Associations between vitamin D levels and glucose metabolism markers among pregnant women and their infants in Puerto Rico.

INTRODUCTION: Objectives: low vitamin D during pregnancy is common and could adversely affect health outcomes. This study evaluated vitamin D status during pregnancy and early in life, and its association with glucose metabolism. Methods: maternal serum 25(OH)D, glucose, and insulin levels were measured longitudinally during pregnancy in Hispanic women with overweight/obesity (n = 31) and their infants at birth and 4 months. Results: insulin and HOMA-IR levels were higher among women with vitamin D below adequate levels compared to those with adequate levels in pregnancy (p < 0.05). Late in pregnancy, as vitamin D increased by one unit (ng/mL), insulin decreased by 0.44 units and HOMA-IR by 0.09 units. Maternal vitamin D late in pregnancy was correlated with infant vitamin D levels at birth (r = 0.89; p < 0.01) and 4 months (r = 0.9; p = 0.04), and with glucose (r = 0.79; p = 0.03) and insulin (r = 0.83; p = 0.04) at 4 months. Conclusion: maternal vitamin D status was associated with maternal and infant glucose metabolism in this sample.

INTRODUCCIÓN: Objetivos: un bajo nivel de vitamina D durante el embarazo es común y puede tener consecuencias adversas en la salud. Este estudio evaluó el nivel de vitamina D en mujeres embarazadas y sus bebés, así como su asociación con los marcadores de glucosa. Métodos: los niveles séricos de 25(OH)D, glucosa e insulina se midieron longitudinalmente en mujeres embarazadas hispanoamericanas con sobrepeso/obesidad (n = 31) y en sus bebés, desde el nacimiento hasta los 4 meses de edad, en Puerto Rico. Resultados: los niveles maternos de insulina y HOMA-IR eran mayores en las mujeres con niveles de vitamina D por debajo de lo considerado adecuado, comparado con aquellas con niveles adecuados durante todo el embarazo (p < 0,05). Al final del embarazo, a medida que los niveles de vitamina D aumentaron, por cada unidad (ng/mL) de aumento, la insulina disminuyo en 0,44 unidades y el HOMA-IR en 0,09 unidades. El nivel de vitamina D al final del embarazo se correlacionó con los niveles del bebé al nacer (r = 0,89; p < 0,01) y a los 4 meses (r = 0,9; p = 0,04), y con los niveles de glucosa (r = 0,79; p = 0,03) e insulina (r = 0,83; p = 0,04) a los 4 meses. Conclusión: el nivel materno de vitamina D se asoció con los marcadores maternos e infantiles de glucosa en esta muestra.

p53-dependent transcriptional suppression of BAG3 protects cells against metabolic stress via facilitation of p53 accumulation.

Solid tumour frequently undergoes metabolic stress during tumour development because of inadequate blood supply and the high nutrient expenditure. p53 is activated by glucose limitation and maintains cell survival via triggering metabolic checkpoint. However, the exact downstream contributors are not completely identified. BAG3 is a cochaperone with multiple cellular functions and is implicated in metabolic reprogramming of pancreatic cancer cells. The current study demonstrated that glucose limitation transcriptionally suppressed BAG3 expression in a p53-dependent manner. Importantly, hinderance of its down-regulation compromised cellular adaptation to metabolic stress triggered by glucose insufficiency, supporting that BAG3 might be one of p53 downstream contributors for cellular adaptation to metabolic stress. Our data showed that ectopic BAG3 expression suppressed p53 accumulation via direct interaction under metabolic stress. Thereby, the current study highlights the significance of p53-mediated BAG3 suppression in cellular adaptation to metabolic stress via facilitating p53 accumulation.

N-Acetylcysteine alleviates gut dysbiosis and glucose metabolic disorder in high-fat diet-fed mice.

BACKGROUND: N-Acetylcysteine (NAC), an antioxidative reagent for clinical diseases, shows potential in the treatment of diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. The aim of the present study was to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. METHODS: Mice (C57BL/6J strain) were fed either a normal chow diet (NCD), NCD plus NAC, a high-fat diet (HFD), or HFD plus NAC for 5 months, after which glucose levels, circulating endotoxins and key metabolism-related proteins were determined. Fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was performed to predict functional changes in gut microbiota. In addition, Spearman's correlation analysis was performed between metabolic biomarkers and bacterial abundance. RESULTS: Treatment with NAC significantly reversed the glucose intolerance, fasting glucose concentrations, and gains in body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated occludin and mucin glycoprotein levels in the proximal colon of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria (i.e. Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum) and decreased populations of diabetes-related genera, including Desulfovibrio and Blautia. In addition, NAC may affect the metabolic pathways of intestinal bacteria, including lipopolysaccharide biosynthesis, oxidative stress, and bacterial motility. Finally, the modified gut microbiota was closely associated with the metabolic changes in NAC-treated HFD-fed mice. CONCLUSIONS: N-Acetylcysteine may be a potential drug to prevent glucose metabolic disturbances by reshaping the structure of the gut microbiota.

A Pecan-Rich Diet Improves Cardiometabolic Risk Factors in Overweight and Obese Adults: A Randomized Controlled Trial.

Evidence from observational and intervention studies has shown a high intake of tree nuts is associated with a reduced risk of cardiovascular disease (CVD), mortality from type 2 diabetes (T2DM), and all-cause mortality. However, there is limited data regarding their effects on indicators of cardiometabolic risk other than hypercholesterolemia, and little is known about the demonstrable health benefits of pecans (Carya illinoensis (Wangenh.) K.Koch). We conducted a randomized, controlled feeding trial to compare the effects of a pecan-rich diet with an isocaloric control diet similar in total fat and fiber content, but absent nuts, on biomarkers related to CVD and T2DM risk in healthy middle-aged and older adults who are overweight or obese with central adiposity. After 4 weeks on a pecan-rich diet, changes in serum insulin, insulin resistance (HOMA-IR) and beta cell function (HOMA-ß) were significantly greater than after the control diet (p < 0.05). Pecan consumption also lowered the risk of cardiometabolic disease as indicated by a composite score reflecting changes in clinically relevant markers. Thus, compared to the control diet, the pecan intervention had a concurrent and clinically significant effect on several relevant markers of cardiometabolic risk.

Activation of AMPK alleviates cardiopulmonary bypass-induced cardiac injury via ameliorating acute cardiac glucose metabolic disorder.

Recent years, studies have demonstrated that hyperglycemia is one of the main manifestations after cardiac surgeries, which contributes to myocardial injuries and increases the chance of subsequent complications and mortality in such patients. However, strategies targeting at glucose metabolic disorder after cardiac surgeries to attenuate myocardial injuries are inadequately studied. In this study, a rat model of cardiopulmonary bypass (CPB) was applied to investigate the role of Adenosine 5'-monophosphate-activated protein kinase (AMPK) in modulating myocardial glucose metabolic-induced cardiac injuries after cardiac surgery. The results revealed that CPB elicited significant cardiac dysfunction, and pronouncedly elevated the markers of myocardial injuries including serum creatine kinase MB and cardiac troponin I. Additionally, blunted myocardial glucose uptake after CPB was associated with decreased membrane glucose transporter 4 (GLUT4) content. However, pretreatment of AMPK agonist 5-aminoimidazole-4-carboxamide1-ß-D-ribofuranoside (AICAR) at the beginning of CPB activated AMPK, enhanced phosphorylation of Akt substrate 160 (AS160), and increased myocardial membrane content of GLUT4. Meanwhile, improved myocardial glucose uptake and more importantly alleviated cardiac injury were also observed after CPB pretreated with AICAR. Moreover, the application of a mutant form of AS160 (AS160-4P) abolished the beneficial effect of AICAR, as evidenced by impaired cardiac glucose uptake, reduced myocardial membrane GLUT-4 translocation, increased cardiac injury markers, and deterioration of cardiac function after CPB. In conclusion, it was suggested in this study that preactivation of AMPK by AICAR improved myocardial glucose uptake by promoting AS160 dependent myocardial membrane GLUT-4 translocation, which ultimately provided a potent cardioprotective effect.

Ginsenoside Rg1 inhibits dietary-induced obesity and improves obesity-related glucose metabolic disorders

Obesity and its consequent type 2 diabetes are significant threats to global health. Emerging evidence indicates that ginsenosides from ginseng (Panax ginseng) have anti-diabetic activity. We hypothesized that ginsenosides Rg1 could suppress dietary-induced obesity and improve obesity-related glucose metabolic disorders. Our results showed that ginsenoside Rg1 attenuated dietary-induced body weight gain and fat accumulation in white adipocyte tissue of mice fed a high-fat diet. Furthermore, we found that ginsenosides Rg1 not only decreased fasting glucose concentration and the 2-h postprandial glucose concentration, but also improved insulin resistance and glucose intolerance in those mice. Ginsenoside Rg1 also activated the AMPK pathway in vitro and in vivo and increased plasma membrane translocation of GLUT4 in C2C12 skeletal muscle cells. In conclusion, our observations suggested that ginsenoside Rg1 inhibited dietary-induced obesity and improved obesity-related insulin resistance and glucose intolerance by activation of the AMPK pathway.

Food in synchrony with melatonin and corticosterone relieves constant light disturbed metabolism.

Circadian disruption is associated with metabolic disturbances such as hepatic steatosis (HS), obesity and type 2 diabetes. We hypothesized that HS, resulting from constant light (LL) exposure is due to an inconsistency between signals related to food intake and endocrine-driven suprachiasmatic nucleus (SCN) outputs. Indeed, exposing rats to LL induced locomotor, food intake and hormone arrhythmicity together with the development of HS. We investigated whether providing temporal signals such as 12-h food availability or driving a corticosterone plus melatonin rhythm could restore rhythmicity and prevent the metabolic disturbances under LL conditions in male rats. Discrete metabolic improvements under these separate treatments stimulated us to investigate whether the combination of hormone treatment together with mealtime restriction (12-h food during four weeks) could prevent the metabolic alterations. LL exposed arrhythmic rats, received daily administration of corticosterone (2.5 µg/kg) and melatonin (2.5 mg/kg) in synchrony or out of synchrony with their 12-h meal. HS and other metabolic alterations were importantly ameliorated in LL-exposed rats receiving hormonal treatment in synchrony with 12-h restricted mealtime, while treatment out of phase with meal time did not. Interestingly, liver bile acids, a major indication for HS, were only normalized when animals received hormones in synchrony with food indicating that disrupted bile acid metabolism might be an important mechanism for the HS induction under LL conditions. We conclude that food-elicited signals, as well as hormonal signals, are necessary for liver synchronization and that HS arises when there is conflict between food intake and the normal pattern of melatonin and corticosterone.

Evaluación de tres metodologías para la predicción del riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad / Evaluation of three methodologies for risk prediction of impaired glucose metabolism in overweighed and obese subjects

Introducción: en la actualidad, en Cuba no existe una estrategia establecida para la pesquisa de las alteraciones del metabolismo de la glucosa. Objetivo: evaluar la capacidad diagnóstica de tres metodologías para predecir el riesgo de alteraciones del metabolismo de la glucosa en sujetos con sobrepeso y obesidad. Métodos: se realizó un estudio de evaluación diagnóstica longitudinal, con los datos de 90 sujetos con edades comprendidas entre 25 y 70 años, analizados 2,5 años después de la evaluación inicial. Se obtuvo la edad, el sexo, los antecedentes patológicos personales, los medicamentos empleados, el peso, la talla, el perímetro de cintura y la tensión arterial, así como las concentraciones de glucosa al inicio y a los 2,5 años ulteriores, la insulina y los triglicéridos, además de calcular la resistencia a la insulina en la evaluación inicial. Se utilizó un modelo de puntaje-riesgo para la diabetes tipo 2. Resultados: la frecuencia de alteraciones del metabolismo de la glucosa (glucemia alterada en ayuna y diabetes tipo 2) a los 2,5 años ulteriores, de acuerdo con la presencia previa o no en los sujetos de glucemia alterada en ayunas, resistencia a la insulina y riesgo moderado/alto de diabetes tipo 2, fue superior en los sujetos con glucemia alterada en ayuna previa (72,4 por ciento [21/29]), con resistencia a la insulina al inicio (65,6 por ciento [40/61]) y con riesgo moderado/alto (54,4 por ciento [43/79]), en relación con aquellos sin glucemia alterada en ayuna, sin resistencia a la insulina y con riesgo bajo de diabetes (41,0 por ciento [25/61], p= 0,005; 20,7 por ciento [6/29], p= 0,006 y 27,3 por ciento [3/11], p< 0,0001 respectivamente). La resistencia a la insulina y el riesgo de diabetes tipo 2 moderado/alto mostraron una elevada sensibilidad para identificar sujetos con alteraciones del metabolismo de la glucosa (87,0 y 93,5 por ciento respectivamente), por el contrario de la glucemia alterada en ayunas, que mostró una baja sensibilidad (45,7 por ciento). De los 19 sujetos que desarrollaron diabetes tipo 2 a los 2,5 años, el 100 por ciento presentó riesgo de diabetes tipo 2 moderado/alto y 94,7 por ciento resistencia a la insulina al inicio. Conclusiones: la resistencia a la insulina y el riesgo de diabetes tipo 2 podrían ser de gran utilidad en la identificación de individuos con alto riesgo para padecer diabetes(AU)

Introduction: at present, there is no set strategy in Cuba for the screening of impaired glucose metabolism. Objective: to evaluate the diagnostic capacity of three methodologies to predict the risk of impaired glucose metabolism in overweighed and obese individuals. Methods: a longitudinal diagnostic evaluation study was carried out using data from 90 subjects aged 25 to 70 years, which were analyzed two and a half years after the initial assessment. Information about age, sex, personal pathological history, used medication, weight, height, waist circumference and blood pressure as well the glucose concentrations at the beginning and two and a half years later, insulin and triglyceride indexes was collected in addition to estimating the insulin-resistance index in the initial evaluation. A risk-score model for type 2 diabetes was also used. Results: the frequency of impaired glucose metabolism (impaired fasting glycemia and type 2 diabetes) after two and a half years, according to the previous existence or not of impaired fasting glycemia, insulin resistance and moderate/high risk of type 2 diabetes, was higher in subjects with previous impaired fasting glycemia (72,4 percent [21/29]), with insulin resistance at the beginning (65.6 percent [40/61]) and with moderate/high risk (54,4 percent [43/79]) than in those individuals without impaired fasting glycemia, insulin resistance and with low diabetes risk (41.0 percent [25/61], p= 0,005; 20.7 percent [6/29], p= 0.006 and 27.3 percent [3/11], p< 0.0001, respectively). Insulin resistance index and moderate/high risk of type 2 diabetes showed high sensitivity to identify subjects with impaired glucose metabolism (87.0 and 93.5 percent, respectively), in contrast to impaired fasting glucose whose sensitivity was low (45.7 percent). Of 19 individuals who developed type 2 diabetes two and a half years later, 100 percent had moderate/high risk of type 2 diabetes and 94.7 percent had insulin resistance at the beginning. Conclusions: insulin resistance and risk of type 2 diabetes could be very useful in detecting individuals with high risk of developing diabetes(AU)

Protective effects of marein on high glucose-induced glucose metabolic disorder in HepG2 cells.

BACKGROUND: Our previous study has shown that Coreopsis tinctoria increases insulin sensitivity and regulates hepatic metabolism in high-fat diet (HFD)-induced insulin resistance rats. However, it is unclear whether or not marein, a major compound of C. tinctoria, could improve insulin resistance. Here we investigate the effect and mechanism of action of marein on improving insulin resistance in HepG2 cells. METHODS: We investigated the protective effects of marein in high glucose-induced human liver carcinoma cell HepG2. In kinase inhibitor studies, genistein, LY294002, STO-609 and compound C were added to HepG2 cells 1h before the addition of marein. Transfection with siRNA was used to knock down LKB1, and 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG), an effective tracer, was used to detect glucose uptake. RESULTS: The results showed for the first time that marein significantly stimulates the phosphorylation of AMP-activated protein kinase (AMPK) and the Akt substrate of 160kDa (AS160) and enhanced the translocation of glucose transporter 1 (GLUT1) to the plasma membrane. Further study indicated that genistein (an insulin receptor tyrosine kinase inhibitor) altered the effect of marein on glucose uptake, and both LY294002 (a phosphatidylinositol 3-kinase inhibitor) and compound C (an AMP-activated protein kinase inhibitor) significantly decreased marein-stimulated 2-NBDG uptake. Additionally, marein-stimulated glucose uptake was blocked in the presence of STO-609, a CaMKK inhibitor; however, marein-stimulated AMPK phosphorylation was not blocked by LKB1 siRNA in HepG2 cells. Marein also inhibited the phosphorylation of insulin receptor substrate (IRS-1) at Ser 612, but inhibited GSK-3ß phosphorylation and increased glycogen synthesis. Moreover, marein significantly decreased the expression levels of FoxO1, G6Pase and PEPCK. CONCLUSIONS: Consequently, marein improved insulin resistance induced by high glucose in HepG2 cells through CaMKK/AMPK/GLUT1 to promote glucose uptake, through IRS/Akt/GSK-3ß to increase glycogen synthesis, and through Akt/FoxO1 to decrease gluconeogenesis. Marein could be a promising leading compound for the development of hypoglycemic agent or developed as an adjuvant drug for diabetes mellitus.

Impact of intermittent fasting on glucose homeostasis.

PURPOSE OF REVIEW: This article provides an overview of the most recent human trials that have examined the impact of intermittent fasting on glucose homeostasis. RECENT FINDINGS: Our literature search retrieved one human trial of alternate day fasting, and three trials of Ramadan fasting published in the past 12 months. Current evidence suggests that 8 weeks of alternate day fasting that produces mild weight loss (4% from baseline) has no effect on glucose homeostasis. As for Ramadan fasting, decreases in fasting glucose, insulin, and insulin resistance have been noted after 4 weeks in healthy normal weight individuals with mild weight loss (1-2% from baseline). However, Ramadan fasting may have little impact on glucoregulatory parameters in women with polycystic ovarian syndrome who failed to observe weight loss. SUMMARY: Whether intermittent fasting is an effective means of regulating glucose homeostasis remains unclear because of the scarcity of studies in this area. Large-scale, longer-term randomized controlled trials will be required before the use of fasting can be recommended for the prevention and treatment of metabolic diseases.

Diet, physical activity and mental health status are associated with dysglycaemia in pregnancy: the Healthy Start Study.

AIMS: To examine the association between dysglycaemia and multiple modifiable factors measured during pregnancy. METHODS: The Healthy Start Study collected self-reported data on modifiable factors in early and mid-pregnancy (median 17 and 27 weeks gestation, respectively) from 832 women. Women received one point for each modifiable factor for which they had optimum scores: diet quality (Healthy Eating Index score ≥64), physical activity level (estimated energy expenditure ≥170 metabolic equivalent task-h/week), and mental health status (Perceived Stress Scale score <6 and Edinburgh Postnatal Depression Scale score <13). Dysglycaemia during pregnancy was defined as an abnormal glucose challenge result, ≥1 abnormal results on an oral glucose tolerance test, or a clinical diagnosis of gestational diabetes. Logistic regression models estimated odds ratios for dysglycaemia as a function of each factor and the total score, adjusted for age, race/ethnicity, pre-pregnancy BMI, history of gestational diabetes, and family history of Type 2 diabetes. RESULTS: In individual analyses, only physical activity was significantly associated with a reduced risk of dysglycaemia (adjusted odds ratio 0.67, 95% CI 0.44-1.00). We observed a significant, dose-response association between increasing numbers of optimal factors and odds of dysglycaemia (adjusted P=0.01). Compared with having no optimal modifiable factors, having all three was associated with a 73% reduced risk of dysglycaemia (adjusted odds ratio 0.27, 95% CI 0.08-0.95). CONCLUSIONS: An increasing number of positive modifiable factors in pregnancy was associated with a dose-response reduction in risk of dysglycaemia. Our results support the hypothesis that modifiable factors in pregnancy are associated with the risk of prenatal dysglycaemia.

Healthy obesity and objective physical activity.

BACKGROUND: Disease risk is lower in metabolically healthy obese adults than in their unhealthy obese counterparts. Studies considering physical activity as a modifiable determinant of healthy obesity have relied on self-reported measures, which are prone to inaccuracies and do not capture all movements that contribute to health. OBJECTIVE: We aimed to examine differences in total and moderate-to-vigorous physical activity between healthy and unhealthy obese groups by using both self-report and wrist-worn accelerometer assessments. DESIGN: Cross-sectional analyses were based on 3457 adults aged 60-82 y (77% male) participating in the British Whitehall II cohort study in 2012-2013. Normal-weight, overweight, and obese adults were considered "healthy" if they had <2 of the following risk factors: low HDL cholesterol, hypertension, high blood glucose, high triacylglycerol, and insulin resistance. Differences across groups in total physical activity, based on questionnaire and wrist-worn triaxial accelerometer assessments (GENEActiv), were examined by using linear regression. The likelihood of meeting 2010 World Health Organization recommendations for moderate-to-vigorous activity (≥2.5 h/wk) was compared by using prevalence ratios. RESULTS: Of 3457 adults, 616 were obese [body mass index (in kg/m²) ≥30]; 161 (26%) of those were healthy obese. Obese adults were less physically active than were normal-weight adults, regardless of metabolic health status or method of physical activity assessment. Healthy obese adults had higher total physical activity than did unhealthy obese adults only when assessed by accelerometer (P = 0.002). Healthy obese adults were less likely to meet recommendations for moderate-to-vigorous physical activity than were healthy normal-weight adults based on accelerometer assessment (prevalence ratio: 0.59; 95% CI: 0.43, 0.79) but were not more likely to meet these recommendations than were unhealthy obese adults (prevalence ratio: 1.26; 95% CI: 0.89, 1.80). CONCLUSIONS: Higher total physical activity in healthy than in unhealthy obese adults is evident only when measured objectively, which suggests that physical activity has a greater role in promoting health among obese populations than previously thought.

Consensus guidelines for enhanced recovery after gastrectomy: Enhanced Recovery After Surgery (ERAS®) Society recommendations.

BACKGROUND: Application of evidence-based perioperative care protocols reduces complication rates, accelerates recovery and shortens hospital stay. Presently, there are no comprehensive guidelines for perioperative care for gastrectomy. METHODS: An international working group within the Enhanced Recovery After Surgery (ERAS®) Society assembled an evidence-based comprehensive framework for optimal perioperative care for patients undergoing gastrectomy. Data were retrieved from standard databases and personal archives. Evidence and recommendations were classified according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system and were discussed until consensus was reached within the group. The quality of evidence was rated 'high', 'moderate', 'low' or 'very low'. Recommendations were graded as 'strong' or 'weak'. RESULTS: The available evidence has been summarized and recommendations are given for 25 items, eight of which contain procedure-specific evidence. The quality of evidence varies substantially and further research is needed for many issues to improve the strength of evidence and grade of recommendations. CONCLUSION: The present evidence-based framework provides comprehensive advice on optimal perioperative care for the patient undergoing gastrectomy and facilitates multi-institutional prospective cohort registries and adequately powered randomized trials for further research.

Durability of the response to peginterferon-α2b and ribavirin in patients with chronic hepatitis C: a cohort study in the routine clinical setting.

OBJECTIVES: To evaluate whether, in chronic hepatitis C-positive naive patients recruited in the routine clinical setting and treated with pegylated-interferon-α2b (Peg-IFN) and ribavirin (RBV), the sustained virologic response (SVR) is durable over the long term and whether it is associated with a decrease in liver complications and incidence of glucose abnormalities. PATIENTS AND METHODS: This was a prospective long-term follow-up study of 182 naive patients enrolled in 2001-2002 and treated with Peg-IFN and RBV and followed up to December 2010, with clinical, biochemical, and virological evaluations every 6-12 months. RESULTS: None of the 115 (63.2%) sustained responders showed late viremic relapse during the follow-up. SVR was better defined at 24 weeks (16/16 relapsers, 100%) than at 12 weeks after the end of therapy (14/16 relapsers, 87.5%). On multivariable analysis, viral genotype (odds ratio 0.16, 95% confidence interval 0.07-0.36, P=0.0001) and a greater than 20% RBV reduction (odds ratio 5.21, 95% confidence interval 1.54-17.67, P=0.008) predicted long-term response (LTR) independently. The incidence of cirrhosis was significantly higher among nonresponders (21.3%) compared with long-term responders (0.9%, P≤0.0001), but the risk of developing glucose abnormalities was not significantly reduced in long-term responders (hazard ratio 1.36, P=0.363). Hepatocellular carcinoma occurred only in three cases. CONCLUSION: SVR achieved in patients treated in the routine clinical setting with Peg-IFN and RBV is durable over the long term and LTR significantly reduces the risk of progression to cirrhosis; however, in a population with mild liver fibrosis, the clinical impact of LTR on the risk of glucose abnormalities seems negligible.

Resveratrol: therapeutic potential for improving cardiometabolic health.

BACKGROUND: Resveratrol, a natural polyphenol, has gained attention in recent years because of its connection with the health benefits of red wine and its anticancer activity in vitro. Studies in animal models have demonstrated beneficial effects on glucose metabolism, vascular function and anti-inflammatory and antioxidant properties. Human studies designed to understand the role of resveratrol in the prevention and treatment of age-related conditions such as diabetes, heart disease, and cancer have recently been undertaken. METHODS: We searched PubMed for original articles that reported studies of resveratrol in humans, using search terms, including resveratrol, human studies, glucose metabolism, vascular function, and inflammation. We also searched the reference lists of identified articles for additional papers and sought expert opinion on relevant studies. RESULTS: Resveratrol treatment has shown beneficial effects on glucose and lipid metabolism in some, but not all studies. Study population, resveratrol source, and dose have varied widely, potentially explaining inconsistent findings. Improvements were noted in endothelial function, systolic blood pressure, and markers of oxidative stress and inflammation in several studies. CONCLUSIONS: Despite the strong preclinical evidence of positive cardiometabolic effects, studies to date have not confirmed resveratrol's benefit in humans. Study variability and methodological issues limit interpretation of available results. Additional research, focusing on subjects with defined metabolic defects and using a range of doses, is needed to advance the field.

[Disorders of carbohydrate metabolism, dyslipidemia, and bone metabolic disease after hematopoietic stem cell transplantation]. / Zaburzenia gospodarki weglowodanowej i tluszczowej oraz metaboliczna choroba kosci po przeszczepieniu komórek krwiotwórczych.

Among long-term survivors after hematopoietic stem cell transplantation (HSCT) late endocrine complications are observed in 20-50%. Very often these complications influence significantly the patient´s life and have to be treated till the end of life. Their proper prevention and monitoring are extremely important in patients who underwent HSCT during childhood. Since the 90s of the last millennium/century, thyroid dysfunction, disorders of somatic and sexual development, and disturbances of fertility have been presented in several publications. In the paper, less known endocrine complications after HSCT published in the last years are discussed. Disorders of carbohydrate metabolism, post-transplant diabetes and insulin resistance are presented. Moreover, dyslipidemia, hypertension, and post-transplant bone metabolic disease are demonstrated/shown. The paper describes the etiopathogenesis, methods of prevention as well as treatment and the results of the treatment of these endocrine complications after HSCT. Moreover, actual recommendations for screening and prevention of endocrine complications in long-term HCT survivors are presented.

Three-year effects on dietary quality of health education: a randomized controlled trial of people with screen-detected dysglycaemia (The ADDITION study, Denmark).

BACKGROUND: Healthy diet is a core component in prevention and self-management of type 2 diabetes and cardiovascular disease. The long-term efficacy was assessed of a theory-based health education programme 'Ready to Act' on dietary quality in people with screen-detected dysglycaemia. METHODS: Five hundred and nine adults with prediabetes (impaired glucose tolerance, impaired fasting glycaemia) or type 2 diabetes were recruited through screening for type 2 diabetes [the ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care) study, DK] and then randomly assigned to health education or to a control group (I = 322; C = 187). The intervention group was offered a 12-week programme in health-related action competence including 2 one-to-one and 8 group sessions (18 h). Dietary quality was measured by the Dietary Quality Score_revised (0-8 points) at baseline and at one- and 3-year follow-up. Changes were analysed by multilevel analyses. RESULTS: The analysis included data from 444 participants (87%). At the 3-year follow-up, the intervention group had significantly increased dietary quality compared with the control group (net change: 0.39 Dietary Quality Score_revised points, P = 0.04). The intake of unsaturated fats used on bread and for cooking increased in the intervention group compared with the control group at the 3-year follow-up (net change: 31 g/week; P = 0.02). A non-significant tendency toward an increased intake of vegetables in the intervention group compared with the control group was seen (net change: 111 g/week; P = 0.16). No changes were seen in fish intake. CONCLUSIONS: Health education aiming at action competence improved the long-term dietary quality in a population with dysglycaemia, especially according to the intake of unsaturated fat. The ADDITION trial was registered at ClinicalTrials.gov ID no NCT00237549.

Dietary antioxidants: Do they have a role to play in the ongoing fight against abnormal glucose metabolism?

Overfeeding, an increased intake of saturated fatty acids, and sugary foods are key dietary changes that have occurred in recent decades in addition to the emergence of the obesity epidemic. In addition to an increase in energy storage as fat, these dietary changes are accompanied by an increase in mitochondrial macronutrient oxidation, leading to an excessive free radical production and, hence, oxidative stress. The latter has long been considered a central mechanism linking nutrient overload, insulin resistance, the metabolic syndrome, and diabetes. However, food, through fruit and vegetable consumption, also can be a great source of antioxidants that protect the body against oxidative damage and insulin resistance and thus help cope with the metabolic backlash of the energy-dense Westernized diet. Experimental data are in favor of the beneficial role conveyed by antioxidants in glucose metabolism, but clinical data in humans remain controversial. This review therefore aimed to sort out any underlying discrepancies and provide an overall clear view of the role of antioxidants in the ongoing fight against abnormal glucose metabolism.

Factors associated with poor glycemic control in older Mexican American diabetics aged 75 years and older.

OBJECTIVE: This study examines the prevalence and correlates of poor glycemic control in Mexican Americans aged 75 years and older with diabetes. METHODS: Data are from the 5(th) wave (2004-05) of the Hispanic Established Population for the Epidemiological Study of the Elderly (H-EPESE). A total of 2,069 Mexican Americans aged 75 and over were interviewed. Six hundred eighty nine subjects (33.5%) reported having been diagnosed with diabetes and 209 (30.3%) subjects agreed to a blood test of their HbA(1)c level. RESULTS: Of the 209 diabetic subjects with an HbA(1)c test, 73 (34.9%) had good glycemic control (HbA(1)c <7%) and 136 (65.1%) had poor glycemic control (HbA(1)c >7%). Bivariate analysis revealed that subjects with poor control had longer disease duration, had lower education, used the glucometer more frequently, and had more diabetes-complications when compared to those in the good glycemic control group. Multivariable logistic regression analysis found the following factors associated with poor glycemic control: <8 years of education, foreign-born, smoking, obesity, longer disease duration, daily glucometer use, and having macro-complications. DISCUSSION: Prevalence of poor glycemic control is very high in this population with very high and rising prevalence of diabetes. Further studies are needed to explore the effect of these and other characteristics on glycemic control among older Mexican Americans and to develop appropriate interventions to improve diabetes outcomes and increase life-expectancy.