Naomi Gronich1, Spyros N Deftereos2, Idit Lavi3, Andreas S Persidis2, Darrell R Abernethy4, Gad Rennert5. 1. Pharmacoepidemiology and Pharmacogenetics Unit, Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel gronichn@clalit.org.il. 2. Biovista Inc., Charlottesville, VA. 3. Pharmacoepidemiology and Pharmacogenetics Unit, Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel. 4. Drug Safety Group, Office of Clinical Pharmacology, U.S. Food and Drug Administration, Silver Spring, MD. 5. Pharmacoepidemiology and Pharmacogenetics Unit, Department of Community Medicine and Epidemiology, Lady Davis Carmel Medical Center, and The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.
Abstract
OBJECTIVE: To identify risk factors for the development of statin-associated diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: The study was conducted in two phases. Phase one involved high-throughput in silico processing of a large amount of biomedical data to identify risk factors for the development of statin-associated DM. In phase two, the most prominent risk factor identified was confirmed in an observational cohort study at Clalit, the largest health care organization in Israel. Time-dependent Poisson regression multivariable models were performed to assess rate ratios (RRs) with 95% CIs for DM occurrence. RESULTS: A total of 39,263 statin nonusers were matched by propensity score to 20,334 highly compliant statin initiators in 2004-2005 and followed until the end of 2010. Within 59,597 statin users and nonusers in a multivariable model, hypothyroidism and subclinical hypothyroidism carried an increased risk for DM (RR 1.53 [95% CI 1.31-1.79] and 1.75 [1.40-2.18], respectively). Hypothyroidism increased DM risk irrespective of statin treatment (RR 2.06 [1.42-2.99] and 1.66 [1.05-2.64] in statin users and nonusers, respectively). Subclinical hypothyroidism risk for DM was prominent only upon statin use (RR 1.94 [1.13-3.34] and 1.20 [0.52-2.75] in statin users and nonusers, respectively). Patients with hypothyroidism treated with thyroid hormone replacement therapy were not at increased risk for DM. CONCLUSIONS: Hypothyroidism is a risk factor for DM. Subclinical hypothyroidism-associated risk for DM is prominent only upon statin use. Identifying and treating hypothyroidism and subclinical hypothyroidism might reduce DM risk. Future clinical studies are needed to confirm the findings.
OBJECTIVE: To identify risk factors for the development of statin-associated diabetes mellitus (DM). RESEARCH DESIGN AND METHODS: The study was conducted in two phases. Phase one involved high-throughput in silico processing of a large amount of biomedical data to identify risk factors for the development of statin-associated DM. In phase two, the most prominent risk factor identified was confirmed in an observational cohort study at Clalit, the largest health care organization in Israel. Time-dependent Poisson regression multivariable models were performed to assess rate ratios (RRs) with 95% CIs for DM occurrence. RESULTS: A total of 39,263 statin nonusers were matched by propensity score to 20,334 highly compliant statin initiators in 2004-2005 and followed until the end of 2010. Within 59,597 statin users and nonusers in a multivariable model, hypothyroidism and subclinical hypothyroidism carried an increased risk for DM (RR 1.53 [95% CI 1.31-1.79] and 1.75 [1.40-2.18], respectively). Hypothyroidism increased DM risk irrespective of statin treatment (RR 2.06 [1.42-2.99] and 1.66 [1.05-2.64] in statin users and nonusers, respectively). Subclinical hypothyroidism risk for DM was prominent only upon statin use (RR 1.94 [1.13-3.34] and 1.20 [0.52-2.75] in statin users and nonusers, respectively). Patients with hypothyroidism treated with thyroid hormone replacement therapy were not at increased risk for DM. CONCLUSIONS:Hypothyroidism is a risk factor for DM. Subclinical hypothyroidism-associated risk for DM is prominent only upon statin use. Identifying and treating hypothyroidism and subclinical hypothyroidism might reduce DM risk. Future clinical studies are needed to confirm the findings.
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