The glucose response to an oral fat tolerance test in young men with a paternal history of premature myocardial infarction: possible early indication of insulin resistance. The EARS 2 study

Background: Concentrations of cholesterol, triglycerides and glucose are higher in young men with a paternal history of premature myocardial infarction than in age- and sex-matched controls. Aim: To test the hypothesis that insulin resistance constitutes the biological expression of increased coronary risk in these subjects. Design: A total of 407 male university students with a paternal history of premature myocardial infarction (cases) and 415 age- and sex-matched controls were investigated for differences in insulin sensitivity. Methods: Four methods of assessing insulin sensitivity were used: (i) insulin and glucose responses to an oral glucose tolerance test (OGTT); (ii) insulin and glucose responses to an oral fat tolerance test (OFTT); (iii) minimal modelling of insulin and glucose data from a frequent sample intravenous glucose tolerance test performed on a subset of 55 cases and 50 controls and (iv) homeostasis model assessment (HOMA) of insulin resistance. Results: The OFTT glucose response discriminated between cases and controls, with a smaller fall in glucose in cases compared with controls. The negative area under the glucose curve (AUC) (mean [standard error of the mean (SEM)]) was -1.42 (0.09) mmol min/L in cases and -1.76 (0.09) in controls ( P = 0.004). Peak height (mean [SEM]) was -0.65 (0.02) mmol/L in cases and -0.73 (0.02) in controls ( P = 0.007). The insulin responses were similar in cases and controls. Insulin AUC (mean [SEM]) was 161 (10) mU min/L in cases and 148 (10) in controls ( P = 0.34). This combination of findings suggests that insulin-stimulated glucose uptake was reduced in the cases. These findings were consistent across European regions. None of the other methods revealed any differences between cases and controls. Conclusion: In young men with a paternal history of myocardial infarction, an OFTT detects altered insulin sensitivity that is not identified by an OGTT, minimal modelling or HOMA.