General summary

Background


Diabetes mellitus is a chronic disorder of glucose metabolism and is the single biggest cause of preventable blindness, the leading cause of non-traumatic lower extremity amputation and a major cause of end-stage renal disease and coronary heart disease in European populations. The lifetime cumulative incidence of diabetes in European populations is 35-40%, it is a major cause of premature mortality and accounts for 5-10% of health care expenditure. The prevalence of diabetes is rising in European populations and thus efforts to understand the aetiology of the condition and develop preventive strategies are key public health targets.


The overall importance of environmental factors in the aetiology of type 2 diabetes is evidenced by observations of increased diabetes risk among individuals from at-risk populations who migrate to countries where lifestyles are more westernised and from cohort studies where the importance of major non-genetic risk factors such as obesity, physical inactivity, and dietary intake of fat have been demonstrated. The strength of causal inference concerning these aetiological factors is high, not only because findings have been replicated in many studies in different populations, but also because interventions aimed at changing these factors have led to reductions in the incidence of diabetes in randomised controlled trials. The importance of genetic factors in leading to type 2 diabetes has been demonstrated by studies of familial aggregation, high concordance in twin studies and the impact of different degrees of high-risk heritage on diabetes risk in high prevalence populations. Progress in discovering the genetic basis of diabetes is accelerating as more powerful genotyping technologies are applied to larger study samples.


The global variation in the prevalence of type 2 diabetes is marked and suggests that an interaction between genes and lifestyles in central to determining diabetes risk. The geographical pattern of variation suggests that prevalence is lowest in rural areas of developing countries, is generally intermediate in developed countries, but is highest in certain ethnic groups who have adopted western lifestyle patterns. One explanation for this variation is the "thrifty genotype" hypothesis which postulates that genetic variation which was advantageous in times of food scarcity would become disadvantageous in times of food abundance. The human genome, tailored to function in a hostile environment, now faces novel stressors, and depending on the genetic subgroup, copes variably with this challenge. The InterAct project is aimed at investigating the basis of these interactions.