Aetiology of non-insulin dependent diabetes.

The importance of genetic factors in the aetiology of NIDDM has been underlined by study of family pedigrees and identical twin pairs. Although in some isolated populations and a tiny minority of Western families inheritance follows an autosomal dominant pattern, a polygenic mode of transmission predominates in Europe and North America. No genetic markers have been identified despite intensive study of the HLA system and gene polymorphisms. Environmental factors appear to play some role, but examination of the evidence for an aetiological effect of the commonly assumed factors, diet and obesity, suggests that they exert no direct effect. However, it is likely that these factors together with physical inactivity could modulate the speed of progression to symptomatic disease. Both beta cell dysfunction and tissue insulin insensitivity are important in producing the syndrome of NIDDM. Insulin insensitivity is present from very early in the time course of the syndrome, but it is clear that the disease cannot develop in the absence of beta cell dysfunction. The recent discovery of islet associated amyloid is exciting as it represents a major step in tracing the pathogenesis of NIDDM backwards towards genetic and non-genetic aetiological influences.