Lipoprotein phenotype and insulin resistance in familial combined hyperlipidemia

The study objective was to investigate the relationship of insulin resistan ce (IR) with the lipoprotein phenotype in familial combined hyperlipidemia (FCH). Thirty-seven FCH men diagnosed by clinical and biochemical criteria and classified as lipoprotein phenotype lla (0 = 9), llb (0 = 17), or IV (n = 11) were compared with a healthy control group of 30 men of similar age, body mass index (BMI), waist to hip ratio (WHR), and systolic and diastoli c blood pressure. In all subjects, the plasma lipoprotein profile and basel ine and post-oral glucose tolerance test (OGTT) glucose and insulin plasma values were measured. An intravenous glucose tolerance test was performed a nd IR was studied by the peripheral insulin sensitivity index (Si). After t he OGTT, significantly higher values for insulinemia (at 0, 60, 90, and 120 minutes) and the area under the curve (AUC) of insulin secretion were obse rved in FCH. The AUC of insulin was greater in FCH subjects with the hypert riglyceridemic phenotype as compared with the controls and significantly lo wer Si levels, indicating greater IR, were found in the three FCH groups (c ontrol, 3.48 a 1.87 mU/L/min; FCH lla, 2.09 +/- 1.08; FCH llb, 1.54 +/- 0.7 7; FCH IV, 1.47 +/- 0.93; P < .001). The prevalence of IR (Si < 2 x 10(-4) mU/L/min) was greater in FCH, independent of the lipoprotein phenotype, as compared with the controls (P < .0001). Higher plasma glucose and insulin l evels at 120 minutes and lower Si values were found in the FCH lla group co mpared with the controls (P < .05), indicating a state of IR in this subgro up of normotriglyceridemic subjects. In conclusion, IR was found in the thr ee FCH lipoprotein phenotypes, being more severe in subjects with hypertrig lyceridemia. Hence, the therapeutic goals in FCH should include measures to normalize plasma lipids and improve peripheral insulin sensitivity. Copyri ght (C) 2000 by W.B. Saunders Company.