Winterstein Almut G, Kubilis Paul, Bird Steve, Cooper-DeHoff Rhonda M, Nichols Greg A, Delaney Joseph A
Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; Epidemiology, Colleges of Public Health and Health Professions and Medicine, University of Florida, Gainesville, FL, USA.
Pharmacoepidemiol Drug Saf. 2014 Aug;23(8):875-81. doi: 10.1002/pds.3656. Epub 2014 Jun 12.
Suspected diabetogenic effects or drug indication may increase testing for diabetes mellitus (DM), resulting in measurement bias when evaluating diabetogenic drug effects. We sought to evaluate the validity of electronic health record data in determining DM risk.
We used time-dependent Cox proportional hazard models within a retrospective cohort design to assess associations between use of antihypertensives, statins, atypical antipsychotics, and antidepressants, and two endpoints: (i) DM onset defined as fasting blood glucose (BG) ≥126 mg/dl, random BG ≥200 mg/dl, HbA1c ≥7.0%, or antidiabetic drug initiation; and (ii) first negative DM test. We used Poisson regression to assess the influence of these drugs on DM testing rates. Patients aged 35-64 years enrolled in Kaiser Permanente Northwest between 1997 and 2010 entered the cohort at the first negative BG test after ≥6 months without manifest DM.
All drug classes showed significant associations not only with DM onset but also with first negative BG test and with DM testing rates. Antipsychotics had the greatest diabetogenic risk (adjusted hazard ratio [HR] = 1.73 [1.44-2.08]), the greatest propensity for a first negative test (adjusted HR = 1.87 [1.74-2.01]), and the highest testing rate (adjusted rate ratio = 1.76 [1.72-1.81]. Although renin-angiotensin system blockers and calcium channel blockers have shown no diabetogenic risk in clinical trials, both were associated with DM (HR = 1.19 [1.12-1.26] and 1.27 [1.17-1.38]), a negative glucose test (1.38 [1.35-1.41] and 1.24 [1.20-1.28]), and increased testing rates (rate ratio = 1.26 [1.24-1.27] and 1.27 [1.25-1.28]).
Caution should be used when diabetogenic risk is evaluated using data that rely on DM testing in general practice.
怀疑有致糖尿病作用或药物适应证可能会增加糖尿病（DM）检测，从而在评估致糖尿病药物作用时导致测量偏倚。我们试图评估电子健康记录数据在确定DM风险方面的有效性。
我们采用回顾性队列设计中的时间依赖性Cox比例风险模型，以评估使用抗高血压药、他汀类药物、非典型抗精神病药和抗抑郁药与两个终点之间的关联：（i）DM发病定义为空腹血糖（BG）≥126mg/dl、随机BG≥200mg/dl、糖化血红蛋白（HbA1c）≥7.0%或开始使用抗糖尿病药物；以及(ii )首次DM检测阴性结果。我们使用泊松回归来评估这些药物对DM检测率的影响。年龄在35 - 64岁之间于1997年至2010年在西北凯撒医疗集团注册的患者，在无明显DM且≥6个月后首次BG检测阴性时进入队列。
所有药物类别不仅与DM发病显著关联，而且与首次BG检测阴性结果以及DM检测率显著相关。抗精神病药具有最大的致糖尿病风险（调整后风险比[HR]=1.73[1.44 - 2.08]），首次检测阴性的倾向最大（调整后HR = 1.87[1.74 - 2.01]），检测率最高（调整后率比 = 1.76[1.72 - 1.81]）。尽管肾素 - 血管紧张素系统阻滞剂和钙通道阻滞剂在临床试验中未显示有致糖尿病风险，但两者均与DM相关（HR = 1.19[1.12 - 1.26]和1.27[1.17 - 1.38]），葡萄糖检测阴性（1.38[1.35 - 1.41]和1.24[1.20 - 1.28]）以及检测率增加（率比 = 1.26[1.24 - 1.27]和1.27[1.25 - 1.28]）。
在使用一般医疗实践中依赖DM检测的数据评估致糖尿病风险时应谨慎。
