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1.
Anticancer Res ; 42(1): 109-113, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34969716

RESUMO

BACKGROUND/AIM: Diabetes mellitus (DM) is one of the most common chronic metabolic disorders. Our research aimed to demonstrate the relationship between DM and oral cancer. PATIENTS AND METHODS: We pursued a retrospective research study in Hungary between January 2019 and December 2020. We investigated 597 inpatient records and compared them to the results of our previous studies (1998-2002 and 2012-2015). RESULTS: The frequency of patients with DM in the oral cancer group is 2.45 times higher today than 20 years ago. The prevalence rate of DM and oral malignancies increased from 14.6% to 35.8%. In the oral cancer group, 54.4% of the patients had elevated blood glucose levels and of these, 61.1% of them had type 2 diabetes, 34.2% had impaired fasting glycemia, and only 4.7% had type 1 diabetes. We observed that 45.3% of them were smokers. Of those whose blood sugar levels were under 6.1 mmol/l, the mean body mass index was 25.33 [standard deviation (SD)=±4.5; range=15.57-39.84], while among patients with DM, it was 26.92 (SD=±5.8; range=18.36-44.08). CONCLUSION: It may be necessary to continuously monitor the patient's blood sugar level to maintain euglycemic levels when managing patients with malignant oral lesions.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Neoplasias Bucais/etiologia , Idoso , Jejum , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Prevalência , Estudos Retrospectivos
2.
Life Sci ; 289: 120232, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34919901

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide health issue primarily due to failure of pancreatic ß-cells to release sufficient insulin. PURPOSE: The present work aimed to assess the antidiabetic potential of arjunolic acid (AA) isolated from Terminalia arjuna in type 2 diabetic rats. STUDY DESIGN: After extraction, isolation and purification, AA was orally administered to type 2 diabetic Sprague Dawley rats to investigate antidiabetic effect of AA. METHOD: T2DM was induced via single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NIC) in adult male rats. After 10 days, fasting and random blood glucose (FBG and RBG), body weight (BW), food and water intake, serum C-peptide, insulin and glycated hemoglobin (HbA1c) was measured to confirm T2DM development. Dose dependent effects of orally administered AA (25 and 50 mg/kg/day) for 4 weeks was investigated by measuring BW variation, fasting and postprandial hyperglycemia, oral glucose tolerance test (OGTT), and levels of serum HbA1c, serum total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), serum and pancreatic C-peptide, insulin, growth differentiation factor 15 (GDF-15), serum and pancreatic inflammatory cytokines. RESULTS: The oral administration of AA in preclinical model of T2DM significantly normalized FBG and RBG, restored BW, controlled polyphagia, polydipsia and glucose tolerance. In addition, AA notably reduced serum HbA1c, TC, TG, LDL with non-significant increase in HDL. On the other hand, significant increase in serum and pancreatic C-peptide and insulin was observed with AA treatment, while serum and pancreatic GDF-15 were non-significantly altered in AA treated diabetic rats. Moreover, AA showed dose dependent reduction in serum and pancreatic proinflammatory cytokines including TNF-α, IL-1ß and IL-6. CONCLUSION: For the first time our findings highlighted AA as a potential candidate in type 2 diabetic conditions.


Assuntos
Glicemia/metabolismo , Citocinas/sangue , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Regulação para Baixo/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inflamação/sangue , Inflamação/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Terminalia/química , Triterpenos/química
3.
J Sci Food Agric ; 102(2): 716-723, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34171123

RESUMO

BACKGROUND: The prevalence of diabetes mellitus worldwide has increased in recent decades. Maintaining the level of blood glucose is the most basic and important issue for diabetics. This study aimed to investigate the hypoglycemic activity of a combination of hypoglycemic peptide-enriched hydrolysates of Corbicula fluminea (ACH) and Chlorella sorokiniana (PCH). RESULTS: Combined supplementation of ACH and PCH synergistically inhibited α-glucosidase and DPP4 activities in vitro. After 4 weeks of treatment with ACH and/or PCH, the plasma glucose concentration and insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR), total cholesterol (TC) and triglyceride (TG) levels significantly decreased. The hypoglycemic peptides in ACH and PCH were purified and assayed for α-glucosidase and DPP4 activity. The hypoglycemic peptides in ACH and PCH effectively decreased α-glucosidase and DPP4 activities. In silico assays showed that these two peptide types have different docking poses, which determined their inhibitory effect against α-glucosidase and DPP4 activity. CONCLUSION: Combined treatment with hypoglycemic peptide-enriched ACH and PCH could modulate blood glucose by synergistically inhibiting α-glucosidase and DPP4 activities. © 2021 Society of Chemical Industry.


Assuntos
Chlorella/química , Corbicula/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores de Glicosídeo Hidrolases/administração & dosagem , Hipoglicemiantes/administração & dosagem , Peptídeos/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/metabolismo , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Inibidores da Dipeptidil Peptidase IV/química , Sinergismo Farmacológico , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hipoglicemiantes/química , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
4.
Nutrients ; 13(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34959760

RESUMO

Hepatokines are liver-derived proteins that may influence metabolic pathways such as insulin sensitivity. Recently, Sparc-related modular calcium-binding protein 1 (SMOC1) was identified as glucose-responsive hepatokine that is dysregulated in the setting of non-alcoholic fatty liver disease (NAFLD). While SMOC1 may influence glucose-insulin homeostasis in rodents, it is unknown if SMOC1 is influenced by NAFLD in humans. It is also unknown if SMOC1 is causally associated with metabolic and disease traits in humans. Therefore, we aimed to determine the effect of NAFLD on SMOC1 gene expression in the liver and aimed to explore the potential causal associations of SMOC1 levels with NAFLD, T2D, and glycemic traits in humans. Using an RNA sequencing dataset from a cohort of 216 patients with NAFLD, we assessed SMOC1 expression levels across the NAFLD spectrum. We performed a series of bidirectional inverse-variance weighted Mendelian randomization (MR) analyses on blood SMOC1 levels using two sources of genome-wide association studies (GWAS) (Fenland study, n = 10,708 and INTERVAL study, n = 3301). We utilized GWAS summary statistics for NAFLD in 8434 cases and 770,180 controls, as well as publicly available GWAS for type 2 diabetes (T2D), body mass index (BMI), waist-to-hip ratio (WHR), fasting blood insulin (FBI), fasting blood glucose (FBG), homeostatic Model Assessment of Insulin Resistance (HOMA-B and HOMA-IR), and hemoglobin A1c (HbA1C). We found that SMOC1 expression showed no significant differences across NAFLD stages. We also identified that the top single-nucleotide polymorphism associated with blood SMOC1 levels, was associated with SMOC1 gene expression in the liver, but not in other tissues. Using MR, we did not find any evidence that genetically predicted NAFLD, T2D, and glycemic traits influenced SMOC1 levels. We also did not find evidence that blood SMOC1 levels were causally associated with T2D, NAFLD, and glycemic traits. In conclusion, the hepatokine SMOC1 does not appear to be modulated by the presence of NAFLD and may not regulate glucose-insulin homeostasis in humans. Results of this study suggest that blood factors regulating metabolism in rodents may not always translate to human biology.


Assuntos
Diabetes Mellitus Tipo 2/genética , Hepatopatia Gordurosa não Alcoólica/genética , Osteonectina/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Expressão Gênica/fisiologia , Estudo de Associação Genômica Ampla , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/genética , Fígado/metabolismo , Análise da Randomização Mendeliana , Hepatopatia Gordurosa não Alcoólica/sangue , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Relação Cintura-Quadril
5.
Nutrients ; 13(12)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34959770

RESUMO

The present prospective study included 2156 women and investigated the effect of gene variants in the vitamin D (VitD) metabolic and glucose pathways and their interaction with VitD levels during pregnancy on gestational diabetes mellitus (GDM). Plasma 25(OH)D concentrations were measured at the first and second trimesters. GDM subtype 1 was defined as those with isolated elevated fasting plasma glucose; GDM subtype 2 were those with isolated elevated postprandial glucose at 1 h and/or 2 h; and GDM subtype 3 were those with both elevated fasting plasma glucose and postprandial glucose. Six Gc isoforms were categorized based on two GC gene variants rs4588 and rs7041, including 1s/1s, 1s/2, 1s/1f, 2/2, 1f/2 and 1f/1f. VDR-rs10783219 and MTNR1B-rs10830962 were associated with increased risks of GDM and GDM subtype 2; interactions between each other as well as with CDKAL1-rs7754840 were observed (Pinteraction < 0.05). Compared with the 1f/1f isoform, the risk of GDM subtype 2 among women with 1f/2, 2/2, 1s/1f, 1s/2 and 1s/1s isoforms and with prepregnancy body mass index ≥24 kg/m2 increased by 5.11, 10.01, 10, 14.23, 19.45 times, respectively. Gene variants in VitD pathway interacts with VitD deficiency at the first trimester on the risk of GDM and GDM subtype 2.


Assuntos
Diabetes Gestacional/genética , Variação Genética , Redes e Vias Metabólicas/genética , Deficiência de Vitamina D/genética , Vitamina D/genética , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Gestacional/sangue , Jejum/sangue , Feminino , Humanos , Gravidez , Trimestres da Gravidez/sangue , Estudos Prospectivos , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/sangue
6.
Isr Med Assoc J ; 23(12): 766-772, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34954914

RESUMO

BACKGROUND: Lumbar spinal stenosis (LSS) is a narrowing of the lumbar canal causing lower back pain, gluteal pain, and neurogenic claudication. LSS has been associated with cardiovascular co-morbidities. Metabolic syndrome (MetS), a pro-inflammatory condition involving a cluster of risk factors for cardiovascular disease and diabetes, is increasingly prevalent worldwide. OBJECTIVES: To evaluate the prevalence of MetS in patients with LSS, compared to age- and sex-matched healthy controls, and to explore potential associations between MetS and LSS-related clinical parameters and cardiovascular risk factors. METHODS: We conducted a cross-sectional study including 64 patients diagnosed as symptomatic LSS (NASS criteria) and 32 controls. MetS was diagnosed using the 2009 Harmonizing criteria adjusted for South Americans. Multivariate logistic regression was used to identify independent risk factors for MetS. The level of statistical significance was set at 5. RESULTS: The prevalence of MetS was significantly higher in the LSS group than in the control group (76.6% vs. 31.3%; P < 0.001). LSS patients displayed greater waist circumference (P = 0.003), blood glucose levels (P = 0.009) and arterial pressure (P < 0.001) than controls. The variables with independent influence on MetS in the logistic regression model were: diabetes (P = 0.008), blood glucose (P = 0.004), and body mass index (P = 0.005). CONCLUSIONS: MetS was significantly more prevalent among LSS patients, and diabetes and elevated body mass index were found to be risk factors for MetS in these LSS patients.


Assuntos
Diabetes Mellitus/epidemiologia , Síndrome Metabólica/epidemiologia , Estenose Espinal/complicações , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco
7.
Front Endocrinol (Lausanne) ; 12: 791476, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34956098

RESUMO

Background: We aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications. Methods: We enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG<6.1mmol/L with no history of diabetes (group 1), patients with FBG<6.1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients. Results: COVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70%; critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p<0.05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P<0.001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P<0.001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3. Conclusion: Our study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels.


Assuntos
Glicemia/metabolismo , COVID-19/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Jejum/sangue , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
8.
Biomolecules ; 11(12)2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34944507

RESUMO

The potential involvement of neuropeptide Q (NPQ) and chemerin (CHEM) in metabolic disorders is yet to be fully elucidated. The aim of this study was to evaluate serum concentrations of NPQ and CHEM and to establish their relationship with cardiometabolic risk factors among individuals with metabolic syndrome. A total of 66 patients with metabolic syndrome (MetS) and 83 healthy volunteers (non-MetS) underwent biochemical, blood pressure, and anthropometric measurements. The concentration of NPQ in the MetS group was significantly lower (0.47 (0.34 ; 0.54) vs. 0.52 (0.43 ; 0.60) ng/mL, p = 0.015) than in non-MetS, while there were no differences in CHEM level. In the entire study population, we observed several negative correlations between NPQ concentration and waist-hip ratio (WHR), visceral adipose tissue, diastolic blood pressure (DBP), triglycerides (TG) along with a positive correlation with high-density lipoprotein (HDL), total muscle mass, and CHEM. Moreover, a negative correlation was observed in the MetS group between NPQ and glycemia. CHEM showed no significant correlations with cardiometabolic risk factors in the study population. In a multiple regression model, the total muscle mass proved to be an independent factor determining NPQ concentration in the population (p < 0.00000001, R2adj = 28.6%). NPQ seems to protect against metabolic disorders correlated with obesity. Thus, it is worth considering NPQ level as a candidate protective biomarker of metabolic syndrome complications.


Assuntos
Quimiocinas/sangue , Regulação para Baixo , Síndrome Metabólica/sangue , Hormônios Peptídicos/sangue , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Estudos de Casos e Controles , Feminino , Humanos , Gordura Intra-Abdominal/metabolismo , Masculino , Pessoa de Meia-Idade , Triglicerídeos/metabolismo , Relação Cintura-Quadril
9.
Nutrients ; 13(12)2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34960058

RESUMO

Postmenopausal breast cancer is the most common obesity-related cancer death among women in the U.S. Insulin resistance, which worsens in the setting of obesity, is associated with higher breast cancer incidence and mortality. Maladaptive eating patterns driving insulin resistance represent a key modifiable risk factor for breast cancer. Emerging evidence suggests that time-restricted feeding paradigms (TRF) improve cancer-related metabolic risk factors; however, more flexible approaches could be more feasible and effective. In this exploratory, secondary analysis, we identified participants following a low-glucose eating pattern (LGEP), defined as consuming energy when glucose levels are at or below average fasting levels, as an alternative to TRF. Results show that following an LGEP regimen for at least 40% of reported eating events improves insulin resistance (HOMA-IR) and other cancer-related serum biomarkers. The magnitude of serum biomarkers changes observed here has previously been shown to favorably modulate benign breast tissue in women with overweight and obesity who are at risk for postmenopausal breast cancer. By comparison, the observed effects of LGEP were similar to results from previously published TRF studies in similar populations. These preliminary findings support further testing of LGEP as an alternative to TRF and a postmenopausal breast cancer prevention strategy. However, results should be interpreted with caution, given the exploratory nature of analyses.


Assuntos
Neoplasias da Mama/prevenção & controle , Dieta/métodos , Jejum/sangue , Obesidade/dietoterapia , Pós-Menopausa/sangue , Biomarcadores/sangue , Glicemia/metabolismo , Mama/metabolismo , Neoplasias da Mama/etiologia , Estudos de Viabilidade , Comportamento Alimentar/fisiologia , Feminino , Humanos , Resistência à Insulina , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações
10.
Pan Afr Med J ; 39: 274, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754351

RESUMO

Introduction: hyperglycemic emergencies (diabetic ketoacidosis and hyperglycemic hyperosmolar state) are the most common serious acute metabolic complications of diabetes which result in significant morbidity and mortality. There is paucity of data on hyperglycemic emergencies in Cameroon. The objective of this study was to investigate the precipitants and outcomes of patients admitted for hyperglycemic emergencies in the Buea Regional Hospital in the South West Region of Cameroon. Methods: in this retrospective study the medical records of patients admitted for hyperglycemic emergencies between 2013 and 2016 in the medical unit of the Buea Regional Hospital were reviewed. We extracted data on demographic characteristics, admission clinical characteristics, precipitants, and treatment outcomes. Logistic regression was used to determine predictors of mortality. Results: data were available for 60 patients (51.7% females) admitted for hyperglycemic emergencies. The mean age was 55.2±16.3 (range 18-86). Overall there were 51 (85%) cases of hyperosmolar hyperglycemic state. Twenty six (43.3%) of the patients had hypertension. The most common precipitants of hyperglycemic emergencies were infections (41.7%), newly diagnosed diabetes (33.3%) and non-adherence to medications (33.3%). Mean admission blood glucose was 574mg/dl±70.0mg/dl. The median length of hospital stay was 6 days. Overall case fatality rate was 21.7%. Six (46.2%) deaths were related to infections. Predictors of mortality were a Glasgow coma score <13(p<0.001), a diastolic blood pressure <60 mmHg (p=0.034) and a heart rate >90(0.057) on admission. Conclusion: admission for hyperglycemic emergencies in this semi-urban hospital is associated with abnormally high case fatality. Infections, newly diagnosed diabetes and non-adherence to medications are the commonest precipitants of hyperglycemic emergencies. Public health measures to reduce morbidity and mortality from hyperglycemic crisis are urgently needed.


Assuntos
Cetoacidose Diabética/diagnóstico , Hiperglicemia/diagnóstico , Coma Hiperglicêmico Hiperosmolar não Cetótico/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Camarões , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/terapia , Emergências , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/mortalidade , Hiperglicemia/terapia , Coma Hiperglicêmico Hiperosmolar não Cetótico/epidemiologia , Coma Hiperglicêmico Hiperosmolar não Cetótico/terapia , Tempo de Internação/estatística & dados numéricos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
11.
Pan Afr Med J ; 39: 206, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603587

RESUMO

Introduction: type 2 diabetes mellitus has become a global public health crisis. The increment in the cases has contributed significantly to the parallel increase in the prevalence of overweight and obesity. This paper aimed to analyse the relationship between lipid profile, waist circumference and body mass index (BMI) with the glycaemic control of the diabetes patients in Kedah. Methods: a cross-sectional study was conducted, using the Kedah audit samples data extracted from the National Diabetes Registry (NDR) from the year 2014 to 2018. A total of 25,062 registered type 2 diabetes mellitus patients were selected using the inclusion and exclusion criteria from the registry. Only patients with complete data on their HbA1C, lipid profile, waist circumference and BMI were analysed using SPSS version 21. Results: the means for the age, BMI and waist circumference of the samples were 61.5 (±10.85) years, 27.3 (±5.05) kg/m2 and 89.46 (±13.58) cm, respectively. Poor glycaemic control (HbA1c>6.5%) was observed in 72.7% of the patients, with females having poorer glycaemic control. The BMI and waist circumference were found to be significantly associated with glycaemic control (P<0.001). The total cholesterol, triglycerides and low-density lipoproteins values showed positive correlation with glycaemic control (r = 0.178, 0.157, 0.145, p<0.001), while high-density lipoproteins values are negatively correlated (r = -0.019, p<0.001). Conclusion: implementing lifestyle changes such as physical activity and dietary modifications are important in the management of BMI, waist circumference and body lipids, which in turn results in improved glycaemic control.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Hemoglobina A Glicada/metabolismo , Lipídeos/sangue , Idoso , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Estilo de Vida , Malásia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Sobrepeso , Sistema de Registros , Circunferência da Cintura/fisiologia
12.
Nutr Metab Cardiovasc Dis ; 31(11): 3024-3030, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34625361

RESUMO

BACKGROUND AND AIMS: Triglyceride-Glucose (TyG) index is an accurate biomarker of insulin resistance, which is potentially associated with adverse cardiovascular events. We aimed to assess the dose-response relationship between Triglyceride-Glucose (TyG) Index and Major Adverse Cardiovascular Events (MACE) in patients with Acute Coronary Syndrome (ACS). METHODS AND RESULTS: A systematic literature search was performed using PubMed, Scopus, and Embase for records published from the inception up until 7 February 2021. Studies that fulfilled all of these criteria were included: 1) prospective or retrospective observational studies reporting patients with ACS and 2) assessing the impact of TyG index on MACE with at least three quantitative classifications. The outcome of interest is MACE across the TyG index intervals. MACE was a composite of all-cause mortality, myocardial infarction, unstable angina pectoris, target vessel revascularization, cerebrovascular accidents, and heart failure. The effect estimates were reported as relative risks (RRs). There are 13,684 subjects from 4 studies included in this meta-analysis. This meta-analysis showed that the highest category of TyG index was associated with twofold MACE (RR 2.09 [1.59, 2.76], p < 0.001; I2: 68.4%, p = 0.02) compared to the lowest category in patients with ACS. Dose-response meta-analysis showed that the relationship between TyG index and MACE was non-linear (p < 0.001), with statistical significance reached around TyG index 8.9 and increased non-linearly. The dose-response curve became significantly steeper after TyG index of 9.1-9.2. CONCLUSION: TyG index was associated with MACE in patients with ACS in a non-linear fashion. PROSPERO: CRD42021235765.


Assuntos
Síndrome Coronariana Aguda/sangue , Glicemia/metabolismo , Diabetes Mellitus/sangue , Resistência à Insulina , Triglicerídeos/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Biomarcadores/sangue , Diabetes Mellitus/diagnóstico , Progressão da Doença , Humanos , Revascularização Miocárdica , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco
13.
FASEB J ; 35(11): e21957, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34606641

RESUMO

The Wnt signaling antagonist, sclerostin, is a potent suppressor of bone acquisition that also mediates endocrine communication between bone and adipose. As a result, Sost-/- mice exhibit dramatic increases in bone formation but marked decreases in visceral and subcutaneous adipose that are secondary to alterations in lipid synthesis and utilization. While interrogating the mechanism by which sclerostin influences adipocyte metabolism, we observed paradoxical increases in the adipogenic potential and numbers of CD45- :Sca1+ :PDGFRα+ adipoprogenitors in the stromal vascular compartment of fat pads isolated from male Sost-/- mice. Lineage tracing studies indicated that sclerostin deficiency blocks the differentiation of PDGFRα+ adipoprogenitors to mature adipocytes in association with increased Wnt/ß-catenin signaling. Importantly, osteoblast/osteocyte-specific Sost gene deletion mirrors the accumulation of PDGFRα+ adipoprogenitors, reduction in fat mass, and improved glucose metabolism evident in Sost-/- mice. These data indicate that bone-derived sclerostin regulates multiple facets of adipocyte physiology ranging from progenitor cell commitment to anabolic metabolism.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adipócitos/metabolismo , Adipogenia/genética , Osso e Ossos/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Células-Tronco/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Células Cultivadas , Técnicas de Inativação de Genes/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/metabolismo , Osteócitos/metabolismo , Osteogênese/genética
14.
PLoS One ; 16(10): e0258212, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34618839

RESUMO

The ectodysplasin receptor (EDAR) is a tumor necrosis factor receptor (TNF) superfamily member. A substitution in an exon of EDAR at position 370 (EDARV370A) creates a gain of function mutant present at high frequencies in Asian and Indigenous American populations but absent in others. Its frequency is intermediate in populations of Mexican ancestry. EDAR regulates the development of ectodermal tissues, including mammary ducts. Obesity and type 2 diabetes mellitus are prevalent in people with Indigenous and Latino ancestry. Latino patients also have altered prevalence and presentation of breast cancer. It is unknown whether EDARV370A might connect these phenomena. The goals of this study were to determine 1) whether EDARV370A is associated with metabolic phenotypes and 2) if there is altered breast anatomy in women carrying EDARV370A. Participants were from two Latino cohorts, the Arizona Insulin Resistance (AIR) registry and Sangre por Salud (SPS) biobank. The frequency of EDARV370A was 47% in the Latino cohorts. In the AIR registry, carriers of EDARV370A (GG homozygous) had significantly (p < 0.05) higher plasma triglycerides, VLDL, ALT, 2-hour post-challenge glucose, and a higher prevalence of prediabetes/diabetes. In a subset of the AIR registry, serum levels of ectodysplasin A2 (EDA-A2) also were associated with HbA1c and prediabetes (p < 0.05). For the SPS biobank, participants that were carriers of EDARV370A had lower breast density and higher HbA1c (both p < 0.05). The significant associations with measures of glycemia remained when the cohorts were combined. We conclude that EDARV370A is associated with characteristics of the metabolic syndrome and breast density in Latinos.


Assuntos
Densidade da Mama/genética , Receptor Edar/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Síndrome Metabólica/genética , Mutação/genética , Adulto , Comitês Consultivos , Arizona , Bancos de Espécimes Biológicos , Glicemia/metabolismo , Ectodisplasinas/genética , Feminino , Frequência do Gene/genética , Hemoglobina A Glicada/metabolismo , Humanos , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Sistema de Registros
15.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638898

RESUMO

The preference for high-calorie foods depends on sex and contributes to obesity development. Fibroblast growth factor 21 (FGF21) beneficially affects taste preferences and obesity, but its action has mainly been studied in males. The aim of this study was to compare the effects of FGF21 on food preferences and glucose and lipid metabolism in C57Bl/6J male and female mice with diet-induced obesity. Mice were injected with FGF21 or vehicle for 7 days. Body weight, choice between standard (SD) and high-fat (HFD) diets, blood parameters, and gene expression in white (WAT) and brown (BAT) adipose tissues, liver, muscles, and the hypothalamus were assessed. Compared to males, females had a greater preference for HFD; less WAT; lower levels of cholesterol, glucose, and insulin; and higher expression of Fgf21, Insr, Ppara, Pgc1, Acca and Accb in the liver and Dio2 in BAT. FGF21 administration decreased adiposity; blood levels of cholesterol, glucose, and insulin; hypothalamic Agrp expression, increased SD intake, decreased HFD intake independently of sex, and increased WAT expression of Pparg, Lpl and Lipe only in females. Thus, FGF21 administration beneficially affected mice of both sexes despite obesity-associated sex differences in metabolic characteristics, and it induced female-specific activation of gene expression in WAT.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/administração & dosagem , Expressão Gênica/efeitos dos fármacos , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/genética , Ácido Graxo Sintase Tipo I/genética , Feminino , Fatores de Crescimento de Fibroblastos/genética , Insulina/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/genética , PPAR alfa/genética , Piruvato Quinase/genética , Fatores Sexuais
16.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638990

RESUMO

Obesity is one of the most prevalent metabolic diseases in the Western world and correlates directly with glucose intolerance and insulin resistance, often culminating in Type 2 Diabetes (T2D). Importantly, our team has recently shown that the TNF superfamily (TNFSF) member protein, TNFSF14, has been reported to protect against high fat diet induced obesity and pre-diabetes. We hypothesized that mimics of TNFSF14 may therefore be valuable as anti-diabetic agents. In this study, we use in silico approaches to identify key regions of TNFSF14 responsible for binding to the Herpes virus entry mediator and Lymphotoxin ß receptor. In vitro evaluation of a selection of optimised peptides identified six potentially therapeutic TNFSF14 peptides. We report that these peptides increased insulin and fatty acid oxidation signalling in skeletal muscle cells. We then selected one of these promising peptides to determine the efficacy to promote metabolic benefits in vivo. Importantly, the TNFSF14 peptide 7 reduced high fat diet-induced glucose intolerance, insulin resistance and hyperinsulinemia in a mouse model of obesity. In addition, we highlight that the TNFSF14 peptide 7 resulted in a marked reduction in liver steatosis and a concomitant increase in phospho-AMPK signalling. We conclude that TNFSF14-derived molecules positively regulate glucose homeostasis and lipid metabolism and may therefore open a completely novel therapeutic pathway for treating obesity and T2D.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Obesidade/complicações , Obesidade/tratamento farmacológico , Peptídeos/administração & dosagem , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/administração & dosagem , Animais , Sítios de Ligação , Glicemia/metabolismo , Simulação por Computador , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Intolerância à Glucose/tratamento farmacológico , Intolerância à Glucose/metabolismo , Homeostase/efeitos dos fármacos , Hiperinsulinismo/tratamento farmacológico , Hiperinsulinismo/metabolismo , Hipoglicemiantes/síntese química , Resistência à Insulina , Receptor beta de Linfotoxina/química , Receptor beta de Linfotoxina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Peptídeos/síntese química , Membro 14 de Receptores do Fator de Necrose Tumoral/química , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/química , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
17.
Medicine (Baltimore) ; 100(37): e27232, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34664864

RESUMO

ABSTRACT: Both pregnancy, as physiological, and polycystic ovary syndrome (PCOS), as a pathological condition, carry the risk for developing glucose metabolism abnormalities. In this retrospective cross-sectional study, we hypothesized that pregnancy as a physiological condition carries a higher likelihood for abnormal oral glucose tolerance test (OGTT) results than PCOS as a pathological condition.We have compared the prevalence and likelihood ratios for abnormal OGTT results between non-pregnant women with PCOS (Group A) and pregnant women at 24 to 28 weeks of gestation (Group B). Participants of both study groups underwent glucose tolerance testing with 75 g glucose OGTT. During the study period, 7411 women were tested, 3932 women encompassed Group A, and 3479 women comprised Group B.The numbers of yearly tested pregnant women and the corresponding proportion of tested women among all study participants have decreased during the study period, from 766 to 131 and 89.1% to 20.5%, respectively. Group A had a significantly lower prevalence (4.4%) of pathological OGTT results compared to Group B (8.1%). This has resulted in a 45.427 likelihood ratio (P < .001) for abnormal OGTT results in pregnant women compared to non-pregnant women with PCOS.We might conclude that pregnancy could have a more challenging influence on glucose metabolism and that carries higher risks for abnormal glucose metabolism than PCOS. The awareness of obstetricians regarding physiological changes during pregnancy that predisposes abnormal glucose metabolism is decreasing over time and the compliance concerning OGTT testing of pregnant women is decreasing too.


Assuntos
Teste de Tolerância a Glucose/estatística & dados numéricos , Síndrome do Ovário Policístico/complicações , Adulto , Glicemia/análise , Glicemia/metabolismo , Índice de Massa Corporal , Estudos Transversais , Feminino , Intolerância à Glucose/epidemiologia , Intolerância à Glucose/etiologia , Teste de Tolerância a Glucose/métodos , Humanos , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/metabolismo , Gravidez , Estudos Retrospectivos
18.
Arch Biochem Biophys ; 713: 109063, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34695409

RESUMO

Although FGF21 ameliorates diabetic nephropathy (DN), the efficacy is not satisfactory. Studies demonstrate that FGF21 combined with Insulin exhibits reciprocal sensitization on glucose and lipid metabolism in mice with type 2 diabetes. However, therapeutic effect of combined use of FGF21 and Insulin on DN has not been reported. Therefore, this study explored therapeutic effect and mechanism of combined use of FGF21 and Insulin on DN. Our results showed that compared with Insulin or FGF21 alone, FGF21 combined with Insulin further ameliorated blood glucose, HbAlc, OGTT, renal function, liver function, blood lipid, histopathological changes, oxidative stress and AGEs in the mice of DN (BKS-Leprem2Cd479/Gpt). Moreover, FGF21 combined with Insulin further reduced expressions of IL-1ß, IL-6, TNF-α via promoting M1 type macrophage into M2 type macrophage. Results of real-time PCR and Western blot showed that FGF21 combined with Insulin upregulated the expressions of autophagy related genes LC3-Ⅱ and BCL-1. Mesangial cells play an important role in the pathological changes of DN mice. However, the effect of FGF21 on mesangial cells has not been reported. In this study, d-glucose was used in high glucose (HG) model in mesangial cells. The results showed that FGF21 significantly reduced the levels of OS, AGEs and cell overproliferation. Meanwhile, FGF21 significantly ameliorated autophagy level via upregulating the phosphorylation of AMPK and downregulating phosphorylation of mTOR. These effects were reversed in siRNA-ß-klotho transfected mesangial cells. In conclusion, our results demonstrate that combination FGF21 with Insulin exhibits a better therapeutic effect on DN compared with FGF21 or Insulin alone. This study provides a theoretical basis for combined used of FGF21 and Insulin as a new treatment for DN and further provides theoretical support for application of FGF21 in treatment of DN.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Fatores de Crescimento de Fibroblastos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Animais , Autofagia/efeitos dos fármacos , Glicemia/metabolismo , Nefropatias Diabéticas/patologia , Combinação de Medicamentos , Produtos Finais de Glicação Avançada/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
19.
Nutrients ; 13(10)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34684308

RESUMO

We examined the glycemic status-stratified relationships between total serum branched-chain amino acid (BCAA) concentrations and cardiometabolic risk factors in middle-aged Caucasian women. The study included 349 women divided into 2 subgroups: a normoglycemic group (NG, n = 184) and a dysglycemic group (DG, n = 165). Blood samples, anthropometric parameters, and blood pressure were measured. HOMA-IR, albumin-corrected calcium (CCa), and fatty liver index (FLI) were calculated. BCAA concentrations were higher in the women with dysglycemia. BCAAs moderately correlated with BMI and FLI in the NG group and with BMI, FLI, total calcium (TCa), CCa, HbA1c, TG/HDL-C, and HDL-C in the DG group. After adjusting for age and BMI, correlations for TCa, CCa, HbA1c, HDL-C, and TG/HDL-C remained significant. The coexistence of increased BCAAs with dysglycemic status was associated with markedly higher concentrations of TCa, CCa, HbA1c, and TG, which were not observed in the DG women with low level of BCAAs. Multiple regression showed that TCa or CCa, age and BCAAs were significantly associated with HbA1c independently of BMI only in the DG group. We conclude that dysglycemia in particular predisposes women to a significant relationship between total BCAAs and circulating calcium and HbA1c, and that these relationships are independent of BMI and may reflect the pathophysiological calcium-dependent mechanisms connecting BCAAs with metabolic disturbances.


Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Glicemia/metabolismo , Fatores de Risco Cardiometabólico , Área Sob a Curva , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade
20.
Nutrients ; 13(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34684324

RESUMO

Granular study of metabolic responses to alterations in the ratio of dietary macro-nutrients can enhance our understanding of how dietary modifications influence patients with impaired glycemic control. In order to study the effect of diets enriched in fat or carbohydrates, fifteen healthy, normal-weight volunteers received, in a cross-over design, and in a randomized unblinded order, two weeks of an iso-caloric high-fat diet (HFD: 60E% from fat) and a high-carbohydrate diet (HCD: 60E% from carbohydrates). A mixed meal test (MMT) was performed at the end of each dietary period to examine glucose clearance kinetics and insulin and incretin hormone levels, as well as plasma metabolomic profiles. The MMT induced almost identical glycemia and insulinemia following the HFD or HCD. GLP-1 levels were higher after the HFD vs. HCD, whereas GIP did not differ. The HFD, compared to the HCD, increased the levels of several metabolomic markers of risk for the development of insulin resistance, e.g., branched-chain amino acid (valine and leucine), creatine and α-hydroxybutyric acid levels. In normal-weight, healthy volunteers, two weeks of the HFD vs. HCD showed similar profiles of meal-induced glycemia and insulinemia. Despite this, the HFD showed a metabolomic pattern implying a risk for a metabolic shift towards impaired insulin sensitivity in the long run.


Assuntos
Voluntários Saudáveis , Adaptação Fisiológica , Adulto , Apetite , Glicemia/metabolismo , Estudos Cross-Over , Diabetes Mellitus/sangue , Dieta Hiperlipídica , Carboidratos da Dieta , Análise Discriminante , Feminino , Polipeptídeo Inibidor Gástrico/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Controle Glicêmico , Humanos , Incretinas/sangue , Insulina/sangue , Resistência à Insulina , Análise dos Mínimos Quadrados , Masculino , Metaboloma , Fatores de Risco
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