Diabetes-associated thigh muscle degeneration mediates knee osteoarthritis-related outcomes: results from a longitudinal cohort study

Abstract

Objectives: We examined the association between diabetes mellitus (DM) and longitudinal MRI biomarkers for thigh muscle degeneration in patients with knee osteoarthritis (KOA) and their mediatory role in worsening KOA-related symptoms.

Methods: The Osteoarthritis Initiative (OAI) participants with radiographic KOA (Kellgren-Lawrence grade ≥ 2) were included. Thighs and corresponding knees of KOA patients with versus without self-reported DM were matched for potential confounders using propensity score (PS) matching. We developed and used a validated deep learning method for longitudinal thigh segmentation. We assessed the association of DM with 4-year longitudinal muscle degeneration in biomarkers of muscle cross-sectional area (CSA) and contractile percentage (non-fat CSA/total CSA). We further investigated whether DM is associated with 9-year risk of KOA radiographic progression, knee replacement (KR), and symptoms worsening. Finally, we evaluated whether the DM-KOA worsening association is mediated through preceding muscle degeneration.

Results: After PS matching, 698 thighs/knees were included (185:513 with:without DM; average ± SD age:64 ± 8-years; female/male:1.4). Baseline DM was associated with a decreased contractile percent of total thigh muscles and quadriceps (mean difference, 95%CI -0.16%/year, -0.25 to -0.07, and -0.21%/year, -0.33 to -0.08). DM was also associated with an increased risk of worsening KOA-related symptoms (hazard ratio, 95%CI 1.70, 1.18-2.46) but not radiographic progression or KR. The decrease in quadriceps contractile percent partially mediated the increased risk of symptoms worsening in patients with DM.

Conclusions: Baseline DM is associated with thigh muscle degeneration and KOA-related symptoms worsening. As a potentially modifiable risk factor, DM-associated longitudinal thigh muscle degeneration may partially mediate the symptoms worsening in patients with DM and coexisting KOA.

Key points: • Diabetes mellitus (DM) is associated with worsening knee osteoarthritis (KOA)-related symptoms. • As a potentially modifiable factor, DM-associated thigh muscle (quadriceps) degeneration partially mediates the worsening of KOA-related symptoms.

Keywords: Diabetes mellitus; Intra-muscular adipose tissue; Knee osteoarthritis; Skeletal muscle degeneration; Symptom worsening.