Glucose Tolerance Index Research Articles

Examination of sex-specific interactions between gut microbiota and host metabolism after 12-week combined polyphenol supplementation in individuals with overweight or obesity

ABSTRACT Polyphenols exert beneficial effects on host metabolism, which may be mediated by the gut microbiota. We investigated sex-specific differences in microbiota composition and interactions with cardiometabolic parameters after polyphenol supplementation in individuals with overweight/obesity. In a double-blind, randomized, placebo-controlled trial, 19 women and 18 men with normal glucose tolerance and body mass index >25 kg/m2 received epigallocatechin-3-gallate and resveratrol (EGCG+RES, 282 + 80 mg/d) or placebo supplements for 12 weeks. Fecal microbiota composition (16S rRNA gene amplicon sequencing, V3-V4 region), in vivo whole-body fat oxidation (indirect calorimetry), and mitochondrial respiration in permeabilized skeletal muscle fibers (SkM-Ox; ex vivo respirometry) were determined pre- and post-intervention. Overall, EGCG+RES supplementation did not affect gut microbiota composition. Akkermansia, Ruminococcaceae UCG-002, Subdoligranulum, and Lachnospiraceae UCG-004 were more abundant, while Veillonella, Tyzzerella 4, Clostridium innocuum group, Ruminococcus gnavus group, Escherichia-Shigella, and an uncultured Ruminococcaceae family genus were less abundant in women compared to men. In women, only baseline Eubacterium ventriosum group abundance correlated with EGCG+RES-induced changes in SkM-Ox. In men, low Dorea, Barnsiella, Anaerotruncus, Ruminococcus, Subdoligranulum, Coprococcus, Eubacterium ventriosum group, Ruminococcaceae UCG-003, and a Ruminococcaceae family genus abundance, and high Blautia abundance at baseline were associated with improvements in SkM-Ox. Changes in whole-body fat oxidation were not associated with gut microbiota features. We conclude that baseline microbiota composition predicts changes in SkM-Ox as a result of EGCG+RES supplementation in men but not in women. Men may be more prone to diet-induced, gut microbiota-related improvements in cardiometabolic health. These sex-differences should be further investigated in future precision-based intervention studies.

Study on the mechanism of modified Gegen Qinlian decoction in regulating the intestinal flora-bile acid-TGR5 axis for the treatment of type 2 diabetes mellitus based on macro genome sequencing and targeted metabonomics integration

BackgroundCurrently, there are many drugs available for the treatment of type 2 diabetes mellitus (T2DM), but most of them cause various side effects due to the need for long-term use. As a traditional Chinese medicine, Gegen Qinlian Decoction (GQD) has shown good efficacy and low side effects in the treatment of T2DM in both clinical and basic research. Based on relevant traditional Chinese medicine theories, dried ginger is innovatively added the formula of traditional GQD to create a modified GQD. This modification reduces the side effects of traditional GQD while exerting its therapeutic effect on T2DM. Previous studies have found that the modified GQD can regulate endoplasmic reticulum stress in the liver, inhibit hepatic gluconeogenesis, protect pancreatic islet β cells, and control blood sugar levels by inhibiting the FXR/neuronal ceramide signaling pathway. GQD can also regulate the intestinal microbiota to achieve therapeutic and protective effects in various gastrointestinal diseases. However, there is no research exploring whether the modified GQD achieves its therapeutic mechanism for T2DM by regulating the intestinal microbiota. PurposeTo explore the mechanism of modified GQD in the treatment of T2DM based on multi-omics, focusing on its effect on the “intestinal flora bile acid TGR5′' axis. MethodsThe T2DM model was established using db/db mice, which were randomly divided into a model group, metformin group, high-dose GQD group, medium-dose GQD group, low-dose GQD group, while m/m mice were used as blank control. The drug intervention lasted for 12 weeks, during which the general conditions, oral glucose tolerance (OGT), blood glucose, and lipid-related indexes were recorded. Additionally, the fasting insulin (FINS), c-peptide, GLP-1 in serum, and cAMP in the ileum were measured by ELISA assay. Furthermore, the composition, abundance, and function of the intestinal microbiota were determined by macro genome sequencing, while bile acid was detected by targeted metabonomics. For histological evaluation, HE staining was used to observe the pathological changes of the ileum and pancreas, and the ultrastructure of the ileum and pancreas was observed by transmission electron microscopy. Apoptosis in the ileum tissue was detected by Tunel staining. Moreover, the mRNA and protein expressions of TGR5, PKA, CREB, PC1/3, GLP-1, and their phosphorylation levels in the ileum were detected by qPCR, immunohistochemistry, and Western blot; The expression of INS in the pancreas was also evaluated using immunohistochemistry. Finally, double immunofluorescence staining was used to detect the co-localization expression of TGR5 and GLP-1, NeuroD1, and GLP-1 in the ileum. ResultsThe modified GQD was found to significantly reduce blood glucose, improve oral glucose tolerance, and blood lipid levels, as well as alleviate the injury of the ileum and pancreas in T2DM mice. Furthermore, modified GQD was found to effectively regulate intestinal flora, improve bile acid metabolism, activate the TRG5/cAMP/PKA/CREB signal pathway, and stimulate GLP-1 secretion. ConclusionGQD can regulate the “intestinal flora-bile acid-TGR5” axis and has a therapeutic effect on T2DM in mice.

7-Hydroxyflavone improves nonalcoholic fatty liver disease by acting on STK24.

The escalating incidence of nonalcoholic fatty liver disease (NAFLD) is closely associated with a high-fat diet, leading to a decline in quality of life and significant health impairment. 7-Hydroxyflavone (7-HY) is a flavonoid known for its anti-inflammatory, anticarcinogenic, and antioxidant effects. This study aims to assess the ameliorative effects of 7-HY on NAFLD induced by a high-fat diet and elucidate underlying mechanisms. Oleic acid/palmitic acid-induced HepG2 cells and C57BL/6 mice on a high-fat diet were utilized as in vitro and in vivo models. In animal experiments, 7-HY was utilized as a dietary supplement. The 15-week in vivo experiment monitored body weight, body fat percentage, glucose tolerance, insulin tolerance, and metabolic indexes. Commercial kits assessed triglyceride (TG) and total cholesterol levels in cells, liver tissue, and blood. Discovery Studio identified potential targets of 7-HY, compared with NAFLD-associated targets in the GeneCards database. Results indicated 7-HY mitigated fat accumulation, hepatic steatosis, and oxidative stress induced by a high-fat diet. Furthermore, 7-HY showed potential efficacy in ameliorating abnormal glucose metabolism and promoting energy metabolism. Reverse target finding and molecular docking demonstrated a robust interaction between 7-HY and serine/threonine kinase 24 (STK24). Subsequent experimental results confirmed 7-HY's ability to inhibit TG deposition in HepG2 cells through interaction with STK24. In conclusion, 7-HY demonstrated the capacity to alleviate high-fat diet-induced NAFLD, presenting a novel strategy for the prevention and treatment of NAFLD.

Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study

Aims/hypothesisAs the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset.MethodsThe LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7–6.4% [39–47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings.ResultsIn the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=−0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; β=−0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p<0.001 for eGDR) and MZ (β=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis.Conclusions/interpretationAn impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.Graphical

The supplementation of the multi-strain probiotics WHHPRO™ alleviates high-fat diet-induced metabolic symptoms in rats via gut-liver axis.

Metabolic syndrome (MS) has emerged as one of the major global health concerns, accompanied by a series of related complications, such as obesity and type-2 diabetes. The gut-liver axis (GLA) is a bidirectional communication between the gut and the liver. The GLA alterations have been revealed to be closely associated with the development of MS. Probiotics within Lactobacillus and Bifidobacterium confer beneficial effects on improving MS symptoms. WHHPRO™ is a mixture of four probiotic strains, with potential MS-improving abilities. This study aimed to investigate the effects of WHHPRO™ on MS symptoms using a high-fat diet (HFD) rat model. Oral administration of WHHPRO™ for 12 weeks improved glucose tolerance, blood lipid, body weight, and liver index in HFD rats. WHHPRO™ shaped the gut microbiome composition by increasing the abundance of Lactobacillus and Akkermansia and normalized the reduced SCFA levels in HFD rats. Besides, WHHPRO™ modulated the fecal bile acids (BAs) profile, with decreased levels of T-b-MCA and 12-KDCA and increased levels of LCA and ILCA. Meanwhile, WHHPRO™ increased total unconjugated BAs in feces and liver and reduced the accumulation of total hepatic BA pool size in HFD rats. Moreover, WHHPRO™ reversed the expression of genes associated with impaired BA metabolism signaling in the ileum and liver. Our findings suggest that WHHPRO™ exerted beneficial effects on improving MS symptoms, involving the modulation of the gut microbiome composition, SCFAs, and the FXR-FGF15 signaling along the GLA. Supplementation of WHHPRO™ may serve as a novel strategy for improving MS symptoms.

Immunotherapeutic approach to reduce senescent cells and alleviate senescence-associated secretory phenotype in mice.

Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and SASP, leading to lower expression of pro-inflammatory genes in peripheral organs. HCW9218 treatment also reverted the pattern of key regulatory circadian gene expression in aged mice to levels observed in young mice and impacted genes associated with metabolism and fibrosis in the liver. Single-nucleus RNA Sequencing analysis further revealed that HCW9218 treatment differentially changed the transcriptomic landscape of hepatocyte subtypes involving metabolic, signaling, cell-cycle, and senescence-associated pathways in naturally aged mice. Long-term survival studies also showed that HCW9218 treatment improved physical performance without compromising the health span of naturally aged mice. Thus, HCW9218 represents a novel immunotherapeutic approach and a clinically promising new class of senotherapeutic agents targeting cellular senescence-associated diseases.

Metabologenomic Approach Reveals Intestinal Environmental Features Associated with Barley-Induced Glucose Tolerance Improvements in Japanese: A Randomized Controlled Trial.

(1) Background: Consumption of barley has been known to exert beneficial effects on glucose tolerance; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. (2) Methods: In the present study, we aimed to understand the relationship between the intestinal environment, including intestinal microbiome and their metabolome, and glucose tolerance. A randomized controlled trial with a 4-week consumption of barley or control food was conducted. We conducted an integrated analysis of the intestinal microbiome and metabolome and analyzed the relationship with improvement of glucose tolerance. (3) Results: We found that metabolites such as azelate were significantly increased after barley consumption. Furthermore, the subjects whose glucose tolerance was slightly impaired showed improvement in their glucose tolerance index following the barley consumption. Additionally, the analysis showed that the increase in the abundance of the Anaerostipes was correlated with the improvement in the glucose tolerance index. (4) Conclusions: Our findings indicate that the effects of barley consumption for glucose tolerance are partly defined by the intestinal environment of consumers, providing a quantitative measurement of the dietary effect based on the intestinal environment.

58-LB: Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice

Prediabetes (PreD) , which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D) . Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici pA1c (pA1c) in a murine model of high-fat diet (HFD) -induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1×10E10 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and ex-amined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length) . We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D. Disclosure M. Cabello: None. M. Oneca: Employee; GENBIOMA APLICACIONES SL. M. J. Pajares: None. J. Ayo: Board Member; Genbioma Aplicaciones S. L., Employee; Genbioma Aplicaciones S. L. I. J. Encío: Other Relationship; Genbioma Aplicaciones SL. M. Araña: None. M. Barajas: None. Funding Government of Navarre (Ref 0011-1365-2020-000290) and the European Regional Development Fund (ERDF) . Maria Oneca is supported by Torres-Quevedo grants from the Spanish Ministry of Science and innovation (Ayudas para contratos Torres Quevedo PTQ2019-010384/AEI/10.13039/501100011033)

Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.

Muscle fiber composition is associated with peripheral insulin action. We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia. Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group 1 (n = 11), area occupied by type I muscle fibers = 61.0 ± 11.8%, and group 2 (n = 8), type I area = 36.0 ± 4.9% (P < 0.001). Biopsies were obtained from the vastus lateralis muscle and analyzed for mitochondrial respiration on permeabilized fibers, muscle fiber composition, and capillary density. An intravenous glucose tolerance test was performed and indices of glucose tolerance, insulin sensitivity, and secretion were determined. Glucose tolerance was similar between groups, whereas whole-body insulin sensitivity was decreased by ~50% in group 2 vs group 1 (P = 0.019). First-phase insulin release (area under the insulin curve during 10 minutes after glucose infusion) was increased by almost 4-fold in group 2 vs group 1 (P = 0.01). Whole-body insulin sensitivity was correlated with percentage area occupied by type I fibers (r = 0.54; P = 0.018) and capillary density in muscle (r = 0.61; P = 0.005) but not with mitochondrial respiration. Insulin release was strongly related to percentage area occupied by type II fibers (r = 0.93; P < 0.001). Assessment of muscle contractile function in young healthy subjects may prove useful in identifying individuals with insulin resistance and enhanced glucose-stimulated insulin secretion prior to onset of clinical manifestations.

Preventive Impact of Long-Term Ingestion of Chestnut Honey on Glucose Disorders and Neurodegeneration in Obese Mice.

The purpose of the present study was to evaluate the impact of long-term honey ingestion on metabolic disorders and neurodegeneration in mice fed a high-fat diet (HFD). Three groups of mice were fed with a standard diet (STD), HFD or HFD supplemented with honey (HFD-H) for 16 weeks. Biochemical, histological, Western blotting, RT-PCR and Profiler PCR array were performed to assess metabolic parameters, peripheral and central insulin resistance and neurodegeneration. Daily honey intake prevented the HFD-induced glucose dysmetabolism. In fact, it reduced plasma fasting glucose, insulin and leptin concentrations and increased adiponectin levels. It improved glucose tolerance, insulin sensitivity and HOMA index without affecting plasma lipid concentration. HFD mice showed a significantly higher number of apoptotic nuclei in the superficial and deep cerebral cortex, upregulation of Fas-L, Bim and P27 (neuronal pro-apoptotic markers) and downregulation of Bcl-2 and BDNF (anti-apoptotic factors) in comparison with STD- and HFD-H mice, providing evidence for honey neuroprotective effects. PCR-array analysis showed that long-term honey intake increased the expression of genes involved in insulin sensitivity and decreased genes involved in neuroinflammation or lipogenesis, suggesting improvement of central insulin resistance. The expressions of p-AKT and p-GSK3 in HFD-H mice, which were decreased and increased, respectively, in HFD mouse brain, index of central insulin resistance, were similar to STD animals supporting the ability of regular honey intake to protect brain neurons from insulin resistance. In conclusion, the present results provide evidence for the beneficial preventative impact of regular honey ingestion on neuronal damage caused by HFD.

Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice.

Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.

Assessing the relationship between people at increased risk of developing diabetes and periodontitis: a systematic review study

AbstractImpaired glucose tolerance is an intermediate condition between diabetes and normal blood glucose, in which blood glucose level has risen and is between 100–126mg/dL. Present evidence suggests that there is a relationship between poor control of diabetes and uncontrolled diabetes with periodontal disease. People with impaired glucose tolerance may have a more unfavourable periodontal condition than the general population with a mechanism similar to those with diabetes. Accordingly, the present study aims to assess the relationship between impaired glucose tolerance and periodontal disease using systematic review criteria.This study is a systematic review. The databases included PubMed, Science Direct, Scopus, Cochrane Library, and Google Scholar search engine. Two individuals independently selected studies based on the inclusion criteria. The Newcastle‐Ottawa Scale (NOS) checklist was used for quality assessment. Search management was conducted using EndNote software.After applying the inclusion and exclusion criteria, seven articles were included in the study. Regarding the pocket depth (PD) index, five studies stated that there is a relationship between impaired glucose tolerance status and the severity of the periodontal disease, and lower periodontal health was observed in groups with higher levels of blood glucose (p&lt;0.05). With regard to the bleeding on probing (BOP) index, it should be stated that most studies have reported that there is a relationship with impaired glucose tolerance indices (p&lt;0.05).This systematic review study suggested that there is a relationship between periodontal indicators and impaired glucose tolerance. Copyright © 2021 John Wiley &amp; Sons.

The effects of Zinc-Methionine on glucose metabolism and insulin resistance during late pregnancy in ewes

This study investigated the effects of dietary supplements of Zinc-Methionine (Zn-Met) on the zinc concentration of the blood and indices such as insulin resistance and glucose tolerance in late-pregnancy ewes to provide a practical solution to prevent metabolic diseases associated with energy status. In this research, 18 Makouei pregnant ewes were selected and randomized into 3 experimental groups: Group 1: Basal diet containing 10.3 mg Zn/kgDM and no zinc supplementation = CTR (Control); Group 2: Basal diet supplemented with low-dose zinc equivalent to the pregnancy requirements (30 mg Zn/kgDM) = LZN; Group 3: Basal diet supplemented with high-dose zinc (300 mg Zn/kgDM) = HZN. Blood samples for insulin resistance and glucose tolerance indices were collected according to standard methods. The results of this study indicated that supplementation of high-dose Zn-Met decreased (P < 0.05) blood glucose and tended (P < 0.1) to reduce the beta-hydroxybutyrate (BHB) concentrations. After intravenous injection of glucose and insulin, none of the glucose tolerance and insulin resistance indices were significant among groups (P > 0.05). However, the intravenous glucose tolerance test (IGTT) showed that the area under the curve (AUC) of serum glucose in the HZN group was numerically lower than that of the LZN and CTR groups. Furthermore, the numerically higher clearance rate (CR) of glucose and more negative glucose AUC following intravenous administration of insulin in Zinc-supplemented groups suggested that the ewes had greater insulin response than control group. The results showed a decrease in blood glucose concentration due to higher zinc intake after insulin injection and supported the evidence for improving insulin sensitivity. In addition, our results showed that ewes receiving zinc supplementation experienced a more favorable state of BHB or NEFA values. In conclusion, Zn-Met supplementation was found to have promising effects in improving energy metabolism in late pregnant ewes. However, further studies are needed to understand the mechanisms involved in regulating lipolysis and energy metabolism.

Berberine Ameliorates Hepatic Insulin Resistance by Regulating microRNA-146b/SIRT1 Pathway.

ObjectiveHepatic insulin resistance is a major initiating factor for type 2 diabetes mellitus. In previous study, Gegen Qinlian Decoction containing berberine could enhance hepatic insulin sensitivity by SIRT1-dependent deacetylation of FOXO1. However, it is not clear whether berberine also can improve hepatic insulin sensitivity by SIRT1/FOXO1 pathway. This study aimed to evaluate the efficacy of berberine for improving hepatic insulin resistance and the possible molecular mechanisms involved.MethodsIn vitro, HepG2 cells were induced with palmitic acid, and glycogen synthesis was examined. In vivo, a high-fat diet (HFD)-fed mouse model was established, and metabolic parameters were assessed. The expressions of miR-146b and sirtuin 1 (SIRT1) in liver were also examined. The relationship between miR-146b and SIRT1 was examined by the dual-luciferase reporter gene assay.ResultsSerum biochemical parameters, such as glucose and HOMA-IR index, were increased in HFD mice; miR-146b and SIRT1 were abnormally expressed in HFD mice and palmitic acid-treated HepG2 cells. Interestingly, berberine reduced body weight and caused a significant improvement in glucose tolerance and HOMA-IR index without altering food intake in mice. Overexpression of miR-146b abolished the protective effect of berberine on palmitic acid-induced impaired glycogen synthesis in HepG2 cells. Luciferase assay showed that miR-146b directly targeted SIRT1.ConclusionThe present findings suggest that berberine could attenuate hepatic insulin resistance through the miR-146b/SIRT1 pathway, which may represent a potential therapeutic target for the prevention and treatment of metabolic diseases, particularly diabetes.

Limited Association between the Total Healthy Eating Index-2015 Score and Cardiovascular Risk Factors in Individuals with Long-Standing Spinal Cord Injury: An Exploratory Study: An Exploratory Study

BackgroundThe healthy eating index-2015 (HEI-2015) reflects diet quality in reference to the 2015-2020 Dietary Guidelines for Americans (DGA). Little is known regarding its application in individuals with chronic spinal cord injury (SCI). ObjectiveTo explore the relationship between diet quality as assessed by the HEI-2015 and cardiovascular risk factors among individuals with chronic SCI. DesignThis is a cross-sectional analysis of baseline data collected from August 2017 through November 2019 for an interventional study that evaluates the effects of a high-protein/low-carbohydrate diet on cardiovascular risk factors in individuals with chronic SCI at the University of Alabama at Birmingham. Participants/settingTwenty-four free-living adults with SCI (mean age, 45 ± 12 y; 8F/16M, level of injury: nine cervical, 15 thoracic; mean duration of injury: 20 ± 13 y) were included. Main outcome measuresParticipants underwent a 2-hour oral glucose tolerance test (OGTT) and a dual-energy x-ray absorptiometry scan. Dietary intake was assessed by three, 24-hour multiple-pass dietary recalls to calculate the HEI-2015 using the simple HEI scoring algorithm method. Data analysisMultiple linear regression analyses were performed to predict indices of lipid metabolism and glucose homeostasis and C-reactive protein (CRP) from the HEI-2015. Principal component analysis was used to reduce the number of covariates (level of injury, sex, and body fat percentage). ResultsOn average, participants’ diets were of low quality (HEI-2015, 47.2 ± 10.8). The regression models for fasting glucose (FG), cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and CRP had moderate to large effect sizes (adjusted R2 ≥ 13%), suggesting good explanatory abilities of the predictors. Small or limited effect sizes were observed for glucose tolerance, fasting insulin, triglycerides, and Matsuda index (adjusted R2 < 13%). The HEI-2015 accounted for a moderate amount of variation in FG (partial omega-squared, ωP2 = 13%). Each 10-point HEI-2015 score increase was associated with a 3.3-mg/dL decrease in FG concentrations. The HEI-2015 accounted for a limited amount of variation in other indices (ωP2 < 5%). ConclusionsAmong participants with SCI, higher conformance to the 2015-2020 DGA was 1) moderately associated with better FG homeostasis; and 2) trivially associated with other cardiovascular risk factors. Because of the small sample size, these conclusions cannot be extrapolated beyond the study sample. Future larger studies are warranted to better understand the relationship between diet quality and cardiovascular disease risks in this population.

Short-term Renoprotective Effect of SGLT-2 Inhibitor for Renal Function and Albuminuria in Type 2 Diabetes: a Retrospective Study

The purpose of this study was to clarify the profiles of patients in whom SGLT-2 inhibitors are more likely to exert a renal protective effect in clinical practice. We retrospectively analyzed the medical record information of sixty-three type 2 diabetic patients (33 males, 30 females, average age 53.0 ± 13.0 years) who were given usual doses of a SGLT-2 inhibitor. We investigated changes in body weight, blood pressure, glucose metabolism index, lipid metabolism index, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin-to-creatinine ratio, UACR) 3 months before and after administration of a SGLT-2 inhibitor. Three months after administration of an SGLT-2 inhibitor, there were improvements in glucose tolerance, weight loss, blood pressure, and lipid indices. In all cases, there was no significant change in eGFR, but UACR decreased significantly. UACR decreased regardless of angiotensin II receptor blocker medication and significantly decreased in nephropathy patients with microalbuminuria or overt albuminuria. UACR decreased only in the group in which blood pressure, body weight, and hemoglobin A1c decreased before and after administration of the SGLT-2 inhibitor. Our study shows that the renoprotective effects of SGLT-2 inhibitors are more likely to be exerted in diabetic nephropathy patients who have advanced to at least microalbuminuria stage, and in addition to direct renal protection, the comprehensive effects of SGLT-2 inhibitors, which lower body weight, blood pressure, and blood glucose, are also important for their renal protection effects.

The Relationship Between Healthy Eating Index-2015 and Cardiometabolic Risk Factors in People with Long-Standing Spinal Cord Injury

Abstract Objectives The Healthy Eating Index (HEI)-2015 is a measure of diet quality in reference to the 2015 Dietary Guidelines for Americans. We examined the relationship between HEI-2015 and several indices of cardiometabolic risk factors among individuals with chronic spinal cord injury (SCI) (&amp;gt;3 years after injury). Methods Twenty-four participants without type 2 diabetes were included (45 ± 12 y, 8F/16 M, 9 Tetraplegia/15 Paraplegia, time since injury: 20 ± 13 y). All participants underwent a 2-hour oral glucose tolerance test (OGTT), a Dual-energy X-ray absorptiometry scan (DXA), and 3 24-hour multiple-pass dietary recalls. HEI-2015 was calculated using the dietary recall data. To build the regression model, firstly, principal component (PC) analysis was used to reduce the number of covariates from 3 (level of injury, gender, percentage body fat estimated from the DXA) to 2 PCs. Multiple linear regression analyses were run to predict indices of lipid metabolism and glucose homeostasis as well as C-reactive protein (CRP) from the HEI and the 2 PC scores. Results The average HEI-2015 score was lower for participants with SCI compared to the general American population (48 ± 11 vs. 59, P &amp;lt; 0.05). The regression models for fasting glucose (FG), Cholesterol, HDL, LDL, and CRP had moderate to large effect sizes (adjusted R2 &amp;gt; 13%), indicating good explanatory ability of the predictors. Small or limited effect sizes were observed for other models (glucose tolerance, fasting insulin, triaglycerides, and Matsuda index, adjusted R2 &amp;lt; 13% for all). Furthermore, the HEI accounted for a moderate amount of variation in FG as evidenced by partial Omega-squared of 13%. Each 10-point increase of the HEI was associated with a 3.3 mg/dL decrease in FG concentrations. However, HEI accounted for a limited amount of variations in other indices (ωP2 &amp;lt; 5% for all). Conclusions Our exploratory analyses suggest that HEI-2015 has limited effects on blood lipids and CRP but may be associated with lower FG concentrations in our sample group. Future larger studies are warranted to delineate the relationship between diet quality and cardiometabolic health outcomes in individuals with SCI. Funding Sources The National Institute on Disability, Independent Living, and Rehabilitation Research.

Increased blood pressure and impaired endothelial function after accelerated growth in IVF/ICSI children.

STUDY QUESTIONWhat is the effect of growth velocity (height and weight) in early infancy on metabolic end-points and endothelial function in children born after ART?SUMMARY ANSWERNeonatal, infant and childhood growth is positively related to blood pressure in 9-year-old IVF/ICSI offspring, while growth in childhood was negatively associated with endothelial function.WHAT IS KNOWN ALREADYOffspring of pregnancies conceived after ART are at risk for later cardiometabolic risk factors. It is well established that early growth is related to numerous later cardiometabolic risk factors such as high blood pressure. This concept is known as the Developmental Origin of Health and Disease theory.STUDY DESIGN, SIZE, DURATIONThe relation between early growth and later cardiometabolic risk profile was studied in the MEDIUM-KIDS study, a prospective observational cohort study in children born after an IVF/ICSI treatment. In 131 children (48.1% males) at the average age of 9.4 years, cardiometabolic outcomes were assessed and growth data from birth until age 9 years were collected from child welfare centers.PARTICIPANTS/MATERIALS, SETTINGS, METHODSThe following cardiometabolic outcomes were assessed: blood pressure, skinfolds, lipid spectrum, hair cortisone and glucose and insulin levels. Data on maximum skin perfusion after transdermal delivery of acetylcholine as a measure of endothelial function were collected.Growth charts were obtained electronically from child welfare centers, which offer free consultations and vaccinations to all Dutch children. At these centers, height and weight are recorded at predefined ages. Growth was defined as z-score difference in weight between two time points. Multivariable linear regression analysis was used to model the relation between growth and cardiometabolic outcomes. The following growth windows were –studied simultaneously in each model: 0–1 month, 1–3 months, 3–6 months, 6–11 months, 11–24 months and 2–6 years. The model was adjusted for height growth in all intervals except for 0–1 month.MAIN RESULTS AND THE ROLE OF CHANCEIn multivariable linear regression analyses, multiple growth windows were positively associated with blood pressure, for example growth from 2–6 years was significantly related to systolic blood pressure: B = 4.13, P = 0.005. Maximum skin perfusion after acetylcholine was negatively associated with height-adjusted weight gain from 2 to 6 years: B = −0.09 (log scale), P = 0.03. Several growth windows (weight 1–3 months, 3–6 months, 6–11 months, 11–24 months, 2–6 years) were positively linked with total adiposity. Lipids, glucose tolerance indices and cortisone were not related to growth.LIMITATIONS, REASONS FOR CAUTIONThis study is of modest size and of observational nature, and we did not include a control group. Therefore, we cannot assess whether the observed associations are causal. It is also not possible to analyze if our observations are specific for, or exacerbated in, the ART population. Ideally, a control group of naturally conceived siblings of IVF/ICSI children should simultaneously be studied to address this limitation and to assess the impact of the ART procedure without the influence of parental (subfertility) characteristics.WIDER IMPLICATIONS OF THE FINDINGSThe results of this study contribute to our understanding of the reported increased risk for hypertension in ART offspring. We speculate that early, accelerated growth may be involved in the reported increased risk for hypertension in ART offspring, with endothelial dysfunction as a possible underlying mechanism. However, additional research into the mechanisms involved is required.STUDY FUNDING/COMPETING INTEREST(S)The study was financially supported by the March of Dimes, grant number #6-FY13-153. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the paper. The authors have no conflict of interest to declare.TRIAL REGISTRATION NUMBERNTR4220

Propolis modulates the gut microbiota and improves the intestinal mucosal barrier function in diabetic rats

Objective: Diabetes mellitus is associated with gut microbiota disturbance and intestinal mucosal injuries. This study investigated the influence of propolis on the gut microbiota and intestinal mucosa in rats with diabetes. Methods: Sprague-Dawley (SD) rats were randomly assigned to the control group, model group, and three propolis groups (supplemented with 80, 160, and 240 mg/kg·bw propolis, respectively). A high-fat diet combined with a streptozotocin (STZ) abdominal injection were used to induce diabetes in the rats. After 4 weeks, the intestinal histopathological analysis of the ileum was observed by transmission electron microscopy. The fasting blood glucose (FBG), plasma insulin, glucose tolerance (OGTT) and glycosylated hemoglobin (HbA1c) levels were measured. The expression of tight junction (TJ) proteins in the ileum was measured using western blotting. The molecular ecology of the fecal gut microbiota was analyzed by 16S rDNA high-throughput sequencing. The contents of the short-chain fatty acids (SCFAs) in feces were measured using high-performance liquid chromatography (HPLC). Results: After propolis treatment, compared to the model group, FBG and HbA1c levels declined, while the glucose tolerance and insulin sensitivity index (ISI) increased. The levels of TJ proteins in the ileum increased in the propolis groups. The tight junctions and gap junctions of the intestinal epithelium were also improved in the propolis groups. The contents of the feces acetic acid, propionic acid and butyrate were increased in the propolis groups. 16S rDNA high-throughput sequencing revealed that the composition of the gut microbiota of rats in the propolis supplement group was significantly improved. Conclusions: Compared to the model group, propolis exerted hypoglycemic effects in diabetic rats, and it repaired intestinal mucosal damage, benefited the communities of the gut microbiota and increased SCFA levels in diabetic rats.

Antidiabetic effects of water-soluble Korean pine nut protein on type 2 diabetic mice

Korean pine nut protein (PNP) has a variety of biological activities, which are good for human health, but its ability to preventing diabetes has not been reported. This study evaluated the effects of water-soluble proteins of Korean pine nut obtained from a dilute alkali extract on carbohydrate metabolism of type 2 diabetic mice on a model of diabetes induced using a high fat diet combined with streptozotocin. The results showed that the hypoglycemic effect of PNP at a middle dose was the most significant, which was 38.7% lower than that of control. The extract significantly improved the oral glucose tolerance and liver indexes, increased the activity of the carbohydrate metabolism enzymes, and regulated the expression of the function of key genes for carbohydrate metabolism. It had a positive effect on both insulin resistance and glycolytic/gluconeogenesis signaling. In conclusion, PNP can regulate fasting blood glucose, improve insulin resistance, correct the glucose metabolism disorder in diabetic mice, and have a positive regulatory role. As the functional food, it has the potential to be beneficial in the treatment of type 2 diabetes mellitus as a new hypoglycemic functional food.