Association of bone derived hormones with obesity and glycemic status

Abstract Background Bone-derived hormones, including lipocalin-2 (LCN2) and osteocalcin, are increasingly recognized for their roles in glucose metabolism and insulin sensitivity. Their patterns across normoglycemia, prediabetes, and type 2 diabetes mellitus (T2DM) remain underexplored. Objectives To evaluate serum LCN2 and osteocalcin levels in obese and non-obese T2DM cases, prediabetic individuals, and healthy controls, and to assess their associations with insulin resistance (IR) and metabolic parameters. Methods In this case–control study, 124 adults aged 30–60 years were equally allocated into four groups: obese T2DM, non-obese T2DM, prediabetes, and healthy controls ( n = 31 each). Anthropometric data, fasting and postprandial glucose, HbA1c, insulin, lipid profile, serum LCN2, and osteocalcin were measured. Results LCN2 levels were significantly lower in diabetics (8.0 ± 1.0 ng/mL) and higher in prediabetics (8.7 ± 0.5 ng/mL) compared to controls (8.7 ± 0.3 ng/mL; p < 0.001). Osteocalcin was higher in diabetics (median 6.6 ng/mL) than in prediabetics (6.1 ng/mL) and controls (5.4 ng/mL), though differences were not significant ( p = 0.327). In multivariate analysis, decreased LCN2 (OR = 0.24, 95% CI 0.07–0.76), higher TGs (OR = 1.03 per mg/dL), and higher insulin (OR = 1.13 per µU/mL) independently predicted T2DM. For prediabetes, TGs were the strongest predictor (OR = 1.03 per mg/dL). LCN2 correlated negatively with fasting glucose ( r =–0.44) and 2-hour postprandial glucose ( r =–0.58) in prediabetes, and positively with osteocalcin in both groups. ROC analysis for LCN2 in predicting diabetes showed an AUC of 0.66 (cut-off ≤ 8.3 ng/mL; 44% sensitivity, 77% specificity). Conclusion LCN2 and osteocalcin demonstrate potential as early markers of metabolic disturbance. Altered LCN2 patterns suggest an inflammation-related response in prediabetes and depletion in overt diabetes.