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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).

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.

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  • Authors+Show Affiliations

    ,

    Kaiser Permanente of Georgia , USA.

    , , , , , , , , ,

    Source

    Archives of internal medicine 166:20 2006 Nov 13 pg 2191-201

    MeSH

    Aged
    Amlodipine
    Angiotensin-Converting Enzyme Inhibitors
    Antihypertensive Agents
    Blood Glucose
    Calcium Channel Blockers
    Chi-Square Distribution
    Chlorthalidone
    Diabetes Mellitus
    Female
    Humans
    Hydroxymethylglutaryl-CoA Reductase Inhibitors
    Hyperlipidemias
    Hypertension
    Incidence
    Lisinopril
    Male
    Middle Aged
    Myocardial Infarction
    Proportional Hazards Models
    Sodium Chloride Symporter Inhibitors
    Treatment Outcome

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17101936

    Citation

    Barzilay, Joshua I., et al. "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)." Archives of Internal Medicine, vol. 166, no. 20, 2006, pp. 2191-201.
    Barzilay JI, Davis BR, Cutler JA, et al. 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). Arch Intern Med. 2006;166(20):2191-201.
    Barzilay, J. I., Davis, B. R., Cutler, J. A., Pressel, S. L., Whelton, P. K., Basile, J., ... Summerson, J. (2006). 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). Archives of Internal Medicine, 166(20), pp. 2191-201.
    Barzilay JI, et al. 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). Arch Intern Med. 2006 Nov 13;166(20):2191-201. PubMed PMID: 17101936.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - 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). AU - Barzilay,Joshua I, AU - Davis,Barry R, AU - Cutler,Jeffrey A, AU - Pressel,Sara L, AU - Whelton,Paul K, AU - Basile,Jan, AU - Margolis,Karen L, AU - Ong,Stephen T, AU - Sadler,Laurie S, AU - Summerson,John, AU - ,, PY - 2006/11/15/pubmed PY - 2007/1/6/medline PY - 2006/11/15/entrez SP - 2191 EP - 201 JF - Archives of internal medicine JO - Arch. Intern. Med. VL - 166 IS - 20 N2 - 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. SN - 0003-9926 UR - https://www.unboundmedicine.com/medline/citation/17101936/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__ L2 - https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/10.1001/archinte.166.20.2191 DB - PRIME DP - Unbound Medicine ER -