Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives.

BACKGROUND: Thiazide diuretics can impair glucose metabolism and increase new-onset diabetes. Adding an angiotensin receptor blocker to diuretics may protect against these metabolic effects; however, the mechanism of this protection is unclear. METHOD: To explore potential mechanisms, a 16-week multicenter trial was conducted to ascertain the relative glucose metabolism effects of combined hydrochlorothiazide and angiotensin receptor blocker (valsartan) therapy compared with hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive individuals (BMI = 35 +/- 7 kg/m, seated BP = 159 +/- 8/94 +/- 8 mmHg, and mean age 56 years). Individuals were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 mg or hydrochlorothiazide, with titration to hydrochlorothiazide 25 mg and amlodipine 10 mg, respectively. Changes from baseline to week 16 in fasting and 2-h postprandial glucose and insulin levels after an oral glucose load were measured. RESULTS: At week 16, clinic blood pressure reductions were similar (P > 0.05) in both groups. Fasting and 2-h glucose levels increased (P < 0.05) with the amlodipine combination but not with the valsartan combination. In concert with these glucose responses, postprandial insulin increases from baseline were substantially greater with valsartan than with amlodipine plus hydrochlorothiazide group (P = 0.001). The glucose responses were inversely related to insulin responses at the study conclusion. CONCLUSION: The novel observation of this investigation was that the combination of valsartan and hydrochlorothiazide was associated with greater glucose-stimulated insulin secretory and lesser glycemic excursion responses than the amlodipine combination group. Thus, this data suggests that adding an angiotensin receptor blocker attenuates the negative effects of thiazides on pancreatic beta-cell glucose-induced insulin secretion.

Responses of inflammatory markers to a low-fat, high-carbohydrate diet: effects of energy intake.

BACKGROUND: Inflammation contributes to atherogenesis. Dietary fats may be proinflammatory. OBJECTIVE: The objective was to determine whether energy intake modulates the effects of low-fat, high-carbohydrate intakes on inflammatory markers. DESIGN: Twenty-two healthy postmenopausal women with a mean (+/-SD) age of 61 +/- 11 y, who were not receiving hormone replacement therapy, were fed eucaloric diets to reduce their fat intake from 35% to 15% of energy. Next, the women consumed a 15%-fat ad libitum diet under free-living conditions. Serum highly sensitive C-reactive protein, interleukin 6, HDL serum amyloid A, and adiponectin concentrations were measured at the end of the eucaloric and ad libitum low-fat, high-carbohydrate intakes. RESULTS: The eucaloric diet decreased adiponectin from 16.3 +/- 2.1 to 14.2 +/- 2.0 mg/L (P < 0.05) and increased triacylglycerol from 131 +/- 11 to 164 +/- 14 mg/dL (P < 0.01). The ad libitum low-fat diet caused 6 kg weight loss and decreased highly sensitive C-reactive protein from 4.3 +/- 0.6 to 2.5 +/- 0.5 mg/L (P < 0.01), decreased HDL serum amyloid A from 10.3 +/- 1.8 to 5.7 +/- 1.3 mg/L (P < 0.001), increased adiponectin from 14.2 +/- 2.0 to 16.3 +/- 1.7 mg/L (P < 0.05), and decreased triacylglycerol from 164 +/- 14 to 137 +/- 15 mg/dL (P < 0.05). CONCLUSION: During the eucaloric phase, the low-fat, high-carbohydrate diet exerted unfavorable effects on the inflammatory markers. In contrast, the ad libitum low-fat, high-carbohydrate intake caused weight loss and affected inflammatory markers favorably. Thus, the energy content of a low-fat, high-carbohydrate diet determines changes in inflammatory markers.