Hyperinsulinemia for the Development of Hypertension: Data from the Hawaii-Los Angeles-Hiroshima Study.

Abstract

The present study was to assess the association of metabolic factors including hyperinsulinemia, with the development of hypertension in Japanese-Americans. One hundred forty normotensive (<140/90 mmHg) subjects aged 40 to 69 years old from the Hawaii-Los Angeles-Hiroshima study were followed for 15 years. Patients with cardiovascular disease were excluded. Body mass index (BMI), blood pressure (BP), serum total cholesterol (TC), triglycerides (TG), uric acid (UA), and glucose and insulin responses at baseline, 1 h, and 2 h after a glucose load were analyzed. Seventeen subjects became hypertensive (systolic BP > or = 160 mmHg, diastolic BP > or = 95 mmHg, or received drug treatment) during follow-up. Age- and sex-adjusted BMI, BP, serum UA, TG, insulin, and changes in fasting glucose during follow-up were higher in subjects who later became hypertensive than in those who did not. There was no difference in the change in BMI. Age- and sex-adjusted relative risks for the development of hypertension by quartiles of BMI, serum UA, TG, and the sum of insulin values (sigmainsulin) during a glucose load were highest in highest quartile of the distribution. When age, sex, systolic BP, BMI, serum UA, TC, TG, fasting glucose, sigmainsulin, and the change in BMI were used in a proportional hazard analysis, hyperinsulinemia, hyperuricemia, and systolic BP were found to be significant risk factors for hypertension. In conclusion, hyperinsulinemia, as well as obesity, hyperuricemia, and hypertriglyceridemia were associated with hypertension in Japanese-Americans. Hyperinsulinemia and hyperuricemia were independent predictors of the development of hypertension.

Uric Acid and the Development of Hypertension

“…[23][24][25] Insulin is known to decrease the renal excretion of uric acid, 4 and hyperinsulinemia predicts the development of hypertension. 26 We do not have serum insulin levels available at the baseline examination; however, the work of Imazu et al 12 suggests that the relationship between uric acid and the development of hypertension is independent of the insulin level. We were able to control for several elements of the metabolic syndrome, including blood pressure, triglyceride level, glucose level, and central adiposity, but we did not have high-density lipoprotein levels to fully define the presence of Total 892 100…”

“…Other studies have included a significant number of women, 10,12,13 suggesting that the relationship between uric acid and risk for hypertension is present in both men and women. Relying on the measurement of the blood pressure at a single visit necessarily was a source of some misclassification.…”

“…Using 160/95 mm Hg, however, is consistent with previous analyses in this 20,34 and other cohorts. 9,10,12 Also, the current definition of hypertension was not established until 1993, 35 30 years after the initiation of this cohort. The SUA level satisfied the proportional hazards assumption, indicating that the relationship between uric acid and the development of hypertension was constant over the follow-up period.…”

“…Previous studies have variably accounted for these confounders. Specifically, some did not adjust for blood pressure, 8,9,17,18 Ն2 elements of the metabolic syndrome, 8 -11,13-15 or alcohol intake, 11,12 and only 1 adjusted for renal function. 13 We, therefore, examined the prospective association of serum uric acid level with the development of hypertension among subjects at risk for the development of hypertension within the NAS cohort, including an analysis of those at risk for the development of hypertension at the time of their first serum creatinine determination.…”

Effects of Angiotensin II Receptor Antagonists on Insulin Resistance Syndrome and Leptin in Sucrose-Fed Spontaneously Hypertensive Rats.

“…Humans with a genetic predisposition to hypertension tend to develop insulin resistance and hyperinsulinemia (2,3). It is suggested that hypertension may be associated with hyperinsulinemia in part via glucose intolerance-induced alterations such as sodium retention, vasculopathy, and nephropathy (4). Therefore, ARA on insulin sensitivity have been conflicting, with some studies showing no influence on insulin sensitivity (10)(11)(12) and others demonstrating an improvement of insulin sensitivity (13)(14)(15).…”