ISOLATED LOW HDL CHOLESTEROL - AN INSULIN-RESISTANT STATE

High levels of very-low-density lipoprotein (VLDL) triglycerides (TGs) and low levels of high-density lipoprotein (HDL) cholesterol have bee n found to be associated with insulin resistance. However, direct evid ence that patients with isolated low HDL cholesterol are insulin resis tant is still lacking. Therefore, we investigated the degree of insuli n resistance and intracellular metabolism of glucose by the euglycemic glucose clamp technique and indirect calorimetry in three groups of s ubjects with normal glucose tolerance: 17 male control subjects with n ormolipidemia, 12 male patients with isolated low HDL cholesterol (low HDL group), and 10 male patients with low HDL cholesterol and hypertr iglyceridemia (low HDL/high TG group). Fasting, 1-h, and 2-h glucose l evels did not differ between the groups in an oral glucose tolerance t est (OGTT). In contrast, insulin levels during an OGTT were significan tly higher in the low HDL group than in the control group (fasting ins ulin: 85 +/- 11 vs. 50 +/- 6 pM, P = 0.005; 1-h insulin: 622 +/- 92 vs . 394 +/- 64 pM, P = 0.004; and 2-h insulin: 343 +/- 73 vs. 194 +/- 40 pM, P = 0.006). Similarly, insulin levels were also higher in the low HDL/high TG group than in the control group (fasting insulin: 82 +/- 14 pM, P = 0.037; 1-h insulin: 795 +/- 179 pM, P = 0.063; and 2-h insu lin: 488 +/- 145 pM, P = 0.040). During the euglycemic hyperinsulinemi c clamp, the rates of whole body glucose uptake were similarly reduced in the low HDL group (46.5 +/- 2.8 mu mol kg(-1) min(-1), P = 0.003) and in the low HDL/high TG group (45.1 +/- 5.4 mu mol kg(-1).min(-1), P = 0.021) compared with those in the control group (58.8 +/- 2.5 mu m ol kg(-1) min(-1)). The rates of glucose oxidation during the euglycem ic clamp were lower in the low HDL patients than in control subjects, but the differences were not statistically significant (low HDL group: 17.3 +/- 0.9 mu mol kg min(-1) P = 0.092; low HDL/high TG group: 17.5 +/- 1.9 pmol.kg(-1) min(-1), P = 0.098; and control group: 21.0 +/- 1 .5 mu mol kg(-1) min(-1)). The rates of glucose nonoxidation were redu ced in the low HDL group (29.3 +/- 2.5 mu mol.kg(-1).min(-1), P = 0.04 2) and in the low HDL/high TG group (27.6 +/- 5.0 mu mol kg(-1) min(-1 ), P = 0.056) compared with those in the control group (37.7 +/- 2.6 m u mol kg(-1) min(-1)), although the latter difference was not statisti cally significant. We conclude that patients with low HDL cholesterol are insulin resistant independently of TG levels.