The DOI matches its Crossref record; 88 of the 89 references it cites were found in a registry or an index.
Why blockade of the renin–angiotensin system reduces the incidence of new-onset diabetes
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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In the citing paper
“Although lowering BP is of paramount importance, studies suggest that antagonizing the RAAS system has special significance in obese patients.168,169”
From Obesity‐Related Hypertension: Pathogenesis, Cardiovascular Risk, and Treatment: A Position Paper of The Obesity Society and the American Society of Hypertension (2013) · cites this paper as [168]
In the citing paper
“In contrast, regimens based on RAAS inhibition are associated with significantly fewer cases of new diabetes.168,170,171”
From Obesity‐Related Hypertension: Pathogenesis, Cardiovascular Risk, and Treatment: A Position Paper of The Obesity Society and the American Society of Hypertension (2013) · cites this paper as [168]
Citations
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Sorted by citations
Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis
Elliott, W. J., & Meyer, P. M. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60108-1 · Cited by 1,016
Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention
Schrader, J., Lüders, S., Kulschewski, A., Hammersen, F., Plate, K., Berger, J., Zidek, W., Dominiak, P., Diener, H., & the MOSES Study Group (2005) · Stroke · doi:10.1161/01.str.0000166048.35740.a9 · Cited by 766
Targeting inflammation in the treatment of type 2 diabetes: time to start
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Renin-angiotensin system and cardiovascular risk
Schmieder, R. E., Hilgers, K. F., Schlaich, M. P., & Schmidt, B. M. W. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60242-6 · Cited by 675
Metadata
- Authors
- Jandeleit-Dahm, K. A., Tikellis, C., Reid, C. M., Johnston, C. I., & Cooper, M. E.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Venue
- Journal of Hypertension
- Published
- 2005-03
- Volume
- 23
- Issue
- 3
- Pages
- 463-473
- ISSN
- 0263-6352 (ISSN-L)
- 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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