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Excess nutrient uptake is one of the main factors of complications related to metabolism disorders. Therefore, efforts have emerged to modulate nutrient transport in the intestine. However, current approaches are mainly invasive interventions with various side effects. Here, a pH-responsive hydrogel is formulated by acidifying the hydroxide compounds within sucralfate to allow electrostatic interactions between pectin and aluminum ions. The pH responsiveness relies on the alternation of cations and hydroxide species, providing reversible shifting from a hydrogel to a complex coacervate system. It acts as a transient physical barrier coating to inhibit intestinal absorption and changes the viscosity and barrier function in different parts of the gastrointestinal tract, showing enhanced mucoadhesive properties. The therapeutic hydrogel remarkably lowers the immediate blood glucose response by modulating nutrient contact with bowel mucosa, suggesting potential in treating diabetes. In addition, it significantly reduces weight gain, fat accumulation, and hepatic lipid deposition in rodent models. This study provides a novel strategy for fabricating pH-responsive hydrogels, which may serve as a competent candidate for metabolism disorder management.

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.

Timely diagnosis of type 2 diabetes and early intervention and treatment of it are important for controlling metabolic disorders, delaying and reducing complications, reducing mortality, and improving quality of life. Type 2 diabetes was diagnosed by Fourier transform mid-infrared (FTIR) attenuated total reflection (ATR) spectroscopy in combination with extreme gradient boosting (XGBoost). Whole blood FTIR-ATR spectra of 51 clinically diagnosed type 2 diabetes and 55 healthy volunteers were collected. For the complex composition of whole blood and much spectral noise, Savitzky-Golay smoothing was first applied to the FTIR-ATR spectrum. Then PCA was used to eliminate redundant data and got the best number of principle components. Finally, the XGBoost algorithm was used to discriminate the type 2 diabetes from healthy volunteers and the grid search algorithm was used to optimize the relevant parameters of the XGBoost model to improve the robustness and generalization ability of the model. The sensitivity of the optimal XGBoost model was 95.23% (20/21), the specificity was 96.00% (24/25), and the accuracy was 95.65% (44/46). The experimental results show that FTIR-ATR spectroscopy combined with XGBoost algorithm can diagnose type 2 diabetes quickly and accurately without reagents.

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., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background and Purpose: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, is closely related to metabolic diseases such as obesity and diabetes. Despite an accumulating number of studies, no pharmacotherapy that targets NAFLD has received general approval for clinical use., Experimental Approach: Inhibition of the sodium-glucose cotransporter 2 (SGLT2) is a promising approach to treat diabetes, obesity, and associated metabolic disorders. In this study, we investigated the effect of a novel SGLT2 inhibitor, NGI001, on NAFLD and obesity-associated metabolic symptoms in high-fat diet (HFD)-induced obese mice., Key Results: Delayed intervention with NGI001 protected against body weight gain, hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, compared with HFD alone. Adipocyte hypertrophy was prevented by administering NGI001. NGI001 inhibited impaired glucose metabolism and regulated the secretion of adipokines associated with insulin resistance. In addition, NGI001 supplementation suppressed hepatic lipid accumulation and inflammation but had little effect on kidney function. In-depth investigations showed that NGI001 ameliorated fat deposition and increased AMPK phosphorylation, resulting in phosphorylation of its major downstream target, acetyl-CoA carboxylase, in human hepatocyte HuS-E/2 cells. This cascade ultimately led to the down-regulation of downstream fatty acid synthesis-related molecules and the up-regulation of downstream β oxidation-associated molecules. Surprisingly, NGI001 decreased gene and protein expression of SGLT1 and SGLT2 and glucose uptake in oleic acid-treated HuS-E/2 cells., Conclusion and Implications: Our findings suggest the novel SGLT2 inhibitor, NGI001 has therapeutic potential to attenuate or delay the onset of diet-induced metabolic diseases and NAFLD., (© 2019 The British Pharmacological Society.)

Background: Olanzapine, regarded as one of the most efficacious antipsychotic medications for the treatment of schizophrenia, is associated with a high risk of weight gain and metabolic dysfunction. ALKS 3831, a clinical candidate for treatment of schizophrenia, is a combination of olanzapine and samidorphan, an opioid receptor antagonist. The addition of samidorphan is intended to mitigate weight gain and the metabolic dysregulation associated with the use of olanzapine., Methods: Non-clinical studies were conducted to assess the metabolic effects of olanzapine and samidorphan alone and in combination at clinically relevant exposure levels., Results: Chronic olanzapine administration in male and female rats shifted body composition by increasing adipose mass, which was accompanied by an increase in the rate of weight gain in female rats. Co-administration of samidorphan normalized body composition in both sexes and attenuated weight gain in female rats. In hyperinsulinemic euglycemic clamp experiments conducted prior to measurable changes in weight and/or body composition, olanzapine decreased hepatic insulin sensitivity and glucose uptake in muscle while increasing uptake in adipose tissue. Samidorphan appeared to normalize glucose utilization in both tissues, but did not restore hepatic insulin sensitivity. In subsequent studies, samidorphan normalized olanzapine-induced decreases in whole-body glucose clearance following bolus insulin administration. Results from experiments in female monkeys paralleled the effects in rats., Conclusions: Olanzapine administration increased weight gain and adiposity, both of which were attenuated by samidorphan. Furthermore, the combination of olanzapine and samidorphan prevented olanzapine-induced insulin insensitivity. Collectively, these data indicate that samidorphan mitigates several metabolic abnormalities associated with olanzapine in both the presence and the absence of weight gain.

Overweight and obesity in children is becoming an increasingly common problem due to the increased access to processed food, overly high energy density diet, and limitation of physical activity in children. Such trends in today's society lead to health consequences that can be observed in the early stages of carbohydrate metabolism disorders. Reduction of body weight and changes in eating habits can prevent the onset of type 2 diabetes. Recently, the benefits of consuming products containing resistant starch, which has the main advantage of influencing the metabolic pathway of glucose, have been increasingly underlined. To date, no recommendations have been made for the daily intake of resistant starch or its content in individual products available on the food market. However, in the medical literature, there are an increasing number of reported cases of the beneficial effect of consuming resistant starch as a factor that supports glycaemic control in children with carbohydrate disorders. Unfortunately, the above topic requires further research in this direction, especially in the developmental age population, which will allow the formulation of precise conclusions regarding its use in the prevention of overweight, obesity, carbohydrate metabolism disorders, and the development of diabetes.

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., (© 2018 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

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-β-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., (© 2019 John Wiley & Sons Ltd.)

Associations between obesity, diabetes type II, and steatosis have long been recognized. However, a pharmacotherapy that acts in a multifactorial manner controlling the interactions between these conditions is not available. A variety of natural plants, functional fatty acids, and other natural dietary compounds have been used in various anti-obesity products. We investigated the effects of oral administration of an antioxidant carotenoid pigment Bixin and Bixin: β-Cyclodextrin in an obese murine model. C57BL/6 male mice (4-5 weeks) received standard diet (2.18 kcal per 1 g) (CT) and high-fat diet (4.38 kcal per 1 g) (CT/OB, BIX and BIX/βCD) (n = 10 per group). After 16 weeks, the BIX and BIX/βCD were treated by gavage (100 μL day-1) for six weeks, with water (CT and CT/OB groups) and (50 mg kg-1 day-1), Bixin (BIX group) or Bix: β-CD (BIX/βCD). Body weight, Lee's Index, adiposity, CHT, TG, CHT/HDL-c, glucose levels (metabolic markers) and, liver markers (AST and ALT) were determined. All metabolic and liver parameters exhibited down-regulation after oral administration of BIX and BIX/βCD. Particularly relevant was Lee's Index and adiposity in BIX- and BIX/βCD-treated groups (339.18 g/cm -BIX and 327.58 g/cm -BIX/βCD vs. 360.68 g/cm -CT/OB animals), this finds associated with the insulin sensitivity test, showed a clear association between reduction of adipose tissue and decrease of peripherical insulin resistant. In conclusion, our study suggested that the oral administration of the Bixin and Bix: β-CD inclusion compound improved the metabolic parameters evaluate in obese mice, being more palatable and hepatoprotective., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: The effectiveness of lifestyle intervention for weight loss on cardiometabolic risk factors among overweight and obese individuals in the community setting remains inconclusive. This study aimed to evaluate the effect of a 6-month weight loss lifestyle intervention on cardiometabolic risk factors among overweight and obese women and the sustainability of the changes in those markers at 12-month follow-up, comparing an intervention group with a control group., Methods: A total of 243 participants from MyBFF@home were included in this study. Fasting blood samples at baseline, 6- and 12-month were assessed for fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. The effect of the intervention on cardiometabolic risk markers were investigated within and between study groups using t-test and general linear model (GLM) repeated measure ANOVA., Results: Results from repeated measures ANOVA showed intervention effect only in TC where significant reduction was found in the intervention group (- 0.26 mmol/L [95% CI: - 0.47 to - 0.06], p < 0.01) compared to the control group (- 0.06 mmol/L [95% CI: - 0.28 to 0.17]) at 12 months. At 6 months, TC was reduced significantly in both groups but only intervention group retained the reduction in maintenance phase while, the level increased significantly in the control group (0.22 mmol/L [95% CI: 0.06 to 0.38]). This attributed to significant increase in TC/HDL-C ratio in the control group during maintenance phase (0.32 [95% CI: 0.15 to 0.50], p < 0.001). The intervention group also showed trend of reduction in FPG at 6 months and further decreased during maintenance phase (- 0.19 mmol/L [95% CI: - 0.32 to - 0.06], p < 0.01). At 6 months HDL-C was maintained in the intervention group but reduced significantly in the control group (- 0.05 mmol/L [95% CI: - 0.10 to - 0.01], p < 0.05). No significant difference was detected in both markers when compared between groups., Conclusions: In the context of low socio-economic communities, this study supports that weight loss related lifestyle modifications over a 6-month period could improve selected cardiometabolic risk factors, particularly fasting glucose, TC and HDL-C in overweight and obese women with favourable sustainability over a 12-month period.

Although metabolic syndrome (MetS) could be handled by lifestyle interventions, its relationship with dietary patterns remains unclear in populations from Central Europe. Using data from the Kardiovize Brno cohort, the present study aims to identify the main dietary patterns and to evaluate their association with MetS risk in a random urban sample from Brno, Czech Republic. In a cross-sectional study of 1934 subjects aged 25⁻65 years (44.3% male), dietary patterns were derived by food frequency questionnaire (FFQ) administration and principal component analysis. Metabolic syndrome was defined according to the International Diabetes Federation statement. Logistic regression models were applied. High adherence to the prudent dietary pattern was associated with lower odds of abdominal obesity, abnormal glucose concentration, and MetS. By contrast, high adherence to the western dietary pattern was associated with higher odds of abnormal glucose, triglycerides and blood pressure levels. Whilst our results confirm the deleterious effect of a western dietary pattern on several metabolic risk factors, they also indicate that the consumption of a diet rich in cereals, fish, fruit and vegetables is associated with a healthier metabolic profile. However, further prospective research is warranted to develop and validate novel potential preventive strategies against MetS and its complications.

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-β) 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., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

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.

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., (© 2017 Society for Endocrinology.)

Data on cardiovascular disease in primary hyperparathyroidism (PHPT) are controversial; indeed, at present, cardiovascular involvement is not included among the criteria needed for parathyroidectomy. Aim of this narrative review is to analyze the available literature in an effort to better characterize cardiovascular involvement in PHPT. Due to physiological effects of both parathyroid hormone (PTH) and calcium on cardiomyocyte, cardiac conduction system, smooth vascular, endothelial and pancreatic beta cells, a number of data have been published regarding associations between symptomatic and mild PHPT with hypertension, arrhythmias, endothelial dysfunction (an early marker of atherosclerosis), glucose metabolism impairment and metabolic syndrome. However, the results, mainly derived from observational studies, are inconsistent. Furthermore, parathyroidectomy resulted in conflicting outcomes, which may be linked to several potential biases. In particular, differences in the methods utilized for excluding confounding co-existing cardiovascular risk factors together with differences in patient characteristics, with varying degrees of hypercalcemia, may have contributed to these discrepancies. The only meta-analysis carried out in PHPT patients, revealed a positive effect of parathyroidectomy on left ventricular mass index (a predictor of cardiovascular mortality) and more importantly, that the highest pre-operative PTH levels were associated with the greatest improvements. In normocalcemic PHPT, it has been demonstrated that cardiovascular risk factors are almost similar compared to hypercalcemic PHPT, thus strengthening the role of PTH in the cardiovascular involvement. Long-term longitudinal randomized trials are needed to determine the impact of parathyroidectomy on cardiovascular diseases and mortality in PHPT., (© 2017 European Society of Endocrinology.)

Objectives: Interrupting prolonged periods of sitting may improve postprandial insulin and glucose although it is unclear whether interruptions need to involve physical activity or simply a change in posture (from sitting to standing) to benefit adults without metabolic impairment. This study examined effects of interrupting sitting with intermittent walking, and intermittent standing on dynamic insulin and glucose responses in men without known metabolic impairment., Design: A randomised three-arm, cross-over experimental study comprising three seven-hour days of sustained sitting., Methods: Twenty-five inactive men (aged 40.2±12.2 years) took part. The three interventions were; SIT-ONLY (uninterrupted sitting), SIT-STAND (sitting interrupted with 2min standing bouts every 20min) and SIT-WALK (sitting interrupted with 2min light-intensity walking bouts every 20min). An oral glucose tolerance test was administered at baseline and a standardised mixed test meal at hour three. Comparisons of Matsuda Index, and area under the curve (AUC) for insulin and glucose were made between interventions using generalised estimating equation models., Results: Matsuda index was 16% higher (mean difference 1.2 [95%CI 0.1, 2.2] p=0.02), AUC for glucose 9% lower (-2.5mmol/L×7h [-3.7, -1.3mmol/L×7h] p<0.001) and AUC for insulin 21% lower (-546.5pmol/L×7h [-723.6, -369.3pmol/L×7h] p<0.001) in SIT-WALK compared to SIT-ONLY. There were no significant differences between SIT-STAND and SIT-ONLY in any main outcome measure., Conclusions: Interrupting sustained sitting with brief repeated bouts of light-intensity walking but not standing reduced insulin demand and improved glucose uptake during a simulated sedentary working day. The benefits of such minor behavioural changes could inform future workplace health interventions., (Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

This study aimed to review and synthesize the available scientific evidence on the relationship between serum 25(OH)D concentrations and glucose metabolism among adolescents. A total of 19 studies were included. Many studies did not find a relation between 25(OH)D concentrations and insulin sensitivity, but most studies have shown that vitamin D status influences glucose dysregulation in youth due to particularities of this life stage. Considering the prevalence of vitamin D deficiency and insufficiency were high among adolescents, the importance for vitamin D status correction in this young group, in which chronic diseases are not expected but getting every day more common, is mandatory.

The perinatal environment has a major influence on long-term health and disease risk. Preterm birth alters early-life environment and is associated with altered metabolic function in adulthood. Whether preterm birth per se or the early nutritional interventions used to support growth in preterm infants underpins this association is unknown. Lambs born preterm, following dexamethasone induction of labour, or spontaneously at term were randomised to receive nutrient supplementation, analogous to the milk fortifier used clinically or water as a control for the first 2 weeks after birth. Thereafter, nutrition was not different between groups. Growth was monitored, and the glucose-insulin axis function was assessed in juvenile (4 months) and adult life (14 months). Early nutrition influenced adult metabolic function and body composition to a greater extent than preterm birth. In supplemented females, arginine-stimulated insulin secretion was increased in preterm but reduced in term-born juveniles compared with controls (repeated-measures ANOVA P<0·01). In supplemented preterm males, adult weight, ponderal index (PI) and fasting insulin concentrations were elevated compared with preterm controls (weight, 75 (sem 3) v. 69 (sem 2) kg; PI, 48·0 (sem 2·1) v. 43·7 (sem 1·7) kg/m3; fasting insulin, 0·19 (sem 0·02) v. 0·10 (sem 0·02) ng/ml). Conversely, supplemented term-born males had reduced adult weight, PI and fasting insulin concentrations compared with term-born controls (weight, 64 (sem 2) v. 70 (sem 2) kg; PI, 44·4 (sem 1·8) v. 48·2 (sem 1·7) kg/m3; fasting insulin, 0·09 (sem 0·02) v. 0·14 (sem 0·02) ng/ml; all group×supplement interactions P<0·05). Adult metabolic health may reflect both gestational age at birth and early nutrition. Human studies are urgently needed to investigate the adult sex-specific health implications of neonatal nutritional strategies.

Background: Many guidelines exist for screening and risk assessment for the primary prevention of cardiovascular disease in apparently healthy persons., Purpose: To systematically review current primary prevention guidelines on adult cardiovascular risk assessment and highlight the similarities and differences to aid clinician decision making., Data Sources: Publications in MEDLINE and CINAHL between 3 May 2009 and 30 June 2016 were identified. On 30 June 2016, the Guidelines International Network International Guideline Library, National Guideline Clearinghouse, National Library for Health Guidelines Finder, Canadian Medical Association Clinical Practice Guidelines Infobase, and Web sites of organizations responsible for guideline development were searched., Study Selection: 2 reviewers screened titles and abstracts to identify guidelines from Western countries containing recommendations for cardiovascular risk assessment for healthy adults., Data Extraction: 2 reviewers independently assessed rigor of guideline development using the Appraisal of Guidelines for Research and Evaluation II instrument, and 1 extracted the recommendations., Data Synthesis: Of the 21 guidelines, 17 showed considerable rigor of development. These recommendations address assessment of total cardiovascular risk (5 guidelines), dysglycemia (7 guidelines), dyslipidemia (2 guidelines), and hypertension (3 guidelines). All but 1 recommendation advocates for screening, and most include prediction models integrating several relatively simple risk factors for either deciding on further screening or guiding subsequent management. No consensus on the strategy for screening, recommended target population, screening tests, or treatment thresholds exists., Limitation: Only guidelines developed by Western national or international medical organizations were included., Conclusion: Considerable discrepancies in cardiovascular screening guidelines still exist, with no consensus on optimum screening strategies or treatment threshold., Primary Funding Source: Barts Charity.

Previously it has been reported that reduced-exertion high-intensity interval training (REHIT; total training time of 3 × 10 min per week) improves maximal aerobic capacity in both sedentary men and women, but improves insulin sensitivity in men only. The aim of the present study was to determine whether there is a true sex difference in response to REHIT, or that these findings can be explained by the large interindividual variability in response inherent to all exercise training. Thirty-five sedentary participants (18 women; mean ± SD age for men and women, respectively: age, 33 ± 9 and 36 ± 9 years; body mass index, 25.1 ± 2.1 and 24.1 ± 3.5 kg·m -2 ; maximal aerobic capacity, 38.6 ± 8.3 and 31.6 ± 4.6 mL·kg -1 ·min -1 ) completed a 6-week REHIT programme consisting of eighteen 10-min unloaded cycling sessions with 1 (first session) or 2 (all other sessions) "all-out" 10-20-s sprints against a resistance of 5% of body mass. Maximal aerobic capacity and oral glucose tolerance test-derived insulin sensitivity were determined before and after training. REHIT was associated with an increase in maximal aerobic capacity (2.54 ± 0.65 vs. 2.78 ± 0.68 L·min -1 , main effect of time: p < 0.01), a trend toward reduced plasma insulin area-under-the-curve (AUC; 6.7 ± 4.8 vs. 6.1 ± 4.0 IU·min -1 ·mL -1 , p = 0.096), but no significant change in plasma glucose AUC or the Cederholm index of insulin sensitivity. Substantial interindividual variability in response to REHIT was observed for all variables, but there was no significant effect of sex. In conclusion, REHIT improves the key health marker of aerobic capacity within a minimal total training time-commitment. There is large interindividual variability in responses to REHIT, but sex differences in the responses are not apparent.

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-3β 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-3β 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., (Copyright © 2016. Published by Elsevier GmbH.)

Purpose of Review: Dietary sugars play a role in noncommunicable diseases and represent a clear target for reduction. In this context, product reformulation can have a positive impact on health. Several technological solutions are available to replace sugar, all with benefits and limitations. The goal of this review is to describe the main sugar replacement alternatives and discuss their impact on health and product physicochemical properties., Recent Findings: Although high intensity sweeteners and polyols have been used for a long time to replace sucrose and despite no clear evidence of harm, the trend is today to look for alternatives such as sweet enhancers or alternative sugars such as allulose or tagatose, which are both low caloric. To replace the physical properties of sugars, new trends are to substitute widely used maltodextrins by dietary fibres to confer added health benefits., Summary: A wide range of solutions is currently available to replace dietary sugars and compensate for the impact on bulking properties and sweetness profile of food products.

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.

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans., (© The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This investigation examines whether a low intermittent dose of rapamycin will avoid the hyperlipidemia and diabetes-like syndrome associated with rapamycin while still decreasing body weight and adiposity in aged obese rats. Furthermore, we examined if the rapamycin-mediated decrease in serum leptin was a reflection of decreased adiposity, diminished leptin synthesis, or both. To these ends, rapamycin (1mg/kg) was administered three times a week to 3 and 24-month old rats. Body weight, food intake, body composition, mTORC1 signaling, markers of metabolism, as well as serum leptin levels and leptin synthesis in adipose tissue were examined and compared to that following a central infusion of rapamycin. Our data suggest that the dosing schedule of rapamycin acts on peripheral targets to inhibit mTORC1 signaling, preferentially reducing adiposity and sparing lean mass in an aged model of obesity resulting in favorable outcomes on blood triglycerides, increasing lean/fat ratio, and normalizing elevated serum leptin with age. The initial mechanism underlying the rapamycin responses appears to have a peripheral action and not central. The peripheral rapamycin responses may communicate an excessive nutrients signal to the hypothalamus that triggers an anorexic response to reduce food consumption. This coupled with potential peripheral mechanism serves to decrease adiposity and synthesis of leptin., (© The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© 2016 Diabetes UK.)

Background: The antioxidant lutein is suggested as being beneficial to cardiometabolic health because of its protective effect against oxidative stress, but evidence has not systematically been evaluated., Objective: We aimed to evaluate systematically the effects of lutein (intake or concentrations) on cardiometabolic outcomes in different life stages., Design: This is a systematic review with meta-analysis of literature published in MEDLINE, Embase, Cochrane Central, Web of Science, PubMed, and Google Scholar up to August 2014. Included were trials and cohort, case-control, and cross-sectional studies in which the association between lutein concentrations, dietary intake, or supplements and cardiometabolic outcomes was reported. Two independent investigators reviewed the articles., Results: Seventy-one relevant articles were identified that included a total of 387,569 participants. Only 1 article investigated the effects of lutein during pregnancy, and 3 studied lutein in children. Furthermore, 31 longitudinal, 33 cross-sectional, and 3 intervention studies were conducted in adults. Meta-analysis showed a lower risk of coronary heart disease (pooled RR: 0.88; 95% CI: 0.80, 0.98) and stroke (pooled RR: 0.82; 95% CI: 0.72, 0.93) for the highest compared with the lowest tertile of lutein blood concentration or intake. There was no significant association with type 2 diabetes mellitus (pooled RR: 0.97; 95% CI: 0.77, 1.22), but higher lutein was associated with a lower risk of metabolic syndrome (pooled RR: 0.75; 95% CI: 0.60, 0.92) for the highest compared with the lowest tertile. The literature on risk factors for cardiometabolic diseases showed that lutein might be beneficial for atherosclerosis and inflammatory markers, but there were inconsistent associations with blood pressure, adiposity, insulin resistance, and blood lipids., Conclusions: Our findings suggest that higher dietary intake and higher blood concentrations of lutein are generally associated with better cardiometabolic health. However, evidence mainly comes from observational studies in adults, whereas large-scale intervention studies and studies of lutein during pregnancy and childhood are scarce., (© 2016 American Society for Nutrition.)

Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released in response to dietary nutrients, which acts through a specific receptor, the GLP-2 receptor (GLP-2R). The physiological effects of GLP-2 are multiple, involving also the intestinal adaptation to high fat diet (HFD). In consideration of the well-known relationship between chronic HFD and impaired glucose metabolism, in the present study we examined if the blocking of the GLP-2 signaling by chronic treatment with the GLP-2R antagonist, GLP-2 (3-33), leads to functional consequences in the regulation of glucose metabolism in HFD-fed mice. Compared with animals fed standard diet (STD), mice at the 10th week of HFD showed hyperglycaemia, glucose intolerance, high plasma insulin level after glucose load, increased pancreas weight and β cell expansion, but not insulin resistance. In HFD fed mice, GLP-2 (3-33) treatment for 4 weeks (from the 6th to the 10th week of diet) did not affect fasting glycaemia, but it significantly increased the glucose intolerance, both fasting and glucose-induced insulin levels, and reduced the sensitivity to insulin leading to insulin-resistance. In GLP-2 (3-33)-treated HFD mice pancreas was significantly heavier and displayed a significant increase in β-cell mass in comparison with vehicle-treated HFD mice. In STD mice, the GLP-2 (3-33) treatment did not affect fasted or glucose-stimulated glycemia, insulin, insulin sensitivity, pancreas weight and beta cell mass. The present study suggests that endogenous GLP-2 may act as a protective factor against the dysregulation of the glucose metabolism that occurs in HFD mice, because GLP-2 (3-33) worsens glucose metabolism disorders., (© 2015 Wiley Periodicals, Inc.)

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.

Insulin resistance is the cornerstone of multiple diseases such as metabolic syndrome, diabetes mellitus, arterial hypertension, dyslipidemia, acute coronary syndrome, etc. There are some medications and changes in lifestyle that can reduce insulin resistance. Not all are suitable for all patients. We discovered another pharmacologic agent that can be successfully added to the old methods already in use.

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., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

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.

The intake of marine n-3 PUFA has been shown to decrease the risk of CVD in a number of studies. Since the development of CVD is often a lifelong process, marine n-3 PUFA intake early in life may also affect the development of later CVD. The aim of the present study was to investigate the association between maternal intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. The study was based on the follow-up of the offspring of a Danish pregnancy cohort who participated in a study conducted from 1988 to 1989. A total of 965 pregnant women were originally included in the cohort and detailed information about the intake of marine n-3 PUFA during the second trimester was collected. In 2008-9, the offspring were invited to participate in a clinical examination including anthropometric, blood pressure (BP) and short-term heart rate variability measurements. Also, a fasting venous blood sample was drawn from them. Multiple linear regression modelling, using the lowest quintile of marine n-3 PUFA intake as the reference, was used to estimate the association with all outcomes. A total of 443 offspring participated in the clinical examination. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and offspring adiposity, glucose metabolism, BP or lipid profile was found. In conclusion, no association between the intake of marine n-3 PUFA during the second trimester of pregnancy and the factors associated with cardiometabolic risk in the 20-year-old offspring could be detected.

The common marmoset (Callithrix jacchus), a laboratory nonhuman primate, is a well-known model of several human diseases and conditions, but the nutritional needs of these animals are not fully understood. Here we describe a 4-mo controlled study in which we increased the dietary fat and protein of subadult male common marmosets by using healthy snacks. Six male marmosets received their normal diet (control), and an additional 6 were given their normal diet supplemented daily with a 14-kcal snack. Cashews and waxworms were used as the snack, given their high-fat content. Although body weight did not differ between the 2 groups, only control male marmosets showed increased chest circumferences over the course of the study. Glucoregulatory function remained consistent in the snack-fed marmosets, whereas control animals had progressed toward higher insulin. Other indices of glucoregulation indicated significant differences in adiponectin and the cortisol:cortisone ratio between the 2 groups, but no differences in lipid concentration were detected. Therefore, the most notable difference attributable to the snack feeding was improved glucoregulation. Because the snacks we used had a high proportion of unsaturated compared with saturated fat, we suggest that these healthy high-fat-high-protein snacks provide an important contribution to the nutrition of this laboratory species. This study also demonstrates the utility of marmosets as a model for understanding the implications of dietary fats in humans.

Background and Aims: To examine differences in cardiometabolic risk factors between children of different BMI and fitness levels., Methods and Results: From a representative sample of 1222 boys and 1188 girls, aged 9-13 years, anthropometric, body composition, physical activity, cardiorespiratory fitness, biochemical and blood pressure data was collected. The prevalence of overweight and obesity was 29.9% and 11.8% respectively. In both genders, plasma HDL cholesterol concentration was higher in the 'leaner and less fit' group (lowest quartile of BMI and lowest quartile of fitness) compared to the 'heavier and more fit' (highest quartile of BMI and highest quartile of fitness) and intermediate (all other children) groups (p < 0.05). Furthermore, the 'leaner and less fit' groups in both genders had lower triacylglycerol concentration, total-to-HDL cholesterol ratio, HOMA-IR, insulin and systolic blood pressure levels compared to the 'heavier and more fit' and/or intermediate groups. Similar trends were observed for hypertension in boys and insulin resistance for both genders. Finally, the effect size of being 'leaner and less fit' on serum levels of cardiometabolic risk indices was mainly small to medium (i.e. Cohen's d 0.2-0.5)., Conclusion: Leaner and less fit boys and girls had better cardiometabolic risk profiles than their heavier and more fit peers, probably suggesting a higher importance of leanness over fitness in children from a cardiometabolic health benefit perspective., (Copyright © 2013 Elsevier B.V. All rights reserved.)

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., (© American Journal of Hypertension, Ltd 2013. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8- and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1-fold increase both after 8- and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. The acute insulin-induced phosphorylation of the analyzed ISP proteins increased 1.3- and 2.3-fold after 8- and 12 wk of melatonin supplementation. The total protein content of the insulin receptor (IR) and the IR substrates (IRS-1, 2) remained unchanged in all investigated tissues, except for the 2-fold increase in the total amount of IRS-1 in the periepididymal adipose tissue. Therefore, the known age-related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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&#95;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&#95;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.

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.

Emerging adulthood, a developmental period from late adolescence to the late twenties, is a critical transition for youths with type 1 diabetes. This article proposes a framework for emerging adults with diabetes during this transitional time, integrating theoretical writings on transitions and emerging adulthood with empirical findings from younger adolescents with diabetes, about whom more is known. Key health, developmental, and behavioral outcomes are proposed, as well as key influential personal and environmental characteristics. Influential transitional events for this age group are also discussed relative to these outcomes and to personal and environmental characteristics. This framework provides a guide for longitudinal studies on the transition to young adulthood among emerging adults with type 1 diabetes. Identifying key times and influential factors will provide information for designing future effective interventions to improve glycemic control and quality of life for these youths as they transition to adulthood., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The use of continuous intravenous regular human insulin (RHI) infusion is often necessary to achieve glycemic control in critically ill patients. Because insulin is a high-risk medication owing to the potential for severe hypoglycemia, it is imperative that insulin infusion algorithms are designed to be safe, effective, and instructionally clear. The safety and efficacy of our intravenous RHI infusion algorithm protocol has been previously established (Nutrition 2008;24:536-45); however, the protocol violations by nursing personnel were not examined. The objective of this study was to assess nursing adherence to our RHI infusion algorithm., Methods: Continuous RHI infusion algorithm violations were retrospectively evaluated in adult patients admitted to a trauma intensive care unit who received concurrent continuous enteral and/or parenteral nutrition therapy and our algorithm for at least 3 d. Blood glucose (BG) monitoring was done every 1 to 2 h with the target BG at 70 to 149 mg/dL (3.9 to 8.3 mmol/L). Nursing adherence to the RHI infusion protocol was evaluated for each patient by comparing the adjustments in insulin infusion rates documented by the nursing personnel with the prescribed adjustments per our graduated continuous intravenous RHI infusion algorithm., Results: A total of 4150 BG measurements necessitating the determination of the appropriate RHI dosage rate by nursing personnel in 40 patients occurred during the observational period. The target BG was achieved for a mean of 20 h/d and none of the patients had an episode of severe hypoglycemia (BG <40 mg/dL or 2.2 mmol/L). The overall rate of algorithm violations was 12.1%. The algorithm violations accounted for a single episode of mild to moderate hypoglycemia (BG 40 to 60 mg/dL or 2.2 to 3.3 mmol/L) in 4 patients and 65 total episodes of hyperglycemia (BG ≥150 mg/dL or 8.3 mmol/L) in 18 patients., Conclusion: An adherence rate of nearly 90% is indicative of excellent nursing adherence compared with other published paper-based algorithms that examined protocol adherence. These data, combined with our previously published glycemic control data, indicate that this RHI infusion algorithm is an effective one for hyperglycemic trauma patients receiving continuous enteral and/or parenteral nutritional therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Since 2003, the U.S. Food and Drug Administration as well as the American Diabetes Association, the American Psychiatric Association, and others have called for routine monitoring of cardiometabolic risk factors for patients of all ages prescribed second-generation antipsychotic medications. This survey of major public and private mental health treatment systems in 2010 found that adherence to such guidelines was limited. The authors describe some of the impediments to widespread monitoring of cardiometabolic risk factors among psychiatric patients taking second-generation antipsychotics and advocate for a nationwide commitment to providing the organizational and financial supports necessary to ensure systematic screening of cardiometabolic health among such patients.

Since the work of Eriksson and Lindgärde, published over two decades ago (Diabetologia 1991;34:891-898), we have known that type 2 diabetes can be prevented or delayed by supervised lifestyle interventions (physical exercise and diet modification) in persons at risk of the disease. Here we discuss a novel, time-efficient approach to physical exercise prescription, low-volume, high-intensity interval training (LVHIT), and its efficacy for inducing a range of health benefits in a variety of populations at risk of inactivity-related diseases. We look to the future and suggest that current guidelines for exercise may need to be revised to include different training techniques to deliver the optimum exercise prescription. Indeed, we predict that subsequent exercise guidelines will include LVHIT as part of a comprehensive 'fitness menu' that allows individuals to select the exercise regimen that best fulfils their medical needs, is suited to their lifestyle and daily time restraints, and meets their personal goals.

Objective: To describe the motivators and barriers to the adoption of a healthy postpartum lifestyle after a pregnancy complicated by preeclampsia, intrauterine growth restriction, and/or gestational diabetes., Methods: Thirty-six women with complicated pregnancies participated in six focus-group interviews that aimed to explore the perceptions of modifiable determinants of postpartum lifestyle., Results: Although women expressed that they intended to live a healthy postpartum lifestyle, it was generally not achieved. The motivators included improving their own current health condition as well as modeling a healthy lifestyle for their children. Important barriers were reported to be lack of knowledge, poor recovery, and lack of professional support after delivery., Conclusions: The reported motivators and barriers can be used to develop a postpartum lifestyle intervention.

The renin-angiotensin-aldosterone system (RAAS) is inappropriately activated in obesity. In individuals at risk for diabetes, RAAS inhibition protects against kidney and heart disease, and also reduces the incidence of diabetes in large clinical trials. At a cellular level, angiotensin II (Ang II) and aldosterone induce insulin resistance by increasing oxidative stress and altering insulin signaling, leading to decreased glucose transport. Ang II also contributes to oxidative stress, inflammation, and apoptosis in pancreatic β cells. Aldosterone diminishes glucose-stimulated insulin secretion in vivo and in vitro from isolated pancreatic islets and cultured β cells through a mineralocorticoid receptor (MR)-independent mechanism. We review these findings in the context of pharmacological strategies interrupting the RAAS to highlight the potential application of these strategies to the prevention of diabetes progression., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Antipsychotic drug-induced weight gain and glucose dysregulation add to the cardiovascular risk of patients with schizophrenia and contribute to their early mortality. The currently recommended interventions to address the metabolic complications of antipsychotic drug treatment are to switch the patient from an antipsychotic drug with high metabolic liability to one with a lower liability and to implement lifestyle changes. These interventions can be quite challenging to carry out. So far the progress in improving the metabolic and cardiovascular outcome of patients with major mental illness has been disappointing. We offer an overview of the literature on metformin for antipsychotic drug-induced weight gain and glucose dysregulation and pertinent literature from the Diabetes Prevention Program. We conclude that young adults with schizophrenia newly exposed to antipsychotic drugs, who show a pattern of rapid weight gain and/or glucose dysregulation, are prime candidates for metformin if switching the antipsychotic medication to one with a lower metabolic burden is not an option or does not curtail the weight gain and/or adverse metabolic effects. Metformin therapy should not preclude healthy lifestyle interventions.