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1.
Signal Transduct Target Ther ; 6(1): 427, 2021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34916489

RESUMO

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism. In this study, we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases, and found new-onset insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 infection increased the expression of RE1-silencing transcription factor (REST), which modulated the expression of secreted metabolic factors including myeloperoxidase, apelin, and myostatin at the transcriptional level, resulting in the perturbation of glucose and lipid metabolism. Furthermore, several lipids, including (±)5-HETE, (±)12-HETE, propionic acid, and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation, especially in insulin resistance. Taken together, our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19, and further illustrated the underlying mechanisms, providing potential therapeutic targets for COVID-19-induced metabolic complications.


Assuntos
COVID-19/sangue , Hiperglicemia/sangue , Resistência à Insulina , Metabolismo dos Lipídeos , Lipídeos/sangue , SARS-CoV-2/metabolismo , Adulto , Idoso , Biomarcadores/sangue , COVID-19/complicações , Feminino , Humanos , Hiperglicemia/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
PLoS One ; 16(10): e0258894, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34673829

RESUMO

INTRODUCTION: Little is known about the influence of hyperglycemia first detected in pregnancy (HFDP) on weight outcomes in exposed offspring in Africa. We investigated the influence of maternal blood glucose concentrations during pregnancy on offspring weight outcomes at birth and preschool age, in offspring exposed to HFDP, in South Africa. RESEARCH DESIGN AND METHODS: Women diagnosed with HFDP had data routinely collected during the pregnancy and at delivery, at a referral hospital, and the offspring followed up at preschool age. Maternal fasting, oral glucose tolerance test 1 and 2-hour blood glucose were measured at diagnosis of HFDP and 2-hour postprandial blood glucose during the third trimester. Offspring were classified as either those exposed to diabetes first recognized in pregnancy (DIP) or gestational diabetes (GDM). At birth, neonates were classified into macrosomia, low birth weight (LBW), large for gestational age (LGA), appropriate (AGA) and small for gestational age (SGA)groups. At preschool age, offspring had height and weight measured and Z-scores for weight, height and BMI calculated. RESULTS: Four hundred and forty-three neonates were included in the study at birth, with 165 exposed to DIP and 278 exposed to GDM. At birth, the prevalence of LGA, macrosomia and LBW were 29.6%, 12.2% and 7.5%, respectively, with a higher prevalence of LGA and macrosomia in neonates exposed to DIP. At pre-school age, the combined prevalence of overweight and obesity was 26.5%. Maternal third trimester 2-hour postprandial blood glucose was significantly associated with z-scores for weight at birth and preschool age, and both SGA and LGA at birth. CONCLUSION: In offspring exposed to HFDP, there is a high prevalence of LGA and macrosomia at birth, and overweight and obesity at preschool age, with higher prevalence in those exposed to DIP, compared to GDM. Maternal blood glucose control during the pregnancy influences offspring weight at birth and preschool age.


Assuntos
Peso ao Nascer/fisiologia , Glicemia , Peso Corporal/fisiologia , Hiperglicemia/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adulto , Pré-Escolar , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperglicemia/sangue , Recém-Nascido , Masculino , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/fisiopatologia , África do Sul , Adulto Jovem
3.
Endocrinol Diabetes Metab ; 4(4): e00291, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34505406

RESUMO

AIM: Diabetes has been identified as a risk factor for poor outcomes in patients with COVID-19. We examined the association of hyperglycaemia, both in the presence and absence of pre-existing diabetes, with severity and outcomes in COVID-19 patients. METHODS: Data from 74,148 COVID-19-positive inpatients with at least one recorded glucose measurement during their inpatient episode were analysed for presence of pre-existing diabetes diagnosis and any glucose values in the hyperglycaemic range (>180 mg/dl). RESULTS: Among patients with and without a pre-existing diabetes diagnosis on admission, mortality was substantially higher in the presence of high glucose measurements versus all measurements in the normal range (70-180 mg/dl) in both groups (non-diabetics: 21.7% vs. 3.3%; diabetics 14.4% vs. 4.3%). When adjusting for patient age, BMI, severity on admission and oxygen saturation on admission, this increased risk of mortality persisted and varied by diabetes diagnosis. Among patients with a pre-existing diabetes diagnosis, any hyperglycaemic value during the episode was associated with a substantial increase in the odds of mortality (OR: 1.77, 95% CI: 1.52-2.07); among patients without a pre-existing diabetes diagnosis, this risk nearly doubled (OR: 3.07, 95% CI: 2.79-3.37). CONCLUSION: This retrospective analysis identified hyperglycaemia in COVID-19 patients as an independent risk factor for mortality after adjusting for the presence of diabetes and other known risk factors. This indicates that the extent of glucose control could serve as a mechanism for modifying the risk of COVID-19 morality in the inpatient environment.


Assuntos
Glicemia , COVID-19/epidemiologia , Diabetes Mellitus/epidemiologia , Hiperglicemia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , COVID-19/mortalidade , Diabetes Mellitus/sangue , Diabetes Mellitus/mortalidade , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
5.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575946

RESUMO

It has become widely accepted that insulin resistance and glucose hypermetabolism can be linked to acute pathologies, such as burn injury, severe trauma, or sepsis. Severe burns can determine a significant increase in catabolism, having an important effect on glucose metabolism and on muscle protein metabolism. It is imperative to acknowledge that these alterations can lead to increased mortality through organ failure, even when the patients survive the initial trauma caused by the burn. By limiting the peripheral use of glucose with consequent hyperglycemia, insulin resistance determines compensatory increased levels of insulin in plasma. However, the significant alterations in cellular metabolism lead to a lack of response to insulin's anabolic functions, as well as to a decrease in its cytoprotective role. In the end, via pathological insulin signaling associated with increased liver gluconeogenesis, elevated levels of glucose are detected in the blood. Several cellular mechanisms have been incriminated in the development of insulin resistance in burns. In this context, the main aim of this review article is to summarize some of the drugs that might interfere with insulin resistance in burns, taking into consideration that such an approach can significantly improve the prognosis of the burned patient.


Assuntos
Queimaduras/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Resistência à Insulina/genética , Sepse/tratamento farmacológico , Queimaduras/sangue , Queimaduras/patologia , Glucose/metabolismo , Humanos , Hiperglicemia/sangue , Hiperglicemia/patologia , Insulina/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Sepse/sangue , Sepse/patologia , Índice de Gravidade de Doença
6.
Nutrients ; 13(9)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34578888

RESUMO

We aimed to study the possible association of stress hyperglycemia in COVID-19 critically ill patients with prognosis, artificial nutrition, circulating osteocalcin, and other serum markers of inflammation and compare them with non-COVID-19 patients. Fifty-two critical patients at the intensive care unit (ICU), 26 with COVID-19 and 26 non-COVID-19, were included. Glycemic control, delivery of artificial nutrition, serum osteocalcin, total and ICU stays, and mortality were recorded. Patients with COVID-19 had higher ICU stays, were on artificial nutrition for longer (p = 0.004), and needed more frequently insulin infusion therapy (p = 0.022) to control stress hyperglycemia. The need for insulin infusion therapy was associated with higher energy (p = 0.001) and glucose delivered through artificial nutrition (p = 0.040). Those patients with stress hyperglycemia showed higher ICU stays (23 ± 17 vs. 11 ± 13 days, p = 0.007). Serum osteocalcin was a good marker for hyperglycemia, as it inversely correlated with glycemia at admission in the ICU (r = -0.476, p = 0.001) and at days 2 (r = -0.409, p = 0.007) and 3 (r = -0.351, p = 0.049). In conclusion, hyperglycemia in critically ill COVID-19 patients was associated with longer ICU stays. Low circulating osteocalcin was a good marker for stress hyperglycemia.


Assuntos
COVID-19/sangue , Hiperglicemia/sangue , Osteocalcina/sangue , Nutrição Parenteral/mortalidade , SARS-CoV-2 , Idoso , Biomarcadores/sangue , COVID-19/complicações , COVID-19/mortalidade , Resultados de Cuidados Críticos , Estado Terminal/mortalidade , Feminino , Humanos , Hiperglicemia/mortalidade , Hiperglicemia/virologia , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Am J Physiol Heart Circ Physiol ; 321(5): H920-H932, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533398

RESUMO

Bone marrow-derived endothelial progenitor cells (EPCs) contribute to endothelial repair and angiogenesis. Reduced number of circulating EPCs is associated with future cardiovascular events. We tested whether dysregulated glucose and/or triglyceride (TG) metabolism has an impact on EPC homeostasis. The analysis of metabolic factors associated with circulating EPC number in humans revealed that postprandial hyperglycemia is negatively correlated with circulating EPC number, and this correlation appears to be further enhanced in the presence of postprandial hypertriglyceridemia (hTG). We therefore examined the effect of glucose/TG spikes on bone marrow lineage-sca-1+ c-kit+ (LSK) cells in mice, because primitive EPCs reside in bone marrow LSK fraction. Repetitive glucose + lipid (GL) spikes, but not glucose (G) or lipid (L) spikes alone, induced senescence-like phenotypes of LSK cells, and this phenomenon was reversible after cessation of GL spikes. G spikes and GL spikes differentially affected transcriptional program of LSK cell metabolism and differentiation. GL spikes upregulated a histone H3K27 demethylase JMJD3, and inhibition of JMJD3 eliminated GL spikes-induced LSK cell senescence-like phenotypes. These observations suggest that postprandial glucose/TG dysmetabolism modulate transcriptional regulation in LSK cells through H3K27 demethylase-mediated epigenetic regulation, leading to senescence-like phenotypes of LSK cells, reduced number of circulating EPCs, and development of atherosclerotic cardiovascular disease.NEW & NOTEWORTHY Combination of hyperglycemia and hypertriglyceridemia is associated with increased risk of atherosclerotic cardiovascular disease. We found that 1) hypertriglyceridemia may enhance the negative impact of hyperglycemia on circulating EPC number in humans and 2) metabolic stress induced by glucose + triglyceride spikes in mice results in senescence-like phenotypes of bone marrow stem/progenitor cells via H3K27me3 demethylase-mediated epigenetic regulation. These findings have important implications for understanding the pathogenesis of atherosclerotic cardiovascular disease in patients with T2DM.


Assuntos
Glicemia/metabolismo , Células da Medula Óssea/enzimologia , Senescência Celular , Metilação de DNA , Diabetes Mellitus Tipo 2/sangue , Células Progenitoras Endoteliais/enzimologia , Epigênese Genética , Hiperglicemia/sangue , Hipertrigliceridemia/sangue , Histona Desmetilases com o Domínio Jumonji/metabolismo , Triglicerídeos/sangue , Adulto , Idoso , Animais , Células da Medula Óssea/patologia , Estudos de Casos e Controles , Linhagem da Célula , Células Cultivadas , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Feminino , Hemoglobina A Glicada , Humanos , Hiperglicemia/enzimologia , Hiperglicemia/genética , Hiperglicemia/patologia , Hipertrigliceridemia/enzimologia , Hipertrigliceridemia/genética , Hipertrigliceridemia/patologia , Histona Desmetilases com o Domínio Jumonji/genética , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fenótipo
8.
Int J Mol Sci ; 22(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34502172

RESUMO

Vascular calcification associated with high plasma phosphate (Pi) level is a frequent complication of hyperglycemia, diabetes mellitus, and chronic kidney disease. BGP-15 is an emerging anti-diabetic drug candidate. This study was aimed to explore whether BGP-15 inhibits high Pi-induced calcification of human vascular smooth muscle cells (VSMCs) under normal glucose (NG) and high glucose (HG) conditions. Exposure of VSMCs to Pi resulted in accumulation of extracellular calcium, elevated cellular Pi uptake and intracellular pyruvate dehydrogenase kinase-4 (PDK-4) level, loss of smooth muscle cell markers (ACTA, TAGLN), and enhanced osteochondrogenic gene expression (KLF-5, Msx-2, Sp7, BMP-2). Increased Annexin A2 and decreased matrix Gla protein (MGP) content were found in extracellular vesicles (EVs). The HG condition markedly aggravated Pi-induced VSMC calcification. BGP-15 inhibited Pi uptake and PDK-4 expression that was accompanied by the decreased nuclear translocation of KLF-5, Msx-2, Sp7, retained VSMC markers (ACTA, TAGLN), and decreased BMP-2 in both NG and HG conditions. EVs exhibited increased MGP content and decreased Annexin A2. Importantly, BGP-15 prevented the deposition of calcium in the extracellular matrix. In conclusion, BGP-15 inhibits Pi-induced osteochondrogenic phenotypic switch and mineralization of VSMCs in vitro that make BGP-15 an ideal candidate to attenuate both diabetic and non-diabetic vascular calcification.


Assuntos
Hiperglicemia/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Oximas/farmacologia , Fosfatos/metabolismo , Piperidinas/farmacologia , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Biomarcadores , Glicemia , Células Cultivadas , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Hiperglicemia/sangue , Osteoblastos/metabolismo , Fosfatos/efeitos adversos , Calcificação Vascular/tratamento farmacológico
9.
Diabetes Metab Syndr ; 15(5): 102244, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34425556

RESUMO

BACKGROUND: We aim to provide a practical guidance on the use of intravenous insulin infusion for managing inpatient hyperglycemia. METHODS AND RESULTS: This document was formulated based on the review of available literature and personal experience of authors. We have used various case scenarios to illustrate variables which should be taken into account when deciding adjustments in infusion rate, including but not restricted to ambient blood glucose level and magnitude of blood glucose change in the previous hour. CONCLUSION: The guidance can be generalized to any situation where dedicated protocols are lacking, trained manpower is not available and resource constraints are present.


Assuntos
Hospitalização , Hiperglicemia/tratamento farmacológico , Insulina/administração & dosagem , Glicemia/metabolismo , Controle Glicêmico/métodos , Controle Glicêmico/normas , Humanos , Hiperglicemia/sangue , Infusões Intravenosas , Pacientes Internados , Guias de Prática Clínica como Assunto
10.
Nutrients ; 13(8)2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34445047

RESUMO

Sargassum fusiforme alginate (SF-Alg) possess many pharmacological activities, including hypoglycemic and hypolipidemic. However, the hypoglycemic mechanisms of SF-Alg remain unclear due to its low bioavailability. In this study, we evaluated the therapeutic effect of SF-Alg on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. SF-Alg intervention was found to significantly reduce fasting blood glucose (FBG), triglycerides (TG), and total cholesterol (TC), while increasing high-density lipoprotein cholesterol (HDL-c) and improving glucose tolerance. In addition, administrating SF-Alg to diabetic mice moderately attenuated pathological changes in adipose, hepatic, and heart tissues as well as skeletal muscle, and diminished oxidative stress. To probe the underlying mechanisms, we further analyzed the gut microbiota using 16S rRNA amplicon sequencing, as well as metabolites by non-targeted metabolomics. Here, SF-Alg significantly increased some benign bacteria (Lactobacillus, Bacteroides, Akkermansia Alloprevotella, Weissella and Enterorhabdus), and significantly decreased harmful bacteria (Turicibacter and Helicobacter). Meanwhile, SF-Alg dramatically decreased branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the colon of T2D mice, suggesting a positive benefit of SF-Alg as an adjvant agent for T2D.


Assuntos
Alginatos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Sargassum/química , Animais , Glicemia/efeitos dos fármacos , Colesterol/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/etiologia , Camundongos , Estreptozocina , Triglicerídeos/sangue
11.
Med Sci Monit ; 27: e932156, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34362862

RESUMO

BACKGROUND Diabetes is one of the most commonly reported comorbidities among patients infected with SARS-CoV-2. This retrospective study of patients with SARS-CoV-2 infection was conducted to evaluate the association between blood glucose levels and the severity of COVID-19 pneumonia and patient mortality. MATERIAL AND METHODS A total of 268 patients with confirmed SARS-CoV-2 infection were included in this retrospective study. We obtained demographic characteristics, clinical symptoms, laboratory data, and survival information from patients' electronic medical records. Blood glucose was measured on admission to the hospital. Comorbidities, including hypertension, diabetes, chronic kidney disease, chronic liver disease, chronic obstructive pulmonary disease, and cardiovascular disease, were collected by self-reported medical history. RESULTS Significantly higher risks of severe COVID-19 were found in patients with blood glucose levels ranging from 5.53 to 7.27 mmol/L (odds ratio [OR], 3.98; 95% confidence interval [CI], 1.81-8.75) and in patients with blood glucose ≥7.27 mmol/L (OR, 12.10; 95% CI, 5.53-26.48) than in those with blood glucose <5.53 mmol/L. There was a trend toward better survival in patients with blood glucose <5.53 mmol/L than in patients with blood glucose from 5.53 to 7.27 mmol/L (hazard ratio [HR], 6.34; 95% CI, 1.45-27.71) and ≥7.27 mmol/L (HR, 19.37; 95% CI, 4.68-80.17). Estimated 10-day overall survival rates were 96.8%, 90.6%, and 69.3% in patients with blood glucose <5.53 mmol/L, 5.53 to 7.27 mmol/L, and ³7.27 mmol/L, respectively. CONCLUSIONS Hyperglycemia was association with severity of COVID-19 pneumonia and with increased patient mortality. These findings support the need for blood glucose monitoring and control of hyperglycemia in patients with COVID-19 pneumonia.


Assuntos
Glicemia/metabolismo , COVID-19/sangue , Hiperglicemia/virologia , Adulto , Idoso , Automonitorização da Glicemia , COVID-19/metabolismo , COVID-19/patologia , COVID-19/virologia , Comorbidade , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Hiperglicemia/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Taxa de Sobrevida
12.
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
13.
J Korean Med Sci ; 36(27): e190, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34254474

RESUMO

We investigated the relationship between glucose variability and frailty. Forty-eight type 2 diabetic patients aged ≥ 65 years were enrolled. The FRAIL scale was used for frailty assessment, and participants were classified into 'healthy & pre-frail' (n = 24) and 'frail' (n = 24) groups. A continuous glucose monitoring (CGM) system was used for a mean of 6.9 days and standardized CGM metrics were analyzed: mean glucose, glucose management indicator (GMI), coefficient of variation, and time in range, time above range (TAR), and time below range. The demographics did not differ between groups. However, among the CGM metrics, mean glucose, GMI, and TAR in the postprandial periods were higher in the frail group (all P < 0.05). After multivariate adjustments, the post-lunch TAR (OR = 1.12, P = 0.019) affected the prevalence of frailty. Higher glucose variability with marked daytime postprandial hyperglycemia is significantly associated with frailty in older patients with diabetes.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/sangue , Hipoglicemiantes/uso terapêutico , Monitorização Fisiológica/métodos , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Fragilidade , Geriatria , Hemoglobina A Glicada/análise , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/epidemiologia , Insulina , Masculino , Projetos Piloto
14.
Biomed Pharmacother ; 139: 111668, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243630

RESUMO

Metabolic Syndrome (MetS) is a complex and multifactorial condition often characterised by obesity, hypertension, hyperlipidaemia, insulin resistance, glucose intolerance and fasting hyperglycaemia. Collectively, MetS can increase the risk of atherosclerotic-cardiovascular disease, which is the leading cause of death worldwide. However, no animal model currently exists to study MetS in the context of atherosclerosis. In this study we developed a pre-clinical mouse model that recapitulates the spectrum of MetS features while developing atherosclerosis. When BPHx mice were placed on a western type diet for 16 weeks, all the classical characteristics of MetS were observed. Comprehensive metabolic analyses and atherosclerotic imaging revealed BPHx mice to be obese and hypertensive, with elevated total plasma cholesterol and triglyceride levels, that accelerated atherosclerosis. Altogether, we demonstrate that the BPHx mouse has all the major components of MetS, and accelerates the development of atherosclerosis.


Assuntos
Aterosclerose/patologia , Dieta/efeitos adversos , Hipertensão/patologia , Síndrome Metabólica/patologia , Animais , Aterosclerose/sangue , Aterosclerose/metabolismo , Glicemia/metabolismo , Colesterol/sangue , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/metabolismo , Intolerância à Glucose/patologia , Hipercolesterolemia/sangue , Hipercolesterolemia/metabolismo , Hipercolesterolemia/patologia , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperlipidemias/sangue , Hiperlipidemias/metabolismo , Hiperlipidemias/patologia , Hipertensão/sangue , Hipertensão/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Obesidade/metabolismo , Obesidade/patologia , Triglicerídeos/sangue
15.
Endocrinol Diabetes Metab ; 4(3): e00279, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34277995

RESUMO

Aims: To evaluate the frequency of diabetes and admission hyperglycaemia in Mexican COVID-19 patients, to describe the clinical and biochemical characteristics of patients with admission hyperglycaemia and to determinate the impact of diabetes and admission hyperglycaemia on COVID-19 severity and mortality. Methods: A multicentric study was performed in 480 hospitalized patients with COVID-19. Clinical and biochemical characteristics were evaluated in patients with admission hyperglycaemia and compared with non-hyperglycaemic patients. The effect of diabetes and admission hyperglycaemia on severity and risk of death were evaluated. Results: Age was 50.7 ± 13.6 years; 68.3% were male. Some 48.5% (n = 233) had admission hyperglycaemia; 29% (n = 139) of these patients had pre-existing diabetes. Patients with admission hyperglycaemia had more requirement of invasive mechanical ventilation (IMV), higher levels of urea, D-dimer and neutrophil-lymphocyte ratio (NLR), as well as lower lymphocyte count. An association between admission hyperglycaemia with IMV and D-dimer with glucose was found. Age ≥50 years (OR 2.09; 95%CI 1.37-3.17), pre-existing diabetes (OR 2.38; 95%CI 1.59-5.04) and admission hyperglycaemia (OR 8.24; 95%CI 4.74-14.32) were risk factors for mortality. Conclusions: Admission hyperglycaemia is presented in 48.5% of COVID-19 patients. Diabetes and admission hyperglycaemia are associated with the severity of disease and mortality. This study shows the devastating conjunction of hyperglycaemia and COVID-19. Clinical trial registration: Clinical characteristics of patients with COVID-19, DI/20/204/04/41 (Hospital General de Mexico) and NR-13-2020 (Hospital Regional de Alta Especialidad Ixtapaluca).


Assuntos
Glicemia , COVID-19/mortalidade , Diabetes Mellitus/epidemiologia , Hiperglicemia/mortalidade , COVID-19/sangue , Diabetes Mellitus/sangue , Humanos , Hiperglicemia/sangue , Taxa de Sobrevida
16.
Mutat Res Rev Mutat Res ; 787: 108369, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34083054

RESUMO

Micronucleus assay has been used as a biomarker of DNA damage, chromosomal instability, cancer risk and accelerated aging. In this review, a meta-analysis was performed to assess the association between micronuclei (MNi) and diseases with increased advanced glycation end products (AGEs) and HbA1c. The review identified eight studies with 632 subjects with disease and 547 controls. The Mean Ratio (MRi) for AGE levels (MRi = 2.92, 95 %CI: 2.06-4.13, P < 0.00001) and HbA1c levels (MRi = 1.32, 95 %CI: 1.12-1.56, P = 0.001) were significantly higher in the disease group compared to healthy controls. The meta-analysis indicated that the overall estimates of MRi for MNi was 1.83 (95 %CI: 1.38-2.42, p < 0.0001) in subjects with disease compared to controls. Significant increases in MRi for MNi were also observed in the following sub-groups: subjects with disease for elevated AGEs (MRi = 1.62, 95 %CI: 1.12-2.35, P = 0.01), elevated HbA1c (MRi = 2.13, 95 %CI: 1.33-3.39, P = 0.002), lymphocytes MNi (MRi = 1.74, 95 %CI: 1.29-2.33, P = 0.0003), exfoliated buccal cells MNi (MRi = 2.86, 95 %CI: 1.19-6.87, P = 0.02), type 2 diabetes mellitus (T2DM) (MRi = 1.99, 95 %CI: 1.17-3.39, P = 0.01), chronic renal disease (MRi = 1.68, 95 %CI: 1.18-2.38, P = 0.004) and other disease groups (MRi = 2.52, 95 %CI: 1.28-4.96, P = 0.008). The results of this review suggest that MNi could be used as a biomarker of DNA damage and chromosomal instability in degenerative disease where increased AGEs and HbA1c are implicated. The lack of heterogeneity for MN frequency when considered either for all studies or subgroup strengthened the MRi of the meta-analysis. However, the lack of significant association between MRi for MNi and MRi for AGEs or HbA1c indicates that the case-control studies investigated may be confounded by other variables. Thus, larger studies with long term AGE exposure is warranted to further understand the role of MN formation in the initiation and progression of diseases caused by excessive glycation.


Assuntos
Biomarcadores/metabolismo , Hiperglicemia/metabolismo , Animais , Hemoglobina A Glicada/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hiperglicemia/sangue , Testes para Micronúcleos
17.
Sci Rep ; 11(1): 11666, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083675

RESUMO

The exposure to extremely low-frequency electromagnetic fields (EMFs) could adversely affect the endocrine system and cellular proliferative response. Nonetheless, the use of 60-Hz EMFs in the form of magneto-therapy exerts beneficial actions on human health but can also induce hyperglycaemia. Therefore, the present study was aimed to search for metabolic responses of fed or fasted male rats to a single EMF exposure. We performed a 15 min-single exposure to 60-Hz (3.8 mT, intensity) EMF, and determined serum levels of glucose, lipids, and indicators of cellular redox state and energy parameters. A single exposure to a 60-Hz EMF induced hyperglycaemia in both animal groups, and an attenuated second serum insulin peak. The 60-Hz EMF also decreased free fatty acids and lactate serum levels, oppositely increasing pyruvate and acetoacetate levels. Significant increases in blood glucose level and rat's glucose metabolism were related to a more oxidized cellular redox state and variations in insulin and glucagon secretion. The 60-Hz EMF's effects were not modified in animals previously subjected to chronic EMFs exposure (14 days). In conclusion, increased serum glucose levels and glucose metabolism induced by a single 60-Hz EMF exposure were closely related to the cellular redox state and the insulin/glucagon ratio.


Assuntos
Campos Eletromagnéticos/efeitos adversos , Glucagon/sangue , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Insulina/sangue , Animais , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metabolismo Energético , Jejum , Hiperglicemia/sangue , Ácido Láctico/sangue , Lipídeos/sangue , Metabolômica , Oxirredução , Ácido Pirúvico/sangue , Ratos
18.
Food Funct ; 12(14): 6540-6548, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34096954

RESUMO

INTRODUCTION: Postprandial hyperglycemia is a risk factor for type 2 diabetes. Insulin resistance (IR) might affect metabolic responses in non-fasting states. Dietary intake and food composition influence postprandial glucose homeostasis. The aims of this study were to evaluate the effects of different test foods varying in the macronutrient composition on postprandial glycemic responses and whether these outcomes are conditioned by the basal glycemic status in senior subjects. METHODS: In a randomized, controlled crossover design, thirty-four adults consumed a test food, a high protein product (n = 19) or a high carbohydrate (CHO) product (n = 15), using the oral glucose tolerance test (OGTT) as a reference. Blood glucose and insulin were measured at fasting and at 15, 30, 45, 60, 90, and 120 min after starting the food intake. For each type of food, the incremental area under the curve (iAUC) for glucose and insulin was calculated. IR was measured using the Homeostatic Model Assessment of IR (HOMA-IR). RESULTS: Consumption of a high protein product significantly lowered the peak and Δ blood glucose concentrations compared to the high CHO product (p < 0.001). Concerning the insulin response, no significant differences between both foods were observed. Fasting glucose was positively correlated with the glucose iAUC only for the high protein product. Positive associations of both fasting insulin and HOMA-IR with the insulin iAUC for all the cases were observed. Linear regression models showed significant positive associations between the glucose iAUC and fasting glucose after adjusting for age and sex. Regarding the insulin iAUC, positive associations were found with fasting insulin and HOMA-IR. Regression models also evidenced that both food test consumptions were able to decrease the glucose and insulin iAUC values when compared with the OGTT product. CONCLUSION: Our research found that not only is the nutritional composition of foods important, but also the baseline glycemic state of individuals when assessing glycemic index estimations and addressing precision nutritional strategies to prevent and treat IR-associated disturbances.


Assuntos
Dieta/métodos , Jejum , Hiperglicemia/dietoterapia , Resistência à Insulina , Nutrientes/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Glicemia/análise , Estudos Cross-Over , Diabetes Mellitus Tipo 2/epidemiologia , Carboidratos da Dieta/administração & dosagem , Proteínas na Dieta/administração & dosagem , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Índice Glicêmico , Humanos , Hiperglicemia/sangue , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial
19.
Sci Rep ; 11(1): 12002, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099748

RESUMO

To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000-1.630, p = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012-1.674, p = 0.040) in multi-variate regression tests. Kaplan-Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group (p < 0.001), and subsequent multivariate Cox proportional analyses revealed that high hemoglobin A1c is an independent predictor for shorter BCR-free survival (HR 1.135, 95% CI 1.016-1.267, p = 0.024). Moreover, the high hemoglobin A1c group showed a significantly longer incontinence-free survival than the low hemoglobin A1c group (p = 0.001), and high preoperative hemoglobin A1c was also an independent predictor for longer incontinence-free survival in multivariate Cox analyses (HR 0.929, 95% CI 0.879-0.981, p = 0.008). The high preoperative hemoglobin A1c level was independently associated with worse oncological outcomes and also with inferior recovery of urinary continence after radical prostatectomy.


Assuntos
Hemoglobina A Glicada/genética , Hiperglicemia/complicações , Recidiva Local de Neoplasia/complicações , Prostatectomia/métodos , Neoplasias da Próstata/complicações , Incontinência Urinária/complicações , Idoso , Glicemia/metabolismo , Seguimentos , Hemoglobina A Glicada/metabolismo , Controle Glicêmico/métodos , Humanos , Hiperglicemia/sangue , Hiperglicemia/mortalidade , Hiperglicemia/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Análise de Sobrevida , Resultado do Tratamento , Incontinência Urinária/sangue , Incontinência Urinária/mortalidade , Incontinência Urinária/cirurgia
20.
JAMA ; 325(22): 2273-2284, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34077502

RESUMO

Importance: Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking. Objective: To estimate clinical outcomes of real-time CGM initiation. Design, Setting, and Participants: Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-in-differences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included. Exposures: Initiation vs noninitiation of real-time CGM (reference group). Main Outcomes and Measures: Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A1c (HbA1c); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits. Results: The real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, -0.40%; 95% CI, -0.48% to -0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, -2.7%; 95% CI, -4.4% to -1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, -7.1%; 95% CI, -9.5% to -4.6%; P < .001) and in the number of outpatient visits (adjusted difference-in-differences estimate, -0.4; 95% CI, -0.6 to -0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason. Conclusions and Relevance: In this retrospective cohort study, insulin-treated patients with diabetes selected by physicians for real-time continuous glucose monitoring compared with noninitiators had significant improvements in hemoglobin A1c and reductions in emergency department visits and hospitalizations for hypoglycemia, but no significant change in emergency department visits or hospitalizations for hyperglycemia or for any reason. Because of the observational study design, findings may have been susceptible to selection bias.


Assuntos
Técnicas Biossensoriais/métodos , Automonitorização da Glicemia/métodos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Adulto , Técnicas Biossensoriais/instrumentação , Automonitorização da Glicemia/estatística & dados numéricos , Intervalos de Confiança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobina A Glicada/análise , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/sangue , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Hipoglicemia/sangue , Hipoglicemia/diagnóstico , Hipoglicemia/epidemiologia , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Números Necessários para Tratar , Pontuação de Propensão , Estudos Retrospectivos , Viés de Seleção , Fatores de Tempo , Resultado do Tratamento
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