Atherosclerosis seems not to be associated with hyperinsulinaemia in patients with familial hypercholesterolaemia.
OBJECTIVE
To study the relationship between hyperinsulinaemia, insulin resistance, leptin and atherosclerosis in subjects with familial hypercholesterolaemia (FH).


METHODS
Case-control cross-sectional study.


METHODS
Lipid clinic, Johannesburg Hospital, South Africa.


METHODS
Fasting serum lipid, glucose, insulin and leptin levels 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. There was no significant difference in calculated insulin resistance between any of the groups. There was also no relationship between the degree of insulin resistance and total or LDL-cholesterol levels. Using Spearman's correlation coefficient (Rs) calculated insulin resistance correlated with triglyceride (Rs = 0.27; P<0.05) and inversely with HDL-cholesterol (Rs = -0.26; P<0.05). Fasting insulin concentrations and calculated insulin resistance were similar in FH subjects with overt CAD compared to those without. Leptin levels were higher in the FH subjects with CAD. However, these subjects were older and had a larger body mass index (BMI), and when adjusted for 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 subjects have normal fasting insulin levels and, in general, they are not insulin resistant. Insulin resistance appears to play little role in the pathogenesis of accelerated atherosclerosis in FH.
Raal
F J
FJ
Department of Medicine, University of the Witwatersrand Medical School, Johannesburg, South Africa. 014fred@chiron.wits.ac.za
Panz
V R
VR
Pilcher
G J
GJ
Joffe
B I
BI
D000293:Adolescent; D000328:Adult; D001161:Arteriosclerosis / Q000097:blood / Q000150:complications*; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003327:Coronary Disease / Q000150:complications; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin; D008055:Lipids / Q000097:blood; D008297:Male; D011506:Proteins / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D008055:Lipids; D011506:Proteins