Supplementary Material for: Multimorbidity and functional disability among older adults - the role of inflammation and glycemic status: An Observational Longitudinal Study

Introduction: Specific multimorbidity combinations, in particular those including arthritis, stroke, and cognitive impairment, have been associated with high burden of ADL-IADL disability in older adults. The biologic underpinnings of these associations are still unclear. Methods: Observational longitudinal study using data from the Health & Retirement Study (N=8,618, mean age=74 years, 58% female, 25% non-White) and negative binomial regression models stratified by sex to evaluate the role of inflammatory and glycemic biomarkers (high-sensitivity C-reactive protein (hs-CRP) and HbA1c) in the association between specific multimorbidity combinations (grouped around one of eight index diseases: arthritis, cancer, cognitive impairment, diabetes, heart disease, hypertension, lung disease, and stroke; assessed between 2006-2014) and prospective ADL-IADL disability (2 years later, 2008-2016). Results were adjusted for sociodemographic characteristics, body-mass index, number of coexisting diseases, and baseline ADL-IADL score. Results: Multimorbidity combinations indexed by arthritis (IRR=1.1, 95%CI=1.01-1.20), diabetes (IRR=1.19, 95%CI=1.09-1.30), and cognitive impairment (IRR=1.11, 95%CI=1.01-1.23) among men, and diabetes-indexed multimorbidity combinations (IRR=1.07, 95%CI=1.01-1.14) among women were associated with higher ADL-IADL scores at increasing levels of HbA1c. Across higher levels of hs-CRP, multimorbidity combinations indexed by arthritis (IRR=1.06, 95%CI=1.02-1.11), hypertension (IRR=1.06, 95%CI=1.02-1.11), heart disease (IRR=1.06, 95%CI=1.01-1.12), and lung disease (IRR=1.14, 95%CI=1.07-1.23) were associated with higher ADL-IADL scores among women, while there were no significant associations among men. Discussion/Conclusion: The findings suggest potential for anti-inflammatory management among older women and optimal glycemic control among older men with these particular multimorbidity combinations as focus for therapeutic/preventive options for maintaining functional health.

引言：特定共病（multimorbidity）组合，尤其是包含关节炎、脑卒中（stroke）与认知障碍（cognitive impairment）的组合，已被证实与老年群体较高的日常生活活动能力-工具性日常生活活动能力（Activities of Daily Living-Instrumental Activities of Daily Living, ADL-IADL）残疾负担显著相关。上述关联的生物学机制目前仍未明确。
方法：本研究为观察性纵向研究，采用健康与退休研究（Health & Retirement Study, HRS）的数据（样本量N=8618，平均年龄74岁，女性占比58%，非白人占比25%），通过按性别分层的负二项回归模型，评估炎症与血糖生物标志物——高敏C反应蛋白（high-sensitivity C-reactive protein, hs-CRP）与糖化血红蛋白（HbA1c）——在特定共病组合与前瞻性随访2年后（2008-2016年）的ADL-IADL残疾之间的关联中的作用。其中，特定共病组合围绕8种指数疾病分组：关节炎、癌症、认知障碍、糖尿病、心脏病、高血压、肺部疾病、脑卒中，评估时间为2006-2014年。研究结果已针对社会人口学特征、体重指数、共存疾病数量及基线ADL-IADL评分进行了校正。
结果：在男性群体中，以关节炎为指数疾病的共病组合（发生率比（Incidence Rate Ratio, IRR）=1.1，95%置信区间（95% Confidence Interval, 95%CI）=1.01~1.20）、以糖尿病为指数疾病的共病组合（IRR=1.19，95%CI=1.09~1.30）及以认知障碍为指数疾病的共病组合（IRR=1.11，95%CI=1.01~1.23），均与随HbA1c水平升高而升高的ADL-IADL评分显著相关；在女性群体中，仅以糖尿病为指数疾病的共病组合（IRR=1.07，95%CI=1.01~1.14）呈现上述关联。在较高的hs-CRP水平下，女性群体中以关节炎（IRR=1.06，95%CI=1.02~1.11）、高血压（IRR=1.06，95%CI=1.02~1.11）、心脏病（IRR=1.06，95%CI=1.01~1.12）及肺部疾病（IRR=1.14，95%CI=1.07~1.23）为指数疾病的共病组合，均与更高的ADL-IADL评分相关，而男性群体未观察到显著关联。
讨论/结论：本研究结果提示，针对存在上述特定共病组合的老年女性采取抗炎管理、老年男性采取优化血糖控制，或可作为维持功能健康的治疗与预防性干预靶点。