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1.
Medicine (Baltimore) ; 100(35): e27104, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477149

RESUMO

ABSTRACT: To evaluate the diagnostic values of shear wave elastography (SWE) alone and in combination with the Toronto clinical scoring system (TCSS) on diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM).The study included 41 DPN patients, 42 non-DPN patients, and 21 healthy volunteers. Conventional ultrasonography and SWE were performed on the 2 sides of the tibial nerves, and cross-sectional area (CSA) and nerve stiffness were measured. TCSS was applied to all patients. A receiver operating characteristic curve analysis was performed.The stiffness of the tibial nerve, as measured as mean, minimum or maximum elasticity, was significantly higher in patients in the DPN group than the other groups (P < .05). The tibial nerve of subjects in the non-DPN group was significantly stiffer compared to the control group (P < .05). There was no significant difference of the tibial nerve CSA among the 3 groups (P > .05). Mean elasticity of the tibial nerve with a cutoff of 71.3 kPa was the most sensitive (68.3%) and had a higher area under the curve (0.712; 0.602-0.806) among the 3 shear elasticity indices for diagnosing DPN when used alone. When combining SWE with TCSS in diagnosing DPN, the most effective parameter was the EMax, which yielded a sensitivity of 100.00% and a specificity of 95.24%.SWE is a better diagnostic tool for DPN than the conventional ultrasonic parameter CSA, and a higher diagnostic value is attained when combining SWE with TCSS.


Assuntos
Nefropatias Diabéticas/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/normas , Projetos de Pesquisa , Idoso , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/complicações , Técnicas de Imagem por Elasticidade/métodos , Técnicas de Imagem por Elasticidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/classificação , Doenças do Sistema Nervoso Periférico/diagnóstico por imagem , Curva ROC , Reprodutibilidade dos Testes
2.
Nutrients ; 13(7)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34371843

RESUMO

The aim of this prospective cohort study was to examine the relationships between the intakes of various vitamins and the loss of muscle mass in older people with type 2 diabetes (T2DM). The change in skeletal muscle mass index (SMI, kg/m2) (kg/m2/year) was defined as follows: (SMI at baseline (kg/m2) - SMI at follow-up (kg/m2))/follow-up period (year). The rate of SMI reduction (%) was calculated as follows (the change in SMI (kg/m2/year)/SMI at baseline (kg/m2)) × 100. The rate of SMI reduction ≥ 1.2% was considered as the loss of muscle mass. Among 197 people with T2DM, 47.2% of them experienced the loss of muscle mass at the 13.7 ± 5.2 month follow-up. Vitamin B1 (0.8 ± 0.3 vs. 0.8 ± 0.3 mg/day, p = 0.031), vitamin B12 (11.2 ± 8.3 vs. 13.4 ± 7.5 µg/day, p = 0.049), and vitamin D (16.5 ± 12.2 vs. 21.6 ± 13.0 µg/day, p = 0.004) intakes in people with the loss of muscle mass were significantly lower than those without. Vitamin D intake was related to the loss of muscle mass after adjusting for sex, age, exercise, alcohol, smoking, body mass index, SMI, glucagon-like peptide-1 agonist, sodium glucose cotransporter-2 inhibitor, insulin, HbA1c, creatinine, energy intake, and protein intake (adjusted odds ratio 0.93, 95% confidence interval: 0.88-0.97, p = 0.003). This study showed that vitamin D intake was related to the loss of muscle mass in older people with T2DM. Vitamin B12 intake tended to be related to the loss of muscle mass, although vitamin A, vitamin B2, vitamin B6, vitamin C, and vitamin E intake were not related.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Dieta/efeitos adversos , Estado Nutricional , Sarcopenia/epidemiologia , Vitaminas/análise , Idoso , Diabetes Mellitus Tipo 2/complicações , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Ingestão de Energia/fisiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Músculo Esquelético/fisiopatologia , Estudos Prospectivos , Sarcopenia/etiologia
3.
Medicine (Baltimore) ; 100(30): e26431, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397684

RESUMO

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. METHODS: We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. RESULTS: Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. CONCLUSIONS: This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Coração/fisiopatologia , Humanos , Rim/fisiopatologia , Metanálise em Rede , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
4.
Nutrients ; 13(8)2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34444839

RESUMO

Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD). The gut microbiota may contribute to the onset and progression of T2D and CVD. The aim of this study was to evaluate the relationship between the gut microbiota and subclinical CVD in T2D patients. This cross-sectional study used echocardiographic data to evaluate the cardiac structure and function in T2D patients. We used a quantitative polymerase chain reaction to measure the abundances of targeted fecal bacterial species that have been associated with T2D, including Bacteroidetes, Firmicutes, Clostridium leptum group, Faecalibacterium prausnitzii, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. A total of 155 subjects were enrolled (mean age 62.9 ± 10.1 years; 57.4% male and 42.6% female). Phyla Bacteroidetes and Firmicutes and genera Bacteroides were positively correlated with the left ventricular ejection fraction. Low levels of phylum Firmicutes were associated with an increased risk of left ventricular hypertrophy. High levels of both phylum Bacteroidetes and genera Bacteroides were negatively associated with diastolic dysfunction. A high phylum Firmicutes/Bacteroidetes (F/B) ratio and low level of genera Bacteroides were correlated with an increased left atrial diameter. Phyla Firmicutes and Bacteroidetes, the F/B ratio, and the genera Bacteroides were associated with variations in the cardiac structure and systolic and diastolic dysfunction in T2D patients. These findings suggest that changes in the gut microbiome may be the potential marker of the development of subclinical CVD in T2D patients.


Assuntos
Doenças Cardiovasculares/microbiologia , Diabetes Mellitus Tipo 2/microbiologia , Angiopatias Diabéticas/microbiologia , Cardiomiopatias Diabéticas/microbiologia , Microbioma Gastrointestinal/fisiologia , Idoso , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Ecocardiografia , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Função Ventricular Esquerda
5.
Nutrients ; 13(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34444742

RESUMO

Type 2 diabetes is associated with an increased risk for sarcopenia. Moreover, sarcopenia correlates with increased risk for falls, fractures, and mortality. This study aimed to explore relationships among nutrient intakes, diet quality, and functional limitations in a sample of adults across levels of glycemic control. Data were examined from 23,487 non-institutionalized adults, 31 years and older, from the 2005-2016 National Health and Nutrition Examination Survey. Hemoglobin A1c (%) was used to classify level of glycemic control: non-diabetes (<5.7%); pre-diabetes (5.7-6.4%); diabetes (≥6.5%). Dietary data were collected from a single 24-h dietary recall. Participants were categorized as meeting or below the protein recommendation of 0.8 g/kg of body weight. Physical functioning was assessed across 19-discrete physical tasks. Adults below the protein recommendation consumed significantly more carbohydrate and had lower diet quality across all glycemic groups compared to those who met the protein recommendation (p < 0.001). Adults with diabetes who did not meet protein recommendations had significantly poorer diet quality and significantly higher mean number of functional limitations. A greater percent of adults with diabetes who did not meet the protein recommendation reported being physically limited for most activities, with more than half (52%) reporting limitations for stooping, crouching, and kneeling. This study underscores the potential for physical limitations associated with low protein intakes, especially in adults with diabetes. In the longer term, low protein intakes may result in increased risk of muscle loss, as protein intake is a critical nutritional factor for prevention of sarcopenia, functional limitations, and falls.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Dieta , Proteínas na Dieta , Valor Nutritivo , Desempenho Físico Funcional , Atividades Cotidianas , Diabetes Mellitus Tipo 2/complicações , Ingestão de Alimentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Necessidades Nutricionais , Sarcopenia/etiologia
6.
Hawaii J Health Soc Welf ; 80(8): 195-198, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34355196

RESUMO

Native Hawaiian and Pacific Islander (NHPI) populations suffer from disproportionately higher rates of chronic conditions, such as type 2 diabetes, that arises from metabolic dysfunction and are often associated with obesity and inflammation. In addition, the global coronavirus disease 2019 pandemic has further compounded the effect of health inequities observed in Indigenous populations, including NHPI communities. Reversible lifestyle habits, such as diet, may either be protective of or contribute to the increasing prevalence of health inequities in these populations via the immunoepigenetic-microbiome axis. This axis offers insight into the connection between diet, epigenetics, the microbiome composition, immune function, and response to viral infection. Epigenetic mechanisms that regulate inflammatory states associated with metabolic diseases, including diabetes, are impacted by diet. Furthermore, diet may modulate the gut microbiome by influencing microbial diversity and richness; dysbiosis of the microbiome is associated with chronic disease. A high fiber diet facilitates a favorable microbiome composition and in turn increases production of intermediate metabolites named short-chain fatty acids (SCFAs) that act on metabolic and immune pathways. In contrast, low fiber diets typically associated with a westernized lifestyle decreases the abundance of microbial derived SCFAs. This decreased abundance is characteristic of metabolic syndromes and activation of chronic inflammatory states, having larger implications in disease pathogenesis of both communicable and non-communicable diseases. Native Hawaiians and Pacific Islanders that once thrived on healthy traditional diets may be more sensitive than non-indigenous peoples to the metabolic perturbation of westernized diets that impinge on the immunoepigenetic-gut microbiome axis. Recent studies conducted in the Maunakea lab at the University of Hawai'i at Manoa John A. Burns School of Medicine have helped elucidate the connections between diet, microbiome composition, metabolic syndrome, and epigenetic regulation of immune function to better understand disease pathogenesis. Potentially, this research could point to ways to prevent pre-disease conditions through novel biomarker discovery using community-based approaches.


Assuntos
Dieta/métodos , Epigênese Genética/fisiologia , Microbioma Gastrointestinal/fisiologia , Disparidades nos Níveis de Saúde , Imunidade/fisiologia , Grupo com Ancestrais Oceânicos , Pesquisa Biomédica , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fibras na Dieta/farmacologia , Ácidos Graxos Voláteis/fisiologia , Hawaii/epidemiologia , Humanos , Mediadores da Inflamação/fisiologia
7.
Front Endocrinol (Lausanne) ; 12: 642452, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234738

RESUMO

Background: We investigated if the concentration and "rangeability" of cystatin C (CysC) influenced the prognosis of coronavirus disease 2019 (COVID-19) in patients suffering from, or not suffering from, type 2 diabetes mellitus (T2DM). Methods: A total of 675 T2DM patients and 572 non-T2DM patients were divided into "low" and "high" CysC groups and low and high CysC-rangeability groups according to serum CysC level and range of change of CysC level, respectively. Demographic characteristics, clinical data, and laboratory results of the four groups were analyzed. Results: COVID-19 patients with a high level and rangeability of CysC had more organ damage and a higher risk of death compared with those with a low level or low rangeability of CysC. Patients with a higher level and rangeability of CysC had more blood lymphocytes and higher levels of C-reactive protein, alanine aminotransferase, and aspartate aminotransferase. After adjustment for possible confounders, multivariate analysis revealed that CysC >0.93 mg/dL was significantly associated with the risk of heart failure (OR = 2.231, 95% CI: 1.125-5.312) and all-cause death (2.694, 1.161-6.252). CysC rangeability >0 was significantly associated with all-cause death (OR = 4.217, 95% CI: 1.953-9.106). These associations were stronger in patients suffering from T2DM than in those not suffering from T2DM. Conclusions: The level and rangeability of CysC may influence the prognosis of COVID-19. Special care and appropriate intervention should be undertaken in COVID-19 patients with an increased CysC level during hospitalization and follow-up, especially for those with T2DM.


Assuntos
Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Cistatina C/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , SARS-CoV-2/isolamento & purificação , Idoso , COVID-19/sangue , COVID-19/virologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
8.
Expert Opin Investig Drugs ; 30(8): 813-825, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34214406

RESUMO

Introduction: Accumulating evidence supports a bidirectional association between nonalcoholic steatohepatitis (NASH) and type 2 diabetes (T2D). There is a clinical challenge to consider pharmaceutical strategies targeting the metabolic dysfunction common to NASH and T2D pathogenesis.Areas covered: By using PubMed, we performed a literature search to review the potential beneficial effect of anti-diabetic and metabolic investigational drugs on NASH.Expert opinion: Since insulin resistance is central in the pathophysiology of both T2D and NASH, there is an urgent need for new insulin sensitizers. Peroxisome proliferator-activated receptor (PPAR) agonists, especially PPARγ and pan-PPARs agonists, have shown some beneficial effects on both NASH and liver fibrosis, but their routine use should be limited by their safety profile. Incretin-based therapies, including glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the polyagonists (GLP-1, GIP, glucagon) under development are the most promising anti-diabetic drugs for NASH treatment, mainly due to their action on body weight loss. Preliminary, preclinical and early phase studies suggest that SGLT2 inhibitors and fibroblast growth factor (FGF)19 and FGF21-based therapies are promising targets for NASH and T2D treatment. The common weakness for all of these drugs is their limited effect on liver fibrosis, potentially due to short-term trial design.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Drogas em Investigação/farmacologia , Humanos , Resistência à Insulina , Cirrose Hepática/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Projetos de Pesquisa
9.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299225

RESUMO

COVID-19 infection poses an important clinical therapeutic problem, especially in patients with coexistent diseases such as type 2 diabetes. Potential pathogenetic links between COVID-19 and diabetes include inflammation, effects on glucose homeostasis, haemoglobin deoxygenation, altered immune status and activation of the renin-angiotensin-aldosterone system (RAAS). Moreover, drugs often used in the clinical care of diabetes (dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, sodium-glucose cotransporter 2 inhibitors, metformin and insulin) may influence the course of SARS-CoV-2 infection, so it is very important to verify their effectiveness and safety. This review summarises the new advances in diabetes therapy and COVID-19 and provides clinical recommendations that are essential for medical doctors and for patients suffering from type 2 diabetes.


Assuntos
COVID-19/terapia , Diabetes Mellitus Tipo 2/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/virologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Metformina/uso terapêutico , SARS-CoV-2/isolamento & purificação , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
10.
Int J Mol Sci ; 22(12)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205470

RESUMO

In cases of patients with rapidly progressive diabetes mellitus (DM), autologous stem cell transplantation is considered as one of the regenerative treatments. However, whether the effects of autonomous stem cell transplantation on DM patients are equivalent to transplantation of stem cells derived from healthy persons is unclear. This study revealed that adipose-derived mesenchymal stem cells (ADSC) derived from type II DM patients had lower transplantation efficiency, proliferation potency, and stemness than those derived from healthy persons, leading to a tendency to induce apoptotic cell death. To address this issue, we conducted a cyclopedic mRNA analysis using a next-generation sequencer and identified G6PC3 and IGF1, genes related to the FoxO signaling pathway, as the genes responsible for lower performance. Moreover, it was demonstrated that the lower transplantation efficiency of ADSCs derived from type II DM patients might be improved by knocking down both G6PC3 and IGF1 genes. This study clarified the difference in transplantation efficiency between ADSCs derived from type II DM patients and those derived from healthy persons and the genes responsible for the lower performance of the former. These results can provide a new strategy for stabilizing the quality of stem cells and improving the therapeutic effects of regenerative treatments on autonomous stem cell transplantation in patients with DM.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Glucose-6-Fosfatase/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Células Cultivadas , Humanos , Transdução de Sinais , Transplante Autólogo
11.
Nutrients ; 13(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200398

RESUMO

Information regarding the spread and effect of coffee and caffeine intake by individuals with type II diabetes remains unclear. This study aims to identify the amount and sources of habitual caffeine intake by individuals with type II diabetes and to investigate its association with other health outcomes, especially HbA1c. This is a cross-sectional survey involving 100 people medically defined as having type II diabetes comprising both genders, recruited from a care centre. All participants completed a caffeine semi-quantitative food frequency questionnaire (C-FFQ) to estimate their caffeine consumption, a two day 24-h recall, and a detailed questionnaire. The average caffeine intake was calculated from all sources and the differences in mean by gender were tested using a regression model (adjusted to important confounders). Regression models were used to verify the association between average caffeine intake on HbA1c and other health outcomes with adjustment for important confounders. A p value < 0.05 represented statistical significance. Arabic coffee (gahwa) and tea were the most common sources of caffeine among Saudi adults living with diabetes. Average caffeine intake for the whole sample was 194 ± 165 mg/day, which is 2.3 ± 2 mg/kg. There was an inverse association between caffeine intake and age: difference in mean -3.26 mg/year (95%CI: -5.34, -1.18; p = 0.003). Males had significantly higher consumption of caffeine compared to females: difference in mean 90.7 mg/day (95%CI: 13.8, 167.6; p = 0.021). No association was found between average caffeine intake and HbA1C or any other cardiovascular risk factors. This information can help public health practitioners and policy makers when assessing the risk of caffeine consumption among this vulnerable group.


Assuntos
Cafeína/farmacologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Comportamento de Ingestão de Líquido , Hemoglobina A Glicada/metabolismo , Adulto , Pressão Sanguínea , Colesterol/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Triglicerídeos/sangue
12.
Biomed Pharmacother ; 138: 111465, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34311522

RESUMO

Acidic mammalian chitinase (CHIA) belongs to the 18-glycosidase family and is expressed in epithelial cells and certain immune cells (such as neutrophils and macrophages) in various organs. Under physiological conditions, as a hydrolase, CHIA can degrade chitin-containing pathogens, participate in Type 2 helper T (Th2)-mediated inflammation, and enhance innate and adaptive immunity to pathogen invasion. Under pathological conditions, such as rhinitis, ocular conjunctivitis, asthma, chronic atrophic gastritis, type 2 diabetes, and pulmonary interstitial fibrosis, CHIA expression is significantly changed. In addition, studies have shown that CHIA has an anti-apoptotic effect, promotes epithelial cell proliferation and maintains organ integrity, and these effects are not related to chitinase degradation. CHIA can also be used as a biomolecular marker in diseases such as chronic atrophic gastritis, dry eye, and acute kidney damage caused by sepsis. Analysis of the authoritative TCGA database shows that CHIA expression in gastric adenocarcinoma, liver cancer, renal clear cell carcinoma and other tumors is significantly downregulated compared with that in normal tissues, but the specific mechanism is unclear. This review is based on all surveys conducted to date and summarizes the expression patterns and functional diversity of CHIA in various organs. Understanding the physiological and pathophysiological relevance of CHIA in multiple organs opens new possibilities for disease treatment.


Assuntos
Encéfalo/enzimologia , Quitinases/metabolismo , Sistema Digestório/enzimologia , Olho/enzimologia , Rim/enzimologia , Sistema Respiratório/enzimologia , Animais , Encéfalo/fisiopatologia , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/fisiopatologia , Sistema Digestório/fisiopatologia , Olho/fisiopatologia , Humanos , Rim/fisiopatologia , Sistema Respiratório/fisiopatologia , Transdução de Sinais
13.
Eur J Endocrinol ; 185(2): 343-353, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34085953

RESUMO

Objective: Hypoglycemia is associated with an increased risk of cardiovascular disease including cardiac arrhythmias. We investigated the effect of hypoglycemia in the setting of acute glycemic fluctuations on cardiac rhythm and cardiac repolarization in insulin-treated patients with type 2 diabetes compared with matched controls without diabetes. Design: A non-randomized, mechanistic intervention study. Methods: Insulin-treated patients with type 2 diabetes (n = 21, age (mean ± s.d.): 62.8 ± 6.5 years, BMI: 29.0 ± 4.2 kg/m2, HbA1c: 6.8 ± 0.5% (51.0 ± 5.4 mmol/mol)) and matched controls (n = 21, age: 62.2 ± 8.3 years, BMI 29.2 ± 3.5 kg/m2, HbA1c: 5.3 ± 0.3% (34.3 ± 3.3 mmol/mol)) underwent a sequential hyperglycemic and hypoglycemic clamp with three steady-states of plasma glucose: (i) fasting plasma glucose, (ii) hyperglycemia (fasting plasma glucose +10 mmol/L) and (iii) hyperinsulinemic hypoglycemia (plasma glucose < 3.0 mmol/L). Participants underwent continuous ECG monitoring and blood samples for counterregulatory hormones and plasma potassium were obtained. Results: Both groups experienced progressively increasing heart rate corrected QT (Fridericia's formula) interval prolongations during hypoglycemia ((∆mean (95% CI): 31 ms (16, 45) and 39 ms (24, 53) in the group of patients with type 2 diabetes and controls, respectively) with similar increases from baseline at the end of the hypoglycemic phase (P = 0.43). The incidence of ventricular premature beats increased significantly in both groups during hypoglycemia (P = 0.033 and P < 0.0001, respectively). One patient with type 2 diabetes developed atrial fibrillation during recovery from hypoglycemia. Conclusions: In insulin-treated patients with type 2 diabetes and controls without diabetes, hypoglycemia causes clinically significant and similar increases in cardiac repolarization that might increase vulnerability for serious cardiac arrhythmias and sudden cardiac death.


Assuntos
Arritmias Cardíacas/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Hipoglicemia/fisiopatologia , Idoso , Arritmias Cardíacas/sangue , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/sangue , Eletrocardiografia , Feminino , Glucagon/sangue , Hormônio do Crescimento/sangue , Frequência Cardíaca/fisiologia , Humanos , Hidrocortisona/sangue , Hipoglicemia/sangue , Masculino , Pessoa de Meia-Idade , Norepinefrina/sangue , Potássio/sangue
14.
Expert Rev Clin Pharmacol ; 14(9): 1091-1103, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34085587

RESUMO

INTRODUCTION: The specific role of testosterone [T] replacement therapy [TRT] on glycometabolic profile and body composition, particularly in patients with metabolic syndrome [MetS] and/or type 2 diabetes mellitus [T2DM], is still the object of an intense debate. AREAS COVERED: To discuss available evidence on the association between T and metabolic diseases and on the possible effect of T administration on metabolic disorder-associated hypogonadism. Both preclinical and clinical data have been considered. In addition, a meta-analysis of the available placebo and non-placebo-controlled randomized clinical trials [RCTs] investigating the effects of TRT in T2DM or MetS in several outcomes has been also performed. EXPERT OPINION: Data derived from preclinical and clinical studies suggest that T administration, by reducing fat mass, can improve body composition and ameliorate some aspects of glucose metabolism. The effects of TRT on sexual function in patients with established metabolic derangements are inconsistent, whereas better results were observed in preclinical conditions or in patients with newly diagnosed T2DM.


Assuntos
Terapia de Reposição Hormonal/métodos , Doenças Metabólicas/tratamento farmacológico , Testosterona/administração & dosagem , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Humanos , Hipogonadismo/tratamento farmacológico , Hipogonadismo/etiologia , Masculino , Doenças Metabólicas/fisiopatologia , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Alzheimers Dis ; 82(3): 1259-1275, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151813

RESUMO

BACKGROUND: Periodontal disease(s) and metabolic illnesses negatively impact the quality of life and, eventually mental health. OBJECTIVE: This study investigated the effect of Porphyromonas gingivalis (W83) oral infection on the development of Alzheimer's disease (AD) pathophysiology in a wild-type obese, diabetic (db/db) mouse model. METHODS: The db/db mice were either orally infected with P. gingivalis and Fusobacterium nucleatum or sham infected for 16 weeks. The presence of amyloid-ß (Aß) and neurofibrillary tangles (NFTs) were assessed using a silver impregnation technique and subsequently by immunohistochemistry for tau and neuroinflammation. The mRNA abundance of a panel of 184 genes was performed using quantitative real-time PCR, and the differentially expressed genes were analyzed by Ingenuity Pathway Analysis. RESULTS: While no Aß plaques and NFTs were evident by silver impregnation, immunohistochemistry (glial cell markers) of the P. gingivalis-infected mice tissue sections exhibited neuroinflammation in the form of reactive microglia and astrocytes. Anti-tau immunopositivity, in addition to cells, was prominent in thickened axons of hippocampal CA neurons. The mRNA abundance of crucial genes in the insulin signaling pathway (INSR, IGF1, IRS, IDE, PIK3R, SGK1, GYS, GSK3B, AKT1) were upregulated, potentially exacerbating insulin resistance in the brain by P. gingivalis oral infection. Increased mRNA abundance of several kinases, membrane receptors, transcription factors, and pro-inflammatory mediators indicated hyperactivation of intracellular cascades with potential for tau phosphorylation and Aß release in the same infection group. CONCLUSION: P. gingivalis W83 infection of db/db mice provides a disease co-morbidity model with the potential to reproduce AD pathophysiology with induced periodontal disease.


Assuntos
Doença de Alzheimer/fisiopatologia , Infecções por Bacteroidaceae/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Obesidade/fisiopatologia , Porphyromonas gingivalis , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Animais , Infecções por Bacteroidaceae/genética , Infecções por Bacteroidaceae/psicologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/psicologia , Camundongos , Camundongos Transgênicos , Obesidade/genética , Obesidade/psicologia
16.
Nutrients ; 13(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072748

RESUMO

The aim of the report was to investigate the impact of soy protein and isoflavones on glucose homeostasis and lipid profile in type 2 diabetes. The studies used in this report were identified by searching through the MEDLINE and EMBASE databases (up to 2020). Meta-regression and subgroup analyses were performed to explore the influence of covariates on net glycemic control and lipid changes. Weighted mean differences and 95% confidence intervals (CI) were calculated by using random-effect models. Changes in the lipid profile showed statistically significant decreases in total cholesterol and LDL-C concentrations: ‒0.21 mmol/L; 95% CI, ‒0.33 to ‒0.09; p = 0.0008 and ‒0.20 mmol/L; 95% CI, ‒0.28 to ‒0.12; p < 0.0001, respectively, as well as in HDL-C (-0.02 mmol/L; 95% CI, -0.05 to 0.01; p = 0.2008 and triacylglycerols (-0.19 mmol/L; 95% CI, -0.48 to 0.09; p = 0.1884). At the same time, a meta-analysis of the included studies revealed statistically insignificant reduction in fasting glucose, insulin, HbA1c, and HOMA-IR (changes in glucose metabolism) after consumption of soy isoflavones. The observed ability of both extracted isoflavone and soy protein with isoflavones to modulate the lipid profile suggests benefits in preventing cardiovascular events in diabetic subjects. Further multicenter studies based on larger and longer duration studies are necessary to determine their beneficial effect on glucose and lipid metabolism.


Assuntos
Diabetes Mellitus Tipo 2 , Controle Glicêmico , Isoflavonas , Lipídeos/sangue , Proteínas de Soja , Idoso , Glicemia/efeitos dos fármacos , Glicemia/fisiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Hemoglobina A Glicada/análise , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade
17.
Medicine (Baltimore) ; 100(23): e26237, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34115010

RESUMO

INTRODUCTION: Severe hypertriglyceridemia (HTG) is a rare complication of insulin resistance. Its presentation with diabetic ketoacidosis (DKA) has been reported in a few cases, where most patients have type-1 diabetes mellitus (DM). Our case represents a unique presentation of DKA associated with severe HTG above 10,000 mg/dL in an adult with type-2 DM. PATIENT CONCERNS AND DIAGNOSIS: Case Report: A 51-year-old man with no prior illnesses presented to the emergency department with abdominal pain and nausea. He was found to have DKA with a blood glucose level of 337 mg/dL, pH of 7.17, beta-hydroxybutyrate of 7.93 mmol/L, and anion gap of 20 mmol/L. His triglyceride levels were >10,000 mg/dL. His serum was found to be lipemic. Computerized tomography scan of the abdomen demonstrated mild acute pancreatitis. Negative GAD65 antibodies supported the diagnosis of type-2 DM. INTERVENTIONS AND OUTCOMES: Endocrinology was consulted and one cycle of albumin-bound plasmapheresis was administered. This therapy significantly improved his HTG. DKA gradually resolved with insulin therapy as well. He was discharged home with endocrinology follow-up. CONCLUSION: This unique case highlights an uncommon but critical consequence of uncontrolled DM. It brings forth the possibility of severe HTG presenting as a complication of uncontrolled type-2 DM. Severe HTG commonly presents with acute pancreatitis, which can be debilitating if not managed promptly. Most patients with this presentation are managed with insulin infusion. The use of plasmapheresis for management of severe HTG has not been well studied. Our case supports the use of plasmapheresis as an effective and rapid treatment for severe HTG.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Cetoacidose Diabética/fisiopatologia , Hipertrigliceridemia/fisiopatologia , Dor Abdominal/etiologia , Complicações do Diabetes/diagnóstico , Cetoacidose Diabética/diagnóstico , Humanos , Hipertrigliceridemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Inquéritos Nutricionais , Plasmaferese/métodos
18.
Nutrients ; 13(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063109

RESUMO

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of ß-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., ß-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.


Assuntos
Desjejum/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Diabetes Mellitus Tipo 2/dietoterapia , Dieta para Diabéticos/métodos , Ingestão de Energia/fisiologia , Apetite/fisiologia , Glicemia/metabolismo , Relógios Circadianos/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Comportamento Alimentar/fisiologia , Humanos , Hiperglicemia , Refeições/fisiologia , Período Pós-Prandial/fisiologia , Fatores de Tempo , Perda de Peso/fisiologia
19.
Diabet Med ; 38(9): e14616, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34062007

RESUMO

The National Diabetes Audit (NDA) collates and analyses data on the quality and variation in clinical care and outcomes for people with diabetes. It also provides opportunities to assess trends, determinants, and outcomes of diabetes to help guide clinical and public health priorities. COHORT: Between 1 January 2003 and 31 March 2020, a total of 5,280,885 people diagnosed with diabetes were included in at least one NDA data collection. To this date, median follow-up was 12 and 8 years for people with type 1 diabetes and type 2 diabetes respectively. Comparisons with the 2019/20 Quality and Outcomes Framework show it included 98% of adults in England and Wales with diagnosed type 1 and type 2 diabetes. Data include demographic characteristics (age, sex, ethnicity, age at diagnosis, deprivation), risk factors (HbA1c , blood pressure, cholesterol, body mass index, smoking status) diabetic and cardiovascular complications and deaths. SECONDARY ANALYSIS: Secondary analyses have included comparisons of HbA1c and blood pressure measurements in cohorts with similar characteristics to the Epidemiology of Diabetes Interventions and Complications study and the UK Prospective Diabetes Study; COVID-19 related mortality in people with type 1 and type 2 diabetes and incidence of type 2 diabetes following admission to intensive care units. FUTURE PLANS: Commissioned NDA reports will continue to inform service development in England and Wales. The same data, with or without linkages to other external datasets, are also a rich resource for clinically orientated research.


Assuntos
COVID-19/epidemiologia , Auditoria Clínica , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , SARS-CoV-2 , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Inglaterra/epidemiologia , Feminino , Seguimentos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Lactente , Masculino , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , Resultado do Tratamento , País de Gales/epidemiologia , Adulto Jovem
20.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071721

RESUMO

Changes in lifestyle in developed countries have triggered the prevalence of obesity and type 2 diabetes mellitus (T2DM) in the latest years. Consequently, these metabolic diseases associated to insulin resistance, and the morbidity associated with them, accounts for enormous costs for the health systems. The best way to face this problem is to identify potential therapeutic targets and/or early biomarkers to help in the treatment and in the early detection. In the insulin receptor signaling cascade, the activities of protein tyrosine kinases and phosphatases are coordinated, thus, protein tyrosine kinases amplify the insulin signaling response, whereas phosphatases are required for the regulation of the rate and duration of that response. The focus of this review is to summarize the impact of transmembrane receptor protein tyrosine phosphatase (RPTPs) in the insulin signaling cascade and secretion, and their implication in metabolic diseases such as obesity and T2DM.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Insulina/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Animais , Humanos , Resistência à Insulina , Obesidade , Prevalência , Proteínas Tirosina Fosfatases/metabolismo , Receptor de Insulina/metabolismo , Transdução de Sinais/fisiologia
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