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Insulin resistance is the primary contributor to the disruption in glucose homeostasis in the body, playing a significant causative role in many metabolic diseases. Insulin resistance is characterized by compensatory insulin secretion and reduced insulin responsiveness in target organs. Dysregulation of the interaction between insulin-secreting cells and insulin-responsive target organs is an important factor driving the progression of insulin resistance. Circulating endocrine hormones are important mediators mediating the interaction between insulin-secreting cells and insulin-responsive target organs. In addition to the classical hormones secreted by endocrine glands and organ-specific hormones secreted by metabolism-related organs (adipose tissue, muscle, liver, etc.), extracellular vesicles have been recognized as a novel class of endocrine hormones with a complex composition. Extracellular vesicles can transport signaling molecules, such as miRNAs and LncRNAs, to vital organs related to insulin resistance, in a manner akin to conventional hormones. The significant role in regulating the development of insulin resistance underscores the increasing interest in extracellular vesicles as essential contributors to this process. In this review, we summarize the three types of hormones (classical hormones, organokines and extracellular vesicles) that play a regulatory role in insulin resistance, and focus on the novel endocrine hormones, extracellular vesicles, to elaborate the mechanism of extracellular vesicles' regulation of insulin resistance progress from two aspects: the impact on insulin-secreting cells and the influence on insulin-responsive target organs. In addition, this paper outlines the clinical applications of extracellular vesicles in insulin resistance. A comprehensive understanding of the regulatory mechanisms and diagnostic status of the inter-organ network in insulin resistance has great potential to advance targeted therapeutic interventions and diagnostic markers, thereby benefiting both the prevention and treatment of insulin resistance.
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Vesículas Extracelulares , Resistencia a la Insulina , Humanos , Vesículas Extracelulares/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/fisiología , Insulina/metabolismo , Hormonas/metabolismo , Animales , Tejido Adiposo/metabolismo , MicroARNs/metabolismo , MicroARNs/genéticaRESUMEN
Importance: An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide additional benefits to patients with type 2 diabetes. Objective: To evaluate the effect of the 5:2 MR on glycemic control among patients with early type 2 diabetes compared with metformin and empagliflozin. Design, Setting, and Participants: The EARLY (Exploration of Treatment of Newly Diagnosed Overweight/Obese Type 2 Diabetes Mellitus) study is a randomized, open-label, active parallel-controlled clinical trial conducted between November 13, 2020, and December 29, 2022, in 9 centers across China. A total of 509 eligible patients underwent screening, out of which 405 were randomly assigned to 3 groups and included in the intention-to-treat analysis. Interventions: Patients were randomly allocated in a 1:1:1 ratio to receive either metformin, empagliflozin, or 5:2 MR. The treatment was 16 weeks, with an 8-week follow-up. Main Outcomes and Measures: The primary end point was the change in hemoglobin A1c (HbA1c) level from baseline to 16 weeks. Secondary end points included changes in body weight, anthropometric measurements, and biochemical parameters. Results: Of the 405 randomized participants (265 men [65.4%]; mean [SD] age, 45.5 [11.0] years; mean [SD] body mass index, 29.5 [4.1]; and mean [SD] HbA1c level, 7.9% [0.6%]), 332 completed the 16-week treatment. From baseline to week 16, participants in the 5:2 MR group showed the greatest reduction in HbA1c (least-squares mean [LSM], -1.9% [SE, 0.2%]), significantly greater than patients receiving metformin (LSM, -1.6% [SE, 0.2%]; adjusted LSM difference, -0.3% [95% CI, -0.4% to -0.1%]) and empagliflozin (LSM, -1.5% [SE, 0.2%]; adjusted LSM difference, -0.4% [95% CI, -0.6% to -0.2%]). At week 16, the mean weight loss in the 5:2 MR group (LSM, -9.7 kg [SE, 2.2 kg]) was greater than that in the metformin group (LSM, -5.5 kg [SE, 2.3 kg]) and empagliflozin group (LSM, -5.8 kg [SE, 2.3 kg]). Conclusions and Relevance: This randomized clinical trial of Chinese adults with overweight or obesity and with early type 2 diabetes found that 5:2 MR could improve glycemic outcomes and weight loss in the short term compared with metformin or empagliflozin, making it a promising initial intervention and early management for type 2 diabetes. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000040656.
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Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Ayuno , Glucósidos , Control Glucémico , Metformina , Humanos , Masculino , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ayuno/sangre , Metformina/uso terapéutico , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Control Glucémico/métodos , Adulto , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéutico , China , Glucemia/análisis , Glucemia/efectos de los fármacos , Ayuno IntermitenteRESUMEN
AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.
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Diabetes Mellitus Tipo 2 , Quimioterapia Combinada , Hemoglobina Glucada , Hipoglucemiantes , Metformina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Glucemia/efectos de los fármacos , Glucemia/metabolismo , China , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Método Doble Ciego , Pueblos del Este de Asia , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Metformina/uso terapéutico , Metformina/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: High mobility group box-1 (HMGB1) is an endogenous danger signal that mediates activation of the innate immune response including NLR pyrin domain containing 3 (NLRP3) inflammasome activation and proinflammatory cytokine release. Although HMGB1 and NLRP3 have been implicated in the pathophysiology of seizures, the correlation between HMGB1 and NLRP3 expression has not been determined in children with febrile seizures (FS). To explore the relationship between extra-cellular HMGB1 and NLRP3 in children with FS, we analyzed serum HMGB1, NLRP3, caspase-1, and proinflammatory cytokines in patients with FS. METHODS: Thirty children with FS and thirty age-matched febrile controls were included in this study. Blood was obtained from the children with FS within 1 h of the time of the seizure; subsequently, the serum contents of HMGB1, NLRP3, caspase-1, interleukin (IL)-1ß, interleukin (IL)-6, and tumour necrosis factor-α (TNF-α) were determined by enzyme-linked immunosorbent assay. The MannâWhitney U test was used to compare serum cytokine levels between FS patients and controls. Spearman's rank correlation coefficient was calculated to detect significant correlations between cytokine levels. RESULTS: Serum levels of HMGB1, NLRP3, caspase-1, IL-1ß, IL-6, and TNF-α were significantly higher in FS patients than in febrile controls (p < 0.05). Serum levels of HMGB1 were significantly correlated with levels of NLRP3 and caspase-1 (both, p < 0.05). Serum levels of caspase-1 were significantly correlated with levels of IL-1ß (p < 0.05). Serum levels of IL-1ß were significantly correlated with levels of IL-6 and TNF-α (p < 0.05). CONCLUSIONS: HMGB1 is up-regulated in the peripheral serum of FS patients, which may be responsible, at least in part, for the increased expression of NLRP3 and Caspase-1. Increased expression of caspase-1 was significantly associated with elevated serum levels of IL-1ß. Given that activated Caspase-1 directly regulates the expression of mature IL-1ß and positively correlates with activation of the NLRP3 inflammasome, our data suggest that increased levels of peripheral HMGB1 possibly mediate IL-1ß secretion through the activation of the NLRP3 inflammasome in children with FS. Thus, both HMGB1 and NLRP3 might be potential targets for preventing or limiting FS.
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Proteína HMGB1 , Convulsiones Febriles , Niño , Humanos , Estudios de Casos y Controles , Caspasas , Citocinas , Inflamasomas/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6 , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor de Necrosis Tumoral alfaRESUMEN
AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.
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Diabetes Mellitus Tipo 2 , Hipoglucemia , Masculino , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina Glargina/efectos adversos , Hipoglucemiantes/efectos adversos , Glucemia , Hemoglobina Glucada , Insulina/efectos adversos , Hipoglucemia/inducido químicamente , Hipoglucemia/prevención & control , Hipoglucemia/tratamiento farmacológico , Insulina Regular Humana/uso terapéuticoRESUMEN
Objective: To study the effects of liraglutide or lifestyle interventions combined with other antidiabetic drugs on glucose metabolism and abdominal fat distribution in patients with obesity and type 2 diabetes mellitus (T2DM). Methods: From April 30, 2020, to April 30, 2022, a prospective randomized controlled study was carried out at the Endocrinology Department of Beijing Hospital, the National Center of Gerontology. According to the in- and exclusion criteria and by the random table method, revisited T2DM patients were selected as the research subjects and were allocated into a Study group (taking liraglutide) and a Control group (underwent lifestyle interventions). All patients received continuous 12-weeks interventions to the endpoint, and the changes of value [Δ=(endpoint)-(baseline)] of physical measurements, blood tests, the energy spectrum CT examination results, and body composition analysis results were analyzed and compared. Results: A total of 85 people completed this study, and among them, 47 were in the Study group and 38 were in the Control group. Compared with the Control group, the changes of hemoglobin A1c (HbA1c) level (-0.78 ± 1.03% vs. -1.57 ± 2.00%, P=0.025), visceral fat area (0.91 ± 16.59 cm2 vs. -7.1 ± 10.17 cm2, P=0.011), and subcutaneous fat area of abdomen [0 (-18.75, 15.5) cm2 vs. -16.5 (-41.75, -2.25) cm2, P=0.014] were all greater in the Study group. The adverse events caused by liraglutide were mainly concentrated in the gastrointestinal system and all of them were minor adverse events. Conclusion: Liraglutide can be the drug of choice for weight management and reduction of abdominal fat distribution in patients with obesity and T2DM.
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Diabetes Mellitus Tipo 2 , Liraglutida , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/farmacología , Grasa Intraabdominal/diagnóstico por imagen , Estilo de Vida , Liraglutida/farmacología , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Estudios Prospectivos , Tomografía Computarizada por Rayos XRESUMEN
The absorption of needle-free fast-acting insulin injected into different body parts of healthy male subjects was studied in an attempt to provide clinical guidance for diabetic patients who take needle-free insulin injections in terms of providing reference in the clinical guidance regarding the correct use of needle-free insulin injections among diabetic patients. This randomized, open-label, cross-over trial was conducted on eight healthy adult male volunteers, in which the skin thickness at three injection sites (abdomen, upper arm, and thigh), the time to peak, peak rate, and area under the glucose infusion rate (GIR) curve of plasma insulin were measured through the hyperinsulin-normal glucose clamp test after the injection of insulin aspart with a needle-free syringe at three different sites to analyze the correlation between insulin absorption index at different injection sites and skin thickness. The values of the skin thickness of the abdomen, upper arm, and thigh measured by ultrasonic wave were 2.45 ± 0.34 mm, 2.18 ± 0.50 mm, and 1.93 ± 0.55 mm, respectively. There was a significant difference in the skin thickness of the abdomen and thigh (P = 0.014). The hyperinsulin-normal glucose clamp model was successfully established for each subject. Approximately 0-2 h after injection of insulin aspart with needle-free syringes, the area under the GIR-time curve of the abdomen, upper arm, and thigh was 29,400.75 ± 2,645.00 ml, 30,230.50 ± 4,937.87 ml, and 30,179.63 ± 6,188.57 ml, respectively. There was no significant difference in the area under the GIR curve between any two injection sites (P >0.05). The time to peak of GIR at different injection sites was 38.68 ± 13.57 min in the abdomen, 40.86 ± 12.70 min in the upper arm, and 37.03 ± 13.29 min in the thigh, respectively, in which no significant difference was found between each of them (P >0.05). The GIR curve after injection at the three different sites was consistent with each other. There was no significant difference in insulin absorption after the injection of insulin aspartate into the abdomen, upper arm, and thigh with a needleless syringe in healthy male adult volunteers, and there was no correlation between skin thickness at the injection site and insulin absorption. Injection sites did not affect the absorption of insulin in needle-free injections.
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Diabetes Mellitus , Insulina Aspart , Adulto , Glucemia , Glucosa , Cuerpo Humano , Humanos , Insulina , MasculinoRESUMEN
OBJECTIVE: Observe the influence of oral nutritional agents rich in soluble dietary (enteral nutritional suspension [TPF-DM]) on intestinal flora of elderly male subjects with malnutrition. METHOD: Seventy-eight subjects with good nutrition were considered as the healthy control group. Twenty-eight male subjects who had malnutrition and were older than 70 years were included and randomly divided into the short-term (3 months) intervention group (n = 20) and the long-term (12 months) group (n = 8). They were provided with enteral nutritional suspension (TPF-DM) 500 mL/day or maximum tolerance dose, so as to observe the changes in nutrition-related indexes and intestinal flora after the elderly take enteral nutritional suspension (TPF-DM). RESULTS: (1) For elderly male subjects with malnutrition, their body weight, body mass index, hemoglobin, total protein, and albumin were significantly lower than the control group with favorable nutrition. (2) There were obvious differences in intestinal flora between healthy elderly male subjects and those with malnutrition. After the treatment of enteral nutritional suspension (TPF-DM), intestinal flora of the malnourished elderly subjects showed recovery toward the healthy elderly subjects. The obvious gradient changes of the flora were mainly in the bacteroidetes, firmicutes, and proteobacteria phyla, and the relative abundance of CAG2 clusters in the malnourished group was higher than that in the healthy control group, and the relative abundance decreased after long-term treatment, and the change approached the healthy control group. The relative abundance of CAG3 and CAG6 clusters in the malnourished group was lower than that in the healthy control group, and the relative abundance increased after long-term treatment, and the change approached the healthy control group. CONCLUSION: Malnutrition has obvious impact on intestinal flora of the elderly. Enteral nutritional suspension (TPF-DM) not only prevents the further decline in the state of nutrition but also helps the recovery in intestinal flora of the elderly. Long-term application can produce better effects.
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BACKGROUND: The safety of hypoglycemic drugs should be paid more attention to in elderly patients with type 2 diabetes mellitus due to their concomitant diseases, physiological decline of liver and kidney function and cognitive decline. The aim of this study was to evaluate the efficacy and safety of DPP-4 inhibitors in elderly patients with type 2 diabetes mellitus. METHODS: From January 2010 to November 2018, 300 patients with type 2 diabetes mellitus who were over 60 years old were enrolled in the outpatient clinic of Geriatric Medical Center. Their medication records and follow-up medical records were used for retrospective analysis. The duration of treatment with DPP-4 inhibitors was more than 3 months. The changes of fasting blood glucose (GLU), glycosylated hemoglobin (HbA1C), body weight, body mass index (BMI) and liver and kidney function were compared before and after treatment. RESULTS: The average age of 300 patients (212 males and 88 females) was 73.7 ± 9.1 years old, BMI was 26.5 ± 2.8 kg/m2 and the duration of diabetes was 10.7 ± 8.2 years. The results of retrospective analysis showed that HbA1C decreased by 0.27% after treatment (P < 0.001). In the group of DPP-4 inhibitors used for less than 12 months, there was no difference in liver transaminase (ALT and AST) between before and after treatment, whereas in the group of DPP-4 inhibitors used formore than 12 months, liver transaminase decreased statistically compared with after treatment (P < 0.001). The incidence of fatty liver in elderly diabetic patients decreased after using DPP-4 inhibitors. There was no significant change in serum creatinine level and creatinine clearance rate in elderly patients with type 2 diabetes mellitus after treatment of DPP-4 inhibitor. In addition, the body weight and BMI of the patients decreased significantly (P < 0.001). No hypoglycemic reaction and gastrointestinal discomfort were found in the medical records. CONCLUSION: After DPP-4 inhibitors were used in elderly patients with type 2 diabetes mellitus, the elevated glycosylated hemoglobin could be controlled with improved safety of liver and kidney, and might have the effect of weight loss.
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Low urinary iodine concentration (UIC) is associated with dyslipidaemia in adults but is not well characterised in adolescents. Because dyslipidaemia is a cardiovascular risk factor, identifying such an association in adolescents would allow for the prescription of appropriate measures to maintain cardiovascular health. The present study addresses this question using data in the 2001-2012 National Health and Nutrition Examination Survey for 1692 adolescents aged 12-19 years. Primary outcomes were UIC, cardiometabolic risk factors and dyslipidaemia. Data for subjects categorised by low and normal UIC and by sex were analysed by univariate and multivariate logistic regression. Treating UIC as the independent variable, physical activity level, apoB and lipid profiles differed significantly between subjects with low and normal UIC. Subjects with low UIC had a significantly greater risk of elevated total cholesterol (TC) (95 % CI 1·37, 2·81), elevated non-HDL (95 % CI 1·33, 2·76) and elevated LDL (95 % CI 1·83, 4·19) compared with those with normal UIC. Treating UIC as a dependent variable, the risk of low UIC was significantly greater in those with higher apoB (95 % CI 1·52, 19·08), elevated TC (≥4·4mmol/l) (95 % CI 1·37, 2·81) and elevated non-HDL (≥3·11mmol/l) (95 % CI 1·33, 2·76) than in those with normal UIC. These results show that male and female adolescents with low UIC tend to be at greater risk of dyslipidaemia and abnormal cardiometabolic biomarkers, though the specific abnormal parameters differed between sexes. These results may help to identify youth who would benefit from interventions to improve their cardiometabolic risk.
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Enfermedades Cardiovasculares/etiología , Dislipidemias/etiología , Yodo/orina , Lípidos/sangre , Adolescente , Biomarcadores/análisis , Niño , Estudios Transversales , Femenino , Humanos , Modelos Logísticos , Masculino , Encuestas Nutricionales , Estado Nutricional , Factores de Riesgo , Adulto JovenRESUMEN
Systemic inflammatory response has been implicated as a contributor to the onset of febrile seizures (FS). The four novel indices of the inflammatory response such as, neutrophil-to-lymphocyte ratio (NLR), mean platelet volume (MPV), platelet count (PLT) ratio and red blood cell distribution width (RDW) have been investigated in FS susceptibility and FS types (simple febrile seizure and complex febrile seizure). However, the potential role of these inflammatory markers and MPV/PLT ratio (MPR) in Chinese children with FS has yet to be fully determined. This study investigated the relevance of NLR, MPV, PLT, MPR and RDW in febrile children with and without seizures. 249 children with FS and 249 age matched controls were included in this study. NLR and MPR were calculated from complete blood cell counts prior to therapy. Differences in age, gender and these inflammatory markers between the FS group and the control group were evaluated using the chi-square test, t-test or logistic regression analysis. Receiver Operating Characteristic (ROC) curve was used to determine the optimal cut-off value of NLR and MPR for FS risk. Interactions between NLR and MPR on the additive scale were calculated by using the relative excess risk due to interaction (RERI), the proportion attributable to interaction (AP), and the synergy index (S). It has been shown that the elevated NLR and MPR levels were associated with increased risk of FS. The optimal cut-off values of NLR and MPR for FS risk were 1.13 and 0.0335 with an area under the curve (AUC) of 0.768 and 0.689, respectively. Additionally, a significant synergistic interaction between NLR and MPR was found on an additive scale. The mean levels of MPV were lower and NLR levels were higher in complex febrile seizure (CFS) than simple febrile seizure (SFS), and the differences were statistically significant. ROC analysis showed that the optimal cut-off value for NLR was 2.549 with 65.9% sensitivity and 57.5% specificity. However, no statistically significant differences were found regarding average values of MPR and RDW between CFS and SFS. In conclusion, elevated NLR and MPR add evidence to the implication of white cells subsets in FS risk, and our results confirmed that NLR is an independent, albeit limited, predictor in differentiating between CFS and SFS. Moreover, NLR and MPR may have a synergistic effect that can influence the occurrence of FS.
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Recuento de Leucocitos , Linfocitos , Volúmen Plaquetario Medio , Neutrófilos , Recuento de Plaquetas , Convulsiones Febriles/sangre , Área Bajo la Curva , Biomarcadores , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Pronóstico , Curva ROC , Factores de Riesgo , Convulsiones Febriles/diagnóstico , Convulsiones Febriles/etiologíaRESUMEN
BACKGROUND: The aim of this study was to clarify the relationship among Rac1 expression and activation, oxidative stress and ß cell dysfunction in obesity. METHODS: In vivo, serum levels of glucose, insulin, oxidative stress markers and Rac1 expression were compared between ob/ob mice and C57BL/6J controls. Then, these variables were rechecked after the administration of the specific Rac1 inhibitor-NSC23766 in ob/ob mice. In vitro, NIT-1 ß cells were cultured in a hyperglycemic and/or hyperlipidemic state with or without NSC23766, and the differences of Rac1 expression and translocation, NADPH oxidase(Nox) enzyme activity, reactive oxygen species (ROS) and insulin mRNA were observed. RESULTS: ob/ob mice displayed abnormal glycometabolism, oxidative stress and excessive expression of Rac1 in the pancreas. NSC23766 injection inhibited the expression of Rac1 in the pancreas, along with amelioration of oxidative stress and glycometabolism in obese mice. Under hyperglycemic and/or hyperlipidemic conditions, Rac1 translocated to the cellular membrane, induced activation of the NADPH oxidase enzyme and oxidative stress, and simultaneously reduced the insulin mRNA expression in NIT-1 ß cells. Inhibiting Rac1 activity could alleviate oxidative stress and meliorate the decline of insulin mRNA in ß cells. CONCLUSIONS: Rac1 might contribute to oxidative stress systemically and locally in the pancreas in obesity. The excessive activation and expression of Rac1 in obesity were associated with ß cell dysfunction through ROS production.
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Células Secretoras de Insulina/patología , Neuropéptidos/metabolismo , Obesidad/metabolismo , Obesidad/patología , Estrés Oxidativo/fisiología , Proteína de Unión al GTP rac1/metabolismo , Aminoquinolinas/farmacología , Animales , Membrana Celular/metabolismo , Hiperglucemia/metabolismo , Hiperglucemia/fisiopatología , Hiperlipidemias/metabolismo , Hiperlipidemias/fisiopatología , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , NADPH Oxidasas/metabolismo , Pirimidinas/farmacología , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: To analyze the impact of atorvastatin on blood lipids and arterial media thickness (IMT) in new-onset type 2 diabetes patients. METHODS: 333 patients, 30-70 years old and diagnosed within one year as type 2 diabetes, were selected from the Chinese Diabetes Complication Prevention Study (CDCPS) to take part in this study. Changes of blood lipids and IMT of carotid, femoral and iliac artery pre and post the administration of atorvastatin were tested and followed for 24 months. RESULTS: Total cholesterol, triglycerides and low-density lipoprotein decreased significantly (P = 0.000) and maintained at a low level. The carotid artery IMT decreased significantly (P = 0.022) at the end of this study, but the femoral and iliac artery IMT did not show any obvious change. There were no serious adverse events noticed, during the study period. CONCLUSION: Long-term use of atorvastatin seemed to be safe and effective in reducing blood lipids in patients with type 2 diabetes thus could delay the development of atherosclerosis.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ácidos Heptanoicos/uso terapéutico , Lípidos/sangre , Pirroles/uso terapéutico , Túnica Media/patología , Adulto , Anciano , Atorvastatina , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To analyze the prevalence rate of diabetic nephropathy (DN) and the related factors on DN among type 2 diabetic patients. METHODS: A total number of 1758 type 2 diabetic patients who were hospitalized in the Beijing Hospital from 2003 to 2010 were analyzed retrospectively. Three groups were divided according to the rate of urinary albumin excretion (UAER). Patients whose UAER < 20 µg/min belonged to normal albuminuria (NA) group. The ones whose UAER from 20 to 200 µg/min belonged to microalbuminuria (MA) group, and the others whose UAER ≥ 200 µg/min belonged to large albuminuia (LA) group. The clinical characteristics were then compared. The related factors of DN were analyzed. RESULTS: (1) There were 1246 patients in NA group, 408 patients in MA group, and 104 patients in LA group. The constituent ratio of nephropathy was 29.1%. (2) The ages of NA group, MA group and LA group were (59.87 ± 12.77, 62.52 ± 12.74, 64.44 ± 12.74) years old, respectively, with body mass index (BMI) as (24.90 ± 3.42, 25.53 ± 4.00, 25.53 ± 3.91) kg/m(2) respectively; duration of diabetes as (8.39 ± 7.12, 10.77 ± 8.02, 12.84 ± 7.97) years; systolic blood pressure (SBP) as (133.42 ± 18.19, 142.72 ± 20.21, 151.12 ± 21.91) mm Hg; diastolic blood pressure as (78.75 ± 10.66, 80.79 ± 12.21, 83.33 ± 13.61) mm Hg; fasting blood sugar (FBS) as (8.25 ± 3.43, 9.02 ± 3.72, 9.22 ± 4.62) mmol/L; glycated hemoglobin (HbA1c) as (8.88 ± 2.10, 9.34 ± 2.36, 9.10 ± 2.36)%; uric acid (UA) as (288.04 ± 90.41, 307.23 ± 96.96, 374.28 ± 105.47) mmol/L; triglyceride as (1.72 ± 1.51, 2.06 ± 1.88, 1.94 ± 1.42) mmol/L, high density lipoprotein cholesterol as (1.08 ± 0.30, 1.02 ± 0.29, 1.07 ± 0.28) mmol/L; fasting insulin as (9.24 ± 9.02, 11.24 ± 9.74, 11.06 ± 9.29) µU/ml; fasting C peptide as (462.31 ± 289.94, 510.02 ± 350.08, 595.93 ± 445.86) pmol/L. There were significant differences between NA, MA and LA groups in all above items (P < 0.01 or P < 0.05). (3) Logistic regression analysis showed that DN were related with duration of diabetes, BMI, SBP, HbA1c, FBS, UA (OR values were 1.041, 1.055, 1.028, 1.116, 1.100, 1.004 respectively, P < 0.05 or P < 0.01). CONCLUSION: It would be helpful to prevent and retard progression of DN that comprehensively controlling high blood glucose, hypertension, hyperuricemia and body weight of type 2 diabetic patients.