Individuals with high total cholesterol/hdl cholesterol ratios are insulin resistant

OBJECTIVES: To define the pathophysiologic characteristics of patients at high risk for coronary heart disease due to an increased ratio of total cholesterol (TC) to high density lipoprotein-cholesterol (HDL-C). DESIGN: Cross-sectional. SETTING: Clinical Research Center. SUBJECTS: One hundred-20 healthy, non-diabetic, normotensive, volunteers were screened for this study. From this pool, 40 individuals (20 females and 20 males) with the highest and the lowest TC/HDL-C ratios were selected for comparison. MAIN OUTCOME MEASURES: Values for body mass index (BMI), ratio of waist to hip girth (WHR), and blood pressure were obtained on all patients. In addition, measurements were made of fasting lipid and lipoprotein concentrations, plasma glucose and insulin responses to an oral glucose challenge, and insulin resistance as assessed by the insulin suppression test. RESULTS: Age, BMI, and WHR were the same in the two groups. However, the group with a high TC/HDL-C ratio had higher (P < 0.05) systolic and diastolic blood pressures. In addition, patients with a high TC/HDL-C ratio had significantly higher (P < 0.001) very low density (VLDL) and low density lipoprotein (LDL)-cholesterol concentrations and lower HDL-cholesterol concentrations, with significant (P < 0.001) correlations between the TC/HDL-C ratio and VLDL (r = 0.60), LDL (r = 0.54), and HDL (r = -0.73) cholesterol concentrations. Patients with a high TC/HDL-C ratio were also significantly (P < 0.05-0.001) more insulin resistant, glucose intolerant with a greater plasma insulin response to oral glucose, and hypertriglyceridemic. CONCLUSIONS: The results indicate that an increase in LDL-cholesterol concentration is not necessarily the major contributor to a high ratio of TC/HDL-C. Furthermore, individuals with this epidemiologic designation are insulin resistant, and liable to all the other abnormalities associated with this metabolic defect.