Associations of Type 2 Diabetes, Body Composition, and Insulin Resistance with Bone Parameters: The Dubbo Osteoporosis Epidemiology Study

Type 2 diabetes (T2D) may be associated with increased risk of fractures, despite preserved bone mineral density (BMD). Obesity and insulin resistance (IR) may have separate effects on bone turnover and bone strength, which contribute to skeletal fragility. We characterized and assessed the relative associations of obesity, body composition, IR, and T2D on bone turnover markers (BTMs), BMD, and advanced hip analysis (AHA). In this cross-sectional analysis of Dubbo Osteoporosis Epidemiology Study, 525 (61.3% women) participants were grouped according to T2D, IR (homeostasis model assessment insulin resistance [HOMA-IR] </≥2.5), and BMI (</≥25 kg/m²): insulin-sensitive lean (IS-L), insulin-sensitive overweight/obese (IS-O), insulin-resistant (IR), and T2D. BMD, AHA, and body composition, including visceral adipose tissue (VAT) (on dual-energy x-ray absorptiometry scan) and fasting BTMs, were assessed. Analyses performed using Bayesian model averaging and principal component analysis. T2D was associated with low BTMs (by 26%-30% [95% confidence interval [CI] 11%-46%] in women, 35% [95% CI 18%-48%] in men compared to IS-L), which persisted after adjustment for VAT. BTMs were similar among IR/IS-O/IS-L. BMD was similar among T2D/IR/IS-O; BMD was low only in IS-L. All groups were similar after adjustment for BMI. Similarly, AHA components were lowest in IS-L (attenuated following adjustment). On multivariate analysis, T2D was independently associated with BTMs. IR was also associated with C-terminal telopeptide of type 1 collagen in men. Age and body size were the strongest independent contributors to BMD and AHA. VAT was inversely associated with section modulus, cross-sectional area, cross-sectional moment of inertia in women, and hip axis length in men. Low bone turnover is associated with T2D and IR (in men), while BMD and hip strength/geometry are predominantly associated with body size. VAT, indicative of dysglycemia, is also associated with impaired bone geometry. Establishing the role of BTMs and AHA fracture risk may improve skeletal assessment in T2D people. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.