Le déclin des performances cognitives au cours du vieillissement représente une problématique majeure dans le contexte actuel de vieillissement de la population. Le processus de vieillissement cognitif est complexe et multifactoriel. Dans la première partie de nos travaux, nous nous sommes intéressés particulièrement au rôle du diabète de type 2 dans le déclin des fonctions cognitives à partir des données longitudinales de la cohorte Whitehall II. Les performances cognitives ont été évaluées à travers une batterie de tests neuropsychologiques chez des individus âgés de 45 à 70 ans lors du premier passage de tests cognitifs. Nous avons ainsi observé que le diabète de type 2 à l'inclusion dans l'étude était associée à de moins bonnes performances cognitives et à un déclin cognitif plus important au cours du suivi, en particulier chez des patients diabétiques de type 2 de longue date. Nous avons observé une relation entre le mauvais équilibre glycémique et le déclin accéléré des fonctions cognitives. Dans la deuxième partie de ce travail de thèse, nous nous sommes intéresses au rôle potentiellement protecteur des médicaments antidiabétiques sur le déclin cognitif dans le cadre d'une méta-analyse des essais contrôles randomisés. Les résultats de la méta-analyse indiquent que le contrôle glycémique strict n'est pas associé à une diminution du risque de déclin cognitif chez les patients diabétiques de type 2. Nos résultats sont en faveur d'une contribution du diabète de type 2 diagnostiqué en milieu de vie au déclin des fonctions cognitives et participent à une meilleure compréhension de ce processus. / Cognitive decline represents a major issue given the current context of population aging. The cognitive aging process is complex and multifactorial. In first part of our work, we addressed in particular the contribution of type 2 diabetes to cognitive decline, based on longitudinal data from the Whitehall 2 study. Cognitive function was assessed through a battery of neuropsychological tests in participants aged 45 to 70 years old at the beginning of cognitive testing. We observed that baseline type 2 diabetes was associated with lower cognitive performance at baseline and greater decline over follow-up, particularly in patients with longer duration of type 2 diabetes. We observed a relationship between poor glycemic control and faster cognitive decline. In second part of our work, we were interested in the potentially protective role of antidiabetic medications on cognitive decline in a meta-analysis of randomized controlled trials. The meta-analysis indicated that intensive glycemic control was not associated with slower cognitive decline. Our results support the hypothesis of a contribution of type 2 diabetes to cognitive decline in midlife and contribute to improve our understanding of this process.

Master of Public Health - MPH / Sub-Saharan African countries including Rwanda are facing a double burden of communicable and non-communicable diseases (NCDs). As HIV and AIDS management improves, the AIDS related mortality rate is thus reduced, and people living with HIV/AIDS (PLWHA) live longer and have more risk of developing diabetes mellitus. Despite the benefits of screening for T2DM on mortality reduction among PLWHA, this practice is not routinely performed in Rwanda. Therefore, data on the burden of T2DM in PLWHA and associated factors are limited in this country.

OBJECTIVE: The key objective of the present investigation was to compare associations between sagittal abdominal diameter (SAD), waist circumference, and BMI to the oral glucose tolerance test (OGTT), along with fasting glucose, HbA1c, and HOMA-IR, in a nationally representative sample of U.S. adults. The study also analyzed the effect of multiple covariates on the anthropometric and glucose metabolism associations. METHODS: A cross-sectional design, including 3,582 subjects, was used. SAD was assessed using an abdominal caliper. All other data were collected following strict NHANES protocol. The OGTT was the primary variable used to index glucose metabolism. Fasting glucose, HbA1c, and HOMA-IR were also evaluated. RESULTS: Mean ± SE values were as follows: SAD: 22.3 ± 0.1 cm; waist circumference: 98.0 ± 0.4 cm; BMI: 28.6 ± 0.2 kg/m2; OGTT: 113.9 ± 1.0 mg/dL; fasting glucose: 99.6 ± 0.3 mg/dL; HbA1c: 5.4 ± 0.01%; HOMA-IR: 3.2 ± 0.1. SAD consistently emerged as the best predictor of all the indices of glucose metabolism, before and after adjusting for the covariates, and with the sample stratified by gender, race, or age. SAD was not a better predictor of OGTT among normal weight adults and non-Hispanic black adults. CONCLUSION: Obesity, especially abdominal obesity, is strongly related to glucose metabolism and type 2 diabetes. In the present study, SAD was the best anthropometric predictor of glucose metabolism, notwithstanding the high correlations among SAD, waist circumference, and BMI. Due to the ease of taking a SAD measurement, we recommend that healthcare providers consider the use of this simple and inexpensive method to more precisely predict diabetes risk, especially among overweight and obese adults.

Background: Glycation influences the ultrastructure and clot kinetics of fibrin clots due to the post-translational modifications in fibrinogen. Methylglyoxal (MG) is used to measure the level of glycation which has been associated with the pathogenesis of type 2 diabetes Melilites (T2DM) and coronary heart disease (CHD). The aim of the study was to determine the role of MG on clot kinetics and fibrin clot structure in CHD patients with and without T2DM to provide insight into the mechanism of pathogenesis of atherosclerosis in T2DM which results in the development of CHD. Methodology: Scanning electron microscopy (SEM) was used to evaluate the morphology of fibrin clots. Thromboelastography (TEG) was used to assess the physiological clot properties (kinetics). Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of methylglyoxal-adducts. Results: The morphology of clots from controls analysed using SEM showed thick and thin fibres which created an organised mesh of fibrin fibres. In T2DM, CHD with T2DM and CHD some alterations in the morphology were observed. The ultrastructure micrographs in CHD shows that some of the fibrin fibres formed have individual fibres with both thick and thin fibres as well as a thick mass of fibres with a net-like structure that forms dense-matted deposits. In addition, the fibrin fibres are not organised. The densitometry analysis between controls and patient groups’ (CHD: mean (standard deviation) 0.42±0.11; CHD+T2DM: 0.31±0.08 and T2DM: 0.29±0.08) was found to be significantly lower in all groups compared to the control which had a mean of 0.57±0.1, p<0.0001. There are no significant differences in the alpha angle between CHD, T2DM, CHD with T2DM and controls (60.88±2.321˚ vs. 60.81±2.385˚ vs. 59.09± 3.185˚ vs. 66.47±1.300˚, p=0.5279). There was no significant difference found in the K-value between T2DM, CHD with T2DM, CHD and control subjects (3.458±0.446mins vs. 5.118±1.589mins vs. 3.758±0.450mins vs. 2.839±0.2156mins, p=0.0102). The maximum amplitude was higher in T2DM patients compared to CHD, CHD with T2DM and controls (40.51±1.914mm vs. 34.10±2.127mm vs. 33.12±3.365mm vs. 33.60±1.525mm, p=0.0102). The MRTG was higher in CHD compared to T2DM, CHD 4 with T2DM and controls (10.74±3.335 dyn cm-2 s -1 vs. 4.268±0.690 dyn cm-2 s -1 vs. 5.046± 0.927 dyn cm-2 s -1 vs. 6.535±0.664 dyn cm-2 s -1 , p=0.0096). The reaction time was higher in CHD with T2DM patients compared to T2DM, CHD and controls (32.58±4.005min vs. 23.92±2.793min vs. 21.29± 2.383min vs. 8.322±0.886min, p<0.0001). There was no significant difference found in the TTG between T2DM, CHD with T2DM, CHD and control subjects (231.3±28.68 dyn cm-2 vs. 258.5±38.15 dyn cm2 vs. 343.7±71.92 dyn cm-2 vs. 287.7±21.37 dyn cm-2 , p=0.8421). The TMRTG was higher in T2DM patients compared to T2DM, CHD with T2DM, CHD and controls (23.91±2.409mins vs. 20.46±3.411mins vs. 14.14±1.287mins vs. 10.16±0.751mins, p<0.0001). To assess if an association between MG-adducts and clot kinetics exists, the Spearman r correlation was completed for each clot parameter. The reaction time (p=0.0047, 95% CI: 0.138 to 0.665) and time taken before maximum speed of the clot growth to be achieved (p=0.3958, 95% CI: 0.072 to 0.644) was significant. This indicates the relationship between the parameters i.e., the higher the level of MGadducts present, the longer it takes for clotting to begin and reach maximum speed of formation. Conclusion: This study showed that there are ultrastructural differences in fibrin fibres formed in CHD patients with T2DM. The viscoelastic parameters indicated that haemostasis was irregular in CHD and T2DM. The levels of MG-adducts were much higher in T2DM, CHD with T2DM and CHD and may be a contributing factor to the pathogenesis associated with altered coagulation in these patients. / Dissertation (MSc (Physiology))--University of Pretoria, 2020. / NRF / Physiology / MSc (Physiology) / Unrestricted

Philosophiae Doctor - PhD / Type 2 Diabetes Mellitus (T2DM) constitutes the highest percentage of diabetes cases. It has become a serious global problem due to rapid cultural and social changes, ageing, increasing urbanisation, dietary changes, reduced physical activity and unhealthy behavioural lifestyles. Furthermore, unidentified diabetes has been found to be common in many parts of Africa, including rural Nigeria, due to factors such as poor accessibility to health facilities, cultural barriers and high rates of health illiteracy. The overall aim of this study is to determine the effectiveness of the Diabetes Self Management Education (DSME) programme among individuals with T2DM in Jigawa State, Nigeria.

Obesity and type 2 diabetes mellitus (T2DM) are both complex diseases with multifactorial etiologies. Together they affect over 640 million people worldwide and have a significant impact on the global healthcare system incurring costs of over 800 billion dollars. The overall goal of my doctoral research has been to elucidate metabolic predictors and underlying mechanisms in obesity and T2DM. Specifically, I have examined mechanisms contributing to disordered oxidative metabolism in skeletal muscle. My research included participants who were recruited from the Ottawa Hospital Weight Management Clinic in which they completed a clinically supervised meal-replacement and lifestyle intervention program. More so, my doctoral studies evaluated characteristics of muscle mitochondrial function in obesity and T2DM and revealed impaired mitochondrial respiration and electron transport chain supercomplex assembly in muscle from patients with T2DM. The first aim was to study the impact of T2DM on weight loss ability in a large population of obese patients participating in a standardized meal replacement and lifestyle modification program. As there is considerable variability in weight loss propensity, it was found that T2DM significantly deters weight loss although the effect is not large. Since skeletal muscle energetics are central in the development and progression of obesity and T2DM, the second and third aims were to study mitochondrial function in this tissue with the idea of uncovering molecular etiologies. The second aim found deficiencies in mitochondrial respiration in individuals with obesity and T2DM compared to individuals with obesity alone. Reductions in mitochondrial respiration were correlated with increasing levels of HbA1C and attributed to paucity in supercomplex formation in the mitochondrial inner membrane (MIM) of the electron transport chain (ETC). The third aim was to delineate differential fuel oxidation mechanisms and circulating protein biomarkers in obese diet-sensitive (ODS) and obese diet-resistant (ODR) participants following a high fat meal (HFM) challenge. Whole-body analyses were conducted in addition to measures in blood, adipose tissue, skeletal muscle and primary cells. Remarkable increases in oxidative capacity were measured post-HFM. In addition, impaired mitochondrial function was found in the ODR group despite lack of differences in mitochondrial content or the assembly of supercomplexes. Differences were also found in circulating acylcarnitines as well as expression of several proteins including Heat shock 70 kDa protein 1A/1B, Tyrosine-protein kinase Fgr, and Peptidyl-prolyl cis-trans isomerase D. Ultimately, a better understanding of mechanisms involved could lead to significant improvements in personalized medical approaches in obesity and T2DM.

Bakgrund: Diabetes typ 2 är en kronisk sjukdom som kanleda till en rad farliga komplikationer. Diabetes typ 2 är ett globalt hälsoproblem och en långtidssjukdom vilket kan medför allvarliga konsekvenser för individen samt enorma kostnader för samhället. För att personer med diabetes typ 2 ska kunna minska framtida komplikationer, är det viktigt att dessa personer accepterar sjukdomen, lär sig om sjukdomen samt får utbildning om egenvård. I det här sammanhanget blir sjuksköterskans roll ännu mer viktig i att utbilda patienter med diabetes typ 2 om egenvård samt uppmuntra den enskilde i att delta i sin vård och för att främja sin hälsa. Syfte: Syftet med denna litteraturöversikt är att beskriva personers upplevelser av att leva med diabetes typ 2. Metod: En litteraturöversikt har genomförts enligt Friberg och databaserna CINAHL Complete och PubMed användes i sökningen för att hitta vetenskapliga artiklar. Nio vetenskapliga artiklar valdes för att använda i resultatet och identifiera teman.  Resultat: I resultatet identifierades 4 teman;Att känna rädsla och oro för framtiden, Motivationens betydelse för att hantera sin sjukdom, Behovet av stöd från familj-, hälso- och sjukvårdspersonal och Betydelsen av vårdrelationenför egenvård. Slutsats: Socialt stöd (familj, vänner, släkter) och en godvårdrelationmed hälso- och sjukvårdpersonal är viktiga faktorer för personen med diabetes typ 2 för att få motiv delta i vården, främja förmåga att hantera sin sjukdom, utföra egenvård angående diabetes typ 2 och uppleva välbefinnande. / Background: Type 2 diabetes is a chronic disease that may lead to a number of dangerous complications. Type 2 diabetes is a global health problem and a long-term disease, which can have serious consequences for the individual and enormous costs for society. In order for people with type 2 diabetes to be able to reduce future complications, it is important that these people accept the disease, learn about the disease and receive training on self-care. In this context, the role of the nurse becomes even more important in educating patients with type 2 diabetes about self-care and encouraging the individual to participate in their care and to promote their health. Aim: The purpose of this literature review is to describe person's experiences of living with type 2 diabetes. Method: A literature review was conducted according to Friberg and the databases CINAHL Complete and PubMed were used in the search to find scientific articles. Nine scientific articles were selected to be used in the results and to identify themes. Results:The result revealed 4 themes; Feeling fear and anxiety about the future, The importance of Motivation in managing one's illness, The need for support from family, health and medical staff and The importance of the care relationship for self-care. Conclusion: Social support (family, friends, relatives) and a good care relationship with health care professionals are important factors for the person with type 2 diabetes to get motives to participate in care, promote the ability to manage their illness, perform self-care regarding type 2 diabetes and experience well-being.

abstract: This dissertation was guided by the Ecological Model of Physical Activity and Ecological Model of Obesity and sought to determine the relationship between active transportation (AT), physical activity, and cardiometabolic health among adults and ethnic minority women. Chapter 2 presents an investigation into the relationship between walking for AT and cardiometabolic health among adults through systematic review. Chapter 3 presents an exploration of the cross-sectional relationships of AT and moderate-to-vigorous physical activity (MVPA) with cardiometabolic health among African American (AA) and Hispanic/Latina (HL) women from Texas. Chapter 4 presents an investigation into the cross-sectional relationship of AT on cardiometabolic health and physical activity among primarily HL women. In Chapter 2, walking for AT was found to be related to smaller waist circumference, lower blood pressure, and lower prevalence of abdominal obesity and hypertension, and that differences may exist based on sex. Walking for AT was not clearly defined, and criteria used to determine the presence of cardiometabolic outcomes were inconsistent. No significant relationships between AT and cardiometabolic health were found in Chapter 3 or 4; however, AT users had slightly better cardiometabolic health. AT users had significantly higher levels of self-reported total physical activity compared to those who did not use AT in Chapter 3. Furthermore, a significant relationship was found between MVPA and diastolic blood pressure. Associations differed by ethnicity, with MVPA being inversely related to body fat in both AA and HL women, but to body mass index only in AA women. AT users were found to be seven times more likely to meet 2018 national MVPA recommendations than non-AT users in Chapter 4. Across all studies, measures of AT were subjective and of low quality, potentially limiting the ability to detect significant findings. High quality randomized controlled studies should be conducted using clearly defined, objective measures of AT, and analyzed based on sex and race/ethnicity. Clinicians should recommend AT use to promote meeting MVPA recommendations where appropriate, potentially resulting in improved cardiometabolic health. Policymakers should advocate for changes to the built environment to encourage AT use and MVPA to improve public health. / Dissertation/Thesis / Doctoral Dissertation Nursing and Healthcare Innovation 2019

Les Polychlorobiphenyls (PCBs) sont des polluants organiques persistants (POPs). L’exposition humaine à ces composés est associée à un accroissement du risque de développement du diabète de type 2 (DT2). D’autres composés présents dans l’alimentation, comme les hydrocarbures aromatic polycyclic (PAH) tel que le benzo (a) pyrene (BaP), sont des ligands du récepteur aryl-hydrocabures (AhR) et augmentent ce risque. Le premier travail rapporté est une étude in vitro, sur les 3T3-L1, des effets "cocktail" de l’exposition à des PCBs (PCB118 et 153) et au BaP. Sur ce modèle, il apparait que le BaP et les PCBs réduisent en partie l’expression des gènes de l’adipogénèse (ADGG) et stimulent l’expression des gènes de l’inflammation (INFG). La seconde étude réalisée chez la souris, a permis d’évaluer les effets "cocktail" d’une exposition chronique au PCB118 et au BaP. Des paramètres biochimiques et l’expression des ADGG et INFG ont été mesurés dans différents tissus. Après ingestion de BaP, l’expression de deux ADGG (Glut4 and Lipin1) et trois INFG (MCP1, CXCL10, IFNγ) sont augmentés dans le tissue adipeux. Ces effets sont soit abolis, soit réduits en réponse à une co-exposition simultanée avec le PCB118. Ceci indique que les effets de chacun des composés peuvent être masqués l’un par l’autre. Dans les autres tissus, on observe également une modulation globale négative par le PCB des effets du BaP. L’ensemble de ces résultats sont discutés en référence au risque de TD2 induits par les POPs, ainsi qu’aux cibles moléculaires potentielles du BaP comme AhR et des PCBs comme CAR et PXR. On discute du rôle possible de l’IFNγ produit par les cellules immunitaires associées au tissu adipeux / The Polychlorobiphenyls (PCBs) are one of the persistent organic pollutants (POPs). Human exposure to these compounds is associated with an increased risk of developing of type 2 diabetes (DT2). Other chemical compounds, such as polycyclic aromtic hydrocarbon (HAP) such as the benzo (a) pyrene (BaP), that presented in food chain are ligands of the aryl hydrocarbon receptor (AhR) and they increase this risk. The first work reported is an in vitro study on the model of pre-adipocyte, 3T3-L1, on the "cocktail" effects of co-exposure to PCBs (PCB118 and 153) and BaP. On this model, it appears that BaP and PCBs partially reduce the expression of genes related to adipogenesis (ADGG) and stimulate the expression of genes related to inflammation (INFG). The second study was conducted in vivo which allow us to evaluate the "cocktail" effects of a chronic exposure to PCB118 and BaP in mice. Biochemical parameters and the expression of ADGG and INFG were measured in different tissues. After the ingestion of BaP, expression of two ADGGs (Glut4 and Lipin1) and three INFGs (MCP1, CXCL10, IFNγ) were increased in the adipose tissue. These effects are either abolished or reduced in response to simultaneous co-exposure with PCB118. This indicates that the effects of each compounds can be masked by one another. In the other tissues, there is also a global negative modulation by PCB on the effects induced by BaP. All these results are discussed with reference to the risk of DT2 induced by POPs, as well as potential molecular targets of BaP (such as AhR) and PCBs (as CAR and PXR). The possible role of IFNγ, produced by the immune cells, associated with adipose tissue is discussed

IntroductionFreeStyle Libre (FSL) has mostly been used by patients with type 1 diabetes. In 2019, newrecommendations were announced regarding prescriptions to patients with type 2 diabetes(T2D) who have insulin treatment (basal/bolus), HbA1c &gt; 70 mmol/mol and/or repeatedhypoglycemic events despite great effort to adjust insulin doses.AimTo evaluate if HbA1c improves with FSL compared with self-monitoring of blood glucose. Thesecondary aim was to investigate if patients with recurrent hypoglycemic events experiencedless hypoglycemic events.MethodsThis study was designed as a retrospective systematic review of medical records of patientswith T2D in Region Örebro County (RÖC) who have received an FSL 1st of January to 13th ofSeptember 2019. A control group (n = 142) was created from the National Diabetes Register tothe indication group HbA1c &gt; 70 mmol/mol. A paired sample t-test was used to assess theprimary endpoint.ResultsHbA1c decreased significantly from 73 mmol/mol to 65 mmol/mol (p &lt;0.001) in the wholestudy population (n = 58). Indication group HbA1c &gt; 70 mmol/mol (n = 38) had the greatestchange, 80 mmol/mol to 68 mmol/mol (p &lt;0.001). The mean HbA1c in the control group was82 mol/mol. There were 15 patients in the indication group with hypoglycemic events (n = 20)who experienced less hypoglycemic events.ConclusionFSL has a positive effect on the metabolic control in patients with T2D who have HbA1c &gt; 70mmol/mol when starting with FSL in RÖC.