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).
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.
Barzilay
Joshua I
JI
Kaiser Permanente of Georgia , USA.
Davis
Barry R
BR
Cutler
Jeffrey A
JA
Pressel
Sara L
SL
Whelton
Paul K
PK
Basile
Jan
J
Margolis
Karen L
KL
Ong
Stephen T
ST
Sadler
Laurie S
LS
Summerson
John
J
D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D016009:Chi-Square Distribution; D002752:Chlorthalidone / Q000009:adverse effects / Q000627:therapeutic use*; D003920:Diabetes Mellitus / Q000097:blood* / Q000139:chemically induced* / Q000453:epidemiology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D015994:Incidence; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D016016:Proportional Hazards Models; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D049993:Sodium Chloride Symporter Inhibitors; D017311:Amlodipine; D017706:Lisinopril; D002752:Chlorthalidone