Background and Aim: Despite having an increased osteoporotic fracture risk, type 2 diabetes (T2D) patients have normal to high bone mineral density (BMD) that may be attributed to increased adiposity, insulin resistance or both. We aimed to assess the relative contribution of fat mass (FM), insulin resistance, hyperinsulinaemia and diabetes per se to BMD in a cohort of lean (n=19), overweight and obese insulin-sensitive (Obsens, n=18), overweight and obese insulin-resistant (Obres, n=17) and T2D patients (n=17).
Methods: Insulin sensitivity was assessed by hyperinsulinaemic (80 mU/m2/min)-euglycaemic (5 mmol/L) clamp. FM, fat-free mass (FFM) and total BMD were determined by dual-energy X-ray absorptiometry.
Results: Non-diabetic overweight and obese individuals were classified as Obsens or Obres based on median glucose infusion rate (GIR, upper vs. bottom, respectively) during the clamp, with separate cut-offs for men and women. Groups were gender- and age- matched (mean age 57±1 years). FM was significantly higher in Obsens, Obres and T2D compared with lean (P<0.001), but not significantly different between the 3 obese groups (P≥0.3). GIR was similar in lean and Obsens (90±5 and 91±8 μmol/min/kg FFM, respectively; P=1) and higher (P<0.001) than Obres and T2D (53±4 and 41±3 μmol/min/kg FFM, respectively; P=0.4 Obresvs. T2D). BMD was significantly higher in Obsens and Obres compared with lean (P≤0.05), but not different between Obsens and Obres (P=1). BMD in T2D was not different from all other groups (P≥0.3). In a multiple linear regression, 39% of the variability in total BMD was explained by gender and FM (P<0.001). Age, insulin resistance and fasting insulin were not retained in the model.
Conclusions: These findings suggest that BMD is largely determined by body fat mass per se. Longitudinal studies are required to assess whether BMD-based risk assessments underestimate fracture risk in obese insulin-resistant individuals and whether obese insulin-sensitive individuals are protected from fracture.
*First 2 authors contributed equally to the work