Pathogenesis, risk assessment and prevention of type 2 diabetes mellitus

Type 2 diabetes mellitus is a complex, polygenic disease with a heterogeneous pathophysiology, mainly characterised by obesity-associated insulin resistance and a progressive failure of pancreatic beta-cells. Predominant risk factors for its development are abdominal obesity and age; other factors that augment the individual disease risk independent of obesity are the nutritional pattern (low consumption of fibres, high consumption of red meat, saturated and trans fat), lifestyle (smoking, low physical activity), and biomarkers such as blood pressure, HbA1c, serum adiponectin and inflammatory cytokines. These variables can provide the basis for a precise risk assessment and a personalised prevention. Genotyping for the presently known gene variants conferring an increased disease risk adds relatively little to the information provided by the phenotypic risk factors and biomarkers. However, genetic information is necessary for a personalised risk assessment and intervention that begins before phenotypic risk factors are detectable. The incidence of type 2 diabetes can significantly be lowered by reduction of the intraabdominal fat mass (by nutritional intervention and exercise), and by pharmacological control of post-prandial blood glucose excursions. Because of the high portion of non-responders to a preventive intervention, current efforts aim at the identification of phenotypic and genetic variables predicting the success of the intervention.