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

摘要 治疗2型糖尿病（T2 D）的专业协会指南认可血红蛋白的血糖目标 A1 c（HbA 1c）<7%对于大多数未怀孕的成年人，以降低并发症的长期风险。但对于 约1200万≥65岁的美国T2 D患者，目前的指南建议个体化治疗 管理和放松血糖控制（即，HbA 1c 7%至<9%），适用于有多种合并症的患者， 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 强化治疗具有显著的风险（例如，低血糖）、治疗负担和费用以及治疗时间 受益可能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潜在的 放松血糖控制，增加老年人感染的风险。因为一项关于 放松与强化血糖控制对感染的影响是不可行的，我们提出了一项观察性研究， 估计与放松血糖控制相关的感染住院的短期风险（HbA 1c 7%） 与强化血糖控制（HbA 1c 6%至<7%）相比，拟议的观察性研究将 使用116，484名年龄≥65岁的不同种族和民族（62%为少数民族）成年人的纵向数据， HbA 1c在指南推荐的6%至<9%范围内的T2 D患者。该项目将确定 与老年T2 D患者因感染住院治疗的12个月风险相关（目的1）;确定 按基线HbA 1c水平列出的感染住院率和风险比（目标2）;并估计 放松血糖控制与强化血糖控制对糖尿病住院风险的独立（无混杂）影响 使用基于倾向分数重叠加权和有向非循环图通知的多变量的感染 调整以减轻潜在混淆（目标3）。在整个项目期间，我们将与 由关键运营和临床健康计划负责人组成的利益相关者咨询理事会， 我们的研究策略，传播我们的研究结果，并计划未来的实施。拟议的研究将 提供所需证据，为老年T2 D患者的安全血糖目标提供建议， 特别是，为了了解放松血糖控制和短期住院风险之间的关系， 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.