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1.
Medicine (Baltimore) ; 98(44): e17736, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689819

RESUMO

To explore associated risk factors and their interactions with type 2 diabetes (T2DM) among the elderly with prediabetes in rural areas in China.A nested case-control study was conducted in a fixed cohort to identify the risk factors for T2DM among the elderly with prediabetes in rural areas of Yiyang City in China. A total of 37 elderly with T2DM were included in the cases group and 111 elderly subjects with prediabetes were matched in the control group. Data related to sociodemographic characteristics, lifestyle behavior, and anthropometric variables were collected by trained staff using standard tools. The risk factors for T2DM were determined using conditional logistic regression analysis, and their additive interactions were also explored.Multivariable conditional logistic regression analysis results showed that overweight/obesity (odds ratio [OR] = 4.80, 95% confidence interval [CI]: 1.20-12.28), family history of diabetes (OR = 3.63, 95% CI: 1.03-12.81), physically inactive (OR = 3.08, 95% CI: 1.14-8.30), high waist-to-hip ratio (WHR) (OR = 3.15, 95% CI: 1.27-7.80), and inadequate diabetes-specific health literacy (DSHL) (OR = 3.92, 95% CI: 1.14-13.48) increased the risk for T2DM. Additive interactions for T2DM were observed between a family history of diabetes and high WHR with a relative excess risk of interaction (RERI) of 10.02 (95% CI: 4.25, 15.78), and between high WHR and overweight or obesity, with an RERI of 3.90 (95% CI: 0.36, 7.44).The independent risk factors for T2DM are overweight or obesity, high WHR, family history of diabetes, physically inactive, and inadequate DSHL. High WHR as a risk factor for T2DM has additive interactions with family history of diabetes and overweight or obesity.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Estado Pré-Diabético/etiologia , População Rural/estatística & dados numéricos , Idoso , Antropometria , Estudos de Casos e Controles , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Exercício , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/fisiopatologia , Risco , Fatores de Risco , Comportamento Sedentário , Relação Cintura-Quadril
3.
Life Sci ; 236: 116836, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31493479

RESUMO

AIMS: The present experiment was conceptualised to explore the therapeutic response of tetramethylpyrazine (TMP), a major active constituent of Ligusticum chuanxiong, a Chinese traditional medicinal plant, in high-fat diet (HFD)-streptozotocin (STZ)-induced diabetes in rats and to identify the possible mechanism of action. MAIN METHODS: Dose-reliant effect of oral treatment of TMP (100, 150 and 200 mg/kg/day) for 28 days was evaluated by calculating the alteration in body weight, level of fasting blood glucose (FBG), plasma insulin, homeostasis model assessment (HOMA), serum lipids, oral glucose & intraperitoneal insulin tolerance and glycosylated haemoglobin in HFD-STZ-induced type-2 diabetic (T2D) rats and underlying molecular mechanisms of TMP was also studied. KEY FINDINGS: TMP treatment prominently reduced the level of FBG, glycosylated haemoglobin and revived body weight gain and level of serum insulin dose-dependently in diabetic rats. TMP treatment considerably improved insulin resistance, as observed in oral glucose tolerance and insulin tolerance tests. Moreover, dose-dependent reduction in the level of pro-inflammatory cytokines, C-reactive protein (CRP) and interleukin-6 (IL-6) was observed and their level was found to be significantly reduced in highest dose TMP (200 mg/kg) treated diabetic rats, pointing towards TMP mediated recovery of insulin signalling and a decrease in insulin resistance. The expressions of p-PI3K-p85/p-Akt/GLUT-4 were also significantly up-regulated by TMP (200 mg/kg), suggesting the connection of the PI3K/Akt signal pathway in the anti-hyperglycemic action of TMP. SIGNIFICANCE: These findings suggest that TMP may be used as a potential agent for type-2 diabetes treatment.


Assuntos
Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 2/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirazinas/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Transportador de Glucose Tipo 4/genética , Masculino , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Wistar , Transdução de Sinais , Vasodilatadores/farmacologia
4.
Zhonghua Nei Ke Za Zhi ; 58(9): 673-679, 2019 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-31461819

RESUMO

Objective: To examine associations of 25-hydroxyvitamin D [25(OH)D] concentrations with sex hormone levels and cardiovascular risk factors. Methods: A total of 697 male subjects were obtained from the thyroid disorders, lodine status and diabetes: a national epidemiological survey-2014 (TIDE) research--Henan sub-center survey through multistage stratified cluster random sampling from December 2015 to March 2016. The associations between 25(OH)D and sex hormones or cardiovascular risk factors were analyzed by linear regression analyses. Results: The age of the subjects was (46.6±15.9) years (19-85 years). Proportions of vitamin D deficient, vitamin D intermediate and vitamin D optimal were 9.3%, 13.1% and 77.6%, respectively. More subjects with vitamin D deficient were in urban area than in rural area (13.3% vs. 5.7%, P=0.001). After fully adjusting for age, residence area, economic status, education, body mass index, waist circumference, homeostasis model assessment of insulin resistance (HOMA-IR), hypertension, diabetes, triglyceride, high-density lipoproteincholesterol, total cholesterol, low-density lipoprotein cholesterol and uric acid, linear regression analyses showed that every 25 nmol/L increase in 25(OH)D levels increased lg FT(FT=free testosterone) by 0.013ng/L (ß=0.013, P=0.036), lg DHT (DHT=dihydrotestosterone) by 0.030 ng/L (ß=0.030, P=0.019), and lg AD (AD=androstenedione) by 0.019 µg/L (ß=0.019, P=0.008). After fully adjusting for age, residence area, economic status and education, every 25 nmol/L increase in 25(OH)D levels lowered glycosylated hemoglobin A1c (HbA1c) by 0.051% (ß=-0.051, P=0.027). Conclusions: Higher 25(OH)D concentrations in men were associated with higher FT, DHT, AD and lower HbA1c levels.


Assuntos
Doenças Cardiovasculares , Hormônios Esteroides Gonadais/sangue , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , População Urbana , Adulto Jovem
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.
BMJ ; 366: l4292, 2019 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345923

RESUMO

OBJECTIVE: To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. DESIGN: Individual participant data meta-analysis. DATA SOURCES: Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and February 2017 through electronic searches in major medical databases (Medline, Embase, and Scopus) and discussion with investigators. REVIEW METHODS: Data from cohort studies or multicohort consortia with available genome-wide genetic data and information about the quality of dietary fat and the incidence of type 2 diabetes in participants of European descent was sought. Prospective cohorts that had accrued five or more years of follow-up were included. The type 2 diabetes genetic risk profile was characterized by a 68-variant polygenic risk score weighted by published effect sizes. Diet was recorded by using validated cohort-specific dietary assessment tools. Outcome measures were summary adjusted hazard ratios of incident type 2 diabetes for polygenic risk score, isocaloric replacement of carbohydrate (refined starch and sugars) with types of fat, and the interaction of types of fat with polygenic risk score. RESULTS: Of 102 305 participants from 15 prospective cohort studies, 20 015 type 2 diabetes cases were documented after a median follow-up of 12 years (interquartile range 9.4-14.2). The hazard ratio of type 2 diabetes per increment of 10 risk alleles in the polygenic risk score was 1.64 (95% confidence interval 1.54 to 1.75, I2=7.1%, τ2=0.003). The increase of polyunsaturated fat and total omega 6 polyunsaturated fat intake in place of carbohydrate was associated with a lower risk of type 2 diabetes, with hazard ratios of 0.90 (0.82 to 0.98, I2=18.0%, τ2=0.006; per 5% of energy) and 0.99 (0.97 to 1.00, I2=58.8%, τ2=0.001; per increment of 1 g/d), respectively. Increasing monounsaturated fat in place of carbohydrate was associated with a higher risk of type 2 diabetes (hazard ratio 1.10, 95% confidence interval 1.01 to 1.19, I2=25.9%, τ2=0.006; per 5% of energy). Evidence of small study effects was detected for the overall association of polyunsaturated fat with the risk of type 2 diabetes, but not for the omega 6 polyunsaturated fat and monounsaturated fat associations. Significant interactions between dietary fat and polygenic risk score on the risk of type 2 diabetes (P>0.05 for interaction) were not observed. CONCLUSIONS: These data indicate that genetic burden and the quality of dietary fat are each associated with the incidence of type 2 diabetes. The findings do not support tailoring recommendations on the quality of dietary fat to individual type 2 diabetes genetic risk profiles for the primary prevention of type 2 diabetes, and suggest that dietary fat is associated with the risk of type 2 diabetes across the spectrum of type 2 diabetes genetic risk.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Adulto , Alelos , Diabetes Mellitus Tipo 2/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
7.
Rev Lat Am Enfermagem ; 27: e3161, 2019 Jul 18.
Artigo em Português, Inglês, Espanhol | MEDLINE | ID: mdl-31340346

RESUMO

OBJECTIVE: to detect the risk of development of type 2 diabetes in nurses and its relationship with metabolic alterations. METHOD: cross-sectional study, with 155 nurses. The variables investigated were: sociodemographic, body mass index, waist circumference, waist-hip index, lipid profile, basal glycemia and oral glucose tolerance curve. The Finnish Diabetes Risk Score was used to collect data. RESULTS: 155 nurses were included, with an average age of 44 years and 85% were overweight or obese. 52% had a family history of diabetes and 21% had occasional hyperglycemia. With respect to the risk, 59% were identified with moderate and very high risk for type 2 diabetes. Glucose, insulin, glycosylated hemoglobin A1c and insulin resistance increased in parallel to the increased risk for type 2 diabetes, although lipids did not increase. 27% of the sample had impaired fasting glycemia. 15% had glucose intolerance and 5% had type 2 diabetes. CONCLUSION: there was a high detection rate of people at risk for type 2 diabetes (59%) and the high and very high risk score was associated with high levels of glycosylated hemoglobin A1c, glucose, insulin and insulin resistance, but not with lipids.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Obesidade/complicações , Sobrepeso/complicações , Adulto , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Hiperglicemia , Resistência à Insulina , México , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Estado Pré-Diabético/complicações , Estado Pré-Diabético/prevenção & controle , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários
8.
Arch Endocrinol Metab ; 63(5): 487-494, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271576

RESUMO

OBJECTIVE: Different pathways may lead from night work to metabolic diseases, including type 2 diabetes. This study aimed to explore the direct and indirect pathways from night work to glycemic levels, considering the role of physical activity, waist circumference and snacking using data from ELSA-Brasil. MATERIALS AND METHODS: A structural equation model was used to confirm the pathways from night work to glycemic levels. The latent variable, "glycemic levels", included fasting glucose, glycated hemoglobin and 2-hour plasma glucose. RESULTS: A total of 10.396 participants were included in the analyses. The final model showed that among women, night work was associated with increased glycemic levels. A statistical significant association between night work and glycemic levels mediated by waist circumference was observed among women and men. CONCLUSIONS: The association between night shift and glycemic levels can be interpreted as an important step toward understanding the pathways that could explain night work as a risk factor for diabetes using epidemiological data.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/etiologia , Hemoglobina A Glicada/análise , Análise de Classes Latentes , Jornada de Trabalho em Turnos/efeitos adversos , Adulto , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Jornada de Trabalho em Turnos/estatística & dados numéricos , Circunferência da Cintura
9.
Diabetes Res Clin Pract ; 155: 107798, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31330161

RESUMO

OBJECTIVES: Lipid accumulation product (LAP) index and Visceral Adiposity Index (VAI) are simple calculations to measure fat accumulation and visceral fat respectively. We aim to study the use of LAP index and VAI as diagnostic parameter and predictor of T2DM. METHODS: We analysed the baseline and longitudinal data from the Indonesian Ministry of Health Cohort Study of Non-communicable Diseases Risk Factors in West Java, comprising 846 men and 2437 women aged 25-65 years. At baseline, the odds ratio for the diagnosis of prediabetes and T2DM among subjects with high LAP Index and VAI was analysed using logistic regression analysis. In the longitudinal analysis, LAP index and VAI as predictor of prediabetes and T2DM was analysed with cox regression analysis. RESULT: Worsening glycemia status was associated with an increased LAP index and VAI (p < 0.001). Subjects with high VAI had an increased OR of having T2DM in both men [OR, 95%CI, 2.29(1.15-4.56), p = 0.018] and women [1.95(1.49-2.54), p < 0.001)]. Association of high LAP with T2DM was found only in women [OR, 95%CI, 2.11(1.16-1.52), p < 0.001]. In terms of T2DM prediction, only women [RR, 95% CI, 2.59 (1.05-6.39), p = 0.038)], with high VAI had an increased risk of T2DM in the future. High LAP index was not associated with an in increased risk of T2DM in the future in both sexes. CONCLUSION: High LAP index was associated with an increased risk of T2DM diagnosis in women but it could not predict the development of T2DM. High VAI was associated with an increased risk of T2DM diagnosis in both sexes, however, it could only predict the development of T2DM in women.


Assuntos
Adiposidade , Diabetes Mellitus Tipo 2/diagnóstico , Produto da Acumulação Lipídica , Doenças não Transmissíveis/epidemiologia , Obesidade Abdominal/complicações , Adulto , Idoso , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Indonésia/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco
10.
Environ Toxicol ; 34(10): 1149-1159, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31313498

RESUMO

Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α-smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Poluentes Ambientais/efeitos adversos , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Coração/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Miocárdio/metabolismo , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada/genética , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo
11.
Lakartidningen ; 1162019 Apr 09.
Artigo em Sueco | MEDLINE | ID: mdl-31192428

RESUMO

Different prediabetic states precede overt type 2 diabetes. Prediabetes also carries an increased cardiovascular risk per seand may be divided into fasting hyperglycemia, impaired glucose tolerance and intermediate hyperglycemia. Mixed forms of these are very common. Prediabetes develops insidiously for many years and usually produces no symptoms until very late. It is possible to prevent prediabetes from progressing to manifest type 2 diabetes and it can also be made to revert to normoglycemia. The importance of lifestyle interventions, pharmacological treatment, surgical treatment and community efforts is discussed.


Assuntos
Estado Pré-Diabético , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta para Diabéticos , Exercício , Promoção da Saúde , Estilo de Vida Saudável , Humanos , Estado Pré-Diabético/complicações , Estado Pré-Diabético/dietoterapia , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/prevenção & controle , Fatores de Risco , Prevenção do Hábito de Fumar
12.
Life Sci ; 229: 80-92, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31095947

RESUMO

PURPOSE: Bile acids (BAs) as a kind of endogenous and signaling molecules altered under the circumstance of T2DM, which could impact on the relevant pathways to further affect the glucose metabolism and insulin secretion and might be associated with the T2DM development and restoration. However, the potential mechanisms still need more various and multifaceted studies. Here, we explored the alterations of BAs features and their mechanisms, and discussed the potential effects of the altered BAs on the glucose metabolic disorder via the relevant signaling pathways. MAIN METHODS: The high-fat diet (HFD) feeding combining with injection of low-dose streptozotocin (STZ) was employed for inducing the T2DM rat model. Based on that, we investigated the alterations of the concentrations and compositions of BAs and their mechanisms, and explored the effects of the altered BAs on the glucose metabolic disorder via farnesoid X receptor (Fxr) and G protein-coupled bile acid receptor (Tgr5)-mediated pathways. KEY FINDINGS: In rats with T2DM, the BAs in rats with T2DM exhibited characteristic alterations, especially the increased ratio of 12α-OH to non-12α-OH BAs in serum, which could be ascribed to the up-regulated Cyp8b1 mRNA expression ratio in the liver. Moreover, Additionally, the altered BAs had negative effects on glucose metabolic disorder via inhibiting the Trg5/Fxr-mediated pathways in colon, liver and pancreas in rats with T2DM. SIGNIFICANCE: BAs in rats with T2DM exhibited the characteristic alterations, which could provide a cue for searching biomarkers of the T2DM diagnosis, and the altered BAs might aggravate the glucose metabolic disorder.


Assuntos
Ácidos e Sais Biliares/metabolismo , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Resistência à Insulina , Estreptozocina/toxicidade , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo dos Lipídeos , Masculino , Ratos , Ratos Wistar , Transdução de Sinais
13.
Int J Mol Sci ; 20(10)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109071

RESUMO

Type 1 and type 2 diabetes mellitus (DM) are chronic diseases that affect nearly 425 million people worldwide, leading to poor health outcomes and high health care costs. High-throughput metabolomics screening can provide vital insight into the pathophysiological pathways of DM and help in managing its effects. The primary aim of this study was to contribute to the understanding and management of DM by providing reliable evidence of the relationships between metabolites and type 1 diabetes (T1D) and metabolites and type 2 diabetes (T2D). Information for the study was obtained from the PubMed, MEDLINE, and EMBASE databases, and leads to additional articles that were obtained from the reference lists of the studies examined. The results from the selected studies were used to assess the relationships between diabetes (T1D and/or T2D) and metabolite markers-such as glutamine, glycine, and aromatic amino acids-in patients. Seventy studies were selected from the three databases and from the reference lists in the records retrieved. All studies explored associations between various metabolites and T1D or T2D. This review identified several plasma metabolites associated with T2D prediabetes and/or T1D and/or T2D in humans. The evidence shows that metabolites such as glucose, fructose, amino acids, and lipids are typically altered in individuals with T1D and T2D. These metabolites exhibit significant predictive associations with T2D prediabetes, T1D, and/or T2D. The current review suggests that changes in plasma metabolites can be identified by metabolomic techniques and used to identify and analyze T1D and T2D biomarkers. The results of the metabolomic studies can be used to help create effective interventions for managing these diseases.


Assuntos
Biomarcadores , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Metaboloma , Metabolômica , Aminoácidos/metabolismo , Animais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Metabolômica/métodos
14.
Molecules ; 24(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096578

RESUMO

A traditional Chinese tea with many pharmacological effects, vine tea (VT) is considered a potential dietary supplement to improve type 2 diabetes (T2D). To investigate the effect and mechanism of VT on glucose and lipid metabolic disorders in T2D rats, Wistar rats fed a normal diet served as the normal control, while rats fed a high-fat diet combined with low-dose streptozotocin (STZ)-induced T2D were divided into three groups: The model group (MOD); the positive control group (MET, metformin at 200 mg/kg/d); and the VT-treated group (VT500, allowed to freely drink 500 mg/L VT). After four weeks of intervention, biochemical metrics indicated that VT significantly ameliorated hyperglycemia, hyperlipidemia and hyperinsulinemia in T2D rats. Metabolomics research indicated that VT regulated the levels of metabolites closely related to glucose and lipid metabolism and promoted glycogen synthesis. Furthermore, VT had a significant influence on the expression of key genes involved in the Akt signaling pathway, inhibited gluconeogenesis through the Akt/Foxo1/Pck2 signaling pathway, and reduced fatty acid synthesis via the SREBP1c/Fasn signaling pathways. In conclusion, VT has great potential as a dietary supplement to ameliorate glucose and lipid metabolic disorders via the Akt signaling pathway in T2D rats.


Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Suplementos Nutricionais , Glucose/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Chá/química , Animais , Biomarcadores , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Metaboloma , Metabolômica/métodos , Ratos
15.
Nat Med ; 25(5): 792-804, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31068711

RESUMO

Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health.


Assuntos
Big Data , Diabetes Mellitus Tipo 2/etiologia , Medicina de Precisão/estatística & dados numéricos , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Exoma , Feminino , Microbioma Gastrointestinal , Humanos , Resistência à Insulina , Estudos Longitudinais , Masculino , Metaboloma , Pessoa de Meia-Idade , Modelos Biológicos , Fatores de Risco , Transcriptoma
16.
Int J Mol Sci ; 20(9)2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064116

RESUMO

Hypercholesterolemia may be causally related to heart failure with preserved ejection fraction (HFpEF). We aimed to establish a HFpEF model associated with hypercholesterolemia and type 2 diabetes mellitus by feeding a high-sucrose/high-fat (HSHF) diet to C57BL/6J low-density lipoprotein receptor (LDLr)-/- mice. Secondly, we evaluated whether cholesterol-lowering adeno-associated viral serotype 8 (AAV8)-mediated LDLr gene transfer prevents HFpEF. AAV8-LDLr gene transfer strongly (p < 0.001) decreased plasma cholesterol in standard chow (SC) mice (66.8 ± 2.5 mg/dl versus 213 ± 12 mg/dl) and in HSHF mice (84.6 ± 4.4 mg/dl versus 464 ± 25 mg/dl). The HSHF diet induced cardiac hypertrophy and pathological remodeling, which were potently counteracted by AAV8-LDLr gene transfer. Wet lung weight was 19.0% (p < 0.001) higher in AAV8-null HSHF mice than in AAV8-null SC mice, whereas lung weight was normal in AAV8-LDLr HSHF mice. Pressure-volume loop analysis was consistent with HFpEF in AAV8-null HSHF mice and showed a completely normal cardiac function in AAV8-LDLr HSHF mice. Treadmill exercise testing demonstrated reduced exercise capacity in AAV8-null HSHF mice but a normal capacity in AAV8-LDLr HSHF mice. Reduced oxidative stress and decreased levels of tumor necrosis factor-α may mediate the beneficial effects of cholesterol lowering. In conclusion, AAV8-LDLr gene therapy prevents HFpEF.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/prevenção & controle , Terapia Genética/métodos , Insuficiência Cardíaca/prevenção & controle , Hipercolesterolemia/terapia , Receptores de LDL/genética , Animais , Colesterol/sangue , Dependovirus/genética , Diabetes Mellitus Tipo 2/etiologia , Cardiomiopatias Diabéticas/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/efeitos adversos , Feminino , Insuficiência Cardíaca/fisiopatologia , Hipercolesterolemia/complicações , Hipercolesterolemia/etiologia , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Receptores de LDL/metabolismo , Volume Sistólico , Fator de Necrose Tumoral alfa/sangue
17.
BMC Public Health ; 19(1): 575, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31092217

RESUMO

BACKGROUND: Sedentary time is associated with increased risk of type 2 diabetes, but the association between objectively measured sedentary time and incident gestational diabetes mellitus (GDM) has not been tested. The purpose of this paper is to test associations between objectively measured sedentary time and self-reported television time during pregnancy with incident GDM and plasma glucose levels among women at high risk for GDM. METHODS: At 20 weeks' gestation, pregnant women (n = 188) in the North East of England with a risk factor for GDM wore an activPAL accelerometer and reported their usual television time. Participants underwent a standard oral glucose tolerance test at 24-28 weeks' gestation. Regression analyses were used to test for associations of total and prolonged sedentary time, breaks in sedentary time, and television time with GDM and fasting and 2-h glucose levels. Interaction terms were applied to examine whether the association between each indicator of sedentary time and glucose levels differed by GDM status. RESULTS: Total sedentary time (hours/day) was not associated with incident GDM (OR 1.00 (95%CI 1.00, 1.01)). The association between total sedentary time and glucose levels depended on GDM status: sedentary time was associated with fasting (ß = 0.16 (95%CI 0.01, 0.31)) and 2-h (ß = 0.15 (95%CI 0.01, 0.30)) glucose levels for those without GDM, while breaks in sedentary time were associated with lower fasting (ß = - 0.55 (95%CI - 0.92, - 0.17)) and 2-h (ß = - 0.40 (95%CI - 0.77, - 0.03)) glucose levels for those with GDM. Prolonged sedentary time was associated with higher fasting glucose levels regardless of GDM status (ß 0.15 (0.01, 0.30)). Television time was associated with development of GDM (OR 3.03 (95%CI 1.21, 7.96)) but not with plasma glucose levels. CONCLUSIONS: This is the first study to test associations between posture-based measures of sedentary time during pregnancy and GDM and glucose levels. The findings presented here suggest the possible importance of minimizing or breaking up sedentary time for the management of glucose levels during pregnancy, at least among women at high risk of GDM. Further research is needed to understand the different roles of total sedentary time and television time in the development of GDM.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Diabetes Gestacional/etiologia , Comportamento Sedentário , Televisão , Acelerometria , Adulto , Glicemia/análise , Inglaterra , Feminino , Teste de Tolerância a Glucose , Humanos , Gravidez , Segundo Trimestre da Gravidez , Análise de Regressão , Fatores de Risco , Autorrelato
18.
Toxicol Lett ; 312: 148-156, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31100493

RESUMO

Cadmium (Cd), lead (Pb) and mercury (Hg) are known nephrotoxicants that have been associated with the risk of developing type-2 diabetes (T2D). The aim of this pilot study was to explore relations between biomarkers of Cd, Pb and Hg exposure, early urinary biomarkers of renal dysfunction (kidney-injured molecule-1 (KIM-1), N-acetylglucosaminidase and retinol-binding protein (RBP)) and plasma biomarkers deemed predictive of the risk of developing T2D (adiponectin, leptin, branched-chain and aromatic amino acids), among 70 participants (age range: (46-87 yrs)) from the Canadian Longitudinal Study on Aging (CLSA) with normal glycemic control (glycated haemoglobin ≤ 6.5%) in all but four of them. Significant (p < 0.05) Spearman correlation coefficients were obtained between: plasma adiponectin and RBP (r = 0.42), urinary Cd (r = 0.32), blood Cd (r = 0.36); KIM-1 and CdU (r = 0.33) as well as HgU (r = 0.37); RBP and isoleucine (r = -0.28), leucine (r = -0.33), tyrosine (r = -0.3) and valine (r = -0.44); CdU and isoleucine and valine (r = -0.27 for both). Multiple linear regression analyses showed that some T2D-related biomarkers are confounders of associations between RBP and Hg or Cd biomarkers. Path analyses support a mediating effect of adiponectin on the relation between urinary Cd and RBP. Concluding, this pilot study originally investigated a comprehensive set of biomarkers on complex interactions between toxic metal exposure, renal function and T2D in a group of aging Canadians. Its findings warrant further investigation of longitudinal data in a greater number of participants.


Assuntos
Cádmio , Diabetes Mellitus Tipo 2/sangue , Nefropatias/urina , Chumbo , Mercúrio , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Canadá , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Exposição Ambiental , Feminino , Humanos , Nefropatias/etiologia , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto
19.
Nat Genet ; 51(5): 804-814, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31043758

RESUMO

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.


Assuntos
Peso ao Nascer/genética , Adulto , Pressão Sanguínea/genética , Estatura/genética , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Desenvolvimento Fetal/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Cardiopatias/etiologia , Cardiopatias/genética , Humanos , Recém-Nascido , Masculino , Herança Materna/genética , Troca Materno-Fetal/genética , Doenças Metabólicas/etiologia , Doenças Metabólicas/genética , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Gravidez , Fatores de Risco
20.
Environ Sci Pollut Res Int ; 26(16): 16261-16273, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30977004

RESUMO

We performed a time series analysis to investigate the potential association between exposure to ambient air pollution and type 2 diabetes (T2D) incidence in the Chinese population. Monthly time series data between 2008 and 2015 on ambient air pollutants and incident T2D (N = 25,130) were obtained from the Environment Monitoring Center of Ningbo and the Chronic Disease Surveillance System of Ningbo. Relative risks (RRs) and 95% confidence intervals (95% CIs) of incident T2D per 10 µg/m3 increases in ambient air pollutants were estimated from Poisson generalized additive models. Exposure to particulate matter < 10 µm (PM10) and sulfur dioxide (SO2) was associated with increased T2D incidence. The relative risks (RRs) of each increment in 10 µg/m3 of PM10 and SO2 were 1.62 (95% CI, 1.16-2.28) and 1.63 (95% CI, 1.12-2.38) for overall participants, whereas for ozone (O3) exposure, the RRs were 0.78 (95% CI, 0.68-0.90) for overall participants, 0.78 (95% CI, 0.69-0.90) for males, and 0.78 (95% CI, 0.67-0.91) for females, respectively. Exposure to PM10 and SO2 is positively associated with T2D incidence, whereas O3 is negatively associated with T2D incidence.


Assuntos
Poluição do Ar/efeitos adversos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Adulto , Poluentes Atmosféricos/análise , Poluição do Ar/análise , China/epidemiologia , Cidades , Intervalos de Confiança , Monitoramento Ambiental , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Ozônio/análise , Ozônio/toxicidade , Material Particulado/análise , Dióxido de Enxofre/análise , Dióxido de Enxofre/toxicidade
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