 (rs13266634) CAPN10 (rs3792267) and HHEX (rs1111875). Four gene variants showed significant association with T2D risk: KCNJII (rs5219), TCF7L2 (rs7903146); CDKALI (rs10946398) and CDKN2A/B (rs10811661).
Study 6: This study examined the utility of a family-based model for replicating the results of genome-wide association studies (GWAS) of T2D. In a total of 232 members of a large consanguineous Omani Arab pedigree, there were 27 diabetics and 50 prediabetics. All 232 individuals were genotyped for 14 known common gene variants of modest effect on T2D risk. Power analysis at a LOD score of 3, gave 80% power to locate a single specific locus that accounts for 52% of the total phenotypic variation. Using MGA, some common gene variants were found to have little (<5%) but significant impact on the heritability of T2D related QTs (KCNJII (r55219), IGF2BP2 (rs4402960), SLC3048 (rs13266634), CAPNIO (rs2975760) and FTO (rs8050136 & rs9939609)]. Sib-TDT analysis showed that some gene variants were significantly associated with T2D risk but didn't reach the level of significance after Bonferroni correction [KCNJII (rs5219) & CAPNIO (41266971)]. We have demonstrated that, in principle, a family-based model with minor limitations could be used to replicate some of the results of large GWAS case-control studies.
