Susceptibility and Risk

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Type-2 diabetes is prevalent in industrially developed societies. It affects up to 30% of some populations [32], suggesting that susceptibility to diabetes is common, though not universal, in as much as some of those apparently at greatest risk - the pathologically obese - never develop the disease.

The probability of developing a multifactorial disorder such as diabetes is made up of genetic susceptibility and environmental risk. Both contribute a proportion to the probability and, if one rises, the other must inevitably fall. If the rising incidence of type-1 diabetes has been the result of rising environmental risk (obesity and insulin resistance), the genetic contribution must have fallen.

Concordance among monozygotic twin pairs is widely believed to reflect the genetic contribution to probability, and lies at around 75% in type-2 diabetes (rising to 95% if those with glucose intolerance alone are included) [33] but only 20% in type 1 [34]. At least, that was historically the case. Recent data from the Danish twin registry suggests that concordance for type-1 diabetes in monozygotic twins is now around 50-60%, and no different from dizygotic twins [35].

Evidence for the rising environmental risk for type-1 diabetes comes from a study in the South of England which shows a progressive rise in body mass index (BMI) at diagnosis over the past 20 years [36]. The hypothesis predicts two outcomes of the corresponding fall in contribution from HLA genes -convergence of the clinical phenotype and loss of the difference in concordance rates between identical and nonidentical twins noted above.

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