HDCN Abstract:  ASN Annual Meeting -- San Francisco  

Shafi T, Parekh RS, Miller ER, et al.

Thiazide-Associated Diabetes in Hypertensive Patients May Be Mediated by Potassium Depletion.

ASN Annual Meeting -- San Francisco
J Am Soc Nephrol (Nov) 18:633A 2007

In hypertensive patients, diabetes (DM) occurs more frequently in those treated with thiazides than with other medications. Potassium (K) depletion by thiazides can reduce insulin secretion and predispose patients to hyperglycemia. The aim of this study was to determine if incident DM with thiazide treatment is potentially mediated by K depletion.

We conducted a post-hoc analysis of the Systolic Hypertension in Elderly Program (SHEP); patients were randomized to chlorthalidone or placebo. Incident DM after randomization was defined as fasting glucose >126 mg/dL or random glucose >200 mg/dL or clinical diagnosis of DM. K depletion was defined as: Baseline K - Lowest K in the 1st yr of study (prior to DM diagnosis).

Of the 4736 SHEP participants, 4012 were non- diabetic at baseline (Chlorthalidone =2016, Placebo =1996). Mean age was 72 yrs, 58% were female and 80% were white. There were 478 incident cases of DM during 16,608 person-yrs of follow-up. The incidence rate (95% CI) of DM was 3.3(2.9-3.7) per 100 person-yrs in the chlorthalidone group and 2.5(2.1-2.8) per 100 person-yrs in the placebo group. Mean K depletion (+SD) was 0.7+0.5 mEQ/L in chlorthalidone group and 0.3+0.5 mEQ/L in placebo group. In Cox regression models (Table), the risk of DM in those assigned to chlorthalidone was significantly higher than placebo (Hazard Ratio (HR): 1.34; 95% CI: 1.10-1.62). After adjustment for K depletion the HR was markedly reduced and was no longer statistically significant suggesting that most of the effect of chlorthalidone on incident DM may be mediated by K depletion.

Our findings, in conjunction with other research, suggest that thiazide-induced K depletion is associated with incident DM. Strategies to prevent DM by avoiding and treating K depletion need to be tested in a clinical trial.

Risk of Incident DM in SHEP*
HAZARD RATIO95% CIp VALUE
WITHOUT K ADJUSTMENT
Chlorthalidone vs. Placebo1.341.10-1.620.003
WITH K ADJUSTMENT
Chlorthalidone vs. Placebo1.090.87-1.360.5
K Depletion (per 1-mEQ/L decline from baseline)1.711.32-2.21<0.001
*Cox regression model adjusted for age, race, gender, BMI, BP, baseline K glucose

© Copyright 2007-2008, American Society of Nephrology. Reproduced with permission.
Until September of 2008, all ASN abstracts from the 2007 Annual Meeting are available at this link

Disclaimer: Abstracts often have errors, both typographical and otherwise. This posting is an electronic translation of submitted abstracts which has not been verified against the original submitted abstract nor with the authors for accuracy. As a result, there may be errors, especially with regard to drug doses, but not limited to these. Abstracts undergo only limited review, and data often are changed as a result of the peer review process, so their reliability is less than manuscripts published in peer-reviewed journals. In using these summaries, you are agreeing that you are aware of these limitations.

The materials are provided on an as-is basis without any warranty of any kind, either express or implied. In addition to errors, the information presented may be incomplete or outdated. The information contained is not intended nor recommended as a substitute for professional medical advice. You are advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each device to be used or drug to be administered to verify the dosage, the method and duration of administration, or contraindications. It is the responsibility of the treating physician or other health care professional, relying on independent experience and knowledge of the patient, to determine drug, disease, and the best treatment for the patient.

To the fullest extent permitted by law, HDCN, ASN and their affiliates and suppliers disclaim all warranties, express or implied, including, but not limited to, any warranty of merchantability, non- infringement or fitness for a particular purpose.

In no event shall HDCN, ASN, or their affiliates or suppliers be liable for any damages whatsoever (including, but not limited to, direct, indirect, incidental, consequential, punitive or exemplary damages, or any damages for loss of profits, use, data, goodwill or other intangibles) arising from or in any way relating to these terms, the materials, or any information, goods or services obtained from or referred to in the materials, whether based on warranty, contract, tort (including, but not limited to, negligence), or any other legal theory, and whether or not any or all of the limited entities is advised of the possibility of such damages.