Relaxed Glycemic Control and the Risk of Infections in Older Adults with Type 2 Diabetes

摘要 专业学会2型糖尿病治疗指南(T2D)认可了血红蛋白的血糖目标 A1C(HbA1c)&lt；7%适用于大多数未怀孕的成年人，以降低长期并发症的风险。然而，对于 ~1200万美国≥65岁患有T2D的人，目前的指南建议个性化 管理和放宽血糖控制(即，糖化血红蛋白7%至9%)， 健康状况不佳或预期寿命有限。放松血糖控制的建议是基于证据 强化治疗有重大风险(例如，低血糖)、治疗负担和费用，而且 福利可能会超过老年患者的预期寿命。然而，目前的指导方针未能认识到这一潜力 放松血糖控制以增加老年人感染的风险。因为这种效果的临床试验 放松与强化血糖控制对感染的控制是不可行的，我们建议进行一项观察性研究 估计与血糖控制放松(HbA1c 7%)相关的感染住院短期风险 与强化血糖控制(HbA1c 6%至7%)相比。拟议的观察性研究将 使用来自116,484名不同种族和民族(62%的少数族裔)的成年人的纵向数据，≥65岁 糖化血红蛋白(HbA1c)在指南推荐的6%至9%范围内的T2D患者。该项目将确定因素 与患有T2D的老年人因感染住院12个月的风险有关(目标1)；确定 按基线HbA1c水平分列的因感染住院的比率和风险比(目标2)；以及估计 放松与强化血糖控制对以下疾病住院风险的独立(无混淆)影响 基于倾向分数的重叠权重和有向无环图信息多变量感染 调整以减少潜在的混淆(目标3)。在整个项目期间，我们将与 主要运营和临床健康计划领导人的利益相关者咨询委员会将进行持续审查 我们的研究战略，传播我们的研究成果，并计划未来的实施。拟议的研究将 提供必要的证据，为老年T2D患者的安全血糖目标提供建议， 特别是，要了解放松的血糖控制与住院的短期风险之间的联系 感染。

Abstract Professional society guidelines for treatment of type 2 diabetes (T2D) endorse a glycemic goal of hemoglobin A1c (HbA1c) <7% for most nonpregnant adults to reduce the long-term risk of complications. However, for the ~12 million Americans ≥65 years of age who have T2D, current guidelines recommend individualized management and relaxed glycemic control (i.e., HbA1c 7% to <9%) for patients with multiple comorbidities, poor health or limited life expectancy. Recommendations for relaxed glycemic control are based on evidence that intensive therapy has significant risks (e.g., hypoglycemia), treatment burden and cost, and that time to benefit may exceed life expectancy in older patients. However, current guidelines fail to recognize the potential for relaxed glycemic control to increase the risk of infection in older adults. Because a clinical trial of the effect of relaxed vs. intensive glycemic control on infection is not feasible, we propose an observational study to estimate the short-term risk of hospitalization for infection associated with relaxed glycemic control (HbA1c 7% to <9%) compared with intensive glycemic control (HbA1c 6% to <7%). The proposed observational study will use longitudinal data from 116,484 racially and ethnically diverse (62% minority) adults ≥65 years of age with T2D who have HbA1c within the guideline-recommended range of 6% to <9%. The project will identify factors associated with 12-month risk of hospitalization for infection among older adults with T2D (Aim 1); determine rates and hazard ratios of hospitalizations for infection by levels of baseline HbA1c (Aim 2); and estimate the independent (unconfounded) effect of relaxed versus intensive glycemic control on risk of hospitalization for infection using propensity score-based overlap weighting and directed acyclic graph-informed multivariate adjustment to mitigate potential confounding (Aim 3). Throughout the project period, we will work closely with a Stakeholder Advisory Council of key operational and clinical health plan leaders to conduct ongoing review of our research strategy, disseminate our findings and plan future implementation. The proposed research will provide evidence needed to inform recommendations for safe glycemic goals in older patients with T2D and, in particular, to understand the association of relaxed glycemic control and short-term risk of hospitalization for infection.