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Effects of antihypertensive treatment on insulin sensitivity with special reference to ACE inhibitors
Abstract:
In 1984, the suspicion that pharmacological treatment may worsen the insulin resistance and associated metabolic abnormalities in lipid and carbohydrate metabolism and contribute to the relative failure of antihypertensive treatment to produce more than marginal reductions in cardiovascular morbidity and mortality led us to start a series of trials aimed at elucidating how antihypertensive drugs affect insulin sensitivity. These trials, which included assessment of insulin sensitivity by the euglycemic insulin clamp, showed that beta-adrenergic blockade and thiazide diuretic treatment (hydrochlorothiazide) increase insulin resistance and basal plasma insulin, whereas Ca(2+)-channel antagonists (verapamil and diltiazem), with the exception of the negative effect of nifedipine, are metabolically neutral. alpha-Adrenergic blockade with prazosin and angiotensin-converting enzyme (ACE) inhibition with captopril enhance insulin sensitivity. The mechanisms underlying the positive effects of ACE inhibition and beta-adrenergic blockade are largely unknown, but hemodynamic factors (vasodilation) may contribute by improving the access of glucose and insulin to skeletal muscle. The drugs, which were favorable or neutral with respect to insulin sensitivity, caused no changes in lipids or glucose homeostasis. In contrast, beta-blockers, except pindolol, had negative effects on triglycerides and high-density lipoprotein cholesterol, and thiazide diuretics caused adverse effects on total serum cholesterol, low-density lipoprotein cholesterol, and total and very-low-density lipoprotein triglyceride. The metabolic action of antihypertensive drugs is an important factor to consider in the choice of a proper treatment strategy in both diabetic and nondiabetic patients with hypertension.
Insights
Certain blood pressure medications, like beta-blockers and thiazide diuretics, can worsen insulin resistance and metabolic issues. Conversely, ACE inhibitors and some calcium channel blockers improve insulin sensitivity, impacting cardiovascular health.
Area of Science:
- Pharmacology
- Metabolic Research
- Cardiovascular Medicine
Background:
- Antihypertensive drug efficacy in reducing cardiovascular events was questioned due to potential adverse metabolic effects.
- Insulin resistance and associated metabolic abnormalities were suspected to be exacerbated by certain pharmacological treatments.
Purpose of the Study:
- To investigate the impact of various antihypertensive drugs on insulin sensitivity.
- To determine the effects of different drug classes on lipid and carbohydrate metabolism.
Main Methods:
- Euglycemic insulin clamp technique to assess insulin sensitivity.
- Evaluation of basal plasma insulin, glucose homeostasis, and lipid profiles.
- Comparison of beta-adrenergic blockade, thiazide diuretics, calcium channel antagonists, alpha-adrenergic blockade, and ACE inhibition.
Main Results:
- Beta-adrenergic blockade and thiazide diuretics increased insulin resistance and basal insulin levels.
- Calcium channel antagonists (verapamil, diltiazem) were metabolically neutral; nifedipine had negative effects.
- Alpha-adrenergic blockade (prazosin) and ACE inhibition (captopril) enhanced insulin sensitivity.
- Beta-blockers (except pindolol) and thiazide diuretics negatively affected lipid profiles (triglycerides, cholesterol).
Conclusions:
- The metabolic actions of antihypertensive drugs are critical considerations for treatment strategies.
- Drugs favorably or neutrally affecting insulin sensitivity did not alter glucose or lipid homeostasis.
- Choosing antihypertensive medications requires careful consideration of their metabolic effects in both diabetic and non-diabetic patients.