Reduced Fasting Blood Glucose Research Articles

Metabolic Adaptations to Morning Versus Afternoon Training: A Systematic Review and Meta-analysis.

Some physiological responses such as circulating glucose as well as muscle performance show a circadian rhythmicity. In the present study we aimed to quantitatively synthesize the data comparing the metabolic adaptations induced by morning and afternoon training. PubMed, SCOPUS, and Web of Science databases were systematically searched for studies comparing the metabolic adaptations (> 2weeks) between morning and afternoon training. A meta-analysis was performed using random-effects models with DerSimonian-Laird methods for fasting blood glucose, hemoglobin A1c (HbAc1), homeostatic model assessment (HOMA), insulin, triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). We identified 9 studies with 11 different populations (n = 450 participants). We found that afternoon exercise was more effective at reducing circulating triglycerides [standardized mean difference (SMD) - 0.32; 95% confidence interval (CI) - 0.616 to - 0.025] than morning training. Moreover, afternoon tended to decrease fasting blood glucose (SMD - 0.24; 95% CI - 0.478 to 0.004) to a greater extent than morning training. Metabolic adaptations to exercise may be dependent on the time of day. Morning training does not show superior effects to afternoon exercise in any of the analyzed outcomes. However, afternoon training is more effective at reducing circulating triglyceride levels and perhaps at reducing fasting blood glucose than morning training. The study was preregistered at PROSPERO (CRD42021287860).

Camel milk peptides alleviate hyperglycemia by regulating gut microbiota and metabolites in type 2 diabetic mice

This study aimed to investigate the hypoglycemic effect of Camel milk peptides (CMPs) on Type 2 diabetes mellitus (T2DM) mice and reveal its related mechanism from the aspect of gut microbiota and metabolites. The administering CMPs significantly alleviated the weight loss, polydipsia and polyphagia, reduced fasting blood glucose (FBG), improved insulin resistance and sensitivity, and restored the level of serum hormones, lipopolysaccharide (LPS), lipid metabolic and tissue damage. Furthermore, CMPs intervention remarkably reversed gut microbiota dysbiosis in T2DM mice by reducing the relative abundance of Proteobacteria, Allobaculum, Clostridium, Shigella and the Firmicutes/Bacteroidetes ratio, while increasing the relative abundance of Bacteroidetes and Blautia. Metabolomic analysis identified 84 different metabolites between T2DM and CMPs-treated groups, participating in three pathways of Pantothenate and CoA biosynthesis, Phenylalanine metabolism and Linoleic acid metabolism. Ureidopropionic acid, pantothenic acid, hippuric acid, hydrocinnamic acid and linoleic acid were identified as key acidic metabolites closely related to hypoglycemic effect. Correlation analysis indicated that CMPs might have a hypoglycemic effect through their impact on gut microbiota, leading to variations in short-chain fatty acids (SCFAs), acidic metabolites and metabolic pathways. These findings suggest that CMPs could be a beneficial nutritional supplement for intervention T2DM.

Effects of aerobic exercises in prediabetes patients: a systematic review and meta-analysis.

To evaluate the effects of different durations of continuous aerobic exercise on prediabetic patients. The research encompassed randomized controlled trials that examined how various durations of aerobic exercise training affected outcomes related to Body Mass Index (BMI), Fasting blood glucose (FBG), 2-hour plasma glucose (2hPG), and glycated hemoglobin (HbA1c) in individuals diagnosed with prediabetes. PubMed, Embase, Web of Science, and the Cochrane Library were searched as of January 7, 2023. The Cochrane Risk of Bias, version 2 (ROB 2) tool was used to assess the risk of bias. A total of 10 RCTs with 815 prediabetic patients were included. The average age of the participants was 56.1 years, with a standard deviation of 5.1 years. Among the participants, 39.2% were male. The interventions consisted of aerobic dance, treadmill running, walking, and a combination of aerobic exercises. The training sessions occurred three or four times per week. In prediabetic patients, aerobic exercise demonstrated a significant reduction in BMI compared to the control group, with a weighted mean difference (WMD) of -1.44 kg/m2 (95% confidence interval [CI] -1.89, -0.98). There was a decrease in FBG levels, with WMD of -0.51 mmol/L (95% CI -0.70, -0.32). Additionally, aerobic training led to significant improvements in 2hPG levels, with a WMD of -0.76 mmol/L (95% CI -1.14, -0.38). Furthermore, prediabetic patients showed a decrease in HbA1c levels after engaging in aerobic training compared to the control group, with a WMD of -0.34% (95% CI -0.45, -0.23). In summary, engaging in aerobic exercise can have a significant positive impact on glycemic levels in individuals with prediabetes. It can also lead to reductions in BMI, FBG, 2hPG, HbA1c, and other relevant indicators. The extent of these improvements may vary slightly depending on the duration of the aerobic exercise intervention. PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023395515.

Fecal Microbiota Transplantation for Weight and Glycemic Control of Obesity as Well as the Associated Metabolic Diseases: Meta-Analysis and Comprehensive Assessment.

Objectives: An analysis of the weight and blood glucose management associated with fecal microbiota transplantation (FMT) as well as metabolic diseases associated with FMT was conducted by the authors in order to provide clinical recommendations regarding the treatment of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). Methods: We searched PubMed, Embase, and the Cochrane Library for papers that were published between the creation of the database and October 2022. We reviewed research that investigated how FMT affected weight and glycemic management in cases of obesity and metabolic conditions that are related to obesity. Studies that were published more than once, lacked the entire text, included insufficient information, or were impossible to extract data from were excluded. Additionally, case reports, reviews, and systematic reviews were excluded from the analysis. In order to analyze the data, STATA 15.1 was used. Outcomes: When we combined all of our findings, we discovered that pooled outcomes showed that weight levels (WMD equals -4.77, 95%CI: -7.40~-2.14), BMI levels (WMD equals -1.59, 95%CI: -2.21~-0.97), HOMA-IR (WMD equals -0.79, 95%CI: -1.57~-0.00), and HbA1c (WMD equals -0.65, 95%CI: -0.75~-0.55) after FMT treatment were significantly lower than before treatment. However, FMT treatment may have no effect on glucose and insulin levels in obese patients at fasting and related metabolic diseases. Additionally, subgroup analysis outcomes found that FMT significantly reduced fasting blood glucose in people with diabetes. Conclusions: As a weight loss and glycemic control therapy, FMT helps to prevent and treat metabolic problems linked to obesity, and is a viable alternative to bariatric surgery for patients who do not wish to undergo the procedure.

761-P: Effect of Orforglipron vs. Placebo and Dulaglutide on Glycemic Control and Body Weight in Patients with Type 2 Diabetes

Orforglipron [OFG (LY3502970)] is an oral, non-peptide, glucagon-like peptide-1 receptor agonist (GLP-1 RA). The 26-week, randomized, double-blind, double placebo, phase 2 study enrolled 383 patients with type 2 diabetes (T2D) treated with diet, exercise, ± metformin. At baseline, mean age was 58.9 yr, HbA1c was 8.1%, and body weight (BW) was 100.3 kg. Patients were randomly assigned to OFG 3, 12, 24, 36, or 45 mg once daily, placebo (PBO), or dulaglutide 1.5 mg (dula). Protocols guided the initial OFG dose and escalation schemes. Primary endpoint was HbA1c change from baseline (CFB) at wk 26 for OFG vs PBO. Secondary endpoints included CFB at wk 26 in HbA1c for OFG vs dula, and CFB in fasting blood glucose (FBG) and body weight (BW) for OFG vs PBO and dula. OFG resulted in improvements in glycemic control and BW (table). At wk 26, HbA1c reduction with OFG ranged from 1.19 to 2.10% vs PBO 0.43% (P<0.001, all doses vs PBO). Significantly greater reductions in HbA1c were also noted with 12, 24, 36, and 45 mg OFG vs dula (p<0.001). Most adverse events (AE) were gastrointestinal (nausea: PBO 5.5%, OFG 30.6%, dula 18.0%) and mild or moderate in severity. OFG resulted in significant reductions in HbA1c, FBG, and BW with an AE profile consistent with other GLP-1RAs. OFG does not have food or water administration restrictions and may provide a safe, effective, and convenient oral treatment option for patients with T2D. Disclosure J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. D.A.Robins: None. S.H.Hsia: Research Support; Eli Lilly and Company. S.Eyde: None. R.Liu: None. X.Ma: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.Konig: None. C.M.Kazda: Employee; Eli Lilly and Company. E.J.Pratt: Employee; Eli Lilly and Company. K.J.Mather: Employee; Eli Lilly and Company.

1793-PUB: Effects of Nonnutritive Sweeteners on Glycemic Indices in Healthy Persons, with Overweight or Obesity, or Diabetes—A Systematic Review and Meta-analysis of Randomized Controlled Trials

Evidence on nonnutritive sweeteners (NNS) and glycemia is controversial due to possible mechanisms promoting glucose intolerance. No study had systematically assessed variations in glycemic outcomes based on NNS type and dose, length of exposure, and nature of the comparator in trials evaluating subjects undergoing different clinical conditions. We conducted a systematic review and meta-analysis summarizing trials contrasting NNS consumers vs. non-consumers to assess the effect on eight glycemic indices. In participants without any major disease at baseline, NNS intake significantly increased fasting blood glucose (FBG). FBG and fasting insulin (FI) were higher among NNS consumers with hyperglycemia, those who followed for > 8wk, consumers of ≤ 350 mg/d, and participants receiving sucralose. Sucralose also increased 2h-glucose and 2h-insulin but reduced HbA1c. Aspartame increased HbA1c. Participants with obesity consuming NNS displayed significantly less FBG, FI, and HOMA. Results were consistent when clustering those with controlled baseline glycemia, subjects followed for ≤ 8wk, consumers of > 350 mg/d, and those replacing sugar with NNS. NNS consumers with baseline hyperglycemia exhibited less FI and HOMA. Participants consuming ≤ 350 mg/d displayed reductions in FBG and HOMA. Trials evaluating stevia consumers reported less FBG and FI levels. We found no overall effect on persons with diabetes. Subgroup assessments revealed that persons with diabetes with uncontrolled glycemia at baseline or who were followed for > 10wk displayed higher FI. In summary, the effect of NNS in glycemia varies across indices and between persons with inequivalent clinical conditions. Higher doses of NNS or longer interventions do not necessarily improve glycemic indices. Better-designed trials evaluating glycemic metabolism are needed to elucidate if NNS can be used as an alternative to sugar. Disclosure S.Golzan: None. A.Espinosa: None. M.Abbasi: None. M.Movahedian: None. M.Fathi: None. A.Hekmatdoost: None.

Effects of therapeutic lifestyle change diets on blood lipids, lipoproteins, glycemic parameters, and blood pressure: a systematic review and meta-analysis of clinical trials.

Cardiovascular disease is the leading cause of death worldwide. Low-calorie, low-fat therapeutic diets (TDs) developed by the US National Cholesterol Education Program, ie, the Step I and II diets and the therapeutic lifestyle changes diet, are approximately similar and are the initial therapeutic interventional approaches for lifestyle modification. This systematic review with meta-analysis was undertaken to evaluate the effects of TDs diet on blood lipids, apolipoprotein A-1, apolipoprotein B, blood pressure, fasting blood glucose, and insulin. A comprehensive search of the PubMed/MEDLINE, Web of Science, Scopus, and Google Scholar databases until October 2022 was performed to identify clinical trials investigating the effects of TDs on the aforementioned parameters. One investigator screened the records and extracted data, and another reviewed the extracted data. A total of 910 records were retrieved. After records were screened for eligibility, 34 clinical trials met the inclusion criteria. The pooled analysis from the random-effects model revealed a significant reduction in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A-1, and apolipoprotein B in the TD intervention group vs the control group. The overall effects of TDs on fasting blood glucose, insulin, and blood pressure were not significant, but the results of subgroup analysis revealed a significant reduction in fasting blood glucose with the Step II diet and an intervention duration of more than 24 weeks. For blood pressure, the Step I diet and an intervention duration of more than 24 weeks resulted in significant reduction. There was no evidence of publication bias, but strong heterogeneity was observed. Therapeutic diets have promising effects on lipid profile parameters, glycemic indexes, and blood pressure, which can promote cardiovascular health. PROSPERO registration no. CRD42021259355.

Low glycaemic index or low glycaemic load diets for people with overweight or obesity.

Low glycaemic index or low glycaemic load diets for people with overweight or obesity.

Pyridylnidulin exerts anti-diabetic properties and improves non-alcoholic fatty liver disease in diet-induced obesity mice.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disorders related to the pathophysiology of type 2 diabetes mellitus (T2DM). Therapeutic strategies are focused on the improvement of energy balance and lifestyle modification. Additionally, the derivative of the bioactive fungal metabolite is of interest to provide health benefits, especially in obese and pre-diabetic conditions. In our screening of anti-diabetic compounds from fungal metabolites and semisynthetic derivatives, a depsidone derivative, namely pyridylnidulin (PN), showed potent glucose uptake-inducing activity. The present study aimed to investigate the liver lipid metabolism and anti-diabetic properties of PN in diet-induced obesity mice. Methods: Male C57BL/6 mice were induced obesity and pre-diabetic conditions by dietary intervention with a high-fat diet (HFD) for 6 weeks. These obese mice were orally administered with PN (40 or 120 mg/kg), metformin (150 mg/kg), or vehicle for 4 weeks. Glucose tolerance, plasma adipocytokines, hepatic gene and protein expressions were assessed after treatment. Results: Improved glucose tolerance and reduced fasting blood glucose levels were found in the PN and metformin-treated mice. Additionally, hepatic triglyceride levels were consistent with the histopathological steatosis score regarding hepatocellular hypertrophy in the PN and metformin groups. The levels of plasma adipocytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were reduced in the PN (120 mg/kg) and metformin-treated mice. In addition, hepatic gene expression involved in lipid metabolism, including lipogenic enzymes was significantly reduced in the PN (120 mg/kg) and metformin-treated mice. The increased protein expression levels of phosphorylated AMP-activated protein kinase (p-AMPK) was also found in PN and metformin-treated mice. Discussion: Considering the increased p-AMPK protein expression levels in PN and metformin-treated mice were revealed as the underlying mechanisms to improve metabolic parameters. These results suggested that PN provided the health benefit to slow the progression of NAFLD and T2DM in obese and pre-diabetic conditions.

347-OR: Methionine Restriction Differentially Protects against High-Fat Diet-Induced Neuroinflammation and Central Insulin Resistance in Male and Female Mice

High-fat diets (HFD) promote central inflammation and insulin resistance (IR). Methionine restriction (MR) improves peripheral insulin sensitivity, lipid metabolism, and cognitive function, at least in part by increasing fibroblast growth factor 21 (FGF21). However, the ability of MR to protect against neuroinflammation and central IR during adolescence has not been examined. Moreover, whether MR depends on FGF21 to protect against HFD-induced changes in central insulin signaling or neuroinflammation is unknown. We sought to determine whether MR protects against HFD-induced neuroinflammation and central IR during adolescence in males and females and whether MR’s effects are dependent on FGF21. Male and female wild-type (WT) and FGF21 knockout (KO) mice, aged 5 to 6 wk, were fed normal (18.9% fat-derived kcal) or high-fat (60% fat-derived kcal) versions of control (0.86% methionine) or MR (0.17% methionine) diets for 5 wk. To investigate insulin action, ITTs were performed after 4 wk on the diet, and saline or insulin (0.6U/kg body weight) was administered 15 min prior to sacrifice. MR significantly decreased weight gain of HFD-fed mice regardless of sex or genotype (p < 0.05). MR increased serum FGF21 of all males and HFD-fed females (p < 0.05), and strongly tended to increase FGF21 in female mice on the normal-fat diet. HFD feeding tended to promote inflammatory gene expression in the hippocampus of WT males, while MR trended to mitigate inflammation independent of FGF21. MR also significantly reduced fasting blood glucose and improved peripheral insulin response in an FGF21-dependent fashion (p < 0.05). Though, neither HFD nor MR had a notable impact on markers of IR in the hypothalamus or hippocampus. Our findings indicate that short-term MR improves metabolic parameters of adolescent mice fed normal or high-fat diets. In addition, MR acts in an FGF21-independent and sex-dependent manner to improve neuroinflammation. Disclosure H.L.Lail: None. R.Lawrence: None. D.Wanders: None.

Hydrogen-Rich Water Ameliorates Metabolic Disorder via Modifying Gut Microbiota in Impaired Fasting Glucose Patients: A Randomized Controlled Study.

Molecular hydrogen (H2) exhibits antioxidant, anti-inflammatory and anti-apoptotic effects, and has shown benefits in glucose and lipid metabolism in certain animal metabolic disorder models. However, the potential benefits of H2 treatment in individuals with impaired fasting glucose (IFG) has seldom been studied. This randomized controlled study (RCT) aims to investigate the effects of hydrogen-rich water (HRW) on IFG subjects and explore the underlying mechanism involved. Seventy-three patients with IFG were enrolled in a randomized, double-blind, placebo-controlled clinical study. These patients were assigned to receive either 1000 mL per day of HRW or placebo pure water (no H2 infusion) for a duration of eight weeks. Metabolic parameters and fecal gut microbiota were assessed at baseline (week 0) and at week 8. A combined analysis of metabolomics and intestinal microbiota was conducted to investigate the correlation between the effect of H2 on the metabolisms and the diversity of intestinal flora in the IGF patients. Both pure water and HRW demonstrated a significant reduction in fasting blood glucose in IFG patients, with a significant difference between pure water and HRW after eight weeks. Among IFG patients with abnormal pre-experimental fatty liver, 62.5% (10/16) in the HRW group and 31.6% (6/19) in the pure water group achieved remission. Furthermore, 16S RNA analysis revealed HRW-modified gut microbiota dysbiosis in the fecal samples of IGF patients. Through Pearson correlation analysis, the differential gut microbiota obtained by 16S analysis was found to be highly correlated with nine metabolites. H2 slightly improved metabolic abnormalities and gut microbiota dysbiosis, providing a novel target and theoretical basis for the prevention and treatment of blood glucose regulation in patients with IFG.

Whole Grain Proso Millet (Panicum miliaceum L.) Attenuates Hyperglycemia in Type 2 Diabetic Mice: Involvement of miRNA Profile.

This work aimed to investigate the hypoglycemic effects and underlying mechanism of whole grain proso millet (Panicum miliaceum L.; WPM) on type 2 diabetes mellitus (T2DM). The results showed that WPM supplementation significantly reduced fasting blood glucose (FBG) and serum lipid levels in T2DM mice induced by a high-fat diet (HFD) combined with streptozotocin (STZ), with improved glucose tolerance, liver and kidney injury, and insulin resistance. In addition, WPM significantly inhibited the expression of gluconeogenesis-related genes G6pase, Pepck, Foxo1, and Pgc-1α. Further study by miRNA high-throughput sequencing revealed that WPM supplementation mainly altered the liver miRNA expression profile of T2DM mice by increasing the expression of miR-144-3p_R-1 and miR-423-5p, reducing the expression of miR-22-5p_R-1 and miR-30a-3p. GO and KEGG analyses showed that the target genes of these miRNAs were mainly enriched in the PI3K/AKT signaling pathway. WPM supplementation significantly increased the level of PI3K, p-AKT, and GSK3β in the liver of T2DM mice. Taken together, WPM exerts antidiabetic effects by improving the miRNA profile and activating the PI3K/AKT signaling pathway to inhibit gluconeogenesis. This study implies that PM can act as a dietary supplement to attenuate T2DM.

Hypoglycemic Potential of African Medicinal Plants in Diabetic and Non-Diabetic Human Subjects: A Review

Africa is blessed with several plants and marine organisms used to treat various diseases including diabetes. The folkloric use of some of these plants in treating diabetes has been documented in various databases and publications, and validated using various diabetes models. However, most of the investigations on African medicinal plants as antidiabetic agents are not taken beyond proof-of-concept stage. Besides, limited number of clinical trials were conducted to validate the efficacy in humans and the few available clinical studies have not been critically reviewed. Therefore, this review is intended to document the antidiabetic potential of African medicinal plants investigated in human subjects as well their safety implications. Relevant articles were harvested from the major scientific databases (Scopus, PubMed, and Google Scholar). According to the present search, eighteen (18) African medicinal plants and one herbal formulation were the only plants investigated for antidiabetic activity in humans. The plants showed no noticeable toxicity throughout the study period. Interestingly, all the 18 plant species were traditionally used to treat diabetes in various parts of Africa. Despite variations in the study period and dosages used, Laportea ovalifolia (Schumach. & Thonn.) Chew. (Urticaceae) and Momordica charantia L. (Cucurbitaceae) were the most effective as they reduced fasting blood glucose by >50% after 10 days and 4 weeks treatment periods, respectively. The available information revealed that African medicinal plants especially L. ovalifolia and M. charantia should be subjected to phase III clinical trial, aimed at getting the natural product-based antidiabetic drugs from Africa.

Ethanol extract of propolis regulates type 2 diabetes in mice via metabolism and gut microbiota.

Propolis is a traditional natural medicine with various activities such as antioxidant and anti-inflammatory, immunomodulatory, anti-tumour, gastroenteritis treatment and prevention, anti-microbial and parasitic, as well as glucose regulation and anti-diabetes, and is expected to be an anti-diabetic candidate with few side effects, but the mechanism of action of propolis on type 2 diabetes mellitus (T2DM) has not been fully elucidated. The purpose of this study was to investigate the mechanism of the effect of ethanol extract of propolis (EEP) on the regulation of blood glucose in T2DM mice. We studied the possible mechanism of EEP on T2DM using an animal model of T2DM induced by a combination of a high-fat diet and intraperitoneal injection of streptozotocin (STZ). The experiment was divided into four groups, namely, the normal group (HC), model group (T2DM), EEP and metformin group (MET). Biochemical indexes and cytokines were measured, and the differences of metabolites in the serum were compared by 1H-NMR. In addition, the diversity of intestinal flora in feces was studied by 16S rDNA amplicon sequencing. The results showed that following treatment with EEP and MET, the weight-loss trend of mice was alleviated, and the fasting blood glucose, insulin secretion level, insulin resistance index, C peptide level and oral glucose tolerance level decreased, whereas the insulin sensitivity index increased, thereby EEP effectively alleviated the occurrence of T2DM and insulin resistance. Compared with the T2DM group, the concentrations of pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) decreased significantly in EEP and MET groups, whereas the concentrations of anti-inflammatory cytokine interleukin-10 (IL-10) increased significantly. Metabolomics results revealed that EEP and MET regulate carbohydrate metabolism and restore amino acid and lipid metabolism. Correlation analysis of intestinal flora in mouse feces showed that compared with the HC group, harmful bacteria such as Bilophila, Eubacterium_ventriosum_group, Mucispirillum and Desulfovibrio were found in the T2DM group, whereas the abundance of beneficial bacteria such as Lactobacillus was significantly reduced. Parabacteroides, Akkermansia, Leuconostoc, and Alloprevotella were abundantly present in the EEP group; however, the MET group showed an increase in the genus Parasutterella, which could regulate energy metabolism and insulin sensitivity. The results showed that EEP and MET reduce fasting blood glucose in T2DM mice, followed by alleviating insulin resistance, improving the inflammatory reaction of mice, regulating the metabolism of mice, and affecting the steady state of gut microbiota. However, the overall therapeutic effect of EEP is better than that of MET.

Dual amylin and calcitonin receptor agonist treatment improves insulin sensitivity and increases muscle-specific glucose uptake independent of weight loss

Dual amylin and calcitonin receptor agonists (DACRAs) are known to induce significant weight loss as well as improve glucose tolerance, glucose control, and insulin action in rats. However, to what extent DACRAs affect insulin sensitivity beyond that induced by weight loss and if DACRAs affect glucose turnover including tissue-specific glucose uptake is still unknown. Hyperinsulinemic glucose clamp studies were carried out in pre-diabetic ZDSD and diabetic ZDF rats treated with either the DACRA KBP or the long-acting DACRA KBP-A for 12 days. The glucose rate of disappearance was assessed using 3-3H glucose and tissue-specific glucose uptake was evaluated using 14C-2-deoxy-D-glucose (14C-2DG). In diabetic ZDF rats, KBP treatment significantly reduced fasting blood glucose and improved insulin sensitivity independent of weight loss. Furthermore, KBP increased the rate of glucose clearance, likely by increasing glucose storage, but without altering the endogenous glucose production. This was confirmed in pre-diabetic ZDSD rats. Direct assessment of tissue-specific glucose uptake showed, that both KBP and KBP-A significantly increased glucose uptake in muscles. In summary, KBP treatment significantly improved insulin sensitivity in diabetic rats and markedly increased glucose uptake in muscles. Importantly, in addition to their well-established weight loss potential, the KBPs have an insulin-sensitizing effect independent of weight loss, highlighting DACRAs as promising agents for the treatment of type 2 diabetes and obesity.

Vitamin D supplementation alleviates insulin resistance in prediabetic rats by modifying IRS-1 and PPARγ/NF-κB expressions.

Prediabetes is a condition of intermediate hyperglycemia that may progress to type 2 diabetes. Vitamin D deficiency has been frequently linked to insulin resistance and diabetes. The study aimed to investigate the role of D supplementation and its possible mechanism of action on insulin resistance in prediabetic rats. The study was conducted on 24 male Wistar rats that were randomly divided into 6 rats as healthy controls and 18 prediabetic rats. Prediabetic rats were induced with a high-fat and high-glucose diet (HFD-G) combined with a low dose of streptozotocin. Rats with the prediabetic condition were then randomized into three groups of 12-week treatment: one group that received no treatment, one that received vitamin D3 at 100 IU/kg BW, and one group that received vitamin D3 at 1000 IU/kg BW. The high-fat and high-glucose diets were continuously given throughout the twelve weeks of treatment. At the end of the supplementation period, glucose control parameters, inflammatory markers, and the expressions of IRS1, PPARγ, NF-κB, and IRS1 were measured. Vitamin D3 dose-dependently improves glucose control parameters, as shown by the reduction of fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated albumin, insulin levels, and markers of insulin resistance (HOMA-IR). Upon histological analysis, vitamin D supplementation resulted in a reduction of the islet of Langerhans degeneration. Vitamin D also enhanced the ratio of IL-6/IL-10, reduced IRS1 phosphorylation at Ser307, increased expression of PPAR gamma, and reduced phosphorylation of NF-KB p65 at Ser536. Vitamin D supplementation reduces insulin resistance in prediabetic rats. The reduction might be due to the effects of vitamin D on IRS, PPARγ, and NF-κB expression.

3-Hydroxybutyrate ameliorates insulin resistance by inhibiting PPARγ Ser273 phosphorylation in type 2 diabetic mice

3-Hydroxybutyrate (3HB) is a small ketone body molecule produced endogenously by the body in the liver. Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic (T2D) patients. However, there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of 3HB. Here we demonstrate that 3HB reduces fasting blood glucose level, improves glucose tolerance, and ameliorates insulin resistance in type 2 diabetic mice through hydroxycarboxylic acid receptor 2 (HCAR2). Mechanistically, 3HB increases intracellular calcium ion (Ca2+) levels by activating HCAR2, thereby stimulating adenylate cyclase (AC) to increase cyclic adenosine monophosphate (cAMP) concentration, and then activating protein kinase A (PKA). Activated PKA inhibits Raf1 proto-oncogene serine/threonine-protein kinase (Raf1) activity, resulting in a decrease in extracellular signal-regulated kinases 1/2 (ERK1/2) activity and ultimately inhibiting peroxisome proliferator-activated receptor γ (PPARγ) Ser273 phosphorylation in adipocytes. Inhibition of PPARγ Ser273 phosphorylation by 3HB altered the expression of PPARγ regulated genes and reduced insulin resistance. Collectively, 3HB ameliorates insulin resistance in type 2 diabetic mice through a pathway of HCAR2/Ca2+/cAMP/PKA/Raf1/ERK1/2/PPARγ.

Effects of Sleeve Gastrectomy on Patients with Obesity and Polycystic Ovary Syndrome: a Meta-analysis.

This study aimed to evaluate the efficacy of sleeve gastrectomy (SG) on patients with obesity and polycystic ovary syndrome (PCOS). We searched PubMed, Embase, Cochrane Library, and Web of Science to identify relevant studies published prior to December 2, 2022. Meta-analysis was performed on menstrual irregularity, total testosterone, sex hormone-binding globulin (SHBG), anti-Mullerian hormone (AMH), glucolipid metabolism indicators, and body mass index (BMI) following SG. Six studies and 218 patients were included in the meta-analysis. Following SG, menstrual irregularity significantly decreased (odds ratio [OR] 0.03; 95% confidence intervals [CIs], 0.00-0.24; P=0.001). Additionally, SG can lower total testosterone levels (MD -0.73; 95% CIs -0.86-0.60; P< 0.0001), as well as BMI (MD -11.59; 95% CIs -13.10-10.08; P<0.0001). A significant increase was observed in the levels of SHBG and high-density lipoprotein (HDL) after SG. In addition to reducing fasting blood glucose, insulin, triglycerides (TG), and low-density lipoprotein levels, SG significantly reduced low-density lipoprotein levels as well. Following SG, we firstly demonstrated significant improvements in menstrual irregularity, testosterone and SHGB levels, glycolipid metabolism indicators, and BMI. Therefore, SG may be considered as a new option for the clinical treatment of patients with obesity and PCOS.

Evaluation of Antidiabetic Effect of Combined Leaf and Seed Extracts of Moringa oleifera (Moringaceae) on Alloxan-Induced Diabetes in Mice: A Biochemical and Histological Study.

Moringa oleifera (Moringaceae) is a medicinal plant rich in biologically active compounds. The aim of the present study was to screen M. oleifera methanolic leaf (L) extract, seed (S) extract, and a combined leaf/seed extract (2L : 1S ratio) for antidiabetic and antioxidant activities in mice following administration at a dose level of 500 mg/kg of body weight/day. Diabetes was induced by alloxan administration. Mice were treated with the extracts for 1 and 3 months and compared with the appropriate control. At the end of the study period, the mice were euthanized and pancreas, liver, kidney, and blood samples were collected for the analysis of biochemical parameters and histopathology. The oral administration of the combined L/S extract significantly reduced fasting blood glucose to normal levels compared with L or S extracts individually; moreover, a significant decrease in cholesterol, triglycerides, creatinine, liver enzymes, and oxidant markers was observed, with a concomitant increase in antioxidant biomarkers. Thus, the combined extract has stronger antihyperlipidemic and antioxidant properties than the individual extracts. The histopathological results also support the biochemical parameters, showing recovery of the pancreas, liver, and kidney tissue. The effects of the combined L/S extracts persisted throughout the study period tested. To the best of our knowledge, this is the first study to report on the antidiabetic, antioxidant, and antihyperlipidemic effects of a combined L/S extract of M. oleifera in an alloxan-induced diabetic model in mice. Our results suggest the potential for developing a natural potent antidiabetic drug from M. oleifera; however, clinical studies are required.

In-vivo hepatoprotective and hypoglycemic effects of methanolic extract of Schumannianthus dichotomus rhizome

BackgroundRhizome of Schumannianthus dichotomus is used in folklore medicine for many years. This study aimed to investigate the hepatoprotective and hypoglycemic activities of the methanolic extract of Schumannianthus dichotomus rhizome. MethodsIn hepatoprotective assay, mice were treated for seven days with extract at a doses of 100, 200 and 400 mg/kg and the standard drug silymarin (100 mg/kg). Thereafter 8 ml/kg of 2% v/v CCl4 was administered on the 5th day to induce acute liver injury. Blood samples were obtained and serum enzymes ALP, AST and ALT were assayed and total protein and total bilirubin levels were also assessed. The hypoglycemic effect was evaluated in the mice model. Fasting blood glucose levels were measured and immediately extracts were administered (100, 200 and 400 mg/kg). Glibenclamide was used as standard. After one-hour dextrose was administered and glucose levels were measured after one hour, two hour and three hours. ResultsIn the hepatoprotective assay, the extract markedly reduced ALP, AST, ALT and bilirubin levels and increased total protein levels in the CCl4-treated mice groups as compared with the standard group. In the hypoglycemic test, the standard drug glibenclamide reduced fasting blood glucose concentration by 57.43% after 3 h while the extract at 400 mg/kg showed 39.84% reduction after the same time span. ConclusionFrom the above results, it can be concluded that the plant extract is capable of managing CCl4-induced hepatotoxicity and dextrose-induced hyperglycemia.