Reduced Fasting Blood Glucose Research Articles

Evaluating the Efficacy of Metformin and Camel Milk on Streptozotocin-nicotinamide Induced Diabetic Albino Rats

Background: This study was intended to evaluate the anti-diabetic activity of metformin and camel milk solely or in combination in streptozotocin- nicotinamide induced type II diabetic albino Wistar rats. Methods: Thirty albino Wistar rats were induced with type II diabetes through streptozotocin (60 mg/kg), followed by the administration of nicotinamide (120 mg/kg) after 15 min. The rats were randomly divided into control, diabetic control, metformin-treated (100 mg/kg), camel milk-treated (50 ml/rat/day) and metformin + camel milk-treated groups for 30 days. For this study, rats with blood glucose levels higher than 250 mg/dL were included. Blood glucose levels and body weight were measured at the beginning of the study and at regular intervals throughout the experiment.Furthermore, histopathological examination of liver, kidney and pancreatic tissue was conducted to determine the effects of metformin and camel milk on these organs. Result: The results showed that treatment with metformin, camel milk, or a combination of both significantly reduced fasting blood glucose levels and improved body weight compared to the diabetic control group. Morphological improvements were also observed in the histopathological examination of liver, kidney and pancreatic tissue. The results of this study are consistent with previous research showing the anti-diabetic effects of metformin and support the emerging role of alternative therapies such as camel milk. However, further research is needed to explore the potential mechanisms underlying the observed effects.

Carboxymethylation of paramylon derived from Euglena gracilis and its hypoglycemic mechanism in diabetic mice.

Paramylon is a polysaccharide primarily composed of β-1,3-glucan, characterized by its high crystallinity and insolubility in water. Enhancing its water solubility through structural modifications presents an effective strategy to unlock its biological activity. In this study, carboxymethylation was employed to produce carboxymethylated paramylon (CEP) with varying carboxyl concentrations. The successful introduction of carboxyl groups led to a notable improvement in water solubility. In vivo experiments demonstrated that CEP reduced fasting blood glucose levels by 24.42%, improved oral glucose tolerance, and enhanced insulin sensitivity in diabetic mice. Additionally, CEP regulated lipid homeostasis and ameliorated liver damage. Through modulation of the adenosine monophosphate-activated protein kinase/phosphoinositide 3-kinase/protein kinase B pathway and the glucose-6-phosphatase/phosphoenolpyruvate carboxykinase pathway, CEP effectively regulated hepatic glucose absorption and production. Furthermore, CEP mitigated diabetes-induced lipid metabolism disorders. These findings suggest that CEP holds significant promise in ameliorating glucose metabolism disorder, indicating its potential as a novel hypoglycemic functional food.

A Neutral Polysaccharide from Medicago sativa L.: Structural Properties and Hypoglycemic Activity in vitro and in vivo.

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3 × 104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1:4.0:1.1:0.4:1.4:1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 μg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity.

Inflammatory markers and noncoding-RNAs responses to low and high compressions of HIIT with or without berberine supplementation in middle-aged men with prediabetes.

This study compared the capacity of two different models of HIIT [high-(HC) and low-(LC) compression], with or without the use of berberine (BBR), on NOD-like receptor pyrin domain-containing protein-3 (NLRP3), H19, interleukin (IL)-1β, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance markers. Fifty-four middle-aged men with overweight or obesity and prediabetes [fasting blood glucose (FBG) 110-180 mg/dL] were randomly and equally assigned to the HC, LC, HC + BBR, LC + BBR, BBR, and non-exercising control (CON) groups. The HC (2:1 work-to-rest) and LC (1:1 work-to-rest) home-based training programs included 2-4 sets of 8 exercises at 80%-95% HRmax, twice a week for 8 weeks. Participants in the berberine groups received approximately 1000 mg daily. All exercise interventions led to a significant reduction in hs-CRP, IL-1β, insulin, FBG, and insulin resistance index (HOMA-IR) versus CON. Notably, there was a significant reduction in FBG and HOMA-IR with the BBR group compared to the baseline. Both NLRP3 and H19 experienced a significant drop only with LC in comparison to the baseline. While both exercise protocols were beneficial overall, LC uniquely exhibited more anti-inflammatory effects, as indicated by reductions in H19 and NLRP3. However, the addition of berberine to the exercise programs did not demonstrate additional benefits.

Early Conversion of Intensive Insulin Therapy to IDegLira Demonstrates Higher Efficacy and Safety in Reducing Fasting Blood Glucose and HbA1c in T2DM Patients

Early Conversion of Intensive Insulin Therapy to IDegLira Demonstrates Higher Efficacy and Safety in Reducing Fasting Blood Glucose and HbA1c in T2DM Patients

The Effect of Sacha Inchi Tempe on Blood Glucose, HOMA-IR, and TNF-ɑ in Rats with Metabolic Syndrome

This research aimed to evaluate the impact of sacha inchi tempe (Plukenetia volubilis L.) on Fasting Blood Glucose (FBG), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and Tumor Necrosis Factor Alpha (TNF-ɑ) levels. In addition, metabolic syndrome was induced in 36 male Wistar rats aged 2 months at 150–200 g weight by giving a High-Fat High-Fructose diet (HFFD) for 2 weeks. The extract was administered through oral gavage in dose-dependent manner and rats were allocated into 6 groups, namely: 1). Normal control or K0; 2). Negative control or K-; 3). Positive control or K+ with 0.18 mg/200 g BB of simvastatin; 4). Intervention with 0.9 g sacha inchi tempe or P1; 5). Intervention with 1.8 g sacha inchi tempe or P2, and; 6). Intervention with 3.6 g sacha inchi tempe or P3. Meanwhile, normal chow rats were used and served as the control group. After 2 and 5 weeks of induction and intervention, blood was drawn to determine FBG. Blood insulin was examined after 5 week of intervention. Rats were euthanized at the end of the intervention for hepatic TNF-α analysis before calculating HOMA-IR. The result showed that there was a significant difference (p<0.05) in FBG, HOMA-IR and hepatic TNF-α levels after sacha inchi tempe treatment. Rats receiving the highest dose of sacha inchi tempe had the most significant reduction (p<0.05) in FBG, HOMA-IR and hepatic TNF-α, when compared to simvastatin group. Therefore, sacha inchi tempe could attenuate glycemic and inflammation profiles in metabolic syndrome.

The novel chimeric multi-agonist peptide (GEP44) reduces energy intake and body weight in male and female diet-induced obese mice in a glucagon-like peptide-1 receptor-dependent manner.

We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2 receptor (Y1R and Y2R) reduced energy intake and body weight (BW) in diet-induced obese (DIO) rats. We hypothesized that GEP44 reduces energy intake and BW primarily through a GLP-1R dependent mechanism. To test this hypothesis, GLP-1R+/+ mice and GLP-1R null (GLP-1R-/-) mice were fed a high fat diet for 4 months to elicit diet-induced obesity prior to undergoing a sequential 3-day vehicle period, 3-day drug treatment (5, 10, 20 or 50 nmol/kg; GEP44 vs the selective GLP-1R agonist, exendin-4) and a 3-day washout. Energy intake, BW, core temperature and activity were measured daily. GEP44 (10, 20 and 50 nmol/kg) reduced BW after 3-day treatment in DIO male GLP-1R+/+ mice by -1.5 ± 0.6, -1.3 ± 0.4 and -1.9 ± 0.4 grams, respectively (P<0.05), with similar effects being observed in female GLP-1R+/+ mice. These effects were absent in male and female DIO GLP-1R-/- mice suggesting that GLP-1R signaling contributes to GEP44-elicited reduction of BW. Further, GEP44 decreased energy intake in both male and female DIO GLP-1R+/+ mice, but GEP44 appeared to produce more consistent effects across multiple doses in males. In GLP-1R-/- mice, the effects of GEP44 on energy intake were only observed in males and not females, suggesting that GEP44 may reduce energy intake, in part, through a GLP-1R independent mechanism in males. In addition, GEP44 reduced core temperature and activity in both male and female GLP-1R+/+ mice suggesting that it may also reduce energy expenditure. Lastly, we show that GEP44 reduced fasting blood glucose in DIO male and female mice through GLP-1R. Together, these findings support the hypothesis that the chimeric peptide, GEP44, reduces energy intake, BW, core temperature, and glucose levels in male and female DIO mice primarily through a GLP-1R dependent mechanism.

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&lt;0.012), fasting plasma glucose (P&lt;0.003), and postprandial glucose levels (P&lt;0.001), along with a reduction in body weight (P&lt;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&lt;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.

Effect of Vitamin C on Blood Glucose Levels, Glycosylated Hemoglobin, and Serum Lipid Profile in Patients with Type 2 Diabetes Mellitus: A Prospective Study

Abstract Background: Vitamin C reduces oxidative stress as well as prevents nonenzymatic glycosylation of proteins because of its structural similarity to glucose. This prospective study was conducted to investigate the impact of vitamin C supplementation on glycemic control and serum lipid profile in newly diagnosed patients with type 2 diabetes mellitus (T2DM). Materials and Methods: Adult patients attending the outpatient department of a tertiary care hospital, diagnosed with T2DM within the last 3 months, with fasting blood glucose (FBG) levels exceeding 126 mg/dL, were randomly assigned to either control group (n = 98) or study group (n = 102). The study group received oral vitamin C (1 g/day) in addition to metformin 500 mg twice daily, while the control group received metformin 500 mg twice daily alone. Baseline characteristics, including age, gender, and comorbidities, were recorded. The parameters FBG, postprandial blood glucose (PPBG), glycosylated hemoglobin (HbA1c), and serum lipid profile were measured at baseline and at the 12th week. Results: Both the control and study groups experienced significant reductions in FBG, PPBG, and HbA1c levels after 12 weeks. However, the study group exhibited greater improvements, with FBG decreasing by 22.42 ± 2.7 mg/dL (P &lt; 0.05), PPBG decreasing by 33.25 ± 4.9 mg/dL (P &lt; 0.05), and HbA1c decreasing by 1.33 ± 0.3 g% (P &lt; 0.05). Additionally, both groups demonstrated significant improvements in serum lipid profile parameters, with the study group showing more significant improvements in high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol levels compared to the control group. Conclusion: Vitamin C supplementation as an adjuvant therapy with metformin for 12 weeks produces beneficial effects in T2DM patients, including improved glycemic control and significant improvement in the lipid profile.

Effects of cinnamon supplementation on metabolic biomarkers in individuals with type 2 diabetes: a systematic review and meta-analysis.

The global prevalence of type 2 diabetes mellitus (DM2) has been rising significantly over the years. Recent studies have shown beneficial effects of cinnamon on metabolic biomarkers. The objective of this review was to assess the effect of cinnamon supplementation on metabolic biomarkers in patients with DM2. The Pubmed/MEDLINE, Cochrane CENTRAL, and Embase databases were searched up to November 10, 2022. A systematic search was performed for randomized controlled trials (RCTs) evaluating the effect of cinnamon supplementation on metabolic biomarkers, in adults and the elderly with DM2, and comparing the data for a cinnamon intervention group with that for a placebo group or a control group. The main exclusion criteria were studies (1) with other types of diabetes (ie, gestational diabetes or type 1 diabetes), (2) without cinnamon consumption, (3) that did not evaluate metabolic biomarkers, or (4) in vitro and animal studies. Two researchers independently screened 924 records, evaluated full-text studies, extracted data, and appraised their quality. A third researcher was consulted to resolve any discrepancies. The data were pooled using random-effects models and expressed as the weighted mean difference (WMD) with 95% CI. Heterogeneity was assessed using Cochran's Q test and quantified using I2 statistics. Risk of bias was assessed using the Joanna Briggs Institute (JBI) instrument. Sensitivity analysis and the GRADE system were used to assess the robustness and certainty of the findings. In total, 28 RCTs with a duration ranging from 30 to 120 days and a total enrollment of 3054 patients with DM2 were included. Participants consuming cinnamon showed a significant reduction in fasting blood glucose (FBG) (WMD: -15.26 mg/dL; 95% CI: -22.23 to -8.30; I2 = 88%), postprandial glucose (WMD: -39.22 mg/dL; 95% CI: -63.90 to -14.55; I2 = 100%), HbA1c (WMD: -0.56 mg/dL; 95% CI: -0.99 to -0.13; I2 = 94%), and HOMA-IR (WMD = -0.76, 95% CI: -1.13 to -0.39; I2 = 22%) compared with the control group. An intervention of cinnamon in capsule form reduced FBG (WMD:-18.43 mg/dL, 95% CI: -26.32 to -10.53; I2 = 89%), postprandial glucose (WMD: -44.83 mg/dL, 95% CI: -70.67 to -18.99; I2 = 100%), HbA1c (WMD: -0.56 mg/dL, 95% CI: -1.02 to -0.09; I2 = 94%), total cholesterol (WMD: -13.39 mg/dL; 95% CI: -24.71 to -2.07; I2 = 96%), LDL-C (WMD: -6.49 mg/dL, 95% CI: -12.69 to -0.29; I2 = 92%), and triglycerides (WND: -19.75 mg/dL; 95% CI, -33.71 to -5.80; I2 = 88%). Both doses (≤2 g/day and >2 g/day) reduced FBG and postprandial glucose. Only cinnamon doses of ≤2 g/day reduced HbA1c (WMD: -0.68 mg/dL, 95% CI: -1.16 to -0.1; I2 = 92%), HOMA-IR (WMD: -0.94 mg/dL; 95% CI: -1.21 to -0.67; I2 = 0%), and BMI (WMD: -1.18 kg/m2; 95% CI: -1.97 to -0.39; I2 = 0%). The data suggest that cinnamon improves the glycemic and lipid profile and reduces the BMI, particularly in DM2 patients who receive cinnamon supplementation in capsule form and at a dose of ≤2 g/day. PROSPERO registration no. CRD42022370332.

Effects of Herbal Tea (Non-Camellia sinensis) on Glucose Homeostasis and Serum Lipids in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Hyperglycemia and hyperlipidemia increase the risk for diabetes and its complications, atherosclerosis, heart failure, and stroke. Identification of safe and cost-effective means to reduce risk factors is needed. Herbal teas may be a vehicle to deliver antioxidants and polyphenols for prevention of complications. This systematic review and meta-analysis were conducted to evaluate and summarize the impact of herbal tea (non-Camellia sinensis) on glucose homeostasis and serum lipids in individuals with type 2 diabetes (T2D). PubMed, FSTA, Web of Science, CINAHL, MEDLINE, and Cochrane Library databases were searched from inception through February 2023 using relevant keyword proxy terms for diabetes, serum lipids, and "non-Camellia sinensis" or "tea." Data from 14 randomized controlled trials, totaling 551 participants, were included in the meta-analysis of glycemic and serum lipid profile end points. Meta-analysis suggested a significant association between drinking herbal tea (prepared with 2-20 g d-1 plant ingredients) and reduction in fasting blood glucose (FBG) (P = .0034) and glycated hemoglobin (HbA1c; P = .045). In subgroup analysis based on studies using water or placebo as the control, significant reductions were found in serum total cholesterol (TC; P = .024), low-density lipoprotein cholesterol (LDL-C; P = .037), and triglyceride (TG; P = .043) levels with a medium effect size. Meta-regression analysis suggested that study characteristics, including the ratio of male participants, trial duration, and region, were significant sources of FBG and HbA1c effect size heterogeneity; type of control intervention was a significant source of TC and LDL-C effect size heterogeneity. Herbal tea consumption significantly affected glycemic profiles in individuals with T2D, lowering FBG levels and HbA1c. Significance was seen in improved lipid profiles (TC, TG, and LDL-C levels) through herbal tea treatments when water or placebo was the control. This suggests water or placebo may be a more suitable control when examining antidiabetic properties of beverages. Additional research is needed to corroborate these findings, given the limited number of studies.

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.

Novel thiosemicarbazide-based β-carboline derivatives as α-glucosidase inhibitors: Synthesis and biological evaluation

In the quest for potent α-glucosidase inhibitors to combat diabetes, a series of novel thiosemicarbazide-based β-carboline derivatives (CTL1∼36) were synthesized and evaluated. CTL1∼36 exhibited remarkable inhibitory effects against α-glucosidase, with IC50 values ranging from 2.81 to 12.40 μM, significantly surpassing the positive control acarbose (IC50 = 564.28 μM). Notably, CTL26 demonstrated the most potent inhibition (IC50 = 2.81 μM) and was characterized as a non-competitive inhibitor. Through a combination assay with fluorescence quenching, 3D fluorescence spectra, CD spectra, and molecular docking, we elucidated that CTL26 formed a complex with α-glucosidase via hydrogen bondings and hydrophobic interactions, leading to α-glucosidase conformation changes that impaired enzymatic activity. In vivo studies revealed that oral administration of CTL26 (25 and 50 mg/kg/d) reduced fasting blood glucose levels, enhanced glucose tolerance, and ameliorated lipid abnormalities in diabetic mice. These findings positioned CTL26 as a promising candidate for the development of α-glucosidase inhibitors with anti-diabetic potential.

The enduring metabolic improvement of combining dual amylin and calcitonin receptor agonist and semaglutide treatments in a rat model of obesity and diabetes.

Long-acting dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for the treatment of type 2 diabetes and obesity due to their beneficial effects on body weight, glucose control, and insulin action. However, how the metabolic benefits are maintained after long-lasting treatment is unknown. This study investigates the long-term anti-obesity and anti-diabetic treatment efficacy of the DACRA KBP-336 alone and combined with the GLP-1 analog semaglutide. Zucker diabetic Sprague Dawley (ZDSD) rats with obesity and diabetes received KBP-336 (4.5 nmol/kg Q3D), semaglutide (50 nmol/kg Q3D), or the combination for 7 mo, and the treatment impact on body weight, food intake, glucose control, and insulin action was evaluated. Furthermore, serum levels of the cardiac fibrosis biomarker endotrophin were evaluated. KBP-336, semaglutide, and the combination lowered body weight significantly compared with the vehicle, with the combination inducing a larger and more sustained weight loss than either monotherapy. All treatments resulted in reduced fasting blood glucose levels and HbA1c levels and improved glucose tolerance compared with vehicle-treated rats. Furthermore, all treatments protected against lost insulin secretory capacity and improved insulin action. Serum levels of endotrophin were significantly lowered by KBP-336 compared with vehicle. This study shows the benefit of combining KBP-336 and semaglutide to obtain significant and sustained weight loss, as well as improved glucose control. Furthermore, KBP-336-driven reductions in circulating endotrophin indicate a clear reduction in the risk of complications. Altogether, KBP-336 is a promising candidate for the treatment of obesity and type 2 diabetes both alone and in combination with GLP-1 analogs.NEW & NOTEWORTHY These studies describe the benefit of combining dual amylin and calcitonin receptor agonists (DACRA) with semaglutide for long-term treatment of obesity and type 2 diabetes. Combination treatment induced sustained weight loss and improved glucose control. A DACRA-driven reduction in a serological biomarker of cardiac fibrosis indicated a reduced risk of complications. These results highlight DACRAs as a promising candidate for combination treatment of obesity and type 2 diabetes and related long-term complications.

Is Curcumin Intake Really Effective for Chronic Inflammatory Metabolic Disease? A Review of Meta-Analyses of Randomized Controlled Trials.

This review aimed to examine the effects of curcumin on chronic inflammatory metabolic disease by extensively evaluating meta-analyses of randomized controlled trials (RCTs). We performed a literature search of meta-analyses of RCTs published in English in PubMed®/MEDLINE up to 31 July 2023. We identified 54 meta-analyses of curcumin RCTs for inflammation, antioxidant, glucose control, lipids, anthropometric parameters, blood pressure, endothelial function, depression, and cognitive function. A reduction in C-reactive protein (CRP) levels was observed in seven of ten meta-analyses of RCTs. In five of eight meta-analyses, curcumin intake significantly lowered interleukin 6 (IL-6) levels. In six of nine meta-analyses, curcumin intake significantly lowered tumor necrosis factor α (TNF-α) levels. In five of six meta-analyses, curcumin intake significantly lowered malondialdehyde (MDA) levels. In 14 of 15 meta-analyses, curcumin intake significantly reduced fasting blood glucose (FBG) levels. In 12 of 12 meta-analyses, curcumin intake significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR). In seven of eight meta-analyses, curcumin intake significantly reduced glycated hemoglobin (HbA1c) levels. In eight of ten meta-analyses, curcumin intake significantly reduced insulin levels. In 14 of 19 meta-analyses, curcumin intake significantly reduced total cholesterol (TC) levels. Curcumin intake plays a protective effect on chronic inflammatory metabolic disease, possibly via improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin as a natural product support the potential for the prevention and treatment of chronic inflammatory metabolic diseases.

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.

Fabrication of losartan-loaded chitosan-cloaked dopamine nanoparticles for improving diabetic nephropathy via regulation of oxidative stress and blood glucose

Diabetic nephropathy (DN) is a significant problem for people with diabetes, and its progression is strongly associated with oxidative stress induced by high blood sugar levels (hyperglycemia). This study presents a novel type of losartan-loaded chitosan-cloaked dopamine nanoparticles (CSDLNPs). It can specifically aggregate in damaged kidneys, lower blood glucose levels, and ameliorate the damage caused by oxidative stress. CSDLNPs exhibit excellent dispersion physiological stability and sensitive release under an acidic pH milieu. Additionally, they have potent scavenging capabilities against a wide range of reactive nitrogen and oxygen radicals. Furthermore, in vitro, investigations validate that CSDLNPs exhibit superior biocompatibility, facilitate specific absorption in the HK-2 proximal tubule epithelial cell line, and effectively mitigate oxidative stress generated by high hyperglycemia. Following CSDLNPs treatment, DN exhibits a reduction in fasting blood glucose (FBG) levels and a restoration of urine and blood indices to levels close to normal. The H&E pathological staining results demonstrate that CSDLNPs effectively suppress collagen deposition, glycogen accumulation, and renal interstitium enlargement, indicating remarkable therapeutic efficacy. Furthermore, dopamine is a drug carrier and antioxidant without needing an external carrier, demonstrating superior biosafety and potential for translation to diabetic nephropathy.

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.