Insulin resistance, a key risk factor for type 2 diabetes, can be defined as when cells fail to respond effectively to insulin. In striated muscle and fat, this manifests as impaired insulin-stimulated glucose uptake due to reduced plasma membrane insertion of the glucose transporter GLUT4. In cell culture models, insulin resistance induced by chronic exposure to insulin, endothelin-1 or glucosamine, is correlated with reduced immunoreactivity of the lipid phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in plasma membrane sheets. However, the reason for this decrease, and whether other factors that induce insulin resistance affect PtdIns(4,5)P2 levels, is unknown. Using L6 skeletal muscle myotubes and 3T3-L1 adipocytes, this project has investigated whether PtdIns(4,5)P2 levels are perturbed in insulin resistance induced by several factors, including exposure to insulin, oxidative stress, and treatment with tumour necrosis factor α, endothelin-1 or angiotensin II (Ang II).All these pre-treatments were found to abolish insulin-stimulated 3H 2-deoxy-glucose uptake, and significantly decrease PtdIns(4,5)P2 levels, measured in cell extracts by quantitative blotting using a PtdIns(4,5)P2-specific probe, developed from the PH domain of phospholipase C (PLC) δ. Importantly the ability of insulin to stimulate glucose uptake can be restored by replenishing PtdIns(4,5)P2 in L6 myotubes treated with insulin and Ang II. PtdIns(4,5)P2 levels are regulated by three families of proteins; PIP kinases, which synthesise it, phosphatases, which remove phosphate groups from the inositol headgroup, and PLCs, which hydrolyse it. Membrane preparations from Ang II- and insulin-induced insulin resistant L6 myotubes showed no differences in PtdIns(4,5)P2 production or dephosphorylation. However a significant increase in PLC activity was detected in membranes from insulin resistant cells and membrane localisation of PLCβ family members was increased in insulin resistant cells. Furthermore, studies using PLC inhibitors show a restoration of PtdIns(4,5)P2 levels in insulin resistant cells, leading to partial reversal of insulin resistance.This study therefore shows a causal link between decreased PtdIns(4,5)P2 levels and insulin resistance in L6 myotubes, and that PLCs are the reason for the PtdIns(4,5)P2 decrease in Ang II- and insulin-induced insulin resistance. PLCs, or their activation pathways, may thus be a novel target for combating insulin resistance, and preventing type 2 diabetes.

O objetivo do presente estudo foi avaliar o papel do treinamento físico aeróbio, resistido ou combinado (aeróbio+resistido) no desenvolvimento do diabetes tipo 2 analisando mecanismos associados às complicações no diabetes em camundongos fêmeas com deficiência na produção leptina (ob/ob). Para tanto, foram utilizadas camundongos fêmeas, inicialmente com 4 semanas de idade, divididas em 6 grupos: ob/ob sedentárias com 4 semanas de vida (OS-4), selvagens sedentárias (SS) ou ob/ob sedentárias (OS-12) acompanhadas até a 12ª semana de vida, ob/ob treinamento aeróbio (OA), ob/ob treinamento resistido (OR) e ob/ob treinamento combinado (OC). Os grupos treinados foram submetidos a 8 semanas de treinamento físico dinâmico aeróbio em esteira (50 a 60% da velocidade máxima do teste de esforço) ou resistido em escada (4060% da carga máxima) ou a associação dos dois treinos (combinado). Foram avaliados: peso corporal; glicose, triglicérides e colesterol total sanguíneos; pressão arterial (PA) e frequência cardíaca (FC); sensibilidade barorreflexa (SBR); modulação autonômica cardiovascular; marcadores inflamatórios e hormonais; e parâmetros de estresse oxidativo. Os animais obesos (OS-12) apresentaram aumento de peso corporal, tecido adiposo, de glicemia, de triglicérides e de intolerância à glicose quando comparado aos animais selvagens (SS). Adicionalmente, o grupo OS-12 apresentou piores resultados nos testes aeróbio e de força. Não observamos diferenças entre os grupos SS e OS-12 em relação a PA e FC, porém o grupo OS-12 apresentou diminuição da variabilidade da frequência cardíaca (VFC) (33 ± 4ms2) e da sensibilidade barorreflexa em relação ao grupo SS (VFC: 178 ± 19 ms2). O grupo OS-12 apresentou aumento de angiotensina 2 nos tecidos renal e cardíaco, diminuição da adiponectina e aumento de citocinas inflamatórias no tecido adiposo e no baço em relação ao grupo SS. Somado a isso, os animais obesos apresentam maior dano a proteínas e lipoperoxidação e diminuição das enzimas antioxidantes em tecido renal e cardíaco em relação ao grupo SS. A comparação entre os grupos OS-4 e OS-12 evidenciou aumento de peso corporal, tecido adiposo, glicemia, intolerância à glicose e de parâmetros de estresse oxidativo no grupo OS-12 em relação ao grupo OS-4. A redução na VFC e na SBR foi observada no grupo OS-4 e no grupo OS-12. O treinamento físico por sua vez, diminuiu o ganho de peso e reduziu a glicemia e a intolerância à glicose nos três grupos treinados em comparação ao grupo OS-12. O treinamento físico aeróbio (61 ± 8ms2 e 6 ± 4 mmHg2) e resistido (66 ± 16ms2 e 6 ± 1,4mmHg2) foram eficientes em aumentar a VFC e diminuir a banda de baixa frequência da PA (simpático vascular) em relação ao grupo OS-12, porém o grupo OC (43 ± 7ms2 e 8 ± 0,9mmHg2) foi semelhante ao grupo OS-12 (10 ± 1,1mmHg2) e aos grupos OA e OR. Além disso, as três modalidades melhoraram a SBR. Os três tipos de treinamento reduziram os níveis de angiotensina 2 e aumentaram os níveis de angiotensina 1-7 em tecido adiposo, rim e coração. O treinamento físico aeróbio foi mais eficiente em melhorar o perfil inflamatório em tecido adiposo e no baço, uma vez que os grupos OA e OC apresentaram aumento de adiponectina e apenas o grupo OC apresentou diminuição de IL-6 e PAI-1 em relação ao grupo OS-12. Em relação ao estresse oxidativo, os três grupos treinados apresentaram diminuição de marcadores de lesão. Concluindo, nossos achados confirmam o desenvolvimento de disfunção metabólica ao longo da vida de camundongos ob/ob. É interessante notar que com 4 semanas de vida camundongos ob/ob apresentaram uma expressiva redução dos parâmetros da VFC. Este desbalanço autonômico, poderiam estar ocorrendo não só no coração, mas para outros tecidos, como o baço e o tecido adiposo, favorecendo a liberação de citocinas inflamatórias que poderiam induzir a longo prazo lesão de órgão alvo, como observado no presente estudo em coração e rins, por aumento de estresse oxidativo. Os grupos treinados, independente da modalidade, apresentaram melhora metabólica e na regulação autonômica cardiovascular, a qual foi acompanhada de alterações favoráveis no sistema renina-angiotensina, em mediadores inflamatórios e no perfil de estresse oxidativo. Neste sentido, acreditamos que a atenuação da disfunção autonômica (precocemente observada neste modelo de DM) pelo treinamento físico, independente do tipo, possa induzir alterações favoráveis (e dependentes do tipo de treino) no sistema renina angiotensina e em mediadores inflamatórios, reduzindo o estresse oxidativo em tecidos importantes para a regulação cardiovascular / The aim of this study was to evaluate the role of aerobic, resistance or combined (aerobic + resistance) exercise training in the development of type 2 diabetes, analyzing mechanisms associated with diabetes complications in female mice with deficiency in leptin production (ob/ob). Female mice, initially with 4 weeks of age, were divided into 6 groups: ob/ob sedentary with 4 weeks of life (OS-4), sedentary wild type (SS) or ob/ob sedentary (OS-12) followed until 12 week life, ob/ob+aerobic training (OA), ob/ob+resistance training (OR) and ob/ob+combined training (OC). The trained groups were submitted to eight weeks of dynamic aerobic exercise training on a treadmill (50-60% of maximum stress test speed) or resistance exercise on a ladder (40-60% of the maximum load) or an association of these two trainings (combined). Body weight; glucose, triglycerides, and total blood cholesterol; blood pressure (BP) and heart rate (HR); baroreflex sensitivity (BRS); cardiovascular autonomic modulation; inflammatory and hormonal markers; and oxidative stress parameters were evaluated. Obese animals (OS-12) showed increased body and fat weight, blood glucose, triglyceride and glucose intolerance when compared to wild type animals (SS). Additionally, OS-12 group showed decreased capacity in aerobic and strength exercise tests. We did not observe differences between the SS and the OS-12 groups regarding BP and HR, however the OS-12 group showed reduced heart rate variability (HRV) (33 ± 4ms2) and baroreflex sensitivity when compared to the SS group (178 ± 19 ms2). The OS-12 group showed increased angiotensin 2 in kidney and heart tissues, decreased adiponectin and increased inflammatory cytokines in adipose tissue and in the spleen in relation to the SS group. Moreover, obese animals presented increased protein oxidation and lipid peroxidation and decreased antioxidant enzymes in kidney and heart tissues when compared to SS group. The comparison between the OS-4 and the OS-12 groups showed increased body and fat weight, blood glucose, glucose intolerance and oxidative stress in OS-12 compared to OS-4 group. The decrease in HRV and in BRS were observed in OS-4 and OS-12 groups. On the other hand, exercise training decreased weight gain and reduced blood glucose and glucose intolerance in all three trained groups compared to OS-12 group. Aerobic (61 ± 8ms2 and 6 ± 4 mmHg2) and resistance exercise training (66 ± 16ms2 and 6 ± 1.4mmHg2) were efficient in increasing the HRV and decrease the low frequency band of BP (vascular sympathetic modulation) as compared to OS-12 group; however OC group (43 ± 7ms2 and 8 ± 0.9mmHg2) was similar to OS-12 group (10±1.1mmHg2) and to OA and OR groups. In addition, the three types of exercsie training improved BRS. The three types of training reduced levels of angiotensin 2 and increased levels of angiotensin 1-7 in adipose tissue, kidney and heart. The aerobic exercise was more efficient in improving inflammatory profile in adipose tissue and spleen, since OA and OC groups showed an increase in adiponectin and only the OC group showed a decrease in IL-6 and PAI-1 in relation to the group OS-12. Regarding oxidative stress, the three trained groups showed a decrease in damage markers. In conclusion, our findings support the development of metabolic dysfunction during lifespan in ob/ob mice. Interestingly, 4 weeks old ob/ob mice showed a significant reduction in HRV parameters. This autonomic imbalance could be occurring not only in the heart, but in other tissues, such as the spleen and the adipose tissue, promoting the release of inflammatory cytokines. These cytokines could induce long-term target organ damage, as observed in this study in heart and kidney by increased oxidative stress. The trained groups, regardless of the type of training, showed improved metabolic and cardiovascular autonomic regulation, which were accompanied by favorable changes in the renin-angiotensin system, inflammatory mediators and oxidative stress profile. In this sense, we believe that the attenuation of autonomic dysfunction (early observed in this model of DM) by exercise training, regardless of the type of training, can induce positive changes (dependent on the type of exercise training) on the renin angiotensin system and inflammatory mediators, reducing oxidative stress in important tissues for cardiovascular regulation

Bakgrund: Typ 2-diabetes är en vanlig förekommande sjukdom hos befolkning i Sverige som kan påverkas av olika faktorer såsom stress, fysisk inaktivitet och kost. Egenvård vid typ 2-diabetes är en viktig del av behandling. Därför ska patientens upplevelse av egenvård studeras för att skapa en omsorgsfull relation med patienten och för att kunna stödja de att klara sitt omvårdnadsbehov på egen hand. Syfte: Författarna vill i denna litteraturstudie beskriva patientens erfarenhet av egenvård vid typ 2-diabetes. Metod: Studien har utförts som en kvalitativ litteraturstudie. Tio vetenskapliga artiklar inkluderades. Artiklarna söktes via databaserna CHINAL och Pub Med. Artiklar med kvalitativ ansats var inkluderades. Resultatet bearbetades, analyserades och sammanställdes. Resultat: Resultaten i studien visar på att patientens med typ 2-diabetes har olika upplevelser som påverkas av olika faktorer och dessa har kategoriserats i tabellen med fyra kategorier och nio underkategorier: 1) Undervisning: Gruppundervisning, 2) Attityd. Kunskap: Teoretisk och praktisk kunskap, 3) Barriärer: Glykemisk kontroll, omgivningen, Brist på motivation, 4) Kännedom: Kost, fysisk aktivitet Konklusion: patienten med typ 2-diabetes behöver insatser och stöd i form av undervisning, information, familjens och vännernas stöd för att kunna hantera sin diabetes. Kunskapsbrist om typ 2-diabetes i personers omgivning påverkar patientens egenvård. Information av dessa kunskapsbrister är ett verktyg som underlättar sjuksköterskans arbete. / Background: The number for people with Type 2-diabetes disease is increasing in Sweden and the disease is affected by various factors such as stress, physical inactivity and diet. Self-care at Type 2-diabetes is an important part of treatment. We therefore seek to study patient experience of self-care to create a careful relationship with the patient and to support them to cope with their nursing needs on their own. Purpose: The authors want to describe in this literature review the patient's self-care experience in type 2 diabetes. Method: The study has been conducted as qualitative literature review. Ten scientific articles were included. The articles were searched through the CHINAL and Pub Med databases. The study included only qualitative articles. The result was processed, analyzed and compiled. Results: The results in the study show that the patient with Type 2-diabetes has different experiences that are influenced by different factors and these have been categorized in the table with four main themes and nine subthemes: 1) Teaching: Group teaching, 2) Attitude. Knowledge: Theoretical Practical, 3) Barriers: Glycemic Control, Environment, Lack of Motivation, 4) Knowledge: Diet, Physical Activity. Conclusion: The patient with Type 2-diabetes needs assistance and support in the form of education, information, family and friends support to manage their diabetes. A lack of knowledge about Type 2-diabetes in people's surroundings affects patient rehabilitation. Information of these knowledge shortages is a tool that facilitates the nurse's work.

La prévalence du diabète de type 2 ne cesse d’augmenter et la tranche d’âge des plus de 65 ans subit la hausse la plus importante. Des différences liées au genre ont été rapportées entre les hommes et les femmes diabétiques de type 2, notamment en ce qui concerne les complications macrovasculaires du diabète mais il n’y a pas, à notre connaissance, d’étude française qui s’est spécialement intéressée à cette question. La majorité des études internationales ne se sont pas intéressées aux sujets âgés mais à toute la population diabétique et beaucoup d’entre elles sont anciennes, datant d’avant l’introduction des nouveaux traitements cardiovasculaires avec un fort niveau de preuve.Ce travail avait comme objectif d’évaluer l’existence de différences liées au genre dans la prise en charge du diabète de type 2 au sein d’une population contemporaine de sujets âgés pris en charge en conditions de vie réelle en soins primaires. Les objectifs spécifiques étaient de comparer l’équilibre du diabète et le contrôle des facteurs de risque cardiovasculaire et la survenue d’événements cliniques majeurs (décès ou événement cardiovasculaire majeur, hospitalisation) entre les hommes et les femmes, et d’évaluer le rôle du genre du médecin traitant dans ces différences potentielles.La cohorte S. AGES diabète de type 2 est une étude observationnelle prospective de sujets âgés de 65 ans ou plus, non institutionnalisés, ayant un diabète de type 2. Au total 983 patients ont été inclus entre avril 2009 et juin 2011 par 213 médecins. L’évolution clinique et la survenue d’événements majeurs ont été renseignées pendant 3 ans. Des modèles mixtes ont été utilisés dans les analyses statistiques en raison de la corrélation entre les mesures répétées du même patient et la corrélation entre les patients du même médecin.Pendant toute la période du suivi, l’équilibre du diabète de type 2, estimé par l’hémoglobine glyquée HbA1c, n’était pas différent entre les hommes et les femmes, le contrôle de la pression artérielle était meilleur chez les hommes que chez les femmes en analyse bivariée mais pas en analyse multivariée. Par contre, le contrôle du cholestérol LDL était meilleur chez les hommes que chez les femmes avec un risque relatif pour les femmes par rapport aux hommes d’avoir un LDL non contrôlé (>1 g/l) de 2,56 (IC à 95 % 1,82-3,59 ; p<0,001). Cette différence était présente dans le groupe traité par statines ainsi que dans le groupe non traité.En ce qui concerne la survenue d’événements cliniques majeurs, les femmes avaient un risque plus faible de développer un événement clinique majeur (décès toutes causes confondues, événement cardiovasculaire majeur) par rapport aux hommes avec un risque relatif de 0,60 (IC à 95 % 0,40-0,91 ; p= 0.016) ou d’être hospitalisées avec un risque relatif de 0,71 (IC à 95 % 0,52-0,96, p=0,029). La majorité des hospitalisations était liée aux pathologies concomitantes autres que le diabète, surtout chez les hommes qui étaient davantage admis en CHU/CHR que les femmes. Le risque de développer des complications microvasculaires du diabète n’est pas différent entre les hommes et les femmes.Enfin, nos analyses n’ont pas montré de différence entre les médecins hommes et les médecins femmes au niveau du contrôle des facteurs de risque cardiovasculaire, de la réalisation d’examens de surveillance, de dépistage des complications, ni de prescription de traitements antidiabétiques et cardiovasculaires.Nos résultats montrent que les différences liées au genre dans cette population de patients diabétiques âgés sont réservées à un cholestérol LDL plus élevé chez les femmes que chez les hommes, mais qui ne s’accompagne pas d’une augmentation du risque de survenue d’événements cliniques majeurs (qui reste plus élevé chez les hommes). Cependant il faut interpréter ces résultats dans le contexte de la cohorte S.AGES avec des biais de sélection au niveau médecin et au niveau patient ainsi qu’une sous-représentation des médecins femmes. / The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide and this trend is projected to persist because of the demographic shift and the obesity pandemic. The elderly represent more than half of subjects with T2DM and this proportion is expected to increase in the future. Cardiovascular disease is the main cause of morbidity and mortality in elderly subjects with T2DM. Moreover, although non-diabetic women have lower risk of developing cardiovascular diseases compared to non-diabetic men of the same age, this “female advantage” seems to diminish or disappear in the setting of T2DM. Indeed, compiled data suggest that type 2 diabetes affects the risk of cardiovascular disease differentially according to gender. To the best of our knowledge, there is no French study that had looked at this issue. The majority of international studies have not focused on the elderly group but on the whole diabetic population and many of them are conducted before the introduction of evidence-based cardiovascular treatments.The aim of the present work was to assess gender-related differences in the management of elderly patients with T2DM followed-up in the primary care. Specifically, we compared the control of T2DM and other cardiovascular risk factors between women and men, the occurrence of major clinical events (all-cause mortality and major vascular events as well as all-cause hospitalization) between women and men, and the influence of physician gender on the quality of care in subjects with T2DM.The S.AGES T2DM cohort is a prospective observational study whose objective was to describe the real-life medical management of subjects aged 65 years or more with T2DM. 983 non institutionalized subjects were included by 213 general practitioners from April 2009 through June 2011 and followed-up for 3 years. For data obtained during the follow-up period, multilevel mixed-effect regression models were used to account for repeated measurements (for each subject) and clustering (A cluster is a group of subjects followed-up by the same GP).Over the follow-up period, T2DM and blood pressure control were not different between the genders but LDL cholesterol was better controlled in men than in women. The odds ratio for women being associated with uncontrolled LDL cholesterol (>1 g/l) was 2.51 (95% CI 1.79–3.53, p<0.001). This gender-related difference in LDL cholesterol levels was independent of statin therapy.Concerning major clinical events, women were at lower risk than men to develop the composite endpoint (all-cause mortality and major vascular events) with a relative risk of 0.60 (95% CI 0.40-0.91, p=0.016) and the hospitalization endpoint (OR 0.71, 95% CI 0.52-0.96, p=0.029). Coexisting diseases were responsible to the majority of hospitalizations especially in men who were more likely to be admitted to a university hospital when compared to female counterparts. The risk of developing microvascular complications and hypoglycemia were not different between men and women.Finally, we didn’t find any significant difference between male and female physicians in terms of quality of care in subjects with T2DM (control of T2DM and other cardiovascular risk factors, tests to screen for diabetes complications, or the prescription of anti-diabetic and cardiovascular treatments).Our results show that gender differences in this population of elderly diabetics are restricted to higher LDL cholesterol in women than in men but this does not seem to increase the risk of major clinical events (which are higher in male subjects). However, these results should be interpreted with cautious because of selection biases at the physician and patient level as well as under-representation of female physicians.

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.