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Association of composite inflammatory indicators with osteoporosis and sarcopenia in type 2 diabetes mellitus: the mediating role of inflammation

J Endocrinol Invest. 2026 May 4. doi: 10.1007/s40618-026-02899-z. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the associations between composite inflammatory indicators and the presence of osteoporosis (OP) and sarcopenia in patients with type 2 diabetes mellitus (T2DM), and to explore the potential mediating role of inflammation in the relationship between sarcopenia and OP.

METHODS: In this cross-sectional study, 756 adults with T2DM were enrolled. Osteoporosis was defined as a Bone Mineral Density (BMD) T-score ≤ -2.5 at the hip or lumbar spine. Sarcopenia was diagnosed according to Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Composite inflammatory indicators, including systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), pan-immune inflammation value (PIV), platelet-to-lymphocyte ratio (PLR), advanced lung cancer inflammation index (ALI), neutrophil-to-albumin percentage ratio (NPAR), platelet-to-neutrophil ratio (PNR), and neutrophil-lymphocyte-platelet ratio (NLPR) were calculated from routine blood parameters. Associations between composite inflammatory indicators and OP as well as sarcopenia were assessed using restricted cubic splines (RCS) and multivariate logistic regression analysis. The ability of composite inflammatory indicators to identify sarcopenia was evaluated using receiver operating characteristic (ROC) curves. Mediation analysis to assess the indirect effect of inflammation on the sarcopenia and osteoporosis relationship.

RESULTS: In this study, the prevalence of osteoporosis was 31.1%, and the prevalence of sarcopenia was 34.0%. RCS analysis revealed that ALI exhibited a linear negative correlation with osteoporosis, and SII, SIRI, NLR, PIV, PLR, NLPR, NPAR exhibited linear positive correlations with sarcopenia (all P for nonlinearity > 0.05). PNR and ALI demonstrated a negative nonlinear association with sarcopenia (all P for nonlinearity < 0.05). Logistic regression analysis indicated that sarcopenia was positively associated with osteoporosis (P< 0.05). However, ALI (aOR 0.99, 95% CI 0.98-1.00) showed inverse association with osteoporosis (P < 0.05). Logistic regression analysis also indicated that osteoporosis was positively associated with sarcopenia (P < 0.05). The multivariable regression analysis showed hs-CRR (aOR 1.03, 95% CI 1.01-1.05), SII (aOR 1.00, 95% CI 1.00-1.00), SIRI (aOR 1.46, 95% CI 1.13-1.93), PIV (aOR 1.00, 95% CI 1.00-1.00), NPAR (aOR 1.11, 95% CI 1.04-1.19), and NLR (aOR 1.20, 95% CI 1.05-1.38) showed positive associations with sarcopenia. Conversely, ALI (aOR 0.98, 95% CI 0.97-0.99) exhibited a inverse association with sarcopenia (P < 0.05). The area under the ROC curve (AUC) for ALI in identifying sarcopenia was 0.68. Mediation analysis showed that ALI mediated the statistical association between sarcopenia and osteoporosis with proportions (%) of 19.58.

CONCLUSION: Sarcopenia is positively associated with osteoporosis in patients with T2DM, and this relationship is partially mediated by systemic inflammation, as captured by the ALI. The ALI may serve as a useful and accessible clinical indicator to identify T2DM patients at higher risk for sarcopenia and osteoporosis, who may benefit from targeted screening and multimodal interventions.

PMID:42081166 | DOI:10.1007/s40618-026-02899-z

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