Evaluating the relationship between glycemic control and bone fragility within the UK biobank: Observational and one-sample Mendelian randomization analyses
Bibliographic record
Abstract
Abstract Aims/hypothesis This study aimed to: (1) examine the relationship between glycemic control, bone mineral density estimated from heel ultrasound (eBMD) and fracture risk in individuals with type 1 and type 2 diabetes and (2) perform a one-sample Mendelian randomization study to explore potential linear and non-linear associations between glycemic control, eBMD, and fractures. Methods This study comprised 452,131 individuals from the UK Biobank with glycated hemoglobin A1C (HbA1c) and eBMD levels. At baseline, 4,078 participants were diagnosed with type 1 diabetes and 23,682 with type 2 diabetes. HbA1c was used to classify patients into “adequately-” (ACD; n=17,078; HbA1c < 7.0%/53mmol/mol) and “inadequately-” (ICD; n=10,682; HbA1c ≥ 7.0%/53mmol/mol) controlled diabetes. The association between glycemic control (continuous and categorical) and eBMD was tested using linear regression, while fracture risk was estimated in Cox regression models, both controlling for covariates. Mendelian randomization (MR) was used to evaluate linear and non-linear causal relationships between HbA1c levels, fracture risk, and eBMD. Results In individuals with type 1 diabetes, a 1% unit (11mmol/mol) increase in HbA1c levels was associated with a 12% increase in fracture risk (HR: 1.12, 95% CI [1.05-1.19]). Individuals with type 1 diabetes had lower eBMD in both the ICD (beta = −0.08, 95% CI [−0.11, −0.04]) and ACD (beta = −0.05, 95% CI [-0.11,0.01]) groups, as compared to subjects without diabetes. Fracture risk was highest in individuals with type 1 diabetes and ICD (HR 2.84, 95%CI [2.53, 3.19]), followed by those with ACD (HR 2.26, 95%CI [1.91, 2.69]). Individuals with type 2 diabetes had higher eBMD in both ICD (beta=0.12SD, 95%CI [0.10, 0.14]) and ACD (beta=0.07SD, 95%CI [0.05, 0.08]) groups. Significant evidence for a non-linear association between HbA1c and fracture risk was observed (F-test ANOVA p-value = 0.002) in individuals with type 2 diabetes, with risk being increased at both low and high levels of HbA1c. Fracture risk between the type 2 diabetes ACD and ICD groups was not significantly different (HR: 0.97, 95%CI [0.91-1.16]), despite increased BMD. In MR analyses genetically predicted higher HbA1c levels were not significantly associated with fracture risk (Causal Risk Ratio: 1.04, 95%CI [0.95-1.14]). However, disease stratified analyses were underpowered. We did observe evidence of a non-linear causal association with eBMD (quadratic test P-value = 0.0002), indicating U-shaped relationship between HbA1c and eBMD. Conclusion/interpretation We obtained evidence that lower HbA1c levels will reduce fracture risk in patients with type 1 diabetes. In individuals with type 2 diabetes, lowering HbA1c levels can mitigate the risk of fractures up to a threshold, beyond which the risk may begin to rise once more. MR analyses demonstrated a causal relationship between genetically predicted HbA1c levels and eBMD, but not fracture risk.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.048 | 0.115 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".