Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population / 中国医学科学院学报

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Predictive Effects of Different Insulin Resistance Indexes on Diabetes Risk in Hypertensive Population / 中国医学科学院学报

Objective To explore the roles of different insulin resistance indexes[triglyceride-glucose (TyG),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and metabolic score for insulin resistance (METS-IR)]and combinations of two indexes in predicting diabetes risk in hypertensive population. Methods The survey of hypertension was conducted for the residents in Wuyuan county,Jiangxi province from March to August in 2018.The basic information of hypertensive residents was collected by interview.Blood was drawn on an empty stomach in the morning and physical measurements were carried out.Logistic regression model was employed to analyze the relationship between different insulin resistance indexes and diabetes,and the area under the receiver operating characteristic curve was used for evaluating the predictive effects of each index on diabetes risk. Results A total of 14 222 hypertensive patients with an average age of (63.8±9.4) years old were included in this study,including 2616 diabetic patients.The diabetic hypertensive population had higher TyG (t=50.323,P<0.001),TG/HDL-C (Z=17.325,P<0.001),and METS-IR (t=28.839,P<0.001) than the non-diabetic hypertensive population.Multivariate analysis showed that each insulin resistance index was positively correlated with diabetes risk.The area under curve of each insulin index was in a descending order of TyG (0.770)> METS-IR (0.673)> TG/HDL-C (0.620).The difference in the area under curve between two indexes was statistically significant[TyG vs.TG/HDL-C (Z=42.325,P<0.001);TyG vs.METS-IR(Z=17.517,P<0.001);METS-IR vs.TG/HDL-C (Z=10.502,P<0.001)]. Conclusions Elevated insulin resistance indexes can increase the risk of diabetes.TyG and the combination of indexes outperform TG/HDL-C and METS-IR in the prediction of diabetes.

Changes of 1, 5-AG in Vitreous Humor of Rabbit Cadavers with Hyperglycemic Metabolism / 法医学杂志

OBJECTIVES@#To investigate the concentration and change characteristics of 1, 5-anhydroglucitol (1, 5-AG) in the vitreous humor of rabbit cadavers with hyperglycemic metabolism, and to explore the value of 1, 5-AG in forensic pathology identification of death caused by hyperglycemic metabolism disorders.@*METHODS@#A diabetic hyperglycemic rabbit model was established by using alloxan. Eighteen rabbits with fasting glucose concentration ≥13.80 mmol/L (experimental group) and 18 healthy rabbits with fasting glucose concentration ≤6.10 mmol/L (control group) were selected. After death from air embolism. The blood samples were collected immediately, and vitreous humor samples were collected at 0 h, 12 h, 24 h and 36 h after death. The concentration of 1, 5-AG in the blood and vitreous humor of rabbits was determined.@*RESULTS@#The blood glucose concentration in the experimental group was (25.10±3.14) mmol/L. At the time of death, there was no significant difference in the concentration of 1, 5-AG in the blood [(0.94±0.20) μg/mL] and in the vitreous humor (0.99±0.05 μg/mL, P>0.05). The concentration of 1, 5-AG in the vitreous humor of the experimental group was lower than that of the corresponding control group at all time points (P<0.05), and there was no significant difference betwwen 1, 5-AG concentration in vitreous humor between earch time point in the experimental group and the control group (P>0.05). Correlation analysis showed that the concentration of 1,5-AG in blood was negatively correlated with blood glucose in both control group and experimental group (control group: r=-0.79, P<0.05; experimental group: r=-0.97, P<0.05).@*CONCLUSIONS@#Vitreous humor can replace blood as an effective test sample for 1,5-AG detection. The concentration of 1, 5-AG in rabbit vitreous humor remains stable within 36 hours after death and is not affected by the change of postmortem interval. If the concentration of 1, 5-AG decreases significantly, it indicates the existence of hyperglycemia in rabbits before death.

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue / 生理学报

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα-/-+ND) group and ketogenic diet (PPARα-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα-/-+ND group, the PPARα-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Validity and reliability of simple surrogate indexes to evaluate beta-cell function and insulin sensitivity

BACKGROUND: Simple surrogate indexes (SSI) to assess beta-cell function, insulin sensitivity (IS) and insulin resistance (IR) are an easy and economic tool used in clinical practice to identify glucose metabolism disturbances. AIM: To evaluate the validity and reliability of SSI that estimate beta-cell function, IS and IR using as a reference the parameters obtained from the frequently sampled intravenous glucose tolerance test (FSIVGTT). MATERIAL AND METHODS: We included 62 subjects aged 20-45 years, with a normal body mass index and without diabetes or prediabetes. SSI were compared with the acute insulin response to glucose (AIRg), insulin sensitivity index (Si) and disposition index (DI) obtained from the FSIVGTT using the minimal model approach. Half of the participants (n = 31) were randomly selected for a second visit two weeks later to evaluate the reliability of all the variables. RESULTS: HOMA1-%B and HOMA2-%B had a significant correlation with AIRg (Spearman Rho (rs) = 0.33 and 0.37 respectively, p 0.50) with Si were fasting insulin, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI, and the McAuley index. The parameters that showed good reliability with an intraclass correlation coefficient (ICC) > 0.75 were AIRg, HOMA1-%S, HOMA2-%S, and QUICKI. Conclusions: Our results suggest that most of the SSI are useful and reliable.

ANTECEDENTES: Los índices simples subrogados (ISS) que evalúan la función de célula beta, sensibilidad a la insulina (SI) y resistencia a la insulina (RI) son herramientas sencillas y económicas que se usan en la práctica clínica para identificar alteraciones del metabolismo de la glucosa. OBJETIVO: Evaluar la validez y confiabilidad de ISS para estimar la función de célula beta, SI y RI usando como referencia los parámetros de la prueba de tolerancia a la glucosa intravenosa con muestreo frecuente (FSIVGTT). MATERIAL Y MÉTODOS: Se incluyeron 62 sujetos de 20-45 años, con índice de masa corporal normal y sin diabetes mellitus o prediabetes. Los ISS se compararon con la respuesta aguda de la insulina a la glucosa (AIRg), índice de sensibilidad a la insulina (Si) e índice de disposición (DI) obtenidos de la FSIVGTT en base al modelo mínimo. La mitad de los participantes (n = 31) se seleccionaron aleatoriamente para acudir dos semanas después y evaluar la confiabilidad de todas las variables. RESULTADOS: HOMA1-%B y HOMA2-%B presentaron una correlación significativa con AIRg (Rho de Spearman (rs) = 0,33 and 0,37, respectivamente, p 0,50) con Si fueron insulina en ayuno, HOMA1-IR, HOMA2-IR, HOMA1-%S, HOMA2-%S, QUICKI y el índice de McAuley. Los parámetros que tuvieron buena confiabilidad (coeficiente de correlación intraclase > 0,75) fueron AIRg, HOMA1-%S, HOMA2-%S y QUICKI. Conclusiones: La mayoría de los ISS son instrumentos útiles y confiables.

Falta de adherencia al tratamiento farmacológico y factores asociados en pacientes mexicanos con diabetes mellitus tipo 2 / Factors associated with the lack of adherence to treatment among patients with type 2 diabetes mellitus

BACKGROUND: Adherence to pharmacological treatment (APT) is crucial for patients with type 2 diabetes mellitus (T2DM) to achieve metabolic control and decrease complications. AIM: To establish the proportion of APT in patients with T2DM, the influence of the same on blood glucose, and the factors involved in a lack of ATP. MATERIAL AND METHODS: Diabetic patients were interrogated about sociodemographic factors, the evolution of the disease, their fasting blood glucose levels, and the use of other treatments. APT was evaluated with the Morisky-Green questionnaire, patient beliefs about treatments with the Beliefs about Medicines Questionnaire (BMQ), and patient knowledge about T2DM with the standard questionnaire. RESULTS: A representative sample of 400 individuals of both sexes was studied, finding a lack of APT in 74.5% of patients. The latter patients showed a significantly greater level of blood glucose while being more preoccupied and less informed about the disease. A lack of APT was associated with the refusal to undergo the blood glucose test among men (Odds ratio (OR)=3.70; 95% confidence intervals (CI), 1.58-8.66) and with the consumption of medicinal plants among women (OR=2.53; IC 95%, 1.23-5.23). CONCLUSIONS: A lack of APT in patients with T2DM is a serious problem and associated with a lack of knowledge about the disease. It is urgent to strengthen the educational programs in relation to T2DM to promote adherence to treatment.

Tetrahydropalmatine alleviated diabetic neuropathic pain by inhibiting activation of microglia via p38 MAPK signaling pathway / 中国中药杂志

Neuropathic pain is one of the common complications of diabetes. Tetrahydropalmatine(THP) is a main active component of Corydalis Rhizoma with excellent anti-inflammatory and pain-alleviating properties. This study aims to investigate the therapeutic effect of THP on diabetic neuropathic pain(DNP) and the underlying mechanism. High-fat and high-sugar diet(4 weeks) and streptozotocin(STZ, 35 mg·kg~(-1), single intraperitoneal injection) were employed to induce type-2 DNP in rats. Moreover, lipopolysaccharide(LPS) was used to induce the activation of BV2 microglia in vitro to establish an inflammatory cellular model. Fasting blood glucose(FBG) was measured by a blood glucose meter. Mechanical withdrawal threshold(MWT) was assessed with von Frey filaments, and thermal withdrawal latency(TWL) with hot plate apparatus. The protein expression levels of OX42, inducible nitric oxide synthase(iNOS), CD206, p38, and p-p38 were determined by Western blot, the fluorescence expression levels of OX42 and p-p38 in the dorsal horn of the rat spinal cord by immunofluorescence, the mRNA content of p38 and OX42 in rat spinal cord tissue by qRT-PCR, and levels of nitric oxide(NO), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and serum fasting insulin(FINS) by enzyme-linked immunosorbent assay(ELISA). RESULTS:: showed that the mo-del group demonstrated significant decrease in MWT and TWL, with pain symptoms. THP significantly improved the MWT and TWL of DNP rats, inhibited the activation of microglia and p38 MAPK signaling pathway in rat spinal cord, and ameliorated its inflammatory response. Meanwhile, THP promoted the change of LPS-induced BV2 microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, suppressed the activation of the p38 MAPK signaling pathway, decreased the expression levels of inflammatory factors NO, IL-1β, IL-6, and TNF-α, and increased the expression level of anti-inflammatory factor IL-10. The findings suggested that THP can significantly ameliorate the pain symptoms of DNP rats possibly by inhibiting the inflammatory response caused by M1 polarization of microglia via the p38 MAPK pathway.

Progress in the role of endometrial glucose metabolism in embryo implantation / 生理学报

The synthesis and decomposition of glycogen adjust the blood glucose dynamically to maintain the energy supply required by the cells. As the only hormone that lowers blood sugar in the body, insulin can promote glycogen synthesis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and increasing glucose transporter translocation, and inhibit gluconeogenesis to lower blood glucose. In the endometrium, glycogen metabolism is active, but gluconeogenesis does not occur. The glycogen metabolism in the endometrium is controlled not only by the classical glucose regulating hormones, but also by the ovarian hormones. The functional activities related to implantation of the endometrium during the implantation window require glucose as energy source. A large amount of glucose is used to synthesize glycogen in the endometrium before implantation, which could meet the increased energy demand for embryo implantation. In diabetes, glycogen metabolism in the endometrium is impaired, which frequently leads to implantation failure and early abortion. This article reviews the glycogen metabolism in the endometrium and discusses its role in embryo implantation, which provide new ideas for embryo implantation research and infertility treatment.

Risk of gestational diabetes recurrence and the development of type 2 diabetes among women with a history of gestational diabetes and risk factors: a study among 18 clinical centers in China / 中华医学杂志(英文版)

BACKGROUND@#Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China.@*METHODS@#A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed.@*RESULTS@#In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P  < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P  = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P  = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P  = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further.@*CONCLUSIONS@#The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.

Effects of psychological suggestion combined with rational food restriction therapy on blood glucose and lipid metabolism and mental resilience in patients with diabetes / 中华预防医学杂志

Objective: To analyze the effect of psychological suggestion combined with rational food restriction therapy on blood glucose, lipid metabolism and mental resilience in patients with diabetes. Methods: Patients with diabetes admitted to the Third Hospital of Nanchang from January 2020 to August 2020 were divided into the control group and the intervention group with randomized controlled and single blind methods. The control group was treated with routine dietary guidance and health education, and the intervention group was treated with psychological suggestion combined with rational diet therapy on the basis of the control group. Both groups were treated for 3 months. Blood glucose, lipid metabolism, mental resilience and quality of life were compared between the two groups at baseline and after 3-month intervention. Differences between groups and within groups were analyzed by t test and χ2 test. Results: 100 patients in the control group and 81 patients in the intervention group completed 3-month intervention. After 3-month intervention, the levels of glycosylated hemoglobin, fasting blood glucose, 2-hour postprandial blood glucose, low-density lipoprotein cholesterol and triglyceride in both groups were lower than those before intervention. The levels of these indicators in intervention group were lower than those in control group (P<0.05). However, the levels of high-density lipoprotein cholesterol and the scores of tenacity, self-reliance, optimism, role function, emotional function, social function, physical function and cognitive function in both groups were higher than those before intervention. These indicators in intervention group were higher than those in control group (P<0.05). Conclusion: Psychological suggestion combined with rational food restriction therapy could effectively improve the glucose and lipid metabolism, mental resilience, and quality of life among patients with diabetes.

Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy

Abstract Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson's Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.

Uso de metformina para prevención primaria de diabetes mellitus en pacientes de bajo riesgo / Use of metformin for primary prevention of diabetes mellitus in low-risk patients

Los autores de este artículo abordan la evidencia disponible sobre la prevención de diabetes tipo 2 mediante la indicación de metformina en pacientes sin alteraciones de la glucemia, a partir de una consulta de la práctica ambulatoria. (AU)

The authors of this article discuss the available evidence on the prevention of type 2 diabetes through the prescription of metformin to patients without glycemic alterations, based on an outpatient practice consultation. (AU)

Diabetes y COVID-19, una relación de ida y vuelta / Diabetes and COVID-19, one relation to go and comeback

Diabetic patients are at risk of developing unfavorably from SARS-COV19 disease, especially when they have poor glycemic control. On the other hand, in the case of diabetic patients with severe COVID, they evolve with severe hyperglycemia, often difficult to manage. Marked hyperglycemia has also been described in people without a known history of previous diabetes, even there have been reported cases of insulin-dependent diabetes debut in days after the disease. The aim of this review is to analyze possible mechanisms involved in the relationship between COVID-19 and DIABETES.

Prevalencia de alteraciones del metabolismo glucídico en familiares de primer grado de pacientes diabéticos tipo 2 / Prevalence of glucidic metabolism alterations in first- degree relatives of type 2 diabetic patients

Introducción: La diabetes mellitus se considera un síndrome heterogéneo con etiología compleja en el que influyen factores genéticos y ambientales. Objetivo: Identificar la presencia de alteraciones del metabolismo glucídico y factores de riesgo aterogénicos en familiares de primera línea de pacientes diabéticos tipo 2. Métodos: Se realizó un estudio descriptivo de corte transversal que incluyó a 120 pacientes adultos, hijos de pacientes diabéticos, en los que no se encontraban antecedentes de alteraciones del metabolismo glucídico, pertenecientes al Policlínico Universitario Héroes del Moncada, del municipio Plaza de la Revolución. Se estudiaron variables sociodemográficas, variables clínicas y relacionadas con los estilos de vida como la tensión arterial, el índice de masa corporal, colesterol, triglicéridos, glucemias (ayunas y posprandial), hábito de fumar, actividad física y hábitos dietéticos. Resultados: Los pacientes tenían una edad promedio de 54,42 años y predominó el sexo femenino. Se detectaron alteraciones del metabolismo glucídico en 28,3 por ciento de los cuales 23,3 por ciento se consideraron prediabéticos y 5 por ciento diabéticos. Los factores de riesgo que predominaron fueron la dieta inadecuada, obesidad abdominal, hipercolesterolemia e hipertrigliceridemia que fueron más evidentes en los pacientes diagnosticados como diabéticos. Conclusiones: Los familiares de primer grado de pacientes diabéticos pueden presentar una alta prevalencia de alteraciones del metabolismo glucídico y factores de riesgo aterogénicos, aún sin sintomatología evidente, lo que refuerza la necesidad de realizar un diagnóstico temprano para evitar la progresión de la enfermedad(AU)

Introduction: Diabetes mellitus is considered a heterogeneous syndrome with a complex etiology, influenced by genetic and environmental factors. Objective: To identify the presence of alterations of the glucidic metabolism and atherogenic risk factors in first- degree relatives of type 2 diabetic patients. Methods: A descriptive cross-sectional study was carried out at Heroes del Moncada University Polyclinic, in Plaza de la Revolution municipality. The study included 120 adult patients, descendants of diabetic patients. They had no history of alterations of the glucidic metabolism. Sociodemographic, clinical variables were studied, and those related to lifestyles such as blood pressure, body mass index, cholesterol, triglycerides, (fasting and postprandial) glycaemia, smoking, physical activity and dietary habits. Results: These patients had average age of 54.42 years and the female sex predominated. Alterations of the glucidic metabolism were detected in 28.3 percent, 23.3 percent of them were considered pre-diabetic and 5 percent diabetic. The predominant risk factors were inadequate diet, abdominal obesity, hypercholesterolemia, and hypertriglyceridemia, which was much evident in patients diagnosed as diabetic. Conclusions: The first-degree relatives of diabetic patients may present high prevalence of alterations of glucidic metabolism and atherogenic risk factors, even with no evident symptoms, which reinforces the need of early diagnosis to avoid the progression of the disease(AU)

Evolução do perfil lipídico, glicêmico e pressórico de prematuros: estudo longitudinal / Evolution of the lipid, glycemic and blood pressure profile of premature infants: a longitudinal study

Objetivo: Relacionar a evolução do perfil lipídico, glicêmico e pressórico de prematuro do nascimento aos 2 anos de idade corrigida com a classificação de peso ao nascer e sexo. Metodologia: Estudo longitudinal, amostra inicial de 71 prematuros, destes, 31 completaram o acompanhamento ambulatorial. Avaliados ao nascer, alta, 6 meses e 2 anos de idade corrigida (peso, idade gestacional, perfil lipídico, glicêmico, pressão arterial). Resultados: Glicemia, colesterol total, pressão arterial e triglicerídeos, não foram estatisticamente significantes em relação ao peso ao nascer e ao longo do seguimento. Colesterol total (p=0,18) e glicemia sofreram efeito de interação com o sexo. Pressão arterial acima do esperado aos 2 anos. Crescimento foi uniforme independente do sexo. Conclusão: O perfil lipídico, glicêmico e pressórico dos prematuros ao longo do acompanhamento não foi influenciado pela classificação de peso ao nascer. O sexo influenciou as concentrações de colesterol e a glicemia.

Objective: To relate the evolution of the lipid, glycemic and blood pressure profile of premature infants from birth to 2 years corrected age with the classification of birth weight and sex. Methodology: Longitudinal study, initial sample of 71 premature infants, of which 31 completed outpatient follow-up. Evaluated at birth, discharge, 6 months and 2 years corrected age (weight, gestational age, lipid, glycemic, blood pressure profile). Results: Blood glucose, total cholesterol, blood pressure and triglycerides were not statistically significant in relation to birth weight nor throughout follow-up. Total cholesterol (p=0.18) and blood glucose underwent interaction with sex. Blood pressure was higher than expected at 2 years old. Growth was uniform regardless of sex. Conclusion: The lipid, glycemic and blood pressure profile of premature infants during follow-up was not influenced by the birth weight classification. The cholesterol and blood glucose concentrations were influenced by sex.

Teoria do risco de padrão glicêmico desequilibrado em adultos e idosos com diabetes mellitus em tratamento / Theory of the Risk of Imbalanced Glycemic Pattern in adults and elderly people with diabetes mellitus under treatment

Introdução: os padrões referentes à glicemia não foram descritos e explicados utilizando-se uma teoria de enfermagem como referencial, nem tão pouco articulados e modelados às estruturas preditoras de interesse para ação da enfermagem diante destas condições. Sendo assim, presume-se a relevância de construir uma teoria de médio alcance que aborde os fatores predisponentes e precipitantes para os padrões de variabilidade relativos à glicemia, explicando relações e predizendo associações que possam suportar o julgamento diagnóstico de enfermagem para a população com diabetes mellitus em tratamento. Objetivo: desenvolver uma teoria de médio alcance sobre variações glicêmicas em adultos e idosos com diabetes mellitus em tratamento tendo por base o Modelo Conceitual da Adaptação de Roy. Método: pesquisa teórica do tipo desenvolvimento de uma nova teoria. Para teorização utilizou-se a proposta de processo geral de pesquisa de Holton e Lowe (2007). Os procedimentos metodológicos desenvolvidos foram implementados em três partes: parte 1 ­ a) entendimento dos fenômenos; b) identificação e recuperação dos estudos na revisão sistemática de etiologia e risco e análise do modelo de adaptação de Roy; c) análise do construto; parte 2 ­ d) identificação de unidades da teoria; e) estipular as leis de interação com a produção de um modelo de interações guiado pelas dez etapas de construção de modelos de causalidade proposto por Jaccard e Jacoby (2010); f) determinação dos limites da teoria; g) especificação dos estados do sistema; h) desenvolvimento das afirmativas axiomáticas; parte 3 ­ i) especificação das proposições da teoria. Resultados: produziu-se a análise do modelo de adaptação de Roy e uma revisão sistemática da literatura sobre fatores de risco para hiperglicemia e hipoglicemia em adultos e idosos com diabetes mellitus em tratamento. Essas estratégias permitiram na análise do construto o desenvolvimento do diagnóstico "Risco de Padrão Glicêmico Desequilibrado no adulto/idoso com Diabetes Mellitus". O processo de teorização determinou as unidades e estados focais, contextuais e residuais da teoria do Risco de Padrão Glicêmico Desequilibrado em adultos e idosocom diabetes mellitus em tratamento. Produziu-se um modelo interativo das unidades focais, nove afirmativas axiomáticas, quatorze proposições teóricas e um modelo representativo da teoria. Conclusões: esta pesquisa elaborou uma teoria de médio alcance, que descreve e explica o Risco de Padrão Glicêmico Desequilibrado, examinando os fatores que influenciam no surgimento da hipoglicemia e hiperglicemia em adultos e idosos com Diabetes Mellitus em tratamento. A presente tese contribui de forma original ao estruturar riscos associados a hipoglicemia e hiperglicemia em um construto de interesse para a enfermagem que pode ter futuros impactos na organização e delimitações de ações do cuidado profissional.

Introduction: the patterns referring to glycemia were not described and explained using a nursing theory as a reference, nor were they articulated and modeled on the predictive structures of interest for nursing action under these conditions. Thus, the relevance of constructing a meddle-range theory that addresses the predisposing and precipitating factors for the variability patterns related to glycemia is presumed, explaining relationships and predicting associations that can support the nursing diagnostic judgment for the population with diabetes mellitus in treatment. Objective: to develop a meddle-range theory on glycemic variations in adults and the elderly with diabetes mellitus undergoing treatment based on Roy's Conceptual Adaptation Model. Method: theoretical research on the type of development of a new theory. For theorizing, Holton and Lowe's (2007) general research process proposal was used. The methodological procedures developed were implemented in three parts: part 1 - a) understanding of the phenomena; b) identification and recovery of studies in the systematic review of etiology and risk and analysis of Roy's adaptation model; c) constructo analysis; part 2 - d) identification of theory units; e) stipulate as laws of interaction with the production of an interaction model guided by the ten stages of construction of causality models addressed by Jaccard and Jacoby (2010); f) determining the limits of the theory; g) replacement of system states; h) development of axiomatic statements; part 3 - i) registration of theory proposals. Results: an analysis of the Roy adaptation model and a systematic review of the literature on risk factors for hyperglycemia and hypoglycemia in adults and the elderly with diabetes mellitus under treatment were carried out. These strategies allowed, in the construct analysis, the development of the diagnosis "Risk of Imbalanced Glycemic Pattern in the adult/ elderly with Diabetes Mellitus". The theorization process determined the focal, contextual and residual units and states of the Imbalanced Glycemic Pattern Risk theory in adults and the elderly with diabetes mellitus being treated. An interactive model of the focal units was produced, nine axiomatic statements, fourteen theoretical propositions and a representative model of the theory. Conclusions: this researcdeveloped a meddle-range theory, which describes and explains the Risk of Imbalanced Glycemic Pattern, examining the factors that influence the appearance of hypoglycemia and hyperglycemia in adults and elderly people with Diabetes Mellitus under treatment. The present thesis contributes in an original way by structuring risks associated with hypoglycemia and hyperglycemia in a construct of interest to nursing that may have future impacts on the organization and delimitations of professional care actions.

Introducción: los patrones que se refieren a la glucemia no se describieron ni explicaron utilizando una teoría de enfermería como referencia, ni se articularon y modelaron sobre las estructuras predictivas de interés para la acción de enfermería en estas condiciones. Por lo tanto, se presume la relevancia de construir una teoría de rango medio que aborde los factores predisponentes y precipitantes para los patrones de variabilidad relacionados con la glucemia, explicando las relaciones y prediciendo asociaciones que pueden apoyar el juicio diagnóstico de enfermería para la población con diabetes mellitus en tratamiento. Objetivo: desarrollar una teoría de rango medio sobre las variaciones glucémicas en adultos y ancianos con diabetes mellitus en tratamiento según el Modelo de Adaptación Conceptual de Roy. Método: investigación teórica como el desarrollo de una nueva teoría. Para la teorización, se utilizó la propuesta del proceso de investigación general de Holton y Lowe's (2007). Los procedimientos metodológicos desarrollados se implementaron en tres partes: parte 1 - a) comprensión de los fenómenos; b) identificación y recuperación de estudios en la revisión sistemática de etiología y riesgo y análisis del modelo de adaptación de Roy; c) análisis de la construcción; parte 2 - d) identificación de unidades teóricas; e) estipular las leyes de interacción con la producción de un modelo de interacción guiado por las diez etapas de construcción de modelos de causalidad propuestos por Jaccard y Jacoby (2010); f) determinar los límites de la teoría; g) especificación de los estados del sistema; h) desarrollo de enunciados axiomáticos; parte 3 - i) especificación de las proposiciones de la teoría. Resultados: se realizó un análisis del modelo de adaptación de Roy y una revisión sistemática de la literatura sobre los factores de riesgo de hiperglucemia e hipoglucemia en adultos y ancianos con diabetes mellitus en tratamiento. Estas estrategias permitieron, en el análisis de la construcción, el desarrollo del diagnóstico "Riesgo de patrón glucémico desequilibrado en adultos / ancianos con diabetes mellitus". El proceso de teorización determinó las unidades y estados focales, contextuales y residuales de la teoría del riesgo de patrón glucémico desequilibrado en adultos y ancianos con diabetes mellitus que se está tratando. Se produjo un modelo interactivo de las unidades focales, nueve declaraciones axiomáticas, catorce proposiciones teóricas y un modelo representativo de la teoría. Conclusiones: esta investigación desarrolló una teoría de rango medio, que describe y explica el riesgo de un patrón glucémico desequilibrado, examinando los factores que influyen en la aparición de hipoglucemia e hiperglucemia en adultos y ancianos con diabetes mellitus bajo tratamiento. La presente tesis contribuye de manera original al estructurar los riesgos asociados con la hipoglucemia y la hiperglucemia en un constructo de interés para la enfermería que puede tener impactos futuros en la organización y delimitaciones de las acciones de atención profesional.

Ingestion of a moderate dose of alcohol enhances physical exercise-induced changes in blood lactate concentration

The consumption of alcoholic beverages influences carbohydrate and lipid metabolism, although it is not yet clear whether metabolism during physical exercise at different intensities is also affected. This was the objective of the present study. Eight young and healthy volunteers performed a treadmill test to identify the running speed corresponding to a lactate concentration of 4 mM (S4mM). At least 48 h later, they were subjected to two experimental trials (non-alcohol or alcohol) in which they performed two 1-km running sessions at the following intensities: 1) S4mM; 2) 15% above S4mM. In both trials, blood lactate, triglycerides, and glucose concentrations were measured before and after exercise. The acute alcohol intake increased triglycerides, but not lactate concentration under resting conditions. Interestingly, alcohol intake enhanced the exercise-induced increase in lactate concentration at the two intensities: S4mM (non-alcohol: 4.2±0.3 mM vs alcohol: 4.8±0.9 mM; P=0.003) and 15% above S4mM trial (P=0.004). When volunteers ingested alcohol, triglycerides concentration remained increased after treadmill running (e.g., at S4mM - at rest; non-alcohol: 0.2±0.5 mM vs alcohol: 1.3±1.3 mM; P=0.048). In contrast, glucose concentration was not modified by either alcohol intake, exercise, or their combination. We concluded that an acute alcohol intake changed lactate and lipid metabolism without affecting blood glucose concentration. In addition, the increase in lactate concentration caused by alcohol was specifically observed when individuals exercised, whereas augmented triglycerides concentration was already observed before exercise and was sustained thereafter.

Modelo metabonômico para avaliação da regressão do diabetes mellitus tipo 2 após cirurgia bariátrica / Metabonomic model for the assessment of type 2 diabetes remission after bariatric/metabolic surgery

RESUMO Objetivo: avaliar as diferenças no perfil metabonômico de pacientes que atingiram remissão de diabetes mellitus tipo 2 (DM2) após cirurgia bariátrica em relação aos que apresentaram manutenção ou recidiva dessa condição após a cirurgia. Métodos: Participaram do estudo 33 pacientes obesos diabéticos tipo 2, dos quais 22 tiveram remissão completa da DM2 e 11 tiveram recidiva da DM2 ou não apresentaram remissão da doença no pós-operatório. Amostras de sangue foram coletadas para avaliação dos perfis metabonômicos séricos através de um estudo metabonômico baseado em RMN de 1H. Resultados: o modelo metabonômico para avaliação da recidiva da diabetes apresentou uma acurácia de 93,9%, sensibilidade de 81,8%, especificidade de 100%, valor preditivo positivo (VPP) igual a 100% e valor preditivo negativo (VPN) igual a 91,7%. Conclusão: a cirurgia bariátrica promove efeitos específicos na distribuição dos metabólitos de pacientes que atingiram remissão de DM2, e essa nova distribuição pode ser avaliada através de um modelo metabonômico.

ABSTRACT Purpose: To evaluate the differences in the metabonomic profile of patients who achieved remisison of Type 2 diabetes mellitus (T2DM) after bariatric surgery in relation to those who presented maintenance or recurrence of this condition after surgery. Methods: Thirthy-three patients with obesity and T2D were submitted to bariatric/metabolic surgery, among which, 22 experienced complete remission of T2D, and 11 did not experience remission in the postoperative period. Blood samples were taken in order to assess the serum profiles through a 1H NMR-based metabonomic study. Results: The metabonomic model for the assessment of T2D recurrence presented an accuracy of 93.9%, sensibility of 81.8%, specificity of 100%, positive predictive value of 100% and a negative predictive value of 91.7%. Conclusion: bariatric surgery provide specific effects on the distribution of metabolites in those patients who achieved remission of T2DM, and this new distribution can be assessed through a metabonomic model.

Análise das emissões otoacústicas transitórias por banda de frequência em adolescentes com diabetes mellitus tipo 1 / Transient otoacoustic emissions analysis by frequency bands in adolescents with type 1 diabetes mellitus

Introdução: A associação entre perda auditiva e Diabetes Mellitus tipo 1 (DM1) é ainda pouco estudada. A perda auditiva é uma das complicações crônicas relacionadas ao grau de controle glicêmico, que os pacientes podem apresentar com a progressão da doença. Objetivo: Investigar o comprometimento auditivo por meio das emissões otoacústicas transitórias (EOAT) por banda de frequência em adolescentes com DM1 e relação com o controle glicêmico. Métodos: Foram incluídos 80 adolescentes, 50% do gênero masculino, entre 10 e 19 anos de idade: 40 com DM1 e 40 controles saudáveis, pareados por gênero e idade. Os dados clínicos e laboratoriais foram pesquisados nos prontuários médicos. O controle glicêmico foi avaliado por meio dos exames de hemoglobina glicada e os pacientes com DM1 analisados de acordo com o controle glicêmico. A avaliação auditiva foi realizada por meio da imitanciometria, audiometria, e posteriormente EOAT, em sala tratada acusticamente, pelo protocolo "TE Test" de clique não-linear (1 KHz a 4 kHz) a 80 dB NPS de intensidade (AuDX - Biologic). Resultados: As respostas às EOAT foram ausentes em 5,12% em pacientes com DM1, com diferença significativa em relação aos controles (p=0,04). A análise das EOAT por bandas de frequência mostrou maior proporção de alteração nos adolescentes com DM1 mal controlados quando comparados aos bem controlados, nas frequências de 1000Hz, 2000Hz e 3000Hz (p<0,05). Conclusão: As EOAT por bandas de frequência permitiram a identificação precoce de comprometimento auditivo em adolescentes com DM1 e mostraram associação entre DM1 mal controlado e perda auditiva. (AU)

Introduction: The association between hearing loss and type 1 diabetes mellitus (DM1) is still poorly studied. Hearing loss is one of the chronic complications related to the degree of glycemic control that patients may present with the progression of the disease. Objective: To investigate auditory impairment through transient otoacoustic emissions (TEOAE) by frequency band in adolescents with DM1 and in relation to glycemic control. Methods: Were included 80 adolescents, 50% males, between 10 and 19 years of age: 40 with DM1 and 40 healthy controls, matched by gender and age. Clinical and laboratory data were taken from the medical records. Glycemic control was evalueted by glycated hemoglobin and the patients with DM1 were analyzed according to glycemic control. To the auditory evaluation were used the immittance and audiometry, and the TEOAE. The test was performed in the acoustically treated room, the non-linear TE test protocol (1 KHz to 4 kHz) at 80 dB SPL (AuDX - Biologic ). Results: TEOAE responses were absent in 5.12% of patients with DM1, with a significant difference in relation to controls (p = 0.04). The analysis of TEOAE by frequency bands showed a higher proportion of alteration in adolescents with DM1 poorly controlled when compared to well controlled ones, in the frequencies of 1000Hz, 2000Hz and 3000Hz (p <0.05). Conclusion: TEOAE by frequency bands allowed the early identification of auditory impairment in adolescents with DM1 and showed an association between poorly controlled DM1 and hearing loss. (AU)