Genetic basis of type 2 diabetes
Genetic factors play a critical role in Type 2 diabetes as shown by family, twin and migration studies. Whilst the rising prevalence of Type 2 diabetes reflects increasing food intake and reduced exercise it is the genetically susceptible individuals and races who are most likely to develop diabetes. Recent evidence has supported a genetic rather than the "fetal malnutrition" explanation of the association of low birth weight with diabetes. Low birth weight in the offspring of men with Type 2 diabetes supports the "fetal insulin hypothesis" which proposes that genes that reduce insulin secretion or action will reduce insulin mediated growth of the fetus, and hence birth weight, as well as predispose to diabetes latter in life.Defining the underlying molecular genetics of Type 2 diabetes has proved to be a "nightmare" due to the late age of onset, major role of environmental factors, and the disease heterogeneity. Progress is now being made with large UK and international collaborative patient collections combining with technical advances enabling rapid, large scale analysis. Major progress has been in defining the genes causing both beta-cell and insulin resistant monogenic diabetes. Common, less severe, variation in these genes can predispose to Type 2 diabetes as seen in PPARγ, IPF-1 and Wolfram1.
The analysis of the molecular genetics of Type 2 diabetes and subsequently gene-gene and gene environment interaction is an important challenge that will require major collaborative studies.