Foi desenvolvido um estudo observacional de corte transversal, com o objetivo de avaliar o status em Mg de pacientes com diabetes mellitus tipo 2. A amostra foi composta por 51 indivíduos de ambos os gêneros, com idade média de 53,6 ± 10,5 anos, os quais foram selecionados no Ambulatório de Endocrinologia do Hospital Universitário Onofre Lopes (HUOL) Natal/RN. O projeto foi aprovado pelos Comitês de Ética em Pesquisa do HUOL e da Faculdade de Ciências Farmacêuticas da USP. Os pacientes foram submetidos à avaliação antropométrica, dietética, do controle glicêmico, função renal, perfil lipídico, Mg plasmático, eritrocitário, urinário e dietético. Foi observada ingestão adequada de macronutrientes, contudo baixo consumo dietético de Mg e de fibras. Identificou-se, ainda, controle glicêmico e perfil lipídico insatisfatórios e função renal sem alterações significativas. Quanto ao status de Mg, 70,6 % da amostra apresentaram algum dos parâmetros bioquímicos relativos a este mineral abaixo dos valores de referência, sendo estes menores nos indivíduos que tinham mais complicações metabólicas e presença de microalbuminúria. Foram observadas correlações inversas entre o Mg plasmático com a glicemia de jejum (r = -0,281, p = 0,046) e a pós-prandial (r = -0,322, p = 0,021), e correlações positivas entre o Mg urinário com a glicemia de jejum (r = 0,291, p = 0,038), a circunferência abdominal (r = 0,288, p = 0,041) e o IMC (r = 0,282, p = 0,045). Deste modo, foram diagnosticadas alterações no status de Mg, as quais foram mais evidentes nos pacientes que tinham mais complicações, demonstrando a associação dos fatores relacionados com essa doença e o Mg. / A cross-sectional study was carried out to evaluate Mg status in patients with type 2 diabetes mellitus. The sample comprehended 51 individuals, both male and female, aged 53.6 ± 10.5 years, selected from the Endocrinology Clinic of the University Hospital Onofre Lopes (HUOL) in Natal/RN, Brazil. The project was approved by the Commission on Ethics in Research of the HUOL and Faculty of Pharmaceutical Sciences of the University of São Paulo. The patients were assessed concerning anthropometry, diet, blood-glucose control, kidney functioning and lipid profile, besides plasma, erythrocyte, urinary and dietary Mg. An adequate intake of macronutrients and a low consumption of dietary Mg and fibers were observed. Unsatisfactory blood-glucose control and lipid profiles, besides kidney functioning without significant alterations, were also observed. Concerning Mg status, 70.6% of the sample presented biochemical parameters for this mineral below the reference values, and such parameters were lower in individuals with more extensive metabolic complications and microalbuminury. Inverse correlations between plasma Mg with fasting (r = -0.281, p = 0.046) and postprandial plasma glucose (r = -0.322, p = 0.021), and a positive correlation between urinary Mg with fasting plasma glucose (r = 0.291, p = 0.038), waist circumference (r = 0.288, p = 0.041) and body weight index (r = 0.282, p = 0.045) were observed. Therefore, alterations in Mg status were detected in the studied population. Such alterations were more evident in patients with more extensive complications, thus demonstrating the association of factors related to this disease and Mg.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2018-05-25T11:52:26Z No. of bitstreams: 1 caiomendesdefreitas.pdf: 4475109 bytes, checksum: b27bb514b29c024ad61c1114d0539e66 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-06-14T11:52:39Z (GMT) No. of bitstreams: 1 caiomendesdefreitas.pdf: 4475109 bytes, checksum: b27bb514b29c024ad61c1114d0539e66 (MD5) / Made available in DSpace on 2018-06-14T11:52:39Z (GMT). No. of bitstreams: 1 caiomendesdefreitas.pdf: 4475109 bytes, checksum: b27bb514b29c024ad61c1114d0539e66 (MD5) Previous issue date: 2018-02-28 / A presente pesquisa insere-se na perspectiva da psiconeuroimunologia e tem por objetivo investigar a sintomatologia depressiva, sua possível associação ao estresse psicológico e a marcadores endócrinos e imunológicos em pacientes portadores de Diabetes Mellitus Tipo 2 (DM2) acompanhados em um centro especializado de condições crônicas em Juiz de Fora (MG). Participaram do estudo 92 pacientes com DM2, divididos nos seguintes grupos: sem depressão (n=58), depressão leve (n=12), depressão moderada (n=8) e depressão grave (n=13). Foram utilizados o Inventário de Depressão de Beck (BDI-II) como medida de depressão, a Escala de Estresse Percebido (PPS-10) para medir o estresse, a escala SF-6D para avaliação do estado de saúde, sobre religiosidade/espiritualidade (R/E) a Medida Multidimensional Breve de Religiosidade/Espiritualidade (BMMRS-P) e outra sobre a felicidade subjetiva (Brazilian Version of The Sujective Happiness Scale). Foram investigadas as diferenças entre os grupos quanto ao estresse, R/E, felicidade, estado de saúde, variáveis bioquímicas (HbA1c e o nível da glicemia em jejum) e imunológicas (leucócitos, neutrófilos, linfócitos, monócitos). O tratamento estatístico foi realizado utilizando-se o teste qui-quadrado (x²) de Pearson para as variáveis categóricas e a análise de variância (ANOVA) e o teste de kruskal-wallis para as variáveis numéricas, seguidos de pos hoc tests (Bonferroni e Mann-Whitney, respectivamente). Obteve-se relações significativas (x²) entre o sexo (feminino) e depressão grave (p=0,021), assim como entre a dimensão fé religiosa/espiritual e gravidade do nível de depressão (p=0,001). Observou-se também uma associação significativa entre estresse percebido e depressão (p=0.000; F=35,212), assim como com estado de saúde (p=0.000; F=20,333) e o suporte religioso (p=0.013; F=3,823), bem como associações significativas entre experiências espirituais religiosas e níveis de depressão (p=0,001; H=17,352), superação religiosa/espiritual (p=0,049; H=7,847), auto-avaliação global religiosa/espiritual (p=0,001; H=13,431), e felicidade subjetiva (p=0,000; H=20,514). Os resultados do estudo podem auxiliar na elaboração de estratégias de promoção, prevenção e intervenção com foco na saúde mental de pacientes com DM, tais como psicoterapia, técnicas de relaxamento (meditação e yoga), assim como educação em diabetes, criando condições propícias para a evolução favorável da doença, tendo como conseqüência a melhoria geral na qualidade de vida destas pessoas. / The aim of the study was to investigate the depressive symptomatology associated to psychological stress in patients with Type 2 Diabetes Mellitus (DM2) in a specialized center of chronic conditions of Juiz de Fora – MG, in a psychoneuroimmunology framework. 92 patients with DM2, divided into four groups, took part in the study: no depression (n=58), mild depression (n=12), moderate depression (n=8) and severe depression (13). Depression [(Beck Depression Inventory (BDI-II)], stress (Perceived Stress scale (PPS-10)], health condition (SF-6D), religiousness/spirituality (R/E) (Brief Multidimensional Measurement of religiousness/Spirituality - BMMRS-P) and the subjective happiness (Brazilian Version of The Sujective Happiness Scale) were measured. The Pearson Qui-square test was used for categorical variables; analysis of variance (ANOVA) and kruskal-wallis test were used for numeric variables all at a significant p < 0.05, as well as pos hoc tests (Bonferroni and Mann-Whitny, respectively). A significant relationship (x²) between feminine gender and severe depression (p=0,021) was found, as well faith and levels of depression (p=0,001). Was also observed a significant relationship between perceived psychological stress and levels of depression (p=0.000; F=35,212), as well as health status (p=0.00; F=20,333) and religious support (p=0.013; F=3,823). In the Kruskal-Wallis test, there was a significant relationship between religious spiritual experiences and levels of depression (p=0,001; H=17,352), as well overcoming (religious / spiritual) (p=0,049; H=17,352), global self-assessment (religious / spiritual) (p=0,001; H=13,431) and subjective happiness (p=0.000; H=20,514). It is intended to use the data to elaborate strategies to promote and prevent, as well as to develop mental health interventions with diabetic patients and/or patients with other metabolic diseases aiming to create conditions for the favourable evolution of the disease, and a general improvement in the quality of life of these patients. Psychotherapy, relaxation techniques (such as meditation and yoga) as well as diabetes education may be relevant tools for more favorable prognoses in the evolution of the condition in question.

Estudo descritivo transversal, cujo objetivo foi analisar a relação das variáveis sociodemográficas, de tratamento, hábitos de vida, clínicas e laboratoriais com as variáveis sintomas e fases do estresse, em pessoas com diabetes mellitus tipo 2, em unidade ambulatorial de hospital de nível terciário de atenção à saúde. A amostra foi constituída por 222 pessoas e os dados foram coletados no período de junho de 2011 a agosto de 2012. O instrumento utilizado foi o Inventário de Sintomas de Stress de Lipp, composto por três quadros de sintomas de estresse, que fornecem porcentagens para classifica-los em quatro fases: alerta, resistência, quase exaustão e exaustão. Entre as características sociodemográficas, de tratamento, hábitos de vida, dados clínicos e laboratoriais, destacam-se que 53,15% das pessoas eram do sexo feminino, 43,85% do masculino, com média de idade de 60,68 anos (DP=8,40), tempo médio de escolaridade de 5,07 anos (DP=4,15), 71,17% viviam com o companheiro, 57,66% procediam da região de Ribeirão Preto (SP), 50,9% eram aposentados/pensionistas, 87,38% referiu fazer uso de insulina, 78,82% antidiabético oral, 68,91% seguir a dieta recomendada e 46,85% não praticava exercícios físicos regulares. O tempo médio de diagnóstico foi de 15,15 (DP=8,03) anos, índice de massa corporal 32,10 (DP=5,75) Kg/m2 , pressão arterial sistólica 180,10 (DP=14,03) mmHg e diastólica 143,7 (DP=23,63) mmHg, taxa de hemoglobina glicada 9,446 (DP=2) %, colesterol total 74,9 (DP=41,95) mg/dl, lipoproteína de alta densidade 35,67 (DP=8,58) mg/dl, lipoproteína de baixa densidade 101,55 (34,52) mg/dl e triglicerídeos 203,60 (DP=147,72) mg/dl. Quanto às variáveis do estresse, destaca-se que a maior média das porcentagens obtidas ocorreu para os sintomas de estresse do quadro 2 (20,16%-DP=20,165). Para fins de análises estatísticas, excluiu-se a fase de alerta e aglutinou-se as de exaustão e quase exaustão. A frequência dos sintomas de estresse referidos pelos participantes nos três quadros distintos permitiu verificar a presença do estresse em 63,51% da amostra, bem como a frequência de 53,60% na fase de resistência ao estresse, e predomínio de sintomas físicos (61,53%). As fases do estresse associaram-se com a idade, procedência, uso de insulina e lipoproteína de baixa densidade; os sintomas do estresse com o uso de antidiabéticos orais, tabagismo, consumo de bebida alcoólica e lipoproteína de baixa densidade. Quanto à porcentagem média obtida nos três quadros, observou-se que houve associação dos sintomas do primeiro quadro com a ocupação; do segundo quadro com o seguimento da dieta, glicemia plasmática de jejum, o colesterol total e lipoproteína de baixa densidade; correlação do terceiro quadro com o índice de massa corporal, de modo positivo e com a renda familiar, de modo negativo. A idade e a hemoglobina glicada correlacionaram-se com o segundo e terceiro quadros, porém de forma negativa e positiva, respectivamente. O presente estudo permitiu conhecer as possíveis relações do estresse com as variáveis sociodemográficas, tratamento da doença, hábitos de vida, clínicas e laboratoriais da pessoa com diabetes mellitus tipo 2 e reitera a importância desse conhecimento na prática clínica para intervenções que desenvolvam habilidades pessoais para o enfrentamento de situações estressantes percebidas pelas pessoas durante o curso da doença / Cross-sectional study aimed to examine the relations of sociodemographic variables, disease treatment, lifestyle, clinical and laboratory variables with the symptoms and phases of stress in people with type 2 diabetes mellitus, in an outpatient unit of a tertiary level hospital of health care. The sample consisted of 222 individuals and the data were collected between June 2011 and August 2012. The instrument used was the Lipp Stress Symptom Inventory, composed of three frames of stress symptoms, which provide percentages for grades them into four phases: alarm, resistance, near exhaustion and exhaustion. Among the sociodemographic characteristics, treatment, lifestyle, clinical and laboratory data, it highlights that 53.15% of those were female, 43.85% male, with a mean age of 60.68 years (SD = 8.40), mean years of education 5.07 years (SD = 4.15), 71.17% lived with a partner, 57.66% were from Ribeirao Preto region (SP) and 50.9% were retired / pensioners, 87.38% reported use insulin, 78.82% oral antidiabetic, 68.91% followed the recommended diet and 46.85% did not practice regular physical exercise. The average time of diagnosis was 15.15 (SD = 8.03) years, mean body mass index 32.10 (SD = 5.75) kg/m2, mean systolic blood pressure 180.10 (SD = 14 03) and diastolic 143.7 mmHg (SD = 23.63) mmHg, glycated hemoglobin rate 9.446 (SD = 2)%, total cholesterol 74.9 (SD = 41.95) mg/dl, high density lipoproteins 35.67 (SD = 8.58) mg/dL, low density lipoproteins 101.55 (34.52) mg/dL and triglycerides rate of 203.60 (SD = 147.72) mg/dl. As for the variables of stress, there is that most average of these percentages occurred to the frame stress symptoms 2 (20.16% - SD = 20.165). For the purpose of statistical analysis, we excluded the alert phase and connect them of exhaustion and near exhaustion. The frequency of symptoms of stress reported by participants in three different frames demonstrated the presence of stress in 63.51% of the sample, and the frequency of 53.60% in stress resistance phase, and predominance of physical symptoms (61,53%). The phases of stress were associated with age, origin, use of insulin and low-density lipoprotein; symptoms of stress with the use of oral antidiabetic drugs, smoking, consumption of alcohol and low-density lipoprotein. The average percentage obtained in the three frames, it was noted that there was an association of the symptoms of the first frame with the occupation; the second frame with the following the diet, fasting plasma glucose, total cholesterol and low-density lipoprotein; the third frame correlation with body mass index in a positive way and to family income, negatively. The age and glycated hemoglobin correlated with the second and third frames, but negatively and positively, respectively. This study helped identify the possible relations of stress with sociodemographic variables, disease treatment, lifestyle, clinical and laboratory of the person with type 2 diabetes mellitus and reiterates the importance of this knowledge in clinical practice to interventions that develop personal skills for coping stressful situations perceived by the people during the course of the disease

>Magister Scientiae - MSc / Type 2 diabetes mellitus is a progressive disease characterised by defects in insulin secretion, insulin action or both. Proper management of diabetes with appropriate drug and lifestyle interventions, guided by proper glycaemic monitoring has shown improved glycaemic control and a substantial decrease in morbidity associated with complications and mortality. Evidence-based guidelines for the appropriate management of diabetes, suggests the use of glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) as monitoring indicators and have set targets levels that indicate appropriate glucose control. In the event of suboptimal control, actions steps to adjust pharmacotherapeutic treatment has been set out. Of the two aforementioned glycaemic monitoring indicators, HbA1c is termed the 'gold standard' as it provides the most comprehensive data i.e. it reflects both fasting and postprandial glucose concentrations over a 3 months period as compared to FPG which only show glucose levels for a few hours. The aim of this study was to describe the use of glycaemic monitoring indicators in patients with type 2 diabetes mellitus, classified as stable, treated at primary health care facilities in the Cape Town Metropolitan Region in South Africa. The study was a descriptive, retrospective and quantitative in design. Data were collected from patient medical records and included glycaemic monitoring tests and results as well as prescribing records for a maximum period of 18 months. The study comprised of 575 participants from five primary health care facilities in the Western Cape Metropole region. All participants had FPG results, while HbA1c results were recorded for 86% of participants at least once. More than 70% of participants with either a FPG or HbA1c result showed suboptimal glucose control i.e. were outside of the target range. In 181 opportunities for intervention in participants with HbA1c results outside target, 113 (62.4%) did not have any therapy adjustments, 19 (10.5%) had the total daily dose increased, 6 (3.3%) had total daily dose decreased, 9 (5.0%) had a step-up in regimen, 5 (2.8%) had a step down in regimen and 29 (16.0%) had a lateral regimen change. In 852 opportunities for intervention in participants with FPG results outside target, 609 (71.5%) did not have any therapy adjustments, 47 (5.5%) had the total daily dose increased, 18 (2.1%) had the total daily dose decreased, 16 (1.9%) had a step-up in regimen, 15 (1.8%) had a step down in regimen and 147 (17.3%) had a lateral change in regimen. This study has demonstrated that in the primary healthcare facilities investigated, FPG was the most often used gycaemic monitoring indicator, glycaemic monitoring of patients mostly show suboptimal glucose control and that opportunities to optimise pharmacotherapy in diabetes management are mostly missed.

Diabetes mellitus is a growing threat to human health. Current pharmacological agents cause undesirable side-effects. Herbal remedies offer the potential for alternative treatment strategies that may prove more cost-effective and devoid of the undesirable side-effects. The purpose of this study was to evaluate the in vitro anti-diabetic activity of aqueous and methanol extracts of Sclerocarya birrea (A. Rich.) Hochst. (Anacardiaceae) and Ziziphus mucronata Willd. (Rhamnaceae), which are traditionally used for the treatment of diabetes mellitus in southern Africa. Polyphenolic contents of extracts were quantified using the aluminium trichloride and Folin-Ciocalteau methods. The capacity of individual extracts to scavenge both the 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl radicals was used as a measure of antioxidant activity. The inhibitory activities of the crude extracts of both plants on the enzymes, α-amylase and α-glucosidase, were determined using colorimetric assays. The effects of the crude extracts on cell viability was assessed in C2C12 myotubes, HepG2 hepatocarcinoma cells, 3T3-L1 adipocytes and RIN-m5F pancreatic β-islet cells, using the Sulforhodamine B assay. Fluorescence detection was used to investigate the effects of the crude extracts on glucose uptake in C2C12, HepG2 and 3T3-L1 cells. Insulin secretion was assessed in RIN-m5F cells, using ELISA. Crude extracts of both plants contained flavonoids and phenols, but flavonoid content was predominantly higher. All the extracts displayed antioxidant activity, with the methanol extract of S. birrea possessing the most potent free radical scavenging ability (IC50 = 2.16 μg/ml). Aqueous and methanol extracts of S. birrea displayed significantly (p < 0.05) greater inhibition of α-amylase, than the positive control, acarbose. Only the methanol extract of Z. mucronata inhibited α-amylase activity. Furthermore, crude extracts of both plants also displayed potent α-glucosidase inhibitory activity. Most of the crude extracts had low toxicity, where concentrations of 100 μg/ml of crude extract of the plants did not induce 50% cell death. iv Although no significant increase in insulin secretion from cultured RIN-m5F cells was noted, the crude extracts of both plants significantly (p < 0.05) increased glucose uptake in C2C12, HepG2 and 3T3-L1 cells, with efficacy significantly (p < 0.05) higher than the positive control, insulin. From the results, the plant extracts appear to exert their hypoglycaemic effects independently of insulin, via an extra-pancreatic mechanism, possibly involving interactions with the different receptors. An additive hypoglycaemic effect originates from the inhibition of both α-amylase and α-glucosidase. The findings of the present study provide evidence that S. birrea and Z. mucronata possess in vitro anti-diabetic activity. Further investigations are required to elucidate the mechanism(s) of action of the crude extracts using more targeted in vitro assays. / Dissertation (MSc)--University of Pretoria, 2013. / gm2014 / Pharmacology / unrestricted

>Magister Scientiae - MSc / About 180 million people have been estimated to suffer from type 2 diabetes (T2DM) in 2006 and the annual death rate due to this disease was 3 million by that time. More than 400 medicinal plants used for the treatment of diabetes mellitus have been recorded, but only a small number of these plants have received scientific and medical evaluation to assess their efficacy. The most common plant used to treat diabetes mellitus is Hypoxis hemerocallidea (HH). The present study was undertaken to investigate the effects of Hypoxis hemerocallidea (HH) on T2DM in rats. Male Wistar rats weighing 200-250 g were used in this experiment. Hypoxis hemerocallidea (HH) corm was used as plant material in the experiment. The study was based on three parts, an acute diabetes study, chronic diabetes study and insulin secretion study. In the acute study, the rats were randomly divided into 2 groups (control and diabetes). The saline solution was added to different concentrations of HH corm to produce concentration of (50, 200, 400, 800 mg/ml). Diabetes was induced by intraperitoneal injections of STZ (65mg/kg). Two weeks after the injection (STZ 65 mg/kg), different concentrations of HHS was administered intraperitoneally after an overnight fast. The blood glucose levels were monitored in the diabetic and control rats at, 30, 60, 120, 180 and 240 minutes post injection. In the chronic study, the rats were randomly divided into 6 different groups (control, HFD, DM, DM-HH, DM-PTHH, and HH). Diabetes mellitus was then induced in the groups of diabetic rats by intraperitoneal injections of STZ (40 mg/kg) and rats were fed a high fat diet (HFD). The body weight of the rats were measured weekly for 7 weeks. An intraperitoneal glucose tolerance test (IPGTT) was performed at the end of week 6. At the end of week 7, rats were killed and serum sample were collected for determination of fatty acid and insulin. Liver and pancreatic tissue was collected for histological evaluation. In the insulin secretion study, Hypoxis hemerocallidea was tested for its effects on insulin secretion by pancreatic islet cells exposed to low (3mM) and high (20mM) glucose medium. Results of the acute study indicated that HHS at a dose 800 mg/ml decreased blood glucose levels fastest in both normal and diabetic rats reaching significance after 30 minutes and 60 minutes respectively and remained below the baseline value until 240 minutes. In the chronic study, it was illustrated that HH had no effect in normal rats on any of the parameters evaluated. Animals in the DM group gained weight the first two weeks, but thereafter began to lose weight. At the end of seven weeks the animals gained significantly less weight than the rest. Animals fed a HFD have more visceral fat compared to the control group. The visceral fat gain occurred in the absence of a significant increase in body weight. We found a markedly lower fasting glucose level in HH treated diabetic animals compared to untreated DM animals. At time zero the blood glucose level of the HFD group (5.8±0.5mmol/l) and the HH group (4.9±0.7mmol/l) were in the normal range, and were not significantly different (P > 0.05) from the control group (5.0±0.2mmol/l). After glucose load peak blood glucose levels was measured after 30 minutes in the control group (9.0±0.6mmol/l), the HFD group (9.8±0.4 mmol/l), the DM-HH group (21±5.7 mmol/l) and the DM-HHPT group (27.8±5.3 mmol/l). In the HH group the blood glucose level reached a peak at 60 minutes (7.6±0.6 mmol/l). In the DM group two peaks were recorded one after 10 minutes (27.2±7.1mmol/l) and another after 60 minutes (31±5.2 mmol/l). In the groups control, HFD, DMHH, DM-HHPT and HH groups the blood glucose level after 120 minutes were not significantly different from the time zero value. The blood glucose level after 120 minutes in the DM group (28.2±7.1 mmol/L) was significantly higher (P ≤ 0.01) than from the time zero value. Serum fatty acid levels were increased in all groups fed a high fat diet. The serum insulin levels in the HFD group (6.2 ± 0.76 μUI/ml protein; P ≤ 0.05 ), the DM group (2.0 ± 0.9 μUI/ml protein; P ≤ 0.001), the DMHH group (3.4 ± 0.7 μUI/ml protein; P ≤ 0.001) and the DM-HHPT group (3.0 ± 1.1 μUI/ml protein; P ≤ 0.001) were significantly lower than the control group. The β-cell function in the HFD group (62 ± 8 %; P ≤ 0.001), the DM group (3 ± 1 %; P ≤ 0.001), the DM-HH (11 ± 9 %; P ≤ 0.001) group and the DM-HHPT group (4 ± 2 %; P ≤ 0.001) were significantly lower than the control group. The histological observation of the liver and the pancreas in rats after 7 weeks on different dietary regimes showed some morphological changes within the liver and pancreas parenchyma of some rats. In the insulin secretion study, glucose stimulated insulin secretion in low (3mM) and high (2mM) glucose concentration. Furthermore, insulin secretion was significantly higher when the glucose concentration was increased from 3mM to 20 mM (1.10 ± 0.13 μUI/ml protein and 1.5 ± 0.17 mIU/mg protein respectively P≤ 0.01). In the presence of low HH (100 µg/ml), there was a marked increase in insulin secretion when exposure to high glucose compared to low glucose concentration, while in the presence of high HH (500 µg/ml), there was no significant different in insulin secretion in the presence of low or high glucose. In conclusion, the results of this experimental study indicate that a concentration 800 mg/kg of HHS produces maximal hypoglycaemic effect in fasted normal and diabetic rats. HH has an antidiabetic activity as it lowers serum glucose levels in T2DM rats and significantly increases glucose tolerance. It also increases body weight of diabetic rats. HH treatment was found to improve insulin secretion in pancreatic islet cells.

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.

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.

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.