Obesity: is Type II diabetes a foregone conclusion or further dependent on genetic susceptibility?

Abstract

ū To date, 32 loci are shown to be significantly associated with BMI and account for 1.45% of the total variation in BMI. ū A proportion of the BMI risk loci are highly expressed in the brain and highlight the importance of energy regulation in overall obesity. „ Genetics of body fat distribution: ū To date, only 1.03% of the variance in waist:hip ratio (WHR), independent of BMI, is explained by the 14 associated loci. ū The 14 WHR-associated loci contain variation associated with cholesterol, insulin and insulin resistance, all linked to the development of Type 2 diabetes (T2D), and half of these loci show sex-specific effects. ū The overlap of loci that are associated with both WHR and T2D suggest a link between specific patterns of body fat, independent of overall obesity, and the development of T2D. „ Role of obesity in T2D: ū While not all obese individuals develop T2D, obesity generally increases the risk of insulin resistance, and consequently, increases the risk of developing T2D. ū While increased intra-abdominal fat is associated with increased T2D risk, the accumulation of gluteal fat is shown to decrease T2D risk; emphasizing the important role of body fat distribution in the development of T2D. „ Conclusion & future perspective: ū Both overall obesity and fat distribution patterns are linked to metabolic disturbances and T2D. ū There is a clear need to improve our understanding of the genes involved in obesity, body fat distribution and T2D. ū Fine mapping, sequencing and functional studies may be required to clarify the exact biological mechanisms for the implicated loci.