Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56.988
Filtrar
1.
Medicine (Baltimore) ; 99(12): e19562, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32195965

RESUMEN

It has been established that prediabetes can causes significant comorbidities, particularly in the elderly. The deterioration of glucose metabolism are generally considered to be results of the impairment of the 4 factors: first, second insulin secretion (FPIS, SPIS, respectively), glucose effectiveness (GE), and insulin resistance. In this study, we enrolled older women to investigate their relationships with prediabetes.Five thousand four hundred eighty-two nonobese, nondiabetic women were included. They were divided into normal glucose tolerance and prediabetes groups. Receiver operating characteristic curve was performed to investigate the effects on whether to have prediabetes for each factors. Two models were built: Model 1: FPIS + SPIS, and Model 2: model 1 + GE. The area under the receiver operating characteristic (aROC) curve was used to determine the predictive power of these models.The aROC curve of GE was significantly higher than the diagonal line followed by SPIS and FPIS accordingly. The aROC curve of Model 1 (0.611) was not different from GE. However, Model 2 improved significantly up to 0.663. Based on this model, an equation was built (-0.003 × GE - 212.6 × SPIS - 17.9 × insulin resistance + 4.8). If the calculated value is equal or higher than 0 (≥0), then the subject has higher chance to have prediabetes (sensitivity = 0.607, specificity = 0.635).Among the 4 factors, GE is the most important contributor for prediabetes in older women. By building a model composed of FPIS, SPIS, and GE, the aROC curve increased significantly. The equation built from this model could predict prediabetes precisely.


Asunto(s)
Grupo de Ascendencia Continental Asiática/etnología , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Secreción de Insulina/fisiología , Estado Prediabético/epidemiología , Anciano , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Humanos , Persona de Mediana Edad , Estado Prediabético/fisiopatología , Prevalencia , Sensibilidad y Especificidad , Taiwán/epidemiología
2.
Eur J Endocrinol ; 182(4): 447-457, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32069218

RESUMEN

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umeå University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification ± metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD11B1 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5α-THF + 5ß-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction.


Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Dieta Reductora/métodos , Ejercicio/fisiología , Glucocorticoides/metabolismo , Pérdida de Peso/fisiología , Adulto , Anciano , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/terapia , Dieta Paleolítica , Terapia por Ejercicio/métodos , Femenino , Técnica de Clampeo de la Glucosa , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/sangre , Resistencia a la Insulina , Hígado/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Resultado del Tratamiento
3.
Zhongguo Zhen Jiu ; 40(2): 129-34, 2020 Feb 12.
Artículo en Chino | MEDLINE | ID: mdl-32100496

RESUMEN

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with lifestyle control on hepatic fat status, hepatic enzymology, glycolipid metabolism and anthropological parameters in patients with obese nonalcoholic fatty liver disease(NAFLD). METHODS: A total of 90 patients with obese NAFLD were randomized into an observation group (45 cases, 4 cases dropped off) and a control group (45 cases, 1 case dropped off). Lifestyle control was implemented in the control group. On the basis of the treatment in the control group, acupuncture was applied at Zhongwan (CV 12), Quchi (LI 11), Shuifen (CV 9), Huaroumen (ST 24), Daheng (SP 15), Guanyuan (CV 4), Qihai (CV 6), etc. EA was provided at Huaroumen (ST 24) and Daheng (SP 15) with dilatational wave, 2 Hz/100 Hz in frequency, 30 min each time, once every other day, 3 times a week. The treatment for 12 weeks was required in both of the two groups. Hepatic fat status [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)], hepatic enzymology [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)], glycolipid metabolism and insulin sensitivity [fasting plasma glucose (FPG), fasting serum lisulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)] and anthropological parameters [body weight (BW), body mass index (BMI), fat percentage (FP), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)] in the two groups were observed before and after treatment. RESULTS: ①Compared before treatment, hepatic CAP, LSM, serum ALT, AST and GGT after treatment were obviously reduced in the two groups (P<0.05, P<0.01). After treatment, CAP and ALT in the observation group were lower than the control group (P<0.05). ②Compared before treatment, FINS, HOMA-IR, LDL-C, TC and TG after treatment were obviously reduced in the two groups (P<0.05, P<0.01),while the levels of HDL-C were increased (P<0.05). Compared before treatment, FPG after treatment in the observation group was reduced (P<0.05). Compared with the control group, FINS, HOMA-IR, TC and TG in the observation group were lower than those in the control group after treatment (P<0.05). ③Compared before treatment, BW BMI, FP, WC, HC, WHR after treatment were obviously reduced in the two groups (P<0.01). After treatment, WC and WHR in the observation group were lower than the control group (P<0.05). CONCLUSION: Electroacupuncture combined with lifestyle control can effectively treat obese nonalcoholic fatty liver disease, and present better therapeutic effect on hepatic fat status, glycolipid metabolism, insulin resistance, WC and WHR.


Asunto(s)
Electroacupuntura , Estilo de Vida , Enfermedad del Hígado Graso no Alcohólico/terapia , Glucemia , Humanos , Resistencia a la Insulina , Metabolismo de los Lípidos , Lípidos/sangre , Hígado/enzimología , Obesidad/complicaciones
4.
J Sports Sci ; 38(6): 682-691, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32050850

RESUMEN

This study aimed to verify the effect of a multicomponent intervention on cardiometabolic risk factors (CMRF), and to determine the prevalence of responders on CMRF among children and adolescents with overweight/obesity. This is a quasi-experimental study, developed with 35 children and adolescents with overweight/obesity (control group (CG) = 18; intervention group (IG) = 17), aged between 7 and 13 years. Participants in IG underwent a multicomponent intervention for 12 weeks. The following variables were evaluated: anthropometric measures, maturational stages and CMRF (body fatness, HOMA-IR, triglycerides, high-density and low-density lipoprotein) (HDL-C, LDL-C), total cholesterol (TC), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and AST/ALT ratio. Mixed analysis of variance and the prevalence of responders were used for statistical analysis. There was a significant time x group interaction on body fatness (p < 0.001), HOMA-IR (p = 0.01), HDL-C (p < 0.001), LDL-C (p = 0.009) and TC (p < 0.001). The prevalence of responders for CMRF in IG and CG was respectively: body fatness (47%; 0%; p = 0.04), HOMA-IR (58.8%; 16.6%; p = 0.04); triglycerides (17.6%; 5.5%; p = 0.31); HDL-C (76.4%; 5.5%; p = 0.01), LDL-C (35.3%; 5%; p = 0.08), TC (64.7%; 5%; p = 0.01), AST (5.8%; 0%; p = 0.87), ALT (29.4%; 11.1%; p = 0.24) and AST/ALT ratio (24.4%; 22.2%; p = 0.67). Multicomponent intervention induced positive changes on CMRF along with a higher prevalence of positive adaptations in IG than the CG in some of the cardiometabolic outcomes assessed.


Asunto(s)
Ejercicio , Sobrepeso/prevención & control , Padres/psicología , Obesidad Pediátrica/prevención & control , Apoyo Social , Adolescente , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Distribución de la Grasa Corporal , Niño , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Homeostasis , Humanos , Resistencia a la Insulina/fisiología , Masculino , Factores de Riesgo , Triglicéridos/sangre
5.
Medicine (Baltimore) ; 99(5): e19023, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32000447

RESUMEN

In the present study, the performance of anthropometric parameters, lipid and glucose indexes, and the combination of anthropometric parameters with the TyG (triglycerides × fasting plasma glucose) metabolic index, was compared in detecting insulin resistance (IR) to evaluate the optimal cut-off points in nondiabetic Chinese individuals. A total of 1067 nondiabetics underwent oral glucose tolerance test, blood lipid, and fasting insulin measurements. The clinical usefulness of various parameters- body mass index (BMI), waist circumference (WC), TyG, triglycerides/ high density lipoprotein cholesterol ratio, and TyG with adiposity status (TyG-BMI [TyG × BMI] and TyG-WC)-was analyzed to identify IR. Spearman correlation and receiver-operating characteristic curve analyses were used to compare the predictive efficacy of different indicators. All indicators showed a positive correlation with IR in both normal glucose and all subjects. However, the correlation between BMI and homeostasis model assessment of IR index was higher than other indicators as assessed by Spearman correlation test (P < .05). Furthermore, BMI and TyG-BMI were better indicators than others as determined by comparing the area under the receiver-operating characteristics curves (P < .05) in detecting IR. BMI is a simple and accurate measure for detecting IR in Chinese subjects. The 27 kg/m threshold was the optimal BMI cut-off point for detecting IR in both normal glucose and all glucose categories subjects.


Asunto(s)
Resistencia a la Insulina , Antropometría , Glucemia/análisis , China , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Lípidos/sangre , Masculino , Persona de Mediana Edad
6.
Medicine (Baltimore) ; 99(8): e19034, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080077

RESUMEN

BACKGROUND: Previous studies showed conflicting results for associations between vitamin D and prediabetes. The study aimed to make a systematic review and meta-analysis for the association between vitamin D and prediabetes. METHODS: We searched for articles identifying associations between vitamin D and prediabetes published in English until July 2019 in following databases (PubMed, Web of Science, EMBASE, Medline, Google Scholar, and Cochrane databases). Finally, we conducted these analyses (heterogeneities examination, meta-regression analyses, sensitivity analysis, and publication bias examination) using STATA 12.0 software (Stata Corporation, College Station, TX, USA). Q test and I were applied to examine heterogeneities between studies. RESULTS: Twelve studies were finally included in the present study. The study included 4 studies to explore the association between serum levels of 25-hydroxy (OH) vitamin D and risks of prediabetes (including 3094 participants). Additionally, the present study included 8 studies (including 865 individuals with prediabetes treated with vitamin D supplementation and 715 patients treated with placebo) to assess differences in therapeutic effects between individuals with prediabetes treated with vitamin D supplementation and those treated with placebo. The present study showed no significant associations between low serum levels of 25(OH) vitamin D and high risk of prediabetes. Additionally, the study showed no significant differences in changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) between individuals with prediabetes treated with vitamin D and those patients given placebo, whereas meta-analysis showed significantly greater changes in 2-hour oral glucose tolerance test (2HPG) in individuals with prediabetes treated with vitamin D, compared with individuals with prediabetes treated with placebo. CONCLUSION: The study supported that low serum levels of 25(OH) vitamin D increased the risk of prediabetes. In addition, vitamin D supplementation improves impaired glucose tolerance in prediabetes. However, more large-scale clinical trials are essential to explore the association between vitamin D and prediabetes.


Asunto(s)
Estado Prediabético/sangre , Estado Prediabético/tratamiento farmacológico , Vitamina D/sangre , Vitaminas/sangre , Glucemia/efectos de los fármacos , Ayuno/sangre , Intolerancia a la Glucosa/tratamiento farmacológico , Prueba de Tolerancia a la Glucosa/métodos , Hemoglobina A Glucada/análisis , Humanos , Resistencia a la Insulina/fisiología , Placebos/administración & dosificación , Factores de Riesgo , Vitamina D/uso terapéutico , Vitaminas/uso terapéutico
7.
Medicine (Baltimore) ; 99(8): e19242, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080127

RESUMEN

The gestational diabetes mellitus (GDM) diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Group (IADPSG) were established based on the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and have been the most commonly used criteria for determining GDM worldwide. Although individuals from mainland China were not included in the HAPO study, the IADPSG criteria have been used in China since 2011. However, the appropriateness of the criteria for evaluating maternal postpartum outcomes in mainland China are unknown. We conducted this study to determine whether the IADPSG criteria are appropriate for Chinese patients for evaluating long-term maternal postpartum outcomes.Eighty-four patients who were diagnosed with hyperglycemia during pregnancy and had delivery in Peking University First Hospital from February 2007 to December 2009 were enrolled in the study. For patients in Group A, GDM was diagnosed using both the National Diabetes Data Group (NDDG) and the IADPSG criteria, while patients in Group B, gestational impaired glucose tolerance (GIGT) was diagnosed using the NDDG criteria while GDM was diagnosed based on the IADPSG criteria. Anthropometric data, glucose metabolism, lipid profiles, ß cell function, and insulin resistance index were evaluated and compared to baseline after 5- to 6-year postpartum period.Patients in group A had significantly higher oral glucose tolerance test (OGTT) fasting, 2-hour and 3-hour plasma glucose levels compared to patients in group B at 24 to 28 weeks of gestation (P < .05). No significant differences were observed between the groups for anthropometric data, postpartum abnormal glucose metabolism (50.91% vs 44.83%, P = .596), type 2 diabetes mellitus (T2DM) (16.36% vs 3.45%, P = .167), lipid profiles, ß cell function (homeostasis model assessment ß-cell function index (HOMA-ß) 1.04 vs 0.99, P = .935) and insulin resistance (homeostasis model assessment insulin resistance index (HOMA-IR) 2.01 vs 1.69, P = .583).Patients diagnosed with GDM using either the NDDG or IADPSG criteria had abnormal glucose levels and lipid metabolism after delivery. Patients with mild hyperglycemia had similar postpartum ß-cell functional impairment and insulin resistance to those with moderate hyperglycemia during pregnancy. Hence, with respect to maternal long-term postpartum outcomes, the IADPSG diagnostic criteria for GDM could be appropriate for patients in mainland China.


Asunto(s)
Diabetes Gestacional/fisiopatología , Periodo Posparto/fisiología , Adulto , Pesos y Medidas Corporales , China , Femenino , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina/fisiología , Células Secretoras de Insulina/metabolismo , Lípidos/sangre , Embarazo
8.
Nat Commun ; 11(1): 213, 2020 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-31924774

RESUMEN

Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively. Fat-specific knockout of HuR significantly enhances adipogenic gene program in adipose tissues, accompanied by a systemic glucose intolerance and insulin resistance. HuR knockout also results in depot-specific phenotypes: it can repress myogenesis program in brown fat, enhance inflammation program in epidydimal white fat and induce browning program in inguinal white fat. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts including Insig1, a negative regulator during adipogenesis. Taken together, our work establishes HuR as an important posttranscriptional regulator of adipogenesis and provides insights into how RNA processing contributes to adipocyte development.


Asunto(s)
Adipogénesis/genética , Adipogénesis/fisiología , Proteína 1 Similar a ELAV/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Tejido Adiposo/patología , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Proteína 1 Similar a ELAV/genética , Regulación de la Expresión Génica , Técnicas de Inactivación de Genes , Intolerancia a la Glucosa/metabolismo , Humanos , Inflamación , Resistencia a la Insulina , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas de la Membrana , Ratones Endogámicos C57BL , Ratones Noqueados
9.
Cardiovasc Diabetol ; 19(1): 11, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-31992297

RESUMEN

BACKGROUND: Insulin resistance may contribute to aortic stiffening that leads to end-organ damage. We examined the cross-sectional association and prospective association of insulin resistance and aortic stiffness in older adults without diabetes. METHODS: We analyzed 2571 men and women at Visit 5 (in 2011-2013), and 2350 men and women at repeat examinations from baseline at Visit 1 (in 1987-1989) to Visit 5 (in 2011-2013). Linear regression was used to estimate the difference in aortic stiffness per standard unit of HOMA-IR, TG/HDL-C, and TyG at Visit 5. Linear mixed effects were used to assess if high, as opposed to non-high, aortic stiffness (> 75th percentile) was preceded by a faster annual rate of change in log-HOMA-IR, log-TG/HDL-C, and log-TyG from Visit 1 to Visit 5. RESULTS: The mean age of participants was 75 years, 37% (n = 957) were men, and 17% (n = 433) were African American. At Visit 5, higher HOMA-IR, higher TG/HDL-C, and higher TyG were associated with higher aortic stiffness (16 cm/s per SD (95% CI 6, 27), 29 cm/s per SD (95% CI 18, 40), and 32 cm/s per SD (95% CI 22, 42), respectively). From Visit 1 to Visit 5, high aortic stiffness, compared to non-high aortic stiffness, was not preceded by a faster annual rate of change in log-HOMA-IR from baseline to 9 years (0.030 (95% CI 0.024, 0.035) vs. 0.025 (95% CI 0.021, 0.028); p = 0.15) or 9 years onward (0.011 (95% CI 0.007, 0.015) vs. 0.011 (95% CI 0.009, 0.013); p = 0.31); in log-TG/HDL-C from baseline to 9 years (0.019 (95% CI 0.015, 0.024) vs. 0.024 (95% CI 0.022, 0.026); p = 0.06) or 9 years onward (- 0.007 (95% CI - 0.010, - 0.005) vs. - 0.009 (95% CI - 0.010, - 0.007); p = 0.08); or in log-TyG from baseline to 9 years (0.002 (95% CI 0.002, 0.003) vs. 0.003 (95% CI 0.003, 0.003); p = 0.03) or 9 years onward (0 (95% CI 0, 0) vs. 0 (95% CI 0, 0); p = 0.08). CONCLUSIONS: Among older adults without diabetes, insulin resistance was associated with aortic stiffness, but the putative role of insulin resistance in aortic stiffness over the life course requires further study.


Asunto(s)
Envejecimiento , Enfermedades Cardiovasculares/fisiopatología , Resistencia a la Insulina , Rigidez Vascular , Factores de Edad , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etnología , Estudios Transversales , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina/etnología , Lípidos/sangre , Masculino , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(1): 65-70, 2020 Jan.
Artículo en Chino | MEDLINE | ID: mdl-31948527

RESUMEN

OBJECTIVE: To study the effect of epigallocatechin-3-gallate (EGCG) on liver lipid metabolism in rats with intrauterine growth restriction (IUGR) and related mechanism. METHODS: A rat model of IUGR was established by food restriction during entire pregnancy, and then the rats were randomly divided into an IUGR group and an EGCG group (n=8 each). The rats in the EGCG group were fed with water containing EGCG from after weaning to 10 weeks. Eight pup rats born from the pregnant maternal rats without food restriction were used as the control group. At the age of 13 weeks, body weight was measured. Blood and liver tissue samples were collected to measure fasting total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), and liver lipids. Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (adipo-IR) were calculated. Pathological sections of the liver were observed and quantitative real-time PCR was used to measure the mRNA expression of related genes in the liver. RESULTS: At the age of 13 weeks, there was no significant difference in body weight between groups (P=0.067). There were significant differences between groups in FPG, FFA, FINS, HOMA-IR, and adipo-IR (P<0.05). There were no significant differences in the serum levels of TC and TG between groups (P>0.05), while the IUGR group had significantly higher levels of TC and TG in the liver than the EGCG group (P<0.05). Oil red staining showed that the IUGR group had a significant increase in hepatic lipid accumulation, while the EGCG group had certain improvement after EGCG treatment. PCR results suggested that compared with the control group, the IUGR group had significant reductions in the mRNA expression of Ampk and Adipor1 and a significant increase in the mRNA expression of Srebf1 (P<0.05), while EGCG increased the mRNA expression of Ampk and reduced the mRNA expression of Srebf1, with no significant differences in the two indices between the EGCG and control groups (P>0.05). CONCLUSIONS: Early EGCG intervention can down-regulate the de novo synthesis of fatty acids through the Ampk/Srebf1 signaling pathway and reduce hepatic lipid accumulation in IUGR rats by improving insulin resistance of hepatocytes.


Asunto(s)
Resistencia a la Insulina , Metabolismo de los Lípidos , Animales , Catequina/análogos & derivados , Femenino , Retardo del Crecimiento Fetal , Lípidos , Hígado , Embarazo , Ratas
11.
Cell Physiol Biochem ; 54(1): 71-87, 2020 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-31972071

RESUMEN

BACKGROUND/AIMS: Diabetes type 2, metabolic syndrome or non-alcoholic fatty liver disease are insulin resistance-related metabolic disorders, which lack a better prognosis before their full establishment. We studied the importance of the intracellular scaffold protein integrin linked kinaes (ILK) as a key modulator in the initial pathogenesis and the early progression of those insulin resistance- related disorders. METHODS: Adult mice with a global transgenic downregulation of ILK expression (cKD-ILK) and littermates without that depletion (CT) were fed with either standard (STD) or high fat (HFD) diets during 2 and 6 weeks. Weights, blood glucose and other systemic biochemical parameters were determined in animals under fasting conditions and after glucose or pyruvate intraperitoneal injections to test their tolerance. In RNA or proteins extracted from insulin-sensitive tissues, we determined by reverse transcription-quantitative PCR and western blot the expression of ILK, metabolites transporters and other metabolism and inflammatory markers. Glucose uptake capacity was studied in freshly isolated tissues. RESULTS: HFD feeding was able to early and progressively increase glycaemia, insulinemia, circulating glycerol, body weight gain, liver-mediated gluconeogenesis along this time lapse, but cKD-ILK have all these systemic misbalances exacerbated compared to CT in the same HFD time lapse. Interestingly, the tisular expression of ILK in HFD-fed CT was dramatically downregulated in white adipose tissue (WAT), skeletal muscle and liver at the same extent of the original ILK downregulation of cKD-ILK. We previously published that basal STD-fed cKD-ILK compared to basal STD-CT have different expression of glucose transporters GLUT4 in WAT and skeletal muscle. In the same STD-fed cKD-ILK, we observed here the increased expressions of hepatic GLUT2 and WAT pro-inflammatory cytokines TNF-α and MCP-1. The administration of HFD exacerbated the expression changes in cKD-ILK of these and other markers related to the imbalanced metabolism observed, such as WAT lipolysis (HSL), hepatic gluconeogenesis (PCK-1) and glycerol transport (AQP9). CONCLUSION: ILK expression may be taken as a predictive determinant of metabolic disorders establishment, because its downregulation seems to correlate with the early imbalance of glucose and glycerol transport and the subsequent loss of systemic homeostasis of these metabolites.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Regulación hacia Abajo , Enfermedades Metabólicas/etiología , Proteínas Serina-Treonina Quinasas/genética , Animales , Femenino , Gluconeogénesis , Inflamación/etiología , Inflamación/genética , Resistencia a la Insulina , Lipólisis , Masculino , Enfermedades Metabólicas/genética , Ratones , Ratones Endogámicos BALB C
12.
Expert Opin Pharmacother ; 21(2): 207-211, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31893931

RESUMEN

Introduction: Approximately 1% of adolescents have polycystic ovary syndrome (PCOS) and almost 40-70% of these patients are overweight or obese. Obese adolescents with PCOS have more severe insulin resistance and hyperandrogenemia, a more adverse lipid profile and a worse quality of life than normal-weight adolescents with PCOS. Accordingly, weight loss is an important component of the management of these patients.Areas covered: The authors discuss the different options for weight loss in obese adolescents with PCOS. Lifestyle changes appear to be effective but adherence to this intervention is suboptimal. There are also limited data regarding the optimal diet in this population. Few small studies have evaluated the effects of pharmacotherapy in these patients. Conflicting data have been reported regarding the effects of metformin on body weight. Notably, agents that have been approved for weight loss in adults have not been evaluated in adolescents with PCOS.Expert opinion: More studies are needed to identify the most appropriate diet for obese adolescents with PCOS. Well-designed randomized controlled studies are also needed to define the safety and efficacy of pharmacotherapy in this population.


Asunto(s)
Estilo de Vida , Obesidad Pediátrica/terapia , Síndrome del Ovario Poliquístico/terapia , Adolescente , Femenino , Humanos , Hiperandrogenismo/terapia , Resistencia a la Insulina , Metformina/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Pérdida de Peso
13.
Expert Opin Investig Drugs ; 29(2): 125-133, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31899984

RESUMEN

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is strongly associated with obesity and insulin resistance. NAFLD refers to a spectrum of disorders ranging from asymptomatic hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), which increases the risk of developing more severe forms of liver disease such as progressive fibrosis, cirrhosis, and liver cancer. Currently, there are no food and drug administration (FDA) approved drugs to treat NASH. Pegbelfermin (BMS-986036) is a PEGylated fibroblast growth factor 21 (FGF21) analogue that is under investigation for the treatment of NASH.Areas covered: We reviewed the (pre)clinical pegbelfermin studies and compared these with other studies that assessed FGF21 and FGF21 analogues in the treatment of NASH.Expert opinion: With no FDA approved treatments available for NASH, there is an urgent need for novel therapies. Pegbelfermin is a systemic treatment with pleiotropic effects on various tissues. Short-term adverse effects are limited, but more research is required to study potential long-term safety issues. In a phase 2a trial, pegbelfermin has shown promising improvements in several NASH related outcomes. However, clinical trials demonstrating long-term benefits on hard outcomes such as liver histology, cirrhosis development, or survival are required for further validation.


Asunto(s)
Factores de Crecimiento de Fibroblastos/análogos & derivados , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , Animales , Progresión de la Enfermedad , Drogas en Investigación/efectos adversos , Drogas en Investigación/farmacología , Drogas en Investigación/uso terapéutico , Factores de Crecimiento de Fibroblastos/efectos adversos , Factores de Crecimiento de Fibroblastos/farmacología , Factores de Crecimiento de Fibroblastos/uso terapéutico , Humanos , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Obesidad/complicaciones , Polietilenglicoles/efectos adversos , Polietilenglicoles/farmacología
14.
Expert Opin Investig Drugs ; 29(2): 191-196, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31928475

RESUMEN

Introduction: NASH and type 2 diabetes (T2D) are clinical definitions that overlap and result from metabolic dysfunction caused by over-nutrition relative to metabolic need. This volume details drug development programs aimed at specific NASH pathology with a focus on liver outcomes; this commentary suggests a metabolic approach that should not be overlooked based on a new understanding of insulin sensitizers.Areas covered: The overlap of NASH and T2D with respect to metabolic syndrome is discussed in the context of new understandings of insulin sensitizers. Adverse clinical outcomes in subjects with advanced NAFLD (e.g. NASH) and advanced metabolic dysfunction (e.g., T2D) are primarily due to cardiovascular issues. Clinical evidence suggests that insulin resistance and hyperinsulinemia predict adverse cardiovascular outcomes. NALFD/NASH significantly contributes to insulin resistance and hyperinsulinemia. A new insulin sensitizer that targets the newly identified mitochondrial pyruvate carrier could provide an approach.Expert opinion: A metabolic approach is needed for the treatment of NASH. Clinical studies are underway to determine whether a new insulin sensitizer that targets pyruvate metabolism can impact NASH, T2D, and cardiovascular disease. A broader view of metabolic disease may provide a more assessable way to track therapeutic benefit.


Asunto(s)
Enfermedades Cardiovasculares/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Animales , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Desarrollo de Medicamentos , Humanos , Resistencia a la Insulina , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/fisiopatología , Afecciones Crónicas Múltiples , Enfermedad del Hígado Graso no Alcohólico/fisiopatología
15.
Expert Opin Investig Drugs ; 29(2): 209-219, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31937152

RESUMEN

Background: Oxidative stress has been implicated in metabolic syndrome (MetS); however, antioxidants such as vitamin E have had limited success in the clinic. This prompts the question of what effects amore potent antioxidant might produce. A prime candidate is the recently developed bioengineered antioxidant, poly(ethylene glycol)-functionalizedhydrophilic carbon clusters (PEG-HCCs), which are capable of neutralizing the reactive oxygen species (ROS) superoxide anion and hydroxyl radical at106/molecule of PEG-HCC. In this project, we tested the potential of PEG-HCCs as a possible therapeutic for MetS.Results: PEG-HCC treatment lessened lipid peroxidation, aspartate aminotransferase levels, non-fastingblood glucose levels, and JNK phosphorylation inob/ob mice. PEG-HCC-treated WT mice had an increased response to insulin by insulin tolerance tests and adecrease in blood glucose by glucose tolerance tests. These effects were not observed in HFD-fed mice, regardless of treatment. PEG-HCCs were observed in the interstitial space of liver, spleen, skeletal muscle, and adipose tissue. No significant difference was shown in gluconeogenesis or inflammatory gene expression between treatment and dietary groups.Expert Opinion: PEG-HCCs improved some parameters of disease possibly due to a resulting increase in peripheral insulin sensitivity. However, additional studies are needed to elucidate how PEG-HCCsare producing these effects.


Asunto(s)
Antioxidantes/farmacología , Síndrome Metabólico/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/química , Bioingeniería , Glucemia/efectos de los fármacos , Carbono/química , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Interacciones Hidrofóbicas e Hidrofílicas , Insulina/metabolismo , Resistencia a la Insulina , Masculino , Síndrome Metabólico/fisiopatología , Ratones , Ratones Endogámicos C57BL , Polietilenglicoles/química , Especies Reactivas de Oxígeno/metabolismo
16.
Life Sci ; 244: 117304, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31953164

RESUMEN

AIMS: Macrophages, as an important member of immune system, engulf and digest pathogens in innate immunity and help initiate adaptive immunity. However, macrophages also involve in occurrence and development of many diseases, such as obesity and type 2 diabetes. Here, we aimed to reveal how activated macrophages cause insulin resistance in skeletal muscle in vitro through simulating body environment. MAIN METHODS: We established RAW264.7 macrophages and C2C12 myotubes co-incubation model in vitro using Transwell filter to simulate body environment and investigated effects of RAW264.7 cells on insulin-regulated glucose metabolism in C2C12 myotubes. Immunofluorescence, Immunoblot and glucose uptake tests were used to assess metabolic changes in C2C12 myotubes. ELISA test detected secretions of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) from RAW264.7 cells. In addition, RNA interference and inhibitor treatment were used. KEY FINDINGS: Activated RAW264.7 cells attenuated insulin response in C2C12 myotubes. Activated RAW264.7 cells secreted a lot of TNF-α and IL-6. We found that TNFα, but not IL-6, caused insulin resistance of skeletal muscle in a dose-dependent manner. The results further indicated that activation of TNF-α downstream proteins, inhibitor of nuclear factor κ-B kinase (IKK) and the jun-N-terminal kinase 1 (JNK1) led to phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser residues and insulin resistance in C2C12 myotubes. SIGNIFICANCE: Our research provided further and direct demonstration on activated macrophage-induced insulin resistance in skeletal muscle, suggesting TNF-α might become a therapeutic target to ameliorate and treat type 2 diabetes.


Asunto(s)
Resistencia a la Insulina , Macrófagos/efectos de los fármacos , Fibras Musculares Esqueléticas/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Animales , Células Cultivadas , Glucosa/metabolismo , Insulina/metabolismo , Macrófagos/patología , Ratones , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Fosforilación , Transducción de Señal
17.
J Agric Food Chem ; 68(7): 2183-2192, 2020 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-31984741

RESUMEN

Obesity is a global chronic disease linked to various diseases. Increased consumption of added sugars, especially in beverages, is a key contributor to the obesity epidemic. It is essential to reduce or replace sugar intake with low-calorie sweeteners. Here, a natural sweet protein, 3M-brazzein, was investigated as a possible sugar substitute. Mice were exposed to 3M-brazzein or 10% sucrose of equivalent sweetness, in drinking water to mimic human obesity development over 15 weeks. Consumption of 3M-brazzein in liquid form did not cause adiposity hypertrophy, resulting in 33.1 ± 0.4 g body weight and 0.90 ± 0.2 mm fat accumulation, which were 35.9 ± 0.7 g (p = 0.0094) and 1.53 ± 0.067 mm (p = 0.0031), respectively, for sucrose supplement. Additionally, 3M-brazzein did not disrupt glucose homeostasis or affect insulin resistance and inflammation. Due to its naturally low-calorie content, 3M-brazzein could also be a potential sugar substitute that reduces adiposity.


Asunto(s)
Enfermedades Metabólicas/metabolismo , Obesidad/metabolismo , Proteínas de Plantas/metabolismo , Edulcorantes/metabolismo , Adiposidad , Animales , Peso Corporal , Ingestión de Energía , Humanos , Resistencia a la Insulina , Kluyveromyces/genética , Kluyveromyces/metabolismo , Masculino , Enfermedades Metabólicas/inmunología , Enfermedades Metabólicas/fisiopatología , Ratones , Ratones Endogámicos C57BL , Obesidad/inmunología , Obesidad/fisiopatología , Proteínas de Plantas/genética
18.
Life Sci ; 243: 117246, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31904367

RESUMEN

AIMS: Obesity induce low-grade inflammation and elicit insulin resistance (IR), exercise training accompanied by a low-fat diet has been prescribed as part of the treatment for managing obesity and IR. The purpose of this study is to evaluate the effect of eccentric exercise accompanied by a low-fat diet on glycolipid metabolism, exercise capacity, and macrophage polarization in obesity-induced IR mice. MATERIALS AND METHODS: Mice were fed with 60% high fat diet (HFD) for 12 weeks and subsequently treated with eccentric exercise or/and dietary restriction for 8 weeks. Related biochemical index were examined both before and during intervention to evaluate the ability of glycolipid metabolism. Exercise capacity was measured to verify the results of biochemical index. At 12 weeks and 12 + 8 weeks, infiltration was observed by H&E staining in adipose tissue, and macrophage polarization was detected by Immunofluorescence staining and ELISA. KEY FINDING: 1) obesity-induced IR model was established by HFD fed for 12 weeks accompanied by impaired exercise ability and increased M1 macrophage, 2) eccentric exercise accompanied by a low-fat diet markedly rescued obesity-induced IR and improved exercise capacity, 3) eccentric exercise accompanied by a low-fat diet markedly inhibited M1 macrophage polarization and activated M2 macrophage. SIGNIFICANCE: Eccentric exercise accompanied by a low-fat diet rescued obesity-induced IR and improved exercise capacity, which were associated with the inhibition of M1 macrophage polarization and the activation of M2 macrophage. These indicate that macrophage polarization provides the potential target of intervention for inflammation and IR in obesity.


Asunto(s)
Dieta Alta en Grasa , Macrófagos/citología , Obesidad/etiología , Condicionamiento Físico Animal/fisiología , Animales , Hipercolesterolemia/prevención & control , Resistencia a la Insulina , Lipoproteínas LDL/sangre , Activación de Macrófagos , Masculino , Ratones , Ratones Endogámicos C57BL
19.
Z Gastroenterol ; 58(1): 57-62, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31931541

RESUMEN

The rising prevalence of the metabolic syndrome has led to an increase of non-alcoholic fatty liver disease (NAFLD), and its progressive-inflammatory form called non-alcoholic steatohepatitis (NASH). In recent years, NAFLD and NASH have become major risk factors for developing liver cirrhosis and hepatocellular carcinoma (HCC). In this case, we report a 46-year-old patient with type 2 diabetes mellitus and metabolic comorbidities including obesity and arterial hypertension, who was referred because of rising liver enzymes. After clinical and diagnostic evaluation, the patient was diagnosed with NASH-associated liver cirrhosis, Child-Pugh stage B. A normal blood sugar level was difficult to achieve, and the patient presented with consistently elevated HbA1c-levels irresponsive to insulin therapy. Due to the underlying liver cirrhosis, the patient was enrolled in the HCC-surveillance program. Sonography during follow up showed a focal lesion. On magnetic resonance imaging (MRI), the diagnosis of HCC (BCLC stage A) was confirmed based on typical contrast enhancement and portal-venous wash-out. The patient was evaluated for liver transplantation with a labMELD of 17, and an intermittent therapy with TACE was initiated. Only 2 months after liver transplantation, the patient developed severe and lethal complications. Overall, this case highlights the different medical issues of patients with metabolic syndrome developing a chronic liver disease. In this patient, a rapid progression from NASH-associated liver cirrhosis to HCC was seen, and therefore highlights the importance of close surveillance to identify and treat potential risk factors early in the course of the disease.


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neoplasias Hepáticas/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Comorbilidad , Resultado Fatal , Humanos , Hipertensión/complicaciones , Resistencia a la Insulina , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/complicaciones
20.
Endocrinol. diabetes nutr. (Ed. impr.) ; 67(1): 43-52, ene. 2020. tab
Artículo en Español | IBECS | ID: ibc-186146

RESUMEN

Antecedentes y objetivos: El alelo de riesgo (G) de la variante rs10830963 en el gen del receptor de melatonina 1 B (MTNR1B) se relaciona con la obesidad. En este trabajo evaluamos el efecto de este SNP sobre los factores de riesgo cardiovascular y la pérdida de peso secundaria a 2 dietas hipocalóricas. Métodos: Trescientos sesenta y un sujetos obesos fueron asignados aleatoriamente durante 3 meses (dieta M: dieta hipocalórica alta en grasas monoinsaturadas vs. dieta P: dieta hipocalórica alta en grasas poliinsaturadas). Se midieron los parámetros antropométricos, glucemia en ayunas, proteína C reactiva, concentración de insulina, resistencia a la insulina (HOMA-IR), perfil de lípidos y los niveles de adipocitoquinas. Se evaluó el genotipo del polimorfismo del gen MTNR1B (rs10830963). Resultados: Todos los parámetros antropométricos, la presión arterial sistólica y los niveles de leptina disminuyeron en todos los sujetos después de ambas dietas. Esta mejora de los parámetros antropométricos fue mayor en los no portadores del alelo G que en los portadores del alelo G. Tras la intervención con dieta M (CC vs. CG + GG), el colesterol total (delta: -10,4 ± 2,1 mg/dl vs. -6,4 ± 1,2 mg/dl: p < 0,05), colesterol LDL (delta: -7,1 ± 0,9 mg/dl vs. –2,8 ± 0,8 mg/dl: p < 0,05), insulina (delta: -3,0 ± 0.8 UI/l vs. -2,0 ± 1,0 UI/l: p < 0,05) y HOMA IR (delta: -3,4 ± 1,0 unidades vs. -2,9 ± 0,9 unidades: p < 0,05) mejoraron en los no portadores del alelo G. Tras la dieta P, en el grupo de sujetos sin alelo G, los niveles de insulina (delta: -2,9 ± 1,0 UI/l vs. -0,6 ± 0,2 UI/l: p < 0,05) y HOMA-IR (delta [CC vs. CG + GG]: -0,8 ± 0,2 unidades vs. -0,4 ± 0,3 unidades: p < 0,05) también disminuyeron. Conclusiones: Nuestro estudio detectó una relación de la variante rs10830963 de MTNR1B con la pérdida de peso corporal y la modificación de la resistencia a la insulina inducida por 2 dietas hipocalóricas diferentes. Solo la dieta hipocalórica enriquecida en grasa monoinsaturada y los no portadores del alelo G mostraron un efecto significativo sobre las lipoproteínas


Background & aims: The risk allele (G) of rs10830963 in the melatonin receptor 1 B (MTNR1B) gene presents an association with obesity. We study the effect of this SNP on cardiovascular risk factors and weight loss secondary to 2hypocaloric diets. Methods: 361 obese subjects were randomly allocated during 3 months (Diet M - high monounsaturated fat hypocaloric diet vs. Diet P – high polyunsaturated fat hypocaloric diet). Anthropometric parameters, fasting blood glucose, C-reactive protein (CRP), insulin concentration, insulin resistance (HOMA-IR), lipid profile and adipocytokines levels were measured. Genotype of MTNR1B gene polymorphism (rs10830963) was evaluated. Results: All anthropometric parameters, systolic blood pressure and leptin levels decreased in all subjects after both diets. This improvement of anthropometric parameters was higher in non G allele carriers than G allele carriers. After dietary intervention with Diet M, (CC vs. CG + GG); total cholesterol (delta: -10.4 ± 2.1 mg/dl vs. -6.4 ± 1.2 mg/dl: P <.05), LDL-cholesterol (delta:-7.1 ± 0.9 mg/dl vs. -2.8 ± 0.8 mg/dl: P <.05), insulin (delta:-3.0 ± 0.8 UI/L vs. -2.0 ± 1.0 UI/L: P<.05) and HOMA-IR (delta:-3.4 ± 1.0 units vs. -2.9 ± 0.9 units: P<.05) improved in no G allele carriers. After Diet P, in the group of subjects without G allele CC, insulin levels (delta: -2.9 ± 1.0 UI/L vs. -0.6 ± 0.2 UI/L: P <.05) and HOMA-IR (delta (CC vs. CG + GG): -0.8 ± 0.2 units vs. -0.4 ± 0.3 units: P <.05) decreased, too. Conclusions: Our study detected a relationship of rs10830963 MTNR1B SNP with body weight loss and insulin resistance modification induced by 2 different hypocaloric. Only monounsaturated enriched hypocaloric diet and in no-G allele carriers showed a significant effect on lipoproteins


Asunto(s)
Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Polimorfismo Genético , Grasas de la Dieta/uso terapéutico , Resistencia a la Insulina , Pérdida de Peso/efectos de los fármacos , Obesidad/dietoterapia , Factores de Riesgo , Grasas de la Dieta/metabolismo , Enfermedades Cardiovasculares , Antropometría , Glucemia , Composición Corporal , Relación Cintura-Cadera , Radioinmunoensayo/métodos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA