Lack of correlation between thiazide-induced hyperglycemia and hypokalemia: Subgroup analysis of results from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study

Steven M. Smith, Shawn D. Anderson, Sheron Wen, Yan Gong, Stephen T Turner, Rhonda M. Cooper-DeHoff, Gary Lee Schwartz, Kent R Bailey, Arlene Chapman, Karen L. Hall, Hua Feng, Eric Boerwinkle, Julie A. Johnson, John G. Gums

Research output: Contribution to journalArticle

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Abstract

Study Objective. To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients. Design. 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. Patients. 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. Measurements and Main 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 μIU/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. Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)1157-1165
Number of pages9
JournalPharmacotherapy
Volume29
Issue number10
DOIs
StatePublished - Oct 2009

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Thiazides
Hypokalemia
Hyperglycemia
Antihypertensive Agents
Potassium
Serum
Glucose
Hydrochlorothiazide
Insulin
Fasting
Hypertension
Pharmacogenomic Testing
Confidence Intervals
Sodium Chloride Symporter Inhibitors
Tertiary Care Centers
Primary Health Care
Diabetes Mellitus

Keywords

  • Hydrochlorothiazide
  • Hyperglycemia
  • Hypokalemia
  • Thiazide diuretics
  • Thiazide-induced hyperglycemia

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Lack of correlation between thiazide-induced hyperglycemia and hypokalemia : Subgroup analysis of results from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study. / Smith, Steven M.; Anderson, Shawn D.; Wen, Sheron; Gong, Yan; Turner, Stephen T; Cooper-DeHoff, Rhonda M.; Schwartz, Gary Lee; Bailey, Kent R; Chapman, Arlene; Hall, Karen L.; Feng, Hua; Boerwinkle, Eric; Johnson, Julie A.; Gums, John G.

In: Pharmacotherapy, Vol. 29, No. 10, 10.2009, p. 1157-1165.

Research output: Contribution to journalArticle

Smith, Steven M. ; Anderson, Shawn D. ; Wen, Sheron ; Gong, Yan ; Turner, Stephen T ; Cooper-DeHoff, Rhonda M. ; Schwartz, Gary Lee ; Bailey, Kent R ; Chapman, Arlene ; Hall, Karen L. ; Feng, Hua ; Boerwinkle, Eric ; Johnson, Julie A. ; Gums, John G. / Lack of correlation between thiazide-induced hyperglycemia and hypokalemia : Subgroup analysis of results from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study. In: Pharmacotherapy. 2009 ; Vol. 29, No. 10. pp. 1157-1165.
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abstract = "Study Objective. To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients. Design. 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. Patients. 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. Measurements and Main 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 μIU/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. Conclusion. 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.",
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T2 - Subgroup analysis of results from the pharmacogenomic evaluation of antihypertensive responses (PEAR) study

AU - Smith, Steven M.

AU - Anderson, Shawn D.

AU - Wen, Sheron

AU - Gong, Yan

AU - Turner, Stephen T

AU - Cooper-DeHoff, Rhonda M.

AU - Schwartz, Gary Lee

AU - Bailey, Kent R

AU - Chapman, Arlene

AU - Hall, Karen L.

AU - Feng, Hua

AU - Boerwinkle, Eric

AU - Johnson, Julie A.

AU - Gums, John G.

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N2 - Study Objective. To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients. Design. 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. Patients. 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. Measurements and Main 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 μIU/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. Conclusion. 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.

AB - Study Objective. To determine whether changes in serum glucose, serum potassium, and plasma insulin levels are correlated in a cohort of hypertensive patients. Design. 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. Patients. 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. Measurements and Main 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 μIU/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. Conclusion. 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.

KW - Hydrochlorothiazide

KW - Hyperglycemia

KW - Hypokalemia

KW - Thiazide diuretics

KW - Thiazide-induced hyperglycemia

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