Cited by 293Renin-Angiotensin System StudiesBlood Pressure and Hypertension StudiesChronic Kidney Disease and Diabetes

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Why blockade of the renin–angiotensin system reduces the incidence of new-onset diabetes

Jandeleit-Dahm, Karin AM, Tikellis, Christos, Reid, Christopher M, Johnston, Colin I, Cooper, Mark E·2005·Journal of Hypertension

DOI 10.1097/01.hjh.0000160198.05416.72

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Abstract

Recent trials have suggested that inhibitors of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs), may reduce the incidence of new-onset diabetes in patients with or without hypertension and at high risk of developing diabetes. In this review, we critically evaluate the evidence from recent clinical trials for such a potential preventive effect of ACE inhibitors and ARBs, including a meta-analysis of these recent trials. The reduced incidence of diabetes in patients at high risk of developing diabetes by ACE inhibitors or ARBs has been explained by haemodynamic effects, such as improved delivery of insulin and glucose to the peripheral skeletal muscle, and non-haemodynamic effects, including direct effects on glucose transport and insulin signalling pathways, all of which decrease insulin resistance. There is now evidence that the pancreas may contain an in situ active RAS, which appears to be upregulated in an animal model of type 2 diabetes. Thus, ACE inhibitors and ARBs may act by attenuating the deleterious effect of angiotensin II on vasoconstriction, fibrosis, inflammation, apoptosis and beta-cell death in the pancreas, thereby protecting a critical beta-cell mass essential for insulin production. New evidence is presented that ACE inhibitors and ARBs may delay or prevent the development of insulin resistance and diabetes, for which novel mechanisms are suggested. The actions of agents that interrupt the RAS on insulin resistance, obesity and diabetes warrant further investigation in other animal models. Prospective clinical studies with the primary endpoint of the prevention of diabetes are now indicated to (i) further explore whether the inhibitors of the RAS are superior compared to other antihypertensive agents such as calcium channel blockers (CCBs) and (ii) to evaluate the potential beneficial effects of combination antihypertensive regimens on the development of diabetes.

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Authors: Jandeleit-Dahm, K. A., Tikellis, C., Reid, C. M., Johnston, C. I., & Cooper, M. E.
Affiliations: Baker Heart and Diabetes Institute (AU)
ORCID: Reid, Christopher M
Cooper, Mark E
Venue: Journal of Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2005-03
Volume: 23
Issue: 3
Pages: 463-473
ISSN: 0263-6352 (ISSN-L)
DOI: 10.1097/01.hjh.0000160198.05416.72
OpenAlex: W2048359273
Cited by: 293
References: 89
Citations by year: 2026: 2 · 2025: 5 · 2024: 4 · 2023: 6 · 2022: 8 · 2021: 4 · 2020: 11 · 2019: 7 · 2018: 15 · 2017: 7 · 2016: 3 · 2015: 10 · 2014: 14 · 2013: 8 · 2012: 17
FWCI: 6.04
Type: journal article
Language: en
Open access: closed
Locations: Journal of Hypertension (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords: renin-angiotensin system, ACE inhibitors, angiotensin receptor blockers, type 2 diabetes prevention, new-onset diabetes, insulin resistance, beta-cell death, angiotensin II, hypertension, obesity, antihypertensive drugs, calcium channel blockers, combination antihypertensive therapy
MeSH terms: Angiotensin-Converting Enzyme Inhibitors, Diabetes Mellitus, Type 2, Humans, Hypertension, Renin-Angiotensin System, Incidence, Angiotensin II Type 1 Receptor Blockers

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Why blockade of the renin–angiotensin system reduces the incidence of new-onset diabetes

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