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).

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.
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.
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).
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.
AuthorsJoshua 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,
JournalArchives of internal medicine (Arch Intern Med) Vol. 166 Issue 20 Pg. 2191-201 (Nov 13 2006) ISSN: 0003-9926 [Print] United States
PMID17101936 (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
  • 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

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