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1.
Arch Pathol Lab Med ; 144(10): 1204-1208, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002153

RESUMO

CONTEXT.­: Glycemic control requires accurate blood glucose testing. The extent of hematocrit interference is difficult to assess to assure quality patient care. OBJECTIVE.­: To predict the effect of patient hematocrit on the performance of a glucose meter and its corresponding impact on insulin-dosing error. DESIGN.­: Multilevel mixed regression was conducted to assess the extent that patient hematocrit influences Roche Accu-Chek Inform II glucose meters, using the Radiometer ABL 837 as a reference method collected during validation of 35 new meters. Regression coefficients of fixed effects for reference glucose, hematocrit, an interaction term, and random error were applied to 4 months of patient reference method results extracted from the laboratory information system. A hospital inpatient insulin dose algorithm was used to determine the frequency of insulin dose error between reference glucose and meter glucose results. RESULTS.­: Fixed effects regression for method and hematocrit predicted biases to glucose meter results that met the "95% within ±12%" for the US Food and Drug Administration goal, but combinations of fixed and random effects exceeded that target in emergency and hospital inpatient units. Insulin dose errors were predicted from the meter results. Twenty-eight percent of intensive care unit, 20.8% of hospital inpatient, and 17.7% of emergency department results were predicted to trigger a ±1 insulin dose error by fixed and random effects. CONCLUSIONS.­: The current extent of hematocrit interference on glucose meter performance is anticipated to cause insulin error by 1-dose category, which is likely associated with low patient risk.


Assuntos
Glicemia/análise , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Erros Médicos , Algoritmos , Hematócrito , Humanos , Medição de Risco , Estados Unidos
2.
Nat Commun ; 11(1): 4933, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004787

RESUMO

The influence of seasons on biological processes is poorly understood. In order to identify biological seasonal patterns based on diverse molecular data, rather than calendar dates, we performed a deep longitudinal multiomics profiling of 105 individuals over 4 years. Here, we report more than 1000 seasonal variations in omics analytes and clinical measures. The different molecules group into two major seasonal patterns which correlate with peaks in late spring and late fall/early winter in California. The two patterns are enriched for molecules involved in human biological processes such as inflammation, immunity, cardiovascular health, as well as neurological and psychiatric conditions. Lastly, we identify molecules and microbes that demonstrate different seasonal patterns in insulin sensitive and insulin resistant individuals. The results of our study have important implications in healthcare and highlight the value of considering seasonality when assessing population wide health risk and management.


Assuntos
Exposição Ambiental , Resistência à Insulina/fisiologia , Redes e Vias Metabólicas/fisiologia , Microbiota/fisiologia , Estações do Ano , Adulto , Idoso , Glicemia/análise , Glicemia/metabolismo , California , Análise por Conglomerados , Feminino , Nível de Saúde , Humanos , Insulina/metabolismo , Estudos Longitudinais , Masculino , Metabolômica , Pessoa de Meia-Idade , RNA-Seq
3.
Nat Commun ; 11(1): 4627, 2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33009389

RESUMO

Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Hipóxia/metabolismo , Metabolismo dos Lipídeos , Transativadores/metabolismo , Animais , Caenorhabditis elegans/embriologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Embrião de Mamíferos/metabolismo , Regulação da Expressão Gênica , Glicogênio/metabolismo , Insulina/metabolismo , Larva/metabolismo , Mutação/genética , Consumo de Oxigênio , Transdução de Sinais , Estresse Fisiológico , Análise de Sobrevida , Transativadores/genética , Transcrição Genética , Vitelogeninas/metabolismo
4.
BMC Endocr Disord ; 20(1): 155, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066762

RESUMO

BACKGROUND: Detailed description of hyperglycemia management in diabetic patients infected with SARS-CoV-2 remain limited, although patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity. Here, we report the case of an extreme and transitory insulin requirement episode in a type 2 diabetic patient presenting an acute respiratory distress syndrome caused by SARS-CoV-2. CASE PRESENTATION: A 57-year-old man resident in Geneva, Switzerland, previously known for type 2 diabetes for 3 years was admitted for an aggravation of his dyspnea. His type 2 diabetes was treated only with metformin and his latest Hb1Ac was 6.1%. Chest CT SCAN showed a bilateral multilobar ground-glass opacification. Twenty-four hours after his admission he presented a worsening of dyspnea and severe hypoxemia requiring a transfer to the intensive care unit rapidly followed by oro-tracheal intubation for mechanical ventilation support. A bronchoalveolar lavage was performed and test of SARS-CoV-2 by RT-qPCR assay was positive. At day 3, he presented a rapidly progressive insulin requirement at a rate of up to 50 units/hour intravenous insulin aspart. Despite the high insulin doses, he maintained an elevated plasma glucose level at 270 mg/dL on average. His extremely high-dose insulin requirement "resolved" at day 9, and the insulin infusion rate was rapidly reduced. CONCLUSIONS: This case may reflect a specific and profound impact of SARS-CoV-2 on metabolic homeostasis, in particular in diabetic patients that appear more prone to complications of COVID-19 infection. Yet, the mechanisms behind this remain to be elucidated. The optimal management of hyperglycemia of diabetic patients infected with SARS-CoV-2 has yet not be defined, however insulin remain the mainstay of treatment approach. Report of extreme dysregulation of chronic conditions such as diabetes in patients with COVID-19 may help clinicians to better take care of patients during the pandemic of SARS-CoV-2. To the best of our knowledge this is the first description of extremely high-dose insulin requirement in patient with COVID-19.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pneumonia Viral/complicações , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Diabetes Mellitus Tipo 2/virologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , Prognóstico
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2217-2220, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018448

RESUMO

Type 1 diabetic patients characteristically exhibit a loss of insulin production, leading to chronic hyperglycemia and related complications. Herein we describe the design, synthesis and screening of novel oligopeptides for their potential to enhance the secretion of insulin from human pancreatic islets. The investigation of these compounds, based off the patented INGAP-PP sequence, aims to identify the peptide features key to maximizing insulin secretion.Clinical Relevance - This report describes the relative efficacy of selected novel compounds for potential Type 1 Diabetes Therapy. Tested on live human pancreatic islets, the compounds are evaluated for their enhancing/inhibitory effect on the secretion of insulin. These studies pave the way for future targeted drug therapies.


Assuntos
Diabetes Mellitus Tipo 1 , Ilhotas Pancreáticas , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Peptídeos/metabolismo
6.
Medicine (Baltimore) ; 99(40): e22337, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019410

RESUMO

At present, glycated hemoglobin (HbA1c) and glycated albumin (GA) are used to evaluate glycemic control in diabetic patients, but they cannot reflect insulin deficiency and/or insulin resistance.We investigated the feasibility of using estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to estimate insulin resistance in young adult diabetes. A total of 387 patients with type 2 diabetes were included and were stratified into 2 groups based on median values of the glycemic index ratio: the GA/A1c ratio <2.09 (n = 91) and ≥2.09 (n = 296); the eAG/fPG ratio <1.69 (n = 155) and ≥1.69 (n = 232). HbA1c, GA, fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c was calculated, and the homeostasis model assessment of ß-cell function and insulin resistance were determined. The homeostasis model assessment of insulin resistance level was significantly associated with the eAG/fPG ratio, but not with the ratio of GA to HbA1c, GA, HbA1c, and fructosamine levels. The ratio of estimated average glucose to fasting plasma glucose level correlates with insulin resistance in young adult diabetes.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Jejum/metabolismo , Resistência à Insulina/fisiologia , Adolescente , Adulto , Peptídeo C/sangue , Criança , Feminino , Frutosamina/sangue , Hemoglobina A Glicada/análise , Índice Glicêmico , Humanos , Insulina/sangue , Masculino , Albumina Sérica/análise , Adulto Jovem
7.
Med Hypotheses ; 143: 110185, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33017914

RESUMO

COVID-19 pandemic is spreading rapidly worldwide, and drug selection can affect the morbidity and mortality of the disease positively or negatively. Alpha-lipoic acid (ALA) is a potent antioxidant and reduces oxidative stress and inhibits activation of nuclear factor-kappa B (NF-kB). ALA reduces ADAM17 activity and ACE2 upregulation. ALA is known to have antiviral effects against some viruses. ALA may show antiviral effect by reducing NF-kB activation and alleviating redox reactions. ALA increases the intracellular glutathione strengthens the human host defense. ALA activates ATP dependent K+ channels (Na+, K+-ATPase). Increased K+ in the cell raises the intracellular pH. As the intracellular pH increases, the entry of the virus into the cell decreases. ALA can increase human host defense against SARS-CoV-2 by increasing intracellular pH. ALA treatment increases antioxidant levels and reduces oxidative stress. Thus, ALA may strengthen the human host defense against SARS-CoV-2 and can play a vital role in the treatment of patients with critically ill COVID-19. It can prevent cell damage by decreasing lactate production in patients with COVID-19. Using ALA with insulin in patients with diabetes can show a synergistic effect against SARS-CoV-2. We think ALA treatment will be beneficial against COVID-19 in patients with diabetes.


Assuntos
Proteína ADAM17/metabolismo , Infecções por Coronavirus/prevenção & controle , Complicações do Diabetes/prevenção & controle , NF-kappa B/metabolismo , Pandemias/prevenção & controle , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/prevenção & controle , Ácido Tióctico/uso terapêutico , Antioxidantes/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/complicações , Complicações do Diabetes/virologia , Diabetes Mellitus/tratamento farmacológico , Humanos , Concentração de Íons de Hidrogênio , Insulina/metabolismo , Oxirredução , Estresse Oxidativo , Pneumonia Viral/complicações
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5093-5096, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019132

RESUMO

The daily challenge for people with type 1 diabetes is maintaining glycaemia in the "normal" range after meals, by injecting themselves the correct amount of insulin. Artificial pancreas systems were developed to adjust insulin delivery based on real-time monitoring of glycaemia and meal patient's report. Meal reporting is a heavy burden for patients as it requires carbohydrate estimation several times per day. To improve patient's quality of life and treatment, several methods aim at detecting unannounced meals. While untreated meals lead to hyperglycaemia and in the long-term to comorbidities, treating falsely detected meals can cause hypoglycaemia and coma. In this paper, we propose to customise the meal detection to the patient's hourly meal probability in order to limit false detection of unannounced meals.


Assuntos
Pâncreas Artificial , Humanos , Hipoglicemiantes/efeitos adversos , Insulina , Refeições , Qualidade de Vida
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5111-5114, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019136

RESUMO

Therapies for treatment of type 2 diabetes (T2D) involve a variety of medications, depending on the stage of T2D progression. It is now an accepted knowledge that in silico trials can help to accelerate drug development and support treatment optimization. A T2D simulator (T2DS), consisting of a model of the glucose-insulin system and an in silico population describing glucose-insulin dynamics in T2D subjects, has been recently developed based on early-stage T2D data, studied with sophisticated experimental techniques. This limits the domain of validity of the simulator to this specific sub-population of T2D. Here we proposed a method for tuning the T2DS to any desired T2D target population, e.g. insulin-naïve (i.e., not experienced with insulin) patients, without the need to resort to complex and expensive clinical studies. This will allow to use the T2DS for testing treatments in the target population. To illustrate the methodology, we used a case study: extending the T2DS to reproduce the behavior of insulin-naïve T2D subjects. The methodology described here can be extended to other stages of T2D, allowing an extensive in silico testing phase of different treatments before human trials.


Assuntos
Diabetes Mellitus Tipo 2 , Glicemia , Clonagem Molecular , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Insulina , Insulina Regular Humana
10.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5502-5505, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019225

RESUMO

Type 1 diabetes (T1D) therapy requires multiple daily insulin injections to compensate the lack of endogenous insulin production due to ß-cells destruction. An empirical standard formula (SF) is commonly used for such a task. Unfortunately, SF does not include information on glucose dynamics, e.g. the glucose rate-of-change (ROC) provided by continuous glucose monitoring (CGM) sensor. Hence, SF can sometimes lead to under/overestimations that can cause critical hypo/hyperglycemic episodes during/after the meal. Recently, to overcome this limitation, we proposed new linear regression models, integrating ROC information and personalized features. Despite the first encouraging results, the nonlinear nature of the problem calls for the application of nonlinear models. In this work, random forest (RF) and gradient boosting tree (GBT), nonlinear machine learning methodologies, were investigated. A dataset of 100 virtual subjects, opportunely divided into training and testing sets, was used. For each individual, a single-meal scenario with different meal conditions (preprandial ROC, BG and meal amounts) was simulated. The assessment was performed both in terms of accuracy in estimating the optimal bolus and glycemic control. Results were compared to the best performing linear model previously developed. The two tree-based models proposed lead to a statistically significant improvement of glycemic control compared to the linear approach, reducing the time spent in hypoglycemia (from 32.49% to 27.57-25.20% for RF and GBT, respectively). These results represent a preliminary step to prove that nonlinear machine learning techniques can improve the estimation of insulin bolus in T1D therapy. Particularly, RF and GBT were shown to outperform the previously linear models proposed.Clinical Relevance- Insulin bolus estimation with nonlinear machine learning techniques reduces the risk of adverse events in T1D therapy.


Assuntos
Diabetes Mellitus Tipo 1 , Insulina , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Hipoglicemiantes , Aprendizado de Máquina , Dinâmica não Linear
11.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5557-5562, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019237

RESUMO

The prevalence of personal health data from wearable devices enables new opportunities to understand the impact of behavioral factors on health. Unlike consumer devices that are often auxiliary, such as Fitbit and Garmin, wearable medical devices like continuous glucose monitoring (CGM) devices and insulin pumps are becoming critical in diabetes care to minimize the occurrence of adverse glycemic events. Joint analysis of CGM and insulin pump data can provide unparalleled insights on how to modify treatment regimen to improve diabetes management outcomes. In this paper, we employ a data-driven approach to study the relationship between key behavioral factors and proximal diabetic management indicators. Our dataset includes an average of 161 days of time-matched CGM and insulin pump data from 34 subjects with Type 1 Diabetes (T1D). By employing hypothesis testing and association mining, we observe that smaller meals and insulin doses are associated with better glycemic outcomes compared to larger meals and insulin doses. Meanwhile, the occurrence of interrupted sleep is associated with poorer glycemic outcomes. This paper introduces a method for inferring disrupted sleep from wearable diabetes-device data and provides a baseline for future research on sleep quality and diabetes. This work also provides insights for development of decision-support tools for improving short- and long-term outcomes in diabetes care.


Assuntos
Automonitorização da Glicemia , Diabetes Mellitus Tipo 1 , Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Insulina/uso terapêutico , Sistemas de Infusão de Insulina
12.
Psychiatr Danub ; 32(Suppl 1): 121-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32890374

RESUMO

BACKGROUND: Factitious hypoglycaemia is a form of factitious disorder imposed on self with high morbidity and mortality. It is therefore important to be aware of the key demographic and contextual risk factors for factitious hypoglycaemia, as well the investigations and management options available for suspected cases. SUBJECTS AND METHODS: In this article we describe a case report and literature review of factitious hypoglycaemia. The search was conducted using the PubMed database and identified 23 case reports of 31 patients aged 18 or over with insulin-induced factitious hypoglycaemia. RESULTS: The average age of these patients was 33.7 (±13.5) years, the female: male ratio was 4.3:1, 38% had medical occupations or past medical training, 53% had diabetes mellitus, and 41% had a positive psychiatric history. Misdiagnoses were common and often resulted in inappropriate treatment. Very few cases discussed psychiatric management. CONCLUSIONS: Factitious hypoglycaemia is more commonly reported in middle-aged females, in a medical profession, with a past medical history of diabetes mellitus and psychiatric illness. However, it may affect a variety of patients and the absence of these features should not discourage a diagnosis. C-peptide levels and insulin assays can help identify factitious hypoglycaemia over other causes of hypoglycaemia, and management should include a greater focus on psychiatric treatment.


Assuntos
Diabetes Mellitus , Transtornos Autoinduzidos , Hipoglicemia , Adolescente , Adulto , Feminino , Humanos , Insulina , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
13.
In Vivo ; 34(5): 3029-3032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871848

RESUMO

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.


Assuntos
Infecções por Coronavirus/terapia , Diabetes Mellitus/terapia , Hiperglicemia/terapia , Insulina/metabolismo , Pneumonia Viral/terapia , Betacoronavirus/patogenicidade , Glicemia/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Diabetes Mellitus/genética , Diabetes Mellitus/virologia , Feminino , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/virologia , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Respiração Artificial , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/terapia , Síndrome Respiratória Aguda Grave/virologia
14.
Zhongguo Gu Shang ; 33(8): 730-5, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32875763

RESUMO

OBJECTIVE: To explore the effect of glucose pretreatment in the rapid rehabilitation surgery of hip replacement patients, and to provide reference for the future clinical treatment. METHODS: From June 2016 to June 2018, 168 patients (100 males, 68 females) were treated with hip replacement. The patients were divided into control group and observation group, 84 cases in each group, aged 25 to 90 (52.05±5.73) years old. Both groups were treated with the concept of rapid rehabilitation surgery, the control group was given traditional fasting water deprivation before operation, and the observation group was given glucose pretreatment before operation. The levels of fasting blood glucose(FBG), C-peptide, fasting insulin(FINS), IgG, IgM, IgA and total lymphocyte count (TLC) were compared before and after operation, and the sensitivity of thirst, nausea, fatigue, sweating, stomach discomfort, anxiety, hunger and dizziness were compared. RESULTS: All the 168 patients were followed up. There was no significant difference in FBG, C-peptide and fins levels between the observation group and the control group (P>0.05). The levels of FBG, C-peptide and fins in the observation group were higher than those in the control group (P<0.05). There was no significant difference in the serum IgG, IgM, IgA and TLC levels between the observation group and the control group(P>0.05);the serum IgG, IgM, IgA and TLC levels after operation were higher than those before operation, and the observation group was higher than the control group(P<0.05). There was no significant difference in the degree of thirst, nausea, fatigue, sweating and stomach discomfort between the observation group and the control group (P>0.05);the degree of anxiety, hunger and dizziness in the observation group was less than that in the control group (P<0.05). CONCLUSION: Glucose pretreatment before hip replacement can relieve insulin resistance, improve immunity and change energy storage under fasting, which can be widely used in clinic.


Assuntos
Artroplastia de Quadril , Resistência à Insulina , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia , Feminino , Glucose , Humanos , Insulina , Masculino , Pessoa de Meia-Idade
15.
Medicine (Baltimore) ; 99(35): e21654, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871878

RESUMO

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Vitamina D/análogos & derivados , Adulto , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , China , Colesterol/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Gravidez , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Vitamina D/sangue
16.
Wei Sheng Yan Jiu ; 49(4): 580-584, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-32928348

RESUMO

OBJECTIVE: To observe the changes of neuropeptide Y(NPY) expression in perirenal adipose tissue and its relationship with insulin resistance in the nutritional transition models of refeeding after calorie restriction. METHODS: SPF Male SD rats, aged 8 weeks, were randomly divided into normal chow group and refeeding with normal chow after calorie restriction for 4 weeks group. NPY gene expression in perirenal adipose tissue were detected by real-time quantitative PCR at the end of 4 and 12 weeks, along with fasting plasma glucose, fasting serum lisulin, free fatty acids and average glucose infusion rate(GIR_(60-120)) of hyperinsulinemic-euglycemic clamp test for 60-120 minutes. NPY gene mRNA expression in perirenal adipose tissue was detected by real-time quantitative PCR. And the relationship between NPY gene expression and insulin resistance was detected by Spearman correlation analysis. RESULTS: The expression level of NPY gene in perirenal adipose tissue in caloric restriction for 4 weeks group was significantly increased by calorie restriction(P<0. 01). After refeeding, the expression level of NPY gene in refeeding with normal group was still slightly increased, which was significantly higher than that in normal group at the end of the experiment(P<0. 01). The levels of fasting plasma glucose and fasting insulin in caloric restriction for 4 weeks group decreased slightly, GIR_(60-120) increased slightly, but there were no statistical differences compared with normal group(P>0. 05), but free fatty acid levels increased significantly(P<0. 01). After refeeding, the levels of fasting insulin, free fatty acid in refeeding with normal group increased significantly, GIR_(60-120) decreased evidently(P<0. 01), but the changes of fasting blood glucose were not obvious. The result of stepwise regression showed that the expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120) and fasting insulin, with R values of-0. 816 and 0. 789 respectively(R~2=0. 892, P<0. 01). The result of correlation analysis showed that in the 4-week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_( 60-120)、fasting insulin and free fatty acid, with R values of-0. 765, 0. 716 and 0. 657 respectively(P<0. 01). In the 12 week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120), fasting insulin and free fatty acid, with R values of-0. 853, 0. 622 and 0. 608 respectively(P<0. 01). CONCLUSION: The mRNA expression of NPY gene in perirenal adipose tissue was closely related to indicators of insulin resistance. It is an important factor affecting insulin sensitivity.


Assuntos
Resistência à Insulina , Tecido Adiposo , Animais , Insulina , Masculino , Neuropeptídeo Y , Ratos , Ratos Sprague-Dawley
17.
PLoS One ; 15(9): e0236081, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32960890

RESUMO

Type 2 diabetes mellitus (T2DM), one of the most common metabolic diseases, is characterized by insulin resistance and inadequate insulin secretion of ß cells. Glycogen phosphorylase (GP) is the key enzyme in glycogen breakdown, and contributes to hepatic glucose production during fasting or during insulin resistance. Pharmacological GP inhibitors are potential glucose lowering agents, which may be used in T2DM therapy. A natural product isolated from the cultured broth of the fungal strain No. 138354, called 2,3-bis(4-hydroxycinnamoyloxy)glutaric acid (FR258900), was discovered a decade ago. In vivo studies showed that FR258900 significantly reduced blood glucose levels in diabetic mice. We previously showed that GP inhibitors can potently enhance the function of ß cells. The purpose of this study was to assess whether an analogue of FR258900 can influence ß cell function. BF142 (Meso-Dimethyl 2,3-bis[(E)-3-(4-acetoxyphenyl)prop-2-enamido]butanedioate) treatment activated the glucose-stimulated insulin secretion pathway, as indicated by enhanced glycolysis, increased mitochondrial oxidation, significantly increased ATP production, and elevated calcium influx in MIN6 cells. Furthermore, BF142 induced mTORC1-specific phosphorylation of S6K, increased levels of PDX1 and insulin protein, and increased insulin secretion. Our data suggest that BF142 can influence ß cell function and can support the insulin producing ability of ß cells.


Assuntos
Cinamatos/farmacologia , Inibidores Enzimáticos/farmacologia , Glutaratos/farmacologia , Glicogênio Fosforilase/antagonistas & inibidores , Secreção de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/efeitos dos fármacos , Ácido Succínico/farmacologia , Animais , Linhagem Celular Tumoral , Cinamatos/química , Inibidores Enzimáticos/química , Glucose/metabolismo , Glutaratos/química , Glicogênio Fosforilase/metabolismo , Glicólise/efeitos dos fármacos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Metilação , Camundongos , Ácido Succínico/química
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(7): 752-758, 2020 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879077

RESUMO

OBJECTIVES: To investigate whether necrostatin-1 (Nec-1) can protect islet cells from the damage induced by TNF-α. METHODS: After isolation and purification, the neonatal porcine islet cell clusters (NICCs) were divided into 3 groups (islets 10 000 IEQ/group): a Nec-1 group (Nec-1+TNF-α was added to the culture medium), a TNF-α group (TNF-α was added to the culture medium), and a control group (pure medium). The number of cells was observed after 48 h of co-culture. The cell death was evaluated by AO/EB staining. Insulin secretion and DNA of islets were detected by chemiluminescence and nucleic acid quantitative analysis. RT-PCR assay was used to examine the mRNA expressions of insulin gene, glueogan gene and somatostatin gene. Flow cytometry analysis was used to detect the viability of B cells. RESULTS: The number of islets in Nec-1 group, TNF-α group and the control group were (8 425±2 187), (4 325±778), and (7 122±1 558) IEQ, respectively. Compared to the other two groups, the number of dead cells in TNF-α group was greatly increased. The insulin/DNA values in the Nec-1 group, TNF-α group and blank control group were (13.21±3.15), (2.47±0.45), and (7.44±0.97) mIU/mg, respectively. Compared to the TNF-α group and the control group, the mRNA relative expression levels of insulin gene (6.73±1.07), glucagon gene (10.13±1.98), somatostatin gene (8.57±1.11) were significantly increased in the Nec-1 group (all P<0.05), the rate of live cells (97.32±1.87)% and live B cells (90.86±3.68)% were increased significantly in the Nec-1 group (all P<0.05). CONCLUSIONS: TNF-α can induce neonatal porcine islet cells damage, which is attenuated in the presence of Nec-1. Nec-1 can increase the content of endocrine cells in NICCs.


Assuntos
Ilhotas Pancreáticas , Fator de Necrose Tumoral alfa/genética , Animais , Imidazóis , Indóis , Insulina , Suínos
19.
BMJ Open ; 10(9): e040644, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928868

RESUMO

OBJECTIVE: To review evidence on routinely prescribed drugs in the UK that could upregulate or downregulate ACE2 and potentially affect COVID-19 disease. DESIGN: Systematic review. DATA SOURCE: MEDLINE, EMBASE, CINAHL, the Cochrane Library and Web of Science. STUDY SELECTION: Any design with animal or human models examining a currently prescribed UK drug compared with a control, placebo or sham group, and reporting an effect on ACE2 level, activity or gene expression. DATA EXTRACTION AND SYNTHESIS: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science and OpenGrey from inception to 1 April 2020. Methodological quality was assessed using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk-of-bias tool for animal studies and Cochrane risk-of-bias tool for human studies. RESULTS: We screened 3360 titles and included 112 studies with 21 different drug classes identified as influencing ACE2 activity. Ten studies were in humans and one hundred and two were in animal models None examined ACE2 in human lungs. The most frequently examined drugs were angiotensin receptor blockers (ARBs) (n=55) and ACE inhibitors (ACE-I) (n=22). More studies reported upregulation than downregulation with ACE-I (n=22), ARBs (n=55), insulin (n=8), thiazolidinedione (n=7) aldosterone agonists (n=3), statins (n=5), oestrogens (n=5) calcium channel blockers (n=3) glucagon-like peptide 1 (GLP-1) agonists (n=2) and Non-steroidal anti-inflammatory drugs (NSAIDs) (n=2). CONCLUSIONS: There is an abundance of the academic literature and media reports on the potential of drugs that could attenuate or exacerbate COVID-19 disease. This is leading to trials of repurposed drugs and uncertainty among patients and clinicians concerning continuation or cessation of prescribed medications. Our review indicates that the impact of currently prescribed drugs on ACE2 has been poorly studied in vivo, particularly in human lungs where the SARS-CoV-2 virus appears to enact its pathogenic effects. We found no convincing evidence to justify starting or stopping currently prescribed drugs to influence outcomes of COVID-19 disease.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Infecções por Coronavirus , Estrogênios/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Hipoglicemiantes/farmacologia , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Pneumonia Viral , Anti-Inflamatórios não Esteroides/farmacologia , Betacoronavirus/metabolismo , Regulação para Baixo , Peptídeo 1 Semelhante ao Glucagon/agonistas , Humanos , Insulina/farmacologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Peptidil Dipeptidase A/metabolismo , Tiazolidinedionas/farmacologia , Reino Unido , Regulação para Cima
20.
Emerg Med Clin North Am ; 38(4): 841-856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981621
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