Investigations at the Intersection of Diabetes and Cardiovascular Disease
Notice bibliographique
Résumé
Cardiovascular disease and diabetes are increasingly prevalent and projected only to increase in numbers in the coming years. As such, more individuals will be dealing with multimorbidity which may synergize to increase vascular and glycemic risks. Type 2 diabetes (T2D) is commonly comorbid with lipid and inflammatory disorders like cardiovascular disease and metabolic dysfunction-associated steatotic liver disease (MASLD), whereas type 1 diabetes (T1D) is an autoimmune disease and is frequently comorbid with other inflammatory autoimmune diseases. Dietary and pharmaceutical interventions are employed to manage cardiometabolic diseases or reduce the risk factors for them. However, management options for one disease may impact the development or management of another. For example, the ketogenic diet (KD) is used for diabetes but likely impacts cardiovascular risk through hypercholesterolemia. Similarly, statins, used to manage cardiovascular risk, potentially increase the risk of T2D. In this thesis, I use mouse models and self-reported human data to assess dietary, autoimmune, and pharmaceutical intersections of cardiovascular disease and diabetes. In the first article, we characterized the impacts of a high saturated fat, high cholesterol KD in obese, atherosclerotic, and control mouse models. Across models and sexes, the KD conferred benefit in either liver lipid accumulation or markers of hepatic inflammation. KD feeding also significantly increased glucagon-like peptide-1 (GLP-1), but insulin secretion was unchanged relative to a chow or western-style high fat diet (HFD). In PCSK9 overexpressing, male atherosclerotic mice, the KD lowered hypercholesterolemia and accordingly slowed the progression of atherosclerosis. However, circulating cholesterol was similar among diet groups in mice with intact LDL receptor signalling. In the second article, we identified that 36.3% of individuals on a Canadian registry of T1D live with at least one additional autoimmune disease. Additional autoimmune diseases were associated with greater vascular, glycemic, and mental health complications. In the third article, we investigated the role of overexpressing miR-192, identified as a potential marker of new-onset diabetes after statin use, on insulin secretion, glycemic control, and Glp1r expression. We found that overexpression of miR-192 in islets in vitro increased Glp1r expression and insulin response to GLP-1 at high glucose. In mice, delivery of miR-192 AAV8 only trended toward improved glucose tolerance but significantly increased GLP-1 amplified insulin secretion in islets isolated from the mice. Together, these data advance our understanding of some of the burdens of multimorbidity and the modulation of comorbidity risk with dietary and pharmaceutical management of diabetes and cardiovascular diseases.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».