Genes, diet and type 2 diabetes mellitus: a review

Abstract

Diabetes mellitus is widely recognized as one of the leading causes of death and disability. While insulin insensitivity is an early phenomenon partly related to obesity, pancreatic beta-cell function declines gradually over time even before the onset of clinical hyperglycemia. Several mechanisms have been proposed to be responsible for insulin resistance, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction, as well as glucotoxicity, lipotoxicity, and amyloid formation for beta-cell dysfunction. Moreover, the disease has a strong genetic component, although only a handful of genes have been identified so far. Diabetic management includes diet, exercise and combinations of antihyperglycemic drug treatment with lipid-lowering, antihypertensive, and antiplatelet therapy. Since many persons with type 2 diabetes are insulin resistant and overweight, nutrition therapy often begins with lifestyle strategies to reduce energy intake and increase energy expenditure through physical activity. These strategies should be implemented as soon as diabetes or impaired glucose homoeostasis (pre-diabetes) is diagnosed.

Figure 1

Simplified model of factors affecting the development of type 2 diabtes.

Figure 2. Interrelation between genes and environmental factors in type 2 diabetes

Genes in combination with environmental factors may lead to obesity, insulin resistance and finally diabetes. Environmental factors may also act in concert together with diabetes candidate and susceptibility genes to trigger the pathogenesis of type 2 diabetes directly.