The main objective of this study was research on biomarkers used in both diagnosis and therapy of diabetic complications. The main focus of our work came to be on one of these biomarkers - glycemic variability (GV). High GV is linked with more frequent occurance of hypoglycemia. There are even indications it might contribute to development of diabetic complications. With modern technology - continuous glucose monitoring (CGM), we are now able to reliably describe, calculate and reduce GV. So far it is unclear whether increased GV can contribute to the development of microvascular complications (MVC) in type 1 diabetes (T1D). Studies published so far have assessed GV primarily from routine self-monitoring of blood glucose (SMBG) using glucometers. In the light of this uncertaity, the first part of this work compares GV calculated from CGM with the presence of MVC in T1D patients. GV calculated from CGM, but not from SMBG, proved to be significantly higher in T1D patients with MVC, even though there was no significant difference in glycated hemoglobin (HbA1c). This finding supports the hypothesis that higher GV is related to higher risk of MVC and that HbA1c does not describe diabetes control completely. Moreover, it was shown that GV calculated from SMBG is insufficient. There is still no fully...

Made available in DSpace on 2017-07-10T18:55:44Z (GMT). No. of bitstreams: 1 Gisele Toyama.pdf: 2839416 bytes, checksum: 2f5dbd1ea8e1b9c003fdb5d06ee443c4 (MD5) Previous issue date: 2014-02-14 / Type 2 diabetes (DM2) and periodontal disease are closely related. DM2 is a risk factor for periodontal disease whereas periodontitis increases hyperglicemia. Although it is known that the treatment of periodontitis improves glycemic control, there is no consensus of what type of treatment is best for diabetics. Objective: Evaluate different types of periodontal treatment in diabetics. Methodology: Two different researches were performed: 40 patients, aged 30 to 60, who were divided into 2 groups: group 1: controlled mechanical + basic periodontal treatment, Group 2: controlled mechanical + basic periodontal treatment + Doxycycline 100 mg orally for 14 days. In the first study, the analyses were made after 0, 3 and 6 months, including probing depth, level of clinical attachment, bleeding on probing. Glycated hemoglobin (HbA1c), fasting glucose and microbiological analysis (FG) were also taken. In study 2, a clinical analysis and an expression of isoforms of interleukin IL1β (IL-1β) test was performed. 20 patients were selected for the second part of the research. They were divided as follow: 1) Conventional periodontal treatment with scaling and root planning + Mechanical control and group 2) Periodontal Treatment (one-stage full-mouth disinfection) + Mechanical control . In this research, the analysis was performed after 0, 3 and 6 months including clinical evaluation, HbA1c and FG tests. The expression of isoforms of interleukin IL1β (IL-1β) were analyzed in the beginning of the study and after 6 months. Results: In the first article, it was shown an improvement in all clinical periodontal parameters evaluated as well as the level of HbA1c in both treated groups after 6 months. In the doxycycline group, there was a greater improvement in gingival index and test of glycated hemoglobin, as well as a smaller amount of Gram- .The second study showed a significant decrease in the expression of IL1- in gingival crevicular fluid in patients in treatment with Doxycycline. In the second research, after 6 months, it was observed better levels of FG, clinical periodontal parameters and gingival crevicular fluid in both groups. Nevertheless, no statistical significance was observed in the expression of IL-1β after 180 days. Conclusion: It is suggested that the basic periodontal therapy associated with the use of doxycycline is more efficient for clinical, glycemic and microbiological control in patients with type 2 Diabetes Mellitus with periodontal disease, as well as in the reduction of IL1- in gingival crevicular fluid. When different types of periodontal treatments are compared, it is possible to observe that the conventional periodontal treatment is the first choice in one-stage full-mouth disinfection for both glycemic control and periodontal parameters related to bleeding on probing and gingival crevicular fluid as well as the relation of variation envolving the expression of IL1-β even in the absence of significant difference among initial and final parameters in each group / O diabetes mellitus tipo 2 (DM2) e a doença periodontal possuem entre si uma relação íntima. O diabetes é um fator de risco para periodontite, assim como, a periodontite aumenta a hiperglicemia. O tratamento da periodontite pode melhorar o controle glicêmico, entretanto, não existe consenso de qual tratamento periodontal é o melhor em diabéticos. Objetivo: Avaliar diferentes modalidades de tratamento periodontal em diabéticos. Metodologia: Foram realizadas duas pesquisa, na primeira, foram selecionados 40 pacientes com DM2, e estes divididos em dois grupos: Grupo 1: Controle mecânico + Tratamento periodontal básico; Grupo 2: Controle mecânico + Tratamento periodontal básico + Doxiciclina 100 mg via oral por 14 dias. No primeiro artigo foram realizadas análises aos 0, 3 e 6 meses, incluindo Profundidade de sondagem, Nível de inserção clínica e Sangramento a sondagem, juntamente com a avaliação de hemoglobina glicada (HbA1c), glicemia em jejum (GJ) e análise microbiológica. No artigo 2, foram realizadas as análises clínicase a análiseda expressão das isoformas da interleucina IL1β (IL-1β). Na segunda pesquisa foram selecionados 20 pacientes com DM2, os quais foram divididos em dois grupos: Grupo 1: Tratamento periodontal básico (RAR) + Controle mecânico (Técnica de Bass + fio dental); Grupo 2: Tratamento periodontal básico (Desinfecção Total de Boca em Estágio Único - DBEU) + controle mecânico (Técnica de Bass + fio dental). Nesta pesquisa as análises também foram realizadas aos 0, 3 e 6 meses, com avaliação clínica periodontal e a avaliação de HbA1c e GJ. A expressão das isoformas de IL-1β foram analisadas no início e após 6 meses. Resultados: No primeiro artigo, houve uma melhora de todos os parâmetros clínicos periodontais e dos níveis de HbA1c em ambos os grupos tratados após 6 meses. No grupo que usou doxiciclina, houve uma melhora mais expressiva do índice gengival e daHbA1c, bem como uma quantidade menor de microrganismos Gram-. O segundo artigo evidenciou uma expressão significantemente menor de IL1- no fluido crevicular gengival dos pacientes em uso de doxiciclinina ao final do experimento. Na segunda pesquisa, após 6 meses, houve uma melhora da GJ, dos parâmetros clínicos periodontais e da quantidade de fluido crevicular gengival em ambos os grupos. Entretanto, não houve diferença estatisticamente significativa na expressão de IL-1β após 180 dias.Conclusão: Foi possível observar que a terapia periodontal básica associada ao uso de doxiciclina é mais eficiente para o controle clínico, glicêmico e microbiológico de pacientes portadores de DM2 e doença periodontal, bem como na menor expressão de IL1- no fluido crevicular gengival deste pacientes. Quando comparado os tipos de tratamento periodontal, foi possível observar que o tratamento periodontal convencional é superior à desinfecção total em estágio único, tanto em relação ao controle glicêmico, quanto em relação aos parâmetros periodontais de sangramento a sondagem e área de fluido gengival, bem como em relação a variação dos valores de expressão de IL1-β, apesar de não haver diferença significativa entre os valores iniciais e finais em cada grupo

Introdução: A polpa farinácea do jatobá-do-cerrado (Hymenaea stigonocarpa Mart.) apresenta alto teor de fibra alimentar, em média 60 g/100 g, que são importantes para a redução do risco e controle de doenças crônicas não transmissíveis (DCNT). A extrusão termoplástica neutraliza aromas intensos, proporciona a formação de amido resistente, aumenta a fibra alimentar solúvel e melhora a textura do produto final. Objetivo: Estudar o efeito das farinhas de jatobá-do-cerrado in natura (FIN) e extrusada (FE) no metabolismo lipídico e parâmetros fermentativos em hamsters, bem como verificar a resposta glicêmica em humanos após a extrusão. Métodos: Processo de extrusão: velocidade de 200 rpm; matriz com 4 mm de diâmetro; taxa de compressão 3:1; alimentação constante de 70 gramas/minuto; temperatura de 150 °C; proporção farinha de jatobá-do-cerrado e amido de milho: 70:30 por cento e umidade a 25 por cento . Foi realizado um experimento animal com hamsters durante 21 dias, em que se analisou alguns parâmetros do metabolismo lipídico e colônico (fermentativos) dos animais, divididos em quatro grupos experimentais, se diferenciando pela dieta. As dietas controle (GC), in natura (GFI) e extrusada (GFE) eram hipercolesterolemizantes (13,5 por cento de gordura de coco e 0,1 por cento de colesterol) e a dieta referência (GR) com óleo de soja como fonte lipídica, não. Todas as dietas apresentavam 15 por cento de fibra alimentar, sendo que as dietas GR e GC tinham como fonte de fibra a celulose, e as dietas GFI e GFE tiveram as próprias fibras como fonte. A resposta glicêmica em humanos foi verificada por meio do ensaio do índice glicêmico e carga glicêmica da FE, com dez voluntários saudáveis que consumiram 25 gramas de carboidratos disponíveis do alimento teste (farinha extrusada) ou do pão branco como alimento controle. Resultados: Não foi observada diferença significativa entre o peso final, ingestão diária média e total, ganho de peso e CEA entre os animais dos quatro grupos. A concentração de triglicerídeos foi menor em 41 por cento e 38 por cento nos animais que receberam as dietas GFI e GFE, em relação aqueles que receberam a dieta GC, assim como também para o colesterol total (55 por cento e 47 por cento ), LDL-c (70 por cento e 53 por cento ) e não-HDL-c (63 por cento e 49 por cento ) séricos, lipídeos totais hepáticos (39 por cento e 45 por cento ) e o peso dos fígados dos animais também foi menor (21 por cento em ambos os grupos). Não houve diferença no colesterol hepático e excretado nas fezes dos animais dos quatro grupos. Os animais do GFE excretaram 57 por cento mais ácidos biliares nas fezes que os animais do GC. Com relação aos parâmetros fermentativos, observou-se maior excreção de fibras (1,24 ± 0,08 e 1,52 ± 0,09 gramas) nos animais dos grupos GR e GC respectivamente, em relação aos do GFI e GFE (0,50 e 0,48 gramas), porém o escore fecal (3,50 ± 0,19 e 3,38 ± 0,18) e o grau de fermentação (54 e 52 por cento ) foi maior nos animais dos grupos GFI e GFE. Houve uma maior produção de AGCC no ceco dos animais dos grupos GFI e GFE (80 e 57,5 µmol/g de ceco respectivamente) e maior diminuição do pH no conteúdo cecal nos animais do grupo GFI (7,49 ± 0,10), em relação ao GC (8,06 ± 0,13). Os ácidos acético e propiônico, estiveram presentes em maior quantidade no ceco dos animais dos grupos GFI (58,5 e 6,1 µmol/g de ceco) e GFE (42,5 e 6,6 µmol/g de ceco) e os animais do GFI produziram mais ácido butírico (15 µmol/g de ceco), em relação aos demais grupos. Quanto à resposta glicêmica da farinha pós extrusão, não houve diferença entre a área de resposta glicêmica da farinha extrusada e do pão branco, o índice glicêmico da farinha extrusada (glicose como controle) foi classificado como moderado, e a carga glicêmica (na porção de 30 gramas), baixa. Conclusão: As FIN e FE favoreceram a redução do colesterol total, LDL-c, não-HDL-c e dos triglicerídeos séricos, além da diminuição do acúmulo de lipídeos hepáticos. Foi observado também aumento expressivo na formação de AGCC e no grau de fermentação. A FE proporcionou um aumento na excreção de ácidos biliares nas fezes e apresentou índice glicêmico moderado e baixa carga glicêmica. / Introduction: The mealy pulp of jatobá-do-cerrado (Hymenaea stigonocarpa Mart.) has high dietary fiber content, on average 60 g/100 g, which is important for reducing risk and control chronic non-communicable diseases (NCDs). The thermoplastic extrusion neutralizes intense flavors, formation of resistant starch, increases soluble dietary fiber and improves the texture of the final product. Objectives: Check the effect of jatobá-do-cerrado flour in natura (IF) and extruded (EF) on lipid metabolism and fermentation parameters in hamsters as well as the glycemic response in humans after extrusion. Methods: Extrusion cooking: speed of 200 rpm; 4 mm die diameter; compression ratio 3:1; constant feed rate 70 g/min; temperature 150 °C; ratio of jatobá-do-cerrado flour to corn starch: 70:30 per cent and 25 per cent moisture. A 21-day biological experiment with hamsters was conducted, in which parameters of the animals lipid metabolism and colonic (fermentation) were analyzed; they were divided into four groups, differing by diet. The control diets (CG), in natura (IFG) and extruded (EFG) were hypercholesterolemic (13.5 per cent coconut fat and 0.1 per cent cholesterol), and the reference diet (RG) with soybean oil as a lipid source was not. All diets had 15 per cent of dietary fiber, being that RG and CG diets had the cellulose fiber source, and IFG and EFG diets had the fibers themselves as a source. The glycemic response in humans was evaluated by the glycemic index and glycemic load test of EF, with ten healthy volunteers who consumed 25 grams of available carbohydrate food test (extruded) or white bread as food control. Results: There was no significant difference between final weight, average total and daily intake, weight gain and FER between animals of the four groups. The values of triglycerides were lower by 41 per cent and 38 per cent in the animals receiving the IFG and EFG diets, for those who received the CG diet, as well as for total cholesterol (55 per cent and 47 per cent ), LDL-c (70 per cent and 53 per cent ) and non-HDL-c levels (63 per cent and 49 per cent ) serum, liver lipids (39 per cent and 45 per cent ) and the animals\' livers weight was lower (21 per cent in both groups). There was no difference in hepatic cholesterol and excreted in feces of animals of the four groups. The animals of the EFG group excrete 57 per cent more bile acids in stool than animals CG. Regarding the fermentation parameters, we observed increased excretion of fibers (1.24 ± 0.08 and 1.52 ± 0.09 g) in animals of RG and CG respectively, in relation to IFG and EFG (0.50 and 0.48 grams), but the fecal score (3.50 ± 0.19 and 3.38 ± 0.18) and the degree of fermentation (54 and 52 per cent ) were higher in animal IFG and EFG groups. There was a greater production of SCFA in the caecum of animals IFG groups and EFG (80 to 57.5 µmol/g caecum respectively) and greater decrease in pH in the cecal contents of IFG animals group (7.49 ± 0.10) compared to the control group (8.06 ± 0.13). The acetic and propionic acids were present in higher amounts in the caecum of animals IFG groups (58.5 and 6.1 µmol/g caecum) and EFG (42.5 and 6.6 µmol/g caecum) and the animals of IFG group produced more butyric acid (15 µmol/g caecum), compared to other groups. Concerning the glycemic response of flour after extrusion, there was no difference between the glycemic response area of extruded flour and white bread, the glycemic index of extruded flour (glucose as a control) was classified as moderate and glycemic load (the portion of 30 grams) low. Conclusion: IF and EF aided in the reduction of total cholesterol, LDL-c, non-HDL-c and triglycerides, as well as decreased the accumulation of liver lipids. A significant increase in the SCFA and degree of fermentation was also observed. The EF increased the excretion of bile acids in stool, and presented moderate glycemic index and low glycemic load.

Introdução: A doença celíaca não tem cura e apresenta como único tratamento a dieta isenta de glúten. Frequentemente observa-se a má absorção de cálcio em celíacos, consequência dos menores níveis de transportadores de cálcio no enterócito desses indivíduos. Os celíacos têm dificuldade em dar sequência ao tratamento dietético devido à escassez de produtos isentos de glúten, tornando fundamental o desenvolvimento de produtos para esta população. Isso pode ser feito por meio do uso de matérias primas isentas de glúten e com valor nutritivo agregado, como o grão de amaranto, e de ingredientes que contribuem para o aumento da absorção de cálcio através de absorção passiva nos colonócitos, como os frutanos inulina e oligofrutose. Objetivo: Desenvolver e otimizar as propriedades nutricionais e sensoriais de produtos à base de amaranto enriquecidos com frutanos, para intervenção nutricional em celíacos. Metodologia: Foram elaborados snacks à base de milho e amaranto (50, 75 e 100%), barras e pães sem glúten, enriquecidos com 4 gramas de frutanos/ porção. Para maximizar a aceitabilidade das barras foi utilizado um planejamento experimental para misturas de amaranto extrusado, estourado e laminado. Para maximizar o valor nutritrivo e a aceitabilidade do pão sem glúten foi utilizado o planejamento experimental para misturas de farinha de arroz, fécula de batata e farinha de amaranto. Os produtos foram caracterizados quanto a composição centesimal, o índice glicêmico (IG) e a carga glicêmica (CG). Também foram avaliadas as propriedades físicas e a aceitabilidade (escala hedônica estruturada de nove pontos) durante o período de armazenamento. Resultados e discussão: Os snacks foram aceitos e apresentaram estabilidade de suas características físicas e da aceitabilidade durante os 135 dias de armazenamento. O efeito combinado do amaranto e dos frutanos gerou redução de 19% do IG e de 56% da CG dos snacks. O amaranto estourado e laminado apresentaram interações sinérgicas para a aceitabilidade das barras (R2(aj)>92%, p=0,00). A formulação à base de amaranto estourado e laminado (½,½) foi diversificada em seis diferentes sabores e apresentou estabilidade de suas propriedades físicas e da aceitabilidade durante os seis meses de armazenamento. A estimativa da resposta glicêmica revelou IG moderado e CG baixa das barras. Pães com 33 e 45% de farinha de amaranto apresentaram destacado valor nutritivo e aceitabilidade. A incorporação de amaranto e de frutanos ocasionou redução de 20% do IG e de até 53% da CG do pão sem glúten. Conclusão: Os produtos desenvolvidos (snacks, barras e pães sem glúten) apresentaram destacado valor nutritivo em relação aos produtos convencionais, atenuação da resposta glicêmica e alta aceitabilidade pelo consumidor, podendo contribuir para uma maior variação e adequação da dieta dos celíacos e também para auxiliar no aumento da absorção de cálcio / Introduction: Celiac disease does not have a cure and the only scientifically proven treatment is strict lifelong adherence to a gluten-free diet. Calcium malabsorption is frequently found in celiac, possibly due to negligible amounts of calcium-binding protein in their enterocytes. Compliance with dietary treatment is often difficult due to the lack of gluten-free products, so it is essential to develop specific products for this population. This can be done through the use of gluten-free raw materials of great nutritional value, such as amaranth grain, and ingredients that contribute to the calcium absorption increasement through passive absorption in colonocytes, such as the fructans inulin and oligofructose. Objective: Develop and optimize the nutritional and sensory properties of amaranth based products enriched with fructans, for nutritional intervention in celiac. Methods: Snacks from blends of corn and amaranth (50, 75 and 100%), amaranth bars and gluten-free bread, all enriched with 4 grams of fructans/ portion, were prepared. A mixture experiment of extruded, popped and flaked amaranth was used to optimize the sensory acceptability of the bars. A mixture experiment of rice flour, potato starch and amaranth flour was used to maximize the nutritional value and sensory acceptability of gluten-free bread. Products chemical composition, glycemic index (GI) and glycemic load (GL), were evaluated. The physical properties and sensory acceptability (nine point hedonic scale) were assessed during the storage time. Results and discussion: Snacks were sensory accepted and maintained their physical characteristics and sensory acceptability during the 135 days of storage. The combined effect of amaranth and fructans resulted in 19% reduction of GI and 56% of GL of snacks. Popped and flaked amaranth present synergistic interactions to sensory acceptability of the bars (R2(adj)>92%, p=0,00). Bars were produced with popped and flaked amaranth (½,½) in six different flavors and its physical properties and sensory acceptability were stable during the six months of storage. The predicted glycemic response showed moderate GI and low GL bars. Breads with 33 and 45% of amaranth flour had higher nutritional value and sensory acceptability. Amaranth and fructans addition led to a reduction of approximately 20% of GI and up to 53% of the GL of gluten-free breads. Conclusion: The developed products (snacks, bars and gluten-free breads) had superior nutritional composition than conventional products, reduced glycemic response, high consumer sensory acceptability, great potential to contribute to variation and adequacy of celiac diet and also help to increase calcium absorption.

Muitas alternativas têm sido propostas para melhorar as características nutricionais dos alimentos, algumas delas utilizando fontes de fibra alimentar ainda pouco conhecidas. Entre estas fontes de fibra alimentar (FA), a farinha de banana verde (FBV) tem se mostrado uma boa alternativa por sua alta concentração de amido resistente (AR) que pode melhorar o valor nutricional de diferentes preparações. Neste trabalho foram estudadas barras de cereal elaboradas com FBV, com o objetivo de avaliar in vivo e in vitro as propriedades nutricionais desses produtos. As amostras consistiam em dois tipos de barras de cereais, uma delas elaborada com FBV (barras FBV) e outra sem este ingrediente (barras controle). A composição centesimal e perfil de carboidratos das barras foram avaliados. A fermentabilidade da fração não-disponível das barras foi avaliada através de testes in vitro utilizando inóculo de ratos. A resposta glicêmica das barras foi avaliada após sua ingestão por voluntários saudáveis (n=16), sendo determinados o índice glicêmico (IG) e carga glicêmica (CG). A principal característica que pôde ser observada é que as barras FBV possuem maior conteúdo de AR que as barras controle (7,22 g/100g e 2,11 g/100g na base integral), resultado da adição de FBV. Esta adição reflete na concentração de carboidratos não-disponíveis (soma de FA e AR) das barras FBV, que é de 18,19 g/100g na base integral. As barras FBV apresentam maior fermentabilidade in vitro em relação às barras controle (p<0,05) de acordo com a produção de ácidos graxos de cadeia curta (AGCC), produzindo 4,04 mmol/g de substrato, enquanto as barras controle produzem apenas 3,51 mmol/g de substrato. As barras FBV apresentam baixo IG (em relação à glicose) (41%) e CG (4), enquanto as barras controle apresentam IG médio (60%) e CG baixa (5). A partir dos resultados apresentados, é possível concluir que a adição de FBV às barras de cereal aumenta seu conteúdo de carboidratos não-disponíveis, representados pelo AR e FA, resultando num produto de alta fermentabilidade e de baixa resposta glicêmica pós-prandial. / Several alternatives have been proposed to improve the nutritional characteristics of foods, some of them using sources of dietary fiber that are still underused. Among these sources of dietary fiber (DF), unripe banana flour (UBF) has been considered a good alternative for its high concentration of resistant starch (RS), which can improve the nutritional value of different preparations. The aim of this study was to evaluate, in vivo and in vitro, the nutritional properties of cereal bars made with UBF. The samples consisted of two types of cereal bars, one made with UBF (UBF bars) and the other one without this ingredient (control bars). The chemical composition and carbohydrate profile of the bars were evaluated. The fermentability of the non-available fraction of bars was assessed in vitro using cecal contents of mice. The glycemic response of the bars was assessed after its ingestion by healthy volunteers (n = 16), being determined the glycemic index (GI) and glycemic load (GL). The main feature that could be observed is that the UBF bars have higher RS content than the control bars (7.22 g/100g and 2.11 g/100g wet weight), a result of the addition of UBF. This addition reflects on the concentration of non-available carbohydrates (sum of DF and RS) in UBF bars, which is 18.19 g/100g wet weight. The UBF bars presented better in vitro fermentability in relation to control bars (p <0.05) according to the production of short chain fatty acids (SCFA), yielding 4.04 mmol / g substrate, while the control bars produce only 3.51 mmol / g substrate. The UBF bars have a low GI (based on glucose) (41%) and CG (4), while the control bars show medium GI (60%) and low CG (5). According to these results, it is possible to conclude that the addition of UBF to cereal bars increases their non-available carbohydrate content, represented by RS and DF, resulting in a product of high fermentability and low postprandial glycemic response.

Background: Puerto Ricans experience high prevalence of type 2 diabetes (diabetes). Stress is a risk factor for diabetes. The allostatic load (AL) model explains how stress influences disease through a chain of physiological changes. Puerto Ricans experience psychological and physiological (obesity and high glycemic load (GL)) stressors linked with diabetes, yet how these stressors impact the AL chain and how their interplay affects glucose metabolism remains unknown. Methods: Using data from the Boston Puerto Rican Health Study, this thesis sought to examine: 1) the relationship between GL and primary AL markers, 2) the interaction between perceived stress and GL on HbA1c, and if primary AL markers mediate this interaction, and 3) the interaction between change in weight and in perceived stress on HbA1c. Results: 1) GL change over 2 years was associated with increases in primary AL markers in women. 2) Women with high perceived stress and high GL had higher HbA1c and primary AL markers did not mediate this interaction. 3) In women, there was an interaction between change in weight and perceived stress on HbA1c over 2 years, with the effect of weight change on HbA1c being greater with increases in perceived stress. None of these associations were observed in men. Conclusion: This study partially confirms the AL model in Puerto Rican women but not in men. It provides data to inform intervention targets to prevent and manage diabetes in Puerto Rican women and identifies women at high risk of diabetes in this minority group.

>Magister Scientiae - MSc / The burden of non-communicable diseases (NCDs) in South Africa is predicted to increase substantially in the next decades if the necessary preventative measures are not taken. The two most common NCDs associated with rapid mortality increase are diabetes mellitus (DM) and hypertension (HTN). Both of these diseases, i.e DM and HTN, can be a result of a combination of modifiable risk factors (behavioral) and non-modifiable risk factors (genetic, physiological, and environmental). New strategies implemented to manage these diseases should include addressing both modifiable and non-modifiable risk factors for patients with NCDs. The aim of this study was to contribute to the reduction of incidence of uncontrolled T2DM among patients taking metformin as a first-line anti-diabetic drug, through the development of individualized therapy for this drug. When implemented, this could be one of the healthcare strategies to address non-modifiable risk factors for patients with T2DM as an important NCD. The first objective of the study was to explore the prevalence and risk factors of DM and HTN in South Africa, especially within the economically disadvantaged population.

Bakgrund: Diabetes Mellitus Typ 2 är en kronisk sjukdom som ger allvarliga långsiktiga skador. En av hörnstenarna för att kontrollera sjukdomen är patientens egenvård.  För att genomföra behandlingen måste patienterna förstå vilken betydelse de har för sjukdomen.    Syfte: Syftet med denna studie är att beskriva Mexikaner sjuksköterskornas upplevelse om deras bidrag till kännedom om egenvård hos patienter med Diabetes Mellitus Typ 2 i Mexiko.   Metod: En kvalitativ design med semi-strukturerade intervjuer och en innehållanalys användes i denna studie.    Resultat: Deltagarna upplever att egenvård är av stor betydelse vid behandling av  Diabetes Mellitus typ 2. Patienterna behöver kunskap och utbildning, och sjuksköterskorna är medvetna om att de är ansvariga för undervisningen. Däremot på grund av tidsbrist,  otillräcklig personal samt överbelastning av patienter kan inte utbildning av patienter ske. Enligt deltagarna är patienternas engagemang och familjestöd  faktorer som påverkar patienternas egenvård.   Slutsats: Deltagarna upplever att egenvård är viktigt för Diabetes Mellitus typ 2. Patienten och sjuksköterskorna har en viktigt roll vid egenvård. En personcentrerad vård kan hjälpa sjuksköterskor att tillgodose patienternas behov. / Background: Type 2 Diabetes Mellitus is a chronic disease that produces serious long-term complications. The self-management of the patient has become the cornerstones to control the disease.  To carry out treatment, patients must understand the role they play at this.        Aim: This study aims to describe the Mexican nurses’ perception of their contribution  to the knowledge of self-management in patients with T2DM in Mexico.   Method: A qualitative approach with semi-structured survey and a content analysis was used in this study.   Result: The participants perception is that self-management is of great importance in the treatment of T2DM. However,  patients need education and knowledge,  and the nurses are aware that they are responsible for  that education. Nevertheless,  the lack of time, inadequate nurse staffing and overwhelming number of patients, are causes that are not allowing them to  educate the patients. According to the participants, the engagement of the patients and family support are factors affecting the patients’ self-management.    Conclusions: The participants perception is that self-management is crucial for T2DM patients and the nurses have an important role in it. The use of a Person-Center Cared approach can help the nurses meet the needs of the patients.

La réduction des excursions glycémiques postprandiales a été proposée comme un moyen pour limiter le risque de développement du diabète de type 2. L’intérêt s’est donc porté sur les outils nutritionnels susceptibles de moduler la biodisponibilité des glucides et ainsi leur impact sur la glycémie postprandiale. Les travaux réalisés au cours de cette thèse avaient pour but d’étudier les effets de différents ingrédients modifiant la biodisponibilité du glucose, non seulement sur la glycémie postprandiale à court terme (2 heures) mais aussi sur les cinétiques du débit d’apparition et de disparition de glucose (total, exogène et endogène - isotopes stables) et les autres paramètres métaboliques de la phase postprandiale au cours de la journée. Dans la première étude (β-glucanes), nous avons montré que l’addition de fibres β-glucanes à un repas glucidique chez des sujets sains en surpoids ralentit l’absorption du glucose dans le plasma. Ceci a prolongé la réponse insulinique et par conséquent l’inhibition de la lipolyse et de la production endogène de glucose. Dans la deuxième étude (Eurostarch), nous avons montré que la diminution de la biodisponibilité du glucose au petit-déjeuner (amidon lentement digestible, index glycémique bas) diminue l’apparition du glucose exogène dans le plasma et pourrait avoir un effet second-repas chez des sujets sains en surpoids. Mais nous n’avons pas mis en évidence d’amélioration de ces effets métaboliques à plus long terme (5 semaines). Dans la troisième étude présentée (Nutriose), nous avons montré que l’addition de dextrine résistante NUTRIOSE®10 (fermentescible) au petit-déjeuner chez des sujets sains, diminue les réponses glycémiques, insuliniques postprandiales et le profil de ghréline au cours de la journée (en comparaison à une maltodextrine). En parallèle, la prolongation observée de la fermentation et l’oxydation du NUTRIOSE®10 pourraient fournir de l’énergie en phase postprandiale tardive. En conclusion, l’analyse des paramètres métaboliques au-delà de 2 heures après le repas, a permis de mettre en évidence les effets métaboliques à plus long terme de la modulation de l’apparition du glucose dans le plasma (ralentissement, prolongation, réduction) sur les cinétiques du glucose, la réponse insulinique, la lipolyse et l’oxydation des substrats / The reduction of the postprandial glycemic excursions has been proposed as to limit risk of type 2 diabetes. There has been growing interest in the development of dietary ingredients that could potentially modulate carbohydrates bioavailability and thus their impact on postprandial glycemia. The aim of this thesis was to investigate the effects of the the modulation of glucose bioavailability by different ingredients on 2-hour glycemic response but also on glucose kinetics (total, exogenous and endogenous – stable isotopes) and on other daylong metabolic parameters. In the first study (β-glucanes), we showed that the addition of β-glucan fiber to a carbohydrate meal in healthy overweight subjects reduced the appearance of glucose in plasma. As a consequence, insulin response was also prolonged and induced a prolonged inhibition on lipolysis and endogenous glucose production. In the second study (eurostarch), the reduction in glucose availability (slowly available glucose, low GI) at breakfast decreased plasma exogenous glucose appearance and tended to improve glucose control at the subsequent lunch. But we did not observe the improvement of such metabolic effects in the long-term (5 weeks). In the last study, we showed that the addition of a resistant dextrin, NUTRIOSE®10, decreased postprandial glycemic and insulinemic response as well as daylong satiety-related ghrelin profile, compared to maltodextrin. In parallel, the prolonged fermentation and oxidation pattern of NUTRIOSE®10 up to 10 hours after ingestion at breakfast could induced an extended energy release with NUTRIOSE®10 in the late postprandial phase. In conclusion, the follow-up of metabolic parameters beyond 2 hours after the meal have highlighted the longer-term metabolic effects of the modulation of glucose appearance in plasma (delay, extension, reduction) on glucose kinetics, insulin response, lipolysis and nutrients oxidation

<p>Obesity and nutrition-related non-communicable diseases continue to be major challenges that are increasing in severity worldwide. Science-centered carbohydrate dietary strategies may be a viable approach to help address such challenges. Recent reports from our laboratory indicate that certain carbohydrates with slow digestion profiles have the ability to trigger the gut-brain axis and reduce food intake and to slow gastric emptying and potentially affect appetite. Slow carbohydrate digestion may have other impacts on energy metabolism that have not been explored. In the current investigations, we sought to better understand the delayed gastric emptying profile of pearl millet-based foods as well as to understand how altering carbohydrate digestion rate impacts substrate utilization for energy.</p> <p>In the first study, the physical breakdown of pearl millet couscous particles in a simulated gastric environment (Human Gastric Simulator) was studied compared to wheat couscous matched in particle size, and select physicochemical properties of each type of couscous were characterized. Because we previously showed that pearl millet couscous had a marked delay in gastric emptying compared to white rice, boiled potatoes, and pasta in a human study in Mali, the objective of the first investigation was to test the hypothesis that pearl millet couscous was more resistant to breakdown in the stomach than wheat couscous and would take longer to empty. Our findings indicated that pearl millet couscous instead broke down into smaller, more numerous particles than wheat couscous. However, pearl millet had a slower starch hydrolysis property compared to wheat couscous per unit surface area. Pearl millet also had a smaller amylose chain length (839-963 DP) compared to wheat (1225-1563 DP), which may enable a denser packing of millet starch molecules that hinders hydrolysis. We also visually observed that the pearl millet particles formed a paste while breaking down that could reasonably generate viscosity in the stomach to potentially delay gastric emptying. </p> <p>Based off the findings from simulated gastric digestion, we next conducted a human study (<i>n</i>=14) in the U.S. to test the hypothesis that pearl millet-based foods (couscous – commercial and self-made, thick porridge) would reduce glycemic response, increase satiety, and delay gastric emptying compared to wheat couscous and white rice. We complemented this human study with additional <i>in vitro </i>work using an advanced gastrointestinal digestion system (TIMagc) to determine if the viscosity of pearl millet couscous particles as they were breaking down in the stomach was contributing to a decrease in gastric emptying. Our findings indicated that all the pearl millet-based foods and wheat couscous had lower overall glycemic response than white rice, but only the self-made millet couscous showed higher satiety through subjective appetitive response ratings. Surprisingly, there were no differences in gastric emptying among the foods. Additionally, the half-emptying times for these foods were all ~3 h, which is similar to the comparably low half-emptying times observed for white rice, boiled potatoes, and pasta in the previous Mali study. We now hypothesize that there may be diet-induced changes in gut-brain axis signaling when slowly digestible carbohydrates are consumed repeatedly over time, perhaps through modulating the number or sensitivity of small intestinal L-cells. We also found that millet couscous did not exhibit high viscosity in the TIMagc, suggesting that viscosity was not impacting its rate of gastric emptying. We conclude that at least some pearl millet-based foods possess a slow digestion property that may act to trigger the gut-brain axis or ileal brake to increase feelings of satiety or slow gastric emptying, but the discrepancy between U.S. and Malian populations requires further study. </p> <p>In the final investigation, we examined how altering carbohydrate digestion affected partitioning of carbohydrate versus fat for oxidation as well as the efficiency of switching oxidation between these two substrates (termed “metabolic flexibility”) in mice. Metabolic flexibility has been associated with good health related to decreased adipose tissue in the body and improved insulin sensitivity and may have implications on weight management. Carbohydrate digestion was adjusted by: (1) testing mice that lacked a complete set of enzymes by knocking out maltase-glucoamylase (Mgam; null) for moderating starch digestion versus testing wild-type mice; (2) using diets in these two groups of mice to moderate starch digestion that had different levels of resistant starch (53%, 35%, and 18%), had only raw corn starch or sucrose, or were high in fat; and (3) providing a supplement of fungal amyloglucosidase (AMG) to the mice treatment groups to increase starch digestion. Respiratory exchange ratio (RER) was measured through indirect calorimetry and mathematical modeling was used to characterize the diurnal shifts in RER (sine equation) as well as carbohydrate versus fat oxidation and metabolic flexibility (percent relative cumulative frequency [PRCF] with Weibull and Mixed Weibull Cumulative Distribution functions). Our results suggest that null mice lacking Mgam had somewhat increased metabolic flexibility than wild-type mice despite exhibiting minimal to no effects on carbohydrate oxidation. Intriguingly, the raw corn starch diet increased fat oxidation and generally promoted metabolic flexibility, although it did not increase carbohydrate oxidation relative to the other carbohydrate-predominant diets. Increasing carbohydrate digestion through AMG supplementation increased carbohydrate oxidation, and generally prompted earlier shifts to carbohydrate oxidation than without AMG supplementation. These findings provide a basis for better understanding the metabolic consequences of altering carbohydrate digestion and establish novel tools that can be utilized in future investigations. Overall, we propose that moderating carbohydrate digestion provides the ideal combination of balancing carbohydrate and fat oxidation while promoting metabolic flexibility. </p> <p>In conclusion, a slow digestion property may enable some types of pearl millet to trigger the ileal brake and gut-brain axis feedback systems to decrease glycemic response and increase satiety. Moreover, consuming carbohydrates with slow digestion may optimize substrate utilization for energy by the body. In addition to triggering the ileal brake and gut-brain axis, modulating carbohydrate digestion to more effectively switch between carbohydrate and fat for oxidation may be beneficial for weight management and metabolic disease prevention.</p>