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1.
BMJ Case Rep ; 14(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518181

RESUMO

Clozapine is an atypical antipsychotic used in refractory schizophrenia, also efficient in alleviating dyskinesia in Parkinson's disease. Despite its potency, this drug is associated with severe metabolic side effects, including increased risk for diabetes. We report the case of a 45-year-old overweight woman with Parkinson's disease who presented with rapid-onset hyperglycaemia within 2 months after starting clozapine for refractory dyskinaesia. She had a history of gestational diabetes. At presentation, her blood glucose level was 505 mg/dL and glycated haemoglobin 12.4%, with no catabolic symptoms. Clozapine was suspended and metformin was started, but adequate glycaemic control was achieved only with insulin therapy, along with exenatide and empagliflozin afterwards. We assume that clozapine acted as a trigger for rapid deterioration of glycaemic control through direct pathophysiological mechanisms, rather than an indirect slowly evolving weight gain-related metabolic syndrome pathway. Clinicians should be aware of this complication, enabling timely diagnosis and proper treatment.


Assuntos
Antipsicóticos , Clozapina , Hiperglicemia , Esquizofrenia , Antipsicóticos/efeitos adversos , Glicemia , Clozapina/efeitos adversos , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Pessoa de Meia-Idade , Esquizofrenia/tratamento farmacológico
2.
Biomed Res Int ; 2021: 5521516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395617

RESUMO

Dibutyl phthalate is an endocrine disruptor used in a wide range of industrial and agriculture applications. The present study focuses on elucidating the effect of subacute exposure (4-weeks) of DBP on insulin and its sensitivity indexes, oxidative status, thyroid function, energy metabolites, serum biochemistry, and anthropometry in rats. A total of 64 rats were divided into 4 treatment groups as mg DBP/Kg body weight per day: (a) 0 mg/Kg (control), (b) 10 mg/Kg (DBP-10), (c) 50 mg/Kg (DBP-50), and (d) 100 mg/Kg (DBP-100). The rats in each treatment (n = 16) were further divided into male (n = 8) and female (n = 8) rats for studying treatment and gender interactions. Intraperitoneal glucose tolerance test (IPGTT) was performed on the 21st day. Anthropometry, nutritional determinants, fasting plasma glucose, fasting plasma insulin, homeostatic model assessment (HOMA), thyroid hormones, energy metabolites, and oxidative status were studied during the experimental period. Two-way ANOVA was used to analyze the data (p < 0.05). Tukey's posthoc test was used for pair-wise comparisons. DBP increased body weight gain and feed efficiency in an inverted nonmonotonic U-shaped fashion. Hyperglycemia and increased blood glucose area under the curve were observed in DBP-100 at 120 minutes in IPGTT. The HOMA also showed a linear monotonic contrast. Thyroxin decreased significantly in the DBP-100 rats, whereas malondialdehyde, nonesterified fatty acids, and beta hydroxyl butyrate were increased with the DBP treatments. In conclusion, DBP could be attributed to the development of hyperglycemia and insulin resistance in rats. Further investigations into the lipid peroxidation pathways can improve our understanding of the mechanisms involved in metabolic disruption.


Assuntos
Dibutilftalato/toxicidade , Hiperglicemia/induzido quimicamente , Resistência à Insulina , Glândula Tireoide/fisiologia , Animais , Feminino , Teste de Tolerância a Glucose , Homeostase/efeitos dos fármacos , Masculino , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Glândula Tireoide/efeitos dos fármacos , Testes de Toxicidade Subaguda
3.
Diabetes Metab Syndr ; 15(4): 102188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34217143

RESUMO

AIM: The pandemic has generated the need for COVID-19 patients to be treated as best as possible; however, the effect of these treatments on glycemic control has not yet been taken into account. This article aims to determine whether the daily variation of glucose is influenced by the use of corticosteroids in COVID-19 patients treated in Lima-Peru. METHODOLOGY: A prospective cohort study was undertook, in which glucose was measured four times a day in 53 patients hospitalized due to COVID-19. These values were associated with the use of corticosteroids and adjusted for other socio-educational variables, all by means of PA-GEE models. RESULTS: Nested multivariate analysis of daily glucose variation found that those using corticosteroids increased the daily average glucose as well as the first and last glucose measurements, this is, at 6am and 10pm, respectively (all p-values <0.026). An increase in glucose levels was also observed in those with diabetes (all p-values <0.001). In contrast, we found that there was a decrease in the last glucose measurement of the day in obese patients (p-value = 0.044). CONCLUSIONS: The patients who used corticosteroids for the treatment of COVID-19 increased the average glucose per day, especially in the first and last measurement.


Assuntos
Corticosteroides/efeitos adversos , Glicemia/análise , COVID-19/tratamento farmacológico , Hiperglicemia/patologia , SARS-CoV-2/isolamento & purificação , Idoso , Automonitorização da Glicemia/métodos , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Masculino , Pessoa de Meia-Idade , Peru/epidemiologia , Estudos Prospectivos
5.
Integr Cancer Ther ; 20: 15347354211032283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34259084

RESUMO

Alpelisib is a α-selective phosphatidylinositol 3-kinase (PI3K) inhibitor approved for treatment of postmenopausal women, and men, with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), PIK3CA-mutated, advanced breast cancer (ABC). Hyperglycemia is a common, on-target adverse effect that impairs treatment efficacy and increases the rate of treatment delays, dose reductions, and discontinuation. Currently, there are no clear guidelines on how to manage hyperglycemia due to alpelisib when metformin is not effective. In this case series, we review 3 subjects with ABC that developed hyperglycemia during alpelisib-fulvestrant therapy and were successfully managed with dietary and pharmacologic interventions. These cases provide anecdotal evidence to support the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and very low carbohydrate diets to minimize hyperglycemia during alpelisib therapy.


Assuntos
Hiperglicemia , Inibidores do Transportador 2 de Sódio-Glicose , Simportadores , Dieta com Restrição de Carboidratos , Feminino , Glucose , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Masculino , Fosfatidilinositol 3-Quinases , Receptor ErbB-2/metabolismo , Sódio , Tiazóis
7.
Medicine (Baltimore) ; 100(25): e26505, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160469

RESUMO

ABSTRACT: Despite advances in treatments for diabetes mellitus (DM), severe acute glycemic crises still occur. In this study, the characteristics of patients who were transported to an emergency department due to acute glycemic crises were investigated.We enrolled patients who were transported to our hospital by ambulance due to hypoglycemia or hyperglycemia during the period from January 2015 to December 2019. Initial glucose levels below 70 mg/dL and above 250 mg/dL were defined as hypoglycemia and hyperglycemia, respectively.In the 5-year period, 16,910 patients were transported to our hospital by ambulance. Of those patients, 87 patients (0.51%) were diagnosed with hypoglycemia, 26 patients (0.15%) were diagnosed with hyperglycemia and 1 patient was diagnosed with lactic acidosis. Compared to patients with hypoglycemia, blood urea nitrogen, serum potassium and hemoglobin levels were higher in patients with hyperglycemia. Systolic blood pressure was lower and pulse rate was higher in patients with hyperglycemia, possibly reflecting dehydration in hyperglycemia. Patients with hyperglycemia were younger (63 vs 70 years old, median), more likely to be hospitalized (92.3% vs 23.0%) with poorer prognosis (23.1% vs 4.6%) than those with hypoglycemia. In 64 DM patients with hypoglycemia, 34 patients were treated with insulin and 24 patients were treated with sulfonylurea or glinide, and their medication was often inappropriate. Excessive alcohol intake and malnutrition were the main causes of hypoglycemia in 23 non-DM patients. The main reasons for hyperglycemia were interrupted treatment, forgetting insulin injection and infection.To avoid acute glycemic crises, optimization of anti-DM therapy and education of patients are needed.


Assuntos
Acidose Láctica/epidemiologia , Hospitais Gerais/estatística & dados numéricos , Hiperglicemia/epidemiologia , Hipoglicemia/epidemiologia , Hipoglicemiantes/efeitos adversos , Acidose Láctica/sangue , Acidose Láctica/induzido quimicamente , Acidose Láctica/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/sangue , Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/tratamento farmacológico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Hiperglicemia/diagnóstico , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Japão/epidemiologia , Masculino , Desnutrição/sangue , Desnutrição/complicações , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
J Med Case Rep ; 15(1): 297, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020705

RESUMO

BACKGROUND: High-dose vitamin C is increasingly used for sepsis and more recently for coronavirus disease 2019 (COVID-19) infections. Proponents argue that the low cost and near perfect safety profile of vitamin C support its early adoption. Yet, adverse events might be underreported and underappreciated. CASE PRESENTATION: We report a 73-year-old non-diabetic white man with end-stage renal disease on peritoneal dialysis admitted to the intensive care unit with septic shock that was suspected to be due to peritonitis. The patient was enrolled in LOVIT (Lessening Organ Dysfunction with VITamin C; ClinicalTrials.gov identifier: NCT03680274), a randomized placebo-controlled trial of high-dose intravenous vitamin C. He developed factitious hyperglycemia, as measured with a point-of-care glucometer, that persisted for 6 days after discontinuation of the study drug, confirmed to be vitamin C after unblinding. He also had short-lived iatrogenic coma because of hypoglycemia secondary to insulin administration. These events triggered a protocol amendment. CONCLUSIONS: Although factitious hyperglycemia has been reported before using certain glucometers in patients treated with high-dose vitamin C, the persistence of this phenomenon for 6 days after the discontinuation of the therapy is a distinguishing feature. This case highlights the importance of monitoring glucose with a core laboratory assay for up to a week in specific populations, such as patients on peritoneal dialysis.


Assuntos
COVID-19 , Hiperglicemia , Diálise Peritoneal , Idoso , Humanos , Hiperglicemia/induzido quimicamente , Masculino , Diálise Peritoneal/efeitos adversos , SARS-CoV-2 , Vitaminas
9.
J Vis Exp ; (171)2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-34028434

RESUMO

Zebrafish (Danio rerio) are an excellent model to investigate the effects of chronic hyperglycemia, a hallmark of Type II Diabetes Mellitus (T2DM). This alternate immersion protocol is a noninvasive, step-wise method of inducing hyperglycemia for up to eight weeks. Adult zebrafish are alternately exposed to sugar (glucose) and water for 24 hours each. The zebrafish begin treatment in a 1% glucose solution for 2 weeks, then a 2% solution for 2 weeks, and finally a 3% solution for the remaining 4 weeks. Compared to water-treated (stress) and mannitol-treated (osmotic) controls, glucose-treated zebrafish have significantly higher blood sugar levels. The glucose-treated zebrafish show blood sugar levels of 3-times that of controls, suggesting that after both four and eight weeks hyperglycemia can be achieved. Sustained hyperglycemia was associated with increased Glial Fibrillary Acidic Protein (GFAP) and increased nuclear factor Kappa B (NF-kB) levels in retina and decreased physiological responses, as well as cognitive deficits suggesting this protocol can be used to model disease complications.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Animais , Glicemia , Modelos Animais de Doenças , Glucose , Hiperglicemia/induzido quimicamente , Imersão , Peixe-Zebra
11.
Am J Case Rep ; 22: e930733, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33907174

RESUMO

BACKGROUND Intravenous (IV) dexamethasone is widely used in critical illness, chemotherapy, or severe COVID-19. Although glucocorticoid-induced hyperglycemia (GCIH) is well-known, there is no report describing the glycemic profile following a single dose of IV dexamethasone as captured on continuous glucose monitoring (CGM) in a patient with diabetes treated with insulin. CASE REPORT A 70-year-old woman with diabetes and pancreatic adenocarcinoma was treated with chemotherapy containing dexamethasone every other week. CGM data of 23 cycles revealed a reproducible triphasic glycemic pattern consisting of a constant hyperglycemia period, followed by a transient improvement, and ending with another hyperglycemic plateau. Given this recurrent pattern, basal insulin and correction insulin were adjusted with subsequent GCIH attenuation. CONCLUSIONS This is the first report of CGM glycemic profile following recurring doses of IV dexamethasone in a patient with diabetes treated with basal-bolus insulin. The understanding of triphasic glycemic pattern allows optimal glycemic management.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/efeitos adversos , Automonitorização da Glicemia/efeitos adversos , Dexametasona/administração & dosagem , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/induzido quimicamente , Insulina/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Administração Intravenosa , Idoso , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Glicemia , COVID-19/tratamento farmacológico , Dexametasona/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/patologia , SARS-CoV-2
12.
Am J Med Genet A ; 185(6): 1854-1857, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33686767

RESUMO

The COVID-19 pandemic has affected the health and healthcare of individuals of all ages worldwide. There have been multiple reports and reviews documenting a milder effect and decreased morbidity and mortality in the pediatric population, but there have only been a small number of reports discussing the SARS-CoV-2 infection in the setting of an inborn error of metabolism (IEM). Here, we report two patients with underlying metabolic disorders, propionic acidemia and glutaric aciduria type 1, and discuss their clinical presentation, as well as their infectious and metabolic management. Our report demonstrates that individuals with an underlying IEM are at risk of metabolic decompensation in the setting of a COVID-19 infection. The SARS-CoV-2 virus does not appear to cause a more severe metabolic deterioration than is typical.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/complicações , Encefalopatias Metabólicas/complicações , COVID-19/complicações , Glutaril-CoA Desidrogenase/deficiência , Acidemia Propiônica/complicações , SARS-CoV-2 , Acidose/etiologia , Acidose/terapia , Acidose Láctica/etiologia , Transfusão de Componentes Sanguíneos , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Terapia Combinada , Proteínas na Dieta/administração & dosagem , Gerenciamento Clínico , Suscetibilidade a Doenças , Ingestão de Energia , Nutrição Enteral , Feminino , Hidratação , Glucose/administração & dosagem , Glucose/efeitos adversos , Humanos , Hiperamonemia/etiologia , Hiperamonemia/terapia , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Lactente , Insulina/uso terapêutico , Unidades de Terapia Intensiva Pediátrica , Oxigenoterapia , Pancitopenia/etiologia , Pancitopenia/terapia , Diálise Renal , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
13.
Am J Physiol Endocrinol Metab ; 320(4): E797-E807, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645253

RESUMO

Application of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements. Clamp operators received initial and repeated training with ongoing feedback based on surveillance of clamp performance. The precision and accuracy of the achieved stage-specific glucose targets were evaluated, including differences by study center. We also evaluated robustness of the method to baseline physiologic differences and on-study treatment effects. The RISE approach produced high overall precision (3%-9% variance in achieved plasma glucose from target at various times across the procedure) and accuracy (SD < 10% overall). Statistically significant but numerically small differences in achieved target glucose concentrations were observed across study centers, within the magnitude of the observed technical variability. Variation of the achieved target glucose over time in placebo-treated individuals was low (<3% variation), and the method was robust to differences in baseline physiology (youth vs. adult, IGT vs. diabetes status) and differences in physiology induced by study treatments. The RISE approach to standardization of the hyperglycemic clamp methodology across multiple study centers produced technically excellent standardization of achieved glucose concentrations. This approach provides a reliable method for implementing glucose clamp methodology across multiple study centers.NEW & NOTEWORTHY The Restoring Insulin Secretion (RISE) study centers undertook hyperglycemic clamps using a simplified methodology and a decision guidance algorithm implemented in an easy-to-use spreadsheet. This approach, combined with active management including ongoing central data surveillance and routine feedback to study centers, produced technically excellent standardization of achieved glucose concentrations on repeat studies within and across study centers.


Assuntos
Glicemia/metabolismo , Técnica Clamp de Glucose/normas , Adolescente , Adulto , Algoritmos , Glicemia/análise , Criança , Diabetes Mellitus Tipo 2/sangue , Feminino , Glucose/administração & dosagem , Glucose/farmacologia , Técnica Clamp de Glucose/métodos , Teste de Tolerância a Glucose/métodos , Teste de Tolerância a Glucose/normas , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Secreção de Insulina/efeitos dos fármacos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
14.
BMJ Case Rep ; 14(3)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762290

RESUMO

An elderly woman with metastatic breast cancer was admitted with hyperglycaemic hyperosmolar state (HHS) and an elevated haemoglobin A1C. For 1 week, she had experienced confusion, nausea and frequent urination. Preceding this, she had completed seven cycles of capecitabine chemotherapy for her breast cancer. She did not have a history of diabetes prior to chemotherapy. Given the temporal dysglycaemia following the patient's chemotherapy regimen, capecitabine was thought to be a probable offending agent. The patient was acutely treated for HHS, and was discharged on a basal-bolus insulin regimen. Her capecitabine was held pending review with her oncology team. The patient was ultimately titrated down to basal insulin only by her family doctor. Given the common use of capecitabine, it is important to recognise the risk of hyperglycaemic and hyperglycaemic emergencies as potential adverse effects. This highlights the need to monitor blood glucose throughout treatment to prevent hyperglycaemic emergencies.


Assuntos
Neoplasias da Mama , Diabetes Mellitus , Hiperglicemia , Coma Hiperglicêmico Hiperosmolar não Cetótico , Idoso , Glicemia , Neoplasias da Mama/tratamento farmacológico , Capecitabina/efeitos adversos , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Coma Hiperglicêmico Hiperosmolar não Cetótico/induzido quimicamente , Coma Hiperglicêmico Hiperosmolar não Cetótico/diagnóstico
15.
Diabetes Res Clin Pract ; 174: 108751, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33722701

RESUMO

AIMS: To investigate the incidence of and risk factors for new-onset type 2 diabetes mellitus (DM) developed during chemotherapy that included steroids in cancer patients without DM. METHODS: This multicenter, prospective, and observational cohort study enrolled 299 cancer patients without DM (aged > 18 years), planning 4-8 cycles of adjuvant chemotherapy. The endpoints were the incidence, remission rate, and independent determinants of new-onset DM during chemotherapy. RESULTS: Between April 2015 and March 2018, 270 subjects with colorectal cancer or breast cancer (mean age, 51.0 years) completed the follow up (mean 39 months). Of whom, 17 subjects (6.3%) developed DM within a median time of 90 days (range, 17-359 days). Male sex (hazard ratio [HR], 15.839; 95% confidence interval [CI], 2.004-125.20) and impaired fasting glucose (IFG) at baseline (HR, 8.307; CI, 1.826-37.786) were independent risk factors. Six months after chemotherapy completion, 11/17 subjects (64.7%) experienced DM remission, associated with a significantly higher C-peptide level at baseline (C-peptide levels, 1.3 ng/mL in subjects with remission and 0.9 ng/mL in subjects without remission, age- and sex-adjusted P = 0.007). CONCLUSIONS: DM incidence was 6.3% in patients who received chemotherapy with dexamethasone. Close monitoring for hyperglycemia is recommended, especially for men with IFG. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03062072).


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Hiperglicemia/epidemiologia , Estado Pré-Diabético/epidemiologia , Glicemia/análise , Neoplasias da Mama/patologia , Neoplasias Colorretais/patologia , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/patologia , Progressão da Doença , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/patologia , Incidência , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/patologia , Prognóstico , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Taxa de Sobrevida
16.
Can J Anaesth ; 68(7): 972-979, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33580878

RESUMO

PURPOSE: Perioperative hyperglycemia is common and is associated with significant morbidity. Although patient characteristics and surgery influence perioperative glucose metabolism, anesthetics have a significant impact. We hypothesized that mice that were obese and insulin-resistant would experience greater hyperglycemia in response to sevoflurane anesthesia compared with lean controls. We further hypothesized that sevoflurane-induced hyperglycemia would be attenuated by salsalate pre-treatment. METHODS: Lean and obese male C57BL/6J mice were anesthetized with sevoflurane for 60 min with or without pre-treatment of 62.5 mg·kg-1 salsalate. Blood glucose, plasma insulin, and glucose uptake into different tissues were measured. RESULTS: Under sevoflurane anesthesia, obese mice had higher blood glucose compared to lean mice. Increases in blood glucose were attenuated with acute salsalate pre-treatment at 60 min under anesthesia in obese mice (mean ± standard error of the mean [SEM], delta blood glucose; vehicle 5.79 ± 1.09 vs salsalate 1.91 ± 1.32 mM; P = 0.04) but did not reach statistical significance in lean mice (delta blood glucose, vehicle 4.39 ± 0.55 vs salsalate 2.79 ± 0.71 mM; P = 0.10). This effect was independent of changes in insulin but associated with an approx. 1.7-fold increase in glucose uptake into brown adipose tissue (vehicle 45.28 ± 4.57 vs salsalate 76.89 ± 12.23 µmol·g-1 tissue·hr-1; P < 0.001). CONCLUSION: These data show that salsalate can reduce sevoflurane-induced hyperglycemia in mice. This indicates that salsalate may represent a new class of therapeutics that, in addition to its anti-inflammatory and analgesic properties, may be useful to reduce perioperative hyperglycemia.


Assuntos
Hiperglicemia , Insulina , Animais , Glicemia , Glucose , Hiperglicemia/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Salicilatos , Sevoflurano
17.
BMC Pregnancy Childbirth ; 21(1): 138, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588801

RESUMO

BACKGROUND: Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration. METHODS: A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids. RESULTS: Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different. CONCLUSIONS: In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect. TRIAL REGISTRATION: The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .


Assuntos
Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Complicações na Gravidez/prevenção & controle , Cuidado Pré-Natal , Adulto , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/metabolismo , Método Duplo-Cego , Feminino , Sofrimento Fetal , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/metabolismo , Trabalho de Parto Prematuro , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/metabolismo , Hemorragia Uterina
18.
PLoS One ; 16(2): e0246175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33600450

RESUMO

OBJECTIVE: To describe maternal and neonatal glycaemic control following antenatal corticosteroid administration to women with diabetes in pregnancy. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Auckland, New Zealand. POPULATION: Women with diabetes in pregnancy who received antenatal corticosteroids from 2006-2016. METHODS: Corticosteroid administration, maternal and neonatal glycaemia data were retrieved from electronic patient records. Demographic data were downloaded from the hospital database. Relationships between variables were analysed using multivariate analysis. MAIN OUTCOME MEASURES: Maternal hyperglycaemia and neonatal hypoglycaemia. RESULTS: Corticosteroids were administered to 647 of 7317 of women with diabetes (8.8%) who gave birth to 715 babies. After an initial course of corticosteroids, 92% and 52% of women had blood glucose concentrations > 7 and > 10 mmol/L respectively. Median peak blood glucose concentration of approximately 10 mmol/L occurred 9 hours after corticosteroid administration and hyperglycaemia lasted approximately 72 hours. Thirty percent of women gave birth within 72 hours of the last dose of corticosteroids. Babies of women who were hyperglycaemic within 24 hours of birth were more likely to develop hypoglycaemia (< 2.6 mmol/L, OR 1.51 [95% CI 1.10-2.07], p = 0.01) and severe hypoglycaemia (≤ 2.0 mmol/L, OR 2.00 [95% CI 1.41-2.85], p < 0.0001) than babies of non-hyperglycaemic mothers. There was no association between maternal glycaemia within 7 days of the last dose of corticosteroids and neonatal hypoglycaemia. CONCLUSIONS: Hyperglycaemia is common in women with diabetes in pregnancy following antenatal corticosteroid administration. Maternal hyperglycaemia in the 24 hours prior to birth is associated with increased risk of neonatal hypoglycaemia. Limitations included the retrospective study design, so that not all data were available for all women and babies and the glucose testing schedule was variable.


Assuntos
Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Diabetes Gestacional/sangue , Controle Glicêmico/estatística & dados numéricos , Mães , Adulto , Estudos de Coortes , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Hiperglicemia/complicações , Recém-Nascido , Gravidez , Estudos Retrospectivos
20.
J Obstet Gynaecol ; 41(1): 83-88, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33583317

RESUMO

Hyperglycaemia can alter placental resistance to blood flow and hyperglycaemia has adverse perinatal outcomes. Oral glucose tolerance testing (OGTT) increases the maternal plasma glucose levels temporarily and mimics metabolic hyperglycaemia. The blood flow of the uterine artery (UtA), umbilical artery (UA), middle cerebral artery (MCA) were assessed before, 1 and 2 h following the OGTT by using Doppler ultrasonography. Z-score of cerebroplacental ratio (CPR), pulsatility index (PI) for three vessels were evaluated separately. All measurements of the MCA, UA, UtA Doppler parameters were not statistically different for fasting, and 1 and 2 h following the 75 g OGTT in the 53 pregnant women with a singleton gestation in the low-risk group. This study results show that acute hyperglycaemia induced by OGTT has no effect on maternal and foetal Doppler parameters in healthy pregnancies.IMPACT STATEMENTWhat is already known on this subject? Foetal glucose is affected by maternal blood glucose concentrations and placental blood flow. Acute hyperglycaemia may have an effect on maternal, and foetal Doppler parameters among healthy pregnanciesWhat do the results of this study add? Our findings indicate that blood flow velocity metric measurements in the UA, MCA and UtA were not affected by the OGTT in healthy pregnant women.What are the implications of these findings for clinical practice and/or further research? Acute hyperglycaemia induced by OGTT does not have any effect on fetomaternal circulation, especially foetal brain blood flow. Other foetal vessels including ductus venosus, renal artery, etc. may be affected by maternal blood glucose levels during the OGTT or in diabetic patients. Future prospective studies consisting of diabetic patients are warranted to verify the exact effect of glucose levels on foetal and maternal circulation.


Assuntos
Teste de Tolerância a Glucose/efeitos adversos , Hiperglicemia/fisiopatologia , Complicações na Gravidez/fisiopatologia , Ultrassonografia Doppler , Ultrassonografia Pré-Natal , Adulto , Glicemia/metabolismo , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/efeitos dos fármacos , Artéria Cerebral Média/embriologia , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/diagnóstico por imagem , Fluxo Pulsátil , Ultrassonografia Doppler/métodos , Ultrassonografia Pré-Natal/métodos , Artérias Umbilicais/diagnóstico por imagem , Artérias Umbilicais/efeitos dos fármacos , Artérias Umbilicais/embriologia , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/efeitos dos fármacos , Artéria Uterina/embriologia , Adulto Jovem
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