The Changing Face of Disease: Implications for Society

By Nick Mascie-Taylor; Jean Peters et al. | Go to book overview

8

Unravelling gene-environment interactions in type 2 diabetes

Nicholas J. Wareham

Type 2 diabetes is an increasingly common disorder which gives rise to considerable morbidity and mortality (Marks 1996). It is the commonest cause of preventable blindness in adults of working age, a major cause of end-stage renal disease (Nelson et al. 1995) and lower limb amputation (The Lower Extremity Amputation Study Group 1995). It is, perhaps most importantly, a major risk factor for coronary heart disease, which occurs at least twice as commonly in people with diabetes (Fuller et al. 1983; Kannel et al. 1979). The pattern of the rise in the prevalence of type 2 diabetes around the world, particularly in previously undeveloped countries, provides support for the notion that this disorder results from an interaction between genetic and environmental factors. This chapter describes the evidence that suggests such interactions exist and debates the most appropriate study designs which could be employed to detect them, using evidence from several recently described examples.


What is the evidence that gene-environment interactions exist in type 2 diabetes?

The global variation in the prevalence of type 2 diabetes is marked. Figure 8.1 shows the prevalence of type 2 diabetes and impaired glucose tolerance in various countries around the world (King and Rewers 1993). These prevalence estimates have been obtained by adding the prevalence of clinically diagnosed diabetes to that of undiagnosed disease. This is necessary because up to half of all potentially detectable cases at any given time are undetected, as this disorder has a slow insidious onset and presents without acute metabolic disturbance (Harris 1993). Therefore clinically the distinction between normality and abnormality is blurred and a standardised test, the 75 g oral glucose tolerance test, has to be utilised to find the clinically undiagnosed cases. The geographical pattern of variation suggests that prevalence rates are lowest in rural areas of developing countries, are generally intermediate in developed countries, but are highest in certain ethnic groups who have adopted western lifestyle patterns (King and Rewers 1993). This is particularly apparent in the two populations with highest prevalence, the Nauruan people in Micronesia and the Pima Indians in Phoenix, Arizona. Both of these populations have undergone rapid changes in dietary and physical activity lifestyle and have

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