Association of insulin resistance and hyperinsulinemia with disturbed lipid metabolism in patients with essential hypertension.

Abstract

To clarify the association of insulin resistance and hyperinsulinemia with lipid metabolism in patients with essential hypertension (EHT), we used the euglycemic hyperinsulinemic glucose clamp technique (GC) and the 75-g oral glucose tolerance test (OGTT) to compare the characteristics of glucose and lipid metabolism in insulin-resistant patients with essential hypertension (EHT-R) with those in insulin-non-resistant patients with essential hypertension (EHT-N) and normotensive subjects (NT). Twenty-eight NT and 42 EHT whose body mass index (BMI) was less than 28 kg/m2 were studied to eliminate the effects of obesity on insulin sensitivity and lipid metabolism. Insulin sensitivity was evaluated by GC and expressed as metabolic clearance rate of glucose (M value, mg/m2/min). Mean -ISD of the M value in NT (145.0 mg/m2/min) was chosen as the cutoff point for insulin resistance. On the basis of this value, 33.3% of the EHT were EHT-R. There was no significant difference in age or BMI among the three groups. Blood samples were collected before GC to measure levels of total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), and HDL cholesterol (HDL-C). EHT-R had significantly higher levels of fasting blood sugar, fasting immunoreactive insulin, insulin at 120 min (IRI-120), and summation of insulin or blood sugar (BS) during the OGTT, as compared with NT and EHT-N. EHT-R also had significantly higher FFA and TG than the other two groups, while there was no difference in FFA or TG between EHT-N and NT. TC and HDL-C were similar in the three groups. There was either a significant negative correlation, or a trend toward negative correlation, between M value and FFA (r= -0.50, p < 0.05) or TG (r= -0.24, p < 0.1). There were significant positive correlations between IRI-120 and FFA (r=0.35, p< 0.05) or TG (r=0.29, p< 0.05). There was a positive correlation (r= -0.36, p< 0.01) between sigma BS and FFA, while no other significant relation was found between sigma BS and serum lipids. In summary, (i) 33.3% of EHT were found to be insulin resistant, when insulin resistance was defined as M value < 145.0 mg/m2/min, i.e., mean -ISD of the M value of NT; (ii) these EHT-R had higher levels of BS, insulin, FFA, and TG than did NT and EHT-N; (iii) EHT-N showed no difference in the levels of BS, insulin, or lipid, as compared with NT; and (iv) the levels of FFA and of TG correlated negatively with insulin sensitivity and positively with the insulin level during the OGTT. These results suggest that disturbances of glucose and lipid metabolism in EHT may be related to both insulin resistance and compensatory hyperinsulinemia, and that EHT-R may have more risk factors for arteriosclerotic complications than EHT-N.