Relationship between familial combined hyperlipidemia and insulin resistance

Familial combined hyperlipidemia is the most frequent hereditary dyslipidemia, usually associated with insulin resistance. Recently, the diagnostic criteria offamilial combined hyperlipidemia were redefined: There should be at least two 1st degree hyperlipidemic relatives with both triglycerides > or = 1.5 mmol x L(-1) and apolipoprotein B > or = 1.20 g L(-1). The aim of this study was to evaluate the relationship between this lipoprotein phenotype and the presence of insulin resistance and to assess the presence of metabolic syndrome.

Lipid parameters and parameters associated with insulin resistance were determined in 90 subjects of families with familial combined hyperlipidemia and 38 controls. The members of affected families were further divided into the hyperlipidemic and normolipidemic group.

The hyperlipidemic group showed only significantly higher fasting proinsulin levels [HL 17,4 +/- 1.5 vs NL 12.8 +/- 1.4 (p = 0.030); and vs CO 11.1 +/- 1.4 (p = 0.003)] in comparison with the normolipidemic and control groups. Differences in fasting insulin [HL 9.40 +/- 0.78 vs NL 7.78 +/- 0.71 (p = NS); and vs CO 7.30 +/- 0.76 (p = NS)], C-peptide [HL 2.56 +/- 0.19 vs NL 2.27 +/- 0.17 (p = NS); and vs CO 2.07 +/- 0.18 (p = NS)], and HOMA [HL 2.16 +/- 0.21 vs NL 1.84 +/- 0.20 (p = NS); and vs CO 1.69 +/- 0.21 (p = NS)] did not reach statistical significance. On the contrary, the members of families with familial combined hyperlipidemia with the presence of metabolic syndrome (NCEP-ATP III) had significantly higher fasting insulin [FCH with MS 12.74 +/- 1.42 vs HL without MS 9.21 +/- 0.92 (p = 0.030); and vs NL without MS 6.75 +/- 0.80 (p = 0.001)], and proinsulin levels [FCH with MS 25.28 vs HL without MS 15.69 +/- 1.75 (p = 0.002); and vs NL without MS 11.20 +/- 1.51 (p = 0.0001)], and HOMA index [FCH with MS 3.03 +/- 0.39 vs HL without MS 2.13 +/- 0.25 (p = 0.042); and vs. NL without MS 1.56 +/- 0.22 (p = 0.003)] in comparison with their relatives without metabolic syndrome and controls.

The presence of the metabolic syndrome could detect the most insulin resistant subjects in families with familial combined hyperlipidemia who are at increased risk of cardiovascular disease.