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1.
Curr Diabetes Rev ; 16(2): 104-116, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31074371

RESUMO

BACKGROUND: Preclinical experimental models historically play a critical role in the exploration and characterization of disease pathophysiology. Further, these in-vivo and in-vitro preclinical experiments help in target identification, evaluation of novel therapeutic agents and validation of treatments. INTRODUCTION: Diabetes mellitus (DM) is a multifaceted metabolic disorder of multidimensional aetiologies with the cardinal feature of chronic hyperglycemia. To avoid or minimize late complications of diabetes and related costs, primary prevention and early treatment are therefore necessary. Due to its chronic manifestations, new treatment strategies need to be developed, because of the limited effectiveness of the current therapies. METHODS: The study included electronic databases such as Pubmed, Web of Science and Scopus. The datasets were searched for entries of studies up to June, 2018. RESULTS: A large number of in-vivo and in-vitro models have been presented for evaluating the mechanism of anti-hyperglycaemic effect of drugs in hormone-, chemically-, pathogen-induced animal models of diabetes mellitus. The advantages and limitations of each model have also been addressed in this review. CONCLUSION: This review encompasses the wide pathophysiological and molecular mechanisms associated with diabetes, particularly focusing on the challenges associated with the evaluation and predictive validation of these models as ideal animal models for preclinical assessments and discovering new drugs and therapeutic agents for translational application in humans. This review may further contribute to discover a novel drug to treat diabetes more efficaciously with minimum or no side effects. Furthermore, it also highlights ongoing research and considers the future perspectives in the field of diabetes.


Assuntos
Diabetes Mellitus/fisiopatologia , Animais , Diabetes Mellitus/etiologia , Diabetes Mellitus/terapia , Modelos Animais de Doenças , Humanos , Técnicas In Vitro
2.
Nat Med ; 25(12): 1822-1832, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31806905

RESUMO

Although intermittent increases in inflammation are critical for survival during physical injury and infection, recent research has revealed that certain social, environmental and lifestyle factors can promote systemic chronic inflammation (SCI) that can, in turn, lead to several diseases that collectively represent the leading causes of disability and mortality worldwide, such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease and autoimmune and neurodegenerative disorders. In the present Perspective we describe the multi-level mechanisms underlying SCI and several risk factors that promote this health-damaging phenotype, including infections, physical inactivity, poor diet, environmental and industrial toxicants and psychological stress. Furthermore, we suggest potential strategies for advancing the early diagnosis, prevention and treatment of SCI.


Assuntos
Doença Crônica/epidemiologia , Inflamação/fisiopatologia , Longevidade/genética , Doenças Autoimunes/etiologia , Doenças Autoimunes/fisiopatologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/fisiopatologia , Humanos , Inflamação/complicações , Inflamação/epidemiologia , Estilo de Vida , Longevidade/fisiologia , Neoplasias/etiologia , Neoplasias/fisiopatologia , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
3.
Diabetes Res Clin Pract ; 158: 107903, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31678625

RESUMO

AIM: We aimed to examine the association between serum magnesium and diabetes and hypertension among Qatari adults. METHODS: In the cross-sectional study, we used data from 9693 Qatari participants aged 20 years and above attending the Qatar Biobank (QBB) Study. Blood samples were analyzed in a central lab. Habitual food consumption was assessed by a food frequency questionnaire. Reduced rank regression was used to construct magnesium related dietary pattern (MRDP) using serum magnesium as a response variable. Diabetes was defined by blood glucose, HbA1c or known diabetes. Prediabetes was defined as HbA1c between 5.7% and 6.4%. Subclinical magnesium deficiency was defined as serum magnesium <0.85 mmol/L. RESULTS: The prevalence of diabetes, prediabetes and subclinical magnesium deficiency was 18.9%, 11.5% and 59.5%, respectively. Across the quartiles of serum magnesium from high to low, the prevalence ratios (PR 95%CI) for diabetes were 1.00, 1.35, 1.88, and 2.70 (95%CI 2.38-3.05), respectively (p for trend <0.001). The presence of hypertension significantly increased the probability of diabetes along a wide range of low serum magnesium. A low intake of MRDP was also positively associated with diabetes and high HbA1c. CONCLUSION: Subclinical magnesium deficiency is common in Qatar and associates with diabetes, prediabetes and hypertension in Qatari adults.


Assuntos
Bancos de Espécimes Biológicos/tendências , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Hipertensão/sangue , Hipertensão/etiologia , Magnésio/metabolismo , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Catar
4.
Medicine (Baltimore) ; 98(48): e17984, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770208

RESUMO

Pediatric patients suffer from chronic pancreatitis (CP), especially those with diabetes mellitus (DM). This study aimed to identify the incidence of and risk factors for DM in pediatric CP.CP patients admitted to our center from January 2000 to December 2013 were assigned to the pediatric (<18 years old) and adult group according to their age at onset of CP. Cumulative rates of DM and risk factors for both groups were calculated and identified.The median follow-up duration for the whole cohort was 7.6 years. In these 2153 patients, 13.5% of them were pediatrics. The mean age at the onset and the diagnosis of CP in pediatrics were 11.622 and 19.727, respectively. DM was detected in 13.1% patients and 31.0% patients in the pediatric group and adult group, respectively. Age at the onset of CP, smoking history, body mass index (BMI), and etiology of CP were identified risk factors for DM in pediatrics.DM was detected in 13.1% pediatric patients. Age at the onset of CP, smoking history, BMI, and etiology of CP were identified risk factors for the development of DM in pediatric CP patients. The high-risk populations were suggested to be monitored frequently. They could also benefit from a lifestyle modification.


Assuntos
Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Pancreatite Crônica/complicações , Adolescente , Criança , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Am Surg ; 85(11): 1239-1245, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31775965

RESUMO

The purpose of this meta-analysis was to compare the clinical outcomes of central pancreatectomy (CP) with distal pancreatectomy (DP). PubMed, Web of Knowledge, and Ovid's database were searched for studies published in English language between January 1990 and December 2018. A meta-analysis was performed to compare the clinical outcomes of CP versus DP. Nineteen trials with 1440 patients were analyzed. Although there were no significant differences in the rate of intraoperative blood transfusion between two groups, CP costs more operative time as well as had more intraoperative blood loss than DP. Furthermore, the overall complication rate, pancreatic fistula rate, and the clinically significant pancreatic fistula rate were significantly higher in the CP group. On the other hand, CP had a lower risk of endocrine (odds ratio: 0.17; 95% confidence interval: 0.10, 0.29; P < 0.05) and exocrine insufficiency (odds ratio: 0.22; 95% confidence interval: 0.10, 0.48; P < 0.05). CP was associated with a higher pancreatic fistula rate, and it should be performed in selected patients who need preservation of the pancreas, which is of utmost importance.


Assuntos
Perda Sanguínea Cirúrgica/estatística & dados numéricos , Duração da Cirurgia , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Fístula Pancreática/etiologia , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias/etiologia , Transfusão de Sangue/estatística & dados numéricos , Intervalos de Confiança , Diabetes Mellitus/etiologia , Humanos , Tempo de Internação , Resultado do Tratamento
6.
Environ Health Perspect ; 127(11): 117005, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31746643

RESUMO

BACKGROUND: Exposure to excessive heat, which will continue to increase with climate change, is associated with increased morbidity due to a range of noncommunicable diseases (NCDs). Whether this is true for diabetes is unknown. OBJECTIVES: We aimed to quantify the relationship between heat exposure and risk of hospitalization due to diabetes in Brazil. METHODS: Data on hospitalizations and weather conditions were collected from 1,814 cities during the hot seasons from 2000 to 2015. A time-stratified case-crossover design was used to quantify the association between hospitalization for diabetes and heat exposure. Region-specific odds ratios (ORs) were used to calculate the attributable fractions (AFs). RESULTS: A total of 553,351 hospitalizations associated with diabetes were recorded during 2000-2015. Every 5°C increase in daily mean temperature was associated with 6% [OR=1.06; 95% confidence interval (CI): 1.04, 1.07] increase in hospitalization due to diabetes with lag 0-3 d. The association was greatest (OR=1.18; 95% CI: 1.13, 1.23) in those ≥80y of age, but did not vary by sex, and was generally consistent by region and type of diabetes. Assuming a causal association, we estimated that 7.3% (95% CI: 3.5, 10.9) of all hospitalizations due to diabetes in the hot season could be attributed to heat exposure during the study period. DISCUSSION: Short-term heat exposure may increase the burden of diabetes-related hospitalization, especially among the very elderly. As global temperatures continue to rise, this burden is likely to increase. https://doi.org/10.1289/EHP5688.


Assuntos
Diabetes Mellitus/epidemiologia , Hospitalização/estatística & dados numéricos , Temperatura Alta/efeitos adversos , Fatores Etários , Brasil/epidemiologia , Estudos Cross-Over , Diabetes Mellitus/etiologia , Geografia , Humanos , Fatores de Risco , Fatores Sexuais
7.
Metabolism ; 100S: 153952, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31610851

RESUMO

Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by persistent hyperglycemia. Its two most common forms are type 1 diabetes (T1D) and type 2 diabetes (T2D), for which genetic and environmental risk factors act in synergy. Because it occurs in children and involves infectious, autoimmune or toxic destruction of the insulin-secreting pancreatic beta-cells, type 1 diabetes has been called juvenile or insulin-deficient diabetes. In type 2, patients can still secrete some insulin but its effectiveness may be attenuated by 'insulin resistance.' There is also a group of rare forms of diabetes in the young which are inherited as monogenetic diseases. Whether one calls the underlying process 'genes vs. environment' or 'nature vs nurture', diabetes occurs at the interface of the two domains. Together with our genetic background we are born tabula rasa-a blank slate upon which the story of life, with all its environmental inputs will be written. There is one proviso: the influence of epigenetic inheritance must also be considered. Thus, in the creation of databases that include "big data" originating from genomic as well as exposome (defined as: the totality of environmental exposure from conception to death), a broad perspective is crucial as these factors act in concert in such chronic illnesses as diabetes that, for example, are likely to require adoption of an appropriate lifestyle change. Also, it is becoming increasingly evident that epigenetic factors can modulate the interplay between genes and environment. Consequently, throughout the life of an individual nature and nurture interact in a complex manner in the development of diabetes. This review addresses the question of the contribution of gene and environment and their interactions in the development of diabetes.


Assuntos
Diabetes Mellitus/etiologia , Interação Gene-Ambiente , Animais , Bases de Dados como Assunto , Epigenômica , Humanos , Insulina/genética , Insulina/metabolismo , Resistência à Insulina/genética
8.
Transplant Proc ; 51(8): 2714-2717, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31477423

RESUMO

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is associated with a higher risk of mortality and graft loss. The reported incidence of PTDM after kidney transplantation (KT) varies from 10% to 74% and varies by country and ethnicity. There are few reports of nationwide cohort studies on PTDM incidence and related factors in Korea. The purpose of this study was to evaluate incidence of PTDM and related factors within 1 year after KT in Korea. METHODS: The KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) enrolled 1080 recipients from July 2012 to August 2016. This study included 723 recipients, excluding 273 patients with pretransplant DM and 84 patients who were lost from follow-up within 1 year after KT. RESULTS: Among 723 recipients, 85 (11.8%) recipients were diagnosed and treated with PTDM. Recipient age, HLA mismatches, hemoglobin A1c (HbA1c), waist-hip ratio (WHR), and use of prednisolone were significantly higher in PTDM group than the nondiabetic group. In the multivariable logistic regression analysis, independent risk factors for PTDM were older recipient age, higher WHR, and HbA1c before KT. CONCLUSION: The incidence of PTDM was 11.8% in a nationwide Korean cohort study. The factors related to the development of PTDM within 1 year after KT were older recipient age and higher WHR, and HbA1c levels before KT. In recipients with high WHR, it is important to control pretransplant abdominal obesity to prevent PTDM after KT.


Assuntos
Diabetes Mellitus/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adulto , Estudos de Coortes , Diabetes Mellitus/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , República da Coreia , Fatores de Risco
9.
Expert Rev Clin Pharmacol ; 12(9): 825-830, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474169

RESUMO

Introduction: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are widely used for cardiovascular disease (CVD) prevention. Long-term use of statins has been linked to the development of diabetes mellitus (DM) which increases CVD risk. Areas covered: We discussed the reported incidence of DM in statin users, various possible mechanisms responsible for the development of DM and the clinical implications of this association on CVD risk. Relevant supporting literature was identified using MEDLINE/EMBASE search. Expert opinion: Data from available RCTs and observational studies suggest a 10-45% higher risk of new-onset DM with statin use compared to nonusers. Several cellular, molecular, and genetic mechanisms, and lifestyle changes have been studied and discussed as potential underlying mechanisms responsible for this elevated DM risk with statin therapy. The mode of the diabetogenic action of statins is still unclear and an interplay of pancreatic and peripheral effects in the pathogenesis of DM is a possibility. Despite these observations, the CVD preventative benefit of statin treatment outweighs the CVD risk associated with of development of new DM. There is a need for further research to identify the exact mechanisms involved so as to specifically target causative factors and individualize treatment.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/etiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Diabetes Mellitus/epidemiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
10.
Transplant Proc ; 51(7): 2228-2231, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474289

RESUMO

BACKGROUND: The aim of this study is to investigate the frequency and risk factors of new-onset diabetes after donation in kidney donors without diabetes. METHODS: Living donors of kidney transplants between 1998 and 2016 were evaluated. To detect the blood glucose profile of the donors, preoperative fasting glucose (pro-G), nephrectomy evening glucose (nG), and postoperative day 1 fasting glucose (post-G) values were measured. RESULTS: A total of 195 cases were included in the study. The mean follow-up time in months ± SD (range) was 56 ± 45 (12-215). Of these, 28 (14.3%) donors developed diabetes. The pro-G (103 ± 7.6 vs 93 ± 9.0), nG (208 ± 122 vs 163 ± 67) and post-G (121 ± 25 vs 111 ± 21) values of the donors with new-onset diabetes were higher. Nineteen donors (9.7%) had normal pro-G, nG, and post-G values (group A). However, there were 153 (78.5%) cases with at least 1 abnormal value (group B) and 25 (12.8%) cases that had abnormal values in all (pro-G, nG, and post-G) measurements (group C). The incidence of new-onset diabetes was 0 (0%) in group A, 11% in group B, and 48% in group C (P < .001). In multiple regression analysis, pro-G (Exp[B], 1.08; 95% CI, 1.04-1.13; P < .001) and basal glomerular filtration rate (Exp[B], 0.96; 95% CI, 0.94-0.99; P < .01) independently associated with new-onset diabetes. CONCLUSIONS: In kidney donors without a history of diabetes, the development of diabetes after donor nephrectomy is an important problem. Pre- and postoperative blood glucose levels provide important information to predict these cases.


Assuntos
Diabetes Mellitus/etiologia , Hiperglicemia/etiologia , Complicações Intraoperatórias/etiologia , Doadores Vivos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Glicemia/análise , Diabetes Mellitus/sangue , Jejum/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Hiperglicemia/sangue , Complicações Intraoperatórias/sangue , Rim/cirurgia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Fatores de Risco
11.
Transplant Proc ; 51(7): 2434-2438, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474298

RESUMO

Owing to impaired immune function, surgical procedures, and multiple hospitalizations, patients with end-stage liver disease are at risk for numerous infectious complications while waiting for transplantation. Infection in transplant recipients remains the main cause of mortality and morbidity, despite advances in surgical techniques and the development of new repressive agents. The purpose of this study is to examine the infections that develop during the pretransplantion period in live donor liver transplant recipients and their effect on post-transplant clinical outcomes. The retrospective analysis of adult live donor liver transplant recipients in the last 4 years was conducted at Ankara University Hospital, a 1900-bed tertiary-care university hospital, in Ankara, Turkey. Demographic characteristics, preoperative infections, and clinical outcomes were analyzed. Patients were divided into 2 groups according to whether they had developed an infection before transplantation. The diagnoses were based on clinical, laboratory, and microbiological findings. Statistical analyses were performed using Stata version 9.0 (StataCorp, College Station, Tex., United States), and P < .05 were considered statistically significant. In univariate analyses, having diabetes mellitus or a pretransplant infection, the number of pretransplant infection attacks, the need for a reoperation, and developing a post-transplant infection were the statistically significant factors associated with 1-year mortality (P < .001, χ2 test). In multivariate analyses, diabetes mellitus (Odds ratio [OR] = 7.44, 95% confidence interval [CI], .03-45.79; P = .013), reoperation (OR = .33, 95% CI, .25-2.20; P < .001), having a pretransplantation infection (OR = 12.47, 95% CI, .011-87.67; P = .013), and the number of pretransplantation infection attacks (OR = .028, 95% CI, .013-.47; P < .001) were found to be statistically significant risk factors for 1-year mortality. Our study showed the effect of pretransplantation infections on post-transplant morbidity but not on rejection or mortality. According to the situation of patients, manageable pretransplantation infection is not an absolute contraindication for liver transplantation. Awareness of the increased risk for post-transplant infections and fast-acting antimicrobial coverage are the most important facts for patient survival.


Assuntos
Doença Hepática Terminal/complicações , Transplante de Fígado/mortalidade , Doadores Vivos , Complicações Pós-Operatórias/mortalidade , Adulto , Contraindicações de Procedimentos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Diabetes Mellitus/mortalidade , Doença Hepática Terminal/mortalidade , Doença Hepática Terminal/cirurgia , Feminino , Hospitalização , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Turquia , Adulto Jovem
12.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491943

RESUMO

PURPOSE: Cataracts in patients with diabetes mellitus (DM) are a major cause of blindness in developed and developing countries. This study aims to examine whether the generation of reactive oxygen species (ROS) via the increased expression of glucose transporters (GLUTs) and the receptor for advanced glycation end products (RAGE) influences the cataract development in DM. METHODS: Lens epithelial cells (LECs) were isolated during cataract surgery from patients without DM or with DM, but without diabetic retinopathy. In a rat model, fructose (10% fructose, 8 or 12 weeks) with or without dapagliflozin (1.2 mg/day, 2 weeks) treatment did induce DM, as verified by blood pressure and serum parameter measurements. Immunofluorescence stainings and immunoblottings were used to quantify the protein levels. Endogenous O2˙¯ production in the LECs was determined in vivo with dihydroethidium stainings. RESULTS: We investigated that GLUT levels in LECs differed significantly, thus leading to the direct enhancement of RAGE-associated superoxide generation in DM patients with cataracts. Superoxide production was significantly higher in LECs from rats with fructose-induced type 2 DM, whereas treatment with the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin prevented this effect in fructose-fed rats. Protein expression levels of the sodium/glucose cotransporter 2 (SGLT2), GLUT1, GLUT5, the nicotinamide adenine dinucleotide phosphate reduced form (NADPH) oxidase subunit p67-phox, NOX2/4 and RAGE were upregulated in fructose-fed animals, whereas dapagliflozin treatment reversed these effects. CONCLUSIONS: In rats with fructose-induced DM, dapagliflozin downregulates RAGE-induced NADPH oxidase expression in LECs via the inactivation of GLUTs and a reduction in ROS generation. These novel findings suggest that the SGLT2 inhibitor dapagliflozin may be a candidate for the pharmacological prevention of cataracts in patients with DM.


Assuntos
Cristalino/citologia , Cristalino/metabolismo , NADPH Oxidases/genética , Estresse Oxidativo/genética , Transportador 2 de Glucose-Sódio/genética , Idoso , Animais , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Modelos Animais de Doenças , Feminino , Frutose/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , NADPH Oxidases/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo
13.
Int J Mol Sci ; 20(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470514

RESUMO

Tobacco smoking (TS) is one of the most addictive habit sand a main public health hazards, impacting the vascular endothelium through oxidative stress (OS) stimuli, exposure to nicotine, and smoking-induced inflammation in a dose-dependent manner. Increasing evidence also suggested that TS increases glucose intolerance and the risk factor of developing type-2 diabetes mellitus (2DM), which, along with TS, is connected to blood-brain barrier (BBB) injuries, and heightens the risk of cerebrovascular disorders. Although the exact mechanism of rosiglitazone (RSG) is unknown, our previous in vitro work showed how RSG, an oral anti-diabetic drug belonging to the family of thiazolidinedione class, can protect BBB integrity through enhancement of nuclear factor erythroid 2-related factor (Nrf2) activity. Herein, we have validated the protective role of rosiglitazone against TS-induced BBB impairment in vivo. Our results revealed that RSG as a peroxisome proliferator-activated receptor gamma (PPARγ), activates counteractive mechanisms primarily associated with the upregulation of Nrf2 and PPARγ pathways which reduce TS-dependent toxicity at the cerebrovascular level. In line with these findings, our results show that RSG reduces inflammation and protects BBB integrity. In conclusion, RSG offers a novel and promising therapeutic application to reduce TS-induced cerebrovascular dysfunction through activation of the PPARγ-dependent and/or PPARγ-independent Nrf2 pathway.


Assuntos
Transtornos Cerebrovasculares/prevenção & controle , Diabetes Mellitus/prevenção & controle , Hipoglicemiantes/farmacologia , Rosiglitazona/farmacologia , Fumar Tabaco/efeitos adversos , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtornos Cerebrovasculares/etiologia , Cotinina/sangue , Cotinina/metabolismo , Diabetes Mellitus/etiologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Nicotina/sangue , Nicotina/metabolismo , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Diabetes Res Clin Pract ; 156: 107828, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31472162

RESUMO

OBJECTIVE: To evaluate the independent or combined effects of gestational diabetes (GDM) and pre-pregnancy and postpartum BMI on the odds of postpartum diabetes and hyperglycemia. METHODS: The study samples included 1263 women with prior GDM and 705 women without GDM. Postpartum 1-7 years diabetes was diagnosed by the standard oral glucose tolerance test. RESULTS: The multivariable-adjusted odds ratios among women with prior GDM, compared with those without it, were 7.52 for diabetes and 2.27 for hyperglycemia. The multivariable-adjusted odds ratios at different postpartum BMI levels (<24, 24-27.9, and ≥ 28 kg/m2) were 1.00, 2.80, and 8.08 for diabetes (Ptrend < 0.001), and 1.00, 2.10, and 4.42 for hyperglycemia (Ptrend < 0.001), respectively. Women with high body fat (≥31.9%) or abdominal obesity (≥85 cm) had a 2.7-6.9-fold higher odds ratio for diabetes or hyperglycemia. Women with both obesity and prior GDM had the highest risk of diabetes or hyperglycemia compared with non-obese women without GDM. Non-obese women with prior GDM had the same risk of diabetes and hyperglycemia as non-GDM women with obesity. When using Cox regression models, the results were very close to those using logistic regression models. CONCLUSIONS: Maternal prior GDM and pre-pregnancy or postpartum obesity contribute equally to postpartum diabetes and hyperglycemia risk.


Assuntos
Diabetes Mellitus/etiologia , Diabetes Gestacional/etiologia , Hiperglicemia/etiologia , Obesidade/complicações , Adulto , Grupo com Ancestrais do Continente Asiático , Feminino , Humanos , Período Pós-Parto , Gravidez , Fatores de Risco
15.
Diabetes Metab Syndr ; 13(4): 2653-2659, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31405690

RESUMO

BACKGROUND: Metabolic syndrome (MS) increases the risk of heart disease, stroke, and other complications. AIM: The aim of this study was to assess the clinical and biochemical parameters of MS and its complications (cerebrovascular accidents, cardiovascular accidents, DN or chronic kidney disease (CKD) compared with healthy controls especially among the younger population in Northern India. MATERIAL AND METHODS: A total of 245 (healthy, MS and it's complicated) aged 18-70 years participated in the Open-Label, Single Centered; hospital-based random selection case-control comparative study. All anthropometric and biochemical assessment was done after proper consent. The metabolic syndrome was determined by IDF criteria. RESULTS: The key risk parameters in three groups i.e. Control, Metabolic syndrome, and Complicated was TG (96.5 ±â€¯46.9, 194.1 ±â€¯87.8, 148.0 ±â€¯102.2). LDL (91.2 ±â€¯27.2, 114.0 ±â€¯31.8, 69.1 ±â€¯42.5, BP (120.1 ±â€¯9.9, 139.3 ±â€¯13.3, 132.1 ±â€¯15.0) and high fasting glucose (81.1 ±â€¯13.7, 164.5 ±â€¯84.3, 138.0 ±â€¯74.5). The hs-CRP is also significantly increased in the complicated group. The subanalysis of data also indicates that younger middle age (36-55 years) group both male and female is obese, hypertensive, diabetic with lipid abnormality according to IDF criteria. CONCLUSION: The risk factors like high TG, low HDL, high BP, and high fasting glucose were found higher particularly in younger population which may lead to diagnosis & complications of diabetes, hypertension and lipid abnormality. Due to changing physiology in young and middle age population these individuals are moving towards metabolic syndrome easily and needs frequent monitoring, preventive checkups, and lifestyle changes to prevent complications.


Assuntos
Biomarcadores/análise , Doenças Cardiovasculares/etiologia , Transtornos Cerebrovasculares/etiologia , Diabetes Mellitus/etiologia , Síndrome Metabólica/complicações , Insuficiência Renal Crônica/etiologia , Adolescente , Adulto , Idoso , Antropometria , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Estudos de Casos e Controles , Transtornos Cerebrovasculares/metabolismo , Transtornos Cerebrovasculares/patologia , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Feminino , Seguimentos , Humanos , Lipídeos/análise , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Adulto Jovem
17.
Nutrients ; 11(8)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366117

RESUMO

There is an increasing number of metabolic syndrome (MetS) patients worldwide, and there is no exception in South Korea. The risk complications of metabolic syndrome have been investigated by many previous research studies, while no data on any current trends of MetS are available. Therefore, the present study investigates the recent prevalence of MetS and its associated risk complications in Korean adults by using the Korean National Health and Nutrition Examination Survey (KNHANES). The Survey respondents (n = 4744) were adults over the age of 30, and they had participated in KNHANES 2016, which is a health survey of a national representative sample of non-institutionalized civilian South Koreans. The cross-tabulation analysis was applied to figure out the general characteristics impacting on the prevalence of MetS; furthermore, the odds ratios and 95% confidence intervals (CIs) using multivariate logistic regression analysis were presented for the risk complications of MetS. Findings from this study indicated that subjective health status, family structure, age, income level, use of nutrition labelling and gender showed significant connections with the prevalence of MetS. The risk diseases, stroke (OR = 2.174, 95% CI = 1.377-3.433, p < 0.01), myocardial infarction (MI) (OR = 2.667, 95% CI = 1.474-4.824, p < 0.01) and diabetes (OR = 6.533, 95% CI = 4.963, p < 0.001) were explored and verified attributable to the prevalence of MetS. The findings in this study suggest that sociodemographic characteristics-concentrated strategies are vital to prevent the prevalence of MetS in South Korea, and relative risk complications ought to be cautiously dealt with as well.


Assuntos
Grupo com Ancestrais do Continente Asiático , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Adulto , Idoso , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Razão de Chances , República da Coreia/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31284480

RESUMO

Background: Early-onset diabetes results in longer lifetime hyperglycemic exposure that consequently leads to earlier chronic diabetes complications and premature death. The aim of this study was to quantify the prevalence and risk factors of undiagnosed diabetes and undiagnosed prediabetes in apparently healthy young adults aged <40 years. Methods: This study used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional, nationally representative survey conducted by the Korean Ministry of Health and Welfare from 2014 to 2017. A total of 4442 apparently healthy young adults enrolled in this study. Multivariate logistic regression analyses were conducted separately to evaluate associated risk factors with undiagnosed diabetes and undiagnosed prediabetes in groups stratified by sex. Results: The prevalence of undiagnosed diabetes and undiagnosed prediabetes was 1.2% and 25.0%, respectively. Obesity (body mass index ≥ 30.0 kg/m2) was a significant risk factor of undiagnosed diabetes regardless of sex (men, odds ratio (OR): 9.808, 95% confidence interval (CI): 1.619-59.412; women, OR: 7.719, 95% CI: 1.332-44.747). Family history of diabetes was significantly associated with undiagnosed diabetes (OR: 3.407, 95% CI: 1.224-9.481) in women only. Increased age, obesity status, and family history of diabetes were significant risk factors for undiagnosed prediabetes. Alcohol consumption was found to be negatively associated with undiagnosed prediabetes in women. Conclusions: Increased attention and implementation of precise strategies for identifying young adults at high risk for undiagnosed diabetes would allow for increased wellbeing as well as reduced healthcare burdens associated with diabetes.


Assuntos
Intolerância à Glucose/epidemiologia , /epidemiologia , Adulto , Estudos Transversais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Feminino , Intolerância à Glucose/diagnóstico , Intolerância à Glucose/etiologia , Humanos , Masculino , Inquéritos Nutricionais , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/etiologia , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Fatores Sexuais , /etiologia , Adulto Jovem
19.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261624

RESUMO

Diabetes Mellitus (DM) is a leading cause of both Cardiovascular Disease (CVD) and End-stage Renal Disease (ESRD). After 2008, there has been much evidence presented, and recently the guidelines for sugar control have changed to focus on being more disease orientated. GLP-1 Receptor Agonists (GLP-1R) and sodium glucose cotransporter-2 inhibitors are suggested as the first line towards fighting all DM, CVD and ESRD. However, the benefits of GLP-1R in organ transplantation recipients remain very limited. No clinical trials have been designed for this particular population. GLP-1R, a gastrointestinal hormone of the incretin family, possesses antidiabetic, antihypertensive, anti-inflammatory, anti-apoptotic and immunomodulatory actions. There are few drug-drug interactions, with delayed gastric emptying being the major concern. The trough level of tacrolimus may not be significant but should still be closely monitored. There are some reasons which support GLP-1R in recipients seeking glycemic control. Post-transplant DM is due to an impaired ß-cell function and glucose-induced glucagon suppression during hyperglycemia, which can be reversed by GLP-1R. GLP-1R infusion tends to relieve immunosuppressant related toxicity. Until now, in some cases, glycemic control and body weight reduction can be anticipated with GLP-1R. Additional renal benefits have also been reported. Side effects of hypoglycemia and gastrointestinal discomfort were rarely reported. In conclusion, GLP-1R could be implemented for recipients while closely monitoring their tacrolimus levels and any potential side effects. Any added benefits, in addition to sugar level control, still require more well-designed studies to prove their existence.


Assuntos
Diabetes Mellitus/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipoglicemiantes/uso terapêutico , Transplante de Rim/efeitos adversos , Síndrome Metabólica/tratamento farmacológico , Diabetes Mellitus/etiologia , Nefropatias Diabéticas/cirurgia , Peptídeo 1 Semelhante ao Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Humanos , Hipoglicemiantes/administração & dosagem
20.
Diabetes Metab Syndr ; 13(2): 1021-1030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31336438

RESUMO

AIMS: Chronic unpredictable environmental stress (CUES) may induce predisposition to diabetes mellitus. This study investigates the role of CUES on impaired homeostasis. MATERIAL AND METHODS: Stressed group mice (n = 20) were exposed to CUES for 16 weeks. Weekly body weight, feed consumption, feed efficiency ratio, fasting blood glucose were monitored. Plasma HbA1c, plasma cortisol, plasma epinephrine and plasma insulin, serum lipids, antioxidants and carbohydrate metabolizing enzymes activity were assessed along with DNA damage and histopathological examination of liver, kidney, pancreas, spleen and skeletal muscles. RESULTS AND CONCLUSION: s: Fasting blood glucose levels & HbA1c in the stressed were significantly higher compared to control (p < 0.001). Serum lipids were found insignificantly higher in stressed mice compared to control. Body weights of the stressed mice and feed efficiency ratio were found significant (p < 0.001). Plasma corticosterone, plasma epinephrine, HOMA-IR was found to be significantly higher in the stressed group (p < 0.001). Plasma insulin level was found to be significantly lower in the stressed group (p < 0.001). Significant changes were observed in antioxidants level, carbohydrate metabolizing enzymes activity, peripheral tissues and DNA integrity. CUES initiates pathogenesis of diabetes.


Assuntos
Biomarcadores/análise , Diabetes Mellitus/etiologia , Exposição Ambiental/efeitos adversos , Intolerância à Glucose/complicações , Homeostase , Lipídeos/análise , Estresse Fisiológico , Animais , Antioxidantes/metabolismo , Glicemia/análise , Peso Corporal , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Feminino , Insulina/sangue , Camundongos , Fatores de Risco
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