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

• Aims/hypothesis: Observational studies indicate that type 2 diabetes mellitus and fasting glucose levels are associated with a greater risk for hip fracture, lower bone area and higher bone mineral density (BMD). However, these findings may be biased by residual confounding and reverse causation. Mendelian randomisation (MR) utilises genetic variants as instruments for exposures in an attempt to deal with these biases. Thereby, we implemented MR to determine whether fasting glucose levels in individuals without diabetes are causally associated with bone area and BMD at the total hip.Methods: We selected 35 single nucleotide polymorphisms strongly associated with fasting glucose (p <5×10−8) in a non-diabetic European-descent population from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) (n=133,010). MR was used to assess the associations of genetically predicted fasting glucose concentrations with total hip bone area and BMD in 4966 men and women without diabetes from the Swedish Mammography Cohort, Prospective Investigation of Vasculature in Uppsala Seniors, and Uppsala Longitudinal study of Adult men. Results: In meta-analysis of the three cohorts, genetically predicted 1 mmol/L increment of fasting glucose was associated with a 2% lower total hip bone area (-0.67 cm2 [95% CI -1.30, -0.03; p=0.039]) yet tended to be associated with a 4% higher total hip BMD (0.040 g/cm2 [95% CI -0.00, 0.07; p=0.060]).Conclusions/interpretation: Fasting glucose may be a causal risk factor for lower bone area at the hip, yet possibly for greater BMD. Further MR studies with larger sample sizes are required to corroborate these findings.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Ortopedi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Orthopaedics (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

Mendelian randomisation

Single nucleotide polymorphisms

Fasting glucose

Bone area

Bone mineral density

Epidemiology

Epidemiologi

Publikations- och innehållstyp

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