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1.
J Assoc Physicians India ; 67(7): 18-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559762

RESUMO

Objectives: Hemoglobin A1C (HbA1C) estimation is the standard and commonly used method for diagnosis and monitoring of diabetes therapy. We conducted a questionnaire based survey to understand the Indian physician's adherence to HbA1C for effectively managing Type 2 diabetes mellitus (T2DM) patients and its influence on the decision making process. Methods: A validated questionnaire comprising of 10 questions was administered to physicians/endocrinologists at the 44th Annual Conference of RSSDI-2016, Hyderabad. The questions of the survey were designed to understand average cutoff HbA1C level for physicians to start the mono-therapy or combination therapy with or without insulin along with preferred class of Oral anti-diabetic drugs (OAD) in Indian T2DM patients. Results: 41% physicians selected HbA1C level in between 7.0-7.4% to start mono-therapy while 94.5% chose metformin as the first line OAD. In metformin uncontrolled patients, 56.8% responders chose to start a DPP4 inhibitor. To initiate dual therapy 42.9% responders chose HbA1c level of 8.0-8.4% while for triple therapy 37.1% responders selected HbA1c level of 9.0-9.4%. Conclusion: This survey shows the management patterns of T2DM patients by Indian physicians are in line with western guidelines especially AACE. Though guidelines do not offer stringent recommendation on first/second add-on class of OADs, DPP4i emerged as preferred choice for mono-therapy in metforminintolerant patients and as first add-on in patients uncontrolled on metformin alone.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hemoglobina A Glicada/metabolismo , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Quimioterapia Combinada , Humanos , Hipoglicemiantes , Índia , Médicos , Inquéritos e Questionários
2.
J Agric Food Chem ; 67(38): 10614-10623, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31483658

RESUMO

Type 2 diabetes (T2D) is a pandemic disease chiefly characterized by hyperglycemia. In this study, the combination of serum lipidomic and metabolomic approach was employed to investigate the effect of arabinoxylan on type 2 diabetic rats and identify the critical biomarkers of T2D. Metabolomics analysis revealed that branched-chain amino acids, 12α-hydroxylated bile acids, ketone bodies, and several short- and long-chain acylcarnitines were significantly increased in T2D, whereas lysophosphatidylcholines (LPCs) were significantly decreased. Lipidomics analysis indicated T2D-related dyslipidemia was mainly associated with the increased levels of acetylcarnitine, free fatty acids (FFA), diacylglycerols, triacylglycerols, and cholesteryl esters and the decreased levels of some unsaturated phosphatidylcholines (less than 22 carbons). These variations indicated the disturbed amino acid and lipid metabolism in T2D, and the accumulation of incompletely oxidized lipid species might eventually contribute to impaired insulin action and glucose homeostasis. Arabinoxylan treatment decreased the concentrations of 12α-hydroxylated bile acids, carnitines, and FFAs and increased the levels of LPCs. The improved bile acid and lipid metabolism by arabinoxylan might be involved in the alleviation of hypercholesterolemia and hyperlipidemia in T2D.


Assuntos
Anticolesterolemiantes/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipolipemiantes/administração & dosagem , Xilanos/administração & dosagem , Aminoácidos de Cadeia Ramificada/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Carnitina/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Metabolismo dos Lipídeos , Lipídeos/química , Metabolômica , Ratos
3.
Rev Assoc Med Bras (1992) ; 65(8): 1042-1047, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531599

RESUMO

BACKGROUND: We investigated the serum annexin V and anti-annexin V levels and their relationship with metabolic parameters in patients recently diagnosed type 2 diabetic. METHODS: A total of 143 patients recently diagnosed type 2 diabetes and 133 control subjects were included in the study. Body mass index (BMI), hs-CRP, HOMA-IR, carotid intima-media thickness, and serum levels of annexin V and anti-annexin V were investigated. RESULTS: HOMA-IR, serum hs-CRP, and carotid intima-media thickness were found to be statistically significant. The Pearson correlation analysis revealed a statistically significant positive relationship between the carotid intima-media thickness and the annexin V level (r=0.29, p=0.006*). A statistically significant positive relationship was also detected between the Annexin V level and level of serum hs-CRP (r=0.29 p=0.006*). CONCLUSION: A positive relationship was observed between the carotid intima-media thickness and annexin V at the end of our investigation. In this regard, we also believe that serum levels of annexin V may be increased for cardiovascular protection in the elevation of carotid intima-media thickness.


Assuntos
Anexina A5/sangue , Autoanticorpos/sangue , Diabetes Mellitus Tipo 2/sangue , Adulto , Idoso , Anexina A5/imunologia , Anexina A5/metabolismo , Índice de Massa Corporal , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade
4.
Chem Pharm Bull (Tokyo) ; 67(8): 824-838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31366832

RESUMO

We synthesized and evaluated novel 5-[2-(thiophen-2-yl)propan-2-yl]-4H-1,2,4-triazole derivatives as 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors. Optimization of the thiophene ring and the substituents on the 1,2,4-triazole ring produced 3,4-dicyclopropyl-5-{2-[3-fluoro-5-(trifluoromethyl)thiophen-2-yl]propan-2-yl}-4H-1,2,4-triazole monohydrochloride (9a), which showed potent and selective inhibitory activity against human 11ß-HSD1. Compound 9a was also metabolically stable against human and mouse liver microsomes. Oral administration of 9a to diabetic ob/ob mice lowered corticosterone levels in adipose tissue, and thereby reduced plasma glucose and insulin levels in a dose-dependent manner.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Diabetes Mellitus Tipo 2/tratamento farmacológico , Descoberta de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Triazóis/farmacologia , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , Administração Oral , Animais , Diabetes Mellitus Tipo 2/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Células HEK293 , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/química , Masculino , Camundongos , Camundongos Obesos , Estrutura Molecular , Relação Estrutura-Atividade , Triazóis/administração & dosagem , Triazóis/química
5.
Pharm Res ; 36(10): 141, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31367840

RESUMO

PURPOSE: The purpose of the present study was to investigate changes of blood-brain barrier (BBB) and brain parenchymal protein expression due to type II diabetes mellitus (T2DM) induced by a high-fat diet (HFD) by using SWATH-based quantitative proteomics. METHODS: Mice were fed a HFD for 2 or 10 weeks, and then SWATH-based quantitative proteomic analysis, western blot analysis, immunohistochemistry and functional transport studies were performed. RESULTS: In brain capillaries, expression levels of BBB transporters (Glut1, P-glycoprotein) and tight-junction proteins (claudin-5, occludin) were significantly reduced in HFD mice at 2 weeks, but recovered to the levels in the normal diet (ND) group at 10 weeks. P-glycoprotein function at the BBB was reduced at 2 weeks. In the cerebral cortex and hippocampus, neurofilament, which is important for neuronal function, was decreased in HFD mice at 2 weeks, but recovered at 10 weeks. CONCLUSION: Our results suggest that changes in the status of insulin resistance influence expression of BBB transporters, which in turn may alter the expression of cognitive function-related proteins.


Assuntos
Encéfalo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Insulina/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/irrigação sanguínea , Capilares/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Filamentos Intermediários/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteômica , Proteínas de Junções Íntimas/metabolismo
6.
Eur J Epidemiol ; 34(9): 853-861, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31399939

RESUMO

Intake of individual antioxidants has been related to a lower risk of type 2 diabetes. However, the overall diet may contain many antioxidants with additive or synergistic effects. Therefore, we aimed to determine associations between total dietary antioxidant capacity and risk of type 2 diabetes, prediabetes and insulin resistance. We estimated the dietary antioxidant capacity for 5796 participants of the Rotterdam Study using a ferric reducing ability of plasma (FRAP) score. Of these participants, 4957 had normoglycaemia and 839 had prediabetes at baseline. We used covariate-adjusted proportional hazards models to estimate associations between FRAP and risk of type 2 diabetes, risk of type 2 diabetes among participants with prediabetes, and risk of prediabetes. We used linear regression models to determine the association between FRAP score and insulin resistance (HOMA-IR). We observed 532 cases of incident type 2 diabetes, of which 259 among participants with prediabetes, and 794 cases of incident prediabetes during up to 15 years of follow-up. A higher FRAP score was associated with a lower risk of type 2 diabetes among the total population (HR per SD FRAP 0.84, 95% CI 0.75; 0.95) and among participants with prediabetes (HR 0.85, 95% CI 0.73; 0.99), but was not associated with risk of prediabetes. Dietary FRAP was also inversely associated with HOMA-IR (ß - 0.04, 95% CI - 0.06; - 0.03). Effect estimates were generally similar between sexes. The findings of this population-based study emphasize the putative beneficial effects of a diet rich in antioxidants on insulin resistance and risk of type 2 diabetes.


Assuntos
Antioxidantes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Resistência à Insulina , Avaliação Nutricional , Estado Pré-Diabético/metabolismo , Adulto , Idoso , Antioxidantes/administração & dosagem , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Frutas , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Fatores de Risco
7.
Internist (Berl) ; 60(9): 903-911, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31375850

RESUMO

BACKGROUND: Inhibitors of sodium-glucose cotransporters type 2 (SGLT-2) are a class of oral antidiabetic drugs with a novel specific mode of action in the kidneys. OBJECTIVE: The effects of SGLT-2 inhibitors on cardiovascular (CV) and renal endpoints in outcome trials with type 2 diabetes patients. MATERIAL AND METHODS: Differential analysis and interpretation of the results of outcome trials with the SGLT-2 inhibitors empagliflozin, canagliflozin and dapagliflozin in type 2 diabetes mellitus. RESULTS: In the EMPA-REG OUTCOME trial, empagliflozin demonstrated a significant reduction in major cardiac adverse events (MACE), hospitalization for heart failure (HHI), renal endpoints, CV and total mortality vs. placebo in >7000 patients with type 2 diabetes and established CV disease over 3.1 years. In the CANVAS program, canagliflozin demonstrated a significant reduction of MACE, HHI and renal endpoints vs. placebo in >10,000 patients with type 2 diabetes and high CV risk over 2.4 years. In the CREDENCE trial, canagliflozin demonstrated a significant reduction of a combined renal endpoint and CV endpoints vs. placebo in >4000 patients with type 2 diabetes and established kidney disease with albuminuria over 2.6 years. In the DECLARE-TIMI 58 trial, dapagliflozin demonstrated a significant reduction in a combined endpoint of CV death and HHI vs. placebo in >17,000 patients with type 2 diabetes and established CV disease or with multiple CV risk factors over 3.1 years. CONCLUSION: Outcome trials with SGLT-2 inhibitors have collectively demonstrated cardioprotective and nephroprotective effects in patients with type 2 diabetes and high CV risk. The use of SGLT-2 inhibitors is recommended in current guidelines and consensus statements as primary combination partners for metformin in patients with type 2 diabetes and established CV disease, high CV risk, heart failure or kidney disease.


Assuntos
Canagliflozina/uso terapêutico , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Nefropatias/fisiopatologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Canagliflozina/efeitos adversos , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Avaliação de Resultados (Cuidados de Saúde) , Guias de Prática Clínica como Assunto , Transportador 2 de Glucose-Sódio/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Resultado do Tratamento
8.
Internist (Berl) ; 60(9): 887-894, 2019 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-31396651

RESUMO

A multitude of short-acting and long-acting insulin analogues are currently available for the treatment of diabetes mellitus, which mimic physiological insulin secretion better than normal insulins. By the use of ultrarapid insulin analogues postprandial glucose increases can be significantly reduced. Newer long-acting insulin analogues have a very stable action profile and reduce the rate of hypoglycemia, especially nocturnal hypoglycemia, even more than first generation long-acting insulin analogues. Future developments focus on a further acceleration of prandial insulin effects with a simultaneous shorter effect time and an even more prolonged action of long-acting insulin analogues.


Assuntos
Medicamentos Biossimilares , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/metabolismo , Insulina/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Hipoglicemia , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Período Pós-Prandial , Qualidade de Vida
9.
BMJ ; 366: l4009, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266749

RESUMO

OBJECTIVE: To assess the association of dietary fatty acids with cardiovascular disease mortality and total mortality among patients with type 2 diabetes. DESIGN: Prospective, longitudinal cohort study. SETTING: Health professionals in the United States. PARTICIPANTS: 11 264 participants with type 2 diabetes in the Nurses' Health Study (1980-2014) and Health Professionals Follow-Up Study (1986-2014). EXPOSURES: Dietary fat intake assessed using validated food frequency questionnaires and updated every two to four years. MAIN OUTCOME MEASURE: Total and cardiovascular disease mortality during follow-up. RESULTS: During follow-up, 2502 deaths including 646 deaths due to cardiovascular disease were documented. After multivariate adjustment, intake of polyunsaturated fatty acids (PUFAs) was associated with a lower cardiovascular disease mortality, compared with total carbohydrates: hazard ratios comparing the highest with the lowest quarter were 0.76 (95% confidence interval 0.58 to 0.99; P for trend=0.03) for total PUFAs, 0.69 (0.52 to 0.90; P=0.007) for marine n-3 PUFAs, 1.13 (0.85 to 1.51) for α-linolenic acid, and 0.75 (0.56 to 1.01) for linoleic acid. Inverse associations with total mortality were also observed for intakes of total PUFAs, n-3 PUFAs, and linoleic acid, whereas monounsaturated fatty acids of animal, but not plant, origin were associated with a higher total mortality. In models that examined the theoretical effects of substituting PUFAs for other fats, isocalorically replacing 2% of energy from saturated fatty acids with total PUFAs or linoleic acid was associated with 13% (hazard ratio 0.87, 0.77 to 0.99) or 15% (0.85, 0.73 to 0.99) lower cardiovascular disease mortality, respectively. A 2% replacement of energy from saturated fatty acids with total PUFAs was associated with 12% (hazard ratio 0.88, 0.83 to 0.94) lower total mortality. CONCLUSIONS: In patients with type 2 diabetes, higher intake of PUFAs, in comparison with carbohydrates or saturated fatty acids, is associated with lower total mortality and cardiovascular disease mortality. These findings highlight the important role of quality of dietary fat in the prevention of cardiovascular disease and total mortality among adults with type 2 diabetes.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Carboidratos da Dieta/metabolismo , Ácidos Graxos Insaturados/metabolismo , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Correlação de Dados , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Pessoal de Saúde/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia
10.
J Agric Food Chem ; 67(33): 9121-9123, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31339705

RESUMO

As part of the 256th American Chemical Society National Meeting that was held in Boston, MA, U.S.A., in August 2018, the symposium on "Health-Promoting Food Ingredients" was organized in collaboration with Dr. Agnes Rimando (rest in peace). This symposium aimed to present the latest advances related to food ingredients (e.g., pure compounds, extracts, or additives) that potentially confer health benefits and reduce the development of lifestyle-related metabolic disorders (e.g., hypertension, obesity, cardiovascular diseases, and diabetes, among others). The studies presented included the evaluation of functional properties of bioactive compounds commonly found in foods, with an emphasis in (poly)phenols (anthocyanins, flavonols, and proanthocyanidins), and dietary fiber and their interaction with gut microbiota. Many studies were focused on whole extracts of foods and the bioactivity measured in vivo at the cellular level. The role of (poly)phenols in the prevention of cardiovascular diseases and type 2 diabetes was highlighted.


Assuntos
Ingredientes de Alimentos/análise , Alimento Funcional/análise , Animais , Doenças Cardiovasculares/dietoterapia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/prevenção & controle , Promoção da Saúde , Humanos
11.
Rev Med Chil ; 147(4): 480-489, 2019 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-31344211

RESUMO

Physical training is recommended in several studies and guidelines for the control of type 2 diabetes mellitus (DM2) and its complications. We performed a systematic review about the effects of aerobic training (AT), resistance (RT) or the combination of both (AT/ RT), on glycated hemoglobin (HbA1c) in patients with DM2. Therefore, we included 15 clinical trials with at least 12 weeks duration about training program or recommendations of physical exercise, that evaluated the reduction in HbA1c levels in patients with DM2. Information was obtained on training modality (AT, RT or AT / RT), training parameters, duration and weekly training frequency. The results showed increases in peak or maximal oxygen uptake, exercise tolerance time and muscle strength, depending on the type of training, and a reduction in HbA1c levels. We conclude that exercise training is associated with reductions of HbA1c in patients with DM2. Thus, it can be a complementary tool in the management of these patients.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/fisiopatologia , Condicionamento Físico Humano/métodos , Treinamento de Resistência/métodos , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glicada/análise , Humanos , Condicionamento Físico Humano/fisiologia , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento
12.
Nat Commun ; 10(1): 2474, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31171772

RESUMO

Diabetes is a global health problem caused primarily by the inability of pancreatic ß-cells to secrete adequate levels of insulin. The molecular mechanisms underlying the progressive failure of ß-cells to respond to glucose in type-2 diabetes remain unresolved. Using a combination of transcriptomics and proteomics, we find significant dysregulation of major metabolic pathways in islets of diabetic ßV59M mice, a non-obese, eulipidaemic diabetes model. Multiple genes/proteins involved in glycolysis/gluconeogenesis are upregulated, whereas those involved in oxidative phosphorylation are downregulated. In isolated islets, glucose-induced increases in NADH and ATP are impaired and both oxidative and glycolytic glucose metabolism are reduced. INS-1 ß-cells cultured chronically at high glucose show similar changes in protein expression and reduced glucose-stimulated oxygen consumption: targeted metabolomics reveals impaired metabolism. These data indicate hyperglycaemia induces metabolic changes in ß-cells that markedly reduce mitochondrial metabolism and ATP synthesis. We propose this underlies the progressive failure of ß-cells in diabetes.


Assuntos
Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Mitocôndrias/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Perfilação da Expressão Gênica , Gluconeogênese , Glicólise , Secreção de Insulina , Metabolômica , Camundongos , Camundongos Transgênicos , NAD/metabolismo , Fosforilação Oxidativa , Consumo de Oxigênio , Canais de Potássio Corretores do Fluxo de Internalização/genética , Proteômica
13.
Zhonghua Gan Zang Bing Za Zhi ; 27(5): 369-375, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31177662

RESUMO

Objective: To investigate the relationship between gut microbiota structure and biochemical changes in patients with different types of nonalcoholic fatty liver disease (NAFLD), in order to provide evidence for clinical diagnosis and prevention of NAFLD. Methods: Forty-eight NAFLD cases (NAFLD group), 40 NAFLD cases with type 2 diabetes mellitus (NAFLD combined with type 2 diabetes mellitus group) and 30 healthy cases (healthy group) were randomly enrolled, and their body mass index, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, total cholesterol, triglyceride, high density lipoprotein, low density lipoprotein and uric acid were measured. Serum levels of TNF-alpha and fasting insulin were measured using ELISA, and then insulin resistance index was calculated. The gut microbiota of three groups of subjects was detected using 16S rDNA-based high-throughput sequencing. Lastly, the correlations between the various factors were analyzed. The comparison among groups was conducted by 2 test, and one-way ANOVA was used for comparison among groups with normal distribution and homogeneity of variance. Furthermore, the LSD method was used to compare the two groups. K-W rank sum test was used for comparison among groups without normal distribution or homogeneity of variance. Results: Body mass index, aspartate aminotransferase, triglyceride, total cholesterol, low density lipoprotein, uric acid, tumor necrosis factor-alpha, fasting insulin and insulin resistance index of NAFLD group were higher than healthy group, while the high-density lipoprotein was lower in the healthy group, and the difference was statistically significant (P< 0.05). Compared with NAFLD group, the life expectancy, fasting blood glucose and insulin resistance index of NAFLD combined with type 2 diabetes mellitus group were higher, while the body mass index, aspartic acid aminotransferase, total cholesterol and HDL levels were decreased, and the difference was statistically significant (P< 0.05). NAFLD group (P= 0.016) had decreased abundance of firmicutes than healthy group, and the abundancy of the firmicutes in the NAFLD combined with type 2 diabetes group was significantly lower (P< 0.001). The abundance of bacteroidetes in NAFLD combined with type 2 diabetes group was higher than healthy group, and the difference was statistically significant (P= 0.006). At the "genus level," the abundance of Roseburia and Subdoligranulum in the NAFLD group was decreased, while the Roseburia in the NAFLD group with type 2 diabetes group was significantly lower (P< 0.05). In addition, the abundance of Faecalibacterium, Blautia, Anaerostipes and Fusicatenibacter in NAFLD combined with type 2 diabetes group was lower than healthy group, and the difference was statistically significant (P< 0.001). Fusicatenibacter, Blautia, Anaerostipes, Faecalibacterium, and Roseburia were negatively correlated with fasting blood glucose and insulin resistance index levels (r< 0,P< 0.05), and positively correlated with high-density lipoprotein levels (r> 0,P< 0.05). Fusicatenibacter was negatively correlated with tumor necrosis factor-alpha (r= -0.211,P= 0.044), and Lachnoclostridium was positively correlated with body mass index, alanine aminotransferase, aspartate aminotransferase levels (r> 0,P< 0.05). Fusobacterium was positively correlated with aspartate aminotransferase level (r= 0.245,P= 0.019). Escherichia-shigella was positively correlated with fasting blood glucose, low-density lipoprotein, alanine aminotransferase, aspartate aminotransferase levels (r > 0,P< 0.05). Megamonas was negatively correlated with high-density lipoprotein levels (r= -0.231,P= 0.027). Conclusion: A structural change of gut microbiota had occurred in patients with NAFLD, suggesting changes in some of these bacterial genuses had relation to insulin resistance and inflammatory response, which may become a new target for the treatment of NAFLD.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/metabolismo , Alanina Transaminase , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações
14.
J Sci Food Agric ; 99(13): 5926-5933, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31206677

RESUMO

BACKGROUND: Diabetes is a common chronic disease with many complications and is associated with the development of cardiovascular diseases (CVD). The present study aimed to investigate the association of diet quality indices and CVD risk factors among diabetic women. This cross-sectional study was conducted in 230 Tehrani women with type 2 diabetes. A validated and reliable food frequency questionnaire was completed to assess the dietary intake. Diet quality indices were considered with respect to adherence to the Healthy Eating Index-2010 (HEI-2010) and Diet Quality Index-International (DQI-I). Anthropometric measurements, blood pressure and biochemical tests were assessed. CVD risk factors were evaluated according to the adult treatment panel III. RESULTS: Patients who were in the top tertile of the DQI consumed less fat, saturated fatty acids and sodium, as well as more protein, fiber, iron and calcium (P < 0.05). Participants who were in the top tertile of diet quality indices consumed less processed and organ meat and more fruits, and vegetables. Patients in the highest tertile of HEI had lower fasting blood sugar levels (148.92 ± 6.05 mg dL-1 versus 171.30 ± 5.79 mg dL-1 , P = 0.021). There was no significant association between DQI-I, HEI and other CVD risk factors. CONCLUSION: There was no association between diet quality indices and CVD risk factors among diabetic patients. © 2019 Society of Chemical Industry.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Adulto , Idoso , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta , Feminino , Frutas/metabolismo , Dieta Saudável , Humanos , Pessoa de Meia-Idade , Fatores de Risco , Verduras/metabolismo
15.
BMC Genomics ; 20(Suppl 6): 434, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189471

RESUMO

BACKGROUND: Biological networks describes the mechanisms which govern cellular functions. Temporal networks show how these networks evolve over time. Studying the temporal progression of network topologies is of utmost importance since it uncovers how a network evolves and how it resists to external stimuli and internal variations. Two temporal networks have co-evolving subnetworks if the evolving topologies of these subnetworks remain similar to each other as the network topology evolves over a period of time. In this paper, we consider the problem of identifying co-evolving subnetworks given a pair of temporal networks, which aim to capture the evolution of molecules and their interactions over time. Although this problem shares some characteristics of the well-known network alignment problems, it differs from existing network alignment formulations as it seeks a mapping of the two network topologies that is invariant to temporal evolution of the given networks. This is a computationally challenging problem as it requires capturing not only similar topologies between two networks but also their similar evolution patterns. RESULTS: We present an efficient algorithm, Tempo, for solving identifying co-evolving subnetworks with two given temporal networks. We formally prove the correctness of our method. We experimentally demonstrate that Tempo scales efficiently with the size of network as well as the number of time points, and generates statistically significant alignments-even when evolution rates of given networks are high. Our results on a human aging dataset demonstrate that Tempo identifies novel genes contributing to the progression of Alzheimer's, Huntington's and Type II diabetes, while existing methods fail to do so. CONCLUSIONS: Studying temporal networks in general and human aging specifically using Tempo enables us to identify age related genes from non age related genes successfully. More importantly, Tempo takes the network alignment problem one huge step forward by moving beyond the classical static network models.


Assuntos
Algoritmos , Evolução Molecular , Redes Reguladoras de Genes , Redes e Vias Metabólicas , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Biologia Computacional/métodos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Doença de Huntington/genética , Doença de Huntington/metabolismo , Pessoa de Meia-Idade , Mapeamento de Interação de Proteínas , Adulto Jovem
16.
Nat Commun ; 10(1): 2581, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197173

RESUMO

Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.


Assuntos
Metilação de DNA/fisiologia , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Insulina/metabolismo , Obesidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Ilhas de CpG/genética , Diabetes Mellitus Tipo 2/metabolismo , Epigênese Genética/fisiologia , Epigenômica/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica/genética , Estudo de Associação Genômica Ampla/métodos , Homeostase/genética , Humanos , Masculino , Redes e Vias Metabólicas/genética , Pessoa de Meia-Idade , Obesidade/metabolismo , Polimorfismo de Nucleotídeo Único/fisiologia , Adulto Jovem
17.
J Physiol Pharmacol ; 70(1)2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31172973

RESUMO

Obesity is characterised by imbalance in lipid metabolism manifested by high concentrations of circulating triacylglycerols and total cholesterol as well as low high-density lipoprotein (HDL) levels. Abnormalities related to these lipids lead to metabolic complications such as type 2 diabetes, arterial hypertension and cardiovascular disease. Despite extensive research, it is still unclear why a subset of obese subjects develop metabolic syndrome, while others do not. The aim of our work was to assess total and plasma membrane expressions of cholesterol transport proteins: adipocyte ATP-binding cassette A1 (ABCA1), adipocyte ATP-binding cassette G1 (ABCG1), class B scavenger receptor (SR-BI) in visceral and subcutaneous adipose tissue of obese subjects with and without metabolic syndrome. To keep our preliminary study group uniform, we focused on women, who constitute the majority of bariatric patients. The study was performed on 34 patients: 24 morbidly obese women subjected to bariatric surgery, half of whom had metabolic syndrome; and 10 lean subjects undergoing elective laparoscopic cholecystectomy. Total and plasma membrane expressions of cholesterol transport proteins (SR-BI, ABCA1 and ABCG1) were assessed in samples of both visceral and subcutaneous adipose and analysed in relation to other clinical and laboratory parameters. We demonstrated lower plasma membrane expressions of ABCG1 in visceral adipose tissue of obese patients with metabolic syndrome as compared to lean ones. In addition, total ABCG1 expressions in both types of adipose tissue were lower in morbidly obese patients with metabolic syndrome compared to those without metabolic syndrome. Plasma membrane ABCA1 expressions in visceral adipose tissue were lower in the group of morbidly obese patients without metabolic syndrome, compared to lean patients. We did not find any significant differences in SR-BI expressions. Because of ABCG1 is responsible for cholesterol efflux to HDL, reduced plasma membrane expression of ABCG1 in VAT of morbidly obese women with metabolic syndrome may leads to a significantly decreased concentration of HDL in serum. This may be also confirmed by high positive correlation between both parameters.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Tecido Adiposo/metabolismo , Síndrome Metabólica/metabolismo , Obesidade Mórbida/metabolismo , Adulto , Idoso , Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Pessoa de Meia-Idade , Receptores Depuradores Classe B/metabolismo , Adulto Jovem
18.
Genet Test Mol Biomarkers ; 23(6): 387-392, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31161820

RESUMO

Background: Diabetic peripheral neuropathy (DPN) affects nearly 50% of the diabetic population. Advanced glycation end products, measured through skin autofluorescence (SAF), play an important role in the diagnosis and prevention of DPN. To date, however, no relevant study has discussed the relationship between SAF and the Chinese population. Objective: We conducted this study to evaluate the association between DPN and SAF among the Chinese population. Methods: In this cross-sectional study, we recruited a total of 820 patients with type 2 diabetes. All of the patients underwent SAF measurements and a nerve conduction study (NCS). Post-SAF characterization, the patients were divided into three groups according to the first and third quartiles of their SAF values (AU) (SAF ≤ 2.2; 2.2 < SAF ≤ 2.7; SAF > 2.7). Based on the results of the NCS, patients were divided into two groups: DPN and non-DPN. Results: When compared with the non-DPN group (n = 275) with the DNP group. The latter had higher SAF values (2.72 ± 0.55 AU vs. 2.17 ± 0.71 AU, P < 0.01). There were significant differences in age, the percentage of DPN, and NCS parameters, including motor nerve conduction velocity, sensory nerve conduction velocity, distal latency, and sensory nerve action potential among the three SAF groups (p < 0.05). The SAF value was positively associated with DPN (r = 0.11, p < 0.01). After adjusting for all potential confounders, the SAF values were still associated with an increased risk of DPN (odds ratio 5.15; 95% confidence interval [1.48-4.53]) (p < 0.01). A receiver operating characteristic analysis indicated that an SAF value >2.57 ng/mL predicts a threefold increased risk of DPN (p < 0.01). Conclusions: SAF is an independent risk factor for DPN, which might be of potential value for screening DPN in Chinese patients with type 2 diabetes.


Assuntos
Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/fisiopatologia , Pele/diagnóstico por imagem , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Imagem Óptica/métodos , Curva ROC , Fatores de Risco , Pele/metabolismo
19.
J Agric Food Chem ; 67(27): 7694-7705, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31250637

RESUMO

Liver plays a central role in modulating blood glucose level. Our most recent findings suggested that supplementation with microbiota metabolite sodium butyrate (NaB) could ameliorate progression of type 2 diabetes mellitus (T2DM) and decrease blood HbA1c in db/db mice. To further investigate the role of butyrate in homeostasis of blood glucose and glycogen metabolism, we carried out the present study. In db/db mice, we found significant hypertrophy and steatosis in hepatic lobules accompanied by reduced glycogen storage, and expression of GPR43 was significantly decreased by 59.38 ± 3.33%; NaB administration significantly increased NaB receptor G-protein coupled receptor 43 (GPR43) level and increased glycogen storage in both mice and HepG2 cells. Glucose transporter 2 (GLUT2) and sodium-glucose cotransporter 1 (SGLT1) on cell membrane were upregulated by NaB. The activation of intracellular signaling Protein kinase B (PKB), also known as AKT, was inhibited while glycogen synthase kinase 3 (GSK3) was activated by NaB in both in vivo and in vitro studies. The present study demonstrated that microbiota metabolite NaB possessed beneficial effects on preserving blood glucose homeostasis by promoting glycogen metabolism in liver cells, and the GPR43-AKT-GSK3 signaling pathway should contribute to this effect.


Assuntos
Ácido Butírico/administração & dosagem , Diabetes Mellitus Tipo 2/metabolismo , Glicogênio Hepático/metabolismo , Animais , Glicemia/análise , Ácido Butírico/metabolismo , Imunofluorescência , Microbioma Gastrointestinal/fisiologia , Transportador de Glucose Tipo 2/análise , Hemoglobina A Glicada/análise , Quinase 3 da Glicogênio Sintase/metabolismo , Células Hep G2 , Homeostase/efeitos dos fármacos , Humanos , Fígado/química , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas-G/análise , Transdução de Sinais/efeitos dos fármacos , Transportador 1 de Glucose-Sódio/análise
20.
Nat Commun ; 10(1): 2679, 2019 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31213603

RESUMO

The islet in type 2 diabetes (T2D) is characterized by amyloid deposits derived from islet amyloid polypeptide (IAPP), a protein co-expressed with insulin by ß-cells. In common with amyloidogenic proteins implicated in neurodegeneration, human IAPP (hIAPP) forms membrane permeant toxic oligomers implicated in misfolded protein stress. Here, we establish that hIAPP misfolded protein stress activates HIF1α/PFKFB3 signaling, this increases glycolysis disengaged from oxidative phosphorylation with mitochondrial fragmentation and perinuclear clustering, considered a protective posture against increased cytosolic Ca2+ characteristic of toxic oligomer stress. In contrast to tissues with the capacity to regenerate, ß-cells in adult humans are minimally replicative, and therefore fail to execute the second pro-regenerative phase of the HIF1α/PFKFB3 injury pathway. Instead, ß-cells in T2D remain trapped in the pro-survival first phase of the HIF1α injury repair response with metabolism and the mitochondrial network adapted to slow the rate of cell attrition at the expense of ß-cell function.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Estresse do Retículo Endoplasmático/fisiologia , Células Secretoras de Insulina/patologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Resposta a Proteínas não Dobradas/fisiologia , Adulto , Animais , Animais Geneticamente Modificados , Apoptose , Linhagem Celular Tumoral , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Glicólise/fisiologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/genética , Masculino , Pessoa de Meia-Idade , Degradação Mitocondrial/fisiologia , Fosforilação Oxidativa , Fosfofrutoquinase-2/metabolismo , Agregados Proteicos/fisiologia , Ratos
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