O Brasil possui diversas frutas nativas, algumas consideradas potentes fontes de compostos bioativos fenólicos (CBF) como, por exemplo, a cagaita (Eugenia dysenterica DC) que é um fruto nativo do bioma cerrado pertencente à família das Mirtáceas. Alguns CBF presentes nos frutos desta família são capazes de inibir as enzimas envolvidas na digestão dos carboidratos &#945;-amilase e &#945;-glicosidase in vitro. A inibição destas enzimas retarda a absorção de glicose sanguínea reduzindo, assim, a glicemia e insulinemia pós-prandial. O objetivo deste trabalho foi avaliar o efeito de sucos de cagaita, clarificado e não clarificado, ricos em elagitaninos e proantocianidinas, sobre a glicemia e insulinemia pós-prandial de indivíduos pré-diabéticos sem uso de fármacos capazes de influenciar o metabolismo de glicose e insulina, após o consumo de 50 g de pão francês. Três diferentes refeições foram consumidas pelos voluntários (n=14). A primeira foi composta por pão branco (50 g) mais água (300 mL) como controle; a segunda, pão branco (50 g) mais suco cagaita clarificado (300 mL), e a última refeição consistia em pão branco (50 g) mais suco de fruta cagaita não clarificado (300 mL). Os resultados mostraram que ambos os sucos reduziram quantidade total de glicose absorvida (AUC) em 56% (suco clarificado) e 71% (não clarificado) e insulina liberada em 59% (suco clarificado) e 69% (não clarificado), após a ingestão do pão branco. Embora a velocidade de incremento da glicose (VIG) não tenha apresentado diferenças significativas, o incremento absoluto de glucose (IAG), incremento percentual de glicose (IPG) e valores de pico de glicose (VPG) e insulina (VPI) foram significativamente menores do que os de controle (p < 0,05). Além disso, após a ingestão de sucos cagaita observou-se um aumento da capacidade antioxidante do plasma em indivíduos que consumiram as refeições (p < 0,05). / Brazil has several native fruits, some of them are considered potential sources of phenolic compounds. Cagaita (Eugenia dysenterica DC) is a native fruit from Cerrado region belonging to the Myrtaceae family. Some polyphenols presents in fruits of this family may be able to act on inhibition of enzymes related to carbohydrates such as &#945;-amylase and &#945;- glucosidase in vitro. The inhibition of those enzymes activities delays blood glucose absorption, thereby reducing postprandial glycemia and insulinemia. This study aimed to assess the effect of cagaita fruit juices, clarified and non-clarified, rich in phenolic compounds including ellagitannins and proanthocyanidins, on the postprandial blood glucose and insulin responses from a bread meal (50 g), in prediabetic humans who were not taking medications known to influence glucose or insulin metabolism. Three different meals were consumed by volunteers (n=14). The first one consisted of white bread (50 g) plus water (300 mL) as a control; the second one, white bread (50 g) plus clarified cagaita fruit juice (300 mL), and the last one white bread (50 g) plus non-clarified cagaita fruit juice (300 mL). The results showed that both cagaita fruit juices reduced the total amount of glucose absorbed (AUC) by 56% (clarified juice) and 71% (non-clarified) and insulin released by 59% (clarified juice) and 69% (non-clarified), after the ingestion of white bread. Although glucose incremental velocity (GIV) did not show significant differences, absolute increase of glucose (AIg), glucose incremental percentage (GIP) and peak values of glucose (GPV) and insulin (IPV) were significantly lower than those of control (p < 0.05). Also, after ingestion of cagaita juices it was observed an increased antioxidant capacity of plasma in subjects that consumed the meals (p < 0.05).

Submitted by (edna.saturno@ufrpe.br) on 2016-10-11T14:32:01Z No. of bitstreams: 1 Graziele Anahy de Sousa Aleixo.pdf: 843230 bytes, checksum: 901bb6f90c73356f618d782d2e601a75 (MD5) / Made available in DSpace on 2016-10-11T14:32:01Z (GMT). No. of bitstreams: 1 Graziele Anahy de Sousa Aleixo.pdf: 843230 bytes, checksum: 901bb6f90c73356f618d782d2e601a75 (MD5) Previous issue date: 2006-03-03 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The increase or decrease in the glucose concentration in the blood is a common endocrine alteration in human beings and animals that can cause serious consequences to their health condition. Dosing the glucose of patient with hypo or hyperglycemia allows the same ones to receive appropriate treatment, propitiating a better life quality. The present work had as object to determine the glycemic values of dogs using a portable glucometer (Accu-Chek® Advantage / Roche) projected for human patients, and to compare the results obtained with that equipment to those acquired with the enzymatic-colorimeter (GOD-POD) according to Trinder laboratorial method, since it is considered a standard technique. Once proving that exists a good correlation among the results obtained with the two methods, it becomes possible for the Veterinary Doctors to use the glucometer in their routine with the intention of diagnosing alteration in their patients' glycemia and nevertheless, obtain important information that will help to govern the therapeutic conducts in animals with diseases such as Diabetes mellitus. Another purpose of this work was to describe which factors can alter the precision of the results obtained with the portable glucometer. For the development of the research 53 animals of the canine species, of varied age, sex, weight and breed, assisted at the Veterinary Hospital of the Department of Veterinary Medicine (DMV) of the Rural Federal University of Pernambuco (UFRPE) were used). In 17 patients it was observed factors of risks that could alter the precision of the results in the glucometer, such as low hematocrit, inadequate soak of the test strip, a part of the sample was over the reagent strip or still, the accomplishment of the test passed the 15 seconds recommended by the manufacturer of the equipment, and as consequence, only 36 animals were considered eligible for the study of the evaluation of the portable glucometer in relation to the laboratorial method. It was concluded that the glucose dosage in dogs using the portable glucometer Accu-Chek® Advantage can be considered clinically useful, because the differences obtained among the methods are inside of the margin established by the regulators entities of the area. / O aumento ou a diminuição da taxa de glicose no sangue é uma alteração endócrina comum em seres humanos e animais, e que pode ocasionar graves conseqüências ao estado de saúde dos mesmos. Dosar a glicose sangüínea de pacientes portadores de hipo ou hiperglicemia permite que eles recebam adequado tratamento, propiciando uma melhor qualidade de vida. O presente trabalho teve como objetivo determinar os valores glicêmicos em cães utilizando um glicosímetro portátil (Accu-Chek® Advantage / Roche Diagnóstica Brasil Ltda.) projetado para pacientes humanos, e comparar os resultados obtidos com esse equipamento àqueles conseguidos com o método laboratorial enzimático-colorimétrico (GOD-POD) segundo Trinder, que é considerado uma técnica padrão. Uma vez comprovada que existe uma boa correlação entre os dois métodos, torna-se possível para os Médicos Veterinários utilizarem o glicosímetro na sua rotina com o intuito de diagnosticar alterações na glicemia de seus pacientes e, ainda assim, obterem informações importantes que vão ajudar a reger as condutas terapêuticas em animUma outra finalidade deste trabalho foi descrever quais fatores de risco podem alterar a precisão dos resultados obtidos com o glicosímetro portátil. Para o desenvolvimento da pesquisa foram utilizados 53 animais da espécie canina, de idades, sexos, pesos e raças variadas, atendidos no Hospital Veterinário do Departamento de Medicina Veterinária (DMV) da Universidade Federal Rural de Pernambuco (UFRPE). Em 17 pacientes foram observados fatores que poderiam alterar a precisão dos resultados no glicosímetro, como baixo hematócrito, embebição inadequada da tira teste, uma parte da amostra ficou por cima da tira reagente ou ainda, a realização do teste ultrapassou os 15 segundos recomendados pelo fabricante do equipamento e, como conseqüência, apenas 36 animais foram considerados elegíveis para o estudo da avaliação do glicosímetro portátil em relação ao método laboratorial. Concluiu-se que a dosagem de glicose em cães utilizando o glicosímetro portátil Accu-Chek® Advantage pode ser considerada clinicamente útil, pois as diferenças obtidas entre os métodos estão dentro da margem estabelecida pelos órgãos reguladores da área.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Individuals who are morbid may present hyperynsulinemia, dyslipidemia, arterial hypertension and insulin resistance. The axis GH/IGF-I is in change of assisting the regulation of numberless functions relates to insulin resistance and to cardiovascular risk factors associated with metabolic syndrome. The present study demonstrates the influence of bariatric surgery in the levels of the same substances in normal individuals. The (10) eutrophic individuals, who presented BMI below 25 kg/m2 as a control group, and ten (10) morbid obese individuals, that were observed during forty-five (45) days in preoperative and postoperative periods and submitted to Capella technique through videolaparoscopy. The Analysis statistics was carried through using test T of Student. Adopts a level of significance p<0, 05. It had significant difference (p= 0,0001) for the one for weight and BMC, between the group preoperative and control group, as well as between the obese individuals, when the preoperative and postoperative periods were compared. The levels of IGF-I had been lesser in group preoperative (p=0,0007) when compared with a control group. In the period of forty-days the level of IGF-I decreased still more, with a difference significant (p=0,0440) between the preoperative and postoperative obese, being the difference between this last group and the control group statistically significant (p=0,0002). The insulin level was significantly reduce when one compared the control and preoperative groups (p= 0,0167), being also significant the difference between preoperative and postoperative group (p=0,0189). It wasn t observe statistically difference in the insulin level between the control group and preoperative group (p= 0,8155). The insulin resistance was bigger for obese, with difference statistically significant between the control and preoperative (0,0190), as well as between the preoperative and postoperative groups (p=0,0340) and after forty five days didn t have more difference statistically significant between the postoperative and control groups (p=05722). Wasn t observed difference statistically significant the glycemia between the groups which were studied. It possible to conclude that bariatric surgery, over the forty-five days, induced significant reduce of body weight and BMI, a decreased of hyperynsulinemia and reduction of insulin resistance, e that the level of IGF-I in absolute values for the obese, before the surgery, was minor who the control group and reduced still more in postoperative. / Em indivíduos com obesidade mórbida, podem estar presentes hiperinsulinemia, dislipidemia, hipertensão arterial e resistência à insulina. O eixo GH/IGF-I tem papel de auxiliar na regulação de inúmeras funções relacionadas à resistência insulínica e aos fatores de risco cardiovasculares associados a síndrome metabólica. O presente estudo mostra a influência da cirurgia bariátrica nos níveis de IGF-I, glicemia e insulina em pacientes obesos mórbidos e a comparação dos níveis das mesmas substâncias em indivíduos normais. Da amostra fizeram parte dez (10) indivíduos eutróficos que apresentavam IMC abaixo de 25kg/m², como grupo controle, e dez (10) indivíduos obesos mórbidos, que foram acompanhados nos períodos pré e pós-operatório de quarenta e cinco (45) dias, submetidos a técnica de Capella por videolaparoscopia. A análise estatística foi realizada utilizando o teste t pareado e não pareado, adotando um nível de significância de p<0,05. Houve uma redução do peso e do IMC com significância estatística (p<0,0001) entre os indivíduos obesos, quando comparados nos períodos pré e pós-operatório. Os níveis de IGF-I no período de quarenta e cinco dias em média reduziram, sendo estatísticamente significantes (p=0,0002) em relação ao grupo controle. O nível de insulina reduziu significativamente com a cirurgia (p= 0,0189), reduzindo também a resistência à insulínica (p=0,0304), voltando o nível do hormônio, neste período observado, para valores sem diferença aos obtidos no grupo controle. A glicemia não apresentou diferença significante entre os grupos estudados. Pode-se concluir que a cirurgia bariátrica promove, no seguimento de 45 dias, redução significante de peso corporal e IMC, diminuição da hiperinsulinemia e redução da resistência à insulina, embora não sendo este período suficiente para se observar a sua influência nas concentrações de IGF-I.

O aumento do consumo de alimentos ricos em gorduras e carboidratos associado à reduzida prática de exercícios físicos pode ter como consequência o desenvolvimento da obesidade e de distúrbios metabólicos, tais como intolerância à glicose, resistência à insulina, diabetes tipo 2 e dislipidemias. O músculo esquelético contribui diretamente para o desenvolvimento e progressão dos distúrbios metabólicos, especialmente em decorrência da disfunção mitocondrial. Uma das ferramentas amplamente utilizada para o tratamento de distúrbios metabólicos é o treinamento físico, pois promove adaptações metabólicas no sentido oposto aos prejuízos metabólicos induzidos por dietas hipercalóricas. O presente estudo teve por objetivo avaliar se o treinamento físico aeróbio seria capaz de prevenir o desenvolvimento de distúrbios metabólicos induzidos por dieta hipercalórica composta por ração de cafeteria mais frutose e sacarose diluídas em água de beber em camundongos, e se essa resposta seria mediada por adaptações no músculo esquelético. Os resultados obtidos revelaram que o treinamento físico aeróbio preveniu os distúrbios metabólicos induzidos por dieta hipercalórica, tais como deposição de gordura, hiperfagia, hiperglicemia e aumento de pressão arterial, bem como melhorou a capacidade aeróbia. Essas respostas foram associadas apenas ao aumento na capilarização do músculo esquelético, já que a capacidade oxidativa determinada pela citrato sintase e a expressão da proteína PGC-1? não modificaram / The increased consumption of foods rich in fats and carbohydrates associated with reduced physical exercise may result in the development of obesity and metabolic disorders such as glucose intolerance, insulin resistance, type 2 diabetes and dyslipidemia. Skeletal muscle contributes directly to the development and progression of metabolic disorders, especially as a result of mitochondrial dysfunction. One of the tools widely used for the treatment of metabolic disorders is physical training, which promotes metabolic adaptations in the opposite direction to metabolic damage induced by hypercaloric diets. The present study aimed to evaluate whether physical training could prevent the development of metabolic disorders induced by hypercaloric diet consisting of cafeteria diet plus fructose and sucrose diluted in drinking water in mice, and if this response was mediated by adaptations in skeletal muscle. The results showed that physical training prevented metabolic disorders induced by hypercaloric diet, such as fat deposition, hyperphagia, hyperglycemia, increased blood pressure, and improved aerobic capacity. These responses were associated only with the increase in skeletal muscle capillarity, because oxidative capacity citrate synthase and protein expression of PGC-1? did not change

O Diabetes mellitus é um distúrbio metabólico de etiologia múltipla que leva a uma hiperglicemia, podendo ocasionar inúmeras disfunções e falências de alguns órgãos e também alterações em cavidade oral. Estudos demonstraram diminuição da glicemia de ratas diabéticas com o uso de laser de baixa potência (LBP) em glândulas salivares. Como o insulin-like growth factor 1 (IGF-1) tem uma estrutura semelhante a da insulina, podendo mimetizar algumas de suas funções, o objetivo do presente trabalho foi analisar o efeito da irradiação com LBP na concentração de IGF-1, nas glândulas parótidas (GP) e submandibulares (GSM), e o efeito na glicemia de ratas diabéticas induzidas por estreptozotocina. Ratas da raça Wistar foram utilizadas e receberam uma injeção intraperitoneal de estreptozotocina ou de tampão conforme o grupo ao qual pertenciam, C (controle) ou D (diabético). Posteriormente, as ratas foram divididas em 4 subgrupos (C0, D0, C5 e D5), de acordo com a dose de irradiação recebida (0 ou 5 J/cm²). O estado diabético dos animais foi confirmado através da glicemia e, após 29 dias, os animais foram submetidos à simulação ou irradiação. O LBP utilizado foi o Photon Lase III (DMC Equipamentos LTDA®). Vinte e quatro horas após o procedimento os animais foram sacrificados para coleta de sangue e das glândulas salivares para as análises da glicemia (método da glicose oxidase e do glicosímetro) e concentração de IGF-1, respectivamente. Os resultados foram analisados pelo teste estatístico de Análise de Variância (ANOVA) e teste de contraste de Tukey, admitindo-se significância de 5%. A glicemia do dia do sacrifício, dos animais diabéticos que receberam irradiação, estava diminuída quando comparada com a glicemia de sacrifício dos animais diabéticos que não receberam o laser (p0,05). Além disso, a glicemia de sacrifício dos animais diabéticos irradiados foi menor que a aferida no dia do diagnóstico, quando foi utilizado o método do glicosímetro (p0,05). A concentração de IGF-1, entretanto, não sofreu influência da doença e nem da irradiação, se mostrando alterada somente quando comparada a GP e GSM. Com base nestes resultados podemos concluir que o LBP pode alterar a glicemia dos animais diabéticos, no entanto, este efeito parece não estar relacionado com a concentração de IGF-1. / Diabetes mellitus is a metabolic disorder of multiple etiologies that leads to hyperglycemia and can cause numerous dysfunctions and failures of some organs and also changes in the oral cavity. Studies have shown a decrease on glucose blood concentration in diabetic rats when low-power laser was used upom salivary glands. As insulin-like growth factor 1 (IGF-1) has a structure similar to insulin, the aim of this study was to analyze the effect of low-power laser irradiation on IGF-1 concentration of the parotid and submandibular glands as well as on glycemia of diabetic rats induced by streptozotocin. Wistar rats were used and received an intraperitoneal injection of streptozotocin or buffer, depending on the group to which they belonged, being C (control) or D (diabetic). Subsequently, the rats were divided into 4 subgroups (C0, D0, C5 and D5) according to the irradiation dose received (0 or 5 J / cm ²). The diabetic state of the animals was confirmed by blood glucose concentration and, after 29 days, the animals were subjected to irradiation or simulation, depending on the group to which they belonged. The laser used was the Photon Lase III (DMC Equipamentos LTDA®). Twenty-four hours after the procedure, the animals were sacrificed and blood and the salivary glands were collected to analyse the glycemia and IGF-1 concentration, respectively. The results were analyzed by Analysis of Variance statistical test (ANOVA) and Tukey\'s contrast test, assuming a significance of 5%. The sacrifice day glycemia of diabetic animals that received irradiation was decreased in comparison with the sacrifice day glycemia of non-irradiated diabetic animals as well as was lower than that measured on the day of diagnosis of irradiated animals (p0,05). The concentration of IGF-1, however, was not affected by diabetes or irradiation. However, IGF-1 concentration was increased on parotid than submandibular glands. Based on these results of the present study, we conclude that LBP can decrease blood glucose concentration of diabetic animals, however, this effect does not appear to be related to the concentration of IGF-1.

Algumas frutas nativas brasileiras podem ser consideradas excelentes fontes de compostos bioativos de natureza fenólica. Destacamos, dentre elas, o cambuci, o araçá, o camu-camu, a cagaita, algumas espécies de maracujá silvestres e a jabuticaba. Alguns destes compostos são capazes de inibir as enzimas do metabolismo de carboidratos in vitro. A inibição das enzimas &#945;-amilase e &#945;-glicosidase retardam e prolonga o tempo de digestão de carboidratos reduzindo, assim, a proporção e a velocidade de glicose absorvida e, consequentemente, o aumento brusco de glicose pós-prandial no plasma. Os objetivos deste trabalho foram avaliar o efeito de sucos clarificados de frutas nativas brasileiras sobre a glicemia pós-prandial em seres humanos, após consumo de uma unidade de pão branco (Tipo pão francês com aproximadamente 55 g), e estudar o efeito dos compostos fenólicos purificados a partir dos sucos sobre as enzimas &#945;-amilase e &#945;-glicosidase in vitro. Os resultados obtidos mostraram que todos os sucos clarificados, excetuando-se o de maracujá-alho (Passiflora tenuifila Killip), tiveram efeito positivo sobre a glicemia pós-prandial, causando redução da quantidade total de glicose absorvida (cambuci (campomanesia phae O.Berg.), cagaita (Eugenia dysenterica DC), camu-camu (Myciaria dúbia Mc Vaugh) e araçá (Psidium guineensis Sw)), aumento no tempo para atingir a concentração sanguínea máxima de glicose (camu-camu e cambuci), diminuição na velocidade de incremento da glicose (cambuci, cagaita, camu-camu, araçá e jabuticaba (Myrciaria cauliflora Berg)) e diminuição do incremento percentual da glicose (todos os sucos exceto o de maracujá-alho). O consumo dos sucos causou ainda aumento da capacidade antioxidante do plasma. Os compostos fenólicos purificados a partir dos sucos testados foram capazes de inibir a atividade das enzimas &#945;-amilase e &#945;-glicosidase in vitro, sendo que, excetuando-se o suco de jabuticaba, todos foram mais eficientes que a acarbose na inibição da &#945;-glicosidase / Some native Brazilian fruit can be considered excellent sources of bioactive compounds of phenolic nature. Featuring, among them, the cambuci, the araça, camu-camu, the cagaita, some species of wild passion and jabuticaba. Some of these compounds are able of inhibiting the enzymes of carbohydrate metabolism in vitro. Inhibition of the enzymes &#945;-amylase and &#945;-glycosidase slow and prolongs the digestion of carbohydrates, thus reducing the rate and velocity of glucose absorbed and therefore the sudden increase of postprandial glucose in plasma. The objectives of this study were to evaluate the effect of fruit juices clarified Brazilian native on postprandial glycemia in humans following consumption of a unit of white bread (French bread type with approximately 55 g), and study the effect of phenolic compounds purified from the juices of the enzymes &#945;-amylase and &#945;-glucosidase in vitro. The results showed that all juices clarified, except the passion fruit garlic (Passiflora tenuifila Killip), had a positive effect on postprandial glycemia, causing reduction in the total amount of glucose absorbed (cambuci (Campomanesia phae O.Berg .), cagaita (Eugenia dysenterica DC), camu-camu (Myciaria dubious Mc Vaughn) and araça (Psidium guineensis Sw)), increase in the time to reach maximum blood concentration of glucose (camu-camu and cambuci), decrease in speed of glucose increment (cambuci, cagaita, camu-camu, araça and jabuticaba (Myrciaria cauliflora Berg)) and decreased percentage increase in glucose (all except the passion garlic fruit juices). The consumption of juice also caused an increase in plasma antioxidant capacity. Phenolic compounds purified from the juices tested were able to inhibit the activity of enzymes &#945;-amylase and &#945;-glycosidase in vitro, and, except for the juice jabuticaba, all were more efficient than acarbose in inhibiting &#945;- glycosidase

Background: The most patients in intensive care experience hyperglycemia. These may include patients with pre-existing diabetes or stress hyperglycemia as an organism's offense reaction. Our aim is not only to correct this hyperglycemia early by a reserve, but also to prevent acceleration of hyperglycemia above their commended level. In addition to insulin, the correct choice of enteral nutrition can prevent not only hyperglycemia but also glycemic variability, which seems to be a much greater risk for these patients than stable tolerable hyperglycemia. In addition to diabetic-specific formulas, whey-based enteral nutrition can support our pursuit of optimal glycemia, due to its insulinotropic effect and its ability to stimulate incretin release. Much evidence will still be needed to confirm these benefits, but we can already look at whey not only as a source of quality protein, but also as a diet with a potential to limit glycemic variability. Objective: The aim of the study was to evaluate the effect of enteral nutrition based on whey (Peptamen Intense) on parameters associated with the assessment of glycemia in intensive care patients. Assess whether there is a relationship between the variables and draw conclusions with possible application in practice. Methods: Thirty-seven patients were...

Objective: To assess whether the prevalence of low physical activity levels and time spent watching TV differ depending on glycemia status. Methods: A secondary analysis using data from a population-based study was conducted. Two were the outcomes: physical activity levels, derived from the International Physical Activity Questionnaire, and sitting time watching TV. The exposure was glycemia status, defined based on results of the oral glucose tolerance tests (OGTT): euglycemia, dysglycemia, and T2DM. The T2DM group was further split into: aware and unaware of T2DM diagnosis. Prevalence ratios (PR) and 95% CI were reported using Poisson regression models. Results: Data of 1607 individuals, mean age 48.2 (SD: 10.6) years, 809 (50.3%) females, were analyzed. Dysglycemia and T2DM was present in 16.9% (95% CI: 15.1%–18.8%) and 11.0% (95% CI: 9.5%–12.6%) of participants, respectively. A total of 605 (37.6%; 95% CI: 35.2%–39.9%) participants had low levels of physical activity and 1019 (63.3%; 95% CI: 60.9%–65.7%) subjects spent ≥2 h per day sitting watching TV. In multivariable model, there was no significant association between glycemia status and physical activity levels (PR = 1.14; 95% CI: 0.95–1.36). Similar result was found between glycemia status and sitting time watching TV. However, those aware of T2DM diagnosis were more likely to have low levels of physical activity (PR = 1.31; 95% CI: 1.06–1.61) compared to the euglycemia group. Conclusions: We found a no relationship between glycemia status and physical activity level or sitting time watching TV, pointing out similar levels of physical (in)activity among those with euglycemia, dysglycemia and T2DM. Individuals aware of having T2DM were 30% more likely to have low physical activity levels compared to the euglycemic group. There is a need to increase physical activity levels among T2DM individuals. / Revisión por pares

Objective: Up-regulated expression of transcription-factor E2F1 in human visceral adipose tissue (VAT) characterizes a dysmetabolic obesity sub-phenotype. An E2F1-miRNA network has been described in multiple cancers. Here we investigated whether elevated VAT-E2F1 in obesity is associated with VAT-miRNA alterations similar to, or distinct from, those described in cancer. Furthermore, we assessed if E2F1-associated miRNA changes may contribute to the link between high- VAT-E2F1 and a dysmetabolic obesity phenotype. Methods: We assembled a cohort of patients with obesity and high-VAT-E2F1, matched by age, sex, ±BMI to patients with low-VAT-E2F1, with and without obesity (8 patients/groupX3 groups). We performed Nanostring -based miRNA profiling of VAT samples from all 24 patients. Candidate E2F1-related miRNAs were validated by qPCR in an independent cohort of patients with extreme obesity, with or without type-2-diabetes (T2DM) (n = 20). Bioinformatic tools and manipulation of E2F1 expression in cells were used to establish the plausibility of the functional VAT-E2F1-miRNA network in obesity. Results: Among n = 798 identified miRNAs, 17 were differentially expressed in relation to E2F1 and not to obesity itself. No evidence for the cancer-related E2F1-miRNA network was identified in human VAT in obesity. In HEK293-cells, overexpression/downregulation of E2F1 correspondingly altered the expression of miRNA-206 and miRNA-210-5p, two miRNAs with reported metabolic functions consistent with those of E2F1. In VAT from both cohorts, the expression of both miRNA-206 and 210-5p intercorrelated, and correlated with the expression of E2F1. In cohort 1 we did not detect significant associations with biochemical parameters. In cohort 2 of patients with extreme obesity, all those with high VAT-E2F1 showed a diabetes-complicated obesity phenotype and higher expression of miRNA-206 and miRNA-210-5p, which also correlated with fasting glucose levels (both miRNAs) and fasting insulin (miRNA-210-5p). Conclusions: Whilst the previously described cancer-related E2F1-miRNA network does not appear to operate in VAT in obesity, miRNAs-206 and 210-5p may link high-E2F1 expression in VAT with diabetes-complicated extreme obesity phenotype.

Introduction: The homeostatic role of the endocannabinoid system (ECS) is mediated through the actions of endocannabinoids. Intake of exogenous cannabinoids found in Cannabis sativa alter the function of the ECS which may then impact other organ systems. Use of cannabis has been inconsistently linked to adverse cardiometabolic outcomes. Rates of cannabis use are high among patients with psychiatric conditions who are already at higher risk of cardiometabolic diseases when compared to the general population. Cannabis use patterns and cardiometabolic risk variables in this population need further study to clarify the links between use and outcomes. Methods: Patients with psychiatric conditions from the St. Joseph’s Healthcare Hamilton Hospital were enrolled into the Cannabis and Physical Health study. Sociodemographic data, medical history, cigarette use, and cannabis use patterns were collected. In addition, cardiometabolic profile data were collected including body mass index, blood pressure, lipids, and HbA1c. Multivariable regression analyses were conducted, and a Bonferroni correction applied. Results: This cross-sectional study enrolled 200 patients (female: n=86, 43.0%), 18 years of age and older. Among 79 cannabis users (female: n=34, 43.0%), the majority (n=53, 67.1%) consumed cannabis daily and had a diagnosis of a moderate cannabis use disorder (CUD; n=57, 72.2%, CUD score = 4.3 ± 3.4). Use of cannabis was initiated on average at 15.2 ± 3.5 years of age and used for an average of 13.5 ± 11.0 years. There was no association between cannabis use and cardiometabolic risk factors when adjusted for age, sex, psychiatric diagnosis, antipsychotic medication use, and cigarette smoking (P>0.006 for all outcomes). Conclusions: Our findings indicate that in this sample of patients with psychiatric diagnoses, patients who use cannabis had a similar cardiometabolic profile to non-users. Patterns of cannabis use highlight the importance of reducing cannabis consumption and preventing or slowing the progression of CUD in this population, as well as limiting adolescent exposure to cannabis. / Thesis / Master of Science (MSc) / The endocannabinoid system regulates several processes in the body via endocannabinoid signaling, and cannabinoids found in cannabis can change endocannabinoid system function. Cardiovascular events and changes in appetite have been noted with cannabis use, and this is especially important in some vulnerable populations at risk of increased cannabis use; one of these groups include patients with psychiatric conditions who tend to use cannabis but also already have an increased cardiometabolic risk. In this thesis, the relationship between cannabis use and cardiometabolic risk was examined in 200 patients, and patterns and determinants of cannabis use explored. Our results demonstrated that of the 79 cannabis users, most consumed cannabis daily, and had a moderate cannabis use disorder. On average, users began cannabis consumption at 15 years of age and for an average duration of 14 years. Moderate cannabis use was not related to cardiometabolic risk in these patients. Our data demonstrate the need to prevent or slow the progression of cannabis use disorder in these patients and the importance of reducing early exposure of adolescents to cannabis.