Atherosclerosis seems not to be associated with hyperinsulinaemia in patients with familial hypercholesterolaemia

Objective. To study the relationship between hyperinsulinaemia, insulin res istance, leptin and atherosclerosis in subjects with familial hypercholeste rolaemia (FH). Design. Case-control cross-sectional study. Setting, Lipid clinic, Johannesburg Hospital, South Africa. Subjects and methods, Fasting serum lipid, glucose, insulin and leptin leve ls were measured in 24 homozygous FH subjects: 20 FH heterozygotes without coronary artery disease (CAD); 22 heterozygotes with documented CAD; and 20 healthy normocholesterolaemic subjects. insulin resistance was calculated using the homeostasis model assessment (HOMA) formula. Results, Mean glucose and insulin levels were similar in all 4 groups, Ther e was no significant difference in calculated insulin resistance between an y of the groups, There was also no relationship between the degree of insul in resistance and total or LDL-cholesterol levels. Using Spearman's correla tion coefficient (R-s) calculated insulin resistance correlated with trigly ceride (R-s = 0.27: P < 0.05) and inversely with HDL-cholesterol (R-s = - 0 .26; P < 0.05). Fasting insulin concentrations and calculated insulin resis tance were similar in FH subjects with overt CAD compared to those without. Leptin levels were higher in the FH subjects with CAD, However, these subj ects were older and had a larger body mass index (BMI), and when adjusted f or age and BMI, only BMI correlated with leptin levels (multiple r = 0.65; P < 0.001), Conclusions,In the absence of other causes of insulin resistance, FH subjec ts have normal fasting insulin levels and, in general, they are not insulin resistant. Insulin resistance appears to play little role in the pathogene sis of accelerated atherosclerosis in FH.