AimThe aims of this study were to determine the role of vitamin D, obesity and physical exercise in the regulation of glycemia in Type 2 Diabetes Mellitus patients in a highly consanguineous population. DesignCase and control study. SettingThe survey was carried out at the Hamad General Hospital and Primary Health Care (PHC) centers in the State of Qatar. SubjectsThe study was conducted from November 2012 to June 2014 among subjects above 30 years of age. Of the 2224 registered with diagnosed diabetes and free diseases attending Hamad General Hospital and PHC centers agreed and gave their consent to study. MethodsQuestionnaire included socio-demographic variables, body mass index (BMI), consanguinity, lifestyle habits, family history of diabetes, blood pressure and development of diabetes complications such as retinopathy, nephropathy, and neuropathy were collected at regular intervals throughout the follow-up. Univariate and multivariate statistical analysis were performed. ResultsThere were statistically significant difference between patients with diabetic and control in terms of ethnicity (p=0.012), level of education (p=0.002), occupation (p<0.001), monthly income (p<0.001), BMI(p=0.024), sport activity (p=0.018), cigarette smoking (p<0.001), consanguinity (p=0.029) and family history of Diabetes Mellitus (p<0.001) and co-morbidity hypertension (p=0.041). Further, the biochemistry values in the studied subjects with T2DM compared to healthy controls and the study revealed that serum Vitamin D, BMI, fasting glucose level, calcium, HbA1c, total cholesterol HDL, LDL, bilirubin, triglycerides, uric acid and blood pressure systolic and diastolic were higher in T2DM compared to their counterparts. Multivariate logistic regression showed that vitamin D deficiency ng/mL, Family History of T2DM, BMI (kg/m2) hypertension, consanguinity, income, mother occupation, ethnicity, educational level and Lack of physical exercise variables were significant predictors of diabetes. In the group of Diabetes Mellitus Type 2 patients, 39.3% as opposed to 51.2% in the control group had vitamin D deficiency, 25(OH) D3 levels≤10ng/ml (p<0.001). In the group of Diabetes Mellitus Type 2 patients, 34.6% as opposed to 37.9% in the control group had vitamin D insufficiency, 25(OH)D3 levels <20ng/ml (p < 0.001). In the group of Diabetes Mellitus Type 2 patients, 22.8% as opposed to 14.2% in the control group had vitamin D sufficiency, 25(OH)D3 levels >30 10ng/ml (p < 0.001). ConclusionVitamin D, family history of diabetes, consanguinity marriages’ and hereditary gene-environment interactions and physical exercise may also contribute to the current diabetes epidemic in Qatari’s Arab populations.