Effect of insulin on renal sodium and uric acid handling in essential hypertension

Abstract

In normal subjects, insulin decreases the urinary excretion of sodium, potassium, and uric acid. We tested whether these renal effects of insulin are altered in insulin resistant hypertension. In 37 patients with essential hypertension, we measured the changes in urinary excretion of sodium, potassium, and uric acid in response to physiological euglycemic hyperinsulinemia (by using the insulin clamp technique at an insulin infusion rate of 6 pmol/min/kg). Glucose disposal rate averaged 26.6 +/- 1.5 mumol/min/kg, i.e., 20% lower than in normotensive controls (33.1 +/- 2.1 mumol/min/kg, P = .015) In the basal state, fasting plasma uric acid concentrations were higher in men than women (P < .001), were positively related to body mass index (r = 0.38, P = .02), waist/hip ratio (r = 0.35, P < .05), and serum triglyceride levels (r = 0.59, P = .0001), and negatively related to HDL cholesterol concentrations (r = -0.59, P = .0001) and glucose disposal rate (r = 0.42, P < .01). Uric acid clearance, on the other hand, was inversely related to body mass index (r = 0.41, P = .01), plasma uric acid (r = 0.65, P < .0001) and triglyceride concentrations (r = 0.39, P < .02), and directly related to HDL cholesterol levels (r = 0.52, P < .001). During insulin infusion, blood pressure, plasma uric acid and sodium concentration, and creatinine clearance did not change. In contrast, hyperinsulinemia caused a significant decrease in the urinary excretion of uric acid (2.67 +/- 0.12 to 1.86 +/- .14 mumol/min/1.73 m2, P = .0001), sodium (184 +/- 12 to 137 +/- 14 mumol/min/1.73 m2, P = .0001), and potassium (81 +/- 7 to 48 +/- 4 mumol/ min/1.73 m2, P = .0001). Both in absolute terms (clearance and fractional excretion rates) and percentagewise, these changes were similar to those found in normotensive subjects. Insulin-induced changes in urate excretion were coupled (r = 0.55, P < .0001) to the respective changes in sodium excretion. In hypertensive patients, higher uric acid levels and lower renal urate clearance rates cluster with insulin resistance and dyslipidemia. Despite insulin resistance of glucose metabolism, acute physiological hyperinsulinemia causes normal antinatriuresis, antikaliuresis, and antiuricosuria in these patients.

Coffee, tea, and caffeine consumption and serum uric acid level: The third national health and nutrition examination survey

“…These findings closely agree with a recent study that found that both caffeinated and decaffeinated coffee were inversely associated with C peptide levels (a marker of endogenous insulin levels), but tea intake and total caffeine intake after adjusting for coffee intake were not (7). Because there is a strong positive relationship between serum insulin resistance and hyperuricemia (23)(24)(25)(26)(27) and insulin reduces the renal excretion of urate (25,28,29), decreased insulin resistance and insulin levels associated with coffee consumption may lead to lower uric acid levels.…”

Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis

“…The hyperinsulinaemia associated with the latter may stimulate sodium and UA absorption from the proximal tubule. 31 However, several studies suggest that SUA may be directly linked with HT. Analysis of a cohort of male workers in southern Italy 32 showed a positive association between UA and the development of HT independent of age, BMI and lipids; similar results (controlled for body-weight, serum creatinine, alcohol consumption, parental history of HT, excessive salt intake and truncal fat) were also reported in a cohort of the Kaiser Permanente Medical Care Programme.…”

The conundrum of hyperuricemia, metabolic syndrome, and renal disease

“…Fasting insulin levels inversely correlate with urinary uric acid clearance and are positively associated with serum uric acid in healthy subjects [28]. Furthermore, exogenously administered insulin decreases urinary excretion of uric acid and this is mediated by stimulating urate reabsorption [33] in healthy subjects as well as in hypertensive patients [33]. These studies suggest that the renal proximal tubule remains sensitive to the effects of insulin even in subjects with hypertension (who are often insulin resistant).…”