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1.
Neurol Sci ; 44(3): 1059-1067, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36401657

RESUMO

INTRODUCTION: Myotonic dystrophy type 2 (DM2) is a rare, multisystemic, autosomal dominant disease with highly variable clinical presentation. DM2 is considered to be highly underdiagnosed. OBJECTIVE: The aim of this study was to determine which symptoms, signs, and diagnostic findings in patients referred to neurological outpatient units are the most indicative to arouse suspicion of DM2. We tried to make a useful and easy-to-administer clinical scoring system for early diagnosis of DM2-DM2 early diagnosis score (DM2-EDS). PATIENTS AND METHODS: Two hundred ninety-one patients with a clinical suspicion of DM2 were included: 69 were genetically confirmed to have DM2, and 222 patients were DM2 negative. Relevant history, neurological, and paraclinical data were obtained from the electronic medical records. RESULTS: The following parameters appeared as significant predictors of DM2 diagnosis: cataracts (beta = 0.410, p < 0.001), myotonia on needle EMG (beta = 0.298, p < 0.001), hand tremor (beta = 0.211, p = 0.001), positive family history (beta = 0.171, p = 0.012), and calf hypertrophy (beta = 0.120, p = 0.043). In the final DM2-EDS, based on the beta values, symptoms were associated with the following values: cataracts (present 3.4, absent 0), myotonia (present 2.5, absent 0), tremor (present 1.7, absent 0), family history (positive 1.4, negative 0), and calf hypertrophy (present 1.0, absent 0). A cut-off value on DM2-EDS of 3.25 of maximum 10 points had a sensitivity of 84% and specificity of 81% to diagnose DM2. CONCLUSION: Significant predictors of DM2 diagnosis in the neurology outpatient unit were identified. We made an easy-to-administer DM2-EDS score for early diagnosis of DM2.


Assuntos
Catarata , Miotonia , Distrofia Miotônica , Humanos , Distrofia Miotônica/diagnóstico , Tremor , Hipertrofia
2.
Int J Mol Sci ; 24(18)2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37762484

RESUMO

Myotonic dystrophy 2 (DM2) is a genetic multi-systemic disease primarily affecting skeletal muscle. It is caused by CCTGn expansion in intron 1 of the CNBP gene, which encodes a zinc finger protein. DM2 disease has been successfully modeled in Drosophila melanogaster, allowing the identification and validation of new pathogenic mechanisms and potential therapeutic strategies. Here, we describe the principal tools used in Drosophila to study and dissect molecular pathways related to muscular dystrophies and summarize the main findings in DM2 pathogenesis based on DM2 Drosophila models. We also illustrate how Drosophila may be successfully used to generate a tractable animal model to identify novel genes able to affect and/or modify the pathogenic pathway and to discover new potential drugs.


Assuntos
Proteínas de Drosophila , Distrofia Miotônica , Animais , Drosophila melanogaster/genética , Distrofia Miotônica/genética , Drosophila , Íntrons/genética , Músculo Esquelético , Proteínas de Ligação a RNA , Proteínas de Drosophila/genética
3.
Crit Rev Food Sci Nutr ; 62(16): 4435-4448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33480268

RESUMO

This study aimed to review the literature on studies that evaluated the effects of omega-3 supplementation on parameters of diabetes in humans. An online search was conducted in the following databases: Pubmed, LILACS, Scielo, Scopus, and Web of Science. It included experimental studies that investigated the effects of omega-3 supplementation for diabetes treatment or prevention and its relationship with fasting blood glucose, insulin resistance, and glycated hemoglobin. Observational, non-human studies and non-randomized clinical trials were excluded. The Cochrane scale assessed the quality of the studies. A meta-analysis was carried out to evaluate the effect of omega-3 on fasting blood glucose, insulin resistance, and glycated hemoglobin. Thirty studies were included in the review. Almost 70% (n = 20) demonstrated at least one significant effect of the omega-3 supplementation related to diabetes. In the meta-analysis, there was a significant effect on the reduction of fasting blood glucose [SMD: -0.48; CI95%: -0.76, -0.19; p = 0.01; I2 = 88%] and insulin resistance [SMD: -0.61; CI95%: -0.98, -0.24; p = 0.01; I2 = 90%]. For glycated hemoglobin, there was no significant effect in the meta-analysis. This systematic review with meta-analysis demonstrated that supplementation with omega-3 has protective effects on diabetes parameters.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Ácidos Graxos Ômega-3 , Resistência à Insulina , Glicemia , Diabetes Mellitus/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Suplementos Nutricionais , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Hemoglobinas Glicadas , Humanos
4.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36499107

RESUMO

Myotonic dystrophy (DM) is a highly variable, multisystemic disorder that clinically affects one in 8000 individuals. While research has predominantly focused on the symptoms and pathological mechanisms affecting striated muscle and brain, DM patient surveys have identified a high prevalence for gastrointestinal (GI) symptoms amongst affected individuals. Clinical studies have identified chronic and progressive dysfunction of the esophagus, stomach, liver and gallbladder, small and large intestine, and rectum and anal sphincters. Despite the high incidence of GI dysmotility in DM, little is known regarding the pathological mechanisms leading to GI dysfunction. In this review, we summarize results from clinical and molecular analyses of GI dysfunction in both genetic forms of DM, DM type 1 (DM1) and DM type 2 (DM2). Based on current knowledge of DM primary pathological mechanisms in other affected tissues and GI tissue studies, we suggest that misregulation of alternative splicing in smooth muscle resulting from the dysregulation of RNA binding proteins muscleblind-like and CUGBP-elav-like is likely to contribute to GI dysfunction in DM. We propose that a combinatorial approach using clinical and molecular analysis of DM GI tissues and model organisms that recapitulate DM GI manifestations will provide important insight into defects impacting DM GI motility.


Assuntos
Distrofia Miotônica , Humanos , Distrofia Miotônica/complicações , Distrofia Miotônica/genética , Processamento Alternativo , Músculo Esquelético/metabolismo , Proteínas de Ligação a RNA/metabolismo
5.
J Shoulder Elbow Surg ; 30(9): 2032-2040, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33571655

RESUMO

BACKGROUND: Metabolic syndrome (MetS) is an abnormal physiological condition that has been increasingly identified as a risk factor for complications after orthopedic surgery. Given the lack of information on the effect of MetS in shoulder arthroplasty (SA), this investigation analyzed the rates of postoperative complications and implant survivorship free from reoperation and revision in patients with and without MetS. METHODS: Between 2007 and 2017, data from 4635 adults who underwent a primary SA were collected and classified based on the presence or absence of MetS. MetS was defined as the existence of type 2 diabetes mellitus and a minimum of 2 of the following diagnoses: hyperlipidemia, hypertension, and body mass index ≥ 30 kg/m2 within 1 year of surgery. Of the 4635 arthroplasties, 714 were performed in patients with MetS (anatomic total shoulder arthroplasty [aTSA] in 289 and reverse shoulder arthroplasty [RSA] in 425) and 3921 were performed in patients without MetS (aTSA in 1736 and RSA in 2185). Demographic characteristics, complications, reoperations, and revision surgery were compared. RESULTS: At a mean of follow-up of 4.5 ± 2.3 years, 67 MetS patients (9.4%) and 343 non-MetS patients (8.7%) had sustained at least 1 postoperative complication (P = .851). Rotator cuff failure was the most common complication overall, with 84 cases (1.8%) (15 MetS cases [2.1%] and 69 non-MetS cases [1.8%], P = .851), and in both MetS and non-MetS patients, followed by infection, with 68 cases (1.2%) (10 MetS cases [1.4%] and 58 non-MetS cases [1.2%], P = .913). For aTSAs, the most common complication was rotator cuff failure (84 shoulders, 1.8%); for RSAs, the most common complication was periprosthetic fracture (52 shoulders, 1.1%). In RSAs, the rates of deep infection (1.9% vs. 0.7%, P = .04), instability (3.1% vs. 1.5%, P = .04), and deep venous thrombosis or pulmonary embolism (0.5% vs. 0.3%, P = .03) were found to be significantly higher in patients with MetS than in those without MetS. Reoperations were observed in 36 MetS patients (5%) and 170 non-MetS patients (4.3%) (P = .4). Revisions were performed in 30 MetS patients (4.2%) and 127 non-MetS patients (3.2%) (P = .19). The Kaplan-Meier 5-year rate of survivorship free from reoperation, revision, and prosthetic joint infection was equal between groups. CONCLUSIONS: A preoperative diagnosis of MetS in patients undergoing primary SA did not significantly increase the risk of postoperative complications, infection, reoperation, or revision following primary SA. However, in the RSA subgroup, complications were significantly more common in patients with MetS. Individual risk factors may be more appropriate than the umbrella diagnosis of MetS prior to aTSA.


Assuntos
Artroplastia do Ombro , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , Articulação do Ombro , Adulto , Artroplastia , Artroplastia do Ombro/efeitos adversos , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Reoperação , Estudos Retrospectivos , Articulação do Ombro/cirurgia , Resultado do Tratamento
6.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34200099

RESUMO

Non-coding RNAs (ncRNAs) have been reported to be implicated in cell fate determination and various human diseases. All ncRNA molecules are emerging as key regulators of diverse cellular processes; however, little is known about the regulatory interaction among these various classes of RNAs. It has been proposed that the large-scale regulatory network across the whole transcriptome is mediated by competing endogenous RNA (ceRNA) activity attributed to both protein-coding and ncRNAs. ceRNAs are considered to be natural sponges of miRNAs that can influence the expression and availability of multiple miRNAs and, consequently, the global mRNA and protein levels. In this review, we summarize the current understanding of the role of ncRNAs in two neuromuscular diseases, myotonic dystrophy type 1 and 2 (DM1 and DM2), and the involvement of expanded CUG and CCUG repeat-containing transcripts in miRNA-mediated RNA crosstalk. More specifically, we discuss the possibility that long repeat tracts present in mutant transcripts can be potent miRNA sponges and may affect ceRNA crosstalk in these diseases. Moreover, we highlight practical information related to innovative disease modelling and studying RNA regulatory networks in cells. Extending knowledge of gene regulation by ncRNAs, and of complex regulatory ceRNA networks in DM1 and DM2, will help to address many questions pertinent to pathogenesis and treatment of these disorders; it may also help to better understand general rules of gene expression and to discover new rules of gene control.


Assuntos
Redes Reguladoras de Genes , MicroRNAs/genética , Distrofia Miotônica/patologia , RNA Circular/genética , RNA Mensageiro/genética , Animais , Humanos , Distrofia Miotônica/genética
7.
J Cell Mol Med ; 22(1): 684-694, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28990324

RESUMO

Stanniocalcins are expressed in the pancreas tissue, and it was suggested a direct correlation between circulating insulin and STC2 concentrations in human. Here, we show a significant correlation between STC1 and both glycaemia and glycosylated haemoglobin among DM2 patients, while DM2 patients who present the greatest glycosylated haemoglobin values exhibited the lowest STC2 expression. However, treatment of patients with antiglycaemic drugs does not significantly modify the expression of both STCs. On the other hand, STC2-/- mice that exhibited neonatal and adult overweight further presented deregulated glycaemia when they were feed with a hypercaloric diet (breeding pellet, BP). This alteration is more evident at the early stages of the animal life. Deregulated glycaemia in these mice was confirmed using glucose oral test. In addition, STC2-/- mice present enhanced pancreas size; thus, the histological analysis reveals that WT mice respond to BP diet by increasing the size of the pancreatic islets through inducing cell division, and STC2-/- mice lack this compensatory mechanism. Contrary, BP fed STC2-/- mice show enhanced number of islets but of similar size than those fed with regular pellet. Histopathological analysis demonstrates tissue structure disruption and erythrocytes infiltrations in STC2-/- mice, possibly due to the stress evoked by the BP diet. Finally, enhanced glucagon immunostaining was observed in the islet of STC2-/- mice, and the glucagon ELISA assay confirmed the increase in the circulating glucagon. Summarizing, we present evidence of the role of STCs, mainly STC2, as a possible early marker during development of diabetes mellitus.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Adulto , Idoso , Animais , Glucagon/sangue , Glicoproteínas/deficiência , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Camundongos Endogâmicos C57BL , Camundongos Obesos , Pessoa de Meia-Idade , Tamanho do Órgão , Pâncreas/metabolismo , Pâncreas/patologia
8.
J Okla State Med Assoc ; 110(4): 206-7, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-29303239

RESUMO

ANSWER: Insufficient evidence. DATE ANSWER WAS DETERMINED: June 28, 2016. PROGRAM NAME: Great Plains Family Medicine Residency Program, Oklahoma City, OK.


Assuntos
Glicemia/análise , Bebidas Gaseificadas , Diabetes Mellitus Tipo 2/sangue , Edulcorantes/administração & dosagem , Humanos
9.
Sensors (Basel) ; 16(9)2016 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-27657085

RESUMO

To obtain efficient data gathering methods for wireless sensor networks (WSNs), a novel graph based transform regularized (GBTR) matrix completion algorithm is proposed. The graph based transform sparsity of the sensed data is explored, which is also considered as a penalty term in the matrix completion problem. The proposed GBTR-ADMM algorithm utilizes the alternating direction method of multipliers (ADMM) in an iterative procedure to solve the constrained optimization problem. Since the performance of the ADMM method is sensitive to the number of constraints, the GBTR-A2DM2 algorithm obtained to accelerate the convergence of GBTR-ADMM. GBTR-A2DM2 benefits from merging two constraint conditions into one as well as using a restart rule. The theoretical analysis shows the proposed algorithms obtain satisfactory time complexity. Extensive simulation results verify that our proposed algorithms outperform the state of the art algorithms for data collection problems in WSNs in respect to recovery accuracy, convergence rate, and energy consumption.

10.
Br J Nutr ; 114(9): 1471-9, 2015 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-26344165

RESUMO

Only one prospective study has analysed the relationship between the inflammatory properties of diet and risk of depression thus far. The aim of this study was to assess the association between the dietary inflammatory index (DII) and the incidence of depression. In a cohort study of 15 093 university graduates, participants completed a validated FFQ at baseline and after 10 years of follow-up. The DII was calculated based on the FFQ. Each of the twenty-eight nutrients or foods received a score based on findings from the peer-reviewed literature reporting on the relationships between diet and inflammatory biomarkers (IL-1ß, IL-4, IL-6, IL-10, TNF-α and C-reactive protein). Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician, antidepressant drugs, or both. Multivariable Cox regression models were used to estimate hazard ratios (HR) of depression according to quintiles of the DII. After a median 8·5 years of follow-up, we observed 1051 incident cases of depression. The HR for participants in the highest quintile of DII (strongly pro-inflammatory) was 1·47 (95% CI 1·17, 1·85) compared with those in the bottom quintile, with a significant dose-response relationship (P trend=0·01). In the subgroup analyses, the association between DII and depression was stronger among participants >55 years and among those with cardiometabolic comorbidities (HR 2·70; 95% CI 1·22, 5·97 and HR 1·80; 95% CI 1·27, 2·57, respectively). A pro-inflammatory diet was associated with a significantly higher risk of depression in a Mediterranean population. This association was stronger among older subjects and subjects with cardiometabolic diseases.


Assuntos
Depressão/sangue , Depressão/epidemiologia , Dieta , Inflamação/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Estudos de Coortes , Depressão/complicações , Ingestão de Energia , Feminino , Seguimentos , Humanos , Incidência , Interleucina-10/sangue , Interleucina-1beta/sangue , Interleucina-4/sangue , Interleucina-6/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Fatores Socioeconômicos , Espanha/epidemiologia , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/sangue
11.
Open Forum Infect Dis ; 11(4): ofae112, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38560607

RESUMO

Objective: The incidence of type 2 diabetes mellitus (T2DM) has risen dramatically. Among people living with HIV (PLHIV), chronic disease (now >15 cases/1000 in the general population worldwide) and long-term exposure to antiretroviral therapy (ART) can alter metabolic processes early, favoring insulin resistance and T2DM. We retrospectively studied the incidence of T2DM and associated factors in the Cohort of the Spanish AIDS Research Network, a prospective cohort of PLHIV enrolled at diagnosis and before initiation of ART. Methods: PLHIV were aged >18 years and ART naive at inclusion. The incidence of new diagnoses of T2DM after initiation of ART (per 1000 person-years) was calculated. Predictors of a diagnosis of T2DM were identified by a Cox proportional hazards model adjusted for statistically significant and clinically relevant variables. Results: Cumulative incidence was 5.9 (95% CI, 5.1-6.7) per 1000 person-years, increasing significantly in persons aged >50 years to 14.4 (95% CI, 10.4-19.3). Median time to diagnosis of T2DM was 27 months. Only age and higher education were significant. Interestingly, higher education was associated with a 33% reduction in the incidence of T2DM. Having received tenofovir disoproxil fumarate + (lamivudine or emtricitabine) + rilpivirine was almost significant as a protective factor (hazard ratio, 0.49; 95% CI, .24-1.01; P = .05). Conclusions: The incidence of T2DM in PLHIV in Spain was high, especially in persons aged >50 years. Age was the factor most closely associated with onset, and educational level was the factor most associated with reduced risk. We highlight the lack of association between HIV-related factors and T2DM and show that, within nonnucleoside reverse transcriptase inhibitors, rilpivirine could prove more benign for metabolic comorbidities.

12.
Cureus ; 16(1): e51632, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38313987

RESUMO

Diabetes mellitus (DM) is a public health concern in Brazil, with deleterious effects on quality of life and increasing mortality rates. The prevalence of diabetes in Brazil is on the rise, and it is imperative to understand its effects on mortality rates in the last two decades in order to effectively mitigate the detrimental impact of diabetes on public health. This study aims to analyze mortality trends related to diabetes in Brazil from 2000 to 2021, encompassing both type 1 and type 2 diabetes, across sex and various age cohorts. Using joinpoint regression analysis, temporal trends in Brazil were assessed, while also incorporating findings from previous studies and considering potential influencing factors, such as government initiatives and cuts in healthcare investment. The study revealed a general upward trend in mortality rates associated with DM1 and DM2 over the study period, in both males and females, with men showing a higher AAPC (average annual percent change), which translated into significantly increased mortality difference at the end of the study. Additionally, it revealed elevated mortality values for extreme age groups in the age cohorts studied, with the exception of middle-aged cohort groups in DM2, which showed an expected higher APC (annual percent change), considering the age of highest incidence of DM2 in those age groups. This comprehensive analysis provides critical insights into the escalating impact of diabetes on mortality rates in Brazil and highlights the urgent need for healthcare strategies. It is expected that the increased prevalence of diabetes in the Brazilian population adds an additional economic burden to healthcare expenditure by the Brazilian government, further worsening the health disparities among different social groups. Unless several political decisions to reduce healthcare expenditure are reversed, greater difficulties in accessing treatments will be detrimental for vulnerable social groups in Brazil. By understanding the nuanced patterns of diabetes-related mortality, healthcare providers and policymakers can allocate resources effectively and implement tailored interventions to better address diabetes in Brazil.

13.
Health Sci Rep ; 7(5): e1954, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698793

RESUMO

Background: The inflammation plays a role in the pathophysiology of type-2 diabetes progression, and the mechanism remains unclear. The systemic immune-inflammation index (SII) is a novel inflammatory marker for type 2 diabetes patients and integrates multiple indicators in complete blood counts and routine blood tests. Aim: Since there is no international diagnostic standard for dry eye disease (DED), this study uses low-cost inflammatory blood biomarkers to investigate the correlation between SII and DM2-DED and determine the diagnosis indices of other biomarkers in DM2-DED. Methodology: A case-control retrospective analysis of totel patients n = 293 randomly selected and categorized into four groups: DED, DM2, DM2-DED, and healthy subjects. Demographic and blood biomarker variables were classified as categorical and continuous variables. The platelet-to-lymphocyte ratio (PLR), lymphocytes-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and SII were calculated platelet count multiply by NLR and analyzed for their correlation for all groups. Results: Focusing on DM2-DED patients was more common in females, 59.6%, than in males, 40.2%. The mean ages were 60.7 ± 11.85 years, a statistically significant difference with all groups. In the study group DM2-DED, there was an increase in all blood markers compared to all remaining groups except PLR. Only neutrophil, hemoglobin A1c (HbA1c), and fasting blood sugar levels were statistically significant differences in DM2-DED patients (p > 0.001, p < 0.001, and p < 0.001, respectively) compared to all groups. There was a positive correlation between HbA1c and PLR, HbA1c and NLR, and HbA1c and SII (r = 0.037, p = 0.705; r = 0.031, p = 0.754; and r = 0.066, p < 0.501, respectively) in the DM2-DED group. Conclusion: This study demonstrated that elevated SII values were linked to elevated HbA1c in DM2-DED patients. The potential of SII and HbA1c as early diagnostic indicators for ocular problems associated with diabetes mellitus is highlighted by their favorable connection in diagnosing DM2-DED.

14.
JMIR Res Protoc ; 13: e56067, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38680116

RESUMO

BACKGROUND: Sodium-glucose-cotransporter 2 inhibitors (SGLT2is) have revolutionized the treatment of type 2 diabetes mellitus (DM2) and chronic kidney disease (CKD), reducing the risk of cardiovascular and renal end points by up to 40%. The underlying mechanisms are not fully understood. OBJECTIVE: The study aims to examine the effects of empagliflozin versus placebo on renal hemodynamics, sodium balance, vascular function, and markers of the innate immune system in patients with DM2, DM2 and CKD, and nondiabetic CKD. METHODS: We conducted 3 double-blind, crossover, randomized controlled trials, each with identical study protocols but different study populations. We included patients with DM2 and preserved kidney function (estimated glomerular filtration rate >60 mL/min/1.73 m2), DM2 and CKD, and nondiabetic CKD (both with estimated glomerular filtration rate 20-60 mL/min/1.73 m2). Each participant was randomly assigned to 4 weeks of treatment with either 10 mg of empagliflozin once daily or a matching placebo. After a wash-out period of at least 2 weeks, participants were crossed over to the opposite treatment. End points were measured at the end of each treatment period. The primary end point was renal blood flow measured with 82Rubidium positron emission tomography-computed tomography (82Rb-PET/CT). Secondary end points include glomerular filtration rate measured with 99mTechnetium-diethylene-triamine-pentaacetate (99mTc-DTPA) clearance, vascular function assessed by forearm venous occlusion strain gauge plethysmography, measurements of the nitric oxide (NO) system, water and sodium excretion, body composition measurements, and markers of the complement immune system. RESULTS: Recruitment began in April 2021 and was completed in September 2022. Examinations were completed by December 2022. In total, 49 participants completed the project: 16 participants in the DM2 and preserved kidney function study, 17 participants in the DM2 and CKD study, and 16 participants in the nondiabetic CKD study. Data analysis is ongoing. Results are yet to be published. CONCLUSIONS: This paper describes the rationale, design, and methods used in a project consisting of 3 double-blind, crossover, randomized controlled trials examining the effects of empagliflozin versus placebo in patients with DM2 with and without CKD and patients with nondiabetic CKD, respectively. TRIAL REGISTRATION: EU Clinical Trials Register 2019-004303-12; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004303-12, EU Clinical Trials Register 2019-004447-80; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004447-80, EU Clinical Trials Register 2019-004467-50; https://www.clinicaltrialsregister.eu/ctr-search/search?query=and+2019-004467-50. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56067.


Assuntos
Compostos Benzidrílicos , Estudos Cross-Over , Diabetes Mellitus Tipo 2 , Glucosídeos , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Insuficiência Renal Crônica/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Glucosídeos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/farmacologia , Método Duplo-Cego , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Taxa de Filtração Glomerular/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Clin Gastroenterol Hepatol ; 11(9): 1108-1114.e5, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23591277

RESUMO

BACKGROUND & AIMS: Central obesity could increase the risk for Barrett's esophagus (BE) and esophageal adenocarcinoma by mechanical and/or metabolic mechanisms, such as hyperinsulinemia. We performed an epidemiologic study to determine whether prior type 2 diabetes mellitus (DM2) is associated with BE. METHODS: We performed a population-based case-control study using the General Practice Research Database, a UK primary care database that contains information on more than 8 million subjects, to identify cases of BE (using previously validated codes; n = 14,245) and matched controls without BE (by age, sex, enrollment date, duration of follow-up evaluation, and practice region by incidence density sampling; n = 70,361). We assessed the association of a prior diagnosis of DM2 with BE using conditional univariate and multivariable regression analysis. Confounders assessed included smoking, obesity measured by body mass index (BMI), and gastroesophageal reflux disease. RESULTS: BE cases were more likely than controls to have smoked (52.4% vs 49.9%), have a higher mean BMI (27.2 vs 26.9), and a higher prevalence of DM2 than controls (5.8% vs 5.3%). On multivariable analysis, DM2 was associated with a 49% increase in the risk of BE, independent of other known risk factors (odds ratio, 1.49; 95% confidence interval, 1.16-1.91). This association was stronger in women than men. Results remained stable with sensitivity analyses. CONCLUSIONS: In a large population-based case-control study, DM2 was a risk factor for BE, independent of obesity (as measured by BMI) and other risk factors (smoking and gastroesophageal reflux disease). These data suggest that metabolic pathways related to DM2 should be explored in BE pathogenesis and esophageal carcinogenesis.


Assuntos
Esôfago de Barrett/epidemiologia , Esôfago de Barrett/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Reino Unido/epidemiologia
16.
Acta Myol ; 32(3): 154-65, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24803843

RESUMO

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present in four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment.


Assuntos
Transtornos Miotônicos/diagnóstico , Transtornos Miotônicos/genética , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/genética , Biópsia , Humanos , Mutação , Transtornos Miotônicos/patologia , Transtornos Miotônicos/terapia , Distrofia Miotônica/patologia , Distrofia Miotônica/terapia , Fenótipo
17.
Arch Phys Med Rehabil ; 94(12): 2465-2470, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23806609

RESUMO

OBJECTIVE: To assess the influence of diabetic neuropathy (DN) on balance and functional strength in patients with diabetes mellitus type 2 (DM2). DESIGN: Cross-sectional study. SETTING: Diabetes outpatient unit. PARTICIPANTS: Adults (N=62; age range, 40-65y): 32 with DM2 (19 subjects without DN and 13 with DN) and 30 without DM2 (control group). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Upright balance, evaluated in 4 situations (fixed platform, unstable platform, with eyes open, with eyes closed), and functional strength, assessed with a five-times-sit-to-stand test, were analyzed using an electromagnetic system, with a sensor placed over C7 to allow maximum trunk displacements in the anterior-posterior and medial-lateral directions. The Berg Balance Scale and the Timed Up & Go test were also used. RESULTS: Subjects with DM2 had greater anterior-posterior displacement (P<.05) in the unstable platform with eyes closed condition compared with those without DM2, whereas no difference in medial-lateral displacement was observed between these groups. A difference in time was observed in the five-times-sit-to-stand test (P<.05), with subjects in the control group performing the tasks faster than either group of subjects with DM2. Additionally, subjects in the control group showed a higher score in the Berg Balance Scale and performed the Timed Up & Go test in less time compared with subjects in other groups. CONCLUSIONS: Subjects with DM2, with or without DN, showed deficits in postural control and functional strength compared with healthy individuals of the same age group.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Força Muscular/fisiologia , Equilíbrio Postural/fisiologia , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia
18.
Cureus ; 15(10): e46745, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022061

RESUMO

Background Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia caused by a defect in the secretion or action or both of insulin. It has a complex pathogenesis. Benign prostatic hyperplasia (BPH) refers to an increase in the size of the prostate; it is one of the most common health problems in men that manifests with age. Lipoxygenase-12 (Lipox-12) is one of the enzymes in the Lipox 12/15 family, which plays a major role in catalyzing a variety of polyunsaturated fatty acids (PUFAs) that are capable of producing different metabolites. Lipox-12 has a significant effect on arachidonic acid metabolism, with PUFA, a pro- and anti-inflammatory mediator, as one of the enzyme isoforms. It also plays a major role in modulating inflammation at multiple checkpoints as diabetes progresses. The present study aims to measure Lipox-12 levels in patients with DM type 2 (DM2) and patients with DM2 + BPH. Methodology This study was conducted in Musayyib General Hospital, south of Baghdad, where a clinical examination was performed on 50 samples from controls (healthy subjects), 50 patients with DM2, and 50 patients with DM2 + BPH after taking each patient's history. The examinations performed included fasting blood sugar (FBS), hemoglobin A1c (HbA1c), prostate-specific antigen (PSA), triglycerides (TG), cholesterol (Chol), and Lipox-12. Results The results showed that both the DM2 and DM2 + BPH groups had higher FBS, HbA1c, TG, and Chol levels than healthy subjects; in contrast, Lipox-12 levels were the lowest in the DM2 group (sensitivity = 79% and specificity = 81%) but higher in the DM2 + BPH group (sensitivity = 80%; specificity = 82%) compared to the control group. Conclusions Lipox-12 had a high sensitivity and specificity in the DM2 and DM2 + BPH groups compared to the control group, and in both cases, it was used to monitor and diagnose DM2 and BPH.

19.
Neuromuscul Disord ; 32(4): 332-346, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35393236

RESUMO

Muscular dystrophies are a group of disorders that cause progressive muscle weakness. There is an increasing interest for the development of biomarkers for these disorders and specifically for Duchene Muscular Dystrophy. Limited research however, has been performed on the biomarkers' development for the most rare muscular dystrophies, like the Facioscapulohumeral Muscular Dystrophy, Limb-Girdle Muscular Dystrophy and Myotonic Dystrophy type 2. Here, we aimed to identify novel serum-based miRNA biomarkers for these rare muscular dystrophies, through high-throughput next-generation RNA sequencing. We identified many miRNAs that associate with muscular dystrophy patients compared to controls. Based on a series of selection criteria, the two best candidate miRNAs for each of these disorders were chosen and validated in a larger number of patients. Our results showed that miR-223-3p and miR-206 are promising serum-based biomarkers for Facioscapulohumeral Muscular Dystrophy type 1, miR-143-3p and miR-486-3p for Limb-Girdle Muscular Dystrophy type 2A whereas miR-363-3p and miR-25-3p associate with Myotonic Dystrophy type 2. Some of the identified miRNAs were significantly elevated in the serum of the patients compared to controls, whereas some others were lower. In conclusion, we provide new evidence that certain circulating miRNAs may be used as biomarkers for three types of rare muscular dystrophies.


Assuntos
MicroRNAs , Distrofia Muscular do Cíngulo dos Membros , Distrofia Muscular Facioescapuloumeral , Distrofia Miotônica , Biomarcadores/sangue , Humanos , MicroRNAs/sangue , MicroRNAs/genética , Distrofia Muscular do Cíngulo dos Membros/sangue , Distrofia Muscular do Cíngulo dos Membros/diagnóstico , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular Facioescapuloumeral/sangue , Distrofia Muscular Facioescapuloumeral/diagnóstico , Distrofia Muscular Facioescapuloumeral/genética , Distrofia Miotônica/sangue , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/genética
20.
Rep Biochem Mol Biol ; 11(3): 400-404, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36718305

RESUMO

Background: Recent research indicates that persistent inflammatory responses may contribute to the rise of diabetic nephropathy (DN) and diabetic cardiovascular disease (DCVD) in type 2 diabetes mellitus patients (DM2). Numerous molecules associated with inflammation and angiogenesis have been implicated in the development and progression of DN and DCVD, respectively. Methods: The subjects were separated into five groups: healthy controls (n= 25), type 2 diabetes mellitus patients (n= 30), type 2 diabetes mellitus patients with nephropathy DN (n= 30), and type 2 diabetes mellitus patients with cardiovascular disease DCVD (n= 30). The blood levels of irisin, IL-8, HbA1C, urea, and creatinine were determined. Results: In current study there was high significant increased irisin levels (p< 0.001) in DN patients than other groups and a high significant decreased IL-8 level in DCVD. Discussion: Serum IL-8 and irisin levels may serve as early indicators of DM2 problems (DN, DCVD).

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