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Background: Gestational diabetes mellitus (GDM) is a common pregnancy-related metabolic disorder associated with adverse maternal and fetal outcomes. Recent research has highlighted the potential role of the oral microbiome in the pathophysiology of various systemic conditions, including diabetes mellitus. However, the impact of GDM on the maternal oral microbiome remains relatively understudied. Understanding alterations in the oral microbiome during pregnancy complicated by GDM could provide valuable insights into the mechanistic links between systemic metabolic disorders and oral health. Objective: The objective of this scoping review was to comprehensively examine the existing literature on the relationship between GDM and maternal oral microbiome composition and diversity. The review sought to identify the microbial changes associated with GDM and explore their potential implications for maternal oral health and pregnancy outcomes. Design: Following PRISMA-ScR guidelines, a systematic search of electronic databases, including “Pubmed” and “Web of Science,” was conducted to identify relevant studies investigating the impact of GDM on the maternal oral microbiome. Eligible studies included those examining microbial diversity, abundance, and composition in pregnant women with GDM and their neonates. Data synthesis involved summarizing key findings and identifying patterns across studies. Results: A total of eight primary studies were identified and included in the scoping review. These studies employed various methodologies, including observational reports, longitudinal analyses, and cohort studies, to investigate the relationship between GDM and the maternal oral microbiome. Findings from these studies revealed distinct alterations in oral microbial profiles among neonates and pregnant women with GDM compared to healthy controls. These alterations encompassed shifts in microbial diversity, abundance, and composition, suggesting potential biomarkers or indicators of GDM status within the oral microbiome. Longitudinal analyses further elucidated dynamic changes in the oral microbiota throughout pregnancy and postpartum, underscoring the temporal nature of these associations. Conclusions: The synthesis of evidence from the scoping review highlights significant associations between GDM and alterations in the maternal oral microbiome. While these findings imply a correlation between GDM and oral microbial changes, causality cannot be directly inferred. Further research is warranted to decipher the underlying mechanisms driving these associations and to explore their potential implications for maternal oral health and pregnancy outcomes. Nonetheless, the insights gleaned from this review underscore the importance of integrating oral health assessments into routine prenatal care protocols for gestational diabetic individuals. By doing so, healthcare providers can enhance risk stratification, early detection, and management of GDM, ultimately improving maternal and neonatal health outcomes.

L'objectif de cette étude était de mieux comprendre les relations entre les infections parasitaires, les réponses au stress physiologique et la condition corporelle des poissons. Nous avons pêché des crapets-soleil (Lepomis gibbosus) infectés naturellement par des douves et ténias (Apophallus sp., Uvulifer sp. et Proteocephalus ambloplitis) du lac Cromwell dans la région laurentienne du Québec et nous les avons soumis à différents traitements de stress aigu en laboratoire. Les niveaux de cortisol dans le plasma ont été mesurés à l’aide de la radio-immunoanalyse (RIA) et l’indice de condition de Fulton K ont été calculés pour chaque individu. Les individus avec une densité plus élevée d’Apophallus sp. et Uvulifer sp. présentaient une meilleure condition corporelle, tandis que ceux qui étaient plus fortement infectés par P.ambloplitis en avaient une plus pauvre. Les réponses au cortisol à la suite d’un stress aigu différaient d’un traitement à l’autre : les poissons ayant reçu le traitement d’un stress aigu unique présentaient des réponses au cortisol plasmatique significativement plus élevées, alors que tous les autres traitements montraient des niveaux de cortisol plus faibles. Cependant, ces différences de taux de cortisol n’étaient pas significativement liées à la densité parasitaire ou à la condition corporelle. Ces résultats suggèrent que, bien que la charge parasitaire influence la condition corporelle, elle ne semble pas affecter les réponses de cortisol causées par le stress. L’absence de relations significatives pourrait être liée à la présence réduite de certains phénotypes dans l’échantillon, ce qui pourrait révéler des tendances écologiques notables sur le cycle de vie des parasites. / The objective of this study was to better understand the relationships among parasite infection, physiological stress responses and the body condition of fish. We collected pumpkinseed sunfish (Lepomis gibbosus) naturally infected with helminthic flukes and tapeworms (Apophallus sp., Uvulifer sp., and Proteocephalus ambloplitis) from Lake Cromwell in the Quebec Laurentian region and subjected them to different stress treatments in the laboratory. Plasma cortisol levels were measured using radioimmunoassay (RIA), and Fulton's condition index K was calculated for each individual. Individuals with higher densities of Apophallus sp. and Uvulifer sp. had better body condition, while those more heavily infected with P. ambloplitis were in poorer condition. Cortisol responses following acute stress differed across treatments: fish that received the single acute stress treatment showed significantly higher plasma cortisol responses, whereas all other treatments showed lower cortisol levels. However, these differences in cortisol were not significantly related to parasite density or body condition. These results suggest that while parasite load influences body condition, it does not appear to directly affect stress-induced cortisol responses. The lack of significant relationships might be linked to the reduced presence of certain phenotypes in the sample, which may reveal important ecological trends on the parasite life cycle.

Objectifs : La majorité des professionnels de la santé (PS) peuvent ne pas rencontrer régulièrement des personnes vivant avec un diabète de type 1 (PVDT1) dans leur pratique, ce qui rend difficile le maintien de leur connaissance des particularités de la condition et leur mise à jour sur les technologies et thérapies en évolution rapide. Les ressources en ligne peuvent aider à atténuer ce problème. La plateforme d'autoformation en ligne Support-Pro couvre les besoins en thérapie et mode de vie du DT1 à travers des modules courts et pratiques. L'objectif de l'étude est d'évaluer le changement du niveau de confiance des PS dans le traitement des PVDT1 et leur satisfaction après avoir utilisé la plateforme. Méthodologie : Essai ouvert, non randomisé, prospectif sur 12 mois avec 144 PS (nutritionnistes, infirmières, pharmaciens, médecins). Après avoir rempli le questionnaire initial en ligne, les participants ont eu accès à Support-Pro. Leur confiance dans le traitement des PVDT1, mesurée avec une échelle de 19 items, a été évaluée au départ, à 3 mois (n=69) et à 12 mois (n=40). La satisfaction a été évaluée à 3 mois. Résultats : Le score moyen de confiance des participants [intervalle de confiance à 95 %] est passé de 53 [51, 56] (n=142) à l’inclusion à 65 [61, 69] (n=69) (/95) après 3 mois. Cette augmentation de confiance a augmenté après 12 mois à 72 [67,77] (n=40). Le score médian de satisfaction [écart interquartile] après 3 mois était de 44/49 [38; 48]. Conclusion : Après avoir utilisé la plateforme, les PS ont signalé une augmentation de la confiance dans le traitement des PVDT1 et des niveaux élevés de satisfaction. Cette plateforme pourrait améliorer la prise en charge des PVDT1 suivis en dehors des cliniques spécialisées. Numéro d'enregistrement de l'essai : NCT04859205 / Aims: The majority of healthcare professionals (HCPs) may not encounter people living with type 1 diabetes (PWT1D) regularly in their practices, making it difficult for them to remain aware of the particularities of the condition and stay up to date on the rapidly evolving technologies and therapies. Online resources can help alleviate this problem. The Support-Pro self-guided online training platform covers T1D therapy and lifestyle needs in short, practical modules. The objective of the study is to evaluate HCPs' change in confidence level in treating PWT1D and their satisfaction after using the platform. Methodology: Open-label, non-randomized, prospective 12-month trial with 144 HCPs (dietitians, nurses, pharmacists, physicians). After completing the online baseline questionnaire, participants had access to Support-Pro. Confidence in treating PWT1D, using a 19-item scale, was assessed at baseline, 3 months (n=69), and 12 months (n=40). Satisfaction was assessed at 3 months. Results: The participants' mean [95% confidence interval] confidence score increased from baseline 53 [51, 56] (n=144) to 65 [61, 69] (n=69) (p<0.001) (/95) after 3 months. This confidence increased further after 12 months to 72 [67,77] (n=40). Their median [interquartile] satisfaction score after 3 months was 44/49 [38;48]. Conclusion: After using the platform, HCPs reported increased confidence in treating PWT1D and high satisfaction levels. This platform could improve the management of PWT1D followed outside of specialty clinics. Trial Registration Number: NCT04859205

The worldwide increasing number of persons affected by largely preventable diseases like diabetes demands better prevention and treatment. Insulin is required for effective utilisation of circulating nutrients. Impaired responsiveness to insulin (insulin resistance, IR) is a hallmark of type 2 diabetes and independently raises the risk of heart attack and stroke. The pathophysiology of IR is incompletely understood. High-throughput measurement of large numbers of circulating biomarkers may provide new insights beyond established risk factors. The aims of this thesis were to (i) use proteomics, metabolomics and genomics methods in large community samples to identify biomarkers of IR; (ii) assess biomarkers for risk prediction and insights into aetiology and consequences of IR; and (iii) use Mendelian randomisation analysis to assess causality. In Study I, analysis of 80 circulating proteins in 70-to-77-year-old Swedes identified cathepsin D as a biomarker for IR and highlighted a tentative causal effect of IR on raised plasma tissue plasminogen activator levels. In Study II, nontargeted fasting plasma metabolomics was used to discover 52 metabolites associated with glycaemic traits in non-diabetic 70-year-old men. Replication in independent samples of several thousand persons provided evidence for a causal effect of IR on reduced plasma oleic acid and palmitoleic acid levels. In Study III, nontargeted metabolomics in plasma samples obtained at three time points during an oral glucose challenge in 70-year-old men identified associations between a physiologic measure of IR and concentration changes in medium-chain acylcarnitines, monounsaturated fatty acids, bile acids and lysophosphatidylethanolamines. Study IV provided evidence in two large longitudinal cohorts for causal effects of type 2 diabetes and impaired insulin secretion on raised coronary artery disease risk. In conclusion, the Studies in this thesis provide new insights into the pathophysiology and adverse health consequences of IR and illustrate the value of combining traditional epidemiologic designs with recent molecular techniques and bioinformatics methods. The results provide limited evidence for the role of circulating proteins and small molecules in IR and require replication in separate studies and validation in experimental designs.

Pharmacometric modelling is widely used in many aspects related to type 2 diabetes mellitus (T2DM), for instance in the anti-diabetes drug development, and in quantifying the disease progression of T2DM. The aim of this thesis were to improve the design of early phase anti-diabetes drug development studies with the focus on the power to identify mechanism of drug action (MoA), and to characterize and quantify the progression from prediabetes to overt diabetes, both the natural progression and the progression with diet and exercise interventions, using pharmacometrics modelling. The appropriateness of a study design depends on the MoAs of the anti-hyperglycaemic drug. Depending on if the focus is power to identify drug effect or accuracy and precision of drug effect, the best design will be different. Using insulin measurements on top of glucose has increase the power to identify a correct drug effect, distinguish a correct MoA from the incorrect, and to identify a secondary MoA in most cases. The accuracy and precision of drug parameter estimates, however, was not affected by insulin. A natural diabetes disease progression model was successfully added in a previously developed model to describe parameter changes of glucose and insulin regulation among impaired glucose tolerance (IGT) subjects, with the quantification of the lifestyle intervention. In this model, the assessment of multiple short-term provocations was combined to predict the long-term disease progression, and offers apart from the assessment of the onset of T2DM also the framework for how to perform similar analysis. Another previously published model was further developed to characterize the weight change in driving the changes in glucose homeostasis in subjects with IGT. This model includes the complex relationship between dropout from study and weight and glucose changes. This thesis has provided a first written guidance in designing a study for pharmacometrics analysis when characterizing drug effects, for early phase anti-diabetes drug development. The characterisation of the progression from prediabetes to overt diabetes using pharmacometrics modelling was successfully performed. Both the natural progression and the progression with diet and exercise interventions were quantified in this thesis.

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