Evaluating the relationship between glycemic control and bone fragility within the UK biobank: Observational and one-sample Mendelian randomization analyses
Notice bibliographique
Résumé
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.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,048 | 0,115 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,001 | 0,002 |
| Bibliométrie | 0,001 | 0,002 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,002 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».