Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 881
Filtrar
1.
Curr Diabetes Rev ; 16(2): 143-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30451115

RESUMO

INTRODUCTION: The Diabetes Prevention Program study results indicated that metformin therapy was not as beneficial as a lifestyle modification for delaying the development of type 2 diabetes in individuals at high risk of the disease. A key feature in the etiology of type 2 diabetes mellitus, which appears in the prediabetic phase, is a significant deficiency, compared to healthy controls, in highly flexible poly-cis-unsaturated fatty acyl chains in membrane phospholipids. This deficiency lowers membrane flexibility, which in turn, reduces the amount of all functional Class I glucose transporters, and thereby reduces glucose-mediated ATP production. This leads to an increase in essentially saturated free fatty acid (FFA) levels for fatty-acid-mediated ATP production, which will set up a vicious cycle of raising the levels of essentially saturated FFAs and lowering the level of transmembrane glucose transport. Metformin suppresses hepatic gluconeogenesis, which reduces the plasma glucose concentration. CONCLUSION: We hypothesize that chronic metformin treatment leads to an additional increase in essentially saturated FFAs, which causes an additional rise in membrane stiffness and hypoxia. So we propose that all these metformin-mediated activities accelerated the onset of type 2 diabetes in the participants of the metformin group in the Diabetes Prevention Program study, compared to the participants of the lifestyle-intervention group in this study. We propose that the biochemical reactions, involved in the fatty-acid-mediated ATP production, play an important part in the increase of the observed essentially saturated FFA concentrations. These statements should also extend to the metformin therapy of individuals with type 2 diabetes.


Assuntos
Membrana Celular/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Ácidos Graxos/metabolismo , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Estado Pré-Diabético/metabolismo , Glicemia/metabolismo , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Progressão da Doença , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/metabolismo , Estilo de Vida Saudável , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Metformina/farmacologia , Metformina/uso terapêutico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/terapia , Medição de Risco , Fatores de Risco
2.
J Ethnopharmacol ; 247: 112263, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580944

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cocoa extracts rich in polyphenols are used as potential agent for treating diabetes. Cocoa polyphenols have been proved to ameliorate important hallmarks of type-2 diabetes (T2D). They can regulate glucose levels by increasing insulin secretion, promoting ß-cell proliferation and a reduction of insulin resistance. In addition, epidemiological evidence indicates that consumption of flavonoid decreases the incidence of T2D. AIM OF THE STUDY: T2D is preceded by a prediabetic state in which the endocrine-metabolic changes described in T2D are already present. Since epidemiological evidence indicates that consumption of flavonoid decreases its incidence, we evaluated possible preventive effects of polyphenol-enriched cocoa extract on a model of prediabetes induced by sucrose. MATERIALS AND METHODS: We determined circulating parameters and insulin sensitivity indexes, liver protein carbonyl groups and reduced glutathione, liver mRNA expression levels of lipogenic enzymes, expression of different pro-inflammatory mediators, fructokinase activity and liver glycogen content. For that, radioimmunoassay, real-time polymerase chain reaction, Western blot, spectrophotometry, and immunohistochemistry were used. RESULTS: We demonstrated that sucrose administration triggered hypertriglyceridemia, insulin-resistance, and liver increased oxidative stress and inflammation markers compared to control rats. Additionally, we found an increase in glycogen deposit, fructokinase activity, and lipogenic genes expression (SREBP-1c, FAS and GPAT) together with a decrease in P-Akt and P-eNOS protein content (P < 0.05). Sucrose-induced insulin resistance, hepatic carbohydrate and lipid dysmetabolism, oxidative stress, and inflammation were effectively disrupted by polyphenol-enriched cocoa extract (PECE) co-administration (P < 0.05). CONCLUSION: Dietary administration of cocoa flavanols may be an effective and complementary tool for preventing or reverting T2D at an early stage of its development (prediabetes).


Assuntos
Cacau/química , Diabetes Mellitus Tipo 2/prevenção & controle , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Estado Pré-Diabético/tratamento farmacológico , Animais , Diabetes Mellitus Tipo 2/metabolismo , Sacarose na Dieta/efeitos adversos , Modelos Animais de Doenças , Humanos , Resistência à Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Polifenóis/isolamento & purificação , Polifenóis/uso terapêutico , Estado Pré-Diabético/sangue , Estado Pré-Diabético/etiologia , Estado Pré-Diabético/metabolismo , Ratos , Triglicerídeos/sangue , Triglicerídeos/metabolismo
3.
J Sports Sci Med ; 18(4): 636-644, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31827347

RESUMO

Prediabetes is associated with impaired oxidative capacity and altered substrate utilization during exercise. The effects of continuous (CONT) versus interval (INT) exercise training on fat oxidation during an acute exercise bout at the same absolute and relative intensities are unknown in this population. Obese females/males (n = 17, n = 5) with prediabetes (BMI 32.2 ± 1.2 kg·m-2; age 62.8 ± 1.6 y; fasting glucose 103.4 ± 1.6 mg·dL-1; 2-hour glucose 153.7 ± 7.1 mg·dL-1; VO2peak 19.9 ± 1.0 mL·kg-1·min-1) were screened with a 75g OGTT. Subjects completed a peak oxygen consumption test and a submaximal exercise substrate utilization test consisting of 5min stages at absolute (30W) and relative (70%HRpeak) intensities before and after randomization to 12 sessions (60min each) of CONT (70% HRpeak) or INT (alternating 3min 90% HRpeak, 3min 50% HRpeak) over a two-week period. Body mass decreased and VO2peak increased more after INT than CONT (INT: -0.6 ± 0.2 kg, CONT: -0.1 ± 0.2 kg; p = 0.04; INT: 1.9 ± 0.6 mL/kg/min, CONT: 0.1 ± 0.6 mL·kg-1·min-1; p = 0.04). Training increased fat oxidation by 0.7 ± 0.2 mL·kg-1·min-1 during the absolute intensity test (p < 0.001), independent of intensity. During the relative intensity test, fat oxidation increased more after INT than CONT (INT: 1.3 ± 0.4 mL·kg-1·min-1, CONT: 0.3 ± 0.3 mL·kg-1·min-1; p = 0.03), with no difference in exercise energy expenditure between groups. Enhanced fat oxidation during the relative test was correlated with increased VO2peak (r = 0.53 p = 0.01). High intensity INT training enhances fat oxidation during the same relative intensity exercise in people with prediabetes.


Assuntos
Tecido Adiposo/metabolismo , Treinamento Intervalado de Alta Intensidade , Obesidade/metabolismo , Estado Pré-Diabético/metabolismo , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Aptidão Cardiorrespiratória/fisiologia , Metabolismo Energético/fisiologia , Feminino , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Oxirredução , Consumo de Oxigênio/fisiologia , Percepção/fisiologia , Esforço Físico/fisiologia , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações
4.
Life Sci ; 238: 116971, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31634462

RESUMO

AIM: High-fat diet (HFD) intake has been associated with changes in intestinal microbiota composition, increased intestinal permeability, and onset of type 2 diabetes mellitus (T2DM). The aim of this work was twofold: 1) to investigate the structural and functional alterations of the tight junction (TJ)-mediated intestinal epithelial barrier of ileum and colon, that concentrate most of the microbiota, after exposure to a HFD for 15, 30 and 60 days, and 2) to assess the effect of in vitro exposure to free fatty acids (FFAs), one of the components of HFD, on paracellular barrier of colon-derived Caco-2 cells. METHODS/KEY FINDINGS: HFD exposure induced progressive metabolic changes in male mice that culminated in prediabetes after 60d. Morphological analysis of ileum and colon mucosa showed no signs of epithelial rupture or local inflammation but changes in the junctional content/distribution and/or cellular content of TJ-associated proteins (claudins-1, -2, -3, and occludin) in intestinal epithelia were seen mainly after a prediabetes state has been established. This impairment in TJ structure was not associated with significant changes in intestinal permeability to FITC-dextran. Exposure of Caco-2 monolayers to palmitic or linoleic acids seems to induce a reinforcement of TJ structure while treatment with oleic acid had a more diverse effect on TJ protein distribution. SIGNIFICANCE: TJ structure in distal intestinal epithelia can be specifically impaired by HFD intake at early stage of T2DM, but not by FFAs in vitro. Since the TJ change in ileum/colon was marginal, probably it does not contribute to the disease onset.


Assuntos
Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Mucosa Intestinal/patologia , Estado Pré-Diabético/patologia , Junções Íntimas/patologia , Animais , Células CACO-2 , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ocludina , Estado Pré-Diabético/etiologia , Estado Pré-Diabético/metabolismo , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Fatores de Tempo
5.
Int J Mol Sci ; 20(17)2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480394

RESUMO

Feeding rats with high-fat diet (HFD) with a single streptozotocin (STZ) injection induced obesity, slightly elevated fasting blood glucose and impaired glucose and insulin tolerance, and caused cardiac hypertrophy and mild diastolic dysfunction as published before by Koncsos et al. in 2016. Here we aimed to explore the renal consequences in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or HFD containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 blood and urine samples were taken and kidney and liver samples were collected for histology, immunohistochemistry and for analysis of gene expression. HFD and STZ increased body weight and visceral adiposity and plasma leptin concentration. Despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1ß mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression, and cortical and medullary mRNA expression of TGF-ß1, Nrf2, and PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while plasma lipid and liver enzyme concentrations were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury.


Assuntos
Colágeno/metabolismo , Glomérulos Renais/lesões , Glomérulos Renais/metabolismo , Lipocalina-2/metabolismo , Obesidade/metabolismo , Estado Pré-Diabético/metabolismo , Tecido Adiposo/metabolismo , Animais , Biomarcadores/metabolismo , Peso Corporal , Dieta Hiperlipídica , Fibrose , Regulação da Expressão Gênica , Inflamação/genética , Inflamação/patologia , Glomérulos Renais/patologia , Lipídeos/sangue , Fígado/enzimologia , Fígado/patologia , Fígado/fisiopatologia , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Obesidade/sangue , Estresse Oxidativo/genética , Fosforilação , Fosfosserina/metabolismo , Estado Pré-Diabético/sangue , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Long-Evans , Estreptozocina
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.
Mol Immunol ; 114: 289-298, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31419705

RESUMO

Programmed cell death 1 ligand 1 (PD-L1) plays a critical role in mediating autoimmune diseases, including type I diabetes (T1D). B cells are important antigen-presenting cells (APCs) that make a major contribution to T1D development. However, B cells expressing low levels of PD-L1 that infiltrate insulitic islets in NOD mice may not inhibit effector T cells and prevent T1D. Here, we generated PD-L1 transgenic NOD (NOD.PD-L1Tg) mice, in which most immune cells overexpress PD-L1, to investigate the ability of B cells overexpressing PD-L1 to inhibit diabetic CD4+ T cells and prevent T1D. The severity of insulitis in NOD.PD-L1Tg mice was significantly lower than in NOD mice and none developed diabetes. In addition, there were no differences in expression of activity markers by APCs following LPS stimulation between two groups. In vitro studies revealed that B cells expressing high levels of PD-L1 inhibited proliferation of and cytokine secretion by pre-diabetic CD4+ T cells, whereas in vivo studies showed that NOD/SCID mice receiving diabetic CD4+ T cells mixed with B cells overexpressing PD-L1 became diabetic at a slower rate. Thus, we propose that B cells showing high expression of PD-L1 protect NOD mice against T1D and downregulate diabetogenic CD4+ T cells.


Assuntos
Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Camundongos Endogâmicos NOD/metabolismo , Animais , Doenças Autoimunes/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Regulação para Baixo/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Estado Pré-Diabético/metabolismo
8.
Nat Commun ; 10(1): 3700, 2019 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-31420552

RESUMO

Little is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions.


Assuntos
Ilhotas Pancreáticas/ultraestrutura , Comunicação Parácrina , Estado Pré-Diabético/patologia , Pseudópodes/ultraestrutura , Células Secretoras de Somatostatina/ultraestrutura , Animais , Glicemia/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/ultraestrutura , Microscopia Intravital , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Imagem Óptica , Optogenética , Estado Pré-Diabético/metabolismo , Pseudópodes/metabolismo , Células Secretoras de Somatostatina/citologia , Células Secretoras de Somatostatina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Diabetes Metab Syndr ; 13(2): 1193-1199, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336464

RESUMO

AIMS: In the present study we intended to study autonomic functions and its association with telomerase level, oxidative stress and inflammation in complete glycemic spectrum. MATERIALS AND METHODS: Age, gender and BMI matched 28 subjects in the age group of 25-50 years were recruited across complete glycemic spectrum as follows: 1) Normoglycemics (controls) 2) Prediabetics and 3) Frank diabetics. We assessed heart rate variability, cardiac autonomic function, lipid profile, adiponectin, malondialdehyde and telomerase level. RESULTS: Time domain parameters and frequency domain parameters were significantly lower, and LFnu and LF/HF ratio were significantly higher in prediabetes and diabetes than control. Serum Adiponectin and HDL levels were significantly lower in diabetes than prediabetes and control, and prediabetes had significantly lower HDL than controls. Other lipid profile parameters (TC, TG, VLDL, LDL, non-HDL & derived lipid parameters were significantly higher in diabetes than prediabetes and control and prediabetes had significantly higher values than controls. MDA levels were significantly higher and TAS was significantly lower in diabetics than prediabetics and control group. Telomerase level was significantly higher in diabetes as compared to prediabetes and control. Telomerase had significantly negative correlation with SDNN, HF, TP, HDL and adiponectin, and significant positive correlation with MDA, fasting insulin, HOMA IR, TC, and AIP. CONCLUSION: Oxidative damage, inflammation and autonomic dysregulation may be involved in Telomere/Telomerase dysregulation in diabetes and telomerase levels can be used as a cardio-metabolic marker of diabetes.


Assuntos
Adiponectina/metabolismo , Biomarcadores/metabolismo , Diabetes Mellitus/fisiopatologia , Inflamação , Estresse Oxidativo , Estado Pré-Diabético/fisiopatologia , Telomerase/metabolismo , Adulto , Glicemia/análise , Estudos de Casos e Controles , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/metabolismo , Feminino , Seguimentos , Humanos , Índia/epidemiologia , Insulina/sangue , Lipídeos/sangue , Masculino , Malondialdeído/metabolismo , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/metabolismo , Prognóstico , Medição de Risco/métodos
10.
Diabetes Metab Syndr ; 13(2): 1543-1547, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336519

RESUMO

AIMS: to assess salivary glucose correlation with blood glucose and its accuracy in diagnosis of diabetes and prediabetes. MATERIALS AND METHODS: A comparative study including 204 adults in 3 groups (104 type 2 diabetics, 50 prediabetics, 50 non-diabetic controls) aging 18-65 years. The participants were interviewed about their socio-demographic, comorbidities, & drug treatment using a predesigned questionnaire. Salivary & blood samples were collected and analyzed. RESULTS: Mean salivary glucose was observed to be 23.40 ±â€¯12.755 mg/dl in control group, 42.68 ±â€¯20.830 mg/dl in prediabetic group and 59.32 ±â€¯19.147 mg/dl in diabetic group with significant difference between the 3 groups (P value < 0.001). Salivary glucose was significantly correlated to FBS with strong positive association (r = 0.67, P value < 0.001 in control group, r = 0.56, P value < 0.001in diabetic group and r = 0.36, P value 0.01 in pre-diabetic group). Salivary glucose could differentiate non-diabetics from diabetics (AUC: 0.928, P value < 0.001) with sensitivity (94.2%) and specificity (62%) & differentiate non-diabetics from prediabetics (AUC: 0.928, P value < 0.001) with sensitivity (94.2%) and specificity (62%). CONCLUSIONS: Salivary glucose estimation can serve as valid and non-invasive test for screening and diagnosis of diabetes & prediabetes.


Assuntos
Biomarcadores/metabolismo , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Estado Pré-Diabético/diagnóstico , Saliva/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/metabolismo , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Adulto Jovem
11.
Diabetes Metab Syndr ; 13(2): 1603-1608, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336528

RESUMO

Prediabetes increases an individual's risk for progress to diabetes. The aim of the study is to assess prediabetic profile before and after life style modification only, lifestyle with metformin and lifestyle with DPP-4 inhibitor. This study was carried out at BIRDEM. The subjects were IGT, IFG or combined. In Group A 50 subjects were advised with lifestyle, 42 were follow up with the results showed that highly significant change in BMI, Fasting & 2 h plasma glucose, serum triglyceride, and reduced HbA1c level, reduction rate of DM is 43%. In Group B 50 subjects were advised with lifestyle plus metformin, 44 were follow up with the results showed that significant change in BMI, Fasting, 2 h plasma glucose, triglyceride, and reduced HbA1c, reduction rate of DM is 58%. In Group C 50 subjects were advised with lifestyle plus DPP4i, 37 were follow up with the results showed that significantly change in BMI, Fasting, 2 h plasma glucose, triglyceride and reduced HbA1c level, reduction rate of DM is 43%. There is significant outcome difference in BMI in between A vs. B and A vs. C group. More mean changed in 2hrs after blood glucose level in group A vs. group B and B vs. C group. There is significant outcome difference in TG level in A vs. B, B vs. C group but no difference in A vs. C group.


Assuntos
Diabetes Mellitus Tipo 2/prevenção & controle , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Hipoglicemiantes/uso terapêutico , Estilo de Vida , Metformina/uso terapêutico , Estado Pré-Diabético/terapia , Adulto , Bangladesh , Biomarcadores/análise , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/metabolismo , Estado Pré-Diabético/patologia , Prognóstico
12.
Metabolism ; 98: 76-83, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31228482

RESUMO

OBJECTIVE: Circulating branched-chain amino acids (BCAAs, isoleucine, leucine, valine) and aromatic amino acids (AAAs, tyrosine and phenylalanine) predicted type 2 diabetes mellitus (T2DM) risk in a Caucasian population. Here, we assessed amino acid levels in relation to incident prediabetes among initially normoglycemic African Americans (AA) and European Americans (EA). RESEARCH DESIGN AND METHODS: Using a nested case-control design, we studied 70 adults (35 AA, 35 EA) who developed prediabetes (progressors) and 70 matched participants who maintained normoglycemia (nonprogressors) during 5.5 years of follow-up in the Pathobiology of Prediabetes in a Biracial Cohort study. Assessments included plasma amino acid levels, insulin sensitivity, and beta-cell function. RESULTS: The total level of all 18 amino acid assayed was significantly associated with lean mass (r = 0.36, P < 0.0001), waist circumference (r = 0.27, P = 0.001), fasting plasma glucose (r = 0.24, P = 0.005), HOMA-IR (r = 0.22, P = 0.01) and HDL cholesterol (r = -0.18, P = 0.03). Individual amino acid levels were significantly associated with insulin sensitivity and insulin secretion. Compared with nonprogressors, progressors had higher baseline levels of asparagine and aspartic acid (P <0.0001), glutamine/glutamic acid (P = 0.005) and phenylalanine (P = 0.02), and lower histidine (P = 0.02) levels. In fully-adjusted logistic regression models, aspartic acid/asparagine (OR 2.72 [95% CI 1.91-3.87]) and histidine (OR 0.90 [95% CI 0.85-0.96]) were the only amino acids that significantly predicted incident prediabetes. CONCLUSIONS: Baseline plasma aspartic acid and asparagine levels predicted progression to prediabetes, whereas histidine levels were protective of prediabetes risk. Thus, the amino acid signature associated with prediabetes in a diverse population may be distinct from that previously linked to T2DM in Caucasians.


Assuntos
Aminoácidos/metabolismo , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/metabolismo , Adulto , Afro-Americanos , Asparagina/metabolismo , Ácido Aspártico/metabolismo , Glicemia/análise , Estudos de Casos e Controles , Estudos de Coortes , Grupos de Populações Continentais , Grupo com Ancestrais do Continente Europeu , Feminino , Seguimentos , Histidina/metabolismo , Humanos , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes
13.
Can J Diabetes ; 43(7): 457-463, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31213408

RESUMO

OBJECTIVES: Recently, a malfunction of the autophagic pathway has been implicated with impaired glucose metabolism and progression from prediabetes to type 2 diabetes. The aims of this study were to investigate the effect of exercise and rapamycin (RAPA) treatment on the autophagic process in peripheral blood mononuclear cells (PBMCs) from people with prediabetes compared with control subjects. METHODS: Two groups matched for age and sex served as participants and included 6 participants with prediabetes (42.4±11.7 years) and 6 control subjects (44.4±11.9 years). Participants exercised at 50% of maximal oxygen consumption for 60 min with 5 min of rest interspersed every 20 min. PBMCs were isolated pre-exercise, immediately postexercise and 4 h after exercise recovery. Additional PBMCs were incubated for 24 h and either exposed to bafilomycin, rapamycin with bafilomycin (RAPA), or no treatment with vehicle (dimethyl sulfoxide). Proteins and mRNA were analyzed via western blot and quantitative real-time polymerase chain reaction, respectively. RESULTS: Exercise increased autophagy immediately postexercise and recovered 4 h after exercise in control participants but not in participants with prediabetes. Autophagy increased in PBMCs from people with prediabetes and control participants after RAPA treatment; however, a significantly impaired autophagic response was observed in people with prediabetes when compared with control subjects. CONCLUSIONS: Our results indicate an impairment in autophagic flux in PBMCs from people with prediabetes when compared with control subjects in response to both exercise and RAPA treatment. Future methods of autophagic upregulation should be investigated to spare malfunctions in autophagy in people with prediabetes.


Assuntos
Autofagia , Diabetes Mellitus Tipo 2/patologia , Exercício , Imunossupressores/uso terapêutico , Leucócitos Mononucleares/patologia , Estado Pré-Diabético/patologia , Sirolimo/uso terapêutico , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/metabolismo , Prognóstico
14.
Clin Obes ; 9(4): e12324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31172667

RESUMO

The prevalence of pre-diabetes and of type 2 diabetes mellitus is increasing. Preventing disease progression is important to improve outcomes. Natural products are becoming popular alternatives to pharmaceutical products for preventative health and treatment of disease; however, the evidence to support the use of natural alternatives for pre-diabetes and type 2 diabetes is lacking. Two such natural medicines include alpha-cyclodextrin (marketed as FBCx), a fibre derived from corn starch that has been found to bind triglycerides in the intestines to prevent its absorption, aiding weight maintenance and lipid control, and hydrolysed ginseng extract (marketed as GINST15), a formula containing high amounts of Compound K, a metabolite of ginsenosides thought to be an active ingredient contributing to the anti-hyperglycaemic effects of ginseng. This paper describes the rationale and design of a 12-month randomized controlled trial to investigate the metabolic effects of these two products in people with pre-diabetes and overweight or obesity. A total of 400 participants will be randomized to one of four groups (FBCx + GINST15, FBCx + placebo, placebo + GINST15, placebo + placebo) for 6 months, followed by 6 months of follow-up. Participants will also receive lifestyle advice for healthy eating and weight loss. Data collected during the trial will include weight, waist circumference, body composition and blood pressure. Blood samples will also be collected to measure lipid profile and glycaemia. If the products are found to improve lipid and glucose levels, it will provide evidence for their use in people with pre-diabetes to help reduce the risk of progression to type 2 diabetes.


Assuntos
Colesterol/metabolismo , Ginsenosídeos/administração & dosagem , Estado Pré-Diabético/tratamento farmacológico , alfa-Ciclodextrinas/administração & dosagem , Adulto , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/dietoterapia , Obesidade/metabolismo , Sobrepeso/tratamento farmacológico , Sobrepeso/metabolismo , Estado Pré-Diabético/metabolismo , Triglicerídeos/metabolismo
15.
J Physiol Biochem ; 75(3): 351-365, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31197649

RESUMO

There is a gap in the knowledge regarding regulation of local renin-angiotensin system (RAS) in skeletal muscle during development of obesity and insulin resistance in vivo. This study evaluates the obesity- and age-related changes in the expression of local RAS components. Since RAS affects skeletal muscle remodelling, we also evaluated the muscle fibre type composition, defined by myosin heavy chain (MyHC) mRNAs and protein content. Gene expressions were determined by qPCR and/or Western blot analysis in musculus quadriceps of 3- and 8-month-old male obese Zucker rats and their lean controls. The enzymatic activity of aminopeptidase A (APA) was determined flourometrically. Activation of renin receptor (ReR)/promyelocytic leukaemia zinc finger (PLZF) negative feedback mechanism was observed in obesity. The expression of angiotensinogen and AT1 was downregulated by obesity, while neutral endopeptidase and AT2 expressions were upregulated in obese rats with aging. Skeletal muscle APA activity was decreased by obesity, which negatively correlated with the increased plasma APA activity and plasma cholesterol. The expression of angiotensin-converting enzyme (ACE) positively correlated with MyHC mRNAs characteristic for fast-twitch muscle fibres. The obesity- and age-related alterations in the expression of both classical and alternative RAS components suggest an onset of a new equilibrium between ACE/AngII/AT1 and ACE2/Ang1-7/Mas at lower level accompanied by increased renin/ReR/PLZF activation. Increased APA release from the skeletal muscle in obesity might contribute to increased plasma APA activity. There is a link between reduced ACE expression and altered muscle MyHC proportion in obesity and aging.


Assuntos
Envelhecimento/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Obesidade/metabolismo , Estado Pré-Diabético/metabolismo , Sistema Renina-Angiotensina , Animais , Resistência à Insulina , Masculino , Ratos , Ratos Zucker
16.
Int. j. morphol ; 37(2): 647-653, June 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1002271

RESUMO

Excessive consumption of carbohydrate and fat increases the risk of cardiovascular disease. We sought to determine the potential ultrastructural alterations in large blood vessels induced by a high fat and fructose diet (HFD) in a rat model of prediabetes. Rats were either fed with HFD (model group) or a standard laboratory chow (control group) for 15 weeks before being sacrificed. The harvested thoracic aorta tissues were examined using transmission electron microscopy (TEM), and blood samples were assayed for biomarkers of pre-diabetes.TEM images showed that HFD induced profound pathological changes to the aortic wall layers, tunica intima and tunica media ultrastructures in the pre-diabetic rats as shown by apoptotic endothelial cells with pyknotic nuclei, damaged basal lamina, deteriorated smooth muscle cells that have irregular plasma membranes, shrunken nucleus with clumped nuclear chromatin, damaged mitochondria and few cytoplasmic lipid droplets and vacuoles. In addition, HFD significantly (p<0.05) decreased adiponectin and increased biomarkers of lipidemia, glycaemia, inflammation, oxidative stress, vascular injury such as soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion protein 1 (sVCAM-1), endothelin-1 (ET-1), and coagulation and thrombosis such as Von Willebrand factor (vWF), and plasminogen activator inhibitor-1 (PAI-1), compared to normal levels of these parameters in the control group. Thus, we demonstrated that feeding rats with a HFDisable to develop a pre-diabetic animal model that is useful to study the aortic ultrastructural alterations.


El consumo excesivo de carbohidratos y grasas aumenta el riesgo de enfermedades cardiovasculares. Intentamos determinar las posibles alteraciones ultraestructurales en los grandes vasos sanguíneos, inducidas por una dieta alta en grasas y fructosa (HFD) en un modelo de rata de prediabetes. Las ratas se alimentaron con HFD (grupo modelo) o una comida de laboratorio estándar (grupo de control) durante 15 semanas antes de ser sacrificadas. Los tejidos de la aorta torácica recolectados se examinaron mediante microscopía electrónica de transmisión (TEM) y las muestras de sangre se analizaron para detectar biomarcadores de prediabetes. Las imágenes TEM mostraron que HFD indujo cambios patológicos profundos en las capas de la pared aórtica, túnica íntima y túnica media en la ratas pre-diabéticas como lo muestran las células endoteliales apoptóticas con núcleos picnóticos, lámina basal dañada, células musculares lisas deterioradas que tienen membranas plasmáticas irregulares, núcleo encogido con cromatina nuclear aglomerada, mitocondrias dañadas y pocas gotitas lipídicas citoplásmicas y vacuolas. Además, HFD presentó disminución significativa de adiponectina (p <0,05), y aumento de biomarcadores de lipidemia, glucemia, inflamación, estrés oxidativo, lesión vascular como la molécula de adhesión intercelular soluble 1 (sICAM-1), proteína de adhesión de células vasculares soluble 1 (sVCAM-1), endotelina 1 (ET-1), y la coagulación y la trombosis, como el factor de Von Willebrand (vWF), y el inhibidor del activador del plasminógeno-1 (PAI -1), en comparación con los niveles normales de estos parámetros en el grupo de control. Por tanto, la alimentación de ratas con HFD es capaz de desarrollar un modelo animal prediabético que es útil para estudiar las alteraciones ultraestructurales aórticas.


Assuntos
Animais , Aorta Torácica/patologia , Aorta Torácica/ultraestrutura , Estado Pré-Diabético/patologia , Aorta/patologia , Aorta/ultraestrutura , Estado Pré-Diabético/metabolismo , Gorduras na Dieta/efeitos adversos , Ratos Sprague-Dawley , Microscopia Eletrônica de Transmissão , Modelos Animais de Doenças , Lesões do Sistema Vascular/etiologia , Lesões do Sistema Vascular/patologia , Frutose
17.
Dis Markers ; 2019: 7901062, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31073344

RESUMO

Introduction: Interleukin-33 (IL-33), the ligand for the receptor ST2, is abundant in adipose tissue, including preadipocytes, adipocytes, and endothelial cells. The IL-33/ST2 axis is protective against obesity, insulin resistance, and type 2 diabetes (T2D) in animal models. We determined whether adipose tissue IL-33 was associated with glycated hemoglobin (HbA1c), as well as mediators of inflammation and immune regulation and beiging of adipose tissue, among individuals with varying degrees of glycemia. Materials and Methods: A total of 91 adults with normoglycemia, prediabetes, and T2D were included. After measuring their anthropometric and biochemical parameters, subcutaneous adipose tissue samples were isolated and mRNA expression of cytokines, chemokines, chemokine receptors, pattern recognition receptors, and mediators involved in beiging of adipose tissue were measured. Results: Adipose tissue IL-33 was inversely associated with HbA1c in individuals with normoglycemia and T2D but not in those with prediabetes and was inversely correlated with fasting plasma glucose in individuals with T2D and with a better glycemic control. IL-33-to-ST2 ratio was inversely correlated with HbA1c in individuals with normoglycemia but not in those with prediabetes or T2D. IL-33 was directly associated with ST2, CD302, fibrinogen-like protein 2 (FGL2), and PR domain containing 16 (PRDM16) but inversely correlated with chemokine (C-C motif) ligand (CCL) 7 and CCL8 in individuals with normoglycemia. Similarly, IL-33 was directly associated with ST2, CD302, FGL2, PRDM16, and, additionally, toll-like receptor (TLR) 3 and IL-12A in individuals with T2D. However, IL-33 was not associated with any of these mediators but was directly and strongly associated with TLR9 in individuals with prediabetes. Conclusions: IL-33 and/or IL-33/ST2 dynamics and biological functions may play a role in overall glycemia among humans and may represent a novel target by which glucose-lowering managements confer their beneficial effects.


Assuntos
Tecido Adiposo/metabolismo , Hiperglicemia/metabolismo , Interleucina-33/metabolismo , Estado Pré-Diabético/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Feminino , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/sangue , Interleucina-33/genética , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue
18.
Endocr J ; 66(8): 663-675, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142688

RESUMO

Dysregulation of glucagon secretion plays an important role in the pathogenesis of type 2 diabetes (T2DM). However it hasn't been elucidated involvement of glucagon dysregulation in pathophysiology of T2DM. Recently a new glucagon sandwich enzyme-linked immunosorbent assay (ELISA) became available that can measure plasma glucagon level with higher accuracy and simpler procedure than the conventional RIA method. We performed OGTT for adult subjects aged 20-69 years to define normal glucose tolerance (NGT, n = 25), borderline glucose intolerance (defined as pre-diabetes mellitus: preDM, n = 15), or diabetes mellitus (DM, n = 13), and we measured glucagon levels with this new ELISA method at fasting and during OGTT. Plasma glucose, insulin, glucagon and active GLP-1 were also measured. This study took place in diabetes outpatient clinic in Kitasato University Hospital and an affiliated outpatient clinic. PreDM and DM exhibited higher fasting plasma glucagon levels than NGT (34.4 ± 4.6 and 44.1 ± 5.0 vs. 20.6 ± 3.6 pg/mL), and statistical significance was observed between NGT and DM (p < 0.05). There was significant correlation between fasting glucagon level and indexes of insulin sensitivity. During OGTT, glucagon levels were less suppressed in DM and preDM than in NGT, whereas no apparent relationship was observed between glucagon and GLP-1 secretion. Significant positive correlation was observed between glucagon levels during OGTT and fasting TG. In conclusion, subjects with mild T2DM exhibited fasting hyperglucagonemia and insufficient suppression to oral glucose load compared to NGT subjects.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Glucagon/metabolismo , Glucose/farmacologia , Estado Pré-Diabético/metabolismo , Adulto , Idoso , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Glucagon/sangue , Intolerância à Glucose/sangue , Intolerância à Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/patologia , Índice de Gravidade de Doença , Adulto Jovem
19.
Nature ; 569(7758): 663-671, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31142858

RESUMO

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.


Assuntos
Biomarcadores/metabolismo , Biologia Computacional , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal , Interações entre Hospedeiro e Microrganismos/genética , Estado Pré-Diabético/microbiologia , Proteoma/metabolismo , Transcriptoma , Adulto , Idoso , Antibacterianos/administração & dosagem , Biomarcadores/análise , Estudos de Coortes , Conjuntos de Dados como Assunto , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Glucose/metabolismo , Voluntários Saudáveis , Humanos , Inflamação/metabolismo , Vacinas contra Influenza/imunologia , Insulina/metabolismo , Resistência à Insulina , Estudos Longitudinais , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade , Estado Pré-Diabético/genética , Estado Pré-Diabético/metabolismo , Infecções Respiratórias/genética , Infecções Respiratórias/metabolismo , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Estresse Fisiológico , Vacinação/estatística & dados numéricos
20.
Am J Clin Nutr ; 109(6): 1738-1745, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31051499

RESUMO

BACKGROUND: Telomere attrition may play an important role in the pathogenesis and severity of type 2 diabetes (T2D), increasing the probability of ß cell senescence and leading to reduced cell mass and decreased insulin secretion. Nutrition and lifestyle are known factors modulating the aging process and insulin resistance/secretion, determining the risk of T2D. OBJECTIVES: The aim of this study was to evaluate the effects of pistachio intake on telomere length and other cellular aging-related parameters of glucose and insulin metabolism. METHODS: Forty-nine prediabetic subjects were included in a randomized crossover clinical trial. Subjects consumed a pistachio-supplemented diet (PD, 50 E% [energy percentage] carbohydrates and 33 E% fat, including 57 g pistachios/d) and an isocaloric control diet (CD, 55 E% carbohydrates and 30 E% fat) for 4 mo each, separated by a 2-wk washout period. DNA oxidation was evaluated by DNA damage (via 8-hydroxydeoxyguanosine). Leucocyte telomere length and gene expression related to either oxidation, telomere maintenance or glucose, and insulin metabolism were analyzed by multiplexed quantitative reverse transcriptase-polymerase chain reaction after the dietary intervention. RESULTS: Compared with the CD, the PD reduced oxidative damage to DNA (mean: -3.5%; 95% CI: -8.07%, 1.05%; P = 0.009). Gene expression of 2 telomere-related genes (TERT and WRAP53) was significantly upregulated (164% and 53%) after the PD compared with the CD (P = 0.043 and P = 0.001, respectively). Interestingly, changes in TERT expression were negatively correlated to changes in fasting plasma glucose concentrations and in the homeostatic model assessment of insulin resistance. CONCLUSIONS: Chronic pistachio consumption reduces oxidative damage to DNA and increases the gene expression of some telomere-associated genes. Lessening oxidative damage to DNA and telomerase expression through diet may represent an intriguing way to promote healthspan in humans, reversing certain deleterious metabolic consequences of prediabetes. This study was registered at clinicaltrials.gov as NCT01441921.


Assuntos
DNA/metabolismo , Pistacia/metabolismo , Estado Pré-Diabético/dietoterapia , Estado Pré-Diabético/genética , Telômero/metabolismo , Adulto , Idoso , Glicemia/metabolismo , Dano ao DNA , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Nozes/química , Nozes/metabolismo , Oxirredução , Pistacia/química , Estado Pré-Diabético/metabolismo , Telomerase/genética , Telomerase/metabolismo , Telômero/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA