Association of statins with diabetes mellitus and diabetic complications: role of confounders during follow-up

Studies have associated statin use with increased risk of diabetes and diabetic complications. These studies often ensure comparability of statin users and non-users at baseline; however, most studies neglect to consider confounders that occur during follow-up. Failure to consider these confounders, such as new medications or procedures, may result in identification of a spurious association between statins and outcomes. The objective of this study was to examine the association of statins with diabetes mellitus and diabetic complications; and to examine potential confounders during the follow-up period that might affect this relationship. We conducted a retrospective cohort study using Tricare data (from October 1, 2003 to March 31, 2012). We propensity score-matched statin users and non-users on 115 baseline characteristics before starting statins; these characteristics would be potentially associated with the use of statins or the outcomes of interest. Outcomes included the risk of diabetes mellitus and diabetic complications. Out of 60,455 patients (10,910 statin users and 49,545 non-users), we propensity score-matched 6728 statin users to 6728 non-users. Statin users had higher ORs for diabetes (OR 1.34, 95% CI 1.24 to 1.44) and diabetes with complications (OR 1.28, 95% CI 1.16 to 1.42). Adjustment for potential confounders that occurred during the follow-up period did not explain or diminish the association between statins and adverse outcomes. Statin users in comparison to similar non-users were more commonly diagnosed with diabetes and diabetic complications, even after adjustment for potential confounders that occurred during the follow-up period.

[1]  E. Halm,et al.  Long-Term Outcomes of Short-Term Statin Use in Healthy Adults: A Retrospective Cohort Study , 2016, Drug Safety.

[2]  I. Mansi Statin Adverse Events in Primary Prevention: Between Randomized Trials and Observational Studies , 2015, The American journal of the medical sciences.

[3]  C. Frei,et al.  Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults , 2015, Journal of General Internal Medicine.

[4]  Hynek Pikhart,et al.  HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials , 2015, The Lancet.

[5]  T. Frayling Statins and type 2 diabetes: genetic studies on target , 2015, The Lancet.

[6]  B. Nordestgaard,et al.  Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study. , 2014, The lancet. Diabetes & endocrinology.

[7]  A. Marette,et al.  Statin-Induced Insulin Resistance Through Inflammasome Activation: Sailing Between Scylla and Charybdis , 2014, Diabetes.

[8]  P. Cawthon,et al.  Statins and physical activity in older men: the osteoporotic fractures in men study. , 2014, JAMA internal medicine.

[9]  C. Tseng,et al.  Different time trends of caloric and fat intake between statin users and nonusers among US adults: gluttony in the time of statins? , 2014, JAMA internal medicine.

[10]  Susan T. Shero,et al.  2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014, Circulation.

[11]  M. Tarnopolsky,et al.  Fluvastatin Causes NLRP3 Inflammasome-Mediated Adipose Insulin Resistance , 2014, Diabetes.

[12]  P. Ridker,et al.  An assessment by the Statin Diabetes Safety Task Force: 2014 update. , 2014, Journal of clinical lipidology.

[13]  P. Lee,et al.  Statins use is associated with poorer glycaemic control in a cohort of hypertensive patients with diabetes and without diabetes , 2014, Diabetology & Metabolic Syndrome.

[14]  Peter Diem,et al.  Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study , 2014, BMJ : British Medical Journal.

[15]  Peter Diem,et al.  Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study , 2013, BMJ.

[16]  D. Mangin,et al.  The comparative risk of new-onset diabetes after prescription of drugs for cardiovascular risk prevention in primary care: a national cohort study , 2013, BMJ Open.

[17]  R. Mutter,et al.  Emergency Department Visits for Adults with Diabetes, 2010 , 2013 .

[18]  P. Chou,et al.  Differential Impact of Statin on New-Onset Diabetes in Different Age Groups: A Population-Based Case-Control Study in Women from an Asian Country , 2013, PloS one.

[19]  L. Bujanda,et al.  Several statins increase body and liver fat accumulation in a model of metabolic syndrome. , 2013, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[20]  E. Mortensen,et al.  The controversy of a wider statin utilization: why? , 2013, Expert opinion on drug safety.

[21]  M. Hernán,et al.  Observational data for comparative effectiveness research: An emulation of randomised trials of statins and primary prevention of coronary heart disease , 2013, Statistical methods in medical research.

[22]  John D. Childs,et al.  Brief psychosocial education, not core stabilization, reduced incidence of low back pain: results from the Prevention of Low Back Pain in the Military (POLM) cluster randomized trial , 2011, BMC medicine.

[23]  Gary King,et al.  MatchIt: Nonparametric Preprocessing for Parametric Causal Inference , 2011 .

[24]  A. Elixhauser,et al.  Hospitalizations Related to Diabetes in Pregnancy, 2008 , 2010 .

[25]  T. Fraze,et al.  Hospital Stays for Patients with Diabetes, 2008 , 2010 .

[26]  L. Brinton,et al.  Oral contraceptive use among women in the military and the general U.S. population. , 2010, Journal of women's health.

[27]  Yasuo Ohashi,et al.  Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials , 2010, The Lancet.

[28]  J. Mehta,et al.  Effect of Statins on Fasting Plasma Glucose in Diabetic and Nondiabetic Patients , 2009, Journal of Investigative Medicine.

[29]  H. Quan,et al.  Assessing validity of ICD-9-CM and ICD-10 administrative data in recording clinical conditions in a unique dually coded database. , 2008, Health services research.

[30]  C. Gantt,et al.  Analysis of weight and associated health consequences of the active duty staff at a major Naval medical center. , 2008, Military medicine.

[31]  Jake Bowers,et al.  Covariate balance in simple stratified and clustered comparative studies , 2008, 0808.3857.

[32]  Samy Suissa,et al.  Immortal time bias in pharmaco-epidemiology. , 2008, American journal of epidemiology.

[33]  Dewey Evans,et al.  Risk adjustment performance of Charlson and Elixhauser comorbidities in ICD-9 and ICD-10 administrative databases , 2008, BMC health services research.

[34]  Gary King,et al.  Matching as Nonparametric Preprocessing for Reducing Model Dependence in Parametric Causal Inference , 2007, Political Analysis.

[35]  A. Rigby,et al.  Insulin Resistance, the Metabolic Syndrome, and Complication Risk in Type 1 Diabetes , 2007, Diabetes Care.

[36]  W. J. Miller,et al.  Common reasons for hospitalization among adult patients with diabetes. , 2006, Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.

[37]  Sun Ha Jee,et al.  Body-mass index and mortality in Korean men and women. , 2006, The New England journal of medicine.

[38]  M. Nakata,et al.  Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control , 2006, Diabetologia.

[39]  C. Steiner,et al.  Conditions With the Largest Number of Adult Hospital Readmissions by Payer, 2011 , 2006 .

[40]  B. Hansen Full Matching in an Observational Study of Coaching for the SAT , 2004 .

[41]  Donald R. Miller,et al.  Who has diabetes? Best estimates of diabetes prevalence in the Department of Veterans Affairs based on computerized patient data. , 2004, Diabetes care.

[42]  R. Pandey,et al.  Simvastatin retards progression of retinopathy in diabetic patients with hypercholesterolemia. , 2002, Diabetes research and clinical practice.

[43]  R. Sorelle US Department of Health and Human Services gives states wider latitude in choosing services to be covered by Medicaid. , 2001, Circulation.

[44]  M. Heo,et al.  Meta-analysis of the effect of excluding early deaths on the estimated relationship between body mass index and mortality. , 1999, Obesity research.

[45]  M. Cowen,et al.  Casemix adjustment of managed care claims data using the clinical classification for health policy research method. , 1998, Medical care.

[46]  M. Kendall,et al.  The effects of combined treatment with beta 1-selective receptor antagonists and lipid-lowering drugs on fat metabolism and measures of fatigue during moderate intensity exercise: a placebo-controlled study in healthy subjects. , 1997, British journal of clinical pharmacology.

[47]  R. Deyo,et al.  Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. , 1992, Journal of clinical epidemiology.

[48]  L. Yannuzzi,et al.  The effects of lipid lowering on diabetic retinopathy. , 1991, American journal of ophthalmology.

[49]  Helen X. Gao,et al.  Prevalence of and trends in diabetes among adults in the United States, 1988-2012. , 2016, Journal of diabetes.

[50]  Susan T. Shero,et al.  2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines , 2014 .

[51]  P. Toth Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Meta-analysis , 2012 .

[52]  B. Poulose,et al.  Risk factors for pressure ulcers in acute care hospitals , 2008, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[53]  M. Buse Hexosamines, insulin resistance, and the complications of diabetes: current status. , 2006, American journal of physiology. Endocrinology and metabolism.

[54]  A. Elixhauser,et al.  Hospitalizations Related to Diabetes in Pregnancy, 2008: Statistical Brief #102 , 2006 .

[55]  C. Steiner,et al.  Comorbidity measures for use with administrative data. , 1998, Medical care.