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).

Abstract

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.

• Authors: Joshua I Barzilay, Barry R Davis, Jeffrey A Cutler, Sara L Pressel, Paul K Whelton, Jan Basile, Karen L Margolis, Stephen T Ong, Laurie S Sadler, John Summerson, ALLHAT Collaborative Research Group
• Journal: Archives of internal medicine (Arch Intern Med) Vol. 166 Issue 20 Pg. 2191-201 (Nov 13 2006) ISSN: 0003-9926 [Print] United States
• PMID: 17101936 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Blood Glucose
• Calcium Channel Blockers
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Sodium Chloride Symporter Inhibitors
• Amlodipine
• Lisinopril
• Chlorthalidone

Topics

• Aged
• Amlodipine (therapeutic use)
• Angiotensin-Converting Enzyme Inhibitors (therapeutic use)
• Antihypertensive Agents (adverse effects, therapeutic use)
• Blood Glucose (analysis, drug effects)
• Calcium Channel Blockers (therapeutic use)
• Chi-Square Distribution
• Chlorthalidone (adverse effects, therapeutic use)
• Diabetes Mellitus (blood, chemically induced, epidemiology)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hyperlipidemias (drug therapy)
• Hypertension (blood, drug therapy)
• Incidence
• Lisinopril (therapeutic use)
• Male
• Middle Aged
• Myocardial Infarction (prevention & control)
• Proportional Hazards Models
• Sodium Chloride Symporter Inhibitors (adverse effects, therapeutic use)
• Treatment Outcome