Professor Mike Kirby explores the relationship between diabetes and the urologist.
The prevalence of type 2 diabetes varies more than 10-fold between the highest and the lowest risk populations. There are significant differences between the less developed countries (<3%), contrasting with populations such as the north American Indians, Pacific Islanders and Australian Aborigines (30-50%). These populations have experienced radical changes from traditional to westernised ‘lifestyles.’ The Pima Indians of Arizona have the highest reported prevalence of type 2 diabetes, >50% in adults age 35 years and over.
Ethnicity is an important determinant of susceptibility to insulin resistance, obesity, type 2 diabetes and other cardiovascular risk factors such as dyslipideamia. Social and behavioural changes, which include decreased levels of physical activity and the over consumption of energy dense foods, interplay with these susceptibilities. There are interesting differences that exist independently of obesity in insulin resistance in different ethnic groups. South Asians tend to have high triglyceride and low HDL cholesterol concentrations, Native Americans generally have high triglycerides and low total cholesterol levels and Peninsula Arabs generally have high triglycerides and high cholesterol levels. West Africans tend to have lower triglyceride levels than South Asians and higher HDL cholesterol levels than Europeans and this may help to explain the relatively low incidence of coronary heart disease (CHD) in West Africa compared with Northern Europe.
In 1962 Neel proposed that certain populations have a higher prevalence of genetic traits which have conferred survival advantages during protracted periods of meagre nutrient supply. But which may now be detrimental due to abundant food supplies and reduced habitual levels of physical activity, the Pima Indians being a good example of this. However, Barker and Hales (Southampton and Cambridge UK) have done work with the Hertfordshire cohort that provides an alternative to the thrifty genotype hypothesis of type 2 diabetes. It proposes that type 2 diabetes results, at least in part, from relative intrauterine malnutrition and that the latter leads to lifelong metabolic programming. This includes a reduced compliment of islet beta cells, combined with insulin resistance in skeletal muscle. Studies in populations in which birth weight has been carefully recorded have consistently demonstrated a correlation between low birth weight and an increased risk of type 2 diabetes in middle age. The risk appears to be particularly high if obesity develops in adulthood. In addition to this other cardiovascular risk factors including hypertension, have been linked to low birth weight.
There are other genetic factors that interplay in any one individual. A lifetime concordance of approximately 90% for identical twins is strongly suggestive of a genetic component to type 2 diabetes. Commonly type 2 patients report a family history of the condition. The lifetime risk associated with having a single parent with type 2 diabetes is approximately 40% and this increases to 50% if both parents are affected. Undoubtedly there are, a multiplicity of factors involved in the genetics of type 2 diabetes. There is much interest in the genes encoding signalling intermediates within the intracellular pathways of insulin action, the genes involved in the lifecycle of the pancreatic beta cells and also the genes involved in the insulin secretory function of the pancreatic beta cells.
Studies of a rare form of diabetes, Maturity-Onset Diabetes of the Young (MODY) have yielded important evidence for single defects. These genes also influence birth weight and therefore it is clear that there is a complex interaction between specific diabetogenic genes and the background genome, which is illustrated by the ethnic variations, and the intrauterine environment, all of which contribute to the familial aggregation of type 2 diabetes. There is evidence of a strong genetic element in the pathogenesis of type 1 diabetes, also illustrated by concordance in identical twins. There is an association between type 1 diabetes and the class 2 histocompatibility (HLA genes on chromosome 6) approximately 95% of patients with type 1 diabetes possess the HLA-DR3 or DR4 alleles or both: the DP and DQ alleles are also common.