Hyperinsulinemia - A link between glucose intolerance, obesity, hypertension, dyslipoproteinemia, elevated serum uric acid and internal cation imbalance

A representative sample (n = 1,211) of the Jewish population in Israel age 40-70 (excluding known diabetics), underwent a glucose tolerance test. Insulin response was found to be independently and positively associated with the GOH conditions - glucose intolerance (p<0.001), obesity (p<0.001), and hypertension (p<0.01) and with elevated serum uric acid (p<0.001) after accounting for the effects of sex, age, serum creatinine and use of antihypertensive medications. In a representative subgroup of 542 individuals, total VLDL and LDL fractions were estimated by standardized values (based on the reference group - individuals free of the GOH conditions), of their cholesterol and triglyceride components. Hyperinsulinemia was characterized by jointly elevated VLDL and LDL with reduced HDL. The risk ratio for this pattern (adjusted for the effects of age, sex, smoking and presence of any of the GOH conditions) was 3.4 (p<0.001). There was no further association of this disturbed lipoprotein profile with the GOH conditions. Cation concentrations were determined in a stratified subsample (n = 89) of the study group. The subsample comprised 30 individuals in the reference group, and 59 representing each of the seven possible combinations of abnormal glucose tolerance, obesity and hypertension (GOH group). Rate of cation imbalance defined as presence of at least one of three cation concentration - red blood cell sodium ≤7.0 mEq/l, red blood cell potassium <92.5 mEd/l or plasma potassium ≥4.5 mEq/l was 88.1% in the GOH, compared to 40.0% in the reference group (p>0.001). This rate was significantly associated with the three biochemical correlates of insulin resistance - insulin response ≥100 mU/l (p>0.01), triglycerides ≥80 mg/dl (p>0.001) and urate >5.5 mg/dl (p>0.001). In the total population sample the rate of untreated hypertension increased significantly (p>0.001) with increase in the number of its above correlates. We conclude that hyperinsulinemia with its attendant insulin resistance is a common pathophysiological mechanism linking the major major risk factors for atherosclerosis.