Treating hypertension while protecting the vulnerable islet in the cardiometabolic syndrome

Abstract

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.

Impact of Abdominal Obesity on Incidence of Adverse Metabolic Effects Associated With Antihypertensive Medications

“…These adverse effects were more prominent in those with abdominal obesity, depite normal potassium levels. Our findings reinforce guidelines and recommendations that indicate thiazide diuretics and β blockers be used with caution in patients with or at risk for developing impaired fasting glucose or MetSyn, in order to prevent the development of diabetes and the associated long term adverse consequences 31,32…”

Is a Diabetes Mellitus–Linked Amino Acid Signature Associated With β-Blocker–Induced Impaired Fasting Glucose?

“…1, 2 Impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and insulin resistance, important early components of cardiometabolic dysfunction, are also prevalent in those with hypertension 3 and significantly increase the risk for diabetes. 4, 5 β blockers, although very effective blood pressure (BP) lowering agents, are associated with adverse metabolic effects, including hyperglycemia, IFG, and diabetes, all of which are associated with adverse cardiovascular consequences long-term.…”

Common Medications Which Lead to Unintended Alterations in Weight Gain or Organ Lipotoxicity

“…Interestingly, several anti-hypertensive medications including thiazide diuretics and beta-blockers have been linked with new onset diabetes and dysglycemia in large trials, not all of which are directly attributable to changes in body weight [41]. Importantly, these properties are not uniform within each drug class [42].…”