Can ACE Inhibitors Prevent Type 2 Diabetes?
January 15, 2002 3 minutes read
Can ACE Inhibitors Prevent Type 2 Diabetes?
Abstract & Commentary
Synopsis: Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals.
Source: Yusuf S, et al. JAMA. 2001;286:1882-1885.
In their article, Yusuf and colleagues state, "Type 2 diabetes is an important and common risk factor for the development of coronary artery disease, strokes, peripheral vascular disease, and renal and eye disease. Currently, in North America, the direct and indirect costs of diabetes and its complications exceeds $100 billion per year."
Recently it has been demonstrated that the ACE inhibitor, ramipril, reduced myocardial infarction, strokes, deaths, and the development of diabetic nephropathy among high-risk people both with and without a diagnosis of diabetes.1 It was also noted that ramipril reduced the development of diabetes in study participants without diabetes at the time of randomization. This study describes the findings in more detail and explores possible explanations.
The randomized, controlled Heart Outcomes Prevention Evaluation (HOPE) trial of 5720 patients older than 55 years without known diabetes but with vascular disease were followed for 4.5 years. The study was conducted in 267 hospitals in 19 countries, between 1994 and 1999. Patients were assigned to receive ramipril (n = 2837) or placebo (n = 2883).
The main outcomes measure was the diagnosis of diabetes compared between the 2 groups.
One hundred two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR] 0.66; P < .001). These results were consistently seen in the subgroups that were examined.
Yusuf et al concluded that ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. They noted that because these results have important clinical and public health implications, that this hypothesis requires prospective confirmation.
Comment by Ralph R. Hall, MD, FACP
This study demonstrates a strong protective effect of ramipril and, presumably, other ACE inhibitors as well. Yusuf et al are careful to point out that the study was not designed to test for the development of diabetes and therefore needs additional confirmation. These studies are now underway. The diabetes reduction assessment with ramipril and rosiglitazone among individuals with impaired glucose tolerance will evaluate prospectively whether ramipril can prevent at least some cases of diabetes.
Yusuf et al note that in the UK Prospective Diabetes Study (UKPDS)1 and in the Captopril Prevention Project2 patients randomized to receive ACE inhibitors had lower levels of HbA1c or less development of diabetes compared to those taking diuretics or beta-blockers. It is not clear, however, whether the differences observed are due to the protective effects of ACE inhibitors or an adverse effect of the diuretics and beta-blockers.
Yusuf et al note that the mechanisms whereby the effect of ACE inhibitors to improve insulin resistance or preserve beta cell function are unknown. They note that the decreased loss of potassium in those taking ACE inhibitors as well as the potential for increased islet cell blood flow due to reducing vasoconstriction to the pancreas may slow or reverse the decline in beta-cell function. It is interesting, however, that both ACE inhibitors and calcium channel blockers have been shown to increase glucose disposal.3 Perhaps any drug that increases glucose disposal may be beneficial.
It would also be interesting to know whether angiotensin II receptor blockers would have the same effect as the ACE inhibitors since they have diverse effects on bradykinin levels. Bradykinin is increased with the ACE inhibitors due to decreased degradation, but not with angiotensin II receptor blockers. Bradykinin is a powerful stimulator of nitric oxide and, therefore, stimulates small vessel blood flow and vasodilation.4
It is important for us to know about the differences in the action of these 2 classes of drugs since whenever possible one would prefer to use the less expensive ACE inhibitors. The pharmaceutical companies seem to be reluctant to test the differences since it might reduce the use of the more profitable angiotensin II receptor blockers.
Dr. Hall, Emeritus Professor of Medicine, University of Missouri-Kansas City School of Medicine, is Associate Editor of Internal Medicine Alert.
References
1. UK Prospective Diabetes Study (UKPDS) Group (UKPDS 33). Lancet. 1998;352:837-853.
2. UK Prospective Diabetes Study (UKPDS) Group (UKPDS 39) BMJ. 1998;317:713-720.
3. Bonora E, et al. J Clin Endocrinol Metab. 1999;84: 1544-1550.
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