Heritability estimates for beta cell function and features of the insulin resistance syndrome in UK families with an increased susceptibility to type 2 diabetes.
Mills GW., Avery PJ., McCarthy MI., Hattersley AT., Levy JC., Hitman GA., Sampson M., Walker M.
AIMS/HYPOTHESIS: The aim of this study was to measure the heritability estimates for metabolic traits and the features of the insulin resistance syndrome in families with an increased genetic susceptibility to Type 2 diabetes. METHODS: A total of 811 non-diabetic relatives from 278 pedigrees of northern European extraction in which there was a sib-pair with Type 2 diabetes were recruited and studied at the six Diabetes UK Warren Type 2 diabetes centres. Heritability estimates were calculated, allowing for key covariates (age, sex, BMI and recruitment centre). Values greater than 0.10 were considered statistically significant in comparison to zero. RESULTS: Fasting glucose concentration and homeostasis model assessment of pancreatic beta cell function (HOMA %B) had the highest heritability estimates of 0.72 and 0.78 respectively. Heritability estimates for the features of the insulin resistance syndrome (BMI, WHR, systolic and diastolic blood pressure, serum lipids and homeostasis model assessment of insulin sensitivity [HOMA %S]) were also high. The heritability estimate for fasting glucose was markedly higher in the present study (0.77 vs 0.21 adjusted for age and sex; p<0.001) than in a comparable study of families from the same background population but with no increased susceptibility to diabetes. However, the estimates for the features of the insulin resistance syndrome were similar in the two studies. CONCLUSIONS/INTERPRETATION: In families with a high risk of Type 2 diabetes, the heritability estimates for fasting glucose, pancreatic beta cell function and the features of the insulin resistance syndrome were all high. The higher heritability estimate for pancreatic beta cell function suggests that this resource may be most effective when investigating genetic susceptibility to beta cell dysfunction.