Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
HemoglobinA1c is a Risk Factor for Changes of Heel Bone Mineral Density: A Mendelian Randomization Study
19 Pages Posted: 30 Mar 2022
More...Abstract
Background: As a valuable blood glucose measurement, HemoglobinA1c (HbA1c) is of great clinical value for diabetes. However, in previous observational studies, studies on its effect on bone mineral density (BMD) have different results. This study aimed to use Mendelian randomization (MR) to assess the effect of HbA1c on bone mineral density and fracture risk, and try to further explore whether this association was achieved through glycemic or non-glycemic factors.
Methods: Take HbA1c measurement as exposure, and BMD estimated from quantitative heel ultrasounds (eBMD) and bone fractures as outcomes. Two-Sample MR Analysis was conducted to assess the causal effect of HbA1C on heel BMD and risk fracture. Then, we performed the analysis using two subsets of these variants, one related to glycemic measurement and the other to erythrocyte indices.
Findings: Genetically increased HbA1C was associated with the lower heel eBMD (odds ratio [OR] 0.91 [95% CI 0.87, 0.96] per %-unit, P = 3 × 10−4(IVW)). Higher HbA1C was associated with lower heel eBMD when using only erythrocytic variants (OR 0.87 [0.82, 0.93], P=2× 10−5(IVW)); However, when using only glycemic variants, this casual association does not hold. In further MR analysis, we tested the association of erythrocytic traits with heel eBMD.
Interpretation: Our study revealed the significant causal effect of HbA1c on eBMD, and this causal link might achieve through non-glycemic pathways (erythrocytic indices). Through this study, genetic evidence for osteoporosis prevention guidelines based on HbA1c levels can be enhanced; HbA1c could also be a potential reference marker for osteoporosis complications in patients.
Funding Information: This study is supported by research grants from Zhejiang Natural Science Foundation (No. LQ21H060006), Zhejiang Province Medical and Health project (NO.2020391395), the National Natural Science Foundation of China (No.82001461), and the fellowship of China Postdoctoral Science Foundation (No.2020M671758).
Declaration of Interests: The authors declare no competing interests.
Ethics Approval Statement: Public data was used and as such ethical approval was not required.
Keywords: Bone mineral density, HemoglobinA1c, Hemoglobin, Mendelian randomization, Osteoporosis.
Suggested Citation: Suggested Citation