Genetic etiology of type 2 diabetes mellitus: a review

Abstract

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes characterized by elevated levels of plasma glucose caused by impairment in both insulin secretion and action. It is becoming an epidemic leading to various complications and its prevalence and incidence are increasing at an alarming rate in developing countries like India, raising a major public health concern. Both the genetic and environmental factors play a strong role in the manifestation of this complex genetic disorder. In the recent years, there has been a spate of molecular genetic investigations, including whole genome scans, to test the association of genetic variants with T2DM in different patho-physiological pathways. A large number of candidate genes have been identified to be associated with T2DM, albeit only a couple of them show consistency in association in different populations/ethnic groups. Given relatively high risk for T2DM in India and immense genetic heterogeneity and substructure of the constituent populations, the number of studies is too small to be able to characterize the genetic basis of the disease in India. The recent dramatic increase in number of affected people indicates that lifestyle factors related to urbanization and sedentary occupations may be particularly important in triggering the genetic elements that cause this type of diabetes. Therefore, it is imperative to precisely establish the underlying genetic and environmental factors behind this complex genetic disorder so that preventive measures can be initiated. We have attempted to review the molecular genetic studies conducted, till date, globally on T2DM along with the epidemiological, environmental and ethnic factors implicated in the manifestation of T2DM.

Zinc Transporters, Mechanisms of Action and Therapeutic Utility: Implications for Type 2 Diabetes Mellitus

“…Several genomewide association studies (GWASs) have implicated ZnT8 in T2DM in humans [8, 155–157]. Thus, having two copies of the at-risk polymorphic variant rs13266634, a nonsynonymous single nucleotide polymorphism (SNP) (Arg325Trp) in ZnT8 is associated with a 43% increase risk of developing diabetes [158].…”

“…The prevalence of this metabolic disorder is expected to increase from 171 million people in 2000 to 366 million in 2030, predominately due to changes in nutrition, reduced physical activity, and obesity [4]. Complications arising from T2DM include renal failure [5], blindness [6], and dyslipidemia [7], and it is widely accepted to be a fundamental and foremost basis for cardiovascular disease [8]. Given this projection, T2DM is becoming a leading cause of morbidity and mortality that results in a significant reduction in quality of life and life expectancy [9].…”

Association of the rs7903146 and rs12255372 polymorphisms in the TCF7L2 gene with type 2 diabetes in a population from northeastern Brazil

“…The different types of diabetes include types 1 and 2 in addition to rare forms of the disease such as gestational diabetes and maturity onset diabetes in youth (MODY) (Kommoju and Reddy, 2011). Type 2 diabetes (T2D) is the most common form of the disease, accounting for approximately 90% of the diabetes cases worldwide.…”

Association of multiple mineral and vitamin B group intake with blood glucose using quantile regression analysis: NHANES 2007–2014

“…Our results also showed that the intake of calcium contributes to maintaining healthy blood glucose levels. The role of genetic factors in the development of diabetes is universally known (37). Therefore, for some people with normal blood glucose and family history of diabetes, we consider that calcium supplementation may appropriately reduce their risk of diabetes.…”