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Fasting Glucose Levels and Incident Diabetes Mellitus in Older Nondiabetic Adults Randomized to Receive 3 Different Classes of Antihypertensive Treatment
A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
Joshua I. Barzilay, MD;
Barry R. Davis, MD, PhD;
Jeffrey A. Cutler, MD, MPH;
Sara L. Pressel, MS;
Paul K. Whelton, MD, MSC;
Jan Basile, MD;
Karen L. Margolis, MD, MPH;
Stephen T. Ong, MD;
Laurie S. Sadler, MD;
John Summerson, MS; for the ALLHAT Collaborative Research Group
Arch Intern Med. 2006;166:2191-2201.
Background Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension. The significance of this finding is uncertain. Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic, calcium-channel blocker, or angiotensin-converting enzyme inhibitor on fasting glucose (FG) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus (DM) in 3 treatment groups.
Methods We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) among nondiabetic participants who were randomized to receive treatment with chlorthalidone (n = 8419), amlodipine (n = 4958), or lisinopril (n = 5034) and observed for a mean of 4.9 years.
Results Mean FG levels increased during follow-up in all treatment groups. At year 2, those randomized to the chlorthalidone group had the greatest increase (+8.5 mg/dL [0.47 mmol/L] vs +5.5 mg/dL [0.31 mmol/L] for amlodipine and +3.5 mg/dL [0.19 mmol/L] for lisinopril). The odds ratios for developing DM with lisinopril (0.55 [95% confidence interval, 0.43-0.70]) or amlodipine (0.73 [95% confidence interval, 0.58-0.91]) vs chlorthalidone at 2 years were significantly lower than 1.0 (P<.01). There was no significant association of FG level change at 2 years with subsequent coronary heart disease, stroke, cardiovascular disease, total mortality, or end-stage renal disease. There was no significant association of incident DM at 2 years with clinical outcomes, except for coronary heart disease (risk ratio, 1.64; P = .006), but the risk ratio was lower and nonsignificant in the chlorthalidone group (risk ratio, 1.46; P = .14).
Conclusions Fasting glucose levels increase in older adults with hypertension regardless of treatment type. For those taking chlorthalidone vs other medications, the risk of developing FG levels higher than 125 mg/dL (6.9 mmol/L) is modestly greater, but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events.
Author Affiliations: Kaiser Permanente of Georgia and the Division of Endocrinology, Emory University School of Medicine, Atlanta (Dr Barzilay); Coordinating Center for Clinical Trials, University of Texas School of Public Health, Houston (Dr Davis and Ms Pressel); Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Cutler); Tulane University Health Sciences Center, New Orleans, La (Dr Whelton); Ralph H. Johnson Veterans Affairs Medical Center, Medical University of South Carolina, Charleston (Dr Basile); Hennepin County Medical Center, Division of Clinical Epidemiology, Minneapolis, Minn (Dr Margolis); Ong Medical Center, Oxon Hill, Md (Dr Ong); Lipid Research Center, St Vincent Charity Hospital, Cleveland, Ohio (Dr Sadler); and Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (Mr Summerson).
Group Information: A list of the ALLHAT Collaborative Research Group members was published in JAMA (2002;288:2981-2997).
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