OR01-4 Metabolic Profiles Associated with Incident Fracture among Older Adults with Type 2 Diabetes Mellitus: A Nested Case-Control Study

Abstract

Abstract Background Type 2 diabetes mellitus (DM) is associated with an increased risk of fracture despite a paradoxically higher average bone mineral density. Additional markers of fracture risk among older adults with DM are needed to identify at-risk individuals. Method The MURDOCK study is an ongoing, longitudinal cohort study, initiated in 2007, of residents in Cabarrus and surrounding counties, based in Kannapolis, North Carolina. At study enrollment, participants completed medical and health questionnaires, and provided biospecimen samples for the biorepository. In this nested case-control analysis, incident fractures since study enrollment among MURDOCK participants were identified by self-reported survey and by query of the electronic medical records (EMR). Fracture cases were matched 2: 1 by age, gender, race/ethnicity, and BMI to participants without incident fracture. Stored biorepository serum samples were analyzed for both conventional metabolites (non-esterified fatty acids (NEFA), triglycerides, lactate, and ketones) and targeted metabolomics (amino acids and acylcarnitines), using the Beckman DxC 600 clinical analyzer and flow injection electrospray ionization tandem mass spectrometry, respectively. Principal components analysis (PCA) was used to identify relevant profiles for metabolomics data. The association between incident fracture and metabolic profile was assessed using conditional logistic regression, stratified by matched group and controlled for multiple confounders including tobacco and alcohol use, medical comorbidities (e.g., coronary artery disease, congestive heart failure, chronic kidney disease, rheumatoid arthritis) and medications (e.g., insulin, metformin, thiazolidinediones). Results 107 incident fractures were identified by self-reported questionnaire and EMR query; 210 controls were matched. The study population was predominantly female (71.8%) and white (90.6%) with mean (SD) age 65.0 (7.7) years and BMI 31.8 (6.2) kg/m2. PCA identified 2 amino acid (AA) profiles: profile 1 (AA1) consisted of the branched chain amino acids, phenylalanine and tyrosine; profile 2 (AA2) consisted of serine, arginine, asparagine/aspartate (Asx) and glutamine/glutamate (Glx). After controlling for multiple risk factors, AA2 was significantly associated with incident fracture (OR 1.72, 95% CI: 1.17–2.54). NEFA were associated with lower odds of fracture (OR 0.06, 95% CI: 0.01–0.31). There was no association of fracture with other conventional metabolites, acylcarnitine factors, nor AA1. Conclusion Given association of NEFA and AA2 with incident fracture, our results indicate novel biomarkers, as well as potential mechanisms of fracture risk among older adults with DM. Higher level of NEFA was associated with lower fracture odds; though not further classified in this study, prior studies have shown direct effects of polyunsaturated and monounsaturated fatty acids on osteoclasts. Higher level of AA2, including the amino acids Glx and Asx, was associated with increased fracture odds. Prior studies have shown direct effects of Glx on both osteoblasts and osteoclasts, and Glx and Asx have also been associated with muscle mass and strength. Presentation: Saturday, June 11, 2022 12:30 p.m. - 12:45 p.m.