O objetivo desse estudo foi avaliar o impacto da atenção farmacêutica em desfechos clínicos e na qualidade de vida de pacientes portadores de diabete melito tipo 2 (DM2) atendidos em um hospital de nível terciário de atenção à saúde. O estudo foi clínico controlado randomizado com 70 pacientes portadores de DM2, com mais de 45 anos, em uso de insulina e hemoglobina glicada (HbA1c) 8%. Os pacientes do grupo controle (GC) (n=36) receberam tratamento usual e os do grupo intervenção (GI) (n=34) receberam acompanhamento farmacoterapêutico individualizado e educação para o DM2. A amostra total foi composta principalmente por mulheres (61,4%), com uma média de idade aproximada de 61 anos e tempo de DM2 de cerca de 14 anos, sendo que os grupos eram homogêneos quanto a essas características (p>0,05). Após seis meses de intervenção, os conhecimentos sobre o diabetes e sobre os medicamentos aumentaram significativamente no GI, de 9,91±2,69 para 15,74±3,03 e de 4,47±0,84 para 6,58±1,29, respectivamente, ambos permanecendo inalterados no GC. A adesão ao tratamento farmacológico, para o GI, segundo o questionário Morisky-Green e o Questionário de Adesão a Medicamentos passou de 17,6% para 70,6% e de 29,4% para 52,9%, respectivamente (p<0,05), permanecendo inalterada no GC. Houve aumentos significativos na realização correta das técnicas de aplicação de insulina e de monitorização de glicemia capilar ao final após a intervenção. No início do estudo, a média de HbA1c era para o GC 9,61±1,38 e, para o GI 9,78±1,55 (p>0,05). Após a intervenção, a média de HbA1c do GI diminuiu significativamente para 9,21±1,41, o que não ocorreu para o GC (9,53±1,68) (p>0,05). Ao final do estudo houve melhora significativa da qualidade de vida relacionada ao diabete no GI enquanto que para o GC esse desfecho piorou significativamente. A atenção farmacêutica resultou em melhora significativa de desfechos clínicos e humanísticos dos pacientes com DM2 após seis meses de intervenção / The aim of this study was to evaluate the impact of a pharmaceutical care program on health outcomes and quality of life in patients with type 2 diabetes mellitus (T2DM) attending in a tertiary care center. The study was a randomized controlled, parallel-group trial with a 6-month follow-up carried out with 70 adults (45 years of age) with T2DM, taking insulin, with an HbA1c 8%. Patients in control group (CG) (n=36) received usual care and for those patients in intervention group (IG) (n=34) an individualized pharmacotherapeutic care plan and diabetes education were provided. Total sample was composed primarily of women (61,4%), with mean age of 61 years and duration of T2DM of 14 years and these characteristics were similar in the groups (p>0,05). After a 6-month follow-up, diabetes knowledge and medication knowledge significantly improved in IG, from 9,75±2,69 to 15,74±3,03 and from 4,47±0,84 to 6,58±1,29, respectively, and both outcomes remained unchanged in the CG. Adherence to medication for the IG according to the Morisky-Green questionnaire and to the Questionário de Adesão a Medicamentos varied, respectively, from 17,6% in baseline to 70,6% at end of the study and from 29,4% to 52,9% (p<0,05), with no changes in CG. There were significant improvements in the correct execution of insulin injections and home blood glucose monitoring techniques in the IG at the end of the study. At the beginning of the study HbA1c mean values were 9,61±1,38 in the CG and 9,78±1,55 in the IG (p>0,05). After the intervention, HbA1c mean values was reduced significantly to 9,21±1,41 in the IG and remained unchanged in the CG (9,53±1,68) (p>0,05). After the intervention the diabetes related quality of life significantly improved in IG while it worsened significantly in the CG. Pharmaceutical care resulted in significant improvement in health outcomes in patients with T2DM after 6-month follow-up

Introdução: A associação positiva entre circunferência da cintura (CC) e hipertensão arterial sistêmica (HAS), diabete melito (DM) e doença cardíaca (DC) é bem estabelecida e avaliada a partir de valores que evidenciaram essa associação em população adulta, porém, essa relação deve ser investigada em indivíduos idosos, devido às alterações fisiológicas desse grupo populacional. Objetivo: Analisar a associação entre valores de CC, mensurados em 2000, e HAS, DM E DC, referidas em 2006, e identificar valores de CC, com melhor capacidade discriminatória do risco para desenvolvimento dessas doenças, em idosos residentes no município de São Paulo. Métodos: Trata-se de estudo longitudinal com utilização de dados do Estudo SABE: Saúde, Bem-estar e Envelhecimento, realizado no município de São Paulo, em 2000 e em 2006. A população de estudo foi composta por idosos que não referiram HAS, DM e DC, em 2000, e que apresentavam valor de CC. As variáveis de estudo foram CC (variável contínua), índice de massa corporal (< 28 kg/m 2 e 28 kg/m 2 ), sexo, grupo etário (60 a 74 e 75) e etnia (caucasiana e outras), dados de 2000, e HAS, DM e DC referidas, em 2006. Para verificar a associação, utilizou-se o teste Rao & Scott (p<0,05) para amostra complexa, e regressão logística múltipla. A área sob a curva (AUC) ROC (Receiver Operating Caracteristics) foi utilizada para estimar o desempenho dos valores de CC, em discriminar corretamente idosos, segundo a referência ou não das doenças associadas à CC. Os valores críticos de CC foram identificados pelos maiores valores de razão de verossimilhança positiva, mantendo razão de verossimilhança negativa igual a zero. Para avaliar a capacidade discriminatória dos valores de CC identificados no presente estudo e dos valores de CC usualmente utilizados (CC 80 ou 88 cm, para mulheres, e CC 94 ou 102 cm, para homens), foi feita a comparação das AUC e respectivos intervalos de confiança de 95 por cento . Todos os cálculos foram realizados pelo programa estatístico Stata versão 10.0. Resultados: Foram analisados 405 idosos, dos quais 26,9 por cento referiram HAS, 4,1 por cento DM e 10,0 por cento DC. A CC, em 2000, manteve-se como fator de risco para referência de DM, em 2006, independente do sexo, grupo etário, etnia e índice de massa corporal (OR 1,10; IC 95 por cento 1,05-1,16; p=0,000; p do modelo=0,000). A AUC mostrou desempenho satisfatório dos valores críticos de CC, na discriminação da referência de DM, para mulheres e homens, de 60-74 anos. Os valores críticos de CC, identificados foram 87 cm para mulheres e 99 cm para homens, os quais apresentaram melhor desempenho segundo o valor de AUC, em comparação aos valores usualmente utilizados. Conclusão: Os valores críticos de CC, identificados no presente estudo, para indivíduos de 60-74 anos, apresentaram melhor capacidade discriminatória da referência de DM, em 6 anos, quando comparado aos valores de CC usualmente utilizados / Background: The positive association between waist circumference (WC) and hypertension (H), diabetes mellitus (DM) and heart disease (HD) is well established and evaluated from critic values that showed this association in adults, however, this relationship must be investigated in the elderly due to physiological changes in this population group. Objective: To analyze the association between WC values, measured in 2000, and H, DM and HD, reported in 2006, and identify WC values, with better discriminatory capacity of the risk for developing these diseases, in elderly residents in the municipality of São Paulo. Methods: This was a longitudinal study using data from the SABE Survey: Health, Wellness and Aging, held in São Paulo, in 2000 and 2006. The study population was comprised of elderly individuals who did not report H, DM and HD in 2000, and who had WC value. The study variables were WC (continuous variable), body mass index (<28 kg/m and 28 kg/m 2 ), sex, age group (60 to 74 and 75), and ethnicity (caucasian and others), information of 2000, and H, DM and HD, reported in 2006. To verify the association, the Rao & Scott test for complex sample was used (p <0.05), and multiple logistic regression. The area under the ROC (Receiver Operating Caracteristics) curve (AUC) was used to estimate the performance of WC values in correctly discriminating elderly, according to the reference or not of diseases associated with WC. WC critical values were identified by the highest positive likelihood ratio, and negative likelihood ratio equal to zero. To assess the discriminatory capacity of WC values identified in this study and the WC values commonly used (WC 80 ou 88 cm, for women, e WC 94 ou 102 cm, for men) was made the comparison of AUC and confidence intervals of 95 per cent . All calculations carried out by using Stata version 10.0. Results: Four hundred five elderly people were analyzed, of which 26.9 per cent reported H, 4.1 per cent DM and 10.0 per cent HD. The WC value in 2000, was a risk factor for DM reference, in 2006, regardless of sex, age group, ethnicity and body mass index (OR 1.10, 95 per cent CI 1.05-1.16, p=0.000, p model=0.000). The AUC showed satisfactory performance of WC critical values, in discriminating the DM reference to women and men of 60-74 years. The WC critical values identified were 87 cm, for women, and 99 cm, for men, which showed better performance according to the AUC value compared to the WC values commonly used. Conclusion: The WC critical values identified in this study, for individuals of 60-74 years, showed better discriminatory ability of reference of DM, in period of 6 years, compared to the WC values commonly used

Diabetes mellitus (DM) is a metabolic disorder of multiple etiology characterized by chronic hyperglycemia resulting from deficiency of insulin production and/or action. This state of hyperglycemia may cause a variety of cardiovascular, renal, neurological and eye complications. Adenosine deaminase (ADA) is an important enzyme responsible for regulation the levels of adenosine (ado) an important component of the system purinergic nucleoside. Changes in ADA activity has been demonstrated in several diseases, including DM. The Rutin (RT) is an abundant polyphenolic flavonoid found in food that exhibits multiple pharmacological activities including antibacterial, antitumoural, vasodilator and hepatoprotective activities. The objective of this study was to investigate the effect of RT on the activity of ADA in serum, tissues and biochemical parameters in models of diabetes induced by streptozotocin (STZ). Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ). RT (100 mg/kg/day) and glibenclamide (10mg/kg/day) were administered for 30 days, except for control groups (non diabetic and diabetic). Six groups of rats were used in the study and grouped based on fasting blood glucose levels after diabetes induction. The results showed an increase in ADA activity in serum and liver of diabetic rats, like transaminases (AST, ALT), -glutamyltransferase (-GT) and glucose. The RT at a concentration of 100 mg/kg was able to reduce the ADA activity in serum and liver tissue when compared with the diabetic control. The protective effect of RT was also observed increases the activity of enzymes ALT and -GT. Significant reductions were also observed in total cholesterol and LDL-cholesterol as well as in blood glucose levels in the diabetic group treated with RT. The results suggest that RT can improve hyperglycemia and hyperlipidemia, and restoring damaged liver function, as well as prevents the increase in ADA activity in serum and liver tissue on diabetic rats treated with this flavonoid. / O Diabetes mellitus (DM) é uma disfunção metabólica de múltipla etiologia caracterizado por hiperglicemia crônica resultante da deficiência da produção e/ou ação da insulina. Esse estado de hiperglicemia pode provocar uma série de complicações cardiovasculares, renais, neurológicas e oculares. A Adenosina deaminase (ADA) é uma importante enzima responsável por regular os níveis de adenosina (ado), um importante nucleosídeo componente do sistema purinérgico. Alterações na atividade da ADA têm sido demonstradas em várias doenças, incluindo o DM. A rutina (RT) é um flavonoide polifenólico abundante nos alimentos que exibe múltiplas atividades farmacológicas como atividade antibacteriana, antitumoral, vasodilatadora e hepatoprotetora. O objetivo deste estudo foi verificar o efeito da RT sobre a atividade da ADA sérica e tecidual e parâmetros bioquímicos em modelos de diabetes induzidos por estreptozotocina (STZ). O diabetes foi induzido através de injeção única intraperitoneal (i.p.) de 55 mg/kg de STZ. A RT (100 mg / kg / dia) e a glibenclamida (10mg/kg/dia) foram administradas durante 30 dias, com exceção dos grupos controles (não diabéticos e diabéticos). Seis grupos de ratos foram utilizados no estudo e agrupados com base nos níveis de glicose em jejum após a indução de diabetes. Os resultados demonstraram um aumento na atividade da ADA no soro e no fígado de ratos diabéticos, assim como das transaminases (AST, ALT), -glutamiltransferase (-GT) e glicose. A RT na concentração de 100 mg/kg foi capaz de reduzir a atividade sérica e em tecido hepático da ADA quando comparado com o controle. O efeito protetor da RT também foi observado sobe a atividade das enzimas ALT e -GT. Reduções significativas foram observadas no colesterol total e LDL-colesterol, bem como, na concentração sérica de glicose no grupo diabético tratado com RT. Os resultados sugerem que a RT pode melhorar a hiperglicemia e dislipidemia, restabelecer danos à função hepática, bem como é capaz de prevenir o aumento da atividade da ADA no soro e no fígado de ratos diabéticos tratados com este flavonoide.

Introdução: A associação positiva entre circunferência da cintura (CC) e hipertensão arterial sistêmica (HAS), diabete melito (DM) e doença cardíaca (DC) é bem estabelecida e avaliada a partir de valores que evidenciaram essa associação em população adulta, porém, essa relação deve ser investigada em indivíduos idosos, devido às alterações fisiológicas desse grupo populacional. Objetivo: Analisar a associação entre valores de CC, mensurados em 2000, e HAS, DM E DC, referidas em 2006, e identificar valores de CC, com melhor capacidade discriminatória do risco para desenvolvimento dessas doenças, em idosos residentes no município de São Paulo. Métodos: Trata-se de estudo longitudinal com utilização de dados do Estudo SABE: Saúde, Bem-estar e Envelhecimento, realizado no município de São Paulo, em 2000 e em 2006. A população de estudo foi composta por idosos que não referiram HAS, DM e DC, em 2000, e que apresentavam valor de CC. As variáveis de estudo foram CC (variável contínua), índice de massa corporal (< 28 kg/m 2 e 28 kg/m 2 ), sexo, grupo etário (60 a 74 e 75) e etnia (caucasiana e outras), dados de 2000, e HAS, DM e DC referidas, em 2006. Para verificar a associação, utilizou-se o teste Rao & Scott (p<0,05) para amostra complexa, e regressão logística múltipla. A área sob a curva (AUC) ROC (Receiver Operating Caracteristics) foi utilizada para estimar o desempenho dos valores de CC, em discriminar corretamente idosos, segundo a referência ou não das doenças associadas à CC. Os valores críticos de CC foram identificados pelos maiores valores de razão de verossimilhança positiva, mantendo razão de verossimilhança negativa igual a zero. Para avaliar a capacidade discriminatória dos valores de CC identificados no presente estudo e dos valores de CC usualmente utilizados (CC 80 ou 88 cm, para mulheres, e CC 94 ou 102 cm, para homens), foi feita a comparação das AUC e respectivos intervalos de confiança de 95 por cento . Todos os cálculos foram realizados pelo programa estatístico Stata versão 10.0. Resultados: Foram analisados 405 idosos, dos quais 26,9 por cento referiram HAS, 4,1 por cento DM e 10,0 por cento DC. A CC, em 2000, manteve-se como fator de risco para referência de DM, em 2006, independente do sexo, grupo etário, etnia e índice de massa corporal (OR 1,10; IC 95 por cento 1,05-1,16; p=0,000; p do modelo=0,000). A AUC mostrou desempenho satisfatório dos valores críticos de CC, na discriminação da referência de DM, para mulheres e homens, de 60-74 anos. Os valores críticos de CC, identificados foram 87 cm para mulheres e 99 cm para homens, os quais apresentaram melhor desempenho segundo o valor de AUC, em comparação aos valores usualmente utilizados. Conclusão: Os valores críticos de CC, identificados no presente estudo, para indivíduos de 60-74 anos, apresentaram melhor capacidade discriminatória da referência de DM, em 6 anos, quando comparado aos valores de CC usualmente utilizados / Background: The positive association between waist circumference (WC) and hypertension (H), diabetes mellitus (DM) and heart disease (HD) is well established and evaluated from critic values that showed this association in adults, however, this relationship must be investigated in the elderly due to physiological changes in this population group. Objective: To analyze the association between WC values, measured in 2000, and H, DM and HD, reported in 2006, and identify WC values, with better discriminatory capacity of the risk for developing these diseases, in elderly residents in the municipality of São Paulo. Methods: This was a longitudinal study using data from the SABE Survey: Health, Wellness and Aging, held in São Paulo, in 2000 and 2006. The study population was comprised of elderly individuals who did not report H, DM and HD in 2000, and who had WC value. The study variables were WC (continuous variable), body mass index (<28 kg/m and 28 kg/m 2 ), sex, age group (60 to 74 and 75), and ethnicity (caucasian and others), information of 2000, and H, DM and HD, reported in 2006. To verify the association, the Rao & Scott test for complex sample was used (p <0.05), and multiple logistic regression. The area under the ROC (Receiver Operating Caracteristics) curve (AUC) was used to estimate the performance of WC values in correctly discriminating elderly, according to the reference or not of diseases associated with WC. WC critical values were identified by the highest positive likelihood ratio, and negative likelihood ratio equal to zero. To assess the discriminatory capacity of WC values identified in this study and the WC values commonly used (WC 80 ou 88 cm, for women, e WC 94 ou 102 cm, for men) was made the comparison of AUC and confidence intervals of 95 per cent . All calculations carried out by using Stata version 10.0. Results: Four hundred five elderly people were analyzed, of which 26.9 per cent reported H, 4.1 per cent DM and 10.0 per cent HD. The WC value in 2000, was a risk factor for DM reference, in 2006, regardless of sex, age group, ethnicity and body mass index (OR 1.10, 95 per cent CI 1.05-1.16, p=0.000, p model=0.000). The AUC showed satisfactory performance of WC critical values, in discriminating the DM reference to women and men of 60-74 years. The WC critical values identified were 87 cm, for women, and 99 cm, for men, which showed better performance according to the AUC value compared to the WC values commonly used. Conclusion: The WC critical values identified in this study, for individuals of 60-74 years, showed better discriminatory ability of reference of DM, in period of 6 years, compared to the WC values commonly used

Le diabète est reconnu comme un problème majeur de santé publique causant des conséquences humaines et économiques redoutables. La phytothérapie s’offre comme une nouvelle avenue thérapeutique pour le contrôle de la glycémie. Le grenadier, Punica granatum, a servi de remède contre le diabète dans le système Unani de la médecine pratiquée en Inde et au Moyen Orient. Des études ont démontré un effet hypoglycémiant des extraits de grenadier via divers mécanismes notamment par une amélioration de la sensibilité à l’insuline et la régénération des cellules béta-pancréatiques. Cependant, aucune étude n’a démontré à ce jour, l’effet de grenadier sur le transport de glucose dans le muscle, étape cruciale dans la régulation de l’homéostasie glucidique postprandiale. De plus, l’effet de la maturation sur le potentiel antidiabétique du fruit de grenadier n’a pas été étudié. Ainsi, le but de ce projet est d’évaluer l’effet antidiabétique des extraits de grenadier sur le transport de glucose dans les cellules musculaires C2C12 en fonction de la variété et du stade de maturation du fruit et d’élucider les mécanismes d’action. Le choix des variétés du grenadier tunisien (Espagnoule [EP] et Gabsi [GB]) a été orienté pour leur pouvoir antioxydant et leur consommation locale. Deux parties de la plante ont été utilisées, les fleurs et les fruits à 3 stades de maturation soit 2, 4 et 6 mois. Les résultats ont montré que seule la variété du grenadier Gabsi stimule significativement le transport de glucose par rapport au contrôle (DMSO), et ceci sans être toxique. Cet effet est plus prononcé au stade de fruit mûr (à 6 mois) que celui de la fleur. De plus, l’extrait de fleurs stimule la voie insulino-indépendante de l’AMPK et augmente le niveau d’expression des transporteurs spécifiques de glucose (GLUT-4). Par contre, l’extrait de fruits mûrs, en plus de ces deux mécanismes, active fortement aussi la voie insulino-dépendante de l’AKT. En conclusion, cette étude présente un nouveau mécanisme d’action antidiabétique de grenadier (plus particulièrement du fruit mûr) qui est dépendant de la variété. / Diabetes is a major public health problem worldwide with astounding human and economic consequences. The seed and the flower of pomegranate (Punica granatum), a native plant of Central Asia and the Mediterranean regions, exhibited a hypoglycaemic effect in in vivo studies. However, the underlying mechanisms have not yet been elucidated. The aim of this project was to evaluate the effect of the flower and the fruit (at 3 maturation stages) of pomegranate on glucose transport in skeletal muscle cells and to determine the molecular mechanisms involved in this effect. To accomplish this, we chose two varieties of pomegranate cultivated in Tunisia (Gabsi [GB] and Espagnoule [EP]), which have been shown to be highly consumed in that area and to possess high antioxidant activity. Differentiated C2C12 cells were treated for 18 hours with 80% ethanolic extract of the flowers and fruits (at 2, 4, and 6 months) of each variety. Our results showed that the Gabsi variety of pomegranate significantly enhances glucose uptake, without any toxicity. This effect is more pronounced in the ripe fruit (6 months) than in the flower. In parallel, the ripe fruit stimulated both the insulin-dependent pathway (Akt) and the insulin-independent pathway (AMPK), while the flower stimulated the latter only. In addition, both flower and ripe fruit treatment resulted in enhanced expression level of GLUT-4 glucose transporter in the muscle. Hence, these results suggest that regulation of glucose transport in skeletal muscle is one of the components involved in the anti-diabetic effect of Tunisian pomegranate.

A síndrome metabólica (SM) e o diabete melito (DM) caracterizam-se por uma série de alterações no metabolismo de lipoproteínas, entre elas a hipertrigliceridemia e a redução nas concentrações de HDL-colesterol (HDL-C). Em estudo prévio demonstramos que indivíduos saudáveis, não obesos, com concentração de HDL-C abaixo de 40mg/dL, quando comparados àqueles com concentração de HDL-C acima de 60mg/dL, apresentam, no plasma, esteróis marcadores de absorção intestinal de colesterol alimentar diminuídos, e de síntese de colesterol aumentados. Achados semelhantes foram descritos por outros autores em portadores de SM e DM, sugerindo que a resistência à insulina participa na origem do distúrbio, embora não se saiba por quais mecanismos. Considerando nossos achados prévios, os objetivos deste estudo são investigar quais os mecanismos moleculares envolvidos nas alterações do metabolismo de colesterol presentes em indivíduos com concentrações alta (HIPERALFA, HDL-C > 60mg/dL, n = 36) ou baixa (HIPOALFA, HDL-C < 40mg/dL, n = 37) de HDL-C por meio de medida de: 1) conteúdo celular de colesterol e expressão gênica de enzimas e receptores críticos para a regulação intracelular de colesterol, tendo como modelo células linfomononucleares de sangue periférico; 2) parâmetros que regulam o metabolismo de lipoproteínas no plasma e que são influenciados pela insulina, tais como lecitina-colesterol aciltransferase (LCAT), lipoproteína lipase (LPL) e lipase hepática (LH) pós-heparina, proteína de transferência de colesterol esterificado (CETP), proteína de transferência de fosfolípides (PLTP) e pré- beta1 HDL. Os critérios de exclusão foram: diabete melito, IMC 30Kg/m2, tabagismo, consumo elevado de álcool e uso de fármacos capazes de interferir no metabolismo de lipoproteínas. Mostramos que, quando comparado ao grupo HIPERALFA, o grupo HIPOALFA apresentou maiores concentrações de insulina, triglicérides, ALT(TGP), índice HOMA, atividade de LCAT e LH, e menor atividade de LPL e concentração de pré-beta1 HDL. Não houve diferença entre os grupos com relação ao conteúdo celular de colesterol, à expressão dos genes estudados (ABCA1, ABCG1, SR-BI, LDLR, HMG CoA redutase, SREBP-1c e LXR alfa), às atividades de CETP e PLTP no plasma e à ultrassonografia de carótidas. Nossos resultados mostram que indivíduos com concentração alta ou baixa de HDL-C no plasma diferem com relação à sensibilidade à insulina, além de parâmetros envolvidos na regulação do metabolismo de lipoproteínas. Estes achados não se relacionaram com o metabolismo celular de colesterol no modelo estudado, mas sugerem que este quadro metabólico, cuja origem é desconhecida, precede o aparecimento, no decorrer da idade, de outras alterações típicas da síndrome metabólica no grupo com baixas concentrações de HDL-C no plasma / The metabolic syndrome (MS) and the diabetes mellitus (DM) are characterized for a series of alterations in lipoprotein metabolism as hypertriglyceridemia and reduced HDL-cholesterol (HDL-C) concentration. In previous study we demonstrated that healthy non obese subjects with HDL-C concentration below 40mg/dL, when compared with those with HDL-C above 60mg/dL, present low plasma sterol markers of alimentary cholesterol intestinal absorption and high plasma sterol markers of cholesterol synthesis. Similar findings have been described by others in subjects with MS and DM, suggesting that insulin resistance participates in the origin of the disorder, although by unknown mechanisms. Considering our previous findings, the objectives of this study are to investigate the molecular mechanisms involved in alterations of cholesterol metabolism in subjects with high HDL-C (HYPERALPHA, HDL-C > 60mg/dL, n = 36) or low HDL-C (HYPOALPHA, HDL-C < 40mg/dL, n = 37) concentration by means of measuring: 1) cellular cholesterol content and gene expression of critical enzymes and receptors involved in the intracellular cholesterol regulation, having peripheral blood mononuclear cells as model; 2) parameters that regulate the plasma lipoproteins metabolism and that are influenced by insulin, such as lecithin: cholesterol acyltransferase (LCAT), post-heparin hepatic (HL) and lipoprotein lipase (LPL), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP) and pre-beta1 HDL. The exclusion criteria were: diabetes mellitus, body mass index 30Kg/m2, smoking, heavy drinking and use of medications that interfere with lipoprotein metabolism. We demonstrated that, as compared with HYPERALPHA, the HYPOALPHA group presented higher insulin, triglycerides and alanine aminotransferase concentrations, HOMA index, LCAT and HL activities and lower LPL activity and pre-beta1 HDL concentration. There was no difference between the groups in the cellular cholesterol content, expression of genes (ABCA1, ABCG1, SR-BI, LDLR, HMG CoA reductase, SREBP-1c and LXR alpha), plasma CETP and PLTP activities and carotid ultrasonography. Our results show that subjects with high or low plasma HDL-C concentration differ in relation to insulin sensitivity and in parameters involved in lipoprotein metabolism regulation. These findings were not related to the cellular cholesterol metabolism in the studied model, but they suggest that this metabolic disturbance, whose origin is unknown, precedes the appearance, in the course of the human life of other typical alterations of metabolic syndrome in the low HDL-C concentration group

A incidência de diabete melito (DM) tem aumentado, principalmente em idosos. Evidências epidemiológicas mostram que obesidade e gordura abdominal constituem fator de risco para o desenvolvimento de DM. Objetivo: Verificar a associação da incidência de DM referida com obesidade e gordura abdominal, em coorte de idosos domiciliados no município de São Paulo/Brasil - 2000 e 2006. Casuística e métodos: Foram utilizados dados do Estudo SABE Saúde, Bem-estar e Envelhecimento, longitudinal, epidemiológico, de base domiciliar, realizado no município de São Paulo, em 2000 (2.143 idosos), e em 2006 (1.115 idosos). A população de estudo foi constituída por idosos ( 60 anos), de ambos os sexos, selecionados por amostra probabilística, e que não referiram DM, em 2000, e que apresentaram todos os dados necessários a este estudo. As variáveis analisadas foram: DM referida, com alternativa de resposta dicotômica (sim ou não), obesidade, pelo índice de massa corporal - IMC 30 kg/m², gordura abdominal (circunferência da cintura CC 88 cm, para mulheres, e 102 cm, para homens; e razão cintura/quadril RCQ 1, para homens, e 0,85, para mulheres) e características sociodemográficas (sexo, grupo etário, escolaridade, companhia no domicílio). Para verificar a associação entre as variáveis, utilizou-se teste Rao Scott, para amostra complexa, e regressão logística múltipla (p<0,05) e o programa Stata/SE 10.0 for Windows. Resultados: Dos 1.115 idosos, foram reavaliados 914, sendo que 72 constituíram os novos casos de Manuela F. de Almeida DM (7,7 por cento /1.000 pessoa/ano). Verificou-se que a maior proporção (58 por cento ) de indivíduos que referiram DM, era composta por mulheres. Ainda que a obesidade tenha se associado, positivamente, com referência de DM, constatou-se que a RCQ (OR=2,32; IC=1,47-3,67) e CC (OR= 2,33; IC=1,44-3,77) foram preditoras para DM referida. Conclusão: De todas as variáveis analisadas, apenas a gordura abdominal constituiu fator de risco para incidência da doença, no período de 6 anos / The incidence of diabetes mellitus (DM) has increased, mainly in aged persons. Epidemiological evidences show that obesity and abdominal fat constitute risk factor for development of DM. Objective: To verify the association the incidence of DM with obesity and abdominal fat, in cohort of elderly domiciled in São Paulo / Brazil - 2000 and 2006. Casuistic and methods: It were analized data of the SABE Survey, a longitudinal, epidemiologic and household based study, carried in the city of São Paulo, in 2000 (2,143 elderlies) and 2006 (1,115 elderlies). The study population was constituted by aged ( 60 years), of both gender, selected by probabilist sample, who did not reported DM, in 2000, with all necessary data to this study. The analized variables were: reported DM, with dicotomic answer (yes or no), obesity, by body mass index - BMI 30 kg/m², abdominal fat (waist circunference - WC 88 cm, for women, and 102 cm, for men; and waist-to-hip ratio WHR 1, for men, and 0.85, for women) and socio-demographics characterstics (gender, age group, educational status and home company). To verify the association among the variables, it was applied the Rao Scott test, for complex samples, multiple logistic regression (p<0.05) and statistical software Stata/SE 10.0 for Windows. Results: Out of the 1,115 elderlies, it were re-assessed 914, being 72 as new cases of DM (7.7 per cent /1,000 people/year). It was verified that a greater proportion (58 per cent ) of the subjects who reported DM, was Manuela F. de Almeida composed by females. Even though obesity was positively associated to reported DM, WHR (OR=2.33; IC=1.47-3.77) and WC (OR= 2.32; IC=1.44-3.67) were predictors for DM. Conclusion: Of all variables analized, only abdominal fat was considered risk factor for the incidence of this disease, in a period of 6 years

Introdução O nível de atividade física (NAF) insuficiente e estado nutricional (EN) inadequado conferem risco de desenvolvimento de hipertensão arterial e diabete, bem como dificultam o controle destas doenças. Assim, infere-se que os custos despendidos pelo SUS com medicamentos, internações e consultas de hipertensos e diabéticos apresentem relação inversa com NAF, incluindo a prática de caminhada e EN. Entretanto, estudos epidemiológicos que descrevam estes custos e analisem essas associações na população idosa são inexistentes no Brasil, o que dificulta a fundamentação para a implementação de políticas publicas para a economia de recursos. Objetivo Descrever os custos com procedimentos de saúde de idosos hipertensos e diabéticos e verificar qual a sua associação com NAF e EN, segundo sexo e grupos etários. Métodos A amostra foi constituída por 806 idosos com autorreferência à hipertensão e/ou diabete ( 60 anos) residentes no município de São PauloSP, participantes das três coortes do Estudo Saúde, Bem-estar e Envelhecimento SABE - em 2010. A variável dependente custo total anual (em Reais), foi estimada com base nos dados autorreferidos sobre uso de medicamentos, uso dos serviços ambulatoriais e internações hospitalares, retroativos a um ano da coleta de dados. A variáveis explanatórias: i) NAF foi estimada a partir de entrevista utilizando o International Physical Activity Questionnaire (IPAQ, versão curta), classificando os idosos segundo duração da realização de atividades físicas moderada, em ativos ( 150 minutos/semana) e insuficientemente ativos (< 150 minutos/semana); ii) Prática de caminhada, categorizada segundo frequência semanal: a) 4 dias/ semana; b) 1 a 3 dias/semana; c) não caminha. iii) EN, identificado pelo índice de massa corporal (IMC), classificando os idosos em dois grupos: a) IMC < 28 kg/ m²; b) IMC 28 kg/ m² (excesso de peso); as variáveis de controle foram o sexo, grupos etários (a. 70 anos; b. 65 a 69 anos; c. 60 a 64 anos); estado civil (a. casado; b. outros) e, escolaridade (a. sem escolaridade; b. 1 ano). A descrição dos custos segundo as NAF e EN foi representada pelos valores de média e IC95 por cento , mediana e P25 P75, valores mínimos e máximos. Modelos de regressão logística múltipla foram empregados para analisar as associações entre variáveis dependentes e explanatórias. O nível de significância foi estabelecido em 5 por cento e todas as análises foram realizadas considerando amostras complexas, por meio do software Stata, 13.0. 9 Resultados: A média de custo total anual por pessoa foi de R$ 732,54 e a soma dos custos relativa a 12 meses para os 806 idosos foi de R$ 609.587,20, sempre superiores para idosos em excesso de peso, com NAF insuficiente e para idosos que não caminham. Idosos em excesso de peso apresentaram chance 50 por cento superior de estarem no grupo de maior custo total anual (OR 1.49, IC95 por cento 1.01 2.18) e mais de 70 por cento superior de maior custo com medicamentos (OR 1.71, IC95 por cento 1.18 2.47). A ausência de caminhada significou a chance superior para maiores custos anuais com medicamentos (OR 1.63, IC95 por cento 1.06 2.51) e custos totais (OR 1.82, IC95 por cento 1.17 2.81). Todas as análises ajustadas por sexo e idade. O NAF não se associou aos custos totais e custo com medicamentos (p>0.05). Conclusão: Os custos para o controle de HAS e DM em idosos são altos e se associam inversamente à prática de caminhada e ao estado nutricional, especialmente em relação ao custo com o uso de medicamentos antihipertensivos e hipoglicemiantes. / Background- The insufficient physical activity level (PAL) as well the inadequate nutritional status (NS) increases the risk of hypertension and the development of diabetes, and difficult the control of theses diaseases. Thus, we can infer that the costs spent by the public health system to the management of hypertension and diabetes in the population would shows an inverse relationship with physical activity level, including engagement in walking, and nutritional status. However, epidemiological studies describing these costs and analyzing these associations among elderly population are non-existent in Brazil, which makes difficult the implementation of public policies for the economy of resource. Aim - To describe the health care costs among hypertensive and diabetic elderly people and to analyze the associations with PAL and NS according to sex and age groups. Methods - The sample consisted of elderly people with self-reported hypertension and/or diabetes ( 60 years-old) living in São Paulo-SP, participants of the three cohorts SABE Study (Health, Wellbeing and Aging), in 2010. The dependent variable (total annual cost - in Reais, R$) was estimated based on self-reported use of medication, use of outpatient services and hospital admissions, retroactive to one year of data collection. The explanatory variables: i) PAL was estimated from interview using the International Physical Activity Questionnaire (IPAQ, short version), classifying the elderly accorind to the time performing in moderate physical activity ( 150 minutes / week) and insufficiently active (< 150 minutes / week). ii) Engagement in walking, categorized according to the weekly frequency: a) 4 days / week; b) 1 to 3 days / week; c) does not walk. a) BMI < 28 kg/m2; b) BMI 28 kg / m² (overweight); the control variables were sex and age groups: a) 70 years; b) 65-69 years; c) 60 to 64 years. The description of the costs according to the PAL and NS was represented by mean values and 95 per cent , median and P25 -P75, minimum and maximum values. Multiple logistic regression models were emplyed to analyze associations. The level of significance was set at 5 per cent and all analyzes were performed considering complex samples, using the Stata software, 10.0. Results - The average of total annual cost was R$ 732.54 and the sum of costs on 12 months was R$ 609,587.20, always higher for elderly with excess weight, insufficient PAL and the elderly who do not engage in walking. The group of elderly with excess weight showed a 50 per cent chance of 11 being in the highest annual total cost group (OR 1:49, 95 per cent 1:01 to 2:18) and 70 per cent higher for the costs with medicine use (OR 1.71, IC95 per cent 1.18 2.47). The absence of walking had higher chance for highest costs with medication (OR 1.63, 95 per cent CI 1:06 to 2:51) and total costs (OR 1.82, 95 per cent CI 1.17 - 2.81). All analyzes adjusted for sex and age. The PAL was not associated to the total costs and cost with medication. Conclusion- The costs related to the control of hypertension and diabetes in the elderly are high and were inversely associated to the engagement in walking and nutritional status, especially in relation to the costs with the use of antihypertensive and hypoglycemic medication.

RESUME Contexte La maladie rénale chronique (MRC) constitue un problème mondial majeur de Santé publique. Son ampleur réelle en Afrique demeure inconnue. Malgré, les progrès réalisés dans lidentification et la prévention de la MRC et le traitement de la phase terminale de la maladie, ces domaines restent un grand défi en Afrique Sub-saharienne à cause du manque cruel des ressources nécessaires. Objectif Ce travail a pour objectif de cerner lépidémiologie de la MRC à Kinshasa en vue délaborer des stratégies de dépistage précoce et de prévention adaptées. Le but ultime est de contribuer à la réduction de la morbidité et la mortalité rénales mais aussi cardiovasculaires. Méthodes : Le présent travail est une revue synthétique de 4 études menées à Kinshasa : Une étude documentaire des 412 cas réalisée aux Cliniques Universitaires de Kinshasa (CUK), durant la période allant de Janvier 2001 à Décembre 2004 pour identifier le profil épidémiologique et clinique des patients atteints de la MRC. Les résultats de cette étude ont motivé le besoin dévaluer lampleur de la maladie dans la population et dans les structures de santé existantes. Il en a résulté trois études. Une étude épidémiologique de type transversal effectuée à partir de 503 ménages sélectionnés de manière aléatoire selon un plan de sondage à plusieurs degrés dans 10 des 35 Zones de santé composant Kinshasa, capitale de la République Démocratique du Congo (RDC). Une seconde étude, aussi de type transversal, réalisée à partir de 527 patients à risque de MRC, fréquentant neuf Centres de santé (CS) de niveau primaire et quatre hôpitaux de référence de la ville de Kinshasa. Une campagne de dépistage de la protéinurie et des facteurs de risque de la MRC chez 3.018 sujets. Résultats : Lanalyse des données enregistrées en milieu hospitalier a montré : Une augmentation annuelle progressive et inquiétante des proportions (60,6%, 65,9%, 67,4% et 70,5%) de la MRC admises aux CUK quasi exclusivement au stade terminal de la maladie nécessitant une prise en charge rapide par la dialyse péritonéale. Malheureusement, 11% seulement pouvaient accéder à ce traitement onéreux. La majorité des malades à prédominance masculine (sexe ratio 2,2/1) décèdent prématurément à un âge moyen (45,8±14,5 ans), à un moment de leur vie où ils sont encore économiquement très productifs. Les causes probables de la MRC chez ces patients sont la glomérulonéphrite chronique (37%), lhypertension artérielle (27%) et le diabète sucré (26%). Les études transversales dans la population générale et les institutions de santé traditionnelles de la ville de Kinshasa ont mis en évidence les caractéristiques épidémiologiques suivantes: La prévalence globale (tous les stades confondus) de la MRC est de 12% dans la population générale, mais 3% seulement sont conscients de leur état de rein. Celle de linsuffisance rénale chronique (IRC) estimée par le débit de filtration glomérulaire (DFGe) < 60 ml/min/1,73 m² est de 8%. Cette MRC touche particulièrement les adultes (52±15 ans). Les facteurs de risque potentiels de la MRC, liés à des maladies non transmissibles (MNT) sont en progression comparativement aux études antérieures. Ces facteurs sont lhypertension (28%), le diabète sucré (12%) et lobésité (15%). Dans les Centres de santé de Kinshasa, la prévalence globale de la MRC méconnue parmi les sujets à risque est le triple de celle rapportée dans la population générale de la même ville. Parmi cette population malade, les proportions de la MRC atteignent 44% chez les hypertendus, 39% chez les diabétiques ; 16% chez les obèses et 12% chez les sujets infectés par le Virus de limmunodéficience humaine (VIH). 82% des diabétiques avaient une glycémie à jeun non contrôlée (> 126 mg/dl) et 78% dhypertendus navaient pas une pression artérielle sous la cible la moins stricte, cest à dire contrôlée à moins de 140/90 mmHg. Les déterminants identifiés de lIRC ont été lhypertension (OR ajusté 3,3), le diabète sucré (OR 2) et la protéinurie (OR 2,9). Les principaux déterminants de DFGe < 60 ml/min/1,73 m² chez les diabétiques étaient lâge et la durée du diabète sucré. Les résultats de la campagne de dépistage de la protéinurie et des facteurs de risque de la MRC ont révélé ce qui suit : La prévalence de la protéinurie a été de 17%. Les autres facteurs de risque de la MRC identifiés chez les sujets en bonne santé apparente ont été: lhypertension (37%), le diabète sucré (9%), lobésité (11%) et le syndrome métabolique (5%). Pour identifier un cas de protéinurie, il est nécessaire de dépister 4 diabétiques, 5 hypertendus, 4 sujets avec syndrome métabolique, 5 sujets âgés de plus de 50 ans et 9 personnes ne présentant aucune des conditions susmentionnées. Les déterminants majeurs de la protéinurie étaient lâge > 50 ans (OR ajusté 1,4), le diabète sucré (OR 1,3), le surpoids (OR 1,2) et le niveau socio-économique bas (OR 1,4). Conclusion : Ces études établissent pour la toute première fois dans une population africaine la forte prévalence de la MRC et ses facteurs de risque notamment lhypertension, le diabète sucré, lobésité, lâge > 50 ans et linfection à VIH. La maladie affecte ladulte encore jeune comparée aux Etats-Unis où elle prédomine à la vieillesse. Nos études ont montré aussi à la fois la forte prévalence de la protéinurie chez les sujets sans facteurs de risque traditionnels précités, le déficit du dépistage précoce de la MRC et de prise en charge des facteurs de risque dans le système de santé traditionnel favorisant la référence tardive et/ou les décès prématurés, ainsi que les limites malheureuses par manque de moyens de la prise en charge de la maladie au stade tardif. Ces études plaident pour la nécessité dun renforcement de la capacité du personnel soignant dans le domaine de détection précoce et de prise en charge des MNT dont la MRC. Elles montrent également quun dépistage annuel de masse de la population de la protéinurie et des facteurs de risque de la MRC est faisable et pourra, nous lespérons, constituer la base dune élaboration dune politique nationale de prévention. Mots-clé : diabète sucré, équation (Cockcroft & Gault, MDRD), hypertension artérielle, maladie rénale chronique, prévalence, protéinurie. SUMMARY Background Chronic kidney disease (CKD) is a worldwide public health problem. Little is known about its burden in Africa. Despite the advances in identification and prevention of CKD and management of end stage renal disease (ESRD), sub-Saharan Africa has been left far behind regarding these advances. This is because of the scarcity of necessary resources. Objective This work was designed to ascertain the epidemiologic knowledge of CKD in Kinshasa in order to define suitable baseline preventive strategies. It would aims ultimately, to reduce the morbidity and mortality from renal disease and related cardiovascular events. Methods: This current work summarises results of 4 studies undertaken in Kinshasa: A retrospective cross sectional study of 412 cases which was done in the Academic hospital of Kinshasa (AHK), from January 2001 to December 2004 to identify the epidemiologic and clinical profile of patients with CKD. The results of this study motivated us to investigate the extent of the burden of CKD in the population and the existing structures of healthcare. Thus, three further studies were carried out; In an epidemiologic cross sectional study, 503 adult residents in 10 of the 35 health zones of Kinshasa, the capital of the DRC were studied in a randomly selected sample; In a second study of higher risk subjects, 527 people in primary and secondary health care areas in the city of Kinshasa were studied from a random sample of at-risk out-patients with hypertension, diabetes, obesity, or who were infected by HIV; Finally, a mass screening for proteinuria and CKD risk factors was conducted in Kinshasa which involved 3,018 subjects. Results: The analysis of the data recorded in health care had showed: An overwhelmingly annual increasing proportion of CKD (60.6%, 65.9%, 67.4% and 70.5%) in AHK, unfortunately for the majority at stage 5, in other words at ESRD. Tragically enough, only 11% of them could be treated by peritoneal dialysis depending on their financial resources. The majority of the patients are young males (sex ratio 2.2/1) undergoing premature death (45.8±14.5). The probable causes of CKD in these subjects were chronic glomerulonephritis (37%), hypertension (27%) and diabetes mellitus (26%). The cross-sectional studies in the general population and the traditional structures of health care (HC) of the city of Kinshasa highlighted the following: The overall prevalence of CKD is 12% in the general population, but only 3% of those with CKD were aware of their condition. The prevalence of chronic renal failure (CRF) (eGFR < 60 ml/min/1.73 m ²) is 8%; CKD affects particularly young adults (52±15 years); Risk factors for CKD considered in this study, including hypertension (28%), diabetes (12%) and obesity (15%), are increasing compared to the former studies. In HC, the overall prevalence of undiagnosed CKD among at-the risk subjects is three times higher the prevalence of CKD in the general population of the same city. In those with the at-risk conditions, the % of CKD was: 44% in the hypertensive, 39% in the diabetics; 16% in the obese and 12% in those who were infected by the human immunodeficiency virus (HIV). 82% of those with history of diabetes had fasting serum glucose levels (> 126 mg/dl), and 78% of those with a history of hypertension did not have blood pressure controlled to less than 140/90 mmHg. The strongest determinants of CRF or CKD 3+ were: hypertension (adjusted OR 3.3), diabetes (OR 2) and proteinuria (OR 2.9). The principal determinants of eGFR < 60 ml/min/1.73 m² in the diabetic patients were age and the duration of diabetes. The results of the campaign of early detection for proteinuria and CKD risk factors revealed that: The prevalence of proteinuria was 17%. The other CKD risk factors identified were: hypertension (37%), diabetes (9%), obesity (11%) and metabolic syndrome (5%). To identify 1 case of proteinuria, one would need to screen 4 persons with diabetes, 5 persons with hypertension, 4 subjects having metabolic syndrome, 5 subjects aged ≥ 50 years and 9 people without any of the conditions mentioned above. The strongest determinants of proteinuria were age > 50 years (adjusted OR 1.4), diabetes (OR 1.3) and overweight (OR 1.2) and low socioeconomic status (OR 1.4). Conclusion: This work documents for the first time in Africa the high prevalence of CKD and its risk factors mainly hypertension, diabetes, obesity and HIV infection. CKD affects younger people in DRC, in contrast to the United States, where CKD is more prevalent in older. Our work also shows the high prevalence of proteinuria among subjects with neither diabetes nor hypertension, the deficit of the early detection and management of CKD risk factors in the traditional health care system leading to late referral or premature deaths, and the limits of renal replacement treatment. They also show that an annual mass screening of the population for proteinuria and CKD risk factors is feasible and will, it is hoped, provide the basis for building a nationwide prevention strategy. Key words: chronic kidney disease, diabetes mellitus, equation (Cockcroft &Gault, MDRD), arterial hypertension, prevalence, proteinuria.

Le diabète est reconnu comme un problème majeur de santé publique causant des conséquences humaines et économiques redoutables. La phytothérapie s’offre comme une nouvelle avenue thérapeutique pour le contrôle de la glycémie. Le grenadier, Punica granatum, a servi de remède contre le diabète dans le système Unani de la médecine pratiquée en Inde et au Moyen Orient. Des études ont démontré un effet hypoglycémiant des extraits de grenadier via divers mécanismes notamment par une amélioration de la sensibilité à l’insuline et la régénération des cellules béta-pancréatiques. Cependant, aucune étude n’a démontré à ce jour, l’effet de grenadier sur le transport de glucose dans le muscle, étape cruciale dans la régulation de l’homéostasie glucidique postprandiale. De plus, l’effet de la maturation sur le potentiel antidiabétique du fruit de grenadier n’a pas été étudié. Ainsi, le but de ce projet est d’évaluer l’effet antidiabétique des extraits de grenadier sur le transport de glucose dans les cellules musculaires C2C12 en fonction de la variété et du stade de maturation du fruit et d’élucider les mécanismes d’action. Le choix des variétés du grenadier tunisien (Espagnoule [EP] et Gabsi [GB]) a été orienté pour leur pouvoir antioxydant et leur consommation locale. Deux parties de la plante ont été utilisées, les fleurs et les fruits à 3 stades de maturation soit 2, 4 et 6 mois. Les résultats ont montré que seule la variété du grenadier Gabsi stimule significativement le transport de glucose par rapport au contrôle (DMSO), et ceci sans être toxique. Cet effet est plus prononcé au stade de fruit mûr (à 6 mois) que celui de la fleur. De plus, l’extrait de fleurs stimule la voie insulino-indépendante de l’AMPK et augmente le niveau d’expression des transporteurs spécifiques de glucose (GLUT-4). Par contre, l’extrait de fruits mûrs, en plus de ces deux mécanismes, active fortement aussi la voie insulino-dépendante de l’AKT. En conclusion, cette étude présente un nouveau mécanisme d’action antidiabétique de grenadier (plus particulièrement du fruit mûr) qui est dépendant de la variété. / Diabetes is a major public health problem worldwide with astounding human and economic consequences. The seed and the flower of pomegranate (Punica granatum), a native plant of Central Asia and the Mediterranean regions, exhibited a hypoglycaemic effect in in vivo studies. However, the underlying mechanisms have not yet been elucidated. The aim of this project was to evaluate the effect of the flower and the fruit (at 3 maturation stages) of pomegranate on glucose transport in skeletal muscle cells and to determine the molecular mechanisms involved in this effect. To accomplish this, we chose two varieties of pomegranate cultivated in Tunisia (Gabsi [GB] and Espagnoule [EP]), which have been shown to be highly consumed in that area and to possess high antioxidant activity. Differentiated C2C12 cells were treated for 18 hours with 80% ethanolic extract of the flowers and fruits (at 2, 4, and 6 months) of each variety. Our results showed that the Gabsi variety of pomegranate significantly enhances glucose uptake, without any toxicity. This effect is more pronounced in the ripe fruit (6 months) than in the flower. In parallel, the ripe fruit stimulated both the insulin-dependent pathway (Akt) and the insulin-independent pathway (AMPK), while the flower stimulated the latter only. In addition, both flower and ripe fruit treatment resulted in enhanced expression level of GLUT-4 glucose transporter in the muscle. Hence, these results suggest that regulation of glucose transport in skeletal muscle is one of the components involved in the anti-diabetic effect of Tunisian pomegranate.