A group of investigators is studying the properties of different antihypertensive agents. They perform an individual, patient-level meta-analysis of several randomized clinical trials and pool the reported adverse effects. According to investigators, the use of a specific class of antihypertensive agents is associated with weight gain and worsening glucose tolerance. Which of the following classes is most likely described by the investigators?

Question

A group of investigators is studying the properties of different antihypertensive agents.  They perform an individual, patient-level meta-analysis of several randomized clinical trials and pool the reported adverse effects.  According to investigators, the use of a specific class of antihypertensive agents is associated with weight gain and worsening glucose tolerance.  Which of the following classes is most likely described by the investigators?

Quizplus · Accepted Answer

Conventional beta blockers, which affect beta-1 receptors (eg, metoprolol, atenolol) or both beta-1 and beta-2 receptors (eg, propranolol), are associated with reduced insulin sensitivity and increased risk of developing type 2 diabetes mellitus. Hemodynamic drug effects on skeletal muscle are likely a major driver of these findings. Normally, alpha-1 receptor stimulation causes vasoconstriction, which reduces glucose uptake into skeletal muscles (due to reduced skeletal muscle blood flow); beta-2 receptor stimulation opposes this effect. In the presence of beta blockade, alpha-1‒mediated effects are unopposed, leading to further reduction in glucose uptake, higher levels of circulating glucose, and resultant increased insulin secretion from the pancreas. Insulin resistance is effectively increased (ie, insulin sensitivity is reduced). As a result, patients experience weight gain. A reduction in lipolysis in adipocytes (which is largely beta-1 receptor-mediated) likely also contributes to weight gain. These side effects make conventional beta blockers an unfavorable option for hypertension management in patients with, or at high risk for, type 2 diabetes mellitus. In contrast, beta blockers with combined vasodilatory alpha-1 receptor‒blocking properties (eg, carvedilol, labetalol) are not associated with reduced insulin sensitivity, which provides further evidence of the importance of the hemodynamic effects on skeletal muscles. (Choices A and C) ACE inhibitors (eg, lisinopril) and angiotensin receptor blockers (eg, losartan, valsartan) may cause hyperkalemia and a reduction in glomerular filtration rate (due to effects on angiotensin and aldosterone). Due to their renal protective properties, these drugs are first-line agents for hypertension management in patients with, or at high risk for, type 2 diabetes mellitus. (Choice B) Orthostatic hypotension is a common and often use-limiting adverse effect of alpha-1 adrenergic blockers (eg, prazosin, doxazosin). These drugs may actually improve insulin sensitivity via increased skeletal muscle blood flow. (Choice E) Dihydropyridine calcium channel blockers (eg, amlodipine, nifedipine) are associated with peripheral edema (due to fluid redistribution) but are not known to affect glucose tolerance. Educational objective: Conventional beta blockers (eg, metoprolol, atenolol, propranolol) are associated with impaired glucose control and increased weight gain, likely via effects on skeletal muscle that lead to reduced insulin sensitivity. Therefore, these drugs are an unfavorable option for hypertension management in patients with, or at high risk for, type 2 diabetes mellitus. References: Effects of beta blockers on glucose and lipid metabolism. (http://www.ncbi.nlm.nih.gov/pubmed/20067434) Antihypertensive treatment with beta blockers and the spectrum of glycemic control. (http://www.ncbi.nlm.nih.gov/pubmed/16766516) Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. (http://www.ncbi.nlm.nih.gov/pubmed/10738048) Effect of antihypertensive therapy on weight loss. The Trial of Antihypertensive Interventions and Management Research Group. (http://www.ncbi.nlm.nih.gov/pubmed/1555871)

A Group of Investigators Is Studying the Properties of Different