Fasting glucose, bone area and bone mineral density: a Mendelian randomisation study.

Area of Science:

• Genetics
• Metabolic Health
• Bone Biology

Background:

• Observational studies link type 2 diabetes and fasting glucose to altered hip fracture risk, bone area, and bone mineral density (BMD).
• Potential biases like confounding and reverse causation limit observational findings.
• Mendelian randomization (MR) offers a method to infer causality using genetic variants.

Purpose of the Study:

• To determine if fasting glucose levels causally influence total hip bone area and BMD in individuals without diabetes.
• To address limitations of previous observational studies using a genetic approach.

Main Methods:

• Utilized 35 single nucleotide polymorphisms (SNPs) strongly associated with fasting glucose from the MAGIC consortium.
• Applied MR to assess genetically predicted fasting glucose concentrations against total hip bone area and BMD.
• Analyzed data from 4966 men and women without diabetes across three Swedish cohorts.

Main Results:

• A genetically predicted 1 mmol/l increase in fasting glucose was associated with a 2% smaller total hip bone area (p=0.039).
• A trend towards a 4% higher total hip BMD was observed, though not statistically significant (p=0.060).

Conclusions:

• Fasting glucose may be a causal factor for reduced hip bone area.
• Evidence suggests a potential causal link between fasting glucose and increased hip BMD, requiring further investigation.
• Larger sample sizes are needed for future MR studies to confirm these associations.