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© 2005 by the American Diabetes Association, Inc.
Letters: Comments and Responses |
Antihypertensive Therapy and Incidence of Type 2 Diabetes in an Elderly Cohort
Response to Padwal et al.
From the Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
Address correspondence to Dr. Peter Tong, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong. E-mail: ptong{at}cuhk.edu.hk
We read the study by Padwal et al. (1) with great interest and feel that it warrants comment. In this retrospective observational cohort study of a large number of elderly patients (n = 725,469, mean age 72–73 years) but of short duration (mean follow-up period of 9.5–11.6 months), the authors found that incidence of new-onset type 2 diabetes was not different among the four major classes of antihypertensive drugs (ACE inhibitors, ß-blockers, calcium channel blockers, and thiazide diuretics). Their findings were in total conflict with other well-conducted prospective studies using ACE inhibitors. For instance, in the CAPPP (Captopril Prevention Project), HOPE (Heart Outcomes Prevention Evaluation), and the more recent PEACE (Prevention of Events with Angiotensin Converting Enzyme Inhibition) studies, it has been consistently shown that patients treated with ACE inhibitors (captopril, ramipril, and trandolapril, respectively) have significantly lower incidence of new-onset type 2 diabetes (2–4). These studies were of a sufficiently long follow-up period (>4 years).
Two factors may account for the surprise findings observed in the Padwal et al. study. First, the study subjects were all elderly patients with a mean age of 72–73 years. Patients who had already developed type 2 diabetes before their enrollment age (
66 years) were excluded. Those who had not developed diabetes were clearly protected by certain intrinsic or environmental factors. Hence, there is a profound element of selection bias, something that is likely to exist in studies that are retrospective in nature. Second, the short mean follow-up duration of 9.5–11.6 months is hardly sufficient for drug-induced glucose intolerance to occur, even for their large sample size. Given these two critical limiting factors, it is not surprising that they even found ß-blockers to be "protective" against the development of diabetes.
References
- Padwal R, Rothwell DM, Mamdani M, Alter DA, Hux JE, Tu K, Laupacis A: Antihypertensive therapy and incidence of type 2 diabetes in an elderly cohort. Diabetes Care 27:2458–2463, 2004
[Abstract/Free Full Text]
- Hansson L, Lindholm LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morlin C, Karlberg BE, Wester PO, Bjorck JE: Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomized trial. Lancet 353:611–616, 1999[Medline]
- Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: the Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342:145–153, 2000
[Abstract/Free Full Text]
- Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, Pfeffer MA, Rice MM, Rosenberg YD, Rouleau JL, the PEACE Trial Investigators: Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 351:2058–2068, 2004
[Abstract/Free Full Text]
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