Abstract
Objectives
Our aim in this study was to identify promising targets for the prevention of type
2 diabetes in addition to weight loss. We conducted a Mendelian randomization (MR)
study to investigate the body mass index (BMI)-independent associations of 16 risk
factors, including diet, lifestyle behaviour and others with type 2 diabetes.
Methods
We selected genetic variants as instrumental variables for diet, sleep traits, smoking,
physical activity, education and blood pressure (BP) from European-descent genome-wide
association studies (GWASs). Summary statistics for type 2 diabetes were derived from
a recent GWAS with 74,124 European cases and 824,006 European controls. The inverse-variance
weighted MR method was used to assess the associations of the risk factors with type
2 diabetes, followed by validation of robustness using different MR methods in sensitivity
analyses.
Results
Genetically predicted insomnia (odds ratio [OR], 1.10; 95% confidence interval [CI],
1.06 to 1.15), smoking initiation (OR, 1.14; 95% CI, 1.06 to 1.21), educational level
(OR, 0.69; 95% CI, 0.65 to 0.74), hypertension (OR, 6.50; 95% CI, 3.13 to 13.50),
systolic BP (OR, 1.02; 95% CI, 1.02 to 1.03) and diastolic BP (OR, 1.03; 95% CI, 1.02
to 1.03) had BMI-independent effects on type 2 diabetes risk. In addition, alcohol
dependence (OR, 1.10 95% CI, 1.05 to 1.16; BMI-adjusted OR, 1.04; 95% CI, 0.98 to
1.09) and vegetarian diet (OR, 0.50; 95% CI, 0.33 to 0.74; BMI-adjusted OR, 0.78;
95% CI, 0.57 to 1.06) appeared to be correlated with type 2 diabetes via a BMI-mediated
pathway. Sensitivity analyses further confirmed the relationship between these factors
and type 2 diabetes.
Conclusions
In this systematic MR study, insomnia, smoking, education and BP had BMI-independent
causal effects on the risk of type 2 diabetes, whereas alcohol dependence and vegetarian
diet were associated with type 2 diabetes through BMI.
Résumé
Objectifs
L’objectif de notre étude était de déterminer les cibles prometteuses dans la prévention
du diabète de type 2, outre la perte de poids. Nous avons mené une étude de randomisation
mendélienne (RM) pour examiner les associations indépendantes de l’indice de masse
corporelle (IMC) de 16 facteurs de risque, à savoir le régime alimentaire, le comportement
lié au mode de vie, etc., au diabète de type 2.
Méthodes
Nous avons sélectionné les variants génétiques tels que les variables instrumentales
du régime alimentaire, des caractéristiques du sommeil, du tabagisme, de l’activité
physique, de la scolarité et de la pression artérielle (PA) issues d’études d’association
pangénomiques (GWAS, de l’anglais genome-wide association studies) qui portaient sur des participants d’ascendance européenne. Les statistiques sommaires
du diabète de type 2 provenaient d’une GWAS récente auprès de 74 124 cas européens
et de 824 006 témoins européens. Nous avons eu recours à la méthode RM pondérée par
l’inverse de la variance pour évaluer les associations des facteurs de risque avec
le diabète de type 2, puis nous avons effectué la validation de la robustesse au moyen
de différentes méthodes RM dans les analyses de sensibilité.
Résultats
L’insomnie génétiquement prévisible (rapport de cotes [RC], 1,10; intervalle de confiance
[CI] à 95 %, de 1,06 à 1,15), le début du tabagisme (RC, 1,14; IC à 95 %, de 1,06
à 1,21), le niveau de scolarité (RC, 0,69; IC à 95 %, de 0,65 à 0,74), l’hypertension
(RC, 6,50; IC à 95 %, de 3,13 à 13,50), la PA systolique (RC, 1,02; IC à 95 %, de
1,02 à 1,03) et la PA diastolique (RC, 1,03; IC à 95 %, de 1,02 à 1,03) ont montré
des effets indépendants de l’IMC sur le risque de diabète de type 2. De plus, la dépendance
à l’alcool (RC, 1,10; IC à 95 %, de 1,05 à 1,16; RC ajusté à l’IMC, 1,04; IC à 95
%, de 0,98 à 1,09) et le régime végétarien (RC, 0,50; IC à 95 %, de 0,33 à 0,74; RC
ajusté à l’IMC, 0,78; IC à 95 %, de 0,57 à 1,06) semblaient être en corrélation avec
le diabète de type 2 par l’intermédiaire des effets médiateurs de l’IMC. Les analyses
de sensibilité ont par ailleurs confirmé la relation entre ces facteurs et le diabète
de type 2.
Conclusions
Dans cette étude systématique RM, l’insomnie, le tabagisme, la scolarité et la PA
ont montré des effets causaux indépendants de l’IMC sur le risque de diabète de type
2, alors que la dépendance à l’alcool et le régime végétarien ont été associés au
diabète de type 2 par l’intermédiaire de l’IMC.
Keywords
Mots clés
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Article Info
Publication History
Published online: June 03, 2022
Accepted:
June 1,
2022
Received in revised form:
March 10,
2022
Received:
October 2,
2021
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Canadian Diabetes Association.
