Reduced Fasting Blood Glucose Research Articles

Treatment Outcomes of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Co-Transporter-2 Inhibitors in Diabetes Mellitus with Poor Glycemic Control

Background: Diabetes, a progressive disease necessitating multifaceted pharmacological interventions for glycemic control, commonly employs Dipeptidyl Peptidase-4 inhibitors (DPP-4i) and Sodium-Glucose Co-Transporter-2 inhibitors (SGLT-2i). The ongoing challenge lies in determining the superior option for safety and efficacy. Objective: This study aims to describe the treatment outcomes of DPP-4 inhibitors (DPP-4i) and Sodium- Glucose Co-Transporter-2 inhibitors (SGLT-2i) in individuals with diabetes mellitus (DM) receiving metformin with poor glycemic control. Methods: This prospective study was conducted at the Endocrinology Outpatient Department of Dhaka Medical College Hospital, Dhaka, and included 90 individuals with diabetes mellitus who met the selection criteria. Divided into two groups, Group I (n=45) received DPP-4 inhibitors plus metformin, and Group II (n=45) received SGLT2 inhibitors plus metformin. Baseline data, including HbA1c, fasting blood glucose (FBG), blood glucose 2 hours after breakfast, weight, lipid profile, and serum creatinine, were recorded at the first visit and 12 weeks. Safety was assessed based on adverse drug effects. Results: After 12 weeks, both groups exhibited significant reductions in HbA1c, FBG, and postprandial blood glucose levels. However, the SGLT-2i group demonstrated significant improvements in HbA1c (P<0.012), fasting plasma glucose (P<0.003), and postprandial glucose levels (P<0.001), along with a reduction in body weight (P<0.042). Hypoglycemia rates were low and balanced between groups. Notably, SGLT-2i usage correlated with an increased incidence of urinary tract infections (13.33% vs. 6.66% in DPP-4i) and exclusive genital infections (11.11%, P<0.022). Conclusion: Diabetic patients receiving SGLT-2 inhibitors had better glycemic control and body weight improvements in comparison to DPP-4 inhibitors. However, SGLT-2 inhibitors encountered more genital infections than DPP-4 inhibitors. J MEDICINE 2024; 25: 107-114

Effects of kaempherol-3-rhamnoside on metabolic enzymes and AMPK in the liver tissue of STZ-induced diabetes in mice

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia. It involves disturbances in carbohydrate, fat, and protein metabolism due to defects in insulin secretion, insulin action, or both. Novel therapeutic approaches are continuously being explored to enhance metabolic control and prevent complications associated with the disease. This study investigates the therapeutic potential of kaempherol-3-rhamnoside, a flavonoid, in managing diabetes by modulating the AMP-activated protein kinase (AMPK) pathway and improving metabolic enzyme activities in streptozotocin (STZ) -induced diabetic mice. Diabetic mice were treated with varying doses of kaempherol-3-rhamnoside and/or insulin over a 28-day period. Glycolytic and gluconeogenesis enzyme activities in the liver, fasting blood glucose levels, serum insulin levels, lipid profiles and oxidative stress markers were assessed. Treatment with kaempherol-3-rhamnoside significantly improved glycolytic enzyme activities, reduced fasting blood glucose, and enhanced insulin levels compared to diabetic controls. The compound also normalized lipid profiles and reduced oxidative stress in the liver, suggesting its potential in reversing diabetic dyslipidemia and oxidative damage. Furthermore, kaempherol-3-rhamnoside activated the AMPK pathway, indicating a mechanism through which it could exert its effects. Kaempherol-3-rhamnoside exhibits promising antidiabetic properties, potentially through AMPK pathway activation and metabolic enzyme modulation. These findings support its potential use as an adjunct therapy for diabetes management. Further clinical studies are warranted to validate these results in human subjects.

Impact of Concurrent Exercise Training on Cardiac Autonomic Modulation, Metabolic Profile, Body Composition, Cardiorespiratory Fitness, and Quality of Life in Type 2 Diabetes with Cardiac Autonomic Neuropathy: A Randomized Controlled Trial.

Background: Type 2 diabetes mellitus (T2DM) often leads to cardiac autonomic neuropathy (CAN), a severe complication affecting cardiovascular health. Exercise training is a proven intervention for improving metabolic control and cardiovascular health in T2DM, but the effects of concurrent exercise training (CET), combining aerobic and resistance exercises, on CAN are not fully understood. Objective: This randomized controlled trial investigates the impact of a structured CET program on cardiac autonomic modulation, metabolic profile, body composition, cardiorespiratory fitness (CRF), and quality of life (QoL) in individuals with T2DM and CAN. Methods: A total of 96 participants, aged 35-70 years, with T2DM and CAN, were randomized into CET (n = 48) and control (n = 48) groups. The CET group engaged in combined aerobic and resistance training three times per week for 13 weeks, while the control group received standard care. Primary outcomes included heart rate variability (HRV) and heart rate recovery (HRR). Secondary outcomes were metabolic profile, body composition, CRF, and QoL, which were assessed using standardized protocols and validated questionnaires. The trial was registered with the Clinical Trials Registry-India (CTRI/2021/09/036711). Results: Significant improvements were noted in the CET group compared to controls. HRV metrics (SDNN, RMSSD, pNN50, TP, LF power, HF power, and LF/HF ratio) and HRR metrics (HRR30s, HRR1, HRR2, and HRR3) all showed significant enhancements (p < 0.01). The CET group also exhibited substantial reductions in fasting blood glucose, postprandial blood glucose, HbA1c, waist circumference, hip circumference, and percentage body fat (p < 0.01). Improvements were observed in lipid profile markers and CRF (VO2max) (p < 0.01). QoL scores improved significantly in the CET group as per the ADDQoL-19 (p < 0.01). Conclusions: CET significantly enhances cardiac autonomic modulation, metabolic profile, body composition, CRF, and QoL in individuals with T2DM and CAN. These findings support the integration of CET into standard T2DM management to improve clinical outcomes and QoL. Further research is needed to explore the long-term benefits and broader applicability of CET in diverse diabetic populations.

MiRNA-133a-3p Attenuates Renal Tubular Epithelial Cell Injury via Targeting MALM1 and Suppressing the Notch Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes characterized by structural and functional changes of kidneys. Human renal tubular epithelial (HK-2) cells are important for kidney recovery post injury and usually used for establishment of DN cell models. The study explored the role of microRNA (miR)-133a-3p in DN cell model and animal model. A cell model for DN was established via high glucose (HG) stimulation to HK-2 cells. Cell viability and apoptotic rate were measured by cell counting kit 8 and flow cytometry. Polymerase chain reaction was performed to quantify levels of miR-133a-3p and targets. Luciferase reporter assay was conducted to verify the binding of miR-133a-3p and MAML1. After establishment of a mouse model of DN, levels of renal function indicators were measured by biochemical analysis. Hematoxylin-eosin and periodic acid-schiff staining of kidney samples were performed to analyze histological changes. Western blotting was conducted to quantify levels of apoptotic markers, MAML1, and factors related to Notch signaling. Results showed that HG induced HK-2 cell apoptosis and the reduction of cell viability. MiR-133a-3p was lowly expressed in HG-stimulated HK-2 cells. Overexpressed miR-133a-3p improved HK-2 cell injury by increasing cell viability and hampering apoptosis under HG condition. In addition, miR-133a-3p directly targets MAML1 3'-untranslated region. MAML1 overexpression countervailed the repressive impact of miR-133a-3p on cell apoptosis in the context of HG. Moreover, miR-133a-3p inhibited the activity of Notch pathway by downregulating MAML1. MiR-133a-3p inhibits DN progression in mice, as evidenced by reduced fasting blood glucose level, improved levels of renal function parameters, and alleviation of kidney atrophy. In conclusion, miR-133a-3p improves HG-induced HK-2 cell injury and inhibits DN progression by targeting MAML1 and inactivating Notch signaling.

Edukasi Diet Diabetes Puasa untuk Mengendalikan Gula Darah Saat Menjalankan Puasa Ramadhan

Background: Fasting during Ramadan could have negative effects on individuals with Type 2 Diabetes Mellitus (T2DM), as it would lead to hypoglycemia or hyperglycemia. Non-compliance with the recommended diet during fasting is one of the factors that can trigger these conditions. Knowledge about the appropriate diet plays a crucial role in successfully adhering to the diet. Objective: The aim of this study is to assess the effect of providing T2DM education during Ramadan fasting on knowledge and fasting blood glucose levels. Method: This study is an experimental research conducted using a randomized controlled trial design with a pretest-posttest control group design. The participants of this study were T2DM patients from Tlogosari Kulon Community Health Center and Kedungmundu Community Health Center who were enrolled in the Prolanis program and did not have any complications related to kidney failure or stroke. A total of 46 participants were divided into a treatment group and a control group. The treatment group received nutritional education on managing their diet while fasting during Ramadan. This education was provided one week prior to the start of Ramadan fasting. Data collection included assessing knowledge, food intake, nutritional status, and fasting blood glucose levels before and after Ramadan fasting. The collected data will be analyzed using univariate analysis to describe the research data and to test the impact of nutrition education on knowledge and fasting blood glucose levels levels. The independent t-test with a significance level of α=0.05 will be used for this analysis.Result: There was a significant difference before and after being given nutrition education in intervention group on increasing knowledge levels in the intervention group (p=0.029) also lowering the blood glucose levels (p = 0.000). Providing education to the intervention group increased the knowledge score from 68.56 +12.81 to 79.26+9.47. There was an increase in knowledge leves by 10.70+3.34 in the intervention group. Nutritioneducation also reduced fasting blood glucose levels in intervention gropus from 177.78 + 79.61 to 141.35 + 43.78. There was a lowering in the blood glucose levels by -36.43 + 71.89 in the intervention group.Conclusion: There is a relationship between fasting ramadhan diabetes education with knowledge and blood glucose levels.

Edukasi Diet Diabetes Puasa untuk Mengendalikan Gula Darah Saat Menjalankan Puasa Ramadhan

Background: Fasting during Ramadan could have negative effects on individuals with Type 2 Diabetes Mellitus (T2DM), as it would lead to hypoglycemia or hyperglycemia. Non-compliance with the recommended diet during fasting is one of the factors that can trigger these conditions. Knowledge about the appropriate diet plays a crucial role in successfully adhering to the diet. Objective: The aim of this study is to assess the effect of providing T2DM education during Ramadan fasting on knowledge and fasting blood glucose levels. Method: This study is an experimental research conducted using a randomized controlled trial design with a pretest-posttest control group design. The participants of this study were T2DM patients from Tlogosari Kulon Community Health Center and Kedungmundu Community Health Center who were enrolled in the Prolanis program and did not have any complications related to kidney failure or stroke. A total of 46 participants were divided into a treatment group and a control group. The treatment group received nutritional education on managing their diet while fasting during Ramadan. This education was provided one week prior to the start of Ramadan fasting. Data collection included assessing knowledge, food intake, nutritional status, and fasting blood glucose levels before and after Ramadan fasting. The collected data will be analyzed using univariate analysis to describe the research data and to test the impact of nutrition education on knowledge and fasting blood glucose levels levels. The independent t-test with a significance level of α=0.05 will be used for this analysis.Result: There was a significant difference before and after being given nutrition education in intervention group on increasing knowledge levels in the intervention group (p=0.029) also lowering the blood glucose levels (p = 0.000). Providing education to the intervention group increased the knowledge score from 68.56 +12.81 to 79.26+9.47. There was an increase in knowledge leves by 10.70+3.34 in the intervention group. Nutritioneducation also reduced fasting blood glucose levels in intervention gropus from 177.78 + 79.61 to 141.35 + 43.78. There was a lowering in the blood glucose levels by -36.43 + 71.89 in the intervention group.Conclusion: There is a relationship between fasting ramadhan diabetes education with knowledge and blood glucose levels.

Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials

BackgroundMetabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters.MethodsWe conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control.ResultsOur analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = −3.999 mmHg, 95% confidence interval [CI] = −7.293 to −0.706, p = 0.017), DBP (WMD = −1.509 mmHg, 95% CI = −2.479 to −0.539, p = 0.002), FBG (WMD: −5.882 mg/dL, 95% CI: −10.747 to −1.018, p = 0.018), TG (WMD: −18.315 mg/dL, 95% CI: −25.628 to −11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: −0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = −0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = −0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group.ConclusionTaurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.

Comparisons of procyanidins with different low polymerization degrees on prevention of lipid metabolism in high-fat diet/streptozotocin-induced diabetic mice

Procyanidins, which are oligomerized flavan-3-ols with a polyphenolic structure, are bioactive substances that exhibit various biological effects. However, the relationship between the degree of polymerization (DP) of procyanidins and their bioactivities remains largely unknown. In this study, the preventive effects of procyanidins with different DP (EC, PB2 and PC1) on glucose improvement and liver lipid deposition were investigated using a high-fat diet/streptozotocin-induced diabetes mouse model. The results demonstrated that all the procyanidins with different DP effectively reduced fasting blood glucose and glucose/insulin tolerance, decreased the lipid profile (total cholesterol, triglyceride, and low-density lipoprotein cholesterol content) in serum and liver tissue as well as the liver oil red staining, indicating the improvement of glucose metabolism, insulin sensitivity and hepatic lipid deposition in diabetic mice. Furthermore, the procyanidins down-regulated expression of glucose regulated 78-kDa protein (GRP78) and C/EBP homologous protein (CHOP), indicating a regulation role of endoplasmic reticulum (ER) stress. The inhibition of ER stress by tauroursodeoxycholic acid (TUDCA) treatment abolished the effects of procyanidins with different DP in PA-induced HepG2 cells, confirming that procyanidins alleviate liver hyperlipidemia through the modulation of ER stress. Molecular docking results showed that EC and PB2 could better bind GRP78 and CHOP. Collectively, our study reveals that the structure of procyanidins, particularly DP, is not directly correlated with the improvement of blood glucose and lipid deposition, while highlighting the important role of ER stress in the bioactivities of procyanidins.

Effect of &lt;i&gt;Vernonia amygdalina&lt;/i&gt; and fish oil-supplemented biscuits on lipid profile parameters and blood glucose concentration of diabetic rats

Biscuit, a popular snack, serve as an ideal vehicle for incorporating therapeutic agents for disease management. This study aimed to assess the effect of Vernonia amygdalina (VO) and fish oil (FO)-supplemented biscuits (VFSB) on the total lipid profile and blood glucose concentration of diabetic rats. Forty-nine Wistar rats were allocated into seven groups (A to G). Upon induction and confirmation of diabetes in experimental rats, fasting blood glucose (FBG) level were monitored weekly using glucometer. Twenty-four hours after the last day of treatment, rats were sacrificed and serum total cholesterol (TC), triglyceride (TG), High-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were assayed using assay kits. Results showed a significant (p &lt; 0.05) reduction in FBG, TC, LDL-c, and TG concentrations in biscuit fed groups D, E, and F compared to group B fed VFSB. High-density lipoprotein cholesterol levels significantly increased (p &lt; 0.05) in groups D, E, and F compared to Group B. In conclusion, Vernonia amygdalina and fish oil-supplemented biscuits exhibited a glucose-lowering effect and mitigated dyslipidemia associated with diabetes mellitus.

The loss of the hormonal function of bilirubin induces adiposity in male and female mice

The prevalence of obesity and its related comorbidities, including diabetes and metabolic dysfunction associated fatty liver disease (MAFLD), are on the rise globally, indicating the importance of new therapeutics for these diseases. Interestingly, serum bilirubin levels are negatively correlated with obesity, diabetes, and MAFLD. We have previously generated pegylated bilirubin nanoparticles (PEGBR) and demonstrated their therapeutic potential in the treatment of obesity and MAFLD. However, it’s unknown whether their beneficial effects are due to bilirubin’s antioxidant properties or its hormonal function by binding to and activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa). To determine this, we used female and male hepatocyte-specific PPARa knockout mice ( PparaHepKO) and floxed ( Pparaflox) control mice on a high-fat diet for 30 weeks to induce adiposity and MAFLD. The mice were treated with vehicle or PEGBR (30 mg/kg) for six weeks. In female Pparaflox mice, PEGBR significantly lowered body weight, but not in the female PparaHepKO mice. A similar trend was seen in the male Pparaflox mice but was not statistically significant. PEGBR significantly reduced hepatic fat mass and triglycerides in the female and male Pparaflox mice but not in the PparaHepKO mice. Using lipidomics, we determined the lipid composition of the liver and how PEGBR changed it. In the male Pparaflox mice, PEGBR significantly reduced 109 lipid species, whereas, in the male PparaHepKO mice, PEGBR only reduced 7 species (93.6% reduction). In the female PparaHepKO mice, there was a 2.7% reduction in the number of lipid species significantly decreased by PEGBR compared to Pparaflox controls. Male Pparaflox mice had an increase in plasma high-density lipoprotein cholesterol and a decrease in very-low-density particle number with PEGBR, but this was not seen in the male PparaHepKO or female mice. In addition to protecting against the development of MAFLD, PEGBR significantly reduced fasting blood glucose and insulin levels only in the Pparaflox mice. Overall, the data indicates that the protective effects of bilirubin on obesity, MAFLD, and glucose tolerance are due to its hormonal function through PPARa. This study also confirms the therapeutic potential of bilirubin nanoparticles for obesity and its associated comorbidities. This work was supported by the National Institutes of Health F31HL170972 (Z.A.K.) and R01DK121797 (T.D.H.J.) and R01DA058933 (T.D.H.J.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Argyreia nervosa Mitigates Insulin Resistance in Liver via IR/IRS-1 Mediated Signaling in Streptozotocin-Induced Type-2 Diabetic Rats

Argyreia nervosa, commonly known as Hawaiian baby woodrose or wooly morning glory, is a plant native to India and is also found in various parts of the world. It is known for its seeds, which have been used traditionally in Ayurvedic and traditional medicine systems for various diseases. The study was aimed at assessing the effect of Argyreia nervosa on insulin signaling molecules of the liver in streptozotocin (STZ)-induced experimental type-2 diabetic rats. Healthy adult male Wistar albino rats -150-180 days old weighing 180-200g was used for the study and divided as Group I - Normal rats; Group II – type-2 diabetic rats; Group III -Diabetic rats + A. nervosa 500 mg/kg b.wt; Group IV-Normal rats + A. nervosa 500 mg/kg b.wt. Fasting blood glucose, and fasting serum insulin were measured by calorimetric methods. Further mRNA expression analysis of insulin receptor (IR) was measured in control and treated animals by quantitative Ream Time PCR analysis. A. nervosa root extract significantly reduced fasting blood glucose and serum insulin concentrations in STZ-induced rats compared with control. In addition, mRNA expression of IR showed a one-fold increase in the expression which shows that A. nervosa is involved in the regulation of insulin signaling in the liver and thereby reduces insulin resistance and type-2 diabetes. Our study concludes that A. nervosa root extract has a significant role on insulin signaling molecules thereby it reduces hyperglycemia and hyperinsulinemia via insulin receptor-mediated pathways. Hence, A. nervosa may be considered as one of the therapeutic natural antidiabetic drugs.

Osthole ameliorates early diabetic kidney damage by suppressing oxidative stress, inflammation and inhibiting TGF-β1/Smads signaling pathway

BackgroundOsthole is a natural active ingredient extracted from the traditional Chinese medicine Cnidium monnieri. It has been demonstrated to have anti-inflammatory, anti-fibrotic, and anti-hyperglycemic properties. However, its effect on diabetic kidney disease (DKD) remains uncertain. This study aims to assess the preventive and therapeutic effects of osthole on DKD and investigate its underlying mechanisms. MethodsA streptozotocin/high-fat and high-sucrose diet induced Type 2 diabetic rat model was established. Metformin served as the positive drug control. Diabetic rats were treated with metformin or three different doses of osthole for 8 weeks. Throughout the treatment period, the progression of DKD was assessed by monitoring increases in urinary protein, serum creatinine, urea nitrogen, and uric acid, along with scrutinizing kidney pathology. Enzyme-linked immunosorbent assay (ELISA) was employed to detect inflammatory factors and oxidative stress levels. At the same time, immunohistochemical staining was utilized to evaluate changes in alpha-smooth muscle actin, fibronectin, E-cadherin, and apoptosis. The alterations in TGF-β1/Smads signaling pathway were ascertained through western blot and immunofluorescence. Furthermore, we constructed a high glucose-stimulated HBZY-1 cells model to uncover its molecular protective mechanism. ResultsOsthole significantly reduced fasting blood glucose, insulin resistance, serum creatinine, uric acid, blood urea nitrogen, urinary protein excretion, and glomerular mesangial matrix deposition in diabetic rats. Additionally, significant improvements were observed in inflammation, oxidative stress, apoptosis, and fibrosis levels. The increase of ROS, apoptosis and hypertrophy in HBZY-1 cells induced by high glucose was reduced by osthole. Immunofluorescence and western blot results demonstrated that osthole down-regulated the TGF-β1/Smads signaling pathway and related protein expression. ConclusionOur findings indicate that osthole exhibits potential preventive and therapeutic effects on DKD. It deserves further investigation as a promising drug for preventing and treating DKD.

Effects of whole grains on glycemic control: a systematic review and dose-response meta-analysis of prospective cohort studies and randomized controlled trials

PurposeWhole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations.MethodsWe searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA1C, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639.ResultsTen prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I2 = 72.39%, P < 0.001) and indicated a monotonic inverse relationship between whole grains and type 2 diabetes rate. In RCTs, whole grains significantly reduced fasting blood glucose (Mean difference (MD) = -0.103 mmol/L, 95% CI: -0.178 to -0.028; I2 = 72.99%, P < 0.01) and had modest effects on HbA1C (MD = -0.662 mmol/mol (-0.06%), 95% CI: -1.335 to 0.010; I2 = 64.55%, P = 0.05) and HOMA-IR (MD = -0.164, 95% CI: -0.342 to 0.013; I2 = 33.38%, P = 0.07). The intake of whole grains and FBG, HbA1C, and HOMA-IR were significantly dose-dependent. The restricted spline curves remained flat up to 150 g/day and decreased afterward. Subgroup analysis showed that interventions with multiple whole-grain types were more effective than those with a single type.ConclusionOur study findings suggest that a daily intake of more than 150 g of whole grain ingredients is recommended as a population approach for diabetes prevention.

The efficacy and safety of GLP-1 receptor agonists in youth with type 2 diabetes: a meta-analysis

BackgroundGlucagon-like peptide 1 receptor agonists have been proven to be effective in adults with diabetes and children with obesity. However, children with type 2 diabetes constitute an underrepresented subpopulation with limited treatment options. This meta-analysis aimed to determine more precise estimates of the efficacy and safety of glucagon-like peptide-1 agonists in pediatric type 2 diabetes mellitus.MethodsThree databases were searched (PubMed, Embase, and Cochrane Central Register of Controlled Trials) for trials published until the end of March 2024. The search indexing terms included 3 categories: [1] type 2 diabetes mellitus [2], youth, and [3] glucagon-like peptide-1 receptor agonist (GLP-1 RA). Randomized controlled trials in youth with type 2 diabetes (age ≤ 18 years) that assessed anthropometric and metabolic parameters were included. A total of 1119 nonduplicate studies were retrieved, and 137 full-text articles were screened. The data were analyzed using mean differences (MDs) with 95% CIs and odds ratios (ORs) with 95% CIs. For outcomes with low heterogeneity, a fixed-effects model was used. Otherwise, we applied a random effects model. Our outcomes were Hb1Ac, fasting blood glucose (FBG), blood pressure, weight, and side effects.ResultsFive studies comprehending 415 children and adolescents were included. On average, GLP-1 RA reduced HbA1c levels (-1.01%; 95% CI, -1.26 to -0.76), fasting blood glucose levels (-1.88 mmol/L; 95% CI, -2.51 to -1.26), and body weight (-1.6 kg; 95% CI, -2.83 to -0.36). No significant reductions in systolic blood pressure (MD -0.19 mmHg; 95% CI, -3.9 to 3.52 mmHg) or diastolic blood pressure (MD 0.3 mmHg; 95% CI, -2.33 to 2.93 mmHg) were observed. Despite a higher incidence of side effects, withdrawal rates from the studies remained low.ConclusionsWithin this specific population, GLP-1 RAs exhibit a notable association with substantial reductions in HbA1c, FBG, and body weight. The administration of these medications is concurrent with an elevated incidence of side effects, which are predominantly gastrointestinal and tolerable.Trial registrationPROSPERO identifier: CRD42023393020.

1,3,4-Oxadiazole Scaffold in Antidiabetic Drug Discovery: An Overview.

Diabetes mellitus is one of the biggest challenges for the scientific community in the 21st century. With the increasing number of cases of diabetes and drug-resistant diabetes, there is an urgent need to develop new potent molecules capable of combating this cruel disease. Medicinal chemistry concerns the discovery, development, identification, and interpretation of the mode of action of biologically active compounds at the molecular level. Oxadiazole-based derivatives have come up as a potential option for antidiabetic drug research. Oxadiazole is a five-membered heterocyclic organic compound containing two nitrogen atoms and one oxygen atom in its ring. Oxadiazole hybrids have shown the ability to improve glucose tolerance, enhance insulin sensitivity, and reduce fasting blood glucose levels. The mechanisms underlying the antidiabetic effects of oxadiazole involve the modulation of molecular targets such as peroxisome proliferator-activated receptor gamma (PPARγ), α-glucosidase, α-amylase and GSK-3β which regulate glucose metabolism and insulin secretion. The present review article describes the chemical structure and properties of oxadiazoles and highlights the antidiabetic activity through action on different targets. The SAR for the oxadiazole hybrids has been discussed in this article, which will pave the way for the design and development of new 1,3,4-oxadiazole derivatives as promising antidiabetic agents in the future. We expect that this article will provide comprehensive knowledge and current innovation on oxadiazole derivatives with antidiabetic potential and will fulfil the needs of the scientific community in designing and developing efficacious antidiabetic agents.

A randomised double-blind placebo-controlled trial of a probiotic combination for manipulating the gut microbiota and managing metabolic syndrome

An increasing number of studies indicate that the occurrence of metabolic syndrome is significantly influenced by the host's gut microbiota and its metabolites. This study evaluated the potential application of a combination of Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631 for the clinical remission of metabolic syndrome. This research comprised 40 individuals with metabolic syndrome, 21 of whom were in the probiotic intervention group and 19 in the placebo control group. The intervention duration was 11 weeks and involved the daily intake of 1 × 1010 CFU of a probiotic combination comprising Bifidobacterium adolescentis CCFM8630 and Lactobacillus reuteri CCFM8631. The serum biochemical indexes of the participants before and after the intervention were measured. After the intervention, faecal samples were collected to comprehensively analyse the gut microbiota of the participants by high-throughput sequencing and the faecal concentrations of target short-chain fatty acids by gas chromatography–mass spectrometry. The results showed that the 11-week probiotic intervention significantly reduced fasting blood glucose, fasting insulin, triglyceride, and low-density lipoprotein cholesterol concentrations in patients with metabolic syndrome and significantly increased the abundance of Bacteroidetes and some genera that produce short-chain fatty acids by regulating the abundance of gut microbial taxa that are strongly correlated with the clinical indicators of metabolic syndrome. These results demonstrated the beneficial effects of the probiotic combination on the clinical remission of metabolic syndrome, suggesting its potential application as an adjuvant strategy for the clinical treatment of metabolic syndrome in the future and laying a foundation for the further study of the mechanism of action of probiotics in alleviating metabolic syndrome.

Non-Pharmacological Interventions for Type 2 Diabetes in People Living with Severe Mental Illness: Results of a Systematic Review and Meta-Analysis.

People with serious mental illnesses (SMIs) such as schizophrenia and bipolar disorder die up to 30 years younger than individuals in the general population. Premature mortality among this population is often due to medical comorbidities, such as type 2 diabetes (T2D). Being a disease directly related to diet, adverse lifestyle choices, and side effects of psychotropic medication, an effective approach to T2D treatment and management could be non-pharmacological interventions. This systematic review and meta-analysis (1) summarise the current evidence base for non-pharmacological interventions (NPI) for diabetes management in people living with SMI and (2) evaluate the effect of these interventions on diverse health outcomes for people with SMI and comorbid diabetes. Six databases were searched to identify relevant studies: PubMed (MEDLINE), PsycINFO, Embase, Scopus, CINAHL, and Web of Science. Studies were included if they reported on non-pharmacological interventions targeted at the management of T2D in people living with SMI. To be eligible, studies had to further involve a control group or report multiple time points of data in the same study population. Whenever there were enough interventions reporting data on the same outcome, we also performed a meta-analysis. Of 1867 records identified, 14 studies were included in the systematic review and 6 were also eligible for meta-analysis. The results showed that there was a reduction, although not significant, in glycated haemoglobin (HbA1c) in the NPI group compared with the control, with a mean difference of -0.14 (95% CI, -0.42, 0.14, p = 0.33). Furthermore, NPI did not significantly reduce fasting blood glucose in these participants, with a mean difference of -17.70 (95% CI, -53.77, 18.37, p = 0.34). However, the meta-analysis showed a significant reduction in psychiatric symptoms: BPRS score, -3.66 (95% CI, -6.8, -0.47, p = 0.02) and MADRS score, -2.63 (95% CI, -5.24, -0.02, p = 0.05). NPI also showed a significant reduction in the level of total cholesterol compared with the control, with a mean difference of -26.10 (95% CI, -46.54, -5.66, p = 0.01), and in low-density lipoprotein (LDL) cholesterol compared with control, with a standardised mean difference of -0.47 (95% CI, -0.90, -0.04, p = 0.03). NPI did not appear to have significant effect (p > 0.05) on body mass index (BMI), health-related quality of life (HRQL), triglycerides, and high-density lipoprotein cholesterol compared with control. This systematic review and meta-analysis demonstrated that NPI significantly (p < 0.05) reduced psychiatric symptoms, levels of total cholesterol, and LDL cholesterol in people with type 2 diabetes and SMI. While non-pharmacological interventions also reduced HbA1c, triglyceride, and BMI levels and improved quality of life in these people, the effects were not significant (p > 0.05).

1H-NMR-based metabolomics reveals the preventive effect of Enteromorpha prolifera polysaccharides on diabetes in Zucker diabetic fatty rats.

The primary objective of this investigation was to explore the beneficial impacts of Enteromorpha prolifera polysaccharide (EP) on dysglycemia in Zucker diabetic fatty (ZDF) rats, while also shedding light on its potential mechanism using 1H-NMR-based metabolomics. The results demonstrated a noteworthy reduction in fasting blood glucose (FBG, 46.3%), fasting insulin (50.17%), glycosylated hemoglobin A1c (HbA1c, 44.1%), and homeostatic model assessment of insulin resistance (HOMA-IR, 59.75%) following EP administration, while the insulin sensitivity index (ISI, 19.6%) and homeostatic model assessment of β-cell function (HOMA-β, 2.5-fold) were significantly increased. These findings indicate that EP enhances β-cell function, increases insulin sensitivity, and improves insulin resistance caused by diabetes. Moreover, EP significantly reduced serum lipid levels, suggesting improvement of dyslipidemia. Through the analysis of serum metabolomics, 17 metabolites were found to be altered in diabetic rats, 14 of which were upregulated and 3 of which were downregulated. Notably, the administration of EP successfully reversed the abnormal levels of 9 out of the 17 metabolites. Pathway analysis further revealed that EP treatment partially restored metabolic dysfunction, with notable effects observed in valine, leucine, and isoleucine metabolism; aminoacyl-transfer RNA (tRNA) biosynthesis; and ketone body metabolism. These findings collectively indicate the potential therapeutic efficacy of EP in preventing glycemic abnormalities and improving insulin resistance. Thus, EP holds promise as a valuable treatment option for individuals with diabetes.

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%–50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function.