A four-stage model explaining the higher risk of Type 2 diabetes mellitus in South Asians compared with European populations.

With approximately 1.5 billion people at risk, the staggeringly high risk of Type 2 diabetes in South Asians comprises a global problem. The causes of this high risk are complex, with 23 major risk factors identified in a Lancet seminar. This paper proposes a four-stage explanatory model: (1) the birth of a small, adipose, lowlean mass South Asian baby--the phenotype tracking through life; (2) in childhood and early adulthood, the deposition of any excess energy intake preferentially in upper body and ectopic fat stores rather than in the lower body or superficial subcutaneous fat stores; (3) as a consequence of points 1 and 2, and exacerbated by an environment of low physical activity and excess calories, the accelerated appearance of high levels of plasma insulin, triglycerides and glucose, and the fatty-liver vicious cycle; (4) β-cell failure as a result of fewer β-cells at birth, exposure to apoptotic triggers such as fat in the pancreas, and high demand from insulin resistance, which causes diabetes. Other risk factors--especially energy-dense hyperglycaemic diet and low physical activity--play into this pathway. The recommended behavioural changes fit with this model, which brings clarity to guide future research, policy, practice and health promotion.