Lack of correlation between thiazide-induced hyperglycemia and hypokalemia: subgroup analysis of results from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study.
OBJECTIVE
To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients.


METHODS
Prespecified subgroup analysis of results from a prospective, multicenter, randomized, open-label, parallel-group study. Setting. Primary care clinics at three tertiary care medical centers.


METHODS
Community-based ambulatory population of 202 patients (age range 17-65 yrs) with a new diagnosis of hypertension, untreated hypertension, or known hypertension, who were previously treated with fewer than three antihypertensive drugs and had no evidence of cardiovascular disease or diabetes mellitus. Intervention. Monotherapy with oral hydrochlorothiazide 12.5 or 25 mg/day for 9 weeks.


RESULTS
Fasting serum glucose, serum potassium, and plasma insulin levels were obtained at baseline (before hydrochlorothiazide therapy was started) and after 9 weeks of therapy. Significant elevations were noted in fasting serum glucose (mean +/- SD 3.42 +/- 10.38 mg/dl, p<0.0001) and plasma insulin (2.35 +/- 9.47 microU/ml, p<0.0001) levels, and a significant reduction in serum potassium level (0.30 +/- 0.44 mEq/L, p<0.0001) was noted. No significant correlation was observed between changes in fasting serum glucose and potassium levels (r = 0.022, 95% confidence interval (CI) -0.120-0.164, p=0.757) or between changes in serum potassium and plasma insulin levels (r = -0.112, 95% CI -0.256-0.037, p=0.140). Changes in serum glucose levels did not differ significantly between patients maintaining serum potassium levels of 4.0 mEq/L or greater and those with levels below 4.0 mEq/L.


CONCLUSIONS
Changes in serum potassium and serum glucose levels were not correlated in individuals receiving hydrochlorothiazide monotherapy; thus maintenance of normal potassium levels may not attenuate the risk of thiazide diuretic-induced hyperglycemia.
Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, Florida, USA.
Steven M
SM
Smith
Shawn D
SD
Anderson
Sheron
S
Wen
Yan
Y
Gong
Stephen T
ST
Turner
Rhonda M
RM
Cooper-Dehoff
Gary L
GL
Schwartz
Kent
K
Bailey
Arlene
A
Chapman
Karen L
KL
Hall
Hua
H
Feng
Eric
E
Boerwinkle
Julie A
JA
Johnson
John G
JG
Gums
D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000139:chemically induced*; D006973:Hypertension / Q000188:drug therapy*; D007008:Hypokalemia / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D006852:Hydrochlorothiazide; D011188:Potassium