A comparison of the effects of low- and conventional-dose thiazide diuretic on insulin action in hypertensive patients with NIDDM.
In conventional doses, thiazide diuretics impair glucose tolerance and decrease insulin sensitivity, making them an unpopular choice for treating diabetic patients with hypertension. However, use of low-dose thiazide diuretics may avoid the adverse metabolic effects seen with conventional doses. In a double-blind, randomised crossover study we assessed peripheral and hepatic insulin action in 13 hypertensive non-insulin-dependent diabetic patients after a 6-week placebo run-in and following two 12-week treatment periods with either low (1.25 mg) or conventional (5.0mg) dose bendrofluazide. There were no differences between doses in their effects on systolic and diastolic blood pressure. Bendrofluazide 1.25 mg had significantly less effect on serum potassium, uric acid, fasting glucose and HbA1C concentrations than the 5.00 mg dose. Exogenous glucose infusion rates required to maintain euglycaemia were significantly different between doses (p < 0.05) with conventional-dose bendrofluazide worsening peripheral insulin resistance compared to baseline (23.8 +/- 2.9 vs 27.3 +/- 3.5 mumol.kg-1.min-1, p < 0.05) and low-dose bendrofluazide producing no change compared to baseline (26.8 +/- 3.6 vs 27.3 +/- 3.5 mumol.kg-1.min-1, p = NS). Postabsorptive endogenous glucose production was higher on treatment with bendrofluazide 5.0 mg compared to 1.25 mg (11.7 +/- 0.5 vs 10.2 +/- 0.3 mumol.kg-1.min-1, p < 0.05) and suppressed to a lesser extent following insulin (4.0 +/- 0.7 vs 2.0 +/- 0.4 mumol.kg-1.min-1, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Harper
R
R
Sir George E. Clark Metabolic Unit, Royal Victoria Hospital, Belfast, UK.
Ennis
C N
CN
Heaney
A P
AP
Sheridan
B
B
Gormley
M
M
Atkinson
A B
AB
Johnston
G D
GD
Bell
P M
PM
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001539:Bendroflumethiazide / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology*; D004232:Diuretics; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008875:Middle Aged; D010919:Placebos; D011188:Potassium / Q000097:blood; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D014527:Uric Acid / Q000097:blood
D000959:Antihypertensive Agents; D001539:Bendroflumethiazide; D001786:Blood Glucose; D004232:Diuretics; D006442:Glycated Hemoglobin; D007328:Insulin; D010919:Placebos; D011188:Potassium; D049993:Sodium Chloride Symporter Inhibitors; D014527:Uric Acid