Angiotensin receptor blocker/diuretic combination preserves insulin responses in obese hypertensives.
BACKGROUND
Thiazide diuretics can impair glucose metabolism and increase new-onset diabetes. Adding an angiotensin receptor blocker to diuretics may protect against these metabolic effects; however, the mechanism of this protection is unclear.


METHODS
To explore potential mechanisms, a 16-week multicenter trial was conducted to ascertain the relative glucose metabolism effects of combined hydrochlorothiazide and angiotensin receptor blocker (valsartan) therapy compared with hydrochlorothiazide and calcium channel blocker (amlodipine) treatment in 412 centrally obese hypertensive individuals (BMI = 35 +/- 7 kg/m, seated BP = 159 +/- 8/94 +/- 8 mmHg, and mean age 56 years). Individuals were randomized to valsartan/hydrochlorothiazide, with force-titration to 320/25 mg or hydrochlorothiazide, with titration to hydrochlorothiazide 25 mg and amlodipine 10 mg, respectively. Changes from baseline to week 16 in fasting and 2-h postprandial glucose and insulin levels after an oral glucose load were measured.


RESULTS
At week 16, clinic blood pressure reductions were similar (P > 0.05) in both groups. Fasting and 2-h glucose levels increased (P < 0.05) with the amlodipine combination but not with the valsartan combination. In concert with these glucose responses, postprandial insulin increases from baseline were substantially greater with valsartan than with amlodipine plus hydrochlorothiazide group (P = 0.001). The glucose responses were inversely related to insulin responses at the study conclusion.


CONCLUSIONS
The novel observation of this investigation was that the combination of valsartan and hydrochlorothiazide was associated with greater glucose-stimulated insulin secretory and lesser glycemic excursion responses than the amlodipine combination group. Thus, this data suggests that adding an angiotensin receptor blocker attenuates the negative effects of thiazides on pancreatic beta-cell glucose-induced insulin secretion.
Sowers
James R
JR
Diabetes and Cardiovascular Center, University of Missouri School of Medicine, and VA Medical Center, Columbia, Missouri 65212, USA. sowersj@health.missouri.edu
Raij
Leopoldo
L
Jialal
Ishwaral
I
Egan
Brent M
BM
Ofili
Elizabeth O
EO
Samuel
Rita
R
Zappe
Dion H
DH
Purkayastha
Das
D
Deedwania
Prakash C
PC
D000368:Aged; D017311:Amlodipine / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D015992:Body Mass Index; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D004232:Diuretics; D007328:Insulin; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine