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1.
J Coll Physicians Surg Pak ; 31(12): 1482-1486, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34794292

RESUMO

OBJECTIVE: To assess the frequency and time of onset of new-onset diabetes after transplant (NODAT) and its associated factors. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Nephrology, Bahria International Hospital, Lahore, Pakistan, from April 2016 to April 2018. METHODOLOGY: NODAT was diagnosed according to American Diabetes Association Criteria with fasting plasma glucose >126 mg/dl or random plasma glucose >200 mg/dl. Those with pre-existing diabetes and follow-up duration less than 12months, were excluded. Patients were divided in two groups: with and without NODAT, for statistical comparison. RESULTS: The study included 115 patients, 101 were males and the median age was 35.0 (29.0-46.0) years. During the one-year period of follow-up, 28 (24.3%) patients developed NODAT. The mean time of onset of NODAT was 5.3 ± 3.6 months. Family history of diabetes was positive in 46% patients in NODAT group, which was significantly higher as compared to 5.7% in non-NODAT group with p-value of <0.001, which is significant. All patients with more than three HLA mismatches developed NODAT. The mean fasting glucose levels (FPG) before transplant in NODAT group was 96.6 ± 15.4 mg/dl, which was significantly higher than FPG of non-NODAT group, where it was 80.5 ± 12.2 mg/dl. It was interesting to note that 35.7% of hepatitis patients developed NODAT as compared to 6 % in non-NODAT group with p =  0.001. CONCLUSION: NODAT was observed in 24.3% patients. The pre-transplant FPG, family history of diabetes, increased HLA mismatches, and hepatitis C infection were the major associated factors. Key Words: New onset diabetes after transplant, Fasting plasma glucose, Renal transplant.


Assuntos
Diabetes Mellitus , Transplante de Rim , Adulto , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Jejum , Humanos , Transplante de Rim/efeitos adversos , Masculino , Paquistão/epidemiologia , Fatores de Risco
2.
Nat Metab ; 3(8): 1071-1090, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34341568

RESUMO

Metabolic health depends on the brain's ability to control food intake and nutrient use versus storage, processes that require peripheral signals such as the adipocyte-derived hormone, leptin, to cross brain barriers and mobilize regulatory circuits. We have previously shown that hypothalamic tanycytes shuttle leptin into the brain to reach target neurons. Here, using multiple complementary models, we show that tanycytes express functional leptin receptor (LepR), respond to leptin by triggering Ca2+ waves and target protein phosphorylation, and that their transcytotic transport of leptin requires the activation of a LepR-EGFR complex by leptin and EGF sequentially. Selective deletion of LepR in tanycytes blocks leptin entry into the brain, inducing not only increased food intake and lipogenesis but also glucose intolerance through attenuated insulin secretion by pancreatic ß-cells, possibly via altered sympathetic nervous tone. Tanycytic LepRb-EGFR-mediated transport of leptin could thus be crucial to the pathophysiology of diabetes in addition to obesity, with therapeutic implications.


Assuntos
Encéfalo/metabolismo , Células Ependimogliais/metabolismo , Receptores ErbB/metabolismo , Leptina/metabolismo , Metabolismo dos Lipídeos , Pâncreas/metabolismo , Receptores para Leptina/metabolismo , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Metabolismo Energético , Células Secretoras de Insulina/metabolismo , Fosforilação
3.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360534

RESUMO

Inorganic phosphate (Pi) is an essential nutrient for living organisms and is maintained in equilibrium in the range of 0.8-1.4 mM Pi. Pi is a source of organic constituents for DNA, RNA, and phospholipids and is essential for ATP formation mainly through energy metabolism or cellular signalling modulators. In mitochondria isolated from the brain, liver, and heart, Pi has been shown to induce mitochondrial reactive oxygen species (ROS) release. Therefore, the purpose of this review article was to gather relevant experimental records of the production of Pi-induced reactive species, mainly ROS, to examine their essential roles in physiological processes, such as the development of bone and cartilage and the development of diseases, such as cardiovascular disease, diabetes, muscle atrophy, and male reproductive system impairment. Interestingly, in the presence of different antioxidants or inhibitors of cytoplasmic and mitochondrial Pi transporters, Pi-induced ROS production can be reversed and may be a possible pharmacological target.


Assuntos
Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Mitocôndrias/patologia , Atrofia Muscular/patologia , Fosfatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Metabolismo Energético , Humanos , Mitocôndrias/efeitos dos fármacos , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo
4.
Sci Rep ; 11(1): 17317, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34453070

RESUMO

Considering the dynamic nature of body mass index (BMI) and its importance in determining cardiovascular risks, this study aimed to investigate the life-course trajectory pattern of women's BMI and its association with cardiovascular risk factors. A total of 1356 couples with 2976 children were recruited and followed up for an average period of 20 years. Latent growth curve modeling was applied to determine women's BMI trajectories; logistic regression was used to investigate the associations between trajectory patterns and cardiovascular risk factors, including hypertension (HTN), dyslipidemia, diabetes mellitus (DM), and obesity. Women were classified into three trajectories, including normal, stage 1 obesity, and stage 2 obesity. Compared to women's in the normal trajectory group, those in obesity trajectories had higher odds ratios for HTN, DM, and dyslipidemia. Men with obese spouses showed a higher rate of HTN 1.54 (95% CI 1.05-2.25) and DM 1.55; (95% CI 1.00-2.44). The odds of men's obesity were higher in obese spouses (OR 1.70; 95% CI 1.10-2.62). Offspring of stage 2 obese (OR 2.39; 95% CI 1.67-3.44) and stage 1 obese (OR 4.81; 95% CI 3.16-7.34) mothers were more likely to be obese. Our findings emphasized paying more attention to women with excessive weight to promote familial cardiovascular health in the communities.


Assuntos
Trajetória do Peso do Corpo , Doenças Cardiovasculares/etiologia , Adulto , Idoso , Índice de Massa Corporal , Diabetes Mellitus/etiologia , Dislipidemias/etiologia , Feminino , Humanos , Hipertensão/etiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/etiologia , Fatores de Risco
6.
J Am Soc Nephrol ; 32(8): 2083-2098, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34330770

RESUMO

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) might be preventable. METHODS: This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant. RESULTS: In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24. CONCLUSIONS: At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.Clinical Trial registration number: NCT03507829.


Assuntos
Diabetes Mellitus/prevenção & controle , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Isófana/uso terapêutico , Transplante de Rim/efeitos adversos , Adulto , Idoso , Glicemia/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Feminino , Hemoglobina A Glicada/metabolismo , Fidelidade a Diretrizes , Humanos , Hiperglicemia/sangue , Hiperglicemia/etiologia , Hipoglicemia/induzido quimicamente , Insulina Lispro/uso terapêutico , Insulina Isófana/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Período Pós-Operatório , Fatores de Risco , Fatores Sexuais , Padrão de Cuidado , Fatores de Tempo
7.
Int J Surg ; 92: 106024, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34252597

RESUMO

BACKGROUND: Single-anastomosis sleeve ileal (SASI) bypass has emerged as a promising bariatric and metabolic procedure. We aimed to review the current literature on the outcome of SASI procedure in terms of weight loss, improvement in comorbidities, and complications. METHODS: We conducted a systematic literature search, querying electronic databases and Google Scholar, for studies that reported the outcome of the SASI bypass. The main outcome measures of the review were change in body mass index (BMI), % of excess weight loss (%EWL), improvement in comorbidities, and complications after SASI bypass. RESULTS: This systematic review comprised ten studies including 941 patients with a median BMI of 45.6 kg/m2. The median %EWL at 6 months was 59.4% and significantly (p = 0.04) increased to 90.1% at 12 months. The weighted mean rate of improvement in diabetes mellitus was 99.1 (95%CI: 98.2-99.9, I2 = 0). The crude percentages of patients with improvement in hypertension, hyperlipidemia, and gastroesophageal reflux disease were 51%, 76.6%, and 92%, respectively. The median operation time was 111.3, ranging between 75 and 148.4 min. Complications were recorded in 116 (12.3%) patients. Longer common limb was associated with less %EWL at 6 months and less complications whereas larger anastomosis size was associated with higher weight loss and greater improvement in hypertension. CONCLUSIONS: SASI bypass was associated with good short-term outcomes in regard to weight loss and improvement in comorbidities, namely diabetes mellitus with an acceptably low complication rate.


Assuntos
Diabetes Mellitus , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Diabetes Mellitus/etiologia , Diabetes Mellitus/cirurgia , Gastrectomia , Humanos , Íleo/cirurgia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
8.
JCI Insight ; 6(16)2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34241597

RESUMO

Evidence suggests an association between severe acute respiratory syndrome-cornavirus-2 (SARS-CoV-2) infection and the occurrence of new-onset diabetes. We examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), the cell entry factors for SARS-CoV-2, using publicly available single-cell RNA sequencing data sets, and pancreatic tissue from control male and female nonhuman primates (NHPs) and humans. We also examined SARS-CoV-2 immunolocalization in pancreatic cells of SARS-CoV-2-infected NHPs and patients who had died from coronavirus disease 2019 (COVID-19). We report expression of ACE2 in pancreatic islet, ductal, and endothelial cells in NHPs and humans. In pancreata from SARS-CoV-2-infected NHPs and COVID-19 patients, SARS-CoV-2 infected ductal, endothelial, and islet cells. These pancreata also exhibited generalized fibrosis associated with multiple vascular thrombi. Two out of 8 NHPs developed new-onset diabetes following SARS-CoV-2 infection. Two out of 5 COVID-19 patients exhibited new-onset diabetes at admission. These results suggest that SARS-CoV-2 infection of the pancreas may promote acute and especially chronic pancreatic dysfunction that could potentially lead to new-onset diabetes.


Assuntos
COVID-19/complicações , Diabetes Mellitus/etiologia , Pâncreas/virologia , SARS-CoV-2/isolamento & purificação , Trombose/etiologia , Enzima de Conversão de Angiotensina 2/análise , Animais , Chlorocebus aethiops , Feminino , Fibrose , Humanos , Macaca mulatta , Masculino , Serina Endopeptidases/análise
9.
Int J Mol Sci ; 22(12)2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34201257

RESUMO

Despite the substantial role played by the hypothalamus in the regulation of energy balance and glucose homeostasis, the exact mechanisms and neuronal circuits underlying this regulation remain poorly understood. In the last 15 years, investigations using transgenic models, optogenetic, and chemogenetic approaches have revealed that SF1 neurons in the ventromedial hypothalamus are a specific lead in the brain's ability to sense glucose levels and conduct insulin and leptin signaling in energy expenditure and glucose homeostasis, with minor feeding control. Deletion of hormonal receptors, nutritional sensors, or synaptic receptors in SF1 neurons triggers metabolic alterations mostly appreciated under high-fat feeding, indicating that SF1 neurons are particularly important for metabolic adaptation in the early stages of obesity. Although these studies have provided exciting insight into the implications of hypothalamic SF1 neurons on whole-body energy homeostasis, new questions have arisen from these results. Particularly, the existence of neuronal sub-populations of SF1 neurons and the intricate neurocircuitry linking these neurons with other nuclei and with the periphery. In this review, we address the most relevant studies carried out in SF1 neurons to date, to provide a global view of the central role played by these neurons in the pathogenesis of obesity and diabetes.


Assuntos
Diabetes Mellitus/patologia , Hipotálamo/patologia , Neurônios/patologia , Obesidade/patologia , Fator Esteroidogênico 1/metabolismo , Animais , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Humanos , Hipotálamo/metabolismo , Neurônios/metabolismo , Obesidade/etiologia , Obesidade/metabolismo
10.
Mol Med Rep ; 24(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34296287

RESUMO

It has been reported that hepatitis B virus (HBV) infection has an impact on intestinal microbiota imbalance to induce diabetes mellitus (DM), but the underlying mechanisms still remain to be explored. The present study aimed to investigate the regulatory role of microRNA­192 (miR­192­5p) and glucagon­like peptide­1 (GLP­1) in intestinal microbiota imbalance by recruiting patients with DM infected with HBV. In the present study, patients with HBV infection and different levels of alanine transaminase (ALT) were recruited and divided into three groups. Intestinal microbiota analysis was performed to evaluate the fecal bacterial composition of patients in various groups. Quantitative PCR was performed to explore the differential expression of miR­192­5p and GLP­1 in the feces, peripheral blood and intestinal mucosal tissue samples of each patient. Immunohistochemistry was used to assess the expression of GLP­1 protein in the intestinal mucosal tissue samples. Luciferase assays were performed by cell transfection of miR­192­5p mimics/precursors/inhibitors to study the inhibitory effect of miR­192­5p on GLP­1 expression. Intestinal microbiota imbalance was observed in hepatitis B surface antigen (HBsAg)­positive patients with high ALT. The expression of miR­192­5p was significantly elevated in the feces, peripheral blood and intestinal mucosal tissue samples of HBsAg­positive patients with high ALT along with decreased GLP­1 mRNA and protein expression. Luciferase activity of GLP­1 vector was inhibited by miR­192­5p mimics and promoted by miR­192­5p inhibitors. Transfection of miR­192­5p precursors resulted in upregulation of miR­192­5p and downregulation of GLP­1, while miR­192­5p inhibitors remarkably suppressed the expression of miR­192­5p and notably induced the expression of GLP­1. These results showed a regulatory network involving HBV infection, intestinal microbiota imbalance, and miR­192­5p and GLP­1 expression.


Assuntos
Microbioma Gastrointestinal , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Hepatite B Crônica/metabolismo , MicroRNAs/metabolismo , Adulto , Alanina Transaminase/sangue , Linhagem Celular Tumoral , Diabetes Mellitus/etiologia , Fezes/microbiologia , Feminino , Peptídeo 1 Semelhante ao Glucagon/antagonistas & inibidores , Peptídeo 1 Semelhante ao Glucagon/genética , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/complicações , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade
11.
Sci Rep ; 11(1): 14546, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34267268

RESUMO

Chlordane compounds (CHLs) are components of technical chlordane listed in the Stockholm convention on persistent organic pollutants identified as endocrine disrupting chemicals (EDCs) and may interfere with hormone biosynthesis, metabolism or action resulting in an unbalanced hormonal function. There is increasing scientific evidence showing EDCs as risk factors in the pathogenesis and development of obesity and obesity-related metabolic syndromes such as type 2 diabetes, but there is no systematized information on the effect of CHLs in humans. Our aim is to identify the epidemiological data on the association between CHLs with adiposity and diabetes using a systematic approach to identify the available data and summarizing the results through meta-analysis. We searched PubMed and Web of Science from inception up to 15 February 2021, to retrieve original data on the association between chlordanes, and adiposity or diabetes. For adiposity, regression coefficients and Pearson or Spearman correlation coefficients were extracted and converted into standardized regression coefficients. Data were combined using fixed effects meta-analyses to compute summary regression coefficients and corresponding 95% confidence intervals (95% CI). For the association between chlordanes and diabetes, Odds ratios (ORs) were extracted and the DerSimonian and Laird method was used to compute summary estimates and respective 95% CI. For both, adjusted estimates were preferred, whenever available. Among 31 eligible studies, mostly using a cross-sectional approach, the meta-analysis for adiposity was possible only for oxychlordane and transchlordane, none of them were significantly associated with adiposity [(ß = 0.04, 95% CI 0.00; 0.07, I2 = 89.7%)] and (ß = 0.02, 95% CI - 0.01; 0.06), respectively. For diabetes, the estimates were positive for all compounds but statistically significant for oxychlordane [OR = 1.96 (95% CI 1.19; 3.23)]; for trans-nonachlor [OR = 2.43 (95% CI 1.64; 3.62)] and for heptachlor epoxide [OR = 1.88 (95% CI 1.42; 2.49)]. Our results support that among adults, the odds of having diabetes significantly increase with increasing levels of chlordanes. The data did not allow to reach a clear conclusion regarding the association with adiposity.


Assuntos
Adiposidade/efeitos dos fármacos , Clordano/toxicidade , Diabetes Mellitus/induzido quimicamente , Disruptores Endócrinos/toxicidade , Adiposidade/fisiologia , Clordano/análogos & derivados , Diabetes Mellitus/etiologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/etiologia , Exposição Ambiental/efeitos adversos , Heptacloro Epóxido/toxicidade , Humanos , Hidrocarbonetos Clorados/toxicidade , Fatores de Risco
12.
Sci Rep ; 11(1): 12830, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145341

RESUMO

Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. This study aimed to evaluate the relationship between FLI and new onset of diabetes mellitus (DM). We investigated the association of FLI with new onset of DM during a 10-year period in subjects who received annual health examinations (n = 28,990). After exclusion of subjects with DM at baseline and those with missing data, a total of 12,290 subjects (male/female: 7925/4365) who received health examinations were recruited. FLI was significantly higher in males than in females. During the 10-year period, DM was developed in 533 males (6.7%) and 128 females (2.9%). Multivariable Cox proportional hazard models with a restricted cubic spline showed that the risk of new onset of DM increased with a higher FLI at baseline in both sexes after adjustment of age, fasting plasma glucose, habits of alcohol drinking and current smoking, family history of DM and diagnosis of hypertension and dyslipidemia at baseline. When the subjects were divided into subgroups according to tertiles of FLI level at baseline (T1-T3) in the absence and presence of impaired fasting glucose (IFG), hazard ratios after adjustment of the confounders gradually increased from T1 to T3 and from the absence to presence of IFG in both male and female subjects. In conclusion, a high level of FLI predicts new onset of DM in a general population of both male and female individuals.


Assuntos
Diabetes Mellitus/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Adulto , Biomarcadores , Comorbidade , Diabetes Mellitus/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/etiologia , Vigilância em Saúde Pública , Curva ROC , Medição de Risco , Fatores de Risco
13.
Metabolism ; 121: 154802, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34090869

RESUMO

Diabetes is a noncommunicable widespread disease that poses the risk of severe complications in patients, with certain complications being life-threatening. Hepatitis C is an infectious disease that mainly causes liver damage, which is also a profound threat to human health. Hepatitis C virus (HCV) infection has many extrahepatic manifestations, including diabetes. Multiple mechanisms facilitate the strong association between HCV and diabetes. HCV infection can affect the insulin signaling pathway in liver and pancreatic tissue and change the profiles of circulating microRNAs, which may further influence the occurrence and development of diabetes. This review describes how HCV infection causes diabetes and discusses the current research progress with respect to HCV infection-related diabetes.


Assuntos
Diabetes Mellitus/virologia , Hepacivirus/fisiologia , Hepatite C/complicações , Animais , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Hepatite C/metabolismo , Hepatite C/patologia , Hepatite C Crônica/complicações , Hepatite C Crônica/metabolismo , Hepatite C Crônica/patologia , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Transdução de Sinais/fisiologia
14.
Lancet Gastroenterol Hepatol ; 6(8): 668-675, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34089654

RESUMO

Diabetes represents a group of diseases involving persistent hyperglycaemia. Exocrine disorders of the pancreas are increasingly recognised to cause or precede the onset of diabetes, which in this context is referred to as pancreatogenic or type 3c diabetes. Diabetes, as a sequela of acute pancreatitis, is observed across the spectrum of severity in acute pancreatitis and can be associated with other clinical complications. The pathophysiology of acute pancreatitis-related diabetes is poorly understood, and observations suggest that it is probably multifactorial. In this Review, we discuss the epidemiology, pathophysiology, and management considerations of diabetes following acute pancreatitis, and highlight knowledge gaps in this topic.


Assuntos
Diabetes Mellitus/etiologia , Pancreatite/complicações , Doença Aguda , Diabetes Mellitus/epidemiologia , Saúde Global , Humanos , Incidência
15.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072329

RESUMO

At the onset of diabetes, the kidney grows large and the glomerular filtration rate becomes abnormally high. These structural and hemodynamics changes affect kidney function and may contribute to the development of chronic kidney disease. The goal of this study is to analyze how kidney function is altered in patients with diabetes and the renal effects of an anti-hyperglyceamic therapy that inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal convoluted tubules. To accomplish that goal, we have developed a computational model of kidney function in a patient with diabetes and conducted simulations to study the effects of diabetes and SGLT2 inhibition on solute and water transport along the nephrons. Simulation results indicate that diabetes-induced hyperfiltration and tubular hypertrophy enhances Na+ transport, especially along the proximal tubules and thick ascending limbs. These simulations suggest that SGLT2 inhibition may attenuate glomerular hyperfiltration by limiting Na+-glucose transport, raising luminal [Cl-] at the macula densa, restoring the tubuloglomerular feedback signal, thereby reducing single-nephron glomerular filtration rate.


Assuntos
Diabetes Mellitus/metabolismo , Suscetibilidade a Doenças , Rim/metabolismo , Rim/fisiopatologia , Modelos Biológicos , Animais , Transporte Biológico/efeitos dos fármacos , Biomarcadores , Diabetes Mellitus/etiologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/metabolismo , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
16.
Medicine (Baltimore) ; 100(24): e26311, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128870

RESUMO

ABSTRACT: Pancreatectomy is an invasive surgery that is sometimes associated with complications. New-onset diabetes mellitus sometimes develops after partial pancreatectomy and severely affects the patient's quality of life. This study aimed to develop a preoperative prediction model of new-onset diabetes mellitus after partial pancreatectomy, which will help patients and surgeons to achieve more easily better common decisions on regarding whether to perform partial pancreatectomy. This retrospective cohort study analyzed medical records of patients who underwent partial pancreatectomy (total pancreatectomy excluded) from April 1, 2008, to February 28, 2016, which were available in the database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). The predictors were preoperative age, body mass index, hemoglobin A1c level, blood glucose level, and indication for partial pancreatectomy. The outcome was the development of new-onset diabetes mellitus at 1 to 12 months after partial pancreatectomy. We used a logistic regression model and calculated the scores of each predictor. To determine test performance, we assessed discrimination ability using the receiver operating characteristic curve and calibration with a calibration plot and the Hosmer-Lemeshow test. We also performed internal validation using the bootstrap method. Of 681 patients, 125 (18.4%) had new-onset diabetes mellitus after partial pancreatectomy. The developed prediction model had a possible range of 0 to 46 points. The median score was 13, and the interquartile range was 9 to 22. The C-statistics of the receiver operating characteristic curve on the score to predict the outcome was .70 (95% confidence interval [CI], .65-.75). Regarding the test performance, the Hosmer-Lemeshow test was not significant (P = .17), and calibration was good. In the bootstrapped cohorts, the C-statistics was .69 (95% CI, .62-.76). We developed a preoperative prediction model for new-onset diabetes mellitus after partial pancreatectomy. This would provide important information for surgeons and patients when deciding whether to perform partial pancreatectomy.


Assuntos
Regras de Decisão Clínica , Diabetes Mellitus/etiologia , Pancreatectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Medição de Risco/métodos , Idoso , Índice de Massa Corporal , Feminino , Hemoglobina A Glicada/análise , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Período Pré-Operatório , Qualidade de Vida , Curva ROC , Estudos Retrospectivos , Fatores de Risco
17.
Int J Mol Sci ; 22(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34072110

RESUMO

Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.


Assuntos
Diabetes Mellitus/metabolismo , Sistema Digestório/metabolismo , Sistema Nervoso Entérico/metabolismo , Neurônios/metabolismo , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Animais , Biomarcadores , Glicemia , Diabetes Mellitus/etiologia , Diabetes Mellitus/patologia , Diabetes Mellitus Experimental , Sistema Digestório/imunologia , Imunofluorescência , Neurônios/imunologia , Especificidade de Órgãos , Suínos
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 50(2): 239-244, 2021 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-34137229

RESUMO

To investigate the postoperative serum triglyceride (TG) levels in predicting the risk of new-onset diabetes mellitus (NODM) in patients following allogeneic liver transplantation. One hundred and forty three patients undergoing allogeneic liver transplantation in Shanghai General Hospital from July 2007 to July 2014 were enrolled in this study. The NODM developed in 33 patients after liver transplantation. The curve of dynamic TG levels in the early period after liver transplantation was generated. Independent risk factors of NODM were determined by univariate and multivariant logistic regression analyses. The clinical value of TG in predicting NODM was analyzed by area under the ROC curve (AUC). Serum TG levels were gradually rising in the first week and then reached the plateau phase (stable TG, sTG) in patients after surgery. The sTG in NODM group were significantly higher than that in non-NODM group (=-2.31, <0.05). Glucocorticoid therapy (=4.054, <0.01), FK506 drug concentration in the first week after operation (=3.482, <0.05) and sTG (=3.156, <0.05) were independent risk factors of NODM. ROC curve analysis showed that the AUC of sTG in predicting NODM was 0.72. TG shows a gradual recovery process in the early period after liver transplantation, and the higher TG level in stable phase may significantly increase the risk of NODM in patients.


Assuntos
Diabetes Mellitus , Transplante de Fígado , China/epidemiologia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Humanos , Transplante de Fígado/efeitos adversos , Fatores de Risco , Tacrolimo/efeitos adversos , Triglicerídeos
19.
ACS Chem Biol ; 16(6): 945-972, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34102834

RESUMO

Iron is an essential mineral that serves as a prosthetic group for a variety of proteins involved in vital cellular processes. The iron economy within humans is highly conserved in that there is no proper iron excretion pathway. Therefore, iron homeostasis is highly evolved to coordinate iron acquisition, storage, transport, and recycling efficiently. A disturbance in this state can result in excess iron burden in which an ensuing iron-mediated generation of reactive oxygen species imparts widespread oxidative damage to proteins, lipids, and DNA. On the contrary, problems in iron deficiency either due to genetic or nutritional causes can lead to a number of iron deficiency disorders. Iron chelation strategies have been in the works since the early 1900s, and they still remain the most viable therapeutic approach to mitigate the toxic side effects of excess iron. Intense investigations on improving the efficacy of chelation strategies while being well tolerated and accepted by patients have been a particular focus for many researchers over the past 30 years. Moreover, recent advances in our understanding on the role of iron in the pathogenesis of different diseases (both in iron overload and iron deficiency conditions) motivate the need to develop new therapeutics. We summarized recent investigations into the role of iron in health and disease conditions, iron chelation, and iron delivery strategies. Information regarding small molecule as well as macromolecular approaches and how they are employed within different disease pathogenesis such as primary and secondary iron overload diseases, cancer, diabetes, neurodegenerative diseases, infections, and in iron deficiency is provided.


Assuntos
Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Ferro/deficiência , Ferro/metabolismo , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Diabetes Mellitus/etiologia , Diabetes Mellitus/metabolismo , Fibrose/etiologia , Fibrose/metabolismo , Humanos , Ferro/análise , Ferro/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Neoplasias/etiologia , Neoplasias/metabolismo , Doenças Neurodegenerativas/etiologia , Doenças Neurodegenerativas/metabolismo
20.
J UOEH ; 43(2): 183-196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34092763

RESUMO

Several previous studies have investigated the effects of occupational stress on the onset of diabetes mellitus (DM), but there are few studies of occupational stress and DM using the Brief Job Stress Questionnaire (BJSQ), a standard stress check method in Japan. This study aimed to determine the relationship between occupational stress factors and the onset of DM using the BJSQ. We examined 6,620 male company workers aged 40 years and above in 2013, using the BJSQ. Overall, 2,604 subjects with impaired glucose tolerance who were free of mental disorders and DM were followed-up for 5 years and re-examined in 2017. A retrospective data analysis was conducted in 2019. We documented 241 new cases of DM in 2017 (diabetes group). Compared with the non-diabetes group, the subjects in the diabetes group had significantly decreased "skill utilization". A binomial logistic regression analysis (generalized linear model) revealed that "skill utilization" was associated with the risk of DM development in 2017 (odds ratio, 1.632; 95% confidence interval, 1.061-2.510). Our results showed that low skill utilization might increase the risk of diabetes development in Japanese male workers.


Assuntos
Diabetes Mellitus , Intolerância à Glucose , Estresse Ocupacional , Adulto , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Seguimentos , Intolerância à Glucose/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estresse Psicológico/complicações , Inquéritos e Questionários
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