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.


OBJECTIVE
To test the hypothesis that insulin resistance constitutes the biological expression of increased coronary risk in these subjects.


METHODS
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.


CONCLUSIONS
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.
Murphy
M J
MJ
Department of Biochemical Medicine, Ninewells Hospital, Dundee DD1 9SY, Scotland, UK. m.j.murphy@dundee.ac.uk
Nicaud
V
V
Martin
B C
BC
O'Reilly
D St J
DS
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis*; D016022:Case-Control Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*
D001786:Blood Glucose; D004041:Dietary Fats