What is Glycaemic Variability and which Pharmacological Treatment Options are Effective? A Narrative Review.

Glycated haemoglobin is currently used for diagnosis and follow-up of diabetes mellitus. However, it has important limitations; as it only reflects the average glycaemia over the last 3 months, it does not allow the identification of crucial events, such as episodes of hypoglycaemia and hyperglycaemia. Strict control of hyperglycaemia can result in severe hypoglycaemia that can be life threatening and can have important sequelae. Recently, the concept of glycaemic variability has been developed to provide information about the magnitude of glycaemic excursions and the duration of these fluctuations. This new approach has the potential to improve outcomes, decrease the risk of hypoglycaemia, and decrease cardiovascular risk. This review describes the most commonly prescribed non-insulin anti-diabetic drugs for diabetes management, their mechanism of action, and the existing evidence about their effectiveness in improving glycaemic variability and diabetes control.

Macrovascular and microvascular type 2 diabetes complications are interrelated in a mouse model.

AIM: Evaluate the development of multiple complications, their interactions, and common mechanisms in the same individual with T2D. MATERIAL AND METHODS: 4-week-old male C57BL/6J mice were divided into: control (n = 6) and T2D (n = 6). T2D was induced through a high-carbohydrate-diet and low doses of streptozotocin. T2D was validated by metabolic parameters. Diabetic neuropathy was evaluated by mechanical and thermal sensitivity tests. We performed a histopathological analysis of the heart, kidney, liver, and parotid salivary glands and changes in bone microarchitecture by µCT. We calculated the relative risk (RR), odd ratios (OR) and Pearson correlation coefficients between the different complications and metabolic features. RESULTS: T2D mice have cardiomyopathy, neuropathy, nephropathy, liver steatosis and fibrosis, structural damage in parotid salivary glands, and bone porosity. RR analysis shows that all complications are interrelated by hyperglycaemia, insulin resistance, obesity, and systemic inflammation. CONCLUSIONS: T2D mice develop multiple complications simultaneously, which are related to each other, and this is associated with metabolic alterations. Our findings open up new approaches for the study and new therapeutic approaches of the pathophysiology of T2D and its complications.

Effect of taurine on glycaemic, lipid and inflammatory profile in individuals with type 2 diabetes: study protocol of a randomised trial.

Type 2 diabetes mellitus (T2DM) is characterised by chronic hyperglycaemia. Despite the efficacy of conventional pharmacotherapy, some individuals do not reach glycaemic goals and require adjuvant therapies. Taurine, a semi-essential amino acid, decreases blood glucose and cholesterol levels in rodents and humans. However, glycated hemoglobin (HbA1c) has not been evaluated in randomised controlled trials after taurine treatment for more than 12 weeks. This study aims to evaluate the effect of taurine administration on glycaemic, lipid, inflammatory, anthropometric and dietary parameters in individuals with T2DM. A randomised, double-blind, placebo-controlled clinical trial will be conducted at the Clinical Research Center of a tertiary public hospital. Participants with T2DM (n 94) will be recruited and randomised to receive 3 g of taurine or placebo, twice/day, orally, for 12 weeks. Blood samples will be collected before and after 12 weeks of treatment, when HbA1c, fasting glucose, insulin, albuminuria, creatinine, total cholesterol and fractions, triglycerides, C-reactive protein, TNF-α, IL 1, 4, 5, 6, 10 and 13 will be evaluated. Anthropometric parameters and 24-hour food recall will also be evaluated. The study will evaluate the effect of taurine treatment on biochemical and anthropometric parameters in individuals with T2DM. These results will guide the decision-making to indicate taurine treatment as an adjunct in individuals with T2DM who have not reached their glycaemic goal.

Comparative study of dietary fat: lard and sugar as a better obesity and metabolic syndrome mice model.

BACKGROUND: Diet macronutrient heterogeneity hinders animal studies' data extrapolation from metabolic disorders to human diseases. OBJECTIVE: The present study aimed to evaluate different fat-diet compositions' effect on inducing lipid/glucose metabolism alterations in mice. METHODS: Swiss male mice were fed for 12 weeks with five different diets: Standard Diet (ST), American Institute of Nutrition 93 for growth (AIN93G) high-butter/high-sugar (HBHS), high-lard/high-sugar (HLHS), and high-oil/high-sugar diet (soybean oil) (HOHS). Several parameters, such as serum biochemistry, histology, and liver mRNA expression, were accessed. RESULTS: The main findings revealed that the HLHS diet dramatically altered liver metabolism inducing hepatic steatosis and increased total cholesterol, triglycerides, VLDL, increasing liver CCAAT/enhancer binding protein (CEBP-α), Acetyl-CoA carboxylase (ACC) and Catalase (CAT) mRNA expression. Moreover, the HLHS diet increased glucose intolerance and reduced insulin sensitivity. CONCLUSIONS: High-fat/high-sugar diets are efficient to induce obesity and metabolic syndrome-associated alterations, and diets enriched with lard and sugar showed more effective results.

Cyperus esculentus L. protects testis and sperm morphology of hyperglycaemic rats / Cyperus esculentus L. protege la morfología de los testículos y los espermatozoides de ratas hiperglicémicas

Cyperus esculentus L. (tiger nut) is a tuberous plant that promotes and protects reproductive functions, which are usually hampered in diabetics. The present study investigated the effect of Cyperus esculentus tuber extract (CETE) on testicular histology and sperm viability of alloxan-induced hyperglycaemic Wistar rats. Twenty-five adult male Wistar rats weighing 150-200g and grouped into five (n=5): Group 1, the control, administered tap water (20mL/kg), while groups 2-5 were administered a single intraperitoneal dose (120mg/kg b.w.) of alloxan, and each further received orally tap water (20mL/kg), CETE (100mg/kg), CETE (500 mg/kg) and metformin (500 mg/kg), respectively for 21 days. The animals were sacrificed, their sperm collected for analysis, while the testes were harvested, and processed for histology. Results showed significantly increased (p<0.05) blood glucose and testosterone, and significantly decreased (p<0.05) sperm pH, motility, count, morphology and density, as well as disruptions and hypertrophy of the spermatogenic and Sertoli cells of the hyperglycaemic group. There were significant (p<0.05) blood glucose decline, while the sperm parameters and testicular weight improved with normal testicular histology in the 100 mg/kg CETE, 500 mg/kg CETE, and metformin-treated groups compared to the control and hyperglycaemic group. Treatment with CETE showed blood glucose amelioration and improved sperm quality, as well as testicular damage attenuation.

Cyperus esculentus L. es una planta tuberosa que promueve y protege las funciones reproductivas, que generalmente se ven afectadas en los diabéticos. El presente estudio investigó el efecto del extracto de tubérculo de Cyperus esculentus (CETE) sobre la histología testicular y la viabilidad de los espermatozoides de ratas wistar con hiperglicemia inducida por alloxan. Veinticinco ratas Wistar macho adultas que pesaban 150-200 g y se agruparon en cinco (n = 5): el grupo 1, el control, administró agua del grifo (20ml / kg), mientras que los grupos 2-5 se les administró una dosis intraperitoneal única (120 mg / kg p.v.) de alloxan, y agua del grifo por vía oral (20ml/kg), CETE (100 mg/kg), CETE (500 mg/kg) y metformina (500 mg/kg), respectivamente durante 21 días. Los animales fueron sacrificados, su esperma recolectada para su análisis, mientras que los testículos fueron retirados y procesados para histología. Los resultados mostraron un aumento significativo (p<0,05) de la glucosa en sangre y la testosterona, y una disminución significativa (p<0,05) del pH, la motilidad, el recuento, la morfología y la densidad de los espermatozoides, así como interrupciones e hipertrofia de las células espermatogénicas y sertoli del grupo hiperglucémico. Hubo una disminución significativa (p<0,05) de la glucosa en sangre, mientras que los parámetros espermáticos y el peso testicular mejoraron con la histología testicular normal en los grupos de 100 mg / kg de CETE, 500 mg / kg de CETE y tratados con metformina en comparación con el grupo de control e hiperglucémico. El tratamiento con CETE mostró una mejora de la glucosa en sangre y una mejora de la calidad de los espermatozoides, así como atenuación del daño testicular.

Enrichment of sulphate-reducers and depletion of butyrate-producers may be hyperglycaemia signatures in the diabetic oral microbiome.

Objectives: This study aimed to investigate oral microbial signatures associated with hyperglycaemia, by correlating the oral microbiome with three glycaemic markers. Potential association between clinical parameters and oral bacterial taxa that could be modulating the hyperglycaemic microbiome was also explored. Methods: Twenty-three individuals diagnosed with type 2 Diabetes Mellitus (T2D) and presenting periodontitis were included, as well as 25 systemically and periodontally healthy ones. Fasting blood glucose, glycated haemoglobin, salivary glucose, periodontitis classification, caries experience and activity and salivary pH were evaluated. The V4 region of the 16S rRNA gene was amplified from total salivary DNA, and amplicons were sequenced (Illumina MiSeq). Results: Hyperglycaemia was correlated with proportions of Treponema, Desulfobulbus, Phocaiecola and Saccharimonadaceae. Desulfobulbus was ubiquitous and the most enriched organism in T2D individuals (log2FC = 4). The Firmicutes/Bacteroidetes ratio was higher at alkali salivary pH than acidic pH. In the network analysis, Desulfobulbus was clustered in a negative association with caries-associated and butyrate-producing bacteria. Conclusion: The salivary microbiome is shaped by systemic hyperglycaemia, as well as changes in the salivary pH, which may be linked to local hyperglycaemia. The enrichment of predictive biomarkers of gut dysbiosis in the salivary microbiome can reflect its capacity for impairment of hyperglycaemia.

Effects of diabetes mellitus on dental pulp: A systematic review of in vivo and in vitro studies.

OBJECTIVES: This systematic review (PROSPERO CRD42021227711) evaluated the influence of diabetes mellitus (DM) on the response of the pulp tissue and in the pulp cells behaviour. MATERIALS AND METHODS: Searches in PubMed/MEDLINE, Embase, Web of Science and OpenGrey were performed until March 2022. Studies evaluating the effects of DM in the pulp tissue inflammation and in the cell behaviour were included, followed by risk of bias assessment (Methodological Index for Non-Randomized Studies and SYRCLE's RoB tools). The meta-analysis was unfeasible, and a narrative synthesis for each outcome was provided. RESULTS: Of the 615 studies, 21 were eligible, mainly with in vivo analysis (16 studies). The pulp inflammation (10 studies) was analysed mainly by haematoxylin-eosin stain; DM increased pulp inflammation/degeneration in 9 studies, especially after dental procedures. The cell viability (5 studies) was analysed mostly using MTT assay; DM and glycating agents decreased cellular viability in 3 studies. DM reduced collagen in all of three studies. There were controversial results regarding mineralization; however, increased alkaline phosphatase was reported in three of four studies. CONCLUSIONS: DM seems to increase inflammation/degeneration and mineralization in the pulp tissue while reducing cell proliferation. Further analyses in human pulp are important to provide stronger evidence.

Selenium intake is not associated with the metabolic syndrome in Brazilian adolescents: an analysis of the Study of Cardiovascular Risk Factors in Adolescents.

Se reduces cellular inflammation and lipid peroxides; therefore, its association with CVD and the metabolic syndrome (MetS) has been studied. We aimed to investigate the association between Se intake and the MetS and its parameters (high waist circumference, hyperglycaemia, high blood pressure, high TAG and low HDL-cholesterol) in Brazilian adolescents between 12 and 17 years old. This research is part of the Study of Cardiovascular Risks in Adolescents (ERICA), a Brazilian nationwide school-based study with regional and national relevance. We assessed: (1) socio-demographic data (sex, age, type of school and maternal education) using a self-administered questionnaire; (2) dietary intake using a 24-h recall applied for the whole sample and a second one applied to a subsample to allow within-person variability adjustment; (3) anthropometric data (weight, height, waist circumference) and blood pressure using standardised procedures; and (4) biochemical analyses (fasting glucose, TAG and HDL-cholesterol). Logistic regression was applied, basing the analysis on a theoretical model. Median Se intake was 98·3 µg/d. Hypertension and hyperglycaemia were more prevalent among boys, while a high waist circumference was more frequent in girls, and low HDL-cholesterol levels were higher among private school students. The prevalence of the MetS was 2·6 %. No association between the MetS and its parameters and Se intake was found. This lack of association could be due to an adequate Se intake in the studied population.

Carbohydrate tolerance in Amazon tambaqui (Colossoma macropomum) revealed by NMR-metabolomics - Are glucose and fructose different sugars for fruit-eating fish?

In the present study, two approaches were followed to evaluate the metabolic responses of tambaqui (Colossoma macropomum), a frugivorous species, to intraperitoneal (IP) administration of glucose (GLU) and fructose (FRU) in fed (FED) and 10-day fasted (FAST) fish. Glucose and fructose tolerance tests were performed to assess the carbohydrate utilization and complementary NMR-metabolomics analyses were done to elucidate the impacts of sugar mobilization on the metabolic profile of plasma, liver and muscle. Blood was sampled from FED groups at 0, 3, 6 and 24 h; and at 0 and 24 h from FAST groups. Significant differences were observed in the hyperglycaemic peak between sugars at 3 h (GLU - 13.7 ± 2.0 mM vs. FRU - 8.7 ± 1.1 mM; saline 6.3 ± 0.6 mM) and on the return to normoglycaemia (GLU - 8.5 ± 2.2 mM vs. FRU - 5.2 ± 0.9 mM; saline 4.9 ± 0.6 mM) 6 h after IP on the FRU fish. The NMR-metabolomics approach allowed to conclude that tambaqui seems to be more responsive to the feeding regime (FED vs. FAST) than to the injected sugar (FRU vs. GLU). From the studied tissues, plasma showed no significant variations between feeding regimes at 24 h after IP, while muscle and liver revealed some variations on the final metabolome profile between FED and FAST groups. The metabolome variations between feeding regimes are indicative of changes on the amino acid utilization. Fish from FAST group seem to utilize amino acids as energy source rather than for protein synthesis and muscle growth. Variations on glucose concentration in muscle can also indicate different utilization of the sugars depending on the feeding regime.

Early Exposure to High-Sucrose Diet Leads to Deteriorated Ovarian Health.

Background: The metabolic syndrome (MetS) is correlated with disorders of the reproductive system, such as the polycystic ovary syndrome (PCOS). While consumption of a diet rich in carbohydrates is linked to the development of MetS, it is still unclear if this diet leads to ovarian dysfunction and PCOS. Objectives: We investigated the influence of a high-sucrose diet (HSD) on the ovarian milieu of Wistar rats and studied the correlation between high consumption of sugary drinks and the prevalence of PCOS in women. Methods: Wistar rats were given a standard laboratory diet (CTR, 10% sucrose, n = 8) or HSD (HSD, 25% sucrose, n = 8) from postnatal day 21 to 120. Animals were evaluated weekly to calculate food intake, feed efficiency and weight gain. Both onset of puberty and estrous cycle were monitored. Metabolic serum biochemistry, organ morphometry and ovarian histology were performed upon euthanasia. In parallel, a fixed-effects multiple linear regression analysis was performed using data from Brazilian states (459 state-year observations) to test the correlation between the consumption of sugar-sweetened beverages (surrogate for HSD intake) and the prevalence of PCOS (surrogate for ovarian dysfunction). Results: HSD animals showed increased adipose tissue accumulation, hyperglycaemia and insulin resistance when compared to CTR. Interestingly HSD rats also entered puberty earlier than CTR. Moreover, ovaries from HSD animals had an increased number of atretic antral follicles and cystic follicles, which were correlated with the hypertrophy of periovarian adipocytes. Finally, there was a positive correlation between the intake of sugary drinks and prevalence of PCOS in women of reproductive age. Conclusions: HSD ingestion leads to ovarian dysfunction in rats and could be correlated with PCOS in women, suggesting these alterations could lead to public health issues. Therefore, we reinforce the deleterious impact of HSD to the ovarian system and suggest that the reduction of added sugars intake could be beneficial to ovarian health.

Diabetic Hyperglycaemia Protects Smooth Muscle Arterial Cells but Not Macrophages and Endothelial Cells from the Cytotoxic Effects of 7-Ketocholesterol: An In Vitro Study

ABSTRACT Plasmatic hyperglycaemia is responsible for positive and negative stimuli. Among responsive cells, smooth muscle cells respond actively, increasing their growth. Diabetes hyperglycaemia and lipidic disorders are frequently associated, resulting in the highest probability of cardiovascular disease, especially atherosclerosis. Endothelial dysfunction and initiation of inflammatory process mediated by macrophages cause the formation of atherosclerotic plaques, rich in oxidized cholesterol, mostly 7-ketocholesterol. In this study, we evaluated the effect of 7-ketocholesterol in rabbit aorta endothelial cells, murine macrophages (J774) and smooth muscle cells (A7R5) maintained in normoglycemic and hyperglycaemic cultures. The 7-ketocholesterol-induced-cell death was observed in the normoglycemic medium three times more than the hyperglycaemic medium in all cells. High glucose medium had a protective effect on arterial smooth muscle cell death.

Mesenchymal stem cells derivatives as a novel and potential therapeutic approach to treat diabetic foot ulcers.

SUMMARY: Diabetic foot ulcer morbidity and mortality are dramatically increasing worldwide, reinforcing the urgency to propose more effective interventions to treat such a devastating condition. Previously, using a diabetic mouse model, we demonstrated that administration of bone marrow mesenchymal stem cells derivatives is more effective than the use of bone marrow mesenchymal stem cells alone. Here, we used the aforementioned treatments on three patients with grade 2 diabetic foot ulcers and assessed their beneficial effects, relative to the conventional approach. In the present study, two doses of cell derivatives, one dose of mesenchymal stem cells or one dose of vehicle (saline solution with 5% of human albumin), were intradermally injected around wounds. Wound healing process and changes on re-epithelialization were macroscopically evaluated until complete closure of the ulcers. All ulcers were simultaneously treated with conventional treatment (PolyMen® dressing). Patients treated with either cell derivatives or mesenchymal stem cells achieved higher percentages of wound closure in shorter times, relative to the patient treated with the conventional treatment. The cell derivative and mesenchymal stem cells approaches resulted in complete wound closure and enhanced skin regeneration at some point between days 35 and 42, although no differences between these two treatments were observed. Moreover, wounds treated with the conventional treatment healed after 161 days. Intradermal administration of cell derivatives improved wound healing to a similar extent as mesenchymal stem cells. Thus, our results suggest that mesenchymal stem cell derivatives may serve as a novel and potential therapeutic approach to treat diabetic foot ulcers. LEARNING POINTS: In diabetic mouse models, the administration of mesenchymal stem cells derivatives have been demonstrated to be more effective than the use of marrow mesenchymal stem cells alone. Mesenchymal stem cells have been explored as an attractive therapeutic option to treat non-healing ulcers. Mesenchymal stem cells derivatives accelerate the re-epithelialization on diabetic foot ulcers.

Pregnancy during the course of Cushing's syndrome: a case report and literature review.

SUMMARY: Cushing's syndrome is an endocrine disorder that causes anovulatory infertility secondary to hypercortisolism; therefore, pregnancy rarely occurs during its course. We present the case of a 24-year-old, 16-week pregnant female with a 10-month history of unintentional weight gain, dorsal gibbus, nonpruritic comedones, hirsutism and hair loss. Initial biochemical, hormonal and ultrasound investigations revealed hypokalemia, increased nocturnal cortisolemia and a right adrenal mass. The patient had persistent high blood pressure, hyperglycemia and hypercortisolemia. She was initially treated with antihypertensive medications and insulin therapy. Endogenous Cushing's syndrome was confirmed by an abdominal MRI that demonstrated a right adrenal adenoma. The patient underwent right laparoscopic adrenalectomy and anatomopathological examination revealed an adrenal adenoma with areas of oncocytic changes. Finally, antihypertensive medication was progressively reduced and glycemic control and hypokalemia reversal were achieved. Long-term therapy consisted of low-dose daily prednisone. During follow-up, despite favorable outcomes regarding the patient's Cushing's syndrome, stillbirth was confirmed at 28 weeks of pregnancy. We discuss the importance of early diagnosis and treatment of Cushing's syndrome to prevent severe maternal and fetal complications. LEARNING POINTS: Pregnancy can occur, though rarely, during the course of Cushing's syndrome. Pregnancy is a transient physiological state of hypercortisolism and it must be differentiated from Cushing's syndrome based on clinical manifestations and laboratory tests. The diagnosis of Cushing's syndrome during pregnancy may be challenging, particularly in the second and third trimesters because of the changes in the maternal hypothalamic-pituitary-adrenal axis. Pregnancy during the course of Cushing's syndrome is associated with severe maternal and fetal complications; therefore, its early diagnosis and treatment is critical.

Estudio descriptivo de las cetoacidosis atendidas en urgencias de un hospital de la Comunidad de Madrid mediante la herramienta Savana Manager / Diabetic ketoacidosis in a emergency department of a hospital in Madrid (Spain) using the Savana Manager tool

Objetivo: El objetivo del estudio fue describir las características y evolución de los pacientes que acudieron a las urgencias de nuestro hospital y fueron diagnosticados de cetoacidosis diabética (CAD) utilizando la novedosa herramienta de Big Data Savana. Método: Estudio retrospectivo descriptivo de los pacientes atendidos en urgencias del Hospital Universitario Infanta Leonor durante los años 2011 al 2016 con diagnóstico de CAD. La búsqueda se realizó con Savana Manager. Resultados: Se diagnosticaron 95 episodios de CAD en 68 pacientes. Del total de episodios de CAD, 57 fueron en diabéticos tipo 1 (de ellos 4 LADA), 25 en diabéticos tipo 2, 2 en diabéticos postpancreatectomía y 12 fueron debuts diabéticos. Del total, 61 (64,2%) requirieron ingreso hospitalario, de ellos 23 (24,2%) ingresaron en UCI. La media de HbA1c fue de 10,6 ± 2,1%. Tres pacientes requirieron reingreso tras el alta. La mortalidad fue muy baja con el fallecimiento en 1 paciente diagnosticado simultáneamente de cáncer pulmonar. Los desencadenantes de la CAD fueron: 35 casos (36,8%) falta de adherencia al tratamiento, 31 (32,6%) infecciones, 12 (12,6%) debuts, 8 (8,4%) varias causas y 9 (9,5%) no se pudo determinar la causa. Se clasificaron como CAD de gravedad leve un 28%, un 38% como de gravedad moderada y 34% como graves. La duración del ingreso no se relacionó con la severidad de la cetoacidosis. Conclusiones: La CAD es una complicación grave que afecta tanto a diabéticos tipo 1 como a tipo 2 con elevado porcentaje de ingresos hospitalarios y en UCI, aunque con baja mortalidad en nuestro medio. La duración de los ingresos no se relaciona con la severidad del cuadro.

Objective: the study was designed to describe the clinical features and evolution of the diabetic patients attended in our hospital emergency department with diabetic ketoacidosis (DKA) using the novel Big Data tool Savana. Method: Retrospective descriptive study of the patients attended in the emergency room of the Infanta Leonor University Hospital during the years 2011 to 2016 with diagnosis of CAD. The search was made with Savana. Results: 95 episodes of DKA were diagnosed in 68 patients. Of the total episodes of CAD 57 were in type 1 diabetics (of which 4 were LADA), 25 in type 2 diabetics, 2 in diabetics postpancreatectomy and 12 were new onset of diabetes. Of the total, 61 (64.2%) required hospital admission, of which 23 (24.2%) were admitted to the intensive care unit (ICU). The mean HbA1c was 10.6 ± 2.1%. Three patients required readmission after discharge. Mortality was very low with death in 1 patient simultaneously diagnosed of lung cancer. The triggers of CAD were: 35 cases (36,8%) lack of adherence to treatment, 31 (32.6%) infections, 12 (12.6%) new onset, 8 (8,4%) various causes and 9 (9.5%) the cause could not be determined. They were classified as mild DKA 28%, 38% as moderate and 34% as severe. The duration of admission was not related to the severity of ketoacidosis. Conclusions: DKA is a serious complication that affects both, type 1 and type 2 diabetics patients, with a high percentage of hospital and ICU admissions, although with low mortality in our environment. The lenght of the stay in hospital is not related to the severity of the DKA.

A hiperglicemia altera o perfil inflamatório e imunometabólico de macrófagos derivados de medula óssea de camundongos / Hyperglycemia alters the inflammatory and immunometabolic profile of mouse bone marrow derived macrophages

O diabetes mellitus é um grupo heterogêneo de distúrbios metabólicos caracterizado pela hiperglicemia. Indivíduos diabéticos possuem maior susceptibilidade a infecções comparado a indivíduos sadios e a hiperglicemia é um dos principais fatores que contribuem para isso, em parte, por alterar a resposta imune. Sendo assim, os macrófagos, como células essenciais para a resposta inflamatória, podem apresentar importante papel na resposta imune alterada de indivíduos diabéticos. Neste estudo, investigamos como a hiperglicemia modula os macrófagos derivados da medula óssea (BMDMs) sob um estímulo inflamatório. Para realizar este estudo, os BMDMs de camundongos C57BL/6 machos não diabéticos e diabéticos (60 mg/kg de aloxana, iv) (CEUA / FCF / USP-488) foram cultivados sob condições normais de glicose (5,5 mM) e alta concentração de glicose (25 mM ou 40 mM) e estimuladas ou não com lipopolissacarídeo (LPS, 100 ng/mL). Em comparação com os BMDMs dos camundongos não diabéticos, os BMDMs dos camundongos diabéticos estimulados com LPS apresentaram menor expressão de CD38 no tempo basal e após 24 horas, além de menor expressão de receptor do tipo Toll (TLR)-4 na superfície celular, menor capacidade fagocítica e redução na secreção de óxido nítrico, lactato, fator de necrose tumoral- e interleucina (IL)-10, porém apresentaram maior expressão de CD80, CD86 e MHC-II, maior consumo de oxigênio e maior fosforilação em quinase ativada por estresse/quinase Jun-amino-terminal (SAPK/JNK) subunidade p46 e em quinase regulada por sinal extracelular (ERK) subunidade p42, proteína quinase B (AKT) e proteína quinase C (PKC)-δ assim como maior secreção de IL-6. Quando os BMDMs dos camundongos não diabéticos foram cultivados sob condições de alta concentração de glicose in vitro e estimulados com LPS, a expressão de TLR4 e os níveis de óxido nítrico e peróxido de hidrogênio foram reduzidos. Por outro lado, os BMDMs diabéticos que também foram cultivados em alta concentração de glicose in vitro apresentaram níveis aumentados de lactato e fosforilação reduzida em AKT e PKC-δ, porém apresentaram fosforilação aumentada em p46 SAPK/JNK. A alta concentração de glicose parece modificar o comportamento dos macrófagos, afetando diferentes aspectos dos BMDMs diabéticos e não diabéticos sob estímulo de LPS, assim a hiperglicemia deixa um legado de glicose, induzindo uma memória glicêmica, alterando o estado basal dos macrófagos, modificando a via de sinalização do TLR4 contribuindo para a susceptibilidade de indivíduos diabéticos a infecções

Diabetes mellitus is a heterogeneous group of metabolic disorders characterized by hyperglycemia. Diabetic individuals are more susceptible to infections compared to healthy subjects, and hyperglycemia is one of the major contributing factors, partly because they alter the immune response. Thus, macrophages, as essential cells for the inflammatory response, may play an important role in the altered immune response of diabetic individuals. In this study, we investigated how hyperglycemia modulates bone marrow derived macrophages (BMDMs) under an inflammatory stimulus. To perform this study, BMDMs from non-diabetic male and diabetic C57BL/6 mice (60 mg / kg aloxane, iv) (CEUA / FCF / USP-488) were cultured under normal glucose conditions (5.5 mM) and high glucose concentration (25 mM or 40 mM) and stimulated or not with lipopolysaccharide (LPS, 100 ng / ml). Compared to non-diabetic mice BMDMs, the BMDMs of LPS-stimulated diabetic mice showed lower expression of CD38 at baseline and after 24 hours, as well as lower Toll-like receptor (TLR)-4 on the cell surface, lower secretion of lactate, tumor necrosis factor-, and interleukin (IL)-10, but showed higher expression of CD80, CD86 and MHC-II, higher oxygen consumption and greater phosphorylation in stress-activated kinase/Jun-amino-terminal kinase (SAPK / JNK) p46 subunit and in extracellular signal regulated kinase (ERK) p42 subunit, protein kinase B (AKT) and protein kinase C (PKC)-δ as well as higher secretion of IL-6. When the BMDMs of nondiabetic mice were cultured under conditions of in vitro high glucose concentration and stimulated with LPS, the levels of TLR4 expression, nitric oxide and hydrogen peroxide were reduced. On the other hand, diabetic BMDMs that were also cultured in high glucose concentration of glucose in vitro showed increased levels of lactate and reduced phosphorylation in AKT and PKC-δ, but showed increased phosphorylation in p46 SAPK/JNK. A high glucose concentration seems to modify the behavior of macrophages, affecting different aspects of diabetic and non-diabetic BMDMs under the same LPS stimulus. Hyperglycemia leaves a glucose legacy, inducing a glycemic memory, altering the basal state of macrophages, modifying the TLR4 signaling pathway, and may play a key role in the high susceptibility of diabetic individuals to infections

Síndrome de corea hiperglicemia y ganglios básales / Chorea hyperglicemia basal ganglia síndrome

Resumen La diabetes mellitus es una enfermedad de alta prevalência, así como también lo son sus complicaciones agudas. Una de ellas es el estado hiperosmolar no cetósico que raramente se asocia con alteraciones involuntarias del movimiento. Sin embargo, existe una condición que asocia alteraciones glucémicas con desórdenes del movimiento, denominado síndrome de corea hiperglicemia y ganglios basales, de la cual presentamos un caso y hacemos revisión de la literatura.

Abstract Diabetes mellitus is a disease of high prevalence, as well as its acute complications. One of them is the nonketotic hyperosmolar state that is rarely associated with involuntary changes in movement. However, there is a condition that associates glycemic alterations with movement disorders, called chorea hyperglycemia basal ganglia syndrome, of which we present a case and review the literature.

Neuroendocrine System Regulatory Mechanisms: Acute Coronary Syndrome and Stress Hyperglycaemia.

Neurohormonal systems are activated in the early phase of acute coronary syndromes to preserve circulatory homeostasis, but prolonged action of these stress hormones might be deleterious. Cortisol reaches its peak at 8 hours after the onset of symptoms, and individuals who have continued elevated levels present a worse prognosis. Catecholamines reach 100-1,000-fold their normal plasma concentration within 30 minutes of ischaemia, therefore inducing the propagation of myocardial damage. Stress hyperglycaemia induces inflammation and endothelial dysfunction, and also has procoagulant and prothrombotic effects. Patients with hyperglycaemia and no diabetes elevated in-hospital and 12-month mortality rates. Hyperglycaemia in patients without diabetes has been shown to be an appropriate independent mortality prognostic factor in this type of patient.

Valor pronóstico de los trastornos de la glucemia en la insuficiencia cardíaca congestiva / Prognostic value of glycemia´s disorders in congestive heart failure

Introducción: Existen escasas evidencias de que la glucemia se pueda utilizar para predecir las complicaciones de la insuficiencia cardiaca congestiva. Por esta razón se determinó medir los valores de glucemia de los pacientes con insuficiencia cardiaca congestiva en varios momentos de su ingreso. Objetivo: Identificar el valor pronóstico de los trastornos de la glucemia en la aparición de complicaciones de la insuficiencia cardiaca congestiva. Métodos: Se incluyeron los pacientes ingresados por insuficiencia cardiaca congestiva entre 2013 y 2015, que cumplieran con los criterios de Framingham y no tuvieran tratamientos hiperglucemiantes ni enfermedad terminal. Se les cuantificó glucemia al ingreso, al siguiente día en ayuno y posprandial, y de estar alteradas se realizó hemoglobina glucosilada para determinar si eran diabéticos previos. Se buscó asociación entre la glucemia y las complicaciones intrahospitalarias. Resultados: Se estudiaron 111 pacientes. Las complicaciones más frecuentes fueron los trastornos electrolíticos, la muerte, el shock y el edema pulmonar; los antecedentes patológicos no influyeron en la aparición de complicaciones. Hubo una asociación entre la hiperglucemia intrahospitalaria (p=0,032) y la hiperglucemia de estrés (p=0,035) con la presencia de complicaciones, la hiperglucemia posprandial fue la que mostró una influencia independiente en dicha evolución clínica (p=0,037). Conclusiones: Se encontró una alta frecuencia de hiperglucemia de ingreso, basal y posprandial y una asociación entre la hiperglucemia intrahospitalaria y la posibilidad de complicación durante los períodos de agudización de la insuficiencia cardiaca congestiva(AU)

Introduction: There are scanty evidences that glycemia can be used for predicting the complications of congestive heart failure (CHF). For this reason, it was decided to measure the glycemia values of patients with CHF in several moments of their admission. Objective: To identify the prognostic value of glycemia´s disorders in the appearance of complications of the congestive heart failure. Methods: There were included the patients admitted due to congestive heart failure between 2013 and 2015, who met with Framingham's criteria and had not been under hyperglycaemic treatments nor presenting a terminal illness. Their glycemia was quantified in the admission moment, also the following day in fasting and postprandial, and of being altered a glusocilada hemoglobin´s test was performed to determine if they were diabetics previously. Association between the glycemia and in-hospital complications was looked-up. Results: 111 patients were studied, finding as more frequent complications electrolytic disorders, death, shocks and pulmonary oedema; the pathological background did not have influence in the appearance of complications. There was an association between the in-hospital hyperglycaemia (p=0.032) and the hyperglycaemia due to stress (p=0.035) with the presence of complications, being the posprandial hyperglycaemia the one that showed an independent influence in the above mentioned clinical evolution (p=0.037). Conclusions: There was found a high frequency of hyperglycaemia in the admission moment, as well as basal and postprandial hyperglycaemia; and an association between the in-hospital hyperglycemia and the possibility of complications during the periods of worsening of the CHF(AU)

Sensitivity of fasting glucose for gestational diabetes mellitus screening in Mexican adolescents based on International Association of Diabetes and Pregnancy Study Groups criteria: a diagnostic accuracy study based on retrospective data analysis.

OBJECTIVE: To evaluate fasting plasma glucose (FPG) as a screening test for gestational diabetes mellitus (GDM) among Mexican adolescents using International Association of Diabetes and Pregnancy Study Groups criteria. DESIGN: Retrospective cohort study. SETTING: Level-three medical institution in Mexico City. PARTICIPANTS: The study population comprised 1061 adolescent women aged 12-19 years with singleton pregnancies, who underwent a 75 g oral glucose tolerance test (OGTT) between 11 and 35 weeks of gestation. PRIMARY AND SECONDARY OUTCOME MEASURES: The sensitivity (Sn), specificity (Sp), positive and negative predictive values (PPV and NPV, respectively), and positive and negative likelihood ratios LR (+) and LR (-), respectively) with 95% CIs for selected FPG cut-off values were compared. Secondary measures were perinatal outcomes in women with and without GDM. RESULTS: GDM was present in 71 women (6.7%, 95% CI 5.3% to 8.4%). The performances of FPG at thresholds of ≥80 (4.5 mmol/L), 85 (4.7 mmol/L) and 90 mg/dL (5.0 mmol/L) were as follow (95% CI): Sn: 97% (89% to 99%), 94% (86% to 97%) and 91% (82% to 95%); Sp: 50% (47% to 53%), 79% (76% to 81%) and 97% (95% to 97%); PPV: 12% (9% to 15%), 23% (18% to 28%) and 64% (54% to 73%); NPV: 99% (98.5% to 99.9%) for all three cut-offs; LR (+): 1.9 (1.8 to 2.1), 4.3 (3.8 to 5.0) and 26.7 (18.8 to 37.1) and LR (-): 0.06 (0.02 to 0.23), 0.07 (0.03 to 0.19) and 0.09 (0.04 to 0.19), respectively. No significant differences in perinatal outcomes were found between adolescents with and without GDM. CONCLUSIONS: An FPG cut-off of ≥90 mg/dL (5.0 mmol/L) is ideal for GDM screening in Mexican adolescent women. An FPG threshold of 90 mg/dL would miss 6 (8.5%) women with GDM, pick up 34 (3.4%) women without GDM and avoid 962 (90.7%) OGTTs.

Mild diabetes: long-term effects on gastric motility evaluated in rats.

Moderate hyperglycaemic levels seem to be related to abnormal gastric motility in diabetes mellitus. However, experimental models designed to evaluate the relationship between motility and diabetes over time are not yet well established. Our objective was to investigate the long-term effects of mild diabetes on gastric motility in rats. Newborn male rats received streptozotocin (mild diabetes groups - MD) or vehicle (control groups - C), and both groups were evaluated after 3 (C3 and MD3) and 6 months (C6 and MD6) postinduction. Mild diabetic animals (MD3 and MD6) showed moderately elevated blood glucose and decreased insulin levels compared with control (C3 and C6). Insulin secretion was enhanced in MD6 compared with MD3, most likely due to partial ß-cell regeneration indicated by HOMA-ß. In HOMA-IR, it was noticed that MD6 animals had impaired insulin response compared with MD3. Gastric emptying was faster, amplitude of contraction was stronger in MD6 compared with MD3, and in both groups, the differences were significant when compared with control animals. A significant abnormal rhythmic index was calculated for the mild diabetic groups, despite unchanged mean frequency of contraction. In conclusion, despite increased insulin levels over time, constant levels of moderate hyperglycaemia are also related to abnormal gastric motility and impairment of gastric function.