Metabolic Impact of Adding a Thiazide Diuretic to Captopril

Abstract

See related article, pp 800–805 Thiazide diuretics are among the antihypertensive agents that demonstrate effectiveness in improving cardiovascular morbidity and mortality. However, there has been concern regarding adverse metabolic effects of thiazide diuretics on insulin sensitivity in those predisposed to diabetes mellitus, such as those individuals who are overweight and have hypertension.1,2 In this regard, population-based studies suggest that incident or new-onset diabetes mellitus increased in groups randomized to thiazide-type diuretic treatment.3 Although the exact mechanism for thiazide-induced impairments in glucose metabolism has yet to be determined, groups have traditionally explored alterations in insulin metabolic signaling mechanisms, as it relates to (1) reductions in glucose disposal and (2) impairments in pancreatic β-cell insulin secretion (Figure). In contrast, therapies directed at reducing renin–angiotensin–aldosterone system (RAAS) have been observed to improve glucose metabolism.4 Figure. Obesity and hypertension predispose individuals to insulin resistance and diabetes mellitus through activation of the renin–angiotensin–aldosterone system (RAAS), and systemic and local tissue inflamation and oxidative stress. Use of thiazide-type diuretics enhance activation of the RAAS and impair insulin sensitivity through potential actions on skeletal muscle glucose disposal, pancreatic β-cell insulin secretion, and hepatic glucose production. Recent data would suggest that inhibition of the RAAS with angiotensin-converting enzyme (ACE) inhibitors (ACEi) or angiotensin receptor blockers (ARB) attenuate the negative metabolic impact of thiazide diuretics through direct actions on early-phase pancreatic β-cell insulin secretion and hepatic insulin sensitivity. Diuretic-induced natiuresis stimulates …