Increasing fasting glucose and fasting insulin associated with elevated bone mineral density—evidence from cross-sectional and MR studies

We performed a cross-sectional study using the National Health Examination and Nutrition Survey (NHANES) data and a Mendelian randomisation (MR) study using the GWAS summary statistics from European populations. The T2D-related indices (fasting plasma glucose (FPG), fasting insulin (FI), and insulin resistance (IR)) were found to associate with elevated bone mineral density (BMD). The known associations amongst FPG, FI, IR, and BMD remain inconsistent. This study aims to explore the abovementioned associations by using cross-sectional and MR designs. Data from adults aged ≥ 20 years (n = 7170) in four rounds of the U.S. NHANES (2005–2010 and 2013–2014) were analysed in this cross-sectional study. Multiple linear and logistic regression models were used for statistical analyses. A two-sample MR study was performed using the genome-wide association study summary statistics obtained from the Meta-analyses of Glucose and Insulin-related traits Consortium (n = 108,557) and Genetic Factors for Osteoporosis Consortium (n = 32,735) to examine the causality of the FI–BMD association. Multiple linear regression revealed that FPG was positively associated with the BMDs at the hip, femur neck, and 1st lumbar spine (L1). Multiple logistic regressions revealed that FPG levels were associated with elevated BMDs at the hip and L1, and FI and IR levels were associated with elevated BMD at the hip. Patients with type 2 diabetes had higher hip BMD than those without diabetes. In the MR study, the lumbar spine BMD increased by 0.49 g/cm2 (95% confidence interval: 0.01, 0.97) in response to per unit increase in log-transformed FI. Findings from our cross-sectional and MR studies revealed the associations between the studied diabetic indices and BMD measurements in the US and European adults.