Hyperglycemia and Glycosuria Due to Thiazide Derivatives Administered in Diabetes Mellitus

Goldner, Martin G.; Zarowitz, H; Akgün, Suat

doi:10.1056/nejm196002252620807

Cited by 204 publications

(63 citation statements)

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“…This investigation corroborates the work of Zilversmit et al 3 ' 5 and Stein et al 6 -7 who have shown that normal aorta can synthesize phospholipids from various radioactive precursors of the phospholipid molecule such as phosphorus-32, acetate-C-14, and carbon-14 free fatty acids. Additional studies carried out by the authors of this editorial have provided evidence that uniformly labeled glucose-C-14 can also serve as a precursor for arterial wall phospholipids presumably by providing a-glycerophosphate.…”

Section: An Hypothesis Relating Phospholipid Synthesis In the Arteriasupporting

confidence: 91%

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Clinical and Physiological Implications of Diabetes Induced by Benzothiadiazines

Wolff¹

1964

Diabetes

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Section: An Hypothesis Relating Phospholipid Synthesis In the Arteriasupporting

confidence: 91%

“…Similar effects were noted by Goldner et al, 3 Halprin, 4 Sugar, 5 Hollis, 6 Wilkins, 7 Freis, 8 Mach, 9 Saudan, 10 and Curchod. 11 Hyperglycemia after BZD was thought to occur in either mildly diabetic patients, or in those suffering from subclinical diabetes.…”

supporting

confidence: 75%

Clinical and Physiological Implications of Diabetes Induced by Benzothiadiazines

Wolff¹

1964

Diabetes

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“…Recently, results of a network meta-analysis, using data from 22 clinical trials comprising 143,153 participants who did not have diabetes at randomization, suggested that the association between antihypertensive agents and incident diabetes is lowest for angiotensinogen receptor blockers and ACE inhibitors followed by calcium channel blockers and placebo, with ␤-blockers and diuretics increasing risk (2). The diabetogenicity of ␤-blockers and diuretics is consistent with their adverse impact on blood glucose levels, which has been reported for several decades (3)(4)(5). In contrast with the adverse effects of diuretics (3,6,7) and ␤-blockers (8) on the incidence of new-onset diabetes (NOD) in randomized trials, the bulk of trial evidence suggests that drugs that block the renin-angiotensin system exert a protective role against the development of NOD (2,9,10).…”

mentioning

confidence: 77%

Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication

et al. 2008

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OBJECTIVE -The purpose of this study was to determine the baseline predictors of newonset diabetes (NOD) in hypertensive patients and to develop a risk score to identify those at high risk of NOD. RESEARCH DESIGN AND METHODS -Among 19,257 hypertensive patients in theAnglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) who were randomly assigned to receive one of two antihypertensive regimens (atenolol Ϯ thiazide or amlodipine Ϯ perindopril), 14,120 were at risk of developing diabetes at baseline. Of these, 1,366 (9.7%) subsequently developed NOD during median follow-up of 5.5 years. A multivariate Cox model was developed to identify the independent predictors of NOD and individual risk scores.RESULTS -NOD was significantly associated with an increase in baseline fasting plasma glucose (FPG), BMI, serum triglycerides, and systolic blood pressure. In contrast, amlodipine Ϯ perindopril in comparison with atenolol Ϯ thiazide treatment (hazard ratio 0.66 [95% CI 0.59 -0.74]), high HDL cholesterol, alcohol use, and age Ͼ55 years were found to be significantly protective factors. FPG was the most powerful predictor with risk increasing by 5.8 times (95% CI 5.23-6.43) for each millimole per liter rise Ͼ5 mmol/l. The risk of NOD increased steadily with increasing quartile of risk score, with a 19-fold increase (95% CI 14.3-25.4) among those in the highest compared with those in the lowest quartile. The model showed excellent internal validity and discriminative ability.CONCLUSIONS -Baseline FPG Ͼ5 mmol/l, BMI, and use of an atenolol Ϯ diuretic regimen were among the major determinants of NOD in hypertensive patients. The model developed from these data allows accurate prediction of NOD among hypertensive subjects. Diabetes Care 31:982-988, 2008O bservational data suggest that hypertension is a risk factor for type 2 diabetes (1); hence, the two conditions frequently coexist. The increased propensity of the hypertensive population to develop diabetes is variably affected by different classes of antihypertensive medication. Recently, results of a network meta-analysis, using data from 22 clinical trials comprising 143,153 participants who did not have diabetes at randomization, suggested that the association between antihypertensive agents and incident diabetes is lowest for angiotensinogen receptor blockers and ACE inhibitors followed by calcium channel blockers and placebo, with ␤-blockers and diuretics increasing risk (2). The diabetogenicity of ␤-blockers and diuretics is consistent with their adverse impact on blood glucose levels, which has been reported for several decades (3-5). In contrast with the adverse effects of diuretics (3,6,7) and ␤-blockers (8) on the incidence of new-onset diabetes (NOD) in randomized trials, the bulk of trial evidence suggests that drugs that block the renin-angiotensin system exert a protective role against the development of NOD (2,9,10). These differential effects have influenced recommendations for antihypertensive drug sequencing contained in British g...

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“…For many years, studies have noted glucose impairment in some patients treated with thiazide‐based diuretics 36, 37. Although still under debate, recent studies have also demonstrated associations with thiazide‐based treatments and increased risk of type II diabetes and subsequently increased the risk of cardiovascular events 38, 39.…”

Section: Discussionmentioning

confidence: 99%

Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes

Rotroff

Shahin

Gurley

et al. 2015

CPT Pharmacometrics Syst. Pharmacol.

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Achieving hypertension (HTN) control and mitigating the adverse health effects associated with HTN continues to be a global challenge. Some individuals respond poorly to current HTN therapies, and mechanisms for response variation remain poorly understood. We used a nontargeted metabolomics approach (gas chromatography time‐of‐flight/mass spectrometry gas chromatography time‐of‐flight/mass spectrometry) measuring 489 metabolites to characterize metabolite signatures associated with treatment response to anti‐HTN drugs, atenolol (ATEN), and hydrochlorothiazide (HCTZ), in white and black participants with uncomplicated HTN enrolled in the Pharmacogenomic Evaluation of Antihypertensive Responses study. Metabolite profiles were significantly different between races, and metabolite responses associated with home diastolic blood pressure (HDBP) response were identified. Metabolite pathway analyses identified gluconeogenesis, plasmalogen synthesis, and tryptophan metabolism increases in white participants treated with HCTZ (P < 0.05). Furthermore, we developed predictive models from metabolite signatures of HDBP treatment response (P < 1 × 10−5). As part of a quantitative systems pharmacology approach, the metabolites identified herein may serve as biomarkers for improving treatment decisions and elucidating mechanisms driving HTN treatment responses.

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Hyperglycemia and Glycosuria Due to Thiazide Derivatives Administered in Diabetes Mellitus

Cited by 204 publications

References 1 publication

Clinical and Physiological Implications of Diabetes Induced by Benzothiadiazines

Clinical and Physiological Implications of Diabetes Induced by Benzothiadiazines

Determinants of New-Onset Diabetes Among 19,257 Hypertensive Patients Randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the Relative Influence of Antihypertensive Medication

Pharmacometabolomic Assessments of Atenolol and Hydrochlorothiazide Treatment Reveal Novel Drug Response Phenotypes

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