Thiazide-induced disturbances in carbohydrate, lipid, and potassium metabolism

Perez-Stable, Eliseo; Caralis, Potoula V.

doi:10.1016/0002-8703(83)90124-2

Cited by 72 publications

(25 citation statements)

References 66 publications

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“…Even though there is an abundance of evidence supporting the beneficial effects of thiazide diuretics on cardiovascular outcomes, these agents may accelerate the onset of T2DM in patients with hypertension (particularly when used in high doses) [77,[87][88][89][90][91][92][93], although older studies often had method limitations [93]. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attacks Trial (ALLHAT) [70], the odds ratio of developing of developing T2DM at 2 years was significantly lower for lisinopril and amlodipine (0.55, P < .…”

Section: Thiazide Diuretics Clinical Datamentioning

confidence: 99%

“…Thiazide diuretics worsen glycemic control in a dose-dependent fashion by decreasing insulin secretion and peripheral insulin sensitivity [77,[87][88][89]97]. Hypokalemia (and perhaps hypomagnesemia) may play an important role in thiazide-induced glucose intolerance [77,[97][98][99], and deterioration in glucose metabolism occurs even with minimal decreases in serum potassium levels [90].…”

Section: Mechanismsmentioning

confidence: 99%

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Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

Hayden

Sowers

2008

Journal of the American Society of Hypertension

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Hypertension, a multifactorial-polygenic disease, interacts with multiple environmental stressors and results in functional and structural changes in numerous end organs, including the cardiovascular system. This can result in coronary heart disease, stroke, peripheral vascular disease, congestive heart failure, end-stage renal disease, insulin resistance, and damage to the pancreatic islet. Hypertension is the most important modifiable risk factor for major health problems encountered in clinical practice. Whereas hypertension was once thought to be a medical condition based on discrete blood pressure readings, a new concept has emerged defining hypertension as part of a complex and progressive metabolic and cardiovascular disease, an important part of a cardiometabolic syndrome. The central role of insulin resistance, oxidative stress, endothelial dysfunction, metabolic signaling defects within tissues, and the role of enhanced tissue renin-angiotensin-aldosterone system activity as it relates to hypertension and type 2 diabetes mellitus is emphasized. Additionally, this review focuses on the effect of hypertension on functional and structural changes associated with the vulnerable pancreatic islet. Various classes of antihypertensive drugs are reviewed, especially their roles in delaying or preventing damage to the vulnerable pancreatic islet, and thus delaying the development of type 2 diabetes mellitus.

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Section: Thiazide Diuretics Clinical Datamentioning

confidence: 99%

Section: Mechanismsmentioning

confidence: 99%

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

Hayden

Sowers

2008

Journal of the American Society of Hypertension

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“…Despite this, concerns have been raised in recent years about the potential long term adverse metabolic effects of diuretics, notably, drug-induced alterations in blood lipids, glucose and uric acid as well as reductions in circulating potassium and magnesium. A sustained clinical debate has centred on the question whether these biochemical abnormalities pose a real threat to health and could even be negating the beneficial effects achieved through lowering blood pressure (Kaplan, 1983;Perez-Stable & Caralis, 1983;Hollifield, 1984). Yet underlying this controversy there has been a failure by physicians to appreciate that these adverse metabolic effects are largely an iatrogenic phenomenon (Lant, 1986).…”

Section: Dosage Considerations and Toxic Profilementioning

confidence: 99%

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

Lant

1987

Brit J Clinical Pharma

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1 The emergence of diuretic drugs and angiotensin converting enzyme (ACE) inhibitors ranks amongst the major therapeutic advances of modern medicine. The discovery of these drug groups arose largely by chance, yet each has dramatically influenced the treatment of congestive cardiac failure and arterial hypertension. 2 The central role which diuretics have had in the management of both oedema and hypertension hinges on their ability to induce a net renal excretion of solute and water by selective interference with either active or passive ion transport processes in different segments of the nephron. Irrespective of sites of action, the continued antihypertensive action of diuretics is characterized by a reduction in plasma volume and extracellular fluid (ECF) volume that lasts for as long as the diuretic is given. The mechanism of this effect remains unclear but may involve autoregulatory reactions that leave cardiac output unaltered but maintain a sustained reduction in total peripheral resistance. 3 ACE inhibitors also lower blood pressure by decreasing total peripheral resistance, leaving cardiac output, plasma volume and ECF volume unchanged. The detailed way these haemodynamic changes are achieved remains unknown but inhibition of converting enzyme present not only in the kidney but also in many extrarenal tissue sites, appears important. In both hypertension and cardiac failure, however, the kidney acts as a key target organ for ACE inhibitors. The increased renal vascular resistance and inappropriate renal salt excretion are reversed with enhanced renal blood flow and saluresis. Both angiotensin II (All) and vasopressin-mediated contraction of glomerular mesangial cells is inhibited, making glomerular filtration more efficient. Reduced aldosterone secondary to blockade of AII formation contributes to saluresis whilst encouraging positive potassium balance. ACE inhibition also impairs breakdown of kinins which may contribute to intrarenal and peripheral vasodilation either on their own or via release of prostaglandins and other vasoactive substances.4 The hypotensive actions of diuretics are potentiated by ACE inhibition primarily through blockade of AII formation and prevention of secondary aldosteronism. In combination, these drugs permit low doses to be used because of their synergistic effects. 5 Caution has to be exercised whenever ACE inhibition is used, without and especially with diuretics, in the management of renovascular hypertension and other low-perfusion states. In these circumstances, AII plays an important autoregulatory role in preserving glomerular filtration through an increase in post-glomerular resistance. Suppression of angiotensin formation with an ACE inhibitor can cause a critical reduction in glomerular perfusion. On the other hand, with careful titration, the dual actions of low-dose loop diuretics and an ACE inhibitor may be highly efficacious in treating severe heart failure and totally prevent such serious metabolic sequelae as azotaemia and hyponatraemia. 6 Unlike the experien...

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“…Potassium depletion with diuretic therapy may create a biologically insulinopenic state and may explain in part the known adverse effects of thiazide-induced lipid disorders. 28 Despite a small but significant fall in levels of serum potassium, this study ruled out a potassium depletion using a total body counter.…”

Section: -173mentioning

confidence: 76%

Serum lipoprotein levels during long-term treatment of hypertension with indapamide.

Meyer‐Sabellek¹,

Gotzen²,

Heitz³

et al. 1985

Hypertension

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SUMMARY The beneficial effect of antihypertensive pharmacotherapy in decreasing morbidity and mortality in hypertensive patients may be counteracted by metabolic and biochemical disturbances, such as hypokalemia, hyperglycemia, hyperuricemia, and hyperlipoproteinemia, that occur with the administration of thiazides and related diuretics. Antiatherogenk high-density lipoprotein cholesterol may be unchanged, whereas the potentially atherogenic low-density lipoprotein cholesterol may be increased by long-term therapy with thiazide diuretics. Indapamide is a methylindoline antihypertensive diuretic with a considerable peripheral vasodilatory effect. At a low dose of 2.5 mg daily, it did not alter total circulating cholesterol, in contrast to chlorthalidone. High-density lipoprotein cholesterol levels increased significantly in 20 hypertensive men after 6 months of therapy with indapamide, resulting in a significant fall of the low-density lipoprotein/high-density lipoprotein ratio, an atherogenic risk factor, regardless of preexisting lipid disorders. (Hypertension 7 [Suppl IT]: II-170-H-174, 1985) KEY WORDS • total body potassium • high-density lipoprotein cholesterolM ULTICENTER trials 13 demonstrated the beneficial effect of antihypertensive pharmacotherapy in decreasing morbidity and mortality in patients with high blood pressure, including mild hypertension. Long-term antihypertensive therapy with thiazides and related diuretics has been associated with distinct biochemical side effects, including changes in total body potassium, 4 hypokalemia, 5 hyperglycemia, 6 and hyperuricemia, 7 and to a lesser degree, decreased glucose tolerance and worsening diabetes mellitus. 8 More recent studies 9 "" focused on impaired lipid metabolism due to long-term therapy with sulfonamide diuretics. Weidmann et al. 12 showed that hydrochlorothiazides and chlorthalidone increase plasma triglycerides and total cholesterol in mildly hypertensive patients. Other investigations also demonstrated a tendency to increased triglyceride and/or total cholesterol levels in patients treated with thiazide diuretics."" 13 Significant increase of the potentially atherogenic serum low-density lipoprotein (LDL) cholesterol accom- panied by a possible increase of very low-density lipoprotein (VLDL) cholesterol fractions may be detected with long-term treatment with thiazide diuretics, whereas the level of antiatherogenic high-density lipoprotein (HDL) cholesterol remains unchanged. It is therefore of considerable importance to study lipoproteins, which are probably more important correlates of atherogenesis than lipid levels per se with any longterm diuretic and/or antihypertensive therapy.Miller et al. w were among the first to note an inverse correlation between HDL cholesterol and the prevalence of coronary heart disease (CHD). Data generated from the Framingham Study 13 showed that the cholesterol ratio (total cholesterol to HDL cholesterol) was higher among men and women with clinical evidence of CHD than among those with standard risk factor...

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Thiazide-induced disturbances in carbohydrate, lipid, and potassium metabolism

Cited by 72 publications

References 66 publications

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

Evolution of diuretics and ACE inhibitors, their renal and antihypertensive actions‐parallels and contrasts.

Serum lipoprotein levels during long-term treatment of hypertension with indapamide.

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