Family history of diabetes in middle-aged Swedish men is a gender unrelated factor which associates with insulinopenia in newly diagnosed diabetic subjects

We have investigated the association of a family history of diabetes with g lucose tolerance in a population of Swedish men. All men 35-54 years of age in 1992 and living in four different local municipalities of the outer Sto ckholm area were screened by questionnaire. From 10236 completed questionna ires 1622 men, selected for presence of such a history but without known di abetes, as well as 1507 men without a family history underwent an oral gluc ose tolerance test. Diabetes (2 h-plasma glucose levels >11.0 mmol/l) was d etected in 55 and impaired glucose tolerance (plasma glucose levels 7.8-11. 0 mmol/l) in 172 subjects. The odds ratio of diabetes, associated with a fa mily history, was 4.1, confidence interval 2.1-8.3 and for impaired glucose tolerance 1.6, confidence interval 1.2-2.3. Influence of a family history was measurable also within the range of normal 2-h glucose concentrations: compared to 2-h glucose levels <3.8 mmol/l; the odds ratio associated with a family history was 1.4, confidence interval 1.1-1.7 and 1.3, confidence i nterval 1.1-1.6 for concentrations 4.8-5.7 mmol/l and 5.8-7.7 mmol/l respec tively. The odds ratio of diabetes and impaired glucose tolerance among men with a family history increased with number and closeness of relatives wit h diabetes but was not affected by the gender of the family member. Overwei ght (BMI > 25.0 kg/m(2)) increased the odds ratio of diabetes in subjects w ith a family history, the odds ratio being 24, confidence interval 3-177, w hen both conditions were present. In subjects with Type II (non-insulin-dep endent) diabetes mellitus discovered during the investigation, the presence of a family history of diabetes was associated with decreased insulin secr etion rather than insulin resistance as assessed by fasting insulin, homeos tasis model assessment, and the 2-h insulin response to the oral glucose to lerance test. We conclude that a family history of diabetes strongly but in dependently of gender associates with decreased glucose tolerance. Furtherm ore, the results are compatible with a major role for low insulin secretion in the diabetogenic influence of a family history of diabetes in middle-ag ed Swedish men. Lastly, the very high risk for diabetes in middle-aged men with both a family history of diabetes and obesity indicates that such peop le should, for the purpose of therapeutic intervention, be identified in th e general population.