Hypoglycemic Effect Research Articles

Revealing the microbial diversity and volatile flavor formation in finger citron kombucha by metagenomic and GC-MS analysis

Kombucha is a kind of health drink formed by the metabolism of Symbiotic Culture of Bacteria and Yeast (SCOBY) composed of yeast, acetic acid bacteria and lactic acid bacteria, which is popular among researchers and fond of consumers because of its antioxidant and hypoglycemic effects. In this study, the finger citron kombucha with different fermentation time (2, 4, 6, 8 day) were analyzed by headspace solid phase micro-extraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) and metagenomic sequencing. The results showed that a total of 76 volatiles were identified, including 15 key volatiles, such as linalool, geraniol, α-terpinene, and limonene, which had a great influence on the flavor of kombucha. Metagenomic analysis showed that unclassified-g-Gluconobacter, Komagataeibacter saccharivorans, Gluconobacter-sp.-R71656 and other microorganisms were the dominant species in finger citron kombucha. Through the correlation heat map analysis of volatiles and microbial composition, it was found that Gluconobacter had a positive effect on the formation of most volatiles of kombucha. In addition, Novacetimonas hansenii, Brettanomyces bruxellensis and Wickerhamiella sorbophila were also closely related to the flavor formation of kombucha. This study provided a theoretical basis for finding the key aroma-producing microorganisms in the fermentation process of finger citron kombucha and the subsequent construction of SCOBY.

Therapeutic potentials of Hibiscus trionum: Antioxidant, anti-lipid peroxidative, hypoglycemic, and hepatoprotective effects in type 1 diabetic rats

Recent advances in diabetes treatment have primarily focused on insulin and hypoglycemic agents; however, there is growing interest in exploring herbal and synthetic alternatives. Numerous studies have highlighted the preventive effectiveness of regular plant consumption in managing chronic conditions, particularly diabetes. Hibiscus, a medicinal plant recognized in various cultures, is known for its diverse health benefits. This study investigated the impact of Hibiscus trionum on glycemic control and assessed its influence on glucose and insulin levels in diabetes-induced rats. The concentrations of antioxidant enzymes, particularly superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were scrutinized across multiple body tissues (plasma, heart, muscle, liver, and kidney). The malondialdehyde (MDA) concentration, an indicator of lipid peroxidation, was examined in both plasma and tissue samples. Serum total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels were evaluated. Diabetic Group (D) exhibited a significant decrease in body weight, increased fluid and food consumption, elevated blood glucose levels, and increased antioxidant enzyme activity. Moreover, the diabetic group also showed increased levels of MDA, TC, TG, AST, and ALT, along with reduced insulin levels, compared to the control group. A substantial improvement in all parameters impaired by diabetes was observed following the application of Hibiscus trionum (HTT) in the Diabetes+HTT group. The antioxidative stress-reducing, lipid peroxidation-improving, and hepatoprotective potential of Hibiscus trionum in mitigating diabetes-induced oxidative stress is noteworthy. These findings indicate that HTT supplementation has valuable beneficial effects in protecting against the harmful impacts of diabetes.

Restoring bone-fat equilibrium: Baicalin's impact on P38 MAPK pathway for treating diabetic osteoporosis

Diabetes can lead to a disorder of bone-fat balance, a significant cause of osteoporosis due to changes in environmental factors. Baicalin (Bai), an active ingredient of Scutellaria baicalensis, has been confirmed to possess antioxidant, hypoglycemic, and anti-osteoporotic effects. However, a comprehensive understanding of Bai's influence on diabetic osteoporosis (DOP), including its effects and underlying mechanisms, remains elusive. This study investigated Bai's impact on the bone-fat equilibrium in rats with DOP. The results indicated that Bai alleviated bone damage in DOP by promoting osteogenesis and inhibiting adipogenesis. Concurrently, through bioinformatics analysis, it was suggested that Bai's mechanism of action might involve the P38-MAPK pathway. In vitro, Bai was found to enhance the development of bone marrow mesenchymal stem cells (BMSCs) towards osteogenic lineages while suppressing their differentiation towards adipogenic lineages. It was discovered that Bai's promotion of BMSC osteogenic differentiation depends on the P38-MAPK pathway. Additionally, the synergistic effect mediated by Bai and P38-MAPK inhibitor suppressed BMSC adipogenic differentiation. Our research indicates that the P38-MAPK pathway play a role in Bai's effects on the osteogenic-adipogenic differentiation of BMSCs, showcasing the potential for DOP treatment. This study highlights Bai's ability to regulate the equilibrium between bone and fat, presenting a novel approach to adressing DOP.

Polysaccharides from Dendrobium officinale delay diabetic kidney disease interstitial fibrosis through LncRNA XIST/TGF-β1

PurposeRenal interstitial fibrosis is a pathological manifestation of the progression of diabetic kidney disease (DKD). Dendrobium officinale polysaccharides (DOP), one of the major active components of Dendrobium officinale, have hypoglycemic and hypolipidemic effects and are used clinically to treat diabetes. However, the role of DOP in delaying DKD progression remains unclear. This study aimed to explore the potential mechanisms by which DOP delays DKD renal interstitial fibrosis. MethodsUsing db/db mice as a model of DKD, we administered DOP by gavage and observed its therapeutic effectiveness. Employing ASO technology, we knocked down lncRNA XIST expression in kidney tissues and detected the expression of lncRNA XIST, TGF-β1, and renal interstitial fibrosis-related molecules. ResultsDOP was primarily composed of monosaccharides, with 91.57% glucose and 1.41% mannose, forming a spheroid-like structure. It has a high polydispersity index with an Mw/Mn of 6.146, and the polysaccharides are mainly connected by 4-Man(p) and 4-Glc(p) linkages. In the kidneys of db/db mice, lncRNA XIST and TGF-β1 are highly expressed; however, their expression is significantly reduced after gastric infusion with DOP, and upon knockdown of lncRNA XIST, it might delay the progression of renal interstitial fibrosis in DKD. ConclusionDOP may delay the progression of DKD renal interstitial fibrosis through the regulation of the LncRNA XIST/TGF-β1 related fibrotic pathway. This provides a new perspective for clinical strategies to delay the progression of DKD renal interstitial fibrosis.

Characterization of tirzepatide-treated patients achieving different glycemic control levels in SURPASS-AP-Combo.

The study objective was to characterize subgroups of Asia-Pacific patients with type 2 diabetes who achieved different glycated hemoglobin (HbA1c) targets on tirzepatide treatment. This was a post hoc analysis of the SURPASS AP-Combo study. Baseline characteristics, changes in metabolic markers, and safety were compared between tirzepatide-treated patients achieving HbA1c <7.0% (<53 mmol/mol) and those achieving ≥7.0% (≥53 mmol/mol) at week 40. Among patients achieving HbA1c <7.0% (<53 mmol/mol), further comparisons were conducted among subgroups achieving HbA1c <5.7% (<39 mmol/mol), 5.7% to 6.5% (39 to 48 mmol/mol), and >6.5% to <7.0% (>48 to <53 mmol/mol). Five hundred ninety-eight patients on tirzepatide treatment without rescue medication were included (56.9% male; mean age: 53.1 years; mean baseline HbA1c: 8.7% [71.6 mmol/mol]). Patients achieving HbA1c <7.0% (<53 mmol/mol) versus ≥7.0% (≥53 mmol/mol) were slightly younger with a shorter disease duration and lower HbA1c at baseline, and they had greater improvements in HbA1c, fasting serum glucose, body weight, BMI, waist circumference, waist-height ratio, diastolic blood pressure, lipids, and self-monitored blood glucose at week 40. Patients achieving HbA1c <5.7% (<39 mmol/mol) versus those achieving 5.7% to 6.5% (39 to 48 mmol/mol) and those achieving >6.5% to <7.0% (>48 to <53 mmol/mol) were much younger, had much lower HbA1c, and had further improvements in metabolic markers. Tirzepatide treatment was well tolerated irrespective of the HbA1c level achieved, with a low incidence of hypoglycemic events. These findings may help to inform clinical decisions in Asia-Pacific patients with type 2 diabetes.

The quality control and hypoglycemic effect of Cinnamomi Cortex aqueous extract

The quality control and hypoglycemic effect of Cinnamomi Cortex aqueous extract

A phase 1, randomized, double-blind, placebo-controlled trial investigating the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide in healthy Chinese subjects.

The trial (NCT04016974) investigated the pharmacokinetics, pharmacodynamics, safety and tolerability of oral semaglutide, the first orally administered glucagon-like peptide-1 analogue for type 2 diabetes, in healthy Chinese subjects. This single-centre, multiple-dose, placebo-controlled trial randomized 32 healthy Chinese adults to once-daily oral semaglutide (3 mg escalating to 14 mg) or placebo for 12 weeks. Blood samples were collected regularly during treatment and follow-up. The primary endpoint was the area under the semaglutide concentration-time curve over a dosing interval (0-24 h) at steady state (AUC0-24h,sema,SS). Secondary pharmacokinetic endpoints included the maximum observed semaglutide plasma concentration at steady state (Cmax,sema,SS). Supportive secondary pharmacodynamics endpoints included changes in body weight and fasting plasma glucose. Treatment with all oral semaglutide doses showed dose-dependent increases in semaglutide exposure in healthy Chinese subjects at steady state, determined by AUC0-24h,sema,SS (233, 552 and 1288 h·nmol/L for 3, 7 and 14 mg of oral semaglutide, respectively) and Cmax,sema,SS. Oral semaglutide treatment was associated with significant reductions in body weight (p = .0001) and fasting plasma glucose (p = .0011) versus placebo at the end of treatment. The safety and tolerability of oral semaglutide were consistent with the known profile of glucagon-like peptide-1 receptor agonists, with no severe or blood-glucose-confirmed symptomatic hypoglycaemic events, serious adverse events or deaths. The most frequent adverse events were gastrointestinal disorders. At steady state, oral semaglutide exposure was dose dependent and close to dose proportionality in healthy Chinese subjects. This is consistent with previous clinical pharmacology results for oral semaglutide.

Antidiabetic Potential and Metabolite Profile of Leaf and Stem Extract of Castanopsis tungurrut (Blume) A.DC.

&lt;p&gt;Diabetes mellitus is a metabolic disorder caused by high blood sugar levels. One species in &lt;em&gt;the Castanopsis&lt;/em&gt; genus is proven with a hypoglycemic effect. Therefore, the study aimed to discover the potential of &lt;em&gt;Castanopsis tungurrut&lt;/em&gt; as an antidiabetic. Sample extraction, α-amylase inhibition, glucose diffusion analysis, GC-MS analysis, and molecular docking were applied in this study. Maceration of the leaf ethanol extract showed the highest yield value of 21.08%, while the stem extract was 14.04%. Leaf ethanol extract and stem ethyl acetate extract showed the highest inhibiting α-amylase activity with an inhibition value of 33.74%±1.54 and 34.45%±1.08 at 1 mg/mL concentration. The glucose entrapment assay showed that these two extracts could inhibit the diffusion of glucose in the dialysis bag. The final result was glucose concentration in dialysate for the two extracts of 0.114±0.001 mg/mL and 0.116±0.001 mg/mL which was lower than acarbose in 0.120±0.004 mg/mL. GC-MS analysis showed 6 metabolites in leaf ethanol extract and 22 metabolites in stems ethyl acetate extract from an alkane, salicylic, cinnamic, terpene, steroid, and fatty acid. Molecular docking resulting between the compounds with α-amylase enzymes complex showed γ-sitosterol and ß-bisabolene from &lt;em&gt;C. tungurrut&lt;/em&gt; extract have the potential to be developed as an antidiabetic drug due to its good inhibitory activity with binding affinity values of -9.1 and -6.9 that considered better and quite close to acarbose as control of -7.7.&lt;/p&gt;

Association of dipeptidyl peptidase-4 inhibitor initiation at glycated haemoglobin

Therapeutic inertia, hypoglycaemia and poor treatment persistence can lead to glycaemic fluctuation and poor outcomes in type 2 diabetes (T2D). We compared glycated haemoglobin (HbA1c) variability, insulin initiation, severe hypoglycaemia and clinical events in patients with T2D initiated dipeptidyl peptidase-4 inhibitors (DPP4is) at low versus high HbA1c thresholds. Using territory-wide electronic medical records in Hong Kong, we curated a propensity score-matched cohort of patients initiated DPP4i at HbA1c <7.5% versus ≥7.5% in 2007-2019. We expressed the HbA1c variability score (HVS) as a proportion of HbA1c varied by ≥0.5% compared with preceding values. We used the Cox model to compare the risks of insulin initiation and clinical outcomes, adjusted for time-varying variables between the two groups. Mediation analysis estimated the effects of HbA1c variability on outcomes. Among 6874 insulin-naïve patients who initiated DPP4i, 88.7% were treated with metformin and 79.6% with sulphonylureas at baseline (54.9% men; mean age 65.2 ± 11.4 years). After a median follow-up of 4.6 years, compared with the high-threshold plus high-HVS group (≥50%), the low-threshold plus low-HVS (<50%) group had reduced hazard ratios (95% confidence interval) of insulin initiation (0.35, 0.31-0.40), severe hypoglycaemia (0.38, 0.34-0.44), major adverse cardiovascular endpoints (0.76, 0.66-0.88), heart failure (0.42, 0.36-0.49), end-stage kidney disease (0.65, 0.36-0.49) and mortality (0.45, 0.35-0.57). Reduced HbA1c variability explained 31.1%-81.2% of the effect size of DPP4i initiation at HbA1c <7.5% versus ≥7.5% on outcomes. In Chinese patients with T2D, avoiding therapeutic inertia with intensified glycaemic control at HbA1c <7.5% using drugs with low risk of hypoglycaemia and good tolerability, such as DPP4i, delayed insulin treatment, reduced HbA1c variability and improved clinical events.

Risk factors and prediction of hypoglycaemia using the Hypo-RESOLVE cohort: a secondary analysis of pooled data from insulin clinical trials.

The objective of the Hypoglycaemia REdefining SOLutions for better liVES (Hypo-RESOLVE) project is to use a dataset of pooled clinical trials across pharmaceutical and device companies in people with type 1 or type 2 diabetes to examine factors associated with incident hypoglycaemia events and to quantify the prediction of these events. Data from 90 trials with 46,254 participants were pooled. Analyses were done for type 1 and type 2 diabetes separately. Poisson mixed models, adjusted for age, sex, diabetes duration and trial identifier were fitted to assess the association of clinical variables with hypoglycaemia event counts. Tree-based gradient-boosting algorithms (XGBoost) were fitted using training data and their predictive performance in terms of area under the receiver operating characteristic curve (AUC) evaluated on test data. Baseline models including age, sex and diabetes duration were compared with models that further included a score of hypoglycaemia in the first 6 weeks from study entry, and full models that included further clinical variables. The relative predictive importance of each covariate was assessed using XGBoost's importance procedure. Prediction across the entire trial duration for each trial (mean of 34.8 weeks for type 1 diabetes and 25.3 weeks for type 2 diabetes) was assessed. For both type 1 and type 2 diabetes, variables associated with more frequent hypoglycaemia included female sex, white ethnicity, longer diabetes duration, treatment with human as opposed to analogue-only insulin, higher glucose variability, higher score for hypoglycaemia across the 6 week baseline period, lower BP, lower lipid levels and treatment with psychoactive drugs. Prediction of any hypoglycaemia event of any severity was greater than prediction of hypoglycaemia requiring assistance (level 3 hypoglycaemia), for which events were sparser. For prediction of level 1 or worse hypoglycaemia during the whole follow-up period, the AUC was 0.835 (95% CI 0.826, 0.844) in type 1 diabetes and 0.840 (95% CI 0.831, 0.848) in type 2 diabetes. For level 3 hypoglycaemia, the AUC was lower at 0.689 (95% CI 0.667, 0.712) for type 1 diabetes and 0.705 (95% CI 0.662, 0.748) for type 2 diabetes. Compared with the baseline models, almost all the improvement in prediction could be captured by the individual's hypoglycaemia history, glucose variability and blood glucose over a 6 week baseline period. Although hypoglycaemia rates show large variation according to sociodemographic and clinical characteristics and treatment history, looking at a 6 week period of hypoglycaemia events and glucose measurements predicts future hypoglycaemia risk.

Research on the effects of intestinal FXR agonists and antibiotics on the regulation of red kidney bean polysaccharides in the liver metabolism in mice with type 2 diabetes

AbstractOur previous study revealed that red kidney bean polysaccharides (RKB) exhibit a pronounced hypoglycemic effect on type 2 diabetic rats, while simultaneously exerting a significant ameliorative impact on hepatic damage in these animals. However, the precise mechanism underlying the effects of RKB on diabetes and liver metabolism remains unproven. In this study, we utilized a mouse model of type 2 diabetes induced by a high‐fat diet combined with streptozotocin to investigate the impact of RKB. We administered a combined intervention involving antibiotics, fexaramine, and RKB to elucidate the mechanism underlying RKB's effects. Our findings demonstrated that RKB significantly ameliorated liver function indices and histopathological injuries. Nevertheless, when antibiotics and fexaramine were introduced as interventions, they hindered the beneficial effects of RKB on liver function in type 2 diabetic mice. Furthermore, our nontargeted metabolomics analysis revealed that antibiotics and fexaramine exerted their inhibitory actions on RKB efficacy through modulation of distinct metabolites involved in glycerophospholipid and purine metabolic pathways.

Generalization of a Deep Learning Model for Continuous Glucose Monitoring-Based Hypoglycemia Prediction: Algorithm Development and Validation Study.

Predicting hypoglycemia while maintaining a low false alarm rate is a challenge for the wide adoption of continuous glucose monitoring (CGM) devices in diabetes management. One small study suggested that a deep learning model based on the long short-term memory (LSTM) network had better performance in hypoglycemia prediction than traditional machine learning algorithms in European patients with type 1 diabetes. However, given that many well-recognized deep learning models perform poorly outside the training setting, it remains unclear whether the LSTM model could be generalized to different populations or patients with other diabetes subtypes. The aim of this study was to validate LSTM hypoglycemia prediction models in more diverse populations and across a wide spectrum of patients with different subtypes of diabetes. We assembled two large data sets of patients with type 1 and type 2 diabetes. The primary data set including CGM data from 192 Chinese patients with diabetes was used to develop the LSTM, support vector machine (SVM), and random forest (RF) models for hypoglycemia prediction with a prediction horizon of 30 minutes. Hypoglycemia was categorized into mild (glucose=54-70 mg/dL) and severe (glucose<54 mg/dL) levels. The validation data set of 427 patients of European-American ancestry in the United States was used to validate the models and examine their generalizations. The predictive performance of the models was evaluated according to the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). For the difficult-to-predict mild hypoglycemia events, the LSTM model consistently achieved AUC values greater than 97% in the primary data set, with a less than 3% AUC reduction in the validation data set, indicating that the model was robust and generalizable across populations. AUC values above 93% were also achieved when the LSTM model was applied to both type 1 and type 2 diabetes in the validation data set, further strengthening the generalizability of the model. Under different satisfactory levels of sensitivity for mild and severe hypoglycemia prediction, the LSTM model achieved higher specificity than the SVM and RF models, thereby reducing false alarms. Our results demonstrate that the LSTM model is robust for hypoglycemia prediction and is generalizable across populations or diabetes subtypes. Given its additional advantage of false-alarm reduction, the LSTM model is a strong candidate to be widely implemented in future CGM devices for hypoglycemia prediction.

#1392 MEST-C score correlation with proteinuria reduction after SGLT2i treatment in patients with IgA nephropathy

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). Data available for the use of the MEST-C score to determine if treatment would benefit IgAN patients is scarce. The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the MEST-C score. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of &amp;gt;0.5 grams/day at screening were included. Patients with secondary IgAN and crescents were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Three repeated measurements of proteinuria (mg/24H) were performed, 90 days before SGLT2i treatment initiation, and only patients with stable proteinuria were enrolled in the study. Results 49 patients (35/14 M/F), with mean age of 41,9 ± 19,6 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 68.21±18,1 ml/min/1.73 m2 and Upr: 2196±1091 mg/24H. The MEST-C scores were correlated with the serum creatinine level, proteinuria, and hematuria. The mean serum creatinine level was higher in M1, E1, S1, and T1 compared with score “0”. It was statistically significant (p = 0.03) only in the T-score. The mean proteinuria level was again higher in M1, S1, and T1 but reached statistical significance (p = 0.037) in only the T1-score. E1 has higher hematuria. The Upr/24H difference for dapagliflozin was −24.7% (95% CI −27.5, −23.2; p &amp;lt; 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs, age, and baseline proteinuria. Among MEST-C score parameters, T1 had a negative impact on the antiproteinuric effect of dapagliflozin (p = 0.01) No hypoglycemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy and maximally tolerated RASi. We analyzed renal outcomes in association with pathologic features. We established that the presence of the T1 score has a negative impact on proteinuria reduction after SGLT2i treatment. Further studies are needed to investigate the impact of the use of the Oxford Classification score for developing individual treatment therapies.

#976 Empagliflozin limits AKI incidence and severity following cardiac surgery: an open-label phase IV randomized pilot study

Abstract Background and Aims Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent complication of cardiac surgery assisted by cardiopulmonary bypass (CPB). Currently, no effective preventative strategies exist to reduce the incidence of acute kidney injury (AKI). Sodium-glucose transport protein 2 (SGLT2) inhibitors are effective in reducing the incidence of AKI in studies conducted in patients with chronic kidney disease. Therefore, we hypothesized that perioperative SGLT2 inhibition could reduce the incidence of CSA-AKI. Method In this open-label phase IV, randomized, parallel-group, balanced (1:1), pilot study, adult patients undergoing elective cardiac surgery with CPB were randomized to receive 10 mg empagliflozin per os once daily three days before surgery until two days after surgery, or standard care. The primary outcome was AKI incidence according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Other outcomes included hypoxia-inducible factor 1 alpha (HIF1A) and urinary Kidney Injury Molecule (KIM-1), urinary neutrophil gelatinase associated lipocalin (NGAL) and metabolic parameters such as plasma ketone and glucose concentrations. Results Between March 2022 and April 2023, 60 patients were randomized to empagliflozin (n = 29) or control (n = 31). All patients who underwent cardiac surgery with CPB were included in the intention-to-treat analysis (n = 25; empagliflozin group, n = 30; control group). SGLT2 inhibition significantly reduced the incidence of all stages of AKI (20% vs 66.7%; absolute difference 46%, 95% CI .13 to .63, P &amp;lt; .001). This decline in AKI incidence was reflected in the kidney biomarkers. SGLT2 inhibition also significantly reduced the number of patients with postoperative hyperglycemia (28% vs 60%; absolute difference 32%, 95% CI −56.8 to −7.2, P = .029). We observed no differences in the incidence of neither ketoacidosis nor hypoglycemic events. Conclusion Perioperative SGLT2 inhibition, compared with standard of care, demonstrated a significant reduction in AKI incidence rates. These findings merit validation in a larger placebo-controlled trial which is currently ongoing. Supplementary figures:

#1679 Relationship between initial eGFR DIP with proteinuria after SGLT2i treatment, in patients with IgA nephropathy. A real-world clinical study

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are associated with better cardiovascular outcomes and with nephroprotection independent of diabetes status. Recent data suggest that SGLT2i significantly reduce proteinuria in patients with IgA nephropathy (IgAN). However, they often cause an initial decline in estimated glomerular filtration rate (eGFR). The aim of our study was to assess the degree of proteinuria reduction after SGLT2i treatment in IgAN and its possible association with the initial functional dip in eGFR. Method 63 adult patients with biopsy-proven IgA nephropathy, eGFR ≥ 30 mL/min/1.73 m2 (CKD-epi), and total urine protein of &amp;gt;0.5 grams/day at screening were included. Patients with secondary IgAN were excluded. All receiving maximally tolerated RASi for at least 12 weeks. All patients started dapagliflozin 10 mg once per day after baseline data were registered. The total follow-up was 12 months. The main outcome was the decline in eGFR and the reduction in 24-hour proteinuria from SGLT2i initiation to 1,3, 6, 9, 12 months, end-stage renal disease, or kidney or cardiovascular death. Results 55 patients (38/17 M/F), with mean age of 44,2±18,3 years, completed follow up. 8 patients discontinued treatment due to adverse events attributed to dapagliflozin. At baseline eGFR was 66.17±19,7 ml/min/1.73 m2 and Upr: 2356±1023 mg/24H. There was a transient decline in eGFR, 30 days after initiation of dapagliflozin (66.17±19,7 min/1.73 m2 at baseline to 57 ml/min/1.73 m2) but then, there was an improvement at month 3 from baseline. The Upr/24H difference for dapagliflozin was −25.1% (95% CI −27.5, −23.2; p &amp;lt; 0.001) at the end of follow-up (month 12). Proteinuria reduction was similar across all eGFRs. Notably, a significant correlation was found between the initial eGFR dip and percentage proteinuria reduction in the 12th month. (R = –0.23; p = 0.03). Consistent results of dapagliflozin treatment on proteinuria were found in all analysis subgroups including sex, baseline proteinuria, systolic blood pressure, and body mass index. No hypoglycaemic events were reported and no deaths occurred. Conclusion In the present study, the use of SGLT2i was associated with a significant reduction of proteinuria in patients with IgA nephropathy in patients with maximally tolerated RASi. Higher initial eGFR dip after treatment initiation was a predictor of a significantly higher reduction in proteinuria at the end of follow-up. The correlation between eGFR dip and proteinuria reduction perhaps reflects the intraglomerular pressure reduction, mediated by tubuloglomerular feedback, one of the numerous.

Effects of purple cabbage anthocyanin extract on the gluten characteristics and the gluten network evolution of high-gluten dough.

Anthocyanins are polyphenolic pigments that have hypoglycemic, antioxidation, anti-aging, and other effects. Research has shown that polyphenols can optimize the processing of dough and improve the texture and nutritional characteristics of dough products. The formation of gluten networks is decisive for the quality of flour products. The effects of purple cabbage anthocyanin (PCA) extract on the structure, microscopic morphology, and network formation of gluten protein were studied, and the types of cross-linking between PCA and gluten protein are discussed. The results show that PCA extract increased the free sulfhydryl (SH) group content and the free amino group of gluten proteins, stimulated an increase in the β-sheet ratio and the decrease of α-helix ratio, and increased the gluten index significantly (P < 0.05). The PCA extract also induced gluten protein aggregation, increased the height of protein molecular chains, and stimulated the formation of gluten networks. When PCA extract concentrations were 4 g kg-1 and 8 g kg-1, the gluten network was more homogeneous, continuous, and dense. Appropriate anthocyanins have a positive effect on the properties of gluten and promote the formation of gluten networks. Excessive anthocyanins destroy gluten protein interaction and harm gluten cross-linking. This study may provide a useful source of data for the production of functional flour products rich in anthocyanins. © 2024 Society of Chemical Industry.

#2209 Hypoglycemia induced by hemodialysis in diabetic and non-diabetic patients, how to prevent it? A prospective study

Abstract Background and Aims Hemodialysis-induced hypoglycemia, a documented complication associated with adverse clinical outcomes, including mortality, is linked to factors such as impaired gluconeogenesis, inadequate nutritional status, reduced insulin clearance, glucose loss to the dialysate, and autonomic neuropathy. Glycemic variability is recognized as an independent risk factor for morbidity and mortality. This study aims to investigate the incidence of hypoglycemia during hemodialysis (HD) by exploring protocol-related factors and their impact, such as in-nutrition during HD. Additionally, the study seeks to examine the relationship between nutritional and inflammatory statuses and variations in intradialytic glycemia in both diabetic and non-diabetic patients. Method This prospective study, conducted between September and December 2023, examined the glycemic profiles of HD patients at a hospital HD program. All patients undergo hemodialysis with a dialysate containing 100 mg/dL of glucose. Plasma glucose levels were assessed at the start, 2:30 hours post-initiation, and the end of sessions. Following the 2:30-hour mark, patients received a meal (523 Kcal). Glycose variability was computed by averaging blood glucose differences across all sessions. Data collected included demographics, hemodialysis specifics, and lab results. Inflammatory and nutritional statuses were evaluated using lab tests at the study's beginning and conclusion [ferritin, protein C reactive (PCR), interleukin 6 (IL-6) and albuminemia, urea, creatinemia, cholesterol, respectively]. Anthropometric measurements and bioimpedance assessments were performed, with values averaged for better representation. Categorical variables are shown with frequencies/percentages, and continuous variables with means/standard deviations or medians/interquartile ranges for skewed distributions. The study used repeated measures ANOVA for glycemic profiles, correlation analyses for outcome influences on glycemia, and parametric/non-parametric tests for relations in diabetic and non-diabetic groups. Significance was set at p&amp;lt;0.05, analyzed with SPSS version 29 for Mac OS 13. Results 63 patients, 67.2% (n=43) were males, the medium age was 72.0±11.8 and 50.8% (n=32) had diabetes. Among 9072 measurements, hypoglycemia was observed in 0.07% (n=6) of diabetic patients and 0.01% (n=1) in non-diabetic individual. The initial blood glucose measurement was 139.5±260.0 mg/dL, the second was 117.05±35 mg/dL, and the third was 132.8±21.3 mg/dL. Significant differences were observed in all measurements [F (1.17, 73.58)=23.62; p&amp;lt;0.001]. The mean glycemic variation between the first and second measurements was 23.8±46.0 mg/dL, and for the third measurement was 5.5±71.5 mg/dL. There was no significant correlation found between glycemic and nutritional parameters neither between inflammatory parameters. In the subgroup analysis comparing diabetic and non-diabetic patients, the diabetic group demonstrated lower serum creatinine levels (6.8±2.7 mg/dL) and total cholesterol (137.4±35.6 mg/dL), coupled with a higher Charlson Index (8.2±1.7). These differences were statistically significant (p=0.055, p=0.035, p&amp;lt;0.001). In the subsequent analysis, no other statistically significant associations were observed. Conclusion Contrary to what is described in the literature, the studied population exhibited a very low incidence of hypoglycemic events. This underscores the importance of nutrition during HD, along with the use of a glucose-containing dialysate, as an effective preventive measure against intradialytic hypoglycemia. Careful consideration of these factors is warranted to prevent adverse health consequences for our patients. It is plausible that diabetic patients may face an elevated risk of malnutrition, necessitating heightened concern and a more proactive preventive approach.

Effects of metformin on the glucose regulation, lipid levels and gut microbiota in high-fat diet with streptozotocin induced type 2 diabetes mellitus rats.

Metformin, an anti-diabetic drug, regulates blood glucose by affecting gut microbiotas. However, the potential mechanism underlying this effect remains unclear. This study aimed to evaluate the effect of metformin on glucose regulation, lipid levels, and the gut microbiota in rats with type 2 diabetes mellitus induced by a high-fat diet with streptozotocin. Thirty Wistar rats was using in this experiment. T2DM rats were administered 300 mg/kg metformin for 8 weeks. The glucose regulation, lipid levels, organ coefficients, and gut microbiotawere measured by 16S rDNA. The metformin-gavaged rats exhibited significant improvements in blood glucose and serum lipid levels, accompanied by alterations in short-chain fatty acid levels and the intestinal microbiota (p < 0.05). In the diabetic rats, metformin potentially increased specific probiotics, thus improving the hypoglycaemic effects of the oral anti-diabetic drug. Further, damage to the liver and kidney was effectively alleviated in the metformin-gavaged rats. This study's findings demonstrate that metformin exerts a positive anti-diabetic effect in HFD- and STZ-induced T2DM rats. These findings potentially provide a basis for the recommended use of metformin as a reliable oral drug for T2DM owing to its positive effect on the intestinal microbiota.

Antioxidant and Alpha Amylase Inhibitory Activity of Apigenin in Alloxan Induced Diabetic Rats

Purpose: to study the antioxidant, inhibitory activity of alpha amylase, antidiabetic, effects of flavonoid Apigeninin in diabetic rats. Methods: The effect of Apigeninon on blood glucose and antioxidant activities were estimated in alloxan induced diabetic and treated rats. The α-amylase inhibitory activity in the serum was assessed after oral administration of 7thday, 14th day, and 21st days treatment of Apigenin. Results: The Apigenin was reduced the serum glucose, α-amylase levels and increased antioxidant levels significantly (P&lt;0.05) in Apigenin alone and combination with Metformin treated groups. Conclusion: The present investigation concludes that flavonoid Apigenin, single drug and combination with Metformin was increased antioxidant and inhibited the alpha-amylase activity and hypoglycemic effect in alloxan induced diabetes rats.

Effects of Satureja Khuzestanica supplementation on glycemic indices and lipid profile in type 2 diabetes patients: a randomized controlled clinical-trial

BackgroundSeveral studies showed the hypoglycemic and hypolipidemic effects of Satureja Khuzestanica (SK) in animal models. This study aimed to determine the effect of SK supplementation on glycemic and lipid outcomes of patients with type 2 diabetes mellitus (T2DM).MethodsThe study was designed as a double-blind, placebo-controlled, randomized clinical trial using block randomization. Seventy-eight T2DM patients were randomly assigned to intervention (n = 39) or placebo (n = 39) groups. They received SK or placebo in 500 mg capsules daily for 12 weeks. Anthropometric, blood pressure, liver enzymes, glycemic, and lipid outcomes were measured before and after the intervention.ResultsAt baseline, there were no significant differences in age, sex, or glycated hemoglobin (HbA1c) levels between the groups. SK supplementation led to a significant decrease in FBS (-12.6 ± 20.7 mg/dl in the intervention group versus 3.5 ± 31.9 mg/dl; p = 0.007), HbA1c (-0.28 ± 0.45 in the intervention group versus 0.11 ± 0.54% in the placebo group; p = < 0.001), insulin (-1.65 ± 6.18 in the intervention group versus 2.09 ± 5.90 mIU/L in the placebo group; p = 0.03), total cholesterol (-14.6 ± 21.1 mg/dl in the intervention group versus 8.2 ± 30.9 mg/dl in the placebo group; p < 0.001), LDL-cholesterol (-4.6 ± 15.2 mg/dl in the intervention group versus 5.8 ± 14.6 mg/dl in placebo group; p < 0.001) levels, and significant increase in HDL-cholesterol (3.9 ± 4.9 mg/dl in the intervention group versus 0.9 ± 5.2 mg/dl in placebo group; p = 0.005).ConclusionBased on the study results, SK supplementation may improve glycemic indices and lipid profile of patients with T2DM. Our findings may provide novel complementary treatments without adverse effects for diabetes complications. These results need to be further confirmed in clinical trials.Registration: This trial has been registered in the Iranian Registry of Clinical Trials (IRCT ID: IRCT20190715044214N1, registration date: 21/02/2021).