Correlation of serum 25-hydroxyvitamin D3 with chronic inflammation and insulin resistance in polycystic ovarian syndrome patients / 中国医师进修杂志

Objective:To discuss the correlation of serum 25-hydroxyvitamin D3[25(OH)D3] with chronic inflammation and insulin resistance (IR) in polycystic ovarian syndrome (PCOS) patients.Methods:One hundred and twenty-four PCOS patients registered from January 2018 to January 2020 in the Second Affiliated Hospital of Hebei North University were selected retrospectively. According to the difference of body mass index (BMI), the patients were divided into PCOS 1 group (BMI<25 kg/m 2, 64 cases) and PCOS 2 group (BMI≥25 kg/m 2, 60 cases). At the same time, 60 patients with simple obesity were selected as the obesity group and 58 healthy subjects were selected as the control group. The somatology indicators, gonadal hormone, serum 25(OH)D3, insulin resistance (IR) related index and chronic inflammation factors were measured, the correlations of serum 25(OH)D3 with relevant indicators were analyzed by Pearson correlation analysis. Results:The BMI, waist hip ratio, testosterone(T), luteinizing hormone (LH) / follicle-stimulating hormone (FSH), free androgen index(FAI), fasting insulin (FINS), fasting plasma glucose (FPG), insulin resistance index (HOMA-IR), insulin sensitivity index (ISI) in the four groups had significant differences ( P<0.05); the level of 25(OH)D3 in the PCOS 1 group was lower than that in the PCOS 2 group: (1.14 ± 0.36) nmol/L vs. (1.83 ± 0.25) nmol/L, P<0.05; the levels of FINS, HOMA-IR in the PCOS 2 group were higher than those in the PCOS 1 group, obesity group and control group: (13.26 ± 2.61) mg/L vs. (5.58 ± 1.03), (6.63 ± 1.42), (4.66 ± 0.85) mg/L, 1.49 ± 0.37 vs. 1.15 ± 0.20, 1.12 ± 0.22, 0.96 ± 0.11, P<0.05; the level of ISI in the PCOS 2 group was lower than that in the PCOS1 group, obesity group and control group: - 4.19 ± 0.78 vs. - 3.52 ± 0.74, - 3.23 ± 0.53, - 3.06 ± 0.54, P<0.05. The levels of interleukin-6(IL-6), transforming growth factor-β(TGF-β), tumor necrosis factor-α(TNF-α) in the four groups had significant differences ( P<0.05); the level of IL-6 in the PCOS 2 group was higher than that in the PCOS 1 group: (18.15 ± 4.93) ng/L vs. (14.77 ± 4.58) ng/L, P<0.05. The results of Pearson correlation analysis showed that the serum of 25(OH)D3 had negative correlation with IL-6, BMI, waist hip ratio, T, FINS, ISI, TGF-β and TNF-α( r = - 0.582, - 0.242, - 0.371, - 0.203, - 0.208, - 0.267, - 0.723, - 0.617, P<0.05). Conclusions:Serum 25(OH)D3 is correlated with chronic inflammation and IR, and involved into the genesis and progression of PCOS.

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation / 医学前沿

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

Asiatic acid improves insulin secretion of β cells in type 2 diabetes through TNF- α/Mfn2 pathway / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg－1·d－1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.

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.

Application of insulin secretion index in disease assessment, multiple organ failure and prognosis prediction in patients with acute respiratory distress syndrome / 中国医师进修杂志

Objective:To investigate the effect of insulin secretion index (HOMA-β) in the evaluation of the condition of patients with acute respiratory distress syndrome (ARDS), multiple organ failure (MOF) and prognosis prediction.Methods:A retrospective analysis of the clinical data of 96 patients with ARDS hospitalized in Hangzhou Hospital of Zhejiang Medical Health Group from January 2019 to February 2021 was divided into MOF group (38 cases) and non-MOF group (58 cases). The baseline HOMA-β, oxygenation index, acute physiology and chronic health score Ⅱ (APACHE Ⅱ), sequential organ failure assessment (SOFA) and 28 d case fatality rate were collected and compared between the two groups. Compare the HOMA-β, oxygenation index, APACHE Ⅱ score, SOFA of ARDS patients with different survival prognosis. Logistic regression model analyzed the influence of HOMA-β, oxygenation index, APACHE Ⅱ, SOFA on the MOF and survival prognosis of ARDS patients. Pearson linear correlation method was used to analyze the relationship between HOMA-β and oxygenation index, APACHE Ⅱ, SOFA in ARDS patients. Receiver operating characteristic (ROC) curve was used to analyze the predictive power of HOMA-β on MOF and prognosis of ARDS patients.Results:The incidence of MOF and 28 d case fatality rate in 96 patients with ARDS were 39.58% (38/96) and 31.25% (31/96), respectively. The HOMA-β and oxygenation index in the MOF group were significantly lower than those in non-MOF group: 126.37 ± 28.75 vs. 178.52 ± 32.66, (125.41 ± 18.77) mmHg (1 mmHg = 0.133 kPa) vs. (153.62 ± 26.42) mmHg, while the APACHE Ⅱ, SOFA and 28 d case fatality rate were significantly higher than those in non-MOF group: (23.61 ± 4.68) points vs. (10.96 ± 2.85) points, (11.24 ± 1.65) points vs. (5.62 ± 0.87) points and 65.79% (25/38) vs. 10.34% (6/58), and there were statistical differences ( P<0.05). The HOMA-β and oxygenation index in dead ARDS patients were significantly lower than those in surviving ARDS patients: 89.62 ± 21.17 vs. 195.43 ± 35.64 and (121.66 ± 21.06) mmHg vs. (158.87 ± 28.71) mmHg, the APACHE Ⅱ and SOFA were significantly higher than those in surviving ARDS patients: (25.78 ± 5.42) points vs. (8.84 ± 2.51) points, (12.38 ± 1.22) points vs. (4.88 ± 0.83) points, and there were statistical differences ( P<0.05). Logistic regression model analysis showed that HOMA-β, oxygenation index, APACHE Ⅱ, SOFA of ARDS patients were all influencing factors of MOF and survival prognosis ( P<0.05). The results of Pearson linear correlation analysis showed that HOMA-β in ARDS patients was positively correlated with its oxygenation index ( P<0.05), and its APACHE Ⅱ and SOFA were negatively correlated ( P<0.05). ROC curve analysis results show that HOMA-β in ARDS patients has a high predictive power for their MOF and prognosis. Conclusions:The level of HOMA-β in ARDS patients is low, and it is closely related to its condition, MOF occurrence and survival prognosis. It can be used as a reference index for disease assessment and MOF and prognosis prediction of ARDS patients.

Study of electrophysiological mechanism of dopamine inhibiting insulin secretion by Kv channels / 中国药理学通报

Aim To study the electrophysiological mechanism of dopamine inhibiting insulin secretion hv voltage-dependent potassium ( Kv) channels.Methods Islets and (3 cells were isolated from male SD rats.D,-like receptor agonist ( SKP38393), D2-like receptor agonist (Quinpirole) and antagonist (Epiclopride) were used according to the experiment.Insulin secretion was detected by insulin radioimmunoassay.Whole-cell j J patch-clamp technique was applied to detect Kv channel currents and action potential duration of p cells.Di- BAC4(3) staining was used to observe membrane potential.Results SKF38393 did not affect insulin secretion and the Kv channel currents.Quinpirole signifi cantly inhibited insulin secretion and increased Kv channel currents.Dopamine significantly inhibited insulin secretion, increased Kv channel currents and shortened action potential duration of p cells, which could be reversed by epiclopride.In addition, dopamine de-creased membrane potential of INS-1 cells.Conclusions Dopamine inhibits insulin secretion by acting on D2-like receptors, resulting in actived Kv channels, shortened action potential duration and decreased cell membrane potential.

The insulinotropic effects and its relevant mechanism of telmisartan in rats / 中国药理学通报

Aim To investigate the insulinotropic effect of telmisartan anrl the underlying electrophysiological mechanism.Methods Islets and cells were isolated from Wistar rats.Islets were incubated with drugs un¬der different conditions, then supernatant liquid was collected for insulin secretion.Intracellular Ca" + ( Ca'+ j) levels of (3-cells were measured by calcium imaging technology.Patch-clamp technology was ap¬plied to detect effects on voltage-gated potassium chan¬nel ( Kv ) , and voltage-gated calcium channel ( VGCC ).Results Not affecting insulin secretion un¬der low glucose condition, telmisartan dose-dependent- ly stimulated insulin secretion under high glucose con¬ dition, and stimulation was enhanced with increasing glucose concentration.Acute increases of Ca' + concentration were elicited by telmisartan under high glucose condition.Telmisartan decreased current den¬sity of Kv channel, and increased VGCC current densi¬ty.Conclusions Telmisartan enhanced Ca~+ ; lev¬els of p-cells through its action on Kv channel and VGCC, thereby amplifying glucose-stimulated insulin secretion.

Fisiopatología y alteraciones clínicas de la diabetes mellitus tipo 2: revisión de literatura / Physiopathology and clinical alterations of diabetes mellitus 2: literature review

Resumen La diabetes mellitus tipo 2 constituye una condición clínica debilitante, degenerativa y multifacética de alta prevalencia a nivel mundial. Dada la complejidad de su fisiopatología y las variadas opciones terapéuticas que existen esta enfermedad presenta un desafío para el médico general, se hace imperativo describir comprensiblemente esta patología para mejorar la resolutividad de ésta en atención primaria. Tras una búsqueda bibliográfica exhaustiva de 103 estudios publicados hasta el año 2010, se identificaron los aspectos más importantes tanto de la fisiología, fisiopatología, complicaciones y terapéuticas de esta patología. La resistencia a la insulina (RI) es una condición metabólica central en la etiopatogenia de esta patología donde se logra reconocer de manera clásica tanto la pérdida de la acción periférica de la insulina por parte de los diferentes tejidos, así como defectos en la secreción de insulina conllevando estados de hiperglucemia constantes asociados tanto a complicaciones agudas como crónicas caracterizadas por provocar disfunción y fallo en diferentes órganos. Es de conocimiento general que parte importante de los resultados en el manejo de esta patología se logran con cambios en el estilo de vida que van desde modificaciones en la dieta a cambios en el patrón de actividad física con pérdida de peso corporal. No obstante, existe a su vez una amplia gama de terapias farmacológicas orientadas a controlar estados hiperglucémicos ante la falla de la terapia no farmacológica. Dentro de este mismo contexto varias son las dianas y objetivos terapéuticos en el tratamiento del diabético tipo 2, sin embargo, todas confluyen en el control metabólico de los estados de hiperglucemia y la prevención de sus complicaciones.

Abstract Type 2 diabetes mellitus is a debilitating, degenerative and multifaceted clinical condition with a high prevalence worldwide. Given the complexity of its pathophysiology and the various therapeutic options that exist, this disease presents a challenge for the general practitioner, it is imperative to understand this pathology to improve its resolution in primary care. After an exhaustive bibliographic search of 103 studies published up to 2010, the most important aspects of both the physiology, pathophysiology, complications, and therapeutics of this pathology were identified. Insulin resistance (IR) is a central metabolic condition in the etiopathogenesis of this pathology. Classically it is possible to recognize both the loss of the peripheral action of insulin by the different tissues as well as defects in the secretion of insulin that leads to constant hyperglycemic states associated with both acute and chronic complications characterized by causing dysfunction and failure in different organs. It is generally known that an important part of the results in the management of this pathology are achieved with changes in lifestyle that range from modifications in diet to changes in the pattern of physical activity with loss of body weight. However, there also is a wide range of pharmacological therapies aimed at controlling hyperglycemic states in the event of the failure of non-pharmacological therapy. Within this same context, there are several therapeutic targets and objectives in the treatment of type 2 diabetics, however, they all converge in the metabolic control of hyperglycemic states and the prevention of their complications

Effect of free fatty acids on insulin secretion, insulin sensitivity and incretin effect - a narrative review

ABSTRACT Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and β-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional β-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of β-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.

Effect of long-chain non-coding RNA GAS5 on insulin secretion of islet cells by targeting miR-29, miR-96, and miR-208 / 中华内分泌代谢杂志

Objective:To investigate the role and mechanism of long non-coding RNA GAS5 in the targeted regulation of miR-29, miR-96, and miR-208 in promoting insulin secretion of pancreatic β-cells.Methods:Q-PCR was used to detect the expression of miR-29, miR-96, and miR-208 in sera of 122 healthy subjects and 88 type 2 diabetic patients; and so of long non-coding RNA GAS5 and miR-208 in the rat islet cell tumor strain ins-1832/13. Effects of silencing and overexpressing GAS5 on insulin secretion of islet β-cells by lentiviral vector construction were observed. Bioinformatics was used to predict that GAS5 had complementary binding sites with miR-29, miR-96, and miR-208, which was further verified by luciferase reporting system. GAS5 siRNA was co-transfected with miR-29, miR-96, and miR-208 inhibitors, and the effect of GAS5 on insulin receptor (INSR), insulin receptor substrate (irs-1) and PI3K levels was detected by the above method, so as to reveal the effect of GAS5 on insulin secretion in islet cells.Results:The expression of GAS5 in serum of T2DM patients was lower than that of healthy control group ( t=4.632, P<0.01), and expression of miR-29, miR-96, and miR-208 were higher than those of healthy control group ( t were 7.832, 9.164, and 12.359, all P<0.01). GAS5 level was negatively correlated with miR-29, miR-96, and miR-208 ( r were -0.50, -0.47, and -0.70, respectively). GAS5 expression was significantly decreased in serum of type 2 diabetic patients compared with that of in healthy subjects. Overexpression of GAS5 by lentivirus resulted in increased glucose-stimulated insulin secretion and increased insulin concentration compared to negative control. In contrast, knockdown of GAS5 led to significant reduction of glucose-stimulated insulin secretion and insulin concentration. GAS5 levels were negatively correlated with miR-29, miR-96, and miR-208 in serum samples of type-2 diabetes patients. GAS5 can negatively regulate the expression of miR-96, miR-29, and miR-208. By bioinformatics tools, we screened miR-29, miR-96 and miR-208 as targets of GAS5, and their interaction was validated with dual luciferase reporter gene assay. shGAS5 significantly decreased the expressions of INSR, IRS-1 and PI3K( P were 0.022, 0.038, and 0.009), while overexpressed GAS5 significantly upregulated the expressions of INSR, IRS-1 and PI3K at both mRNA and protein levels( P were 0.024, 0.045, and 0.016). Conclusion:GAS5 could stimulate insulin secretion of islet cell through its inhibitry regulationor of expressions of miR-29, miR-96, and miR-208, therely up-regulating INSR, IRS-1, and PI3K that may be the potential targets of these miRNAs, and stimulate insulin secretion of islet cells.

Hypoglycemic effects of Tibetan medicine Huidouba in STZ-induced diabetic mice and db/db mice / 中草药·英文版

Objective: Huidouba (HDB) is a Chinese folk medicine used to treat diabetes in Sichuan Province, China. Therefore, we investigated the anti-diabetic effects of HDB and its underlying mechanisms. We hypothesized that HDB treatment could enhance glucose tolerance and insulin sensitivity, and thus prevent a hyperglycemia state. Methods: To test the hypothesis, streptozotocin (STZ)-induced diabetic mice and db/db mice, widely used models of hyperglycemia and insulin-resistant diabetes, were either treated with HDB, metformin, or acarbose. Blood glucose, oral glucose tolerance test, insulin tolerance test, pancreatic histopathology and serum biochemistry were detected to assess the hypoglycemic effect of HDB. Results: HDB treatments were found to show the effect in reducing glucose levels. HDB also resulted in a significant reduction in body weight and food intake in the STZ-induced diabetic mouse model. Furthermore, it significantly improved glucose and insulin tolerance in the two diabetic mouse models. Importantly, insulin, glucagon, pancreatic polypeptide, and somatostatin immunohistochemistry revealed that HDB treatment improved the function and the location of the cells in the islets compared with the other two treatments. HDB treatment resulted in significant restoration of islet function. Our results illustrated the underlying mechanism of HDB in the progression of diabetes, and HDB can be an effective agent for the treatment of diabetes. Conclusion: The results of this study suggested that HDB can reduce blood glucose levels in STZ-induced hyperglycemic mice and db/db mice.

Utilidad de la prueba de tolerancia de comida mixta con Nutrial I para la evaluación de la función de las células beta en diabetes tipo 1 / Usefulness of the tolerance test of mixed food with Nutrial I for the assessment of beta cells function in diabetes type 1

RESUMEN Introducción: La prueba de tolerancia de comida mixta es considerada la prueba de oro para la medición de la producción de insulina endógena en pacientes con diabetes tipo 1. Objetivo: Determinar la utilidad de la prueba de tolerancia de comida mixta con Nutrial I para evaluar la función de las células ß en diabéticos tipo 1 de diagnóstico reciente y la relación de esa función con algunas características clínicas y bioquímicas. Métodos: Se estudiaron variables bioquímicas como la glucemia, hemoglobina glucosilada (HbA1c), péptido C y fracciones lipídicas. La prueba de tolerancia de comida mixta con Nutrial I se aplicó a 18 sujetos con diabetes tipo 1 de diagnóstico reciente y a 8 voluntarios con edades comprendidas entre 19 y 35 años. El consumo del suplemento Nutrial I se calculó según el peso del paciente. Se obtuvieron muestras para glucemia y péptido C a los -10, 0, 30, 60, 90 y 120 minutos. Resultados: Se observaron concentraciones elevadas de glucemia y disminuidas de péptido C durante la prueba de tolerancia de comida mixta en los diabéticos tipo 1 de diagnóstico reciente, en comparación con los voluntarios, así como, diferencias en las áreas bajo la curva de péptido C (AUC-pc) (p= 0,001). En los diabéticos tipo 1 de diagnóstico reciente se evidenció una correlación negativa entre el AUC-pc con los niveles de glucemia en ayunas (r= -0,747; p ( 0,0001) y la HbA1c (r= -0,535; p= 0,022). Por el contrario, se encontró una correlación positiva entre el AUC-pc y el péptido C en ayunas (r= 0,722; p= 0,001). El AUC-pc después de la prueba de tolerancia de comida mixta es mayor en los sujetos con glucemia en ayunas si GA < 7 mmol/L con respecto a los sujetos con glucemia en ayunas ( 7 mmol/L (p= 0,012). Conclusiones: El empleo del Nutrial I en la prueba de tolerancia de comida mixta fue útil en la evaluación de la función de las células β en diabéticos tipo 1 de diagnóstico reciente. Los valores bajos de glucemia en ayunas durante esta prueba son marcadores indirectos de una función residual de células ( más conservada en los diabéticos tipo 1 de diagnóstico reciente(AU)

ABSTRACT Introduction: The tolerance test of mixed food is considered the gold standard for the measurement of endogenous insulin production in patients with diabetes type 1. Objective: To determine the usefulness of the tolerance test of mixed food with Nutrial I to assess the ß-cells function in patients with diabetes type 1 of recent diagnosis and the relation of this function with some clinical and biochemical characteristics. Methods: There were studied biochemical variables as the blood glucose, glycosylated haemoglobin (HbA1c), C-peptide and lipid fractions. The tolerance test of mixed food with Nutrial I was applied to 18 individuals with diabetes type 1 of recent diagnosis and in 8 volunteers aged between 19 and 35 years old. The consumption of Nutrial I supplement was calculated according to the weight of the patient. Samples were obtained for blood glucose and C-peptide at -10, 0, 30, 60, 90 and 120 minutes. Results: There were observed high concentrations of glycemia and decreased amounts of C-peptide during the tolerance test of mixed food in recently diagnosed type 1 diabetics in comparison with the volunteers, as well as differences in areas under the curve of C-peptide (AUC-pc) (p= 0.001). In the recently diagnosed type 1 diabetics was evident a negative correlation between the AUC-pc with fasting plasma glucose levels (r= -0,747; p(0.0001) and HbA1c (r= -0,535; p= 0.022). On the contrary, it was found a positive correlation between the AUC-pc and fasting C-peptide (r = 0.722; p = 0.001). The AUC-pc after the tolerance test of mixed food was greater in subjects with fasting blood glucose < 7 mmol/L with respect to the subjects with fasting blood glucose ( 7 mmol/L (p= 0.012). Conclusions: The use of Nutrial I in the tolerance test of mixed food was useful in the assessment of the role of the β-cells in patients with recently diagnosed diabetes type 1. Low values of fasting blood glucose during this test are indirect markers of a residual function of (cells more preserved in type 1 diabetics of recent diagnosis(AU)

Inhibition of miR-802 on insulin secretion by targeting Hnf1B / 中国药科大学学报

@#To investigate the effect of miR-802 on insulin secretion by islet β cells and its mechanism, miR-802 was overexpressed or knocked down in primary islet cells and Min6 cells via transfecting miR-802 mimic and miR-802 inhibitor, respectively. The effect of miR-802 on insulin secretion was detected by ELISA. The target gene of miR-802 was confirmed by miRNA target gene database prediction, luciferase report and Western blot. The function recovery experiment was carried out to clarify the mechanism of miR-802 regulating β cell secretion of insulin. The results showed that overexpression of miR-802 in islet primary cells and Min6 cells inhibited insulin secretion. qPCR and Western blot showed that miR-802 inhibited insulin secretion by inhibiting the transcription and translation of the target gene, hepatocyte nuclear factor 1β(Hnf1B).

The relationships between hemoglobin and insulin resistance, glucose effectiveness, and first- and second-phase insulin secretion in adult Chinese

ABSTRACT Objective We denote the four major factors related to the development of type 2 diabetes (T2D) as "diabetes factor" (DF); increased insulin resistance (IR); decreased glucose effectiveness (GE); and the first-and-second-phase of insulin secretion (FPIS, SPIS). The level of hemoglobin (Hb) was found to be related to IR and FPIS, but no-known studies focused on its role in relation to SPIS and GE. In this study, we aim to evaluate the relationships between Hb and all four DFs in the same individual. Subjects and methods We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured according to equations published in our previous studies. To compare the slopes between Hb and the four DFs with different units, we converted their units to percent of change per unit of increased Hb. Results Age, HDL-cholesterol and GE were higher in women; BMI, blood pressure, LDL-cholesterol, TG, Hb, FPIS, SPIS and IR were higher in men. After they were converted into percentage, the closeness of their relationships to Hb, from the highest to the lowest, were GE, IR, FPIS and SPIS for women and IR, GE, FPIS and SPIS for men. GE was the only one negatively related to Hb. Conclusions Our data showed that IR, FPIS and SPIS were both positively and, GE negatively, related to the Hb in adult Chinese. For women, GE had the closest association with Hb; for men, it was IR. Both phases of insulin secretion had relatively weaker relationships than IR and GE.

¿Influye el consumo de comidas ricas en proteínas y grasas en la glucemia postprandial de pacientes con diabetes tipo 1 que realizan conteo de hidratos de carbono? / Does the consumption of meals rich in proteins and fats influence on the postprandial glucemia of patients with diabetes type 1 that follow carbohydrate counting?

Introducción: el tratamiento de la diabetes tipo 1 (DM1) requiere de la administración de insulina exógena; dentro de las variables a tener en cuenta para calcular la dosis se encuentra el contenido de hidratos de carbono (HC) de la comida a ingerir. Este macronutriente es considerado, desde hace varios años, el responsable del aumento de la glucemia postprandial (GPP). El conteo de hidratos de carbono (CHC) es el método más aceptado y utilizado actualmente en el tratamiento nutricional, aunque cada vez existe más evidencia de que hay otros macronutrientes, como las proteínas y las grasas, que pueden influir en la variación de la GPP. Objetivo: el objetivo de esta revisión bibliográfica es reunir los resultados de publicaciones científicas que analizaron la respuesta glucémica (RG) al consumo de comidas con alto contenido de proteínas y grasas y hacer un análisis de las diferentes intervenciones. Materiales y método: búsqueda bibliográfica en PUBMED, inicialmente 196 artículos. Luego de aplicar los criterios de inclusión y exclusión se seleccionaron 26 artículos realizados en personas con DM1 de los últimos 10 años (2007-2017) referidos al consumo de comidas altas en proteínas y grasas. Resultados: hay una significativa variación interpersonal en los requerimientos de insulina en respuesta a las grasas y proteínas dietarias, que puede fluctuar en un 65% ± 10%. En los estudios randomizados se logró determinar que en las comidas altas en grasas el pico de GPP fue demorado y la sensibilidad a la insulina fue menor. Uno de los estudios logró demostrar que el 100% de las comidas altas en grasa se asociaron con hiperglucemia tardía. En relación a las dos revisiones sistemáticas encontradas, se hace hincapié en la búsqueda de datos para mejorar el tratamiento intensificado de la DM1, siendo el control de la GPP el indicador principal, ponderando la importancia de considerar la ingesta proteica y grasa de manera adicional al CHC. Conclusión: se concluye que el efecto de una comida con un alto contenido en proteínas y grasas sobre la glucemia suele presentarse entre las 3 a 6 hs de consumidas, siempre teniendo en cuenta la respuesta individual y el modo de administrar la insulina. La tarea del equipo interdisciplinario es fundamental para conocer la respuesta individual en el paciente con DM1 ante el consumo de comidas altas en proteínas y grasas, pudiendo así orientar la toma de decisión(AU).

Introduction: the treatment of type 1 diabetes (DM1) requires the administration of exogenous insulin, being the carbohydrate (HC) content of the meal to be ingested one of the variables to be considered to calculate the insulin dose. For several years, this macronutrient has been considered responsible for the increase in postprandial glycemia (PPG). Carbohydrate Counting (CHC) is the most accepted and currently used method in the nutritional treatment, although there is enough evidence that other macronutrients, such as protein and fat, can influence on the variation of PPG. Objective: to gather the results of scientific publications which analysed the glycemic response (GR) to the consumption of high-protein and high-fat meals and to analyse de different interventions. After applying the inclusion and exclusion criteria, 24 articles were selected including those with individuals with DM1 from the past 10 years (with the exception of one) referring to the consumption of high-protein and high-fat meals. Results: there is a significant interpersonal variation in insulin requirements in response to dietary fat and protein, which can fluctuate by 65% +/- 10%. Randomized studies showed that in the high-fat meals, the peak of PPG was delayed and insulin sensitivity was lower. One of the studies showed that 100% of high-fat meals were associated with late hyperglycemia. Both systematic reviews emphasize the need to search for data to improve the intensive treatment of DM1, with the control of PPG being the main indicator, considering protein and fat intake, in addition to CHC. Conclusion: the effect on blood glucose of high-protein and high-fat meals usually occurs between 3 to 6 hours after being consumed, always considering the individual response and the insulin administration method. The task of the interdisciplinary team is essential to know the individual response in the DM1 patient to the consumption of high-protein and high-fat meals, thus being able to guide the decision-making process(AU).

Pancreatic ß-cell function is inhibited by miR-3666 in type 2 diabetes mellitus by targeting adiponectin

Type 2 diabetes mellitus (T2D) is a common endocrine and metabolic disorder, and poses threats to human health worldwide. Recently, microRNAs (miRNAs) have been suggested to play important roles in the pathophysiology of T2D. In this study, we explored the role of miR-3666 in T2D. miR-3666 was significantly down-regulated in the serum of T2D patients when compared to that of healthy volunteers, and miR-3666 expression level was negatively correlated with blood glucose levels of T2D patients. Overexpression of miR-3666 inhibited cell proliferation, reduced insulin secretion, and promoted cell apoptosis of pancreatic β-cell line (INS-1 cells). On the other hand, knockdown of miR-3666 had the opposite effects in INS-1 cells. The bio-informatics analysis using TargetScan revealed that adiponectin (ADIPOQ) was a downstream target of miR-3666, and the interaction between miR-3666 and ADIPOQ was validated by luciferase reporter assay. In addition, miR-3666 negatively regulated the mRNA and protein expression of ADIPOQ. Overexpression of ADIPOQ promoted insulin secretion after glucose stimulation, promoted cell proliferation, inhibited cell apoptosis, and partially abolished the effects of miR-3666 overexpression on insulin secretion, cell proliferation, and cell apoptosis of INS-1 cells. In conclusion, our results revealed that miR-3666 inhibited pancreatic cell proliferation, reduced insulin sensitivity, and promoted apoptosis by targeting ADIPOQ.

The Association of Adiponectin and Visceral Fat with Insulin Resistance and β-Cell Dysfunction

BACKGROUND: Obesity is a risk factor for metabolic abnormalities. We investigated the relationship of adiponectin levels and visceral adiposity with insulin resistance and β-cell dysfunction. METHODS: This cross-sectional study enrolled 1,347 participants (501 men and 846 women aged 30–64 years) at the Cardiovascular and Metabolic Diseases Etiology Research Center. Serum adiponectin levels and visceral fat were measured using enzyme-linked immunosorbent assay kits and dual-energy X-ray absorptiometry, respectively. Insulin resistance was evaluated using the homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index. β-cell dysfunction was evaluated using the homeostatic model assessment of β-cell function (HOMA-β), insulinogenic index, and disposition index. RESULTS: Regarding insulin resistance, compared with individuals with the highest adiponectin levels and visceral fat mass < 75th percentile, the fully adjusted odds ratios (ORs) for HOMA-IR ≥ 2.5 and Matsuda index < 25th percentile were 13.79 (95% confidence interval, 7.65–24.83) and 8.34 (4.66–14.93), respectively, for individuals with the lowest adiponectin levels and visceral fat ≥ 75th percentile. Regarding β-cell dysfunction, the corresponding ORs for HOMA-β< 25th percentile, insulinogenic index < 25th percentile, and disposition index < 25th percentile were 1.20 (0.71–2.02), 1.01 (0.61–1.66), and 1.87 (1.15–3.04), respectively. CONCLUSION: Low adiponectin levels and high visceral adiposity might affect insulin resistance and β-cell dysfunction.

Research progress of oxytocin and diabetes / 中华内分泌代谢杂志

Oxytocin is a classic neuropeptide hormone. In recent years, basic and clinical researches have shown that oxytocin is involved in the regulation of blood glucose homeostasis by protecting islet β cells, promoting insulin secretion and peripheral tissue glucose uptake. This article reviews the recent evidence of the linkage between oxytocin and diabetes mellitus.

Effect of vitamin D intervention on the outcome of glucose metabolism in patients with impaired glucose regulation / 中华临床营养杂志

Objective To explore the intervention effect of low-dose vitamin D on glucose metabolism of patients with impaired glucose regulation. Methods A total of196 subjects receiving oral glucose tolerance test were enrolled in this study, including individuals with normal glucose tolerance ( NGT group, n=67) and indi-viduals with impaired glucose regulation (IGR group, n=129). The IGR group was divided into intervention group ( n=64) and non-intervention group ( n=65) according to vitamin D intervention ( for 1 year) performed or not. Clinical data and biochemical parameters were collected. Results The level of serum 25(OH)D3 was significantly lower in the IGR group than that of normal control group ( P<0. 05) . After 1 year of low-dose vita-min D intervention, insulin sensitivity increased and insulin resistance decreased in the intervention group as compared with non-intervention group. Diabetes developed less frequently in the intervention group ( 25 of 64 [ 39. 1％] ) compared with non-intervention group ( 30 of 65 [ 46. 2％] ) . But there was no significant differ-ent in diabetes prevalence between the two groups. Conclusions Vitamin D intervention can improve insulin sensitivity and reduce insulin resistance in patients with impaired glucose regulation. Low dose vitamin D can improve the abnormal glucose metabolism outcome in patients with impaired glucose regulation.

Changes in Glucose Metabolism with Aging / 임상당뇨병

The increasing risk of glucose intolerance and diabetes associated with aging is well established. However, it is difficult to determine whether changes in glucose metabolism result from biological aging itself or due to various environmental factors that occur during the aging process. Many epidemiologic studies have shown that plasma glucose levels after oral glucose tolerance test rise consecutively for every decade of age, but many of these studies also demonstrated the effects of environmental factors including obesity and exercise. In some studies, the development of insulin resistance and insulin secretion defects due to biological aging itself have also been identified as major etiologic factors of glucose intolerance. However, the rate of diabetes development due to these factors is expected to be very slow and largely preventable by addressing environmental risk factors.