Comparison of effects of captopril used either alone or in combination with a thiazide diuretic on insulin action in hypertensive Type 2 diabetic patients: a double‐blind crossover study

Hunter, Steven; Wiggam, M I; Ennis, C. N.; Whitehead, H. M.; Sheridan, B.; Atkinson, A. B.; Bell, P. M.

doi:10.1046/j.1464-5491.1999.00010.x

Cited by 16 publications

(15 citation statements)

References 41 publications

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“…21,27 It has been suggested that because of the potential positive impact of ACE inhibition on insulin action, combining diuretics with ACE inhibitor may in part ameliorate adverse effects of thiazides; 28 however, in patients with essential hypertension, there was still a negative effect when high-dose bendrofluazide was combined with captopril. 9 In hypertensive type 2 diabetic patients, both conventional (2.5 mg) 29 and low-dose (1.25 mg) bendroflumethiazide 11 combined with captopril, when compared with captopril alone, resulted in increased insulin resistance. The current study aimed to establish whether these negative effects were also present when lowdose thiazide in combination with ACE inhibitor was given to nondiabetic patients with essential hypertension.…”

Section: Discussionmentioning

confidence: 99%

Effects on Insulin Action of Adding Low-Dose Thiazide to Angiotensin-Converting Enzyme Inhibitor in Essential Hypertension

McHenry

Atkinson²,

Hunter³

et al. 2013

Hypertension

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Abstract-Concern exists regarding adverse metabolic effects of antihypertensive agents. In the United States, diuretics are recommended first-line but additional agents, usually angiotensin-converting enzyme (ACE) inhibitors, are often required to meet blood pressure targets. We have previously shown that the combination of low-dose diuretic with an ACE inhibitor has detrimental effects on insulin action compared with ACE inhibitor alone in hypertensive type 2 diabetic patients. Our aim was to establish whether similar effects occur in nondiabetic hypertensive patients using this combination. A randomized doubleblind placebo-controlled crossover design was used. After a 6-week run-in, when regular antihypertensive medications were withdrawn and placebo substituted, patients received captopril 50 mg twice daily with either bendroflumethiazide 1.25 mg (CB) or placebo (CP) for 12 weeks with a 6-week wash-out between treatments. Insulin action was assessed by hyperinsulinemic euglycemic clamp after the 6-week run-in and at the end of each treatment period. There were no differences between treatments in fasting glucose or insulin concentrations. Glucose infusion rates required to maintain euglycemia were the same with each treatment (CP 22.1±2.

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Section: Discussionmentioning

confidence: 99%

Effects on Insulin Action of Adding Low-Dose Thiazide to Angiotensin-Converting Enzyme Inhibitor in Essential Hypertension

McHenry

Atkinson²,

Hunter³

et al. 2013

Hypertension

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“…Of note, studies comparing treatment of an ACE inhibitor with the combination of this ACE inhibitor with high-dose diuretic showed deterioration of IS with the combination in spite of the presence of the ACE inhibitor [18]. Collectively, these findings suggest an adverse effect of diuretics on IS, but because most of these studies were rather small and short in duration [13][14][15][16]18] the possibility that different diuretic doses had different effects on IS requires further investigation.…”

Section: Antihypertensive Agents and Insulin Sensitivitymentioning

confidence: 99%

“…Collectively, these findings suggest an adverse effect of diuretics on IS, but because most of these studies were rather small and short in duration [13][14][15][16]18] the possibility that different diuretic doses had different effects on IS requires further investigation.…”

Section: Antihypertensive Agents and Insulin Sensitivitymentioning

confidence: 99%

Antihypertensive agents, insulin sensitivity, and new-onset diabetes

Sarafidis

McFarlane²,

Bakris³

2007

Curr Diab Rep

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The effects of the antihypertensive drugs on carbohydrate metabolism and the development of diabetes have been a major research field for more than two decades. Many clinical studies have investigated the effects of the antihypertensive classes on insulin sensitivity and glycemic control, whereas several observational studies and large outcome trials have examined associations of antihypertensive agents with diabetes incidence. In general, thiazide diuretics and conventional beta blockers decrease insulin sensitivity and increase new-onset diabetes, whereas angiotensin-converting enzyme inhibitors, calcium channel blockers, and angiotensin II receptor blockers have neutral or beneficial effects on these parameters. However, several issues in this field, such as the specific properties of newer agents and the relationship of adverse metabolic outcomes and cardiovascular risk, remain to be fully elucidated. This article presents and evaluates the current knowledge in this important area.

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“…A potential mechanism by which inhibition of the RAS can improve glucose tolerance or insulin sensitivity is that of amelioration of the diuretic-induced hypokalemia; however, studies have demonstrated that diuretics can impair peripheral insulin sensitivity independent of lowering serum potassium levels [2,7,11–13]. Combination RAS blockade (ACE-I or ARB) with diuretic therapy has been reported to cause fewer adverse effects on glucose metabolism than diuretic therapy alone [13–15]; however, in some of these studies, the negative metabolic effects of diuretics were not completely ameliorated by RAS blockade [8,11,16–17]. …”

Section: Introductionmentioning

confidence: 99%

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

Sowers

Raij

Jialal

et al. 2010

Journal of Hypertension

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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. 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 to hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive subjects (BMI = 35±7 kg/m 2 , seated BP = 159±8/94±8 mmHg, and mean age 56 years). Subjects were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 Address correspondence to James R. Sowers, MD, Professor of Medicine, Physiology and Pharmacology, Director, Diabetes Cardiovascular Center, University of Missouri-Columbia, D109 Diabetes Center UHC, 1 Hospital Drive, Columbia, Missouri 65212, Phone: (573) 884-0769; Fax: (573) 884-5530 sowersj@health.missouri.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Clinical trial number: NCT00439738 Conflict NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript mg or amlodipine plus hydrochlorothiazide titrated to 10 mg 25 mg, respectively. Changes from baseline to Week 16 in fasting and 2-hour postprandial glucose and insulin levels after an oral glucose load were measured. At Week 16, clinic blood pressure reductions were similar (P>0.05) in both groups. Fasting and 2-hour 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. 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.

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Comparison of effects of captopril used either alone or in combination with a thiazide diuretic on insulin action in hypertensive Type 2 diabetic patients: a double‐blind crossover study

Abstract: Combination of bendrofluazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.

Cited by 16 publications

References 41 publications

Effects on Insulin Action of Adding Low-Dose Thiazide to Angiotensin-Converting Enzyme Inhibitor in Essential Hypertension

Effects on Insulin Action of Adding Low-Dose Thiazide to Angiotensin-Converting Enzyme Inhibitor in Essential Hypertension

Antihypertensive agents, insulin sensitivity, and new-onset diabetes

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

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