Low Bone Turnover Associates with Lower Insulin Sensitivity in Newly Diagnosed Drug-naïve Persons with Type 2 Diabetes

Abstract Context Bone turnover markers (BTMs) are lower in type 2 diabetes (T2D). The relationships between bone turnover, β-cell function, and insulin sensitivity in T2D are uncertain. Objective To investigate if fasting levels of BTMs in persons with T2D are associated with β-cell function or insulin sensitivity. Methods We defined three T2D phenotypes: the insulinopenic (low β-cell function, high insulin sensitivity), the classical (low β-cell function, low insulin sensitivity) and the hyperinsulinemic (high β-cell function, low insulin sensitivity) phenotypes, in the Danish Centre for Strategic Research in T2D cohort, using the homeostatic assessment model. We selected age and gender matched subgroups to represent the three T2D phenotypes, yielding 326 glucose-lowering treatment naïve persons with T2D. Median values of BTMs between the three T2D phenotypes were compared. Regression models were applied to assess the association between BTMs, β-cell function and insulin sensitivity, adjusted for potential confounders. Results Median serum levels of procollagen type I N-terminal propeptide, C-terminal telopeptide of type I collagen and osteocalcin were higher in the insulinopenic phenotype (52.3 (μg/L) IQR [41.6, 63.3], 259.4 (ng/L) [163.4, 347.7], 18.0 (μg/L) [14.4, 25.2], respectively) compared to the classical (41.4 [31.0, 51.4], 150.4 [103.5, 265.1], 13.1 [10.0, 17.6], respectively) and the hyperinsulinemic (43.7 [32.3, 57.3], 163.3 [98.9, 273.1], 15.7 [10.2, 20.8], respectively) phenotypes (all p < 0.01). These differences persisted after adjustment for age, sex, waist-to-hip ratio, or fasting plasma glucose (p < 0.01). Conclusion BTMs are lower in newly diagnosed persons with T2D characterized by low insulin sensitivity.