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The purpose of this study was to compare the effects of quinoa versus multigrain supplementation on glycemia and lipid metabolism among individuals with impaired glucose tolerance (IGT). In total, 207 participants diagnosed with IGT were randomly assigned to the quinoa group (QG; 100 g day -1 , replacing about half of the total daily staple food), multiple whole grain group (WGG; 100 g day -1 ), or control group (CG) and followed for one year. Biomarkers were measured before and after the intervention. At the efficacy endpoint, the quinoa group (QG) demonstrated significantly longer time in range (TIR) and normal glucose tolerance (NGT) conversion rate, along with lower rates of 2-hour postprandial glucose (2hPG), fasting insulin (FINS), homeostatic model assessment of insulin resistance (HOMA-IR), 14-day mean blood glucose (14dMBG), and diabetes mellitus development compared to those of the multigrain and control groups ( P < 0.05). Significant improvements in glycated hemoglobin (HbA1c) were also found in both the quinoa and multigrain groups compared to the control group ( P < 0.05). No significant difference in glycemic variability (CV) was observed between the quinoa and control groups, while a significant difference was observed between the quinoa and multigrain groups ( P < 0.05). These results suggest that quinoa consumption is significantly more effective than a multiple whole-grain diet in controlling IGT by reducing postprandial glucose and HbA1c levels, improving insulin resistance, and enhancing lipid profiles, making it a superior dietary choice for managing IGT.

Consumption of different types of high-calorie foods leads to the development of various metabolic disorders. However, the effects of multi-strain probiotics on different types of diet-induced obesity and intestinal dysbiosis remain unclear. In this study, mice were fed a control diet, high-fat diet (HFD; 60% kcal fat and 20% kcal carbohydrate), or western diet (WD; 40% kcal fat and 43% kcal carbohydrate) and administered with multi-strain AB-Kefir containing six strains of lactic acid bacteria and a Bifidobacterium strain, at 10 9 CFU per mouse for 10 weeks. Results demonstrated that AB-Kefir reduced body weight gain, glucose intolerance, and hepatic steatosis with a minor influence on gut microbiota composition in HFD-fed mice, but not in WD-fed mice. In addition, AB-Kefir significantly reduced the weight and size of adipose tissues by regulating the expression of CD36 , Igf1 , and Pgc1 in HFD-fed mice. Although AB-Kefir did not reduce the volume of white adipose tissue, it markedly regulated CD36 , Dgat1 and Mogat1 mRNA expression. Moreover, the abundance of Eubacterium&#95;coprostanoligenes&#95; group and Ruminiclostridium significantly correlated with changes in body weight, liver weight, and fasting glucose in test mice. Overall, this study provides important evidence to understand the interactions between probiotics, gut microbiota, and diet in obesity treatment.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released from enteroendocrine L cells in response to meal ingestion. GLP-1 receptor agonists and GLP-1 enhancers have been clinically employed to treat diabetes owing to their glucose-dependent insulin-releasing activity. The release of GLP-1 is primarily stimulated by macronutrients such as glucose and fatty acids, which are nutritionally indispensable; however, excessive intake of sugar and fat is responsible for the development of obesity and diabetes. Therefore, GLP-1 releasing food factors, such as dietary peptides and non-nutrients, are deemed desirable for improving glucose tolerance. Human and animal studies have revealed that dietary proteins/peptides have a potent effect on stimulating GLP-1 secretion. Studies in enteroendocrine cell models have shown that dietary peptides, amino acids, and phytochemicals, such as quercetin, can directly stimulate GLP-1 secretion. In our animal experiments, these food factors improved glucose metabolism and increased GLP-1 secretion. Furthermore, some dietary peptides not only stimulated GLP-1 secretion but also reduced plasma peptidase activity, which is responsible for GLP-1 inactivation. Herein, we review the relationship between GLP-1 and food factors, especially dietary peptides and flavonoids. Accordingly, utilization of food factors with GLP-1-releasing/enhancing activity is a promising strategy for preventing and treating obesity and diabetes.

Background: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity., Methods: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity., Results: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) ( n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group., Conclusions: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity.

Background and Aims: The objectives were to evaluate the relationship between ketogenic diets, the ketone body beta-hydroxybutyrate (BHB), parameters known to increase risk for cardiovascular and metabolic diseases in both sexes, using a pre-clinical model of obesity., Methods and Results: Rats had access to a diet high in fat and sugar (HFS) for 12 weeks. After HFS, they switched to chow (HFS-CH) or ketogenic diet (HFS-KD) for 3 weeks to model a dietary intervention. Body weight, adiposity, and food intake were measured. Glucose tolerance and corticosterone response to stress were measured after HFS, then again after the intervention. Both sexes increased body weight, food intake, and adiposity compared to control (CTL) while on HFS. HFS females showed impaired glucose tolerance. HFS males developed a dampened corticosterone to stress, whereas HFS females developed an exacerbated response. The effects of HFS on adiposity and corticosterone were reversed in HFS-CH males. These same improvements were observed in HFS-CH females, although they still had impaired glucose tolerance. HFS-KD males showed some improvements, however, they still had higher body weight and adiposity than CTL. The same pattern was observed in females. These beneficial effects of KD correlated with plasma BHB levels in females but not in males., Conclusions: These data model effects reported in clinical literature and serve as a valuable translational tool to further test causal mechanisms that lead to desirable outcomes of KD. These sex-specific relationships are important, as KD could potentially affect endocrine mechanisms differently in males and females., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow-up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1-year follow-up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL-c, HDL-c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1-year follow-up (adjOR 1.05 [1.00-1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile., (© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

The increased prevalence of obese, pregnant women who have a higher risk of glucose intolerance warrants the need for nutritional interventions to improve maternal glucose homeostasis. In this study, the effect of a low-glycemic load (GL) ( n = 28) was compared to a high-GL ( n = 34) dietary intervention during the second half of pregnancy in obese women (body mass index (BMI) > 30 or a body fat >35%). Anthropometric and metabolic parameters were assessed at baseline (20 week) and at 28 and 34 weeks gestation. For the primary outcome 3h-glucose-iAUC (3h-incremental area under the curve), mean between-group differences were non-significant at every study timepoint ( p = 0.6, 0.3, and 0.8 at 20, 28, and 34 weeks, respectively) and also assessing the mean change over the study period ( p = 0.6). Furthermore, there was no statistically significant difference between the two intervention groups for any of the other examined outcomes ( p ≥ 0.07). In the pooled cohort, there was no significant effect of dietary GL on any metabolic or anthropometric outcome ( p ≥ 0.2). A post hoc analysis comparing the study women to a cohort of overweight or obese pregnant women who received only routine care showed that the non-study women were more likely to gain excess weight ( p = 0.046) and to deliver large-for-gestational-age (LGA) ( p = 0.01) or macrosomic ( p = 0.006) infants. Thus, a low-GL diet consumed during the last half of pregnancy did not improve pregnancy outcomes in obese women, but in comparison to non-study women, dietary counseling reduced the risk of adverse outcomes.

Obesity represents a risk factor for metabolic syndrome and cardiovascular and psychiatric disorders. Excessive caloric intake, particularly in dietary fats, is an environmental factor that contributes to obesity development. Thus, the observation that switching from long-standing dietary obesity to standard diet (SD) can ameliorate the high-fat diet-induced metabolic, memory, and emotionality-related impairments are particularly important. Herein we investigated whether switching from the high-fat diet (HFD) to SD could improve the metabolic and behavioral impairments observed in middle-aged females C57Bl/6 mice. During twelve weeks, the animals received a high-fat diet (61 % fat) or SD diet. After 12-weeks, the HFD group's diet was switched to SD for an additional four weeks. It was observed a progressive deleterious effect of HFD in metabolic and behavioral parameters in mice. After four weeks of HFD-feeding, the animals showed glucose intolerance and increased locomotor activity. A subsequent increase in the body mass gain, hyperglycemia, and depressive-like behavior was observed after eight weeks, and memory impairments after twelve weeks. After replacing the HFD to SD, it was observed an improvement of metabolic (loss of body mass, normal plasma glucose levels, and glucose tolerance) and behavioral (absence of memory and emotional alterations) parameters. These results demonstrate the temporal development of metabolic and behavioral impairments following HFD in middle-age female mice and provide new evidence that these alterations can be improved by switching back the diet to SD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Over recent years, the link between obesity, metabolic syndrome and Hidradenitis suppurativa (HS) has been explored. It has been demonstrated that HS patients have a high prevalence of the metabolic syndrome and an increased frequency of insulin resistance. The objective of our study is to estimate the effectiveness of an oral supplementation based on myo-inositol (MI), folic acid and liposomal magnesium (Levigon ® , Sanitpharma; Milan, Italy) on the clinical and metabolic profile of patients affected by HS., Methods: Twenty subjects with HS and an impaired glucose metabolism were enrolled. Group A: 10 subjects received for 6 months MI 2000 mg, liposomal magnesium and folic acid associated to topical antibiotic therapy (clindamycin gel 1%), systemic antibiotic therapy (clindamycin 300 mg b.i.d. and rifampicin 600 mg daily for 6 weeks) and a normocaloric diet group B: 10 subjects received topical and systemic antibiotic therapy associated to a normocaloric diet for 6 months., Results: After 6 months group A patients showed an average reduction of Sartorius Score from 38.3±7.75 to 27.3±13.53 (P value <0.04) while in the control group there was a reduction of the Sartorius from 38.4±7.88 to 31.1±8.02 (P value =0.55). Moreover in group A Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly reduced from 2.43±0.35 to 2.1±0.31 (P<0.01) whereas in group B HOMA-IR did not significantly decrease (2.51±0.65 at T0 at 2.40±0.67 at T1)., Conclusions: Our study underlines the importance of the evaluation of metabolic profile in patients with HS. Moreover, it suggests that the supplementation of MI, folic acid and liposomal magnesium in HS can improve the efficacy of concomitant therapies and the metabolic profile.

The search for bioactive compounds from enzymatic hydrolysates has increased in the last few decades. Fish by-products have been shown to be rich in these valuable molecules; for instance, herring milt is a complex matrix composed of lipids, nucleotides, minerals, and proteins. However, limited information is available on the potential health benefits of this by-product. In this context, three industrial products containing herring milt hydrolysate (HMH) were tested in both animal and cellular models to measure their effects on obesity-related metabolic disorders. Male C57Bl/6J mice were fed either a control chow diet or a high-fat high-sucrose (HFHS) diet for 8 weeks and received either the vehicle (water) or one of the three HMH products (HMH1, HMH2, and HMH3) at a dose of 208.8 mg/kg (representing 1 g/day for a human) by daily oral gavage. The impact of HMH treatments on insulin and glucose tolerance, lipid homeostasis, liver gene expression, and the gut microbiota profile was studied. In parallel, the effects of HMH on glucose uptake and inflammation were studied in L6 myocytes and J774 macrophages, respectively. In vivo, daily treatment with HMH2 and HMH3 improved early time point glycemia during the oral glucose tolerance test (OGTT) induced by the HFHS diet, without changes in weight gain and insulin secretion. Interestingly, we also observed that HMH2 consumption partially prevented a lower abundance of Lactobacillus species in the gut microbiota of HFHS diet-fed animals. In addition to this, modulations of gene expression in the liver, such as the upregulation of sucrose nonfermenting AMPK-related kinase (SNARK), were reported for the first time in mice treated with HMH products. While HMH2 and HMH3 inhibited inducible nitric oxide synthase (iNOS) induction in J774 macrophages, glucose uptake was not modified in L6 muscle cells. These results indicate that milt herring hydrolysates reduce some metabolic and inflammatory alterations in cellular and animal models, suggesting a possible novel marine ingredient to help fight against obesity-related immunometabolic disorders.

Chronic isoleucine supplementation prevents diet-induced weight gain in rodents. Acute-isoleucine administration improves glucose tolerance in rodents and reduces postprandial glucose levels in humans. However, the effect of chronic-isoleucine supplementation on body weight and glucose tolerance in obesity is unknown. This study aimed to investigate the impact of chronic isoleucine on body weight gain and glucose tolerance in lean and high-fat-diet (HFD) induced-obese mice. Male C57BL/6-mice, fed a standard-laboratory-diet (SLD) or HFD for 12 weeks, were randomly allocated to: (1) Control: Drinking water; (2) Acute: Drinking water with a gavage of isoleucine (300 mg/kg) prior to the oral-glucose-tolerance-test (OGTT) or gastric-emptying-breath-test (GEBT); (3) Chronic: Drinking water with 1.5% isoleucine, for a further six weeks. At 16 weeks, an OGTT and GEBT was performed and at 17 weeks metabolic monitoring. In SLD- and HFD-mice, there was no difference in body weight, fat mass, and plasma lipid profiles between isoleucine treatment groups. Acute-isoleucine did not improve glucose tolerance in SLD- or HFD-mice. Chronic-isoleucine impaired glucose tolerance in SLD-mice. There was no difference in gastric emptying between any groups. Chronic-isoleucine did not alter energy intake, energy expenditure, or respiratory quotient in SLD- or HFD-mice. In conclusion, chronic isoleucine supplementation may not be an effective treatment for obesity or glucose intolerance.

Dietary Apigenin (AP), a natural flavonoid from plants, could alleviate high-fat diet (HFD) induced obesity and its complication. Nonetheless, the direct correlation between dietary AP and their effects in adipose tissues remained unclear. In this study, male C57BL/6 mice were fed with low-fat diet, HFD with or without 0.04% (w/w) AP for 12 weeks. Dietary AP ameliorated HFD induced body weight gain, glucose intolerance, and insulin resistance. Energy expenditure was increased with no influence on energy intake, which indicated us that AP prevented obesity by enhancing energy export. Interestingly, AP activated lipolysis (ATGL/FOXO1/SIRT1) without higher cycling free fatty acids (FFAs). FFAs were consumed by the upregulation of fatty acid oxidation (AMPK/ACC), thermogenesis, and browning (UCP-1, PGC-1α). Additionally, adipose tissue metabolic inflammation (NF-кB, MAPK) was also reduced by AP. Our study proposed that dietary AP could be explored as a new dietary strategy to combat obesity and related insulin resistance., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: High intake of cereal fibre is associated with reduced risk for type 2 diabetes and long-term complications. Within the first long-term randomized controlled trial specifically targeting cereal fibre, the Optimal Fibre Trial (OptiFiT), intake of insoluble oat fibre was shown to significantly reduce glycaemia. Previous studies suggested that this effect might be limited to subjects with impaired fasting glucose (IFG)., Aim: We stratified the OptiFiT cohort for normal and impaired fasting glucose (NFG, IFG) and conducted a secondary analysis comparing the effects of fibre supplementation between these subgroups., Methods: 180 Caucasian participants with impaired glucose tolerance (IGT) were randomized to twice-a-day fibre or placebo supplementation for 2 years ( n  = 89 and 91, respectively), while assuring double-blinded intervention. Fasting blood sampling, oral glucose tolerance test and full anthropometry were assessed annually. At baseline, out of 136 subjects completing the first year of intervention, 72 (54 %) showed IFG and IGT, while 64 subjects had IGT only (labelled "NFG"). Based on these two groups, we performed a stratified per-protocol analysis of glycometabolic and secondary effects during the first year of intervention., Results: The NFG group did not show significant differences between fibre and placebo group concerning anthropometric, glycometabolic, or other biochemical parameters. Within the IFG stratum, 2-h glucose, HbA1c, and gamma-glutamyl transferase levels decreased more in the fibre group, with a significant supplement x IFG interaction effect for HbA1c. Compared to NFG subjects, IFG subjects had larger benefits from fibre supplementation with respect to fasting glucose levels. Results were robust against adjustment for weight change and sex. An ITT analysis did not reveal any differences from the per-protocol analysis., Conclusions: Although stratification resulted in relatively small subgroups, we were able to pinpoint our previous findings from the entire cohort to the IFG subgroup. Cereal fibre can beneficially affect glycemic metabolism, with most pronounced or even isolated effectiveness in subjects with impaired fasting glucose., Competing Interests: S.K. and C.H. received a travel grant from Rettenmaier & Soehne, Holzmuehle, Germany, including conference fees and acccomodation. The authors declare no further conflicts of interest associated with this manuscript. The sponsors were neither involved in study design, data collection nor publication.

Skeletal muscle is the major site for glucose uptake and thus plays an important role in initiating insulin resistance in type 2 diabetes mellitus. This study evaluated the effects of tocotrienols (TT) and green tea polyphenols (GTP) individually or in combination on glucose homeostasis and skeletal muscle metabolism in obese mice with insulin resistance and elevation of blood glucose. Forty-eight male mice were fed a high-fat diet and assigned to 4 groups in a 2 (no TT vs. 400 mg TT/kg diet) × 2 (no GTP vs. 0.5% vol/wt GTP in water) for 14 weeks. Both GTP and TT improved area under curve of insulin intolerance; while GTP increased serum insulin levels in obese mice, probably due to the addition of sweetener in drinking water. An interaction (TT×GTP) was observed in glucose tolerance test, total pancreas insulin concentration, and citrate synthase activity of soleus in mice. Neither TT nor GTP affected insulin and glucagon protein expression in pancreas based on immunohistochemistry. Both TT and GTP individually increased soleus muscle weight of mice; while only GTP increased gastrocnemius muscle weight of mice. The TT+GTP group had the greatest gastrocnemius muscle cross sectional area than other groups. GTP, not TT, induced cytochrome c oxidase activity and reduced thiobarbituric acid reactive substances levels in soleus muscle. Our results suggest that TT and GTP, individually or synergistically have the potential to improve skeletal muscle metabolism in obese mice by improving glucose homeostasis, reducing lipid peroxidation, and increasing rate limiting enzymes of oxidative phosphorylation., (Copyright © 2019. Published by Elsevier Inc.)

Scope: The mechanisms and involvement of uncoupling protein 1 (UCP1) in the protection from obesity and insulin resistance induced by intake of a high-fat diet rich in omega-3 (n-3) fatty acids are investigated., Methods and Results: C57BL/6J mice are fed either a low-fat (control group) or one of two isocaloric high-fat diets containing either lard (HFD) or fish oil (HFN3) as fat source and evaluated for body weight, adiposity, energy expenditure, glucose homeostasis, and inguinal white and interscapular brown adipose tissue (iWAT and iBAT, respectively) gene expression, lipidome, and mitochondrial bioenergetics. HFN3 intake protected from obesity, glucose and insulin intolerances, and hyperinsulinemia. This is associated with increased energy expenditure, iWAT UCP1 expression, and incorporation of n-3 eicosapentaenoic and docosahexaenoic fatty acids in iWAT and iBAT triacylglycerol. Importantly, HFN3 is equally effective in reducing body weight gain, adiposity, and glucose intolerance and increasing energy expenditure in wild-type and UCP1-deficient mice without recruiting other thermogenic processes in iWAT and iBAT, such as mitochondrial uncoupling and SERCA-mediated calcium and creatine-driven substrate cyclings., Conclusion: Intake of a high-fat diet rich in omega-3 fatty acids protects both wild-type and UCP1-deficient mice from obesity and insulin resistance by increasing energy expenditure through unknown mechanisms., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

L-Leucine has been used to improve metabolic outcomes in glucose-intolerant rodent models. However, because studies have used different experimental models and conditions it is difficult to establish the best approach for new clinical trials evaluating the potential effects of L-leucine on glucose homeostasis. We performed a systematic review to report the effect of L-leucine supplementation on glucose homeostasis in rodents with glucose intolerance. The search engines MEDLINE and ScienceDirect were applied using MeSH terms. Thirty-four studies were included in this systematic review. Based on the current data, ingestion of 90-140 mg day -1 of isolated L-leucine in diet-induced obesity (DIO) models shows improvement in metabolic markers if offered during the development of the metabolic disorder in almost all the studies, but not after. Branched-chain amino acid supplementation was effective in streptozotocin-induced β-cells death but not in DIO models. L-Leucine supplementation seems to have an optimal dose and timing for supplementation to improve glucose homeostasis in DIO.

Foxtail millet has relatively low starch digestibility and moderate glycemic index compared to other grains. Since there are still no clinical researches regarding its long-term effect on blood glucose, this self-controlled study was conducted to investigate the glucose-lowering effect of foxtail millet in free-living subjects with impaired glucose tolerance (IGT). Fifty g/day of foxtail millet was provided to enrolled subjects throughout 12 weeks and the related clinical parameters were investigated at week 0, 6 and 12, respectively. After 12 weeks of foxtail millet intervention, the mean fasting blood glucose of the subjects decreased from 5.7 ± 0.9 mmol/L to 5.3 ± 0.7 mmol/L ( p < 0.001) and the mean 2 h-glucose decreased from 10.2 ± 2.6 mmol/L to 9.4 ± 2.3 mmol/L ( p = 0.003). The intake of foxtail millet caused a significant increase of serum leptin ( p = 0.012), decrease of insulin resistance ( p = 0.007), and marginal reduction of inflammation. Furthermore, a sex-dependent difference in glucose-lowering effect of foxtail millet was observed in this study. Foxtail millet could improve the glycemic control in free-living subjects with IGT, suggesting that increasing the consumption of foxtail millet might be beneficial to individuals suffering from type 2 diabetes mellitus.

Background: Dietary advice is a standard component of treatment for pregnant women with impaired glucose tolerance (IGT) and gestational diabetes (GDM), yet few studies report glycemic profiles in response to dietary therapies and the optimal dietary approach remains uncertain., Aim: To assess changes in maternal glycemic profile and pregnancy outcomes among women with diet-controlled IGT and GDM., Methods: Pregnant women who had one or more elevated values on a 3-h oral glucose tolerance test were enrolled. All participants received dietary advice and glucose monitoring as part of routine clinical care. Fasting and 1-h post-prandial blood samples, collected prior to initiation of clinical treatment and repeated 4-6 weeks later, were analyzed for glucose, insulin, and C-peptide. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Women who required pharmacological therapy for glucose control were excluded from analyses., Results: Participants (N = 93) were of moderately older age (mean 33 years), with a high rate of overweight/obesity (mean body mass index (BMI) = 28.65 kg/m 2 ), and were diagnosed late in gestation (mean 29 weeks). Fasting (mean ± SD 4.82 ± 0.53 to 4.60 ± 0.42 mmol/l; p < 0.001) and post-prandial glucose (7.01 ± 1.19 to 6.47 ± 1.10; p = 0.004) decreased significantly following the intervention. Baseline HOMA-IR was elevated (3.12 ± 1.03) but did not significantly decrease (2.78 ± 1.52; p = 0.066). There were high rates of macrosomia (24.7%) and cesarean delivery (32.3%)., Conclusions: Although improvements in blood glucose levels were observed among women with diet-controlled IGT and GDM, this was insufficient to significantly affect insulin resistance or perinatal outcome. Late diagnosis and treatment of IGT/GDM may have contributed to such outcomes.

Background/objectives: The study aimed to compare the effects of two eucaloric meal patterns (3 vs 6 meals/day) on glycaemic control and satiety in subjects with impaired glucose tolerance and plasma glucose (PG) levels 140-199mg/dL at 120min (IGT-A) or PG levels 140-199mg/dL at 120min and >200mg/dL at 30/60/90min post-oral glucose load on 75-g OGTT (IGT-B), or overt treatment-naïve type 2 diabetes (T2D)., Subjects/methods: In this randomized crossover study, subjects with IGT-A (n=15, BMI: 32.4±5.2kg/m 2 ), IGT-B (n=20, BMI: 32.5±5kg/m 2 ) or T2D (n=12, BMI: 32.2±5.2kg/m 2 ) followed a weight-maintenance diet (45% carbohydrates, 20% proteins, 35% fats) in 3 or 6 meals/day (each intervention lasting 12 weeks). Anthropometrics, diet compliance and subjective appetite were assessed every 2 weeks. OGTT and measurements of HbA1c and plasma lipids were performed at the beginning and end of each intervention period., Results: Body weight and physical activity levels remained stable throughout the study. In T2D, HbA1c and PG at 120min post-OGTT decreased with 6 vs 3 meals (P<0.001 vs P=0.02, respectively). The 6-meal intervention also improved post-OGTT hyperinsulinaemia in IGT-A subjects and hyperglycaemia in IGT-B subjects. In all three groups, subjective hunger and desire to eat were reduced with 6 vs 3 meals/day (P<0.05). There were no differences in HOMA-IR or plasma lipids between interventions., Conclusion: Although weight loss remains the key strategy in hyperglycaemia management, dietary measures such as more frequent and smaller meals may be helpful for those not sufficiently motivated to adhere to calorie-restricted diets. Our study shows that 6 vs 3 meals a day can increase glycaemic control in obese patients with early-stage T2D, and may perhaps improve and/or stabilize postprandial glucose regulation in prediabetes subjects., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

In this study, the level of gamma-aminobutyric acid (GABA) in wheat bran was increased to be six times higher through the action of endogenous glutamate decarboxylase compared with untreated bran. The process of GABA formation in wheat bran also led to an increased level of phenolic compounds with enhanced antioxidant capacity 2 times higher than the untreated status. The interventional effect of a diet containing GABA-enriched bran on hyperinsulinemia induced by a high-fat diet (HFD) was investigated in a rat model. The results showed that, when compared with animals fed with HFD-containing untreated bran (NB group), the consumption of HFD-containing GABA-enriched bran (GB group) demonstrated a greater improvement of insulin resistance/sensitivity as revealed by the changes in the homeostatic model assessment for insulin resistance index (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). The expression of hepatic genes, cytochrome P450 family 7 subfamily A member 1 (Cyp7a1) and ubiquitin C (Ubc), which are involved in the adipogenesis-associated PPAR signalling pathway, was found to be significantly down-regulated in the GB group compared with the HFD group (P = 0.0055). Meanwhile, changes in the expression of a number of genes associated with lipid metabolism and gluconeogenesis were also noted in the GB group versus the HFD group, but not in the NB group, indicating different regulatory patterns between the two brans in a high-fat diet. More importantly, the analysis of key genes related to glucose metabolism further revealed that the expression of insulin-induced gene 1/2 (Insig-1/2) was increased following GB intervention with a corresponding reduction in phosphoenolpyruvate carboxykinase 1 (Pepck) and glucose-6-phosphatase, catalytic subunit (G6pc) expression, suggesting that glucose homeostasis is greatly improved through the intervention of GABA-enriched bran in the context of a high-fat diet.

We hypothesized that along with exercise, casein peptide supplementation would have a higher impact on improving glucose tolerance than intact casein. Male 6-week-old ICR mice were provided a high-fat diet to induce obesity and glucose intolerance. The mice were randomly divided into 4 treatment groups: control (Con), endurance training (Tr), endurance training with intact casein supplementation (Cas+Tr), and endurance training with casein peptide supplementation (CP+Tr). The mice in each group were orally administrated water, intact casein, or casein peptide (1.0 mg/g body weight, every day), and then subjected to endurance training (15-25 m/min, 60 min, 5 times/week for 4 weeks) on a motor-driven treadmill 30 min after ingestion. Our results revealed that total intra-abdominal fat was significantly lower in CP+Tr than in Con (p < 0.05). Following an oral glucose tolerance test, the blood glucose area under the curve (AUC) was found to be significantly smaller for CP+Tr than for Con (p < 0.05). Moreover, in the soleus muscle, glucose transporter 4 (GLUT4) protein levels were significantly higher in CP+Tr than in Con (p < 0.01). However, intra-abdominal fat, blood glucose AUC, and GLUT4 protein content in the soleus muscle did not alter in Tr and Cas+Tr when compared with Con. These observations suggest that pre-exercise casein peptide supplementation has a higher effect on improving glucose tolerance than intact casein does in mice fed a high-fat diet.

Context: A diet low in cholesterol and fat is commonly recommended to prevent metabolic and cardiovascular diseases; however, its effect on glucose tolerance is largely unknown., Objective: We examined whether and by which mechanisms a chronic reduction of cholesterol and fat intake affects glucose tolerance in nondiabetic individuals, independently of weight changes., Design and Participants: In this crossover, randomized clinical trial, 30 healthy subjects, including 15 with family history of type 2 diabetes (T2D) (T2D offspring), underwent a 75-g oral glucose tolerance test (OGTT) after two 14-day isocaloric high-cholesterol, high-fat (HChF) or low-cholesterol, and low-fat (LChF) diets., Main Outcome Measures: We evaluated changes in glucose tolerance, β cell function, insulin clearance, and insulin sensitivity by modeling plasma glucose, insulin, and C-peptide levels during the OGTT., Results: The shift from the HChF to the LChF diet was neutral on body weight but increased glucose tolerance (mean glucose -5%, P = 0.01) and three components of β cell function: glucose sensitivity (+17%, P = 0.01), insulin secretion at fasting glucose (+20%, P = 0.02), and potentiation (+19%, P = 0.03). The LChF diet improved insulin sensitivity (+7%, P = 0.048) only in T2D offspring, who tended to be more susceptible to the positive effect of the diet on glucose tolerance., Conclusions: A chronic and isocaloric decrease in dietary cholesterol and fat intake improves glucose tolerance by diffusely ameliorating β cell function in nondiabetic subjects. Individuals genetically predisposed to develop T2D tend to be more susceptible to the positive effect of this dietary intervention on glucose tolerance and insulin sensitivity., (Copyright © 2017 Endocrine Society)

Obesity and diabetes mellitus type 2 (DM2) are characterized by chronic inflammation and oxidative stress [Donath et al. 2013] and this leads to cardiovascular diseases [Hulsmans & Holvoet 2010]. Whey proteins (WP) have antioxidant [Chitapanarux et al. 2009], anti-inflammatory [Sugawara et al. 2012] and hypoglycemic activities [Mignone et al. 2015], while data on weight, body composition [Frestedt et al. 2008; Aldrich et al. 2011] and blood pressure are conflicting [Kawase et al. 2000; Lee et al. 2007]. WP have unpleasant taste and smell [Patel 2015], but a new WP isolate (ProLYOtin®) seems to be more palatable. 40 g/die of ProLYOtin® were supplemented to overweight people (n=31) with impaired fasting glucose/DM2 for 12 weeks. Markers of antioxidant status (total antioxidant status, glutathione peroxidase, glutathione reductase, uric acid), oxidative damage (thiobarbituric acid reactive substances, advanced oxidation protein products, 8-hydroxydeoxyguanosine), inflammation (interleukin-6, high sensitive reactive protein C) and glicemic status (fasting glucose, insulin, glycated hemoglobin), anthropometric data (weight, height, waist circumference), body composition (body cell mass, fat mass), blood pressure, hand grip strength and skin autofluorescence were measured before and at the end of supplementation. Isolate palatability was evaluated. An increase in glutathione peroxidase, a decrease in uric acid and no change in glutathione reductase, total antioxidant status, oxidative damage, inflammation and glucose markers were found. Significant improvements in anthropometric parameters and fat mass were detected. There wasn't any change in blood pressure, skin autofluorescence and physical performance. Two-thirds of subjects judged the supplement positively. ProLYOtin® seems suitable for treatment of OS and overweight., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Several studies have demonstrated the beneficial impact of dried peas and their components on glucose tolerance; however, the role of gut microbiota as a potential mediator is not fully examined. In this study, we investigated the effect of dietary supplementation with raw and cooked pea seed coats (PSC) on glucose tolerance, microbial composition of the gut, select markers of intestinal barrier function, and short chain fatty acid profile in glucose intolerant rats. Male Sprague Dawley rats were fed high fat diet (HFD) for six weeks to induce glucose intolerance, followed by four weeks of feeding PSC-supplemented diets. Cooked PSC improved glucose tolerance by approximately 30% ( p < 0.05), and raw and cooked PSC diets reduced insulin response by 53% and 56% respectively ( p < 0.05 and p < 0.01), compared to HFD (containing cellulose as the source of dietary fiber). 16S rRNA gene sequencing on fecal samples showed a significant shift in the overall microbial composition of PSC groups when compared to HFD and low fat diet (LFD) controls. At the family level, PSC increased the abundance of Lachnospiraceae and Prevotellaceae ( p < 0.001), and decreased Porphyromonadaceae ( p < 0.01) compared with HFD. This was accompanied by increased mRNA expression of mucin genes Muc1, Muc2, and Muc4 in ileal epithelium ( p < 0.05). Serum levels of acetate and propionate increased with raw PSC diet ( p < 0.01). These results indicate that supplementation of HFD with PSC fractions can improve glycemia and may have a protective role against HFD-induced alterations in gut microbiota and mucus layer., Competing Interests: The authors declare no conflict of interest.

Diet-induced obesity, insulin resistance, impaired glucose tolerance, chronic inflammation, and oxidative stress represent the main features of type 2 diabetes mellitus. The present study was conducted to examine the efficacy and mechanisms of shrimp oil on glucose homeostasis in obese rats. Male CD rats fed a high-fat diet (52 kcal% fat) and 20% fructose drinking water were divided into 4 groups and treated with the dietary replacement of 0%, 10%, 15%, or 20% of lard with shrimp oil for 10 weeks. Age-matched rats fed a low-fat diet (10 kcal% fat) were used as the normal control. Rats on the high-fat diet showed impaired (p < 0.05) glucose tolerance and insulin resistance compared with rats fed the low-fat diet. Shrimp oil improved (p < 0.05) oral glucose tolerance, insulin response, and homeostatic model assessment-estimated insulin resistance index; decreased serum insulin, leptin, hemoglobin A1c, and free fatty acids; and increased adiponectin. Shrimp oil also increased (p < 0.05) antioxidant capacity and reduced oxidative stress and chronic inflammation. The results demonstrated that shrimp oil dose-dependently improved glycemic control in obese rats through multiple mechanisms.

Background: Obesity and related complications have now became epidemic both in developed and developing countries. Cafeteria type diet mainly composed of high fat high carbohydrate components which plays a significant role in the development of obesity and metabolic syndrome. This study investigated the effect of Syzygium cumini seed powder on fat accumulation and dyslipidemia in high carbohydrate high fat diet (HCHF) induced obese rats., Method: Male Wistar rats were fed with HCHF diet ad libitum, and the rats on HCHF diet were supplemented with Syzygium cumini seed powder for 56 days (2.5% w/w of diet). Oral glucose tolerance test, lipid parameters, liver marker enzymes (AST, ALT and ALP) and lipid peroxidation products were analyzed at the end of 56 days. Moreover, antioxidant enzyme activities were also measured in all groups of rats., Results: Supplementation with Syzygium cumini seed powder significantly reduced body weight gain, white adipose tissue (WAT) weights, blood glucose, serum insulin, and plasma lipids such as total cholesterol, triglyceride, LDL and HDL concentration. Syzygium cumini seed powder supplementation in HCHF rats improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and alkaline phosphatase (ALP) activities. Syzygium cumini seed powder supplementation also reduced the hepatic thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme superoxide dismutase (SOD) and catalase (CAT) activities as well as increased glutathione (GSH) concentration. In addition, histological assessment showed that Syzygium cumini seed powder supplementation prevented inflammatory cell infiltration; fatty droplet deposition and fibrosis in liver of HCHFD fed rats., Conclusion: Our investigation suggests that Syzygium cumini seed powder supplementation prevents oxidative stress and showed anti-inflammatory and antifibrotic activity in liver of HCHF diet fed rats. In addition, Syzygium cumini seed powder may be beneficial in ameliorating insulin resistance and dyslipidemia probably by increasing lipid metabolism in liver of HCHF diet fed rats.

Structured lifestyle interventions can reduce diabetes incidence and cardiovascular disease (CVD) risk among persons with impaired glucose tolerance (IGT), but it is unclear whether they should be implemented among persons without IGT. We conducted a systematic review and meta-analyses to assess the effectiveness of lifestyle interventions on CVD risk among adults without IGT or diabetes. We systematically searched MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Library, and PsychInfo databases, from inception to May 4, 2016. We selected randomized controlled trials of lifestyle interventions, involving physical activity (PA), dietary (D), or combined strategies (PA+D) with follow-up duration ≥12 months. We excluded all studies that included individuals with IGT, confirmed by 2-hours oral glucose tolerance test (75g), but included all other studies recruiting populations with different glycemic levels. We stratified studies by baseline glycemic levels: (1) low-range group with mean fasting plasma glucose (FPG) <5.5mmol/L or glycated hemoglobin (A1C) <5.5%, and (2) high-range group with FPG ≥5.5mmol/L or A1C ≥5.5%, and synthesized data using random-effects models. Primary outcomes in this review included systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Totally 79 studies met inclusion criteria. Compared to usual care (UC), lifestyle interventions achieved significant improvements in SBP (-2.16mmHg[95%CI, -2.93, -1.39]), DBP (-1.83mmHg[-2.34, -1.31]), TC (-0.10mmol/L[-0.15, -0.05]), LDL-C (-0.09mmol/L[-0.13, -0.04]), HDL-C (0.03mmol/L[0.01, 0.04]), and TG (-0.08mmol/L[-0.14, -0.03]). Similar effects were observed among both low-and high-range study groups except for TC and TG. Similar effects also appeared in SBP and DBP categories regardless of follow-up duration. PA+D interventions had larger improvement effects on CVD risk factors than PA alone interventions. In adults without IGT or diabetes, lifestyle interventions resulted in significant improvements in SBP, DBP, TC, LDL-C, HDL-C, and TG, and might further reduce CVD risk.

Many studies have investigated the effect of crude tomato peel in vivo, but no studies have determined the dose-effect of dry tomato peel (DTP) on glucose intolerance, insulin resistance, and atherogenic dyslipidemia induced by a high-saturated-fat (HSF) diet in vivo. The aim of this study was to investigate the effects of different doses of DTP on the levels of oxidative stress in mice fed an HSF and cholesterol-rich diet for 12 weeks. The main outcomes are glucose and insulin tolerance, plasma lipids, and hepatic steatosis and inflammation. BALB/c male mice (n=40) (8 weeks old, weighing 22.2±1.0 g) were divided into four treatment groups (10 mice/group): (a) high-fat control diet (HF Ctrl), which contains sunflower oil as a sole source of fat; (b) HSF/high-cholesterol (HC) diet; (c) HSF/HC diet supplemented with 9% DTP and (d) HSF/HC diet supplemented with 17% DTP. The HSF/HC diet significantly increased body weight gain, adipose tissue weight, fasting plasma glucose, fasting plasma insulin and lipid peroxidation and caused the development of liver steatosis and inflammation. Supplementation with DTP increased plasma lycopene concentration and reduced the development of indicators of metabolic syndrome, with no consistent effect of the DTP dose. Hepatic steatosis and inflammation were not reversed with DTP supplementation. Among mice fed the HSF/HC diet, DTP supplementation appears to have a beneficial effect on insulin resistance, which confirms the antiatherogenic effect of DTP., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Dietary advice is fundamental in the prevention and management of type 2 diabetes (T2DM). Advice is improved by individual assessment but existing methods are time-consuming and require expertise. We developed a twenty-five-item questionnaire, the UK Diabetes and Diet Questionnaire (UKDDQ), for quick assessment of an individual's diet. The present study examined the UKDDQ's repeatability and relative validity compared with 4 d food diaries., Design: The UKDDQ was completed twice with a median 3 d gap (interquartile range=1-7 d) between tests. A 4 d food diary was completed after the second UKDDQ. Diaries were analysed and food groups were mapped on to the UKDDQ. Absolute agreement between total scores was examined using intra-class correlation (ICC). Agreement for individual items was tested with Cohen's weighted kappa (κ w)., Setting: South West of England., Subjects: Adults (n 177, 50·3 % women) with, or at high risk for, T2DM; mean age 55·8 (sd 8·6) years, mean BMI 34·4 (sd 7·3) kg/m2; participants were 91 % White British., Results: The UKDDQ showed excellent repeatability (ICC=0·90 (0·82, 0·94)). For individual items, κ w ranged from 0·43 ('savoury pastries') to 0·87 ('vegetables'). Total scores from the UKDDQ and food diaries compared well (ICC=0·54 (0·27, 0·70)). Agreement for individual items varied and was good for 'alcohol' (κ w=0·71) and 'breakfast cereals' (κ w=0·70), with no agreement for 'vegetables' (κ w=0·08) or 'savoury pastries' (κ w=0·09)., Conclusions: The UKDDQ is a new British dietary questionnaire with excellent repeatability. Comparisons with food diaries found agreements similar to those for international dietary questionnaires currently in use. It targets foods and habits important in diabetes prevention and management.

Background: Cereal fermentations have shown significant potential in improvement and design of the nutritional quality and health effects of foods and ingredients. In the present study, the effect of supplementary Lactobacillus plantarum dy-1 fermented barley (LFB) on obesity in high-fat diet (HFD)-induced obese rats was investigated., Results: LFB treatment showed a lower rate of increase in body weight and percentage of body fat and a reversal of HFD-induced glucose intolerance, with ameliorated hyperinsulinemia, decreased levels of triglycerides and total cholesterol, and inhibited concentration of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. Moreover, LFB treatment also showed the strongest inhibition of nuclear factor (NF)-kB activation and exhibited the greatest effects in blocking the degradation of the inhibitor of NF-kB and inhibiting p38 and JNK1 phosphorylation compared with HFD and raw barley treatment., Conclusions: It was clear that Lactobacillus plantarum dy-1 fermentation significantly improves the anti-obesity properties of barley. The results establish the foundation for ameliorating diet-induced obesity of product with LFB as nutritional supplements. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Epidemiological studies suggest that a diet high in processed meat, with a high glycemic index is associated with an increased risk of type 2 diabetes. It is not clear if this is due to altered insulin sensitivity or an enhanced postprandial glucose. We aimed to compare the acute metabolic response of two different types of meals after ingestion of the matching diet for four weeks. The study was a randomized, crossover acute meal study. Volunteers consumed either a red meat/refined grain meal or a dairy/chicken/nuts/wholegrain meal after four weeks of the matching diet. After a three-week washout period and four weeks of the alternate diet, they consumed the matching meal. The diets differed with respect to both protein and carbohydrate sources. Blood samples were taken for 180 min for the measurement of glucose, insulin, C-peptide and triglyceride. Fifty-one participants (age: 35.1 ± 15.6 years; body mass index: 27.7 ± 6.9 kg/m², 17 with normal and 34 with impaired glucose tolerance) completed two meal tests. The area under the curve ( p < 0.001) and incremental area under the curve ( p = 0.001) for insulin was significantly higher after the red meat/refined grain diet than after the dairy/chicken/nuts/whole grain diet. There was an interaction between meal and glucose tolerance group ( p < 0.05) in the area under the curve (AUC) and the incremental area under the curve (iAUC) of glucose; the red meat/refined grain diet increased glucose relative to the dairy/chicken/nuts/whole grain diet only in the normal group (+2.5 mmol/L/3 h). The red meat/refined grain diet increased glucose and insulin responses compared with the dairy/chicken/nuts/whole grain diet. This meal pattern would increase pancreatic stress long term and may account for the increased risk of type 2 diabetes with this diet., Competing Interests: The authors declare no conflict of interest.

Dietary administration of cocoa flavanols may be an effective complementary strategy for alleviation or prevention of metabolic syndrome, particularly glucose intolerance. The complex flavanol composition of cocoa provides the ability to interact with a variety of molecules, thus allowing numerous opportunities to ameliorate metabolic diseases. These interactions likely occur primarily in the gastrointestinal tract, where native cocoa flavanol concentration is high. Flavanols may antagonize digestive enzymes and glucose transporters, causing a reduction in glucose excursion, which helps patients with metabolic disorders maintain glucose homeostasis. Unabsorbed flavanols, and ones that undergo enterohepatic recycling, will proceed to the colon where they can exert prebiotic effects on the gut microbiota. Interactions with the gut microbiota may improve gut barrier function, resulting in attenuated endotoxin absorption. Cocoa may also positively influence insulin signaling, possibly by relieving insulin-signaling pathways from oxidative stress and inflammation and/or via a heightened incretin response. The purpose of this review is to explore the mechanisms that underlie these outcomes, critically review the current body of literature related to those mechanisms, explore the implications of these mechanisms for therapeutic utility, and identify emerging or needed areas of research that could advance our understanding of the mechanisms of action and therapeutic potential of cocoa flavanols., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP., (© 2016 American Heart Association, Inc.)

This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals' access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity.

Objective: We evaluated whether patients with histologically verified nonalcoholic fatty liver disease (NAFLD) have an impaired incretin effect and hyperglucagonaemia., Methods: Four groups matched for age, sex and body mass index were studied: (i) 10 patients with normal glucose tolerance and NAFLD; (ii) 10 patients with type 2 diabetes and NAFLD; (iii) eight patients with type 2 diabetes and no liver disease; and (iv) 10 controls. All participants underwent a 50-g oral glucose tolerance test (OGTT) and an isoglycaemic intravenous glucose infusion (IIGI). We determined the incretin effect by relating the beta cell secretory responses during the OGTT and IIGI. Data are presented as medians (interquartile range), and the groups were compared by using the Kruskal-Wallis test., Results: Controls exhibited a higher incretin effect [55% (43-73%)] compared with the remaining three groups (P < 0.001): 39% (44-71%) in the nondiabetic NAFLD patients, 20% (-5-50%) in NAFLD patients with type 2 diabetes, and 2% (-8-6%) in patients with type 2 diabetes and no liver disease. We found fasting hyperglucagonaemia in NAFLD patients with [7.5 pmol L(-1) (6.8-15 pmol L(-1))] and without diabetes [7.5 pmol L(-1) (5.0-8.0 pmol L(-1))]. Fasting glucagon levels were lower but similar in patients with type 2 diabetes and no liver disease [4.5 pmol L(-1) (3.0-6.0 pmol L(-1))] and controls [3.4 pmol L(-1) (1.8-6.0 pmol L(-1) )]. All groups had similar glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide responses., Conclusions: Patients with NAFLD have a reduced incretin effect and fasting hyperglucagonaemia, with the latter occurring independently of glucose (in)tolerance., (© 2016 The Association for the Publication of the Journal of Internal Medicine.)

Aim: to evaluate if a supplementation with n-3 PUFAs at high doses could give a regression of the condition of impaired glycemia., Methods: we enrolled 281 overweight/obese patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT); 138 subjects were randomized to n-3 PUFAs group, 1 g three times a day, and 143 to placebo for 18 months. We assessed at baseline, and after 9, and 18 months: circumferences, body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), HOMA-index, lipid profile. At baseline and at the end of the study, all patients underwent an oral glucose tolerance test (OGTT)., Results: we observed a decrease of glycemia and HOMA-IR with n-3 PUFAs, compared to baseline, and to placebo. Fasting plasma insulin decreased with n-3 PUFAs and increased with placebo. HDL-cholesterol increased after 18 months of n-3 PUFAs, while triglycerides decreased compared to baseline and to placebo. After OGTT performed at the end of the study, more patients returned to a condition of euglycemia with n-3 PUFAs compared to placebo., Conclusions: n-3 PUFAs were effective in reducing glycemia in patients affected by IFG or IGT and seem to be helpful to slow the development of type 2 diabetes mellitus. © 2016 BioFactors, 42(3):316-322, 2016., (© 2016 International Union of Biochemistry and Molecular Biology.)

The ketogenic diet (KD) has been widely used in weight and glycemic control, although potential side effects of long-term KD treatment have caused persistent concern. In this study, we hypothesized that the KD would ameliorate the progression of diabetes but lead to disruptions in lipid metabolism and hepatic steatosis in a mouse model of diabetes. In type 2 diabetic mouse model, mice were fed a high-fat diet and administered streptozotocin treatment before given the test diets for 8 weeks. Subsequently, ameliorated glucose and insulin tolerance in KD-fed diabetic mice was found, although the body weight of high-fat diet- and KD-fed mice was similar. Interestingly, the weight of adipose tissue in KD mice was greater than in the other groups. The KD diet resulted in higher serum triacylglycerol and cholesterol levels in diabetic mice. Moreover, the KD-fed mice showed greater hepatic lipid accumulation. Mice fed the KD showed significant changes in several key genes such as sterol regulatory element-binding protein, fibroblast growth factor 21, and peroxisome proliferator-activated receptor α, which are all important in metabolism. In summary, KD ameliorates glucose and insulin tolerance in a mouse model of diabetes, but severe hepatic lipid accumulation and hepatic steatosis were observed, which should be considered carefully in the long-term application of KD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To investigate the influence of medical nutrition therapy (MNT) on borderline glucose intolerance (BGI) in pregnant Taiwanese women., Methods: A total of 5194 singleton pregnant women were enrolled in this prospective, non-randomized study. The participants were subjected to the 50 g 1-h glucose challenge test (GCT) and 100 g 3-h oral glucose tolerance test (OGTT) to screening gestational diabetes mellitus (GDM). BGI was defined as a positive GCT and normal OGTT results. GDM was defined as a positive GCT and abnormal OGTT results. The women were categorized into the following groups: (1) GCT-negative, n = 3881; (2) BGI with MNT, n = 273; (3) BGI without MNT, n = 712; and (4) GDM, n = 328. Multiple logistic analyses were used to estimate the risks of pregnancy outcomes., Results: The odds ratios (95% confidence interval) for total cesareans, third- or fourth-degree perineal lacerations, gestational hypertension or preeclampsia and macrosomia were 1.24 (1.04-1.49), 1.55 (1.06-1.28), 1.78 (1.21-2.61) and 2.50 (1.28-4.91) in the BGI without MNT group compared to the GCT-negative group. There was no difference between BGI with MNT and GCT-negative groups., Conclusions: Women with BGI who did not receive MNT had increased risks of adverse pregnancy outcomes, whereas who received MNT had no different risk with GCT-negative women.

Background: Transmission of obesity across generations is of concern. Offspring of obese women have short- and long-term increased morbidities. A high intake of carbohydrate during pregnancy combined with impaired glucose tolerance is postulated to result in high birth weight, which is linked to subsequent metabolic disease., Objective: The objective was to examine the association between carbohydrate intake in obese pregnant women and their offspring's body composition., Design: Secondary analyses were performed in an observational setting of 222 pregnant women with a pregestational BMI (in kg/m(2)) ≥30 participating in a randomized controlled trial. Diet was assessed at gestational weeks 11-14 and 36-37 by using a semiquantitative food-frequency questionnaire. Body composition in the offspring was assessed at birth by dual-energy X-ray absorptiometry. Relative fat mass (%) was the primary outcome. Absolute measures (total fat, abdominal fat, and lean body mass) were secondary outcomes., Results: Mean ± SD weight and absolute and relative fat mass in the offspring at birth were 3769 ± 542 g, 436 ± 214 g, and 11% ± 4%, respectively. Maternal intake of digestible carbohydrates was associated with the offspring's relative fat mass in late (P-trend = 0.006) but not early (P-trend = 0.15) pregnancy. A comparison of mothers in the highest (median: 238 g/d) compared with the lowest (median: 188 g/d) quartile of digestible carbohydrate intake showed a mean adjusted higher value in the offspring's relative fat mass of 2.1% (95% CI: 0.6%, 3.7%), which corresponded in absolute terms to a 103-g (95% CI: 27, 179-g) higher fat mass. Abdominal fat mass was also higher. In a strata of women with well-controlled glucose (2-h glucose values ≤6.6 mmol/L), no association between carbohydrate intake and offspring fat mass was observed, but the associations became significant and increased in strength with higher intolerance (strata with 2-h glucose values between 6.7-7.7 and ≥7.8 mmol/L)., Conclusion: In obese women, even those without gestational diabetes but with impaired glucose tolerance, a lower carbohydrate intake at moderate levels in late gestation is associated with a lower fat mass in their offspring at birth. The TOP study was registered at clinicaltrials.gov as NCT01345149., (© 2015 American Society for Nutrition.)

Background: Alterations in intestinal microbiota correlate with risk of development of obesity and type 2 diabetes. Probiotics have been suggested to play an important role in the management of dysglycemia, although the evidence is limited. In this study, we aim to explore the efficacy and safety of probiotics intervention in preventing type 2 diabetes in Chinese patients with impaired glucose tolerance., Methods/design: A 24-month randomized intervention is conducted from January 2014 to December 2016. The target sample size for intervention is 200 middle-aged men and women aged 30-65 year-old with impaired glucose tolerance. Participants with persistent impaired glucose tolerance were assigned to group A (tablet A) and B (tablet B) in sequential order. The participants and investigators were blinded to the assignment. The primary outcome is development of diabetes. The secondary outcome measures include body composition, biochemical variables and the safety of the probiotics., Discussion: The results from this trial will provide the evidence on the efficacy and safety of probiotics administration in preventing conversion of impaired glucose tolerance to diabetes in a Chinese context., Trial Registration: ChiCTRTRC13004024.

Aim: To examine changes in glucose metabolism (fasting and 2-h glucose) during follow-up in people with impaired fasting glucose in comparison with changes in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes at baseline, among those who participated in a diabetes prevention programme conducted in Finland., Methods: A total of 10 149 people at high risk of Type 2 diabetes took part in baseline examination. Of 5351 individuals with follow-up ≥ 9 months, 1727 had impaired glucose metabolism at baseline and completed at least one lifestyle intervention visit. Most of them (94.6%) were overweight/ obese., Results: Fasting glucose decreased during follow-up among overweight/obese people in the combined impaired fasting glucose and impaired glucose tolerance group (P = 0.044), as did 2-h glucose in people in the isolated impaired glucose tolerance group (P = 0.0014) after adjustment for age, sex, medication and weight at baseline, follow-up time and changes in weight, physical activity and diet. When comparing changes in glucose metabolism among people with different degrees of glucose metabolism impairment, fasting glucose concentration was found to have increased in those with isolated impaired glucose tolerance (0.12 mmol/l, 95% Cl 0.05 to 0.19) and it decreased to a greater extent in those with screening-detected Type 2 diabetes (-0.54 mmol/l, 95% Cl -0.69 to -0.39) compared with those with impaired fasting glucose (-0.21 mmol/l, 95% Cl -0.27 to -0.15). Furthermore, 2-h glucose concentration decreased in the isolated impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.04 to -0.60), in the combined impaired fasting glucose and impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.07 to -0.58) and in the screening-detected Type 2 diabetes group (-1.52, 95% Cl -1.96 to -1.08) compared with those in the impaired fasting glucose group (0.26 mmol/l, 95% Cl 0.10 to 0.43). Results were statistically significant even after adjustment for covariates (P < 0.001 in all models)., Conclusions: Changes in glucose metabolism differ in people with impaired fasting glucose from those in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Subjects with impaired glucose tolerance (IGT) have increased myocardial partitioning of dietary fatty acids (DFAs) with left ventricular dysfunction, both of which are improved by modest weight loss over 1 year induced by lifestyle changes. Here, we determined the effects of a 7-day hypocaloric diet (-500 kcal/day) low in saturated fat (<7% of energy) (LOWCAL study) versus isocaloric with the usual amount saturated fat (∼10% of energy) diet (ISOCAL) on DFA metabolism in subjects with IGT. Organ-specific DFA partitioning and cardiac and hepatic DFA fractional uptake rates were measured in 15 IGT subjects (7 males/8 females) using the oral 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid positron emission tomography method after 7 days of an ISOCAL diet versus a LOWCAL diet using a randomized crossover design. The LOWCAL diet led to reductions in weight and postprandial insulin area under the curve. Myocardial DFA partitioning over 6 h was increased after the LOWCAL diet (2.3 ± 0.1 vs. 1.9 ± 0.2 mean standard uptake value, P < 0.04). However, the early (90-120 min) myocardial DFA fractional uptake was unchanged after the LOWCAL diet (0.055 ± 0.025 vs. 0.046 ± 0.009 min(-1), P = 0.7). Liver DFA partitioning was unchanged, but liver fractional uptake of DFA tended to be increased. Very short-term caloric and saturated fat dietary restrictions do not lead to the same changes in organ-specific DFA metabolism as those associated with weight loss in subjects with IGT., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated postmenopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, the effects of BB supplementation on obese postmenopausal mice using a chemically induced menopause model were examined., Methods: After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed., Results: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation., Conclusions: BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and these effects are independent of body weight., (© 2015 The Obesity Society.)

Aims: Among women with gestational diabetes mellitus (GDM), the aggravation of glucose intolerance during gestation differs substantially. We retrospectively investigated whether the glucose intolerance of women diagnosed with GDM during early gestation (i.e., early-onset GDM) improved in the mid-gestation under appropriate nutrition therapy., Methods: We conducted a longitudinal analysis of glucose tolerance derived from 75-g oral glucose tolerance test (OGTT) in 41 Japanese women with early-onset GDM defined by International Association of Diabetes and Pregnancy Study Group criteria during early gestation (<20 weeks). Glucose tolerance was also evaluated in mid-gestation (24-32 weeks) and postpartum. Insulin sensitivity, insulin secretion, and β-cell function were assessed at each period., Results: The glucose tolerance in 18 of the 41 early-onset GDM patients normalized during mid-gestation with appropriate nutrition therapy, defined as GDM→NGT. These women did not require insulin therapy during their pregnancies, whereas 39.1% of women who retained GDM in mid-gestation (defined as GDM→GDM) required insulin therapy. The frequency of the postpartum development of type 2 diabetes or impaired glucose tolerance was significantly lower (5.6% vs. 39.1% in GDM→NGT vs. GDM→GDM, p=0.03). Primiparity was determined as a predictive factor whether or not glucose intolerance was improved by nutrition therapy, but results of plasma glucose levels from OGTT at early gestation were not, in a multivariate logistic regression analysis., Conclusions: Appropriate nutrition therapy for women with early-onset GDM seemed effective to improve glucose tolerance during pregnancy. OGTT retesting during their mid-gestation seemed effective for predicting the appropriate treatment after the second trimester., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: The pandemic of obesity in Western countries is mainly due to the high-fat, high-energy diet prevailing there. Obesity-associated metabolic disorders are the consequence of fat mass increase leading to altered adipokine secretion, hyperlipemia, oxidant stress, low-grade inflammation, and eventually glucose intolerance. Yet not all people consuming a Western diet become obese, and the question is raised whether these people are also at risk of developing metabolic disorders., Methods: Glucose tolerance, lipid profile, and oxidant and inflammation status were investigated longitudinally in lean Göttingen minipigs receiving for 16 weeks either a normal diet (ND), a Western diet (WD), or a Western diet supplemented with a whey protein isolate (WPI) rich in α-lactalbumin known to improve glucose tolerance. ND and WD were supplied isoenergetically., Results: Lean minipigs fed WD displayed glucose intolerance and altered lipid profile after 6 weeks of diet but no inflammation or oxidative stress. Supplementation with WPI alleviated glucose intolerance by improving insulin secretion, but not lipid profile., Conclusions: Western diet consumption is deleterious for glucose tolerance even in the absence of fat mass accretion, and dyslipemia is a major determinant for this metabolic dysfunction. Stimulating insulin secretion with a WPI is an effective strategy to improve glucose tolerance., (© 2014 The Obesity Society.)

Recent evidence suggests that immune cells play an important role in differentiation of inflammatory macrophages in adipose tissue, which contributes to systemic chronic inflammation. Dietary ribonucleic acid (RNA) has been shown to modulate immune function. We hypothesized that RNA affects immune cell function in adipose tissue and then improves inflammatory response in adipose tissue. C57/BL6 mice and recombination activating gene-1 (RAG-1) knockout mice on a C57BL/6 mice background were fed a high-fat diet containing 1% RNA for 12 wk. An oral glucose tolerance test was performed. Supplementation of dietary RNA in C57BL/6 mice fed a high-fat diet resulted in a smaller area under the curve (AUC) after oral glucose administration than that for control mice. The mRNA expression levels of inflammation-related cytokines in adipose tissue and serum interleukin-6 levels were reduced by dietary RNA supplementation. Interestingly, reduction of the AUC value by RNA supplementation was abolished in T and B cell-deficient RAG-1 knockout mice. These results indicate that RNA improves inflammation in adipose tissue and reduces the AUC value following oral glucose administration in a T and B cell-dependent manner.