Relationship of insulin sensitivity and ApoB levels to intra-abdominal fatin subjects with familial combined hyperlipidemia

Familial combined hyperlipidemia (FCHL) is one of the most common familial dyslipidemias associated with premature heart disease. Subjects with FCHL t ypically have elevated apolipoprotein B (apoB) levels, variable elevations in cholesterol and/or triglycerides, and a predominance of small, dense, lo w density lipoprotein particles. It is thought that insulin resistance is i mportant in the expression of the combined hyperlipidemia phenotype. To fur ther characterize the relationship between insulin resistance and increased apoB levels, 11 subjects from well-characterized FCHL families and normal control subjects matched for weight and/or age underwent measurement of int ra-abdominal Fat (IAF) and subcutaneous fat (SQF) by CT scan, insulin sensi tivity (Si) by the frequently sampled intravenous glucose tolerance test, a nd lipoprotein levels. Body mass index and IAF were higher and Si was lower (more insulin resistant) in the FCHL group than in the age-matched group, but the values were similar in the FCHL group and the age- and weight-match ed control group. When the relationship between body fat distribution and S i was tested with multiple linear regression, only IAF was significantly co rrelated with Si after the addition of SQF and body mass index as independe nt variables. For any level of insulin sensitivity or IAF, however, apoB le vels remained higher in the FCHL subjects than in the control groups. In co nclusion, in FCHL, visceral obesity is an important determinant of insulin resistance. Visceral obesity and insulin resistance, however, do not fully account for the elevated levels of apoB in this disorder, and this study pr ovides physiological support for separate, but additive, genetic determinan ts in the etiology of the lipid phenotype.