Probiotics and synbiotics for glycemic control in diabetes: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: The escalating prevalence of diabetes mellitus may benefit from add-on therapeutic approaches. Given the recognized need for an updated synthesis of the literature, this systematic review and meta-analysis aimed to synthesize and critically assess the available randomized controlled trials (RCTs) that investigate the efficacy of probiotics and synbiotics on glycemic control in patients with Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus. METHODS: Comprehensive searches were conducted on PubMed, Embase, CINAHL, Scopus, and Web of Science, focusing on adults with T1DM or T2DM. All comparators were deemed eligible. Primary outcomes included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and insulin levels. Only RCTs were included, and the Cochrane RoB2 tool assessed the risk of bias. Random-effect models facilitated data analysis, supplemented by sensitivity, subgroup analyses, and meta-regressions. RESULTS: A total of 537 records were screened, resulting in 41 RCTs for analysis, which comprises 2991 (54% females) patients with diabetes. The meta-analysis revealed statistically significant improvements in HbA1c (standardized mean difference (SMD) = -0.282, 95% CI: [-0.37, -0.19], p < 0.001), FPG (SMD = -0.175, 95% CI: [-0.26, -0.09], p < 0.001), and insulin levels (SMD = -0.273, 95% CI: [-0.35, -0.20], p < 0.001). A medium degree of heterogeneity between studies was found in HbA1c (I2 = 62.5%), FPG (I2 = 71.5%), and insulin levels (I2 = 66.4%) analyses. Subgroup analyses indicated that the efficacy varied based on the type of strains used and the country. Multispecies strains were particularly effective in improving HbA1c levels. CONCLUSION: The study findings suggest that probiotics and synbiotics may be effective as complementary therapies for managing diabetes. Additionally, the study underscores the need for further tailored research that considers variables such as strain types and geographical factors to deepen the understanding of the role of these interventions in diabetes care. REVIEW REGISTRATION NUMBER: PROSPERO (CRD42023396348).

Probiotic co-supplementation with absorbent smectite for pancreatic beta-cell function in type 2 diabetes: a secondary-data analysis of a randomized double-blind controlled trials.

Introduction: There is growing evidence from animal and clinical studies suggesting probiotics can positively affect type 2 diabetes (T2D). In a previous randomized clinical study, we found that administering a live multistrain probiotic and absorbent smectite once a day for eight weeks to patients with T2D could reduce chronic systemic inflammatory state, insulin resistance, waist circumference and improve the glycemic profile. However, there is a lack of evidence supporting the efficacy of probiotic co-supplementation with absorbent smectite on pancreatic ß-cell function in T2D. Aim: This secondary analysis aimed to assess the effectiveness of an alive multistrain probiotic co-supplementation with absorbent smectite vs placebo on ß-cell function in T2D patients. Material and methods: We performed a secondary analysis on a previously published randomized controlled trial (NCT04293731, NCT03614039) involving 46 patients with T2D. The main inclusion criteria were the presence of ß-cell dysfunction (%B<60%) and insulin therapy alone or combined with oral anti-diabetic drugs. The primary outcome was assessing ß-cell function as change C-peptide and %B. Results: We observed only a tendency for improving ß-cell function (44.22 ± 12.80 vs 55.69 ± 25.75; р=0.094). The effectiveness of the therapy probiotic-smectite group was confirmed by fasting glycemia decreased by 14% (p=0.019), HbA1c - 5% (p=0.007), HOMA-2 - 17% (p=0.003) and increase of insulin sensitivity by 23% (p=0.005). Analysis of the cytokine profile showed that statistical differences after treatment were in the concentration of both pro-inflammatory cytokines: IL-1ß (22.83 ± 9.04 vs 19.03 ± 5.57; p=0.045) and TNF-α (31.25 ± 11.32 vs 26.23 ± 10.13; p=0.041). Conclusion: Adding a live multistrain probiotic and absorbent smectite supplement slightly improved ß-cell function and reduced glycemic-related parameters in patients with T2D. This suggests that adjusting the gut microbiota could be a promising treatment for diabetes and warrants further investigation through more extensive studies.

The Efficacy and Safety of Astragalus as an Adjuvant Treatment for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis evaluated the beneficial and potential adverse effects of Astragalus in the treatment of patients with type 2 diabetes mellitus (T2DM). Methods: The authors searched for randomized controlled trials of Astragalus treatment for patients with T2DM in the following databases: PubMed, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Wanfang Data, China Science and Technology Journal Database (CQVIP), and SinoMed. Two reviewers conducted independent selection of studies, data extraction, and coding, as well as the assessment of risk of bias in the studies included. Standard meta-analysis and, if appropriate, meta-regression were performed using the STATA, v.15.1, software. Results: This meta-analysis encompasses 20 studies and a total of 953 participants. Compared to the control group (CG), the observation group (OG) decreased fasting plasma glucose (FPG) (WMD = -0.67, 95% CI: -1.13∼-0.20, P = 0.005), 2 hours postprandial plasma glucose (2hPG) (WMD = -0.67 (95% CI: -1.13∼-0.20, P=0.005), glycated hemoglobin A1C (HbA1c) (WMD = -0.93, 95% CI: -1.22∼-0.64, P = 0.000), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD = -0.45, 95% CI: -0.99∼0.99, P = 0.104), insulin sensitive index (WMD = 0.42, 95% CI: 0.13-0.72, P = 0.004). The total effective ratio of the OG is more effective than CG (RR = 1.33, 95% CI: 1.26-1.40, P = 0.000), the significant effective ratio (RR = 1.69, 95% CI: 1.48-1.93, P = 0.000). Conclusions: Astragalus may provide specific benefits for T2DM patients as an adjuvant treatment. Nonetheless, the certainty of the evidence and risk of bias fell short of optimal performance, indicating the need for additional clinical research to ascertain potential effects. PROSPERO REGISTRATION NUMBER CRD42022338491.

Preanalytical impact on the accuracy of measurements of glucagon, GLP-1 and GIP in clinical trials.

BACKGROUND: Plasma concentrations of glucagon, GLP-1 and GIP are reported in numerous clinical trials as outcome measures but preanalytical guidelines are lacking. We addressed the impact of commonly used blood containers in metabolic research on measurements of glucagon, GLP-1 and GIP in humans. METHODS: Seventeen overweight individuals were subjected to an overnight fast followed by an intravenous infusion of amino acids to stimulate hormonal secretion. Blood was sampled into five containers: EDTA-coated tubes supplemented with DMSO (control), a neprilysin inhibitor, aprotinin (a kallikrein inhibitor) or a DPP-4 inhibitor, and P800 tubes. Plasma was kept on ice before and after centrifugation and stored at -80 Celsius until batch analysis using validated sandwich ELISAs or radioimmunoassays (RIA). RESULTS: Measures of fasting plasma glucagon did not depend on sampling containers, whether measured by ELISA or RIA. Amino acid-induced hyperglucagonemia was numerically higher when blood was collected into P800 tubes or tubes with aprotinin. The use of p800 tubes resulted in higher concentrations of GLP-1 by RIA compared to control tubes but not for measurements with sandwich ELISA. Plasma concentrations of GIP measured by ELISA were higher in control tubes and negatively affected by P800 and the addition of aprotinin. CONCLUSIONS: The choice of blood containers impacts on measurements of plasma concentrations of glucagon, GLP-1 and GIP, and based on this study, we recommend using EDTA-coated tubes without protease inhibitors or P800 tubes for measurements of glucagon, GLP-1 and GIP in clinical trials.

Effect of coadministration of omega-3 fatty acids with glimepiride on glycemic control, lipid profile, irisin, and sirtuin-1 in type 2 diabetes mellitus patients: a randomized controlled trial.

BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is caused by insulin resistance or tissue insensitivity to insulin, as well as relative insulin insufficiency. Diabetes that is uncontrolled for an extended period of time is linked to substantial comorbidities and organ damage. The purpose of the current study is to assess the effect of coadministration of omega-3 fatty acids with glimepiride on blood glucose, lipid profile, serum irisin, and sirtuin-1 levels in T2DM patients. METHODS: This clinical trial involved 70 type 2 diabetic patients randomly assigned to glimepiride 3 mg with either omega-3 capsules contained fish oil 1000 mg, 13% of eicosapentaenoic acid (EPA) and 9% docosahexaenoic acid (DHA) (omega-3 group, n = 35) or placebo capsules contained corn oil and linoleic acid (control group, n = 35) daily for three months. Blood samples were obtained at the start of the study and 12 weeks later for biochemical examination of HbA1c%, FBG, fasting insulin, and lipid profile. In addition, the atherogenic index of plasma (AIP) was calculated. Human enzyme-linked immunosorbent assay (ELISA) kits were utilized for assessing serum irisin and sirtuin-1 levels before and after the intervention. RESULTS: Compared to the control group, omega-3 fatty acids decreased serum fasting blood glucose (FBG, p < 0.001), glycated hemoglobin percent (HbA1C%, p < 0.001), total cholesterol (TC, p < 0.001), triglycerides (TGs, p = 0.006), low density lipoprotein (LDL, p = 0.089), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR, p = 0.021) after three months of intervention. However, a significant increase was reported in serum irisin and high density lipoprotein (HDL) between both groups after intervention (p = 0.026 and p = 0.007, respectively). The atherogenic index of plasma (AIP) increased in the control group but decreased in the omega-3 group, with significant differences between the two groups (p < 0.001). CONCLUSION: The present study found that supplementing with omega-3 fatty acids might dramatically enhance blood irisin levels, as well as improve glycemic control and lipid profile in type 2 diabetes mellitus patients using glimepiride. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov under identifier NCT03917940 . (The registration date: April 17, 2019).

The effect of vitamin D supplementation on some metabolic parameters in patients with nonalcoholic fatty liver disease: A systematic review and meta-analysis of 8 RCTs.

BACKGROUND: To systematically evaluate the effects of vitamin D supplementation in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: National Library of Medicine, Cochrane Library, Elsevier, China National Knowledge Infrastructure, Web of Science, WANFANG databases, and Google Scholar were retrieved to collect relevant randomized controlled trials, which are published from the earliest records the time the database was created to April 2023. Meta-analysis was conducted by using Review Manager 5.4 software after evaluating in terms of inclusion and exclusion criteria. The outcome indicators include 25-hydroxyvitamin D [25(OH)D] levels, insulin resistance index (homeostasis model assessment of insulin resistance), fasting blood glucose, and fasting insulin levels (FINS). RESULTS: Eight randomized controlled trials with a total of 657 patients are included. Vitamin D supplementation increased 25(OH)D levels significantly (mean difference [MD] = 2.01, 95% confidence intervals [CI]: 0.94 to 3.08, P < .05) and vitamin D supplementation had a significant effect on insulin resistance index (MD = -0.54, 95% CI: -1.28 to 0.20, P = .16), fasting glucose (MD = -0.59, 95% CI: -1.50 to 0.32, P = .20), and FINS levels (MD = -0.30, 95% CI: -0.77 to 0.17, P = .21) had no significant effect. CONCLUSION: Vitamin D supplementation improves 25(OH)D levels in patients with nonalcoholic fatty liver disease, but there is no effect on homeostasis model assessment of insulin resistance, fasting blood glucose, or FINS.

The effects of purslane (Portulaca oleracea) on glycemic indices: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Although several studies have revealed the benefits of purslane on glycemic indices, the results of some studies reject such effect. Therefore, aim of this meta-analysis of randomized controlled trials (RCTs) was to assess the effects of purslane supplementation on glycemic indices. Scientific international databases as Scopus, Web of Sciences, PubMed, Embase, and the Cochrane library were searched up to December 2022. For net changes in glycemic indices, weighted mean differences (WMDs) were calculated using random-effects models. Purslane supplementation had a statistically significant reduction in fasting blood glucose [FBG, WMD: -6.37; 95% CI: -9.34, -3.40, p < 0.001]. In addition, purslane did not significant effect on serum levels of insulin [WMD: -0.74; 95% CI: -2.58, 1.10; p = 0.430], homeostasis model assessment for insulin resistance [HOMA-IR, WMD: -0.25; 95% CI: -0.88, 0.37, p = 0.429], and QUICKI [WMD: -0.01; 95% CI: -0.01, 0.03, p = 0.317] compared with the control group. The results of our meta-analysis revealed a beneficial effect of purslane supplementation as a tool to decrease FBG levels, but not to HOMA-IR, insulin, and QUICKI levels. However, future high-quality, long-term clinical trials are needed to confirm our results.

Effects of curcumin/turmeric supplementation on glycemic indices in adults: A grade-assessed systematic review and dose-response meta-analysis of randomized controlled trials.

INTRODUCTION: Glycemic control is of utmost importance both as a preventive measure in individuals at risk of diabetes and in the management of patients with disturbed glycemia. Turmeric/curcumin has been extensively studied in this field. In the present systematic review and meta-analysis, we aimed at investigating the impact of turmeric/curcumin supplementation on glycemic control. METHODS: Major online databases (PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar) were systematically searched from inception up to October 2022. Relevant randomized controlled trials (RCTs) meeting our eligible criteria were included. Weighted mean differences (WMDs) with confidence intervals (CIs) were expressed using a random-effect model. Subgroup analyses were conducted to find the sources of heterogeneities. To detect risk of bias in the included studies, we used the Cochrane risk-of-bias tool. The registration number was CRD42022374874. RESULTS: Out of 4182 articles retrieved from the initial search, 59 RCTs were included. Our findings suggested that turmeric/curcumin supplementation was significantly effective in improving fasting blood sugar (WMD: 4.60 mg/dl; 95% CI: 5.55, -3.66), fasting insulin levels (WMD: 0.87 µIU/ml; 95% CI: 1.46, -0.27), hemoglobin A1c (HbA1c) (WMD: 0.32%; 95% CI: 0.45, -0.19), and homeostatic model assessment of insulin resistance (HOMA-IR) (WMD: 0.33; 95% CI: 0.43, -0.22). CONCLUSION: Our results indicate that turmeric/curcumin supplementation can be considered as a complementary method in the management of disturbed glycemia.

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

Untargeted metabolomics and phenotype data indicate the therapeutic and prophylactic potential of Lysimachia candida Lindl. towards high-fat high-fructose-induced metabolic syndrome in rats.

The present study evaluated the therapeutic potential of the medicinal plant Lysimachia candida Lindl. against metabolic syndrome in male SD rats fed with a high-fat high-fructose (HFHF) diet. Methanolic extract of Lysimachia candida Lindl. (250 mg kg-1 body weight p.o.) was administrated to the HFHF-fed rats daily for 20 weeks. Blood samples were collected, and blood glucose levels and relevant biochemical parameters were analysed and used for the assessment of metabolic disease phenotypes. In this study, Lysimachia candida decreased HFHF diet-induced phenotypes of metabolic syndrome, i.e., obesity, blood glucose level, hepatic triglycerides, free fatty acids, and insulin resistance. Liquid chromatography-mass spectrometry-based metabolomics was done to study the dynamics of metabolic changes in the serum during disease progression in the presence and absence of the treatment. Furthermore, multivariate data analysis approaches have been employed to identify metabolites responsible for disease progression. Lysimachia candida Lindl. plant extract restored the metabolites that are involved in the biosynthesis and degradation of amino acids, fatty acid metabolism and vitamin metabolism. Interestingly, the results depicted that the treatment with the plant extract restored the levels of acetylated amino acids and their derivatives, which are involved in the regulation of beta cell function, glucose homeostasis, insulin secretion, and metabolic syndrome phenotypes. Furthermore, we observed restoration in the levels of indole derivatives and N-acetylgalactosamine with the treatment, which indicates a cross-talk between the gut microbiome and the metabolic syndrome. Therefore, the present study revealed the potential mechanism of Lysimachia candida Lindl. extract to prevent metabolic syndrome in rats.

Investigating the nutraceutical potential of apple peel extract supplementation for regulating the glucose metabolism in hyperlipidemic Female human subjects.

Hyperglycemia is a condition often observed in diabetics, dyslipidemia and obese. It is a major factor behind the development of diabetes and the reasons can be genetics, environmental factors, dietary choices and obesity. Many medicinal plants have anti-diabetic potential. This study investigated the anti-hyperglycemic effect of apple peel extract. This study also investigated the chemical characterization of apple peel. Phytochemicals including total phenolics and flavonoids were determined. Encapsulated 350mg/day was given to treatment groups. Random blood sugar, fasting blood sugar and HbA1c of 45 diabetic female adults was measured on the 0-day and 45th day. Results showed that apple peel contained moisture (14.71±3.57)%, ash (17.82±2.13)%, nitrogen free extract (32.12±3.52)%, crude protein (6.89±0.83)%, crude fiber (19.17±0.21)% and crude fat (9.91±2.31)%. Findings showed that apple peel contains magnesium (6.61±1.088), calcium (8.17±0.32), zinc (14.08±1.21) and potassium (67.21±1.86). These findings were shown in mg in kg. Apple peel extract contained total phenolic content (TPC) of 8.14±1.07 and total phenolic content (TFC) of 4.89±1.81. Apple peel extract showed a significant reduction in all blood parameters of hyperglycemia. All results were significant at p<0.05.

Short-Term Effect of Continuous Subcutaneous Insulin Infusion and Multiple Daily Injection in Perioperative Patients with Type 2 Diabetes Mellitus.

Background: Hyperglycemia is common and difficult to control in perioperative patients with type 2 diabetes mellitus (T2DM), which impacts their prognosis after operation. Our study investigated the short-term effect of continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI) in perioperative T2DM patients using the data envelopment analysis (DEA). Methods: T2DM patients (n = 639) who underwent surgeries in Guangdong Provincial Hospital of Traditional Chinese Medicine (2009.01-2017.12) were included. Insulin was provided to each patient during the study and separated into a CSII group (n = 369) and an MDI group (n = 270). DEA was performed to compare the therapeutic indexes and investigate the short-term effect of the CSII group and MDI group. Results: Scale efficiencies of the CSII group with CCR model and BCC model were better than that of the MDI group. Regarding slack variables, with higher surgical levels, the CSII group was closer to the ideal state than the MDI group, which indicated in improving the average fasting blood glucose (AFBG), antibiotic use days (AUD), preoperative blood glucose control time (PBGCT), first postoperative day fasting blood glucose (FPDFBG), and postoperative hospitalization days (PHD). Conclusion: CSII could effectively control blood glucose levels and shorten perioperative hospitalizing time for T2DM patients, indicating that CSII was beneficial in perioperative period and should be promoted clinically.

Evaluation of Antidiabetic and Antioxidant Activities of Fruit Pulp Extracts of Cucurbita moschata Duchesne and Cucurbita maxima Duchesne.

Objective: To evaluate and compare the antidiabetic and antioxidant activities of fruit pulp extracts from Cucurbita moschata (PCMOS) and Cucurbita maxima (PCMAX). Methods: The antidiabetic activity was carried out in vivo by orally and daily giving the extracts at a dose of 500 mg/kg·b.w. to the streptozotocin-induced diabetic male albino Wistar rats for six weeks. After the period of administration, blood glucose levels, body weight, serum insulin, morphology of islets of Langerhans, biochemical parameters, and haematological values of the rats were determined. Meanwhile, the antioxidant activity was carried out in vitro by determination of total phenolic and flavonoid contents, DPPH radical scavenging activity, and ferric reducing antioxidant power. Results: PCMAX significantly (p < 0.05) reduced blood glucose levels but increased the body weight, serum insulin levels, size and number of islets of Langerhans, and ß-cell number of the treated diabetic rats more than PCMOS did. However, they did not alter biochemical parameters and haematological values of the treated diabetic rats. PCMAX possessed total phenolic and flavonoid contents and showed DPPH scavenging and FRAP reducing antioxidant power more significantly (p < 0.05) than PCMOS. Conclusions: According to the obtained results, it is indicated that PCMOS and PCMAX possess antidiabetic and antioxidant activities. PCMAX possesses more potent antidiabetic and antioxidant activities than PCMOS. These are probably due to PCMAX providing polysaccharide and total phenolic and flavonoid contents more than PCMOS.

The association between the essential metal mixture and fasting plasma glucose in Chinese community-dwelling elderly people.

BACKGROUND: Epidemiological studies about the effect of essential metal mixture on fasting plasma glucose (FPG) levels among elderly people are sparse. The object of this study was to examine the associations of single essential metals and essential metal mixture with FPG levels in Chinese community-dwelling elderly people. METHODS: The study recruited 2348 community-dwelling elderly people in total. Inductively coupled plasma-mass spectrometry was adopted to detect the levels of vanadium (V), selenium (Se), magnesium (Mg), cobalt (Co), calcium (Ca), and molybdenum (Mo) in urine. The relationships between single essential metals and essential metal mixture and FPG levels were evaluated by linear regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: In multiple-metal linear regression models, urine V and Mg were negatively related to the FPG levels (ß = - 0.016, 95 % CI: - 0.030 to - 0.003 for V; ß = - 0.021, 95 % CI: - 0.033 to - 0.009 for Mg), and urine Se was positively related to the FPG levels (ß = 0.024, 95 % CI: 0.014-0.034). In BKMR model, the significant relationships of Se and Mg with the FPG levels were also found. The essential metal mixture was negatively associated with FPG levels in a dose-response pattern, and Mg had the maximum posterior inclusion probability (PIP) value (PIP = 1.0000), followed by Se (PIP = 0.9968). Besides, Co showed a significant association with decreased FPG levels in older adults without hyperlipemia and in women. CONCLUSIONS: Both Mg and Se were associated with FPG levels, individually and as a mixture. The essential metal mixture displayed a linear dose-response relationship with reduced FPG levels, with Mg having the largest contribution to FPG levels, followed by Se. Further prospective investigations are necessary to validate these exploratory findings.

The effects of vitamin C supplementation on glycemic control in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND AND AIM: It has been suggested that taking vitamin C supplements may improve glycemic control in patients with type 2 diabetes mellitus (T2DM). However, there has not been a thorough evaluation of the actual impact or certainty of the findings. This systematic review and meta-analysis was conducted to determine the effect of vitamin C supplementation on glycemic profile in T2DM patients. METHODS: A systematic search was performed across online databases including Scopus, Web of Science, and PubMed/Medline to identify relevant randomized controlled trials (RCTs) published until July 2022. A random-effects model was applied for the meta-analysis. RESULTS: The present meta-analysis included a total of 22 RCTs with 1447 patients diagnosed with T2DM.A pooled analysis revealed a significant decrease in levels of serum hemoglobin A1c (HbA1c), fasting insulin, and fasting blood glucose (FBG) in vitamin C-treated T2DM patients compared with their untreated counterparts. The dose-response evaluation displayed a substantial linear association between the intervention duration and changes in serum HbA1c levels. However, the analysis did not demonstrate any significant effect of vitamin C on serum values of homeostasis model assessment of insulin resistance(HOMA-IR) in diabetic patients. Subgroup analyses indicated that high-dose vitamin C administration (≥1000 mg/d) considerably decreased serum HOMA-IR levels. CONCLUSION: These findings suggest that long-term (≥12 weeks) and high-dose vitamin C supplementation (≥1000 mg/d) may ameliorate glycemic profile in T2DM patients. However, additional high-quality RCTs are necessary to validate these results.

Antidiabetic, hypolipidemic, and antioxidant activities of Pistacia atlantica: A systematic review and meta-analysis of preclinical studies.

To determine the pharmaceutical applications, we assessed the evidence from preclinical studies about the hypoglycemic, hypolipidemic, and antioxidant potential of Pistacia atlantica (PA) as a natural source for prevention and treatment of diabetes. A comprehensive literature search of the articles published until March 12, 2022 was conducted on PubMed, Embase, Web of Sciences, and Scopus databases, using relevant keywords. This meta-analysis included 12 articles that examined the blood glucose (BG), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), malondialdehyde (MDA) and superoxide dismutase (SOD). A random-effects model was used to estimate the pooled effect size. Findings indicated that PA supplementation significantly decreased BG, HOMA-IR, TC, TG, and MDA, and increased insulin and SOD in diabetic animals compared with control group (p < .05). However, PA supplementation had no significant effects on HDL-C (p > .05). The subgroup analysis also confirmed the beneficial effect of PA supplementation with longer duration (>4 weeks) and higher doses (≥100 mg/kg/day) as well as in the extract type. The studies have heterogeneity associated with methodological diversity and there were some concerns about the risk of bias, especially about randomization and blind outcome assessment. This meta-analysis provided convincing evidence for antidiabetic, hypolipidemic, and antioxidant activity of PA in animals. Further high-quality studies are needed to firmly establish the clinical efficacy of the plant.

Association of iron homeostasis biomarkers in type 2 diabetes and glycaemic traits: a bidirectional two-sample Mendelian randomization study.

BACKGROUND: Mendelian randomization (MR) studies show iron positively associated with type 2 diabetes (T2D) but included potentially biasing hereditary haemochromatosis variants and did not assess reverse causality. METHODS: We assessed the relation of iron homeostasis with T2D and glycaemic traits bidirectionally, using genome-wide association studies (GWAS) of iron homeostasis biomarkers [ferritin, serum iron, total iron-binding capacity (TIBC), transferrin saturation (TSAT) (n ≤ 246 139)], T2D (DIAMANTE n = 933 970 and FinnGen n = 300 483), and glycaemic traits [fasting glucose (FG), 2-h glucose, glycated haemoglobin (HbA1c) and fasting insulin (FI) (n ≤ 209 605)]. Inverse variance weighting (IVW) was the main analysis, supplemented with sensitivity analyses and assessment of mediation by hepcidin. RESULTS: Iron homeostasis biomarkers were largely unrelated to T2D, although serum iron was potentially associated with higher T2D [odds ratio: 1.07 per standard deviation; 95% confidence interval (CI): 0.99 to 1.16; P-value: 0.078) in DIAMANTE only. Higher ferritin, serum iron, TSAT and lower TIBC likely decreased HbA1c, but were not associated with other glycaemic traits. Liability to T2D likely increased TIBC (0.03 per log odds; 95% CI: 0.01 to 0.05; P-value: 0.005), FI likely increased ferritin (0.29 per log pmol/L; 95% CI: 0.12 to 0.47; P-value: 8.72 x 10-4). FG likely increased serum iron (0.06 per mmol/L; 95% CI: 0.001 to 0.12; P-value: 0.046). Hepcidin did not mediate these associations. CONCLUSION: It is unlikely that ferritin, TSAT and TIBC cause T2D although an association for serum iron could not be excluded. Glycaemic traits and liability to T2D may affect iron homeostasis, but mediation by hepcidin is unlikely. Corresponding mechanistic studies are warranted.

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

Background: 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. Method: 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. Results: 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. Conclusion: 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.

Identification of Hypothalamic Glucoregulatory Neurons That Sense and Respond to Changes in Glycemia.

To investigate whether glucoregulatory neurons in the hypothalamus can sense and respond to physiological variation in the blood glucose (BG) level, we combined continuous arterial glucose monitoring with continuous measures of the activity of a specific subset of neurons located in the hypothalamic ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) obtained using fiber photometry. Data were collected in conscious, free-living mice during a 1-h baseline monitoring period and a subsequent 2-h intervention period during which the BG level was raised either by consuming a chow or a high-sucrose meal or by intraperitoneal glucose injection. Cross-correlation analysis revealed that, following a 60- to 90-s delay, interventions that raise the BG level reliably associate with reduced VMNPACAP neuron activity (P < 0.01). In addition, a strong positive correlation between BG and spontaneous VMNPACAP neuron activity was observed under basal conditions but with a much longer (∼25 min) temporal offset, consistent with published evidence that VMNPACAP neuron activation raises the BG level. Together, these findings are suggestive of a closed-loop system whereby VMNPACAP neuron activation increases the BG level; detection of a rising BG level, in turn, feeds back to inhibit these neurons. To our knowledge, these findings constitute the first evidence of a role in glucose homeostasis for glucoregulatory neurocircuits that, like pancreatic ß-cells, sense and respond to physiological variation in glycemia. ARTICLE HIGHLIGHTS: By combining continuous arterial glucose monitoring with fiber photometry, studies investigated whether neurons in the murine ventromedial nucleus that express pituitary adenylate cyclase activating peptide (VMNPACAP neurons) detect and respond to changes in glycemia in vivo. VMNPACAP neuron activity rapidly decreases (within <2 min) when the blood glucose level is raised by either food consumption or glucose administration. Spontaneous VMNPACAP neuron activity also correlates positively with glycemia, but with a longer temporal offset, consistent with reports that hyperglycemia is induced by experimental activation of these neurons. Like pancreatic ß-cells, neurons in the hypothalamic ventromedial nucleus appear to sense and respond to physiological variation in glycemia.

Analysis of Antidiabetic Activity of Squalene via In Silico and In Vivo Assay.

Squalene has been tested widely in pharmacological activity including anticancer, antiinflammatory, antioxidant, and antidiabetic properties. This study aims to examine antidiabetic activity of squalene in silico and in vivo models. In the in silico model, the PASS server was used to evaluate squalene antidiabetic properties. Meanwhile, the in vivo model was conducted on a Type 2 Diabetes Mellitus (T2DM) with the rats separated into three groups. These include squalene (160 mg/kgbw), metformin (45 mg/kgbw), and diabetic control (DC) (aquades 10 mL/kgbw) administered once daily for 14 days. Fasting Blood Glucose Level (FBGL), Dipeptidyl Peptidase IV (DPPIV), leptin, and Superoxide Dismutase (SOD) activity were measured to analysis antidiabetic and antioxidant activity. Additionally, the pancreas was analysed through histopathology to examine the islet cell. The results showed that in silico analysis supported squalene antidiabetic potential. In vivo experiment demonstrated that squalene decreased FBGL levels to 134.40 ± 16.95 mg/dL. The highest DPPIV level was in diabetic control- (61.26 ± 15.06 ng/mL), while squalene group showed the lowest level (44.09 ± 5.29 ng/mL). Both metformin and squalene groups showed minor pancreatic rupture on histopathology. Leptin levels were significantly higher (p < 0.05) in diabetic control group (15.39 ± 1.77 ng/mL) than both squalene- (13.86 ± 0.47 ng/mL) and metformin-treated groups (9.22 ± 0.84 ng/mL). SOD activity were higher in both squalene- and metformin-treated group, particularly 22.42 ± 0.27 U/mL and 22.81 ± 0.08 U/mL than in diabetic control (21.88 ± 0.97 U/mL). In conclusion, in silico and in vivo experiments provide evidence of squalene antidiabetic and antioxidant properties.