Effect of blood flow restriction and electrical muscle stimulation on human glycemic response to a glucose challenge.

PURPOSE: To determine whether reduced tissue oxygen availability through blood flow restriction (BFR) alone, or in combination with electrically induced muscle contractions, can improve glucose clearance after an acute glucose challenge. METHODS: In a randomized crossover design, 21 young participants (females: 12) were allocated to perform 1) electrical muscle stimulation (EMS), 2) BFR, 3) EMS + BFR or 4) no treatment (control). Participants completed each condition immediately preceding a 2 h oral glucose tolerance test (100 g). Primary analyses were performed on the glucose area under the curve (AUC) at time points 0-30, 30-120, and 0-120 min. Secondary analyses were performed on glycemic responses based on biological sex and estimated muscle phenotype. RESULTS: Compared to the control (322±25 mM∙min), the 0-30 min AUC was reduced following EMS (293±22 mM∙min, p = 0.0004), and EMS + BFR (298±36 mM∙min., p = 0.006), whereas BFR in isolation did not differ (306±30 mM∙min, p = 0.1). The 30-120 and 0-120 min glucose AUCs were similar across conditions. Based on effect size from the control conditions, our secondary analysis suggests different 0-30 min glycemic responses after EMS + BFR between females (dz = 0.206) vs. males (dz = 1.461) and/or slow (dz = 0.426) vs. fast (dz = 1.075) muscle phenotype. CONCLUSION: Reducing tissue oxygen availability with BFR did not augment the effects of EMS in the overall group; however, we provide preliminary data to suggest possible sex and/or muscle phenotypic responses in glycemic regulation with these modalities.

Food-derived dipeptidyl peptidase IV inhibitory peptides: Production, identification, structure-activity relationship, and their potential role in glycemic regulation.

Dipeptidyl Peptidase IV (DPP-IV) inhibitory peptides are attracting increasing attention, owing to their potential role in glycemic regulation by preventing the inactivation of incretins. However, few reviews have summarized the current understanding of DPP-IV inhibitory peptides and their knowledge gaps. This paper reviews the production, identification and structure-activity relationships (SAR) of DPP-IV inhibitory peptides. Importantly, their bioavailability and hypoglycemic effects are critically discussed. Unlike the traditional method to identifying peptides after separation step by step, the bioinformatics approach identifies peptides via virtual screening that is more convenient and efficient. In addition, the bioinformatics approach was also used to investigate the SAR of peptides. Peptides with proline (Pro) or alanine (Ala) residue at the second position of N-terminal are exhibit strong DPP-IV inhibitory activity. Besides, the bioavailability of DPP-IV inhibitory peptides is related to their gastrointestinal stability and cellular permeability, and in vivo studies showed that the glucose homeostasis has been improved by these peptides. Especially, the intestinal transport of DPP-IV inhibitory peptides and cell biological assays used to evaluate their potential role in glycemic regulation are innovatively summarized. For further successful development of DPP-IV inhibitory peptides in glycemic regulation, future study should elucidate their SAR and in vivo hypoglycemic effects .

A comprehensive metabolic profiling of the metabolically healthy obesity phenotype.

BACKGROUND: The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as "metabolically healthy obese" (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity. METHODS: In this cross-sectional study, men and women (18-70 years) with obesity (body mass index (BMI) ≥ 30 kg/m2) or normal weight (NW) (BMI ≤ 25 kg/m2) were classified with MHO (n = 9), MUO (n = 10) or NW (n = 11) according to weight, lipid profile and glycemic regulation. We characterized individuals by comprehensive metabolic profiling using a commercial available high-throughput proton NMR metabolomics platform. Plasma fatty acid profile, including short chain fatty acids, was measured using gas chromatography. RESULTS: The concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) subclasses were overall significantly higher, and high density lipoprotein (HDL) subclasses lower in MUO compared with MHO. VLDL and IDL subclasses were significantly lower and HDL subclasses were higher in NW compared with MHO. The concentration of isoleucine, leucine and valine was significantly higher in MUO compared with MHO, and the concentration phenylalanine was lower in NW subjects compared with MHO. The fatty acid profile in MHO was overall more favorable compared with MUO. CONCLUSIONS: Comprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects. CLINICAL TRIAL REGISTRATION NUMBER: NCT01034436, Fatty acid quality and overweight (FO-study).

A Hemoglobin Bionics-Based System for Combating Antibiotic Resistance in Chronic Diabetic Wounds via Iron Homeostasis Regulation.

Owing to the increased tissue iron accumulation in patients with diabetes, microorganisms may activate high expression of iron-involved metabolic pathways, leading to the exacerbation of bacterial infections and disruption of systemic glucose metabolism. Therefore, an on-demand transdermal dosing approach that utilizes iron homeostasis regulation to combat antimicrobial resistance is a promising strategy to address the challenges associated with low administration bioavailability and high antibiotic resistance in treating infected diabetic wounds. Here, it is aimed to propose an effective therapy based on hemoglobin bionics to induce disturbances in bacterial iron homeostasis. The preferred "iron cargo" is synthesized by protoporphyrin IX chelated with dopamine and gallium (PDGa), and is delivered via a glucose/pH-responsive microneedle bandage (PDGa@GMB). The PDGa@GMB downregulates the expression levels of the iron uptake regulator (Fur) and the peroxide response regulator (perR) in Staphylococcus aureus, leading to iron nutrient starvation and oxidative stress, ultimately suppressing iron-dependent bacterial activities. Consequently, PDGa@GMB demonstrates insusceptibility to genetic resistance while maintaining sustainable antimicrobial effects (>90%) against resistant strains of both S. aureus and E. coli, and accelerates tissue recovery (<20 d). Overall, PDGa@GMB not only counteracts antibiotic resistance but also holds tremendous potential in mediating microbial-host crosstalk, synergistically attenuating pathogen virulence and pathogenicity.

Effects of Wheat Biscuits Enriched with Plant Proteins Incorporated into an Energy-Restricted Dietary Plan on Postprandial Metabolic Responses of Women with Overweight/Obesity.

This study investigates the effect of daily consumption of wheat biscuits enriched with plant proteins in postprandial metabolic responses of women with overweight/obesity who follow an energy-restricted diet. Thirty apparently healthy women participated in a 12-week randomized controlled trial and were assigned either to a control (CB) or an intervention (PB) group. Participants consumed daily either a conventional (CB) or an isocaloric wheat biscuit enriched with plant proteins (PB) containing high amounts of amino acids with appetite-regulating properties, i.e., BCAAs and L-arg. At baseline and the end of the intervention, a mixed meal tolerance test was performed. The responses of glucose, insulin, ghrelin, GLP-1, and glicentin were evaluated over 180 min. After 12 weeks, both groups experienced significant decreases in body weight, fat mass, and waist circumference. In the PB group, a trend towards higher weight loss was observed, accompanied by lower carbohydrate, fat, and energy intakes (p < 0.05 compared to baseline and CB group), while decreases in fasting insulin and the HOMA-IR index were also observed (p < 0.05 compared to baseline). In both groups, similar postprandial glucose, ghrelin, and GLP-1 responses were detected, while iAUC for insulin was lower (p < 0.05). Interestingly, the iAUC of glicentin was greater in the PB group (p < 0.05 compared to baseline). Subjective appetite ratings were beneficially affected in both groups (p < 0.05). Consumption of wheat biscuits enriched in plant proteins contributed to greater weight loss, lower energy intake, and insulin resistance and had a positive impact on postprandial glicentin response, a peptide that can potentially predict long-term weight loss and decreased food intake.

Oat Polar Lipids Improve Cardiometabolic-Related Markers after Breakfast and a Subsequent Standardized Lunch: A Randomized Crossover Study in Healthy Young Adults.

It has been suggested that intake of polar lipids may beneficially modulate various metabolic variables. The purpose of this study was to evaluate the effect of oat polar lipids on postprandial and second meal glycemic regulation, blood lipids, gastrointestinal hormones, and subjective appetite-related variables in healthy humans. In a randomized design, twenty healthy subjects ingested four liquid cereal-based test beverages (42 g of available carbohydrates) containing: i. 30 g of oat oil with a low concentration (4%) of polar lipids (PLL), ii. 30 g of oat oil containing a high concentration (40%) of polar lipids (PLH), iii. 30 g of rapeseed oil (RSO), and iv. no added lipids (NL). The products were served as breakfast meals followed by a standardized lunch. Test variables were measured at fasting and during 3 h after breakfast and two additional hours following a standardized lunch. PLH reduced glucose and insulin responses after breakfast (0-120 min) compared to RSO, and after lunch (210-330 min) compared to RSO and PLL (p < 0.05). Compared to RSO, PLH resulted in increased concentrations of the gut hormones GLP-1 and PYY after the standardized lunch (p < 0.05). The results suggest that oat polar lipids have potential nutraceutical properties by modulating acute and second meal postprandial metabolic responses.

Associations of sleep duration, sedentary behaviours and energy expenditure with maternal glycemia in pregnancy.

BACKGROUND: Women with high levels of physical activity (PA) are less likely to develop gestational diabetes mellitus (GDM), but the relations with sleep and sedentary behaviours (SB) are more controversial. We aimed to investigate all three components (sleep, PA, and SB) and their association with maternal glucose in pregnancy. METHODS: We included 766 pregnant women recruited at first trimester and that we followed at second trimester. We collected blood samples, anthropometry and standardized questionnaires about lifestyle including PA, SB, and sleep duration at both visits. Women completed a 50 g glucose challenge test at first trimester and 75-g oral glucose tolerance test (OGTT) at second trimester. We conducted regression analyses to test cross-sectional associations between sleep, PA, and SB with maternal glucose levels while taking into account potential confounders (maternal age, pre-pregnancy body mass index (BMI), gravidity, and smoking). We considered linear and quadratic relationships. RESULTS: At first trimester, we observed a linear relationship between shorter sleep duration and higher glucose levels, which was attenuated after adjustments for confounders. At second trimester, we found a quadratic relationship between sleep and glucose showing lowest levels at fasting and 1 h-post OGTT for women who slept 6-10 h/night. This association remained significant after adjusting for confounders and taking into account PA and/or SB. Greater amount of SB was associated with higher 1 h-glucose after adjustment for confounders (ß = 0.132; SE = 0.047; P = 0.005). CONCLUSIONS: Sleep duration is associated with glucose regulation in pregnancy, independently of PA and SB, and this association varies according to the period of gestation.

Dietary Fiber, Gut Microbiota, and Metabolic Regulation-Current Status in Human Randomized Trials.

New knowledge about the gut microbiota and its interaction with the host's metabolic regulation has emerged during the last few decades. Several factors may affect the composition of the gut microbiota, including dietary fiber. Dietary fiber is not hydrolyzed by human digestive enzymes, but it is acted upon by gut microbes, and metabolites like short-chain fatty acids are produced. The short-chain fatty acids may be absorbed into the circulation and affect metabolic regulation in the host or be a substrate for other microbes. Some studies have shown improved insulin sensitivity, weight regulation, and reduced inflammation with increases in gut-derived short-chain fatty acids, all of which may reduce the risk of developing metabolic diseases. To what extent a dietary intervention with fiber may affect the human gut microbiota and hence metabolic regulation, is however, currently not well described. The aim of the present review is to summarize recent research on human randomized, controlled intervention studies investigating the effect of dietary fiber on gut microbiota and metabolic regulation. Metabolic regulation is discussed with respect to markers relating to glycemic regulation and lipid metabolism. Taken together, the papers on which the current review is based, suggest that dietary fiber has the potential to change the gut microbiota and alter metabolic regulation. However, due to the heterogeneity of the studies, a firm conclusion describing the causal relationship between gut microbiota and metabolic regulation remains elusive.

FGF21 and glycemic control in patients with T1D.

PURPOSE: Fibroblast growth factor (FGF) 21 is a circulating hormone with an important role in metabolic regulation. FGF21 production in humans responds positively to glucose consumption and we hypothesize that serum FGF21 concentration is associated to glycemic control. METHODS: We enrolled 31 patients with type 1 diabetes (T1D) based on their HbA1c (well-regulated (HbA1c <53 mmol/mol), (n = 18) or poorly-regulated (HbA1c >69 mmol/mol), (n = 13). Twelve patients (39%) were diagnosed with retinopathy. Twenty healthy individuals comparable for age and gender distribution were included as a reference group. Serum FGF21, intact FGF21, fibroblast activation protein (FAP), adiponectin, and C-Reactive Protein (CRP) were measured by immunoassays. RESULTS: No correlation between FGF21 concentration and HbA1c was found. Patients with T1D had lower levels of circulating FGF21 as compared with the reference group, but the difference was nonsignificant (p = 0.12). Dividing the patients according to retinopathy, we found that T1D patients with retinopathy had significantly lower FGF21 concentrations (10.0 ng/L) as compared with the healthy reference group (37.1 ng/L), (p = 0.02). We found significantly higher levels of the FGF21 cleaving enzyme, FAP, in patients with T1D (97.2 µg/L) as compared with the healthy control group (78.5 µg/L), (p = 0.006). Interestingly, serum FAP levels correlated significantly with circulating FGF21 levels in T1D patients, but this correlation was not found in the healthy controls. CONCLUSIONS: We found no association between circulating FGF21 levels and HbA1c. T1D patients with retinopathy had significantly lower FGF21 levels as compared with healthy individuals, but it remains unclear if the lower levels of FGF21 are pathogenically related to the development of microvascular complications. Of note, serum FAP levels were significantly higher in all T1D patients as compared with the healthy individuals.

Saliva Proteomics Analysis Offers Insights on Type 1 Diabetes Pathology in a Pediatric Population.

The composition of the salivary proteome is affected by pathological conditions. We analyzed by high resolution mass spectrometry approaches saliva samples collected from children and adolescents with type 1 diabetes and healthy controls. The list of more than 2000 high confidence protein identifications constitutes a comprehensive characterization of the salivary proteome. Patients with good glycemic regulation and healthy individuals have comparable proteomic profiles. In contrast, a significant number of differentially expressed proteins were identified in the saliva of patients with poor glycemic regulation compared to patients with good glycemic control and healthy children. These proteins are involved in biological processes relevant to diabetic pathology such as endothelial damage and inflammation. Moreover, a putative preventive therapeutic approach was identified based on bioinformatic analysis of the deregulated salivary proteins. Thus, thorough characterization of saliva proteins in diabetic pediatric patients established a connection between molecular changes and disease pathology. This proteomic and bioinformatic approach highlights the potential of salivary diagnostics in diabetes pathology and opens the way for preventive treatment of the disease.

Laparoscopic Ileal Interposition with Diverted Sleeve Gastrectomy Versus Laparoscopic Transit Bipartition with Sleeve Gastrectomy for Better Glycemic Outcomes in T2DM Patients.

BACKGROUND: Metabolic procedures provide better outcomes for obese patients with type 2 diabetes mellitus. Our aim was to compare the glycemic regulation in patients that have undergone the laparoscopic ileal interposition with diverted sleeve gastrectomy (II-DSG), laparoscopic transit bipartition with sleeve gastrectomy (TB-SG), and laparoscopic sleeve gastrectomy (LSG) throughout a 12-month follow-up period retrospectively. METHODS: This study considered patients with T2DM who underwent metabolic procedures. The postoperative changes in the glucose, C-peptide, HbA1c, HOMA-IR, insulin, cholesterol, body mass index, and total weight loss (TWL) were compared retrospectively. The intended outcome was to reach a long lasting fasting blood glucose (FBG) <126 mg/dl. A multivariate regression analysis was applied to define the predictive markers in glucose regulation. RESULTS: Present study consisted of 83 patients with a mean age of 47.25 ± 6.58 years, mean preoperative BMI of 37.36 ± 2.71 kg/m2, and mean outcomes in the HbA1C and FBG of 9.05 ± 1.33% and 237 ± 15 mg/dl, respectively. There were similar correlations in BMI and total weight loss (TWL). At 12-month follow up period, compared to LSG group, TB-SG and II-DSG groups have higher remission proportions (35.3, 67.9, 54.7, respectively, p < 0.05) with similar TWL% (22.35, 27.14, 23.16%) outcomes. The II-DSG and TB-SG results drew closer together toward the end of this study interval unlike the LSG group. CONCLUSION: Our results showed that II-DSG and TB-SG ensured significant regression rates during the follow-up period. Since the TB-SG achieved these outcomes by finite anastomoses and intervening segments, it was considered to be a superior procedure compared to II-DSG and LSG procedures.

Serum Magnesium Concentrations in the Canadian Population and Associations with Diabetes, Glycemic Regulation, and Insulin Resistance.

Total serum magnesium (Mg) concentration (SMC) is commonly used to assess Mg status. This study reports current SMCs of Canadians and their associations with demographic factors, diabetes, and measures of glycemic control and insulin resistance using results from the Canadian Health Measures Survey cycle 3 (2012-2013). Associations were examined in adults aged 20-79 years using linear mixed models. Mean SMCs and percentile distributions for 11 sex-age groups between 3 and 79 years (n = 5561) are reported. SMCs were normally distributed and differences (p < 0.05) among sex and age groups were small. Between 9.5% and 16.6% of adult sex-age groups had a SMC below the lower cut-off of a population-based reference interval (0.75-0.955 mmol·L-1) established in the United States population as part of the NHANES I conducted in 1971-1974. Having diabetes was associated with 0.04 to 0.07 mmol·L-1 lower SMC compared to not having diabetes in the various models. Body mass index, glycated hemoglobin, serum glucose and insulin concentrations, and homeostatic model assessment of insulin resistance were negatively associated with SMC. This is the first study to report SMCs in a nationally representative sample of the Canadian population. A substantial proportion of Canadians are hypomagnesaemic in relation to a population-based reference interval, and SMC was negatively associated with diabetes and indices of glycemic control and insulin resistance.

Overview of food products and dietary constituents with antidiabetic properties and their putative mechanisms of action: a natural approach to complement pharmacotherapy in the management of diabetes.

Diabetes is one of the fastest growing chronic, noncommunicable diseases worldwide. Currently, 11 major classes of pharmacotherapy are available for the management of this metabolic disorder. However, the usage of these drugs is often associated with undesirable side effects, including weight gain and hypoglycemia. There is thus a need for new, safe and effective treatment strategies. Diet is known to play a major role in the prevention and management of diabetes. Numerous studies have reported the putative association of the consumption of specific food products, or their constituents, with the incidence of diabetes, and mounting evidence now suggests that some dietary factors can improve glycemic regulation. Foods and dietary constituents, similar to synthetic drugs, have been shown to modulate hormones, enzymes, and organ systems involved in carbohydrate metabolism. The present article reviews the major classes and modes of action of antidiabetic drugs, and examines the evidence on food products and dietary factors with antidiabetic properties as well as their plausible mechanisms of action. The findings suggest potential use of dietary constituents as a complementary approach to pharmacotherapy in the prevention and/or management of diabetes, but further research is necessary to identify the active components and evaluate their efficacy and safety.

Enhanced glucose tolerance in pancreatic-derived factor (PANDER) knockout C57BL/6 mice.

Pancreatic-derived factor (PANDER; also known as FAM3B) is a uniquely structured protein strongly expressed within and secreted from the endocrine pancreas. PANDER has been hypothesized to regulate fasting and fed glucose homeostasis, hepatic lipogenesis and insulin signaling, and to serve a potential role in the onset or progression of type 2 diabetes (T2D). Despite having potentially pivotal pleiotropic roles in glycemic regulation and T2D, there has been limited generation of stable animal models for the investigation of PANDER function, and there are no models on well-established genetic murine backgrounds for T2D. Our aim was to generate an enhanced murine model to further elucidate the biological function of PANDER. Therefore, a pure-bred PANDER knockout C57BL/6 (PANKO-C57) model was created and phenotypically characterized with respect to glycemic regulation and hepatic insulin signaling. The PANKO-C57 model exhibited an enhanced metabolic phenotype, particularly with regard to enhanced glucose tolerance. Male PANKO-C57 mice displayed decreased fasting plasma insulin and C-peptide levels, whereas leptin levels were increased as compared with matched C57BL/6J wild-type mice. Despite similar peripheral insulin sensitivity between both groups, hepatic insulin signaling was significantly increased during fasting conditions, as demonstrated by increased phosphorylation of hepatic PKB/Akt and AMPK, along with mature SREBP-1 expression. Insulin stimulation of PANKO-C57 mice resulted in increased hepatic triglyceride and glycogen content as compared with wild-type C57BL/6 mice. In summary, the PANKO-C57 mouse represents a suitable model for the investigation of PANDER in multiple metabolic states and provides an additional tool to elucidate the biological function and potential role in T2D.