Metabolic and Inflammatory Biomarkers, Multimorbidity Combinations and Disability Burden Among Older Americans

Specific multimorbidity combinations, in particular those including arthritis, stroke, or cognitive impairment have been associated with high burden of ADL/IADL disability. However, the biologic underpinnings of these associations are still unclear. We used data from the Health & Retirement Study (N=5,359, age 65 years or older at baseline) and negative binomial regression models to evaluate if metabolic and inflammatory biomarkers [HbA1c, HDL-cholesterol, C-Reactive Protein (CRP)] mediate the association between specific multimorbidity combinations (at baseline in 2010-2012; grouped around one of eight index diseases: arthritis, cancer, cognitive impairment, diabetes, heart disease, hypertension, lung disease, and stroke) and ADL/IADL disability (at subsequent wave in 2012-2014). Results were adjusted for sociodemographic characteristics, body-mass index, number of coexisting chronic diseases, and baseline ADL/IADL score. HbA1c (IRR=1.01, p=0.004) and CRP (IRR=1.01, p=0.003), but not HDL, were positively associated with the number of coexisting diseases. After adjustment for coexisting diseases, higher HbA1c was associated with greater ADL/IADL limitations for multimorbidity combinations including arthritis (IRR=1.11, p=0.047) and stroke (IRR=1.11, p=0.047), but not for combinations centered around other diseases, while CRP was no longer significantly associated with ADL/IADL limitations for any of the multimorbidity combinations. Models accounting for HbA1c and CRP, respectively, showed that only combinations including cognitive impairment had greater ADL/IADL limitations (IRR=1.45, p=0.015) compared to combinations without cognitive impairment. Insulin resistance and inflammation are strongly associated with the burden of multimorbidity; this strong association, rather than the biomarkers per se, appears to explain the greater ADL/IADL burden observed with all disease-specific multimorbidity combinations, except cognitive impairment.