OBESE MEN WITH TYPE-IIB HYPERLIPIDEMIA ARE INSULIN-RESISTANT

By using the euglycemic clamp technique and indirect calorimetry, we determined the degree of insulin resistance in 12 obese (body mass index >27.0 kg /M2 ), normotensive patients with type IIB hyperlipidemia (HLIIB) (total cholesterol greater-than-or-equal-to 6.5 mmol/L and total triglycerides greater-than-or-equal-to 2.0 mmol/L) and 17 control subjects (total cholesterol less-than-or-equal-to 6.1 mmol/L and total triglycerides < 1.8 mmol/L) who were carefully matched for sex, age, and obesity. Fasting plasma insulin was higher in HLIIB patients than in control subjects (18.4 +/- 4.6 versus 8.9 +/- 1.2 mU/L, respectively; P=.010). The rates of whole-body glucose uptake were significantly lower in HLIIB patients than in control subjects during the last hour of the clamp (42.2 +/- 3.9 versus 54.6 +/- 2.8 mumol/kg per minute, respectively; P=.013). Glucose oxidation during the last 30 minutes of the euglycemic clamp was lower in HLIIB patients than in control subjects (14.6 +/- 0.9 versus 19.0 +/- 1.3 mumol/kg per minute, respectively; P=.017). Nonoxidative glucose disposal during the last 30 minutes of the euglycemic clamp was also lower in HLIIB patients than in control subjects, but the difference was not statistically significant (27.6 +/- 3.3 versus 35.8 +/- 2.8 mumol/kg per minute, respectively; P=.069). Lipid oxidation during the clamp was completely suppressed in control subjects (-0.24 +/- 0.44 mumol/kg per minute) but was significantly less suppressed in the HLIIB patients (0.94 +/- 0.29 mumol/kg per minute, P=.024). Our study shows for the first time that obese patients with type IIB hyperlipidemia are insulin resistant and that this insulin resistance affects both oxidative and nonoxidative glucose metabolism.