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 been found to be associated with insulin resistance. However, direct evidence that patients with isolated low HDL cholesterol are insulin resistant is still lacking. Therefore, we investigated the degree of insulin resistance and intracellular metabolism of glucose by the euglycemic glucose clamp technique and indirect calorimetry in three groups of subjects with normal glucose tolerance: 17 male control subjects with normolipidemia, 12 male patients with isolated low HDL cholesterol (low HDL group), and 10 male patients with low HDL cholesterol and hypertriglyceridemia (low HDL/high TG group). Fasting, 1-h, and 2-h glucose levels did not differ between the groups in an oral glucose tolerance test (OGTT). In contrast, insulin levels during an OGTT were significantly higher in the low HDL group than in the control group (fasting insulin: 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 insulin: 488 ± 145 pM, P = 0.040). During the euglycemic hyperinsulinemic clamp, the rates of whole body glucose uptake were similarly reduced in the low HDL group (46.5 ± 2.8 μmol · kg⁻¹ · min⁻¹, P = 0.003) and in the low HDL/high TG group (45.1 ± 5.4 μmol · kg⁻¹ · min⁻¹, P = 0.021) compared with those in the control group (58.8 ± 2.5 μmol · kg⁻¹ · min⁻¹). The rates of glucose oxidation during the euglycemic 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 μmol · kg⁻¹ · min⁻¹ P = 0.092; low HDL/high TG group: 17.5 ±1.9 μmol · kg⁻¹ · min⁻¹ P = 0.098; and control group: 21.0 ±1.5 junol · kg⁻¹ · min⁻¹). The rates of glucose nonoxidation were reduced in the low HDL group (29.3 ± 2.5 μmol · kg⁻¹ · min⁻¹, P = 0.042) and in the low HDL/high TG group (27.6 ± 5.0 μmol · kg⁻¹ · min⁻¹, P = 0.056) compared with those in the control group (37.7 ± 2.6 μmol · · kg⁻¹ · min⁻¹), although the latter difference was not statistically significant. We conclude that patients with low HDL cholesterol are insulin resistant independently of TG levels.