The Role and Mechanism of Probiotics Supplementation in Blood Glucose Regulation: A Review.

With economic growth and improved living standards, the incidence of metabolic diseases such as diabetes mellitus caused by over-nutrition has risen sharply worldwide. Elevated blood glucose and complications in patients seriously affect the quality of life and increase the economic burden. There are limitations and side effects of current hypoglycemic drugs, while probiotics, which are safe, economical, and effective, have good application prospects in disease prevention and remodeling of intestinal microecological health and are gradually becoming a research hotspot for diabetes prevention and treatment, capable of lowering blood glucose and alleviating complications, among other things. Probiotic supplementation is a microbiologically based approach to the treatment of type 2 diabetes mellitus (T2DM), which can achieve anti-diabetic efficacy through the regulation of different tissues and metabolic pathways. In this study, we summarize recent findings that probiotic intake can achieve blood glucose regulation by modulating intestinal flora, decreasing chronic low-grade inflammation, modulating glucagon-like peptide-1 (GLP-1), decreasing oxidative stress, ameliorating insulin resistance, and increasing short-chain fatty acids (SCFAs) content. Moreover, the mechanism, application, development prospect, and challenges of probiotics regulating blood glucose were discussed to provide theoretical references and a guiding basis for the development of probiotic preparations and related functional foods regulating blood glucose.

Nutrition and health effects of pectin: A systematic scoping review of human intervention studies.

Pectin is composed of a group of complex polysaccharides that are naturally found in various plants and are associated with a range of beneficial health effects. Health outcomes from dietary pectin can vary depending on botanical origin, dietary dose and structure of pectin. The objective of this scoping review is to build a comprehensive overview of the current evidence available on intervention studies conducted in humans and to better understand the possible knowledge gaps in terms of structure-function relationships across the different health-related effects. PubMed and Embase databases were searched using PRISMA-ScR guidelines, yielding 141 references (from the initial 3704), representing 134 intervention studies performed between 1961 and 2022 that met inclusion criteria. Studies were divided into six categories, which included gut health, glycaemic response and appetite, fat metabolism, bioavailability of micronutrients, immune response and other topics. Review of these human intervention studies identified a variety of cohort characteristics and populations (life stage, health status, country), sources/types of pectin (i.e. citrus, sugarbeet, apple, other and non-defined), intervention timeframes (from one single intake to 168 d) and doses (0.1-50 g/d) that were tested for health outcomes in people. Gut health, post-prandial glucose regulation and maintenance of blood cholesterol represented the largest categories of studied outcomes. Further research to strengthen the structure-function relationships for pectin with health properties and associated outcomes is warranted and will benefit from a more precise description of physico-chemical characteristics and molecular compositions, such as degree of esterification, weight, degree of branching, viscosity, gel formation and solubility.

Hereditary Severe Insulin-resistance Syndrome and Acanthosis Nigricans Caused by Novel Mutations in the INSR Gene.

Most cases associated with Hereditary Severe Insulin Resistance Syndrome (H-SIRS) are linked to mutations in the insulin receptor (INSR) gene. Patients with H-SIRS typically manifest symptoms of hyperinsulinemia, insulin resistance, and diabetes mellitus. Other symptoms include impaired glucose regulation, hyperandrogenism, and the presence of acanthosis nigricans (AN). In this report, we present two cases of H-SIRS in female children exhibiting various symptoms, such as hyperinsulinemia, fasting hypoglycemia, postprandial hyperglycemia, overweight, fatty liver, hyperandrogenism, and varying degrees of AN. One patient also presented with mental retardation. Gene sequencing identified specific mutations in the INSR gene for both patients: c.2663A > G (p.Tyr888Cys) and c.38_61del (p.Pro13_Ala20del). These mutations have the potential to disrupt the interaction between INSR and insulin, leading to abnormal insulin signaling, insulin resistance, and various clinical manifestations.

Effects of exercise modality combined with moderate hypoxia on blood glucose regulation in adults with overweight.

Purpose: This study aimed to investigate the combined effects of moderate hypoxia with three different exercise modes on glucose regulation in healthy overweight adults. Methods: Thirteen overweight males (age: 31 ± 4 years; body fat 26.3 ± 3.2%) completed three exercise trials in a randomized crossover design involving 60 min cycling exercise at 90% lactate threshold (LOW), sprint interval training (20 × 4 s all-out; SIT) and lower limb functional bodyweight exercises (8 sets of 4 × 20 s; FEX) under moderate hypoxia (FiO2 = 16.5%). Post-exercise oral glucose tolerance test (OGTT) was performed following each trial. Heart rate, oxygen saturation (SpO2), physical activity enjoyment scale (PACES), and perceptual measures were recorded during each exercise session. Venous blood was collected pre-, immediately post-, and 24 h post-exercise and analysed for plasma glucose and insulin, incremental area under curve (iAUC), and circulating microRNA expression (c-miRs-486-5p, -126-5p, and -21-5p). Interstitial glucose concentrations were measured using continuous glucose monitoring (CGM). Results: Post-exercise OGTT iAUC for plasma glucose and insulin concentration were lower in SIT and LOW vs. control (p < 0.05) while post-exercise interstitial glucose iAUC and c-miRs were not different between exercise modes. Heart rate was greater in SIT vs. LOW and FEX, and FEX vs. LOW (p < 0.05), SpO2 was lower in SIT, while PACES was not different between exercise modes. Perceptual measures were greater in SIT vs. LOW and FEX. Conclusion: Acute SIT and LOW under moderate hypoxia improved post-exercise plasma insulin compared to FEX exercises. Considering SIT was also time-efficient, well tolerated, and enjoyable for participants, this may be the preferred exercise modality for improving glucose regulation in adult males with overweight when combined with moderate hypoxia.

Comparative evaluation of the antihyperglycemic effects of three extracts of sea mustard (Undaria pinnatifida): In vitro and in vivo studies.

Undaria pinnatifida (UP) contains multiple bioactive substances, such as polyphenols, polysaccharides, and amino acids, which are associated with various biological properties. This study aimed to evaluate the antihyperglycemic effects of three extracts obtained from UP. UP was extracted under three different conditions: a low-temperature water extract at 50 °C (UPLW), a high-temperature water extract at 90 °C (UPHW), and a 70 % ethanol extract (UPE). Nontargeted chemical profiling using high-performance liquid chromatography-triple/time-of-flight mass spectrometry (HPLC-Triple TOF-MS/MS) was conducted on the three UP extracts. Subsequently, α-glucosidase inhibitory (AGI) activity, glucose uptake, and the mRNA expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) were evaluated in Caco-2 cell monolayers. Furthermore, an oral carbohydrate tolerance test was performed on C57BL/6 mice. The mice were orally administered UP at 300 mg/kg body weight (B.W.), and the blood glucose level and area under the curve (AUC) were measured. Compared with glucose, UPLW, UPHW and UPE significantly inhibited both glucose uptake and the mRNA expression of SGLT1 and GLUT2 in Caco-2 cell monolayers. After glucose, maltose, and sucrose loading, the blood glucose levels and AUC of the UPLW group were significantly lower than those of the control group. These findings suggest that UPLW has antihyperglycemic effects by regulating glucose uptake through glucose transporters and can be expected to alleviate postprandial hyperglycemia. Therefore, UPLW may have potential as a functional food ingredient for alleviating postprandial hyperglycemia.

Participatory Development of an Integrated, eHealth-Supported, Educational Care Pathway (Diabetes Box) for People With Type 2 Diabetes: Development and Usability Study.

BACKGROUND: Type 2 diabetes (T2D) tremendously affects patient health and health care globally. Changing lifestyle behaviors can help curb the burden of T2D. However, health behavior change is a complex interplay of medical, behavioral, and psychological factors. Personalized lifestyle advice and promotion of self-management can help patients change their health behavior and improve glucose regulation. Digital tools are effective in areas of self-management and have great potential to support patient self-management due to low costs, 24/7 availability, and the option of dynamic automated feedback. To develop successful eHealth solutions, it is important to include stakeholders throughout the development and use a structured approach to guide the development team in planning, coordinating, and executing the development process. OBJECTIVE: The aim of this study is to develop an integrated, eHealth-supported, educational care pathway for patients with T2D. METHODS: The educational care pathway was developed using the first 3 phases of the Center for eHealth and Wellbeing Research roadmap: the contextual inquiry, the value specification, and the design phase. Following this roadmap, we used a scoping review about diabetes self-management education and eHealth, past experiences of eHealth practices in our hospital, focus groups with health care professionals (HCPs), and a patient panel to develop a prototype of an educational care pathway. This care pathway is called the Diabetes Box (Leiden University Medical Center) and consists of personalized education, digital educational material, self-measurements of glucose, blood pressure, activity, and sleep, and a smartphone app to bring it all together. RESULTS: The scoping review highlights the importance of self-management education and the potential of telemonitoring and mobile apps for blood glucose regulation in patients with T2D. Focus groups with HCPs revealed the importance of including all relevant lifestyle factors, using a tailored approach, and using digital consultations. The contextual inquiry led to a set of values that stakeholders found important to include in the educational care pathway. All values were specified in biweekly meetings with key stakeholders, and a prototype was designed. This prototype was evaluated in a patient panel that revealed an overall positive impression of the care pathway but stressed that the number of apps should be restricted to one, that there should be no delay in glucose value visualization, and that insulin use should be incorporated into the app. Both patients and HCPs stressed the importance of direct automated feedback in the Diabetes Box. CONCLUSIONS: After developing the Diabetes Box prototype using the Center for eHealth and Wellbeing Research roadmap, all stakeholders believe that the concept of the Diabetes Box is useful and feasible and that direct automated feedback and education on stress and sleep are essential. A pilot study is planned to assess feasibility, acceptability, and usefulness in more detail.

Observer-based control for plasma glucose regulation in type 1 diabetes mellitus patients with unknown input delay.

This article introduces an observer-based control strategy tailored for regulating plasma glucose in type 1 diabetes mellitus patients, addressing challenges like unknown time-varying delays and meal disturbances. This control strategy is based on an extended Bergman minimal model, a nonlinear glucose-insulin model to encompass unknown inputs, such as unplanned meals, exercise disturbances, or delays. The primary contribution lies in the design of an observer-based state feedback control in the presence of unknown long delays, which seeks to support and enhance the performance of the traditional artificial pancreas by considering realistic scenarios. The observer and control gains for the observer-based control are computed through linear matrix inequalities formulated from Lyapunov conditions that guarantee closed-loop stability. This design deploys a soft and gentle dynamic response, similar to a natural pancreas, despite meal disturbances and input delays. Numerical tests demonstrate the scheme's effectiveness in glycemic level regulation and hypoglycemic episode avoidance.

Safety and effects of acetylated and butyrylated high amylose maize starch in recently diagnosed youths with type 1 diabetes; a Pilot Study.

Acetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic shown to be effective in type 1 diabetes (T1D) prevention in mouse models and is safe in adults with established T1D. HAMS-AB alters the gut microbiome profile with increased bacterial fermenters that produce short chain fatty acids (SCFAs) with anti-inflammatory and immune-modulatory effects. We performed a pilot study using a cross-over design to assess the safety and efficacy of 4 weeks of oral HAMS-AB consumption by recently diagnosed (< 2 years of diagnosis) youths with T1D. Seven individuals completed the study. The mean±SD age was 15.0±1.2 years, diabetes duration 19.5±6.3 months, 5/7 were female and 4/7 were White, all with a BMI of < 85th%. The prebiotic was safe. Following prebiotic intake, gut microbiome changes were seen, including a notable increase in the relative abundance of fermenters such as Bifidobacterium and Faecalibacterium. Treatment was also associated with changes in bacterial functional pathways associated with either improved energy metabolism (upregulation of tyrosine metabolism) or anti-inflammatory effects (reduced geraniol degradation). There were no differences in stool SCFA levels. Plasma metabolites associated with improved glycemia, such as hippurate, were significantly increased after treatment and there were positive and significant changes in the immune regulatory function of mucosal associated invariant T cells. There was a significant decrease in the area under the curve glucose but not C-peptide, as measured during a mixed meal tolerance testing, following the prebiotic consumption. In summary, the prebiotic HAMS-AB was safe in adolescents with T1D and showed promising effects on the gut microbiome composition, function and immune regulatory function.

Morin-Based Nanoparticles for Regulation of Blood Glucose.

Morin, a naturally occurring bioactive compound shows great potential as an antioxidant, anti-inflammatory agent, and regulator of blood glucose levels. However, its low water solubility, poor lipid solubility, limited bioavailability, and rapid clearance in vivo hinder its application in blood glucose regulation. To address these limitations, we report an enzymatically synthesized nanosized morin particle (MNs) encapsulated in sodium alginate microgels (M@SA). This approach significantly enhances morin's delivery efficiency and therapeutic efficacy in blood glucose regulation. Utilizing horseradish peroxidase, we synthesized MNs averaging 305.7 ± 88.7 nm in size. These MNs were then encapsulated via electrohydrodynamic microdroplet spraying to form M@SA microgels. In vivo studies revealed that M@SA microgels demonstrated prolonged intestinal retention and superior efficacy compared with unmodified morin and MNs alone. Moreover, MNs notably improved glucose uptake in HepG2 cells. Furthermore, M@SA microgels effectively regulated blood glucose, lipid profiles, and oxidative stress in diabetic mice while mitigating liver, kidney, and pancreatic damage and enhancing anti-inflammatory responses. Our findings propose a promising strategy for the oral administration of natural compounds for blood glucose regulation, with implications for broader therapeutic applications.

Molecular-Level Dysregulation of Insulin Pathways and Inflammatory Processes in Peripheral Blood Mononuclear Cells by Circadian Misalignment.

Circadian misalignment due to night work has been associated with an elevated risk for chronic diseases. We investigated the effects of circadian misalignment using shotgun protein profiling of peripheral blood mononuclear cells taken from healthy humans during a constant routine protocol, which was conducted immediately after participants had been subjected to a 3-day simulated night shift schedule or a 3-day simulated day shift schedule. By comparing proteomic profiles between the simulated shift conditions, we identified proteins and pathways that are associated with the effects of circadian misalignment and observed that insulin regulation pathways and inflammation-related proteins displayed markedly different temporal patterns after simulated night shift. Further, by integrating the proteomic profiles with previously assessed metabolomic profiles in a network-based approach, we found key associations between circadian dysregulation of protein-level pathways and metabolites of interest in the context of chronic metabolic diseases. Endogenous circadian rhythms in circulating glucose and insulin differed between the simulated shift conditions. Overall, our results suggest that circadian misalignment is associated with a tug of war between central clock mechanisms controlling insulin secretion and peripheral clock mechanisms regulating insulin sensitivity, which may lead to adverse long-term outcomes such as diabetes and obesity. Our study provides a molecular-level mechanism linking circadian misalignment and adverse long-term health consequences of night work.

Preconception opioids interact with mouse strain to alter morphine withdrawal in the next generation.

RATIONALE: Transgenerational effects of preconception morphine exposure in female rats have been reported which suggest that epigenetic modifications triggered by female opioid exposure, even when that exposure ends several weeks prior to pregnancy, has significant ramifications for their future offspring. OBJECTIVE: The current study compares two mouse strains with well-established genetic variation in their response to mu opioid receptor agonists, C57BL/6J (BL6) and 129S1/svlmJ (129) to determine whether genetic background modifies the impact of preconception opioid exposure. METHODS: Adolescent females from both strains were injected daily with morphine for a total of 10 days using an increasing dosing regimen with controls receiving saline. Several weeks after their final injection, aged-matched BL6 and 129 morphine (Mor-F0) or saline (Sal-F0) females were mated with drug naïve males to generate Mor-F1 and Sal-F1 offspring, respectively. As adults, F1 mice were made morphine dependent using thrice daily morphine injections for 4 days. On day 5, mice were administered either saline or morphine followed 3 h later by naloxone. Behavioral and physiological signs of withdrawal were then measured. RESULTS: Regardless of strain or sex, morphine-dependent Mor-F1 mice had significantly lower levels of withdrawal-induced corticosterone but significantly higher glucose levels when compared to Sal-F1 controls. In contrast, both strain- and preconception opioid exposure effects on physical signs of morphine dependence were observed.

Effects of energy-restricted diets with or without nuts on weight, body composition and glycaemic control in adults: a scoping review.

Energy-restricted (ER) diets promote weight loss and improve body composition and glycaemic control. Nut consumption also improves these parameters. However, less is known about the combined benefit of these two strategies. This scoping review implemented a systematic search of Medline, Embase and Scopus to identify randomised controlled trials evaluating the effect of ER diets with or without nuts on body mass, body composition and glycaemic control in adults. After reviewing titles and abstracts, twenty-nine full-text articles were screened, resulting in seven studies reported in eight papers that met the inclusion criteria. Energy restriction was achieved by prescribing a set energy target or reducing intake by 1000-4200 kJ from daily energy requirements. Interventions ranged from 4 to 52 weeks in duration and contained 42-84 g/d of almonds, peanuts, pistachios or walnuts. While all studies reported that energy restriction resulted in significant weight loss, the addition of nuts to ER diets demonstrated significantly greater weight loss in only approximately half of the included studies (4/7 studies). There was limited evidence to support additional benefits from nuts for body composition measures or glycaemic control. Although improvements in weight loss and glycaemia were not consistent when nuts were included in ER diets, no study revealed an adverse effect of nut consumption on health outcomes. Future studies could explore the effect of consuming different types and amounts of nuts, combined with various levels of energy restriction on weight, body composition and glycaemic control.

Changes in Isoleucine, Sarcosine, and Dimethylglycine During OGTT as Risk Factors for Diabetes.

CONTEXT: Current metabolomics studies in diabetes have focused on the fasting state, while only a few have addressed the satiated state. OBJECTIVE: We combined the oral glucose tolerance test (OGTT) and metabolomics to examine metabolite-level changes in populations with different glucose tolerance statuses and to evaluate the potential risk of these changes for diabetes. METHODS: We grouped participants into those with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and newly diagnosed type 2 diabetes (NDM). During the OGTT, serum was collected at 0, 30, 60, 120, and 180 minutes. We evaluated the changes in metabolite levels during the OGTT and compared metabolic profiles among the 3 groups. The relationship between metabolite levels during the OGTT and risk of diabetes and prediabetes was analyzed using a generalized estimating equation (GEE). The regression results were adjusted for sex, body mass index, fasting insulin levels, heart rate, smoking status, and blood pressure. RESULTS: Glucose intake altered metabolic profile and induced an increase in glycolytic intermediates and a decrease in amino acids, glycerol, ketone bodies, and triglycerides. Isoleucine levels differed between the NGT and NDM groups and between the NGT and IGR groups. Changes in sarcosine levels during the OGTT in the diabetes groups were opposite to those in glycine levels. GEE analysis revealed that during OGTT, isoleucine, sarcosine, and acetic acid levels were associated with NDM risks, and isoleucine and acetate levels with IGR risks. CONCLUSION: Metabolic profiles differ after glucose induction in individuals with different glucose tolerance statuses. Changes in metabolite levels during OGTT are potential risk factors for diabetes development.

A Quantitative Systems Pharmacology Model of the Incretin Hormones GIP and GLP1, Glucagon, Glucose, Insulin, and the Small Molecule DPP-4 Inhibitor, Linagliptin.

In the current study, we established a comprehensive quantitative systems pharmacology (QSP) model using linagliptin as the model drug, where drug disposition, drug intervention on dipeptidyl peptidase-4 (DPP-4), glucose-dependent insulinotropic peptide (GIP), Glucagon-like peptide-1 (GLP-1), glucagon, glucose, and insulin are integrated together with the cross talk and feedback loops incorporated among the whole glycemic control system. In the final linagliptin QSP model, the complicated disposition of linagliptin was characterized by a 2-compartment pharmacokinetic (PK) model with an enterohepatic cycling (EHC) component as well as target-mediated drug disposition (TMDD) processes occurring in both tissues and plasma, and the inhibitory effect of linagliptin on DPP-4 was determined by the linagliptin-DPP-4 complex in the central compartment based on target occupancy principle. The integrated GIP-GLP1-glucagon-glucose-insulin system contains five indirect response models as the "skeleton" structure with 12 feedback loops incorporated within the glucose control system. Our model adequately characterized the substantial nonlinear PK of linagliptin, time course of DPP-4 inhibition, as well as the kinetics of GIP, GLP-1, glucagon, and glucose simultaneously in humans. Our model provided valuable insights on linagliptin pharmacokinetics/pharmacodynamics and complicated glucose homeostasis. Since the glucose regulation modeling framework within the QSP model is "drug-independent", our model can be easily adopted by others to evaluate the effect of other DPP-4 inhibitors on the glucose control system. In addition, our QSP model, which contains more components than other reported glucose regulation models, can potentially be used to evaluate the effect of combination antidiabetic therapy targeting different components of glucose control system.

The effect of pre-dosing with metformin on the insulin response to oral sugar in insulin-dysregulated horses.

BACKGROUND: A single dose of metformin administered 1 h prior to oral glucose challenge was previously shown to reduce insulinaemic responses in horses with experimentally-induced insulin dysregulation (ID). Targeted administration could be useful for controlling post-prandial hyperinsulinaemia in horses with naturally-occurring ID. OBJECTIVES: The objective was to compare the insulinaemic and glycaemic responses to oral sugar testing (OST) performed at different intervals after a single dose of metformin in horses with naturally-occurring ID. We hypothesised that pre-treatment with one dose of metformin would significantly decrease the insulinaemic response to OST. STUDY DESIGN: Randomised cross-over in vivo experiment. METHODS: Eight university-owned adult horses with naturally-occurring ID underwent OST 1, 2 and 6 h following a single oral dose of metformin (30 mg/kg) or 1 h after placebo (240 mL water) with a 7-day washout between treatments over a period of 3 weeks. Plasma insulin, C-peptide and glucose concentrations were measured at 0, 60 and 90 min after 0.45 mL/kg light corn syrup and the effect of treatment (and the interval since dosing) examined using a mixed effects linear regression model. RESULTS: Metformin treatment had no significant effect on plasma glucose, insulin or C-peptide concentrations at any time point compared with placebo (p > 0.05). For OST 1 h post metformin, median (IQR) plasma insulin was 91.3 (62.4-114.9) µIU/mL at 60 min versus 76.2 (59.1-134.5) for placebo (p = 0.8) and 62.7 (31.4-109.7) at 90 min versus 51.8 (29.2-126.3) for placebo (p = 0.9). MAIN LIMITATIONS: Small sample size may limit identification of more subtle decreases in insulin concentration with metformin pre-dosing. The results of this study are relevant only for one pre-treatment dose (30 mg/kg) which limits extrapolation to predictions about the effects of longer-term metformin administration on insulin and glucose dynamics in the horse. CONCLUSIONS AND CLINICAL IMPORTANCE: The results do not support the use of targeted metformin treatment to reduce post-prandial hyperinsulinaemia in horses with naturally-occurring ID.

Common risk factors for dental caries and impaired glucose regulation in Guangxi, China.

OBJECTIVES: To assess the prevalence of caries and impaired glucose regulation (IGR) and try to investigate their common risk factors among adult residents in Guangxi province. METHODS: A cross-sectional study was conducted on a sample of 2993 adults from five different areas of Guangxi province. The sociodemographic data, history of personal habits such as diet and physical activities, physical measurements, oral examination results and biochemical laboratory test data were collected to establish a database and prepare a sound research model. Chi-square test and multiple logistic regression were used to analyse the risk factors for dental caries and IGR. RESULTS: The prevalence rate for caries was 85.9%, and the mean DMFT score was 7.35. In multiple logistic regression, after adjustment, education level, occupation, daily consumption of vegetables, weekly consumption of carbonated beverages and weekly exercise were associated with caries (odds ratio [OR]: 2.10, OR: 1.80, OR: 1.40, OR: 2.45, OR: 2.38). The prevalence of IGR was 33.5%, and after adjustment, results showed that occupation, body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, high-density lipoprotein-C levels and low-density lipoprotein-C levels were significantly associated with IGR (OR: 0.80, OR: 1.70, OR: 1.56, OR: 1.88, OR: 1.60, OR: 1.43, OR: 1.48). The strength of association between caries/IGR and risk factors was a weak association or moderate association. CONCLUSIONS: We have not found common risk factors between dental caries and IGR. Therefore, further studies are needed to explore these common risk factors to prevent caries and IGR.

Chronic consumption of imbalance diets high in sucrose or fat induces abdominal obesity with different pattern of metabolic disturbances and lost in Langerhans cells population.

AIM: Obesity is a worldwide health issue, associated with development of type 2 Diabetes Mellitus. The aim of this study is to analyze the effect of consumption of two hypercaloric diets on metabolic disturbance and beta cells damage. MAIN METHODS: Male Wistar rats were subjected to twelve months consumption of three diets: a Control balanced diet (CTD, carbohydrates 58 %, proteins 29 %, lipids 13 %) and two hypercaloric diets, high in sucrose (HSD, carbohydrates 68 %, proteins 22 %, lipids 10 %) or high in fat (HFD, carbohydrates 31 %, proteins 14 %, lipids 55 %). Serum levels of glucose, triglycerides and free fatty acids were measured after zoometric parameters determination. Antioxidant enzymes activity and oxidative stress-marker were measured in pancreas tissue among histological analysis of Langerhans islets. KEY FINDINGS: Although diets were hypercaloric, the amount of food consumed by rats decreased, resulting in an equal caloric consumption. The HSD induced hypertriglyceridemia and hyperglycemia with higher levels in free fatty acids (FFA, lipotoxicity); whereas HFD did not increased neither the triglycerides nor FFA, nevertheless the loss of islets' cell was larger. Both diets induced obesity with hyperglycemia and significant reduction in Langerhans islets size. SIGNIFICANCE: Our results demonstrate that consumption of HSD induces more significant metabolic disturbances that HFD, although both generated pancreas damage; as well hypercaloric diet consumption is not indispensable to becoming obese; the chronic consumption of unbalanced diets (rich in carbohydrates or lipids) may lead to abdominal obesity with metabolic and functional disturbances, although the total amount of calories are similar.

Effect of serum 25(OH)D and immune-related factors on subclinical atherosclerosis in patients with impaired glucose regulation / 中国免疫学杂志

Objective:To explore the correlation between abnormal expression of serum 25(OH)D and immune-related fac-tors and subclinical atherosclerosis(AS)in patients with impaired glucose regulation.Methods:A total of 142 patients with im-paired glucose regulation admitted to Zaozhuang Municipal Hospital from December 2019 to April 2021 were selected.The patients with impaired glucose regulation were selected as the control group(n=86)and patients with subclinical atherosclerosis were selected as the observation group(n=56)according to carotid ultrasound examination and bramolecular pulse wave conduction velocity.The serum 25(OH)D and immune factors were compared between the two groups.Carotid ultrasound was used to measure the carotid inti-media thickness,and Pearson method was used to determine the correlation between the intimedia thickness,25(OH)D and immune factors.Baseline data and hematological indicators were collected,univariate and multivariate Logistic regression analysis was per-formed to determine the influencing factors of subclinical atherosclerosis,and ROC curve was used to evaluate the diagnostic efficacy of serum 25(OH)D and immune factors in subclinical atherosclerosis.Results:The serum 25(OH)D[(24.01±4.87)mmol/L vs(30.74±5.01)mmol/L,t=7.909,P=0.000)in the observation group was significantly lower than that of control group.TNF-α[(48.32±8.02)ng/L vs(33.21±9.00)ng/L,t=10.199,P=0.000)and IL-6[(41.22±9.43)ng/L vs(30.21±7.01)ng/L,t=7.492,P=0.000)in ob-servation group were significantly higher than those in control group.Carotid intima-media thickness was negatively correlated with se-rum 25(OH)D(r=-0.428,P<0.001),and was positively correlated with serum TNF-α and IL-6(r=0.574,0.577,P<0.001).Logis-tic regression analysis showed that serum 25(OH)D(OR=0.520,95%CI:0.401～0.675),serum TNF-α(OR=1.667,95%CI:1.131～2.457)and serum IL-6(OR=1.478,95%CI:1.213～1.802)were the influencing factors of subclinical atherosclerosis.ROC curve showed that the optimal cut-off value of serum 25(OH)D was 28.32 mmol/L,and the corresponding sensitivity,specificity and AUC were 69.64%,70.93%and 0.803(95%CI:0.749～0.855),respectively.The critical value of serum TNF-α was 40.56 ng/L,corre-sponding sensitivity was 71.43%,specificity was 72.09%,and AUC was 0.761(95%CI:0.717～0.823).Serum IL-6 cut-off value was 36.13 ng/L,corresponding sensitivity was 60.71%,specificity was 60.47%,and AUC was 0.627(95%CI:0.566～0.702).The sensitivity,specificity and AUC of regression analysis were 85.71%,81.40%and 0.889(95%CI:0.830～0.915).Conclusion:Serum 25(OH)D and immune-related factors alone and in combination can effectively predict the occurrence of subclinical atherosclerosis,which is correlated with carotid intima-media thickness,and serum 25(OH)D and immune-related factors are predictors of subclinical atherosclerosis.

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

OBJECTIVE: Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum. METHODS: The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed. RESULTS: 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y. CONCLUSIONS: 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

Glucose-sensitive hypothalamic nuclei traced through functional magnetic resonance imaging.

Introduction: Hypothalamic glucose-sensitive neural circuits, which regulate energy metabolism and can contribute to diseases such as obesity and type 2 diabetes, have been difficult to study in humans. We developed an approach to assess hypothalamic functional connectivity changes during glucose loading using functional magnetic resonance imaging (fMRI). Methods: To do so, we conducted oral glucose tolerance tests while acquiring functional images before, and 10 and 45 min after glucose ingestion in a healthy male and cross-sectionally in 20 healthy participants on two different diets. Results: At group level, 39 fMRI sessions were not sufficient to detect glucose-mediated connectivity changes. However, 10 repeated sessions in a single subject revealed significant intrinsic functional connectivity increases 45 min after glucose intake in the arcuate, paraventricular, and dorsomedial nuclei, as well as in the posterior hypothalamic area, median eminence, and mammillary bodies. Discussion: Our methodology allowed to outline glucose-sensitive hypothalamic pathways in a single human being and holds promise in delineating individual pathophysiology mechanisms in patients with dysglycemia.