Pless Lora Lee, Mitchell-Miland Chantele, Seo Yeon-Jung, Bennett Charles B, Freyberg Zachary, Haas Gretchen L
VISN 4 Mental Illness Research Education and Clinical Center (MIRECC), VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
Schizophrenia (Heidelb). 2025 Apr 17;11(1):63. doi: 10.1038/s41537-025-00616-y.
Co-occurrence of type 2 diabetes mellitus (T2D) and serious mental illnesses (SMI) is prevalent yet underappreciated, and significantly contributes to increased morbidity and reduced lifespan. There is, therefore, a need to identify T2D risk factors to inform preventative approaches to the care of SMI-diagnosed patients. Our objective was to use predictive modeling methods to capture risk factors for T2D in a sample of 618,203 Veterans using data obtained from hospital electronic health records (EHR). This case-control study assessed VISN4 Veterans with and without T2D diagnoses and SMI diagnoses (schizophrenia, SZ; schizoaffective, SZA; bipolar disorder, BD; major depression, MDD; 2009-2019). Demographic variables and medications were obtained from the EHR. Following rigorous data quality control, 543,979 Veterans qualified for analysis (Age = 65.9[17.6]years; body mass index(BMI) = 28.6[6.0]kg/m; N = 157,457[29%]; and N = 506,257[93.1%]). Veterans with co-occurring SMI + T2D included N = 2,087(36.5%), N = 1,345(36.3%), N = 10,540(29.2%), and N = 20,510(30%) compared to 112,973(28.6%) non-SMI controls (NSC) with T2D. Factors that predicted T2D (R = 34%) included age, sex, BMI, race/ethnicity, psychiatric diagnoses, and commonly prescribed psychiatric medications. Significant interactions were found between age (centered) and BMI on the odds of T2D (P < 0.001), as well as interaction between sex and BMI (P < 0.001), after adjusting for confounders. Veterans with SMI (SZ, MDD, SZA, and BD) had a higher likelihood of experiencing T2D, compared to the NSCs (OR = 1.30, 95% CI = 1.21-1.40; OR = 1.07, 95% CI = 1.05-1.10; OR = 1.26, 95% CI = 1.16-1.38; OR = 1.05, 95% CI = 1.01-1.08). Finally, Veterans exposed to both selective serotonin reuptake inhibitor (SSRI) antidepressants and mood stabilizers had a 2.11 times increase in the odds of having T2D (95% CI = 2.06-2.16; P < 0.001) compared to Veterans not taking either medication. Four major psychiatric disorders (SZ, SZA, MDD, and BD) and several classes of medications used to treat them increased T2D risk. Our findings suggest that the measures assayed offer a potentially useful signal, that along with clinical, anthropometric, and biochemical measures can be used to ascertain metabolic risk. If confirmed with an independent sample, these findings could also inform medication choices made by prescribers.
2型糖尿病（T2D）与严重精神疾病（SMI）并存的情况很普遍，但却未得到充分认识，并且显著导致发病率增加和寿命缩短。因此，有必要确定T2D的风险因素，以便为SMI诊断患者的预防性护理方法提供依据。我们的目标是使用预测建模方法，利用从医院电子健康记录（EHR）获得的数据，在618,203名退伍军人样本中找出T2D的风险因素。这项病例对照研究评估了2009年至2019年期间患有和未患有T2D诊断以及SMI诊断（精神分裂症，SZ；分裂情感性障碍，SZA；双相情感障碍，BD；重度抑郁症，MDD）的VISN4退伍军人。人口统计学变量和药物信息从EHR中获取。经过严格的数据质量控制后，543,979名退伍军人符合分析条件（年龄 = 65.9[17.6]岁；体重指数（BMI）= 28.6[6.0]kg/m²；N = 157,457[29%]；N = 506,257[93.1%]）。与112,973名患有T2D的非SMI对照（NSC）相比，同时患有SMI + T2D的退伍军人包括N = 2,087（36.5%），N = 1,345（36.3%），N = 10,540（29.2%）和N = 20,510（30%）。预测T2D的因素（R = 34%）包括年龄、性别、BMI、种族/民族、精神疾病诊断以及常用的精神科药物。在调整混杂因素后，发现年龄（中心化）与BMI之间在T2D发生几率上存在显著交互作用（P < 0.001），以及性别与BMI之间的交互作用（P < 0.001）。与NSC相比，患有SMI（SZ、MDD、SZA和BD）的退伍军人患T2D的可能性更高（OR = 1.30，95% CI = 1.21 - 1.40；OR = 1.07，95% CI = 1.05 - 1.10；OR = 1.26，95% CI = 1.16 - 1.38；OR = 1.05，95% CI = 1.01 - 1.08）。最后，与未服用任何一种药物的退伍军人相比，同时服用选择性5-羟色胺再摄取抑制剂（SSRI）类抗抑郁药和心境稳定剂的退伍军人患T2D的几率增加了2.11倍（95% CI = 2.06 - 2.16；P < 0.001）。四种主要精神疾病（SZ、SZA、MDD和BD）以及用于治疗它们的几类药物会增加T2D风险。我们的研究结果表明，所检测的指标提供了一个潜在有用的信号，该信号与临床、人体测量和生化指标一起可用于确定代谢风险。如果通过独立样本得到证实，这些发现也可为开处方者的用药选择提供参考。
