The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial.

BACKGROUND: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels. METHODS: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated. RESULTS: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively. CONCLUSION: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl. TRIAL REGISTRATION: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 .

Optimized extraction, enrichment, identification and hypoglycemic effects of triterpenoid acids from Hippophae rhamnoides L pomace.

The Hippophae rhamnoides L. pomace was generated in the production process for juice, wine of food industry. To expand the application of pomace, the extraction process optimization, enrichment and identification of triterpene acids were performed in this study. The extraction yield was 14.87% under optimal ultrasound-assisted extraction techniques performed via response surface methodology. The extract was subsequently purified to obtain the triterpenoid acid enrichment fraction (TPF) with the content of 75.23% ± 1.45%. 13 triterpenoid acids were identified via UPLC-Triple-TOF MS/MS and further semi-quantified through comparison with triterpenoid acid standards. TPF exhibited a strong inhibitory effect on α-glucosidase with IC50 value of 5.027 ± 0.375 µg/mL, as determined via enzyme inhibition experiment and molecular docking. Additionally, the TPF significantly reduced postprandial glucose levels, as revealed via carbohydrate tolerance tests, as well as ameliorate serum lipid profiles. Therefore, pomace may be a promising resource of functional food components with therapeutic and commercial values.

Retrospective Observational Study on Assessing Sitagliptin and Dapagliflozin as a Fixed-Dose Combination in the Indian Population With Type 2 Diabetes Mellitus: The SIDAXA Study.

Introduction Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, necessitates multifaceted treatment approaches. Emerging studies highlight the cardiovascular advantages of sodium-glucose transport protein 2 (SGLT2) and dipeptidyl peptidase 4 (DPP-4) inhibitors in T2DM. This investigation delves into the synergistic effects of the fixed-dose combination (FDC) of sitagliptin and dapagliflozin, offering insights into its safety and efficacy for the Indian population. Methods This real-world, retrospective, observational study spanned 328 cases across 111 Indian centres, evaluating the safety, efficacy, and clinical utilization of the sitagliptin and dapagliflozin FDC in T2DM patients after obtaining ethical approval. Assessments at baseline, week four, and week 12 encompassed hemoglobin A1C (HbA1C), fasting plasma glucose (FPG), postprandial blood glucose (PPBG), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP), and weight change. The statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 29.0.1.0(171) (IBM Corp., Armonk, NY, USA) with a significance level p<0.05. Results Study participants [mean age: 51.14±5.55 years, 77.74% (n=255) males, 22.26% (n=73) females] exhibited prevalent risk factors like sedentary lifestyle (n=167, 50.91%) and smoking (n=147, 44.82%). Comorbidities included hypertension (n=235, 71.65%) and dyslipidaemia (n=139, 42.38%). Metformin (n=282, 85.98%) and sulfonylurea (n=134, 40.85%) were commonly prescribed concomitant oral antidiabetic agents (OADs). FDC administration significantly reduced HbA1c by 1.05 ± 0.83% (p < 0.0001) at week 12. FPG and PPBG showed significant reductions of 22.98 ± 22.23 mg/dL (p < 0.0001), 165.50 ± 37.02 mg/dL and 40.94 ± 36.04 mg/dL (p < 0.0001) at four weeks respectively. By week 12, significant reductions were noted in SBP (14.61±13.98mmHg reduction, p-value <0.0001), DBP (7.80±8.45mmHg reduction, p-value <0.0001), and LDL-C levels (18.14±23.95 mg/dL reduction, p-value <0.0001). In patients with established cardiovascular disease, there was reduction in HbA1c levels by 1.02 ± 0.63% after 12 weeks, with FPG decreasing by 54.52 ± 32.67 mg/dL and PPBG decreasing by 88.73 ± 44.90 mg/dL. Treatment-emergent adverse events included headache, changes in micturition, genital mycotic infection, and nausea and diarrhoea which were mild, transient, and necessitated no treatment discontinuation. Conclusion The FDC of sitagliptin and dapagliflozin significantly improved glycaemic control and lipid profiles in T2DM patients, particularly those with coronary artery disease. It demonstrated a favourable safety profile in the Indian population, signifying its potential as an effective and well-tolerated therapeutic option in patients with established cardiovascular disease.

Effects of Dexamethasone on Postoperative Glycemic Control in Patients After Primary Total Joint Arthroplasty: A Randomized Double-Blind Controlled Trial.

BACKGROUND: In patients undergoing total joint arthroplasty, the use of dexamethasone (DEX) may cause perioperative blood glucose (BG) disorders, leading to complications even in patients who do not have diabetes. We aimed to evaluate the effects of different DEX doses on perioperative BG levels. METHODS: A total of 135 patients who do not have diabetes were randomized into three groups: preoperative intravenous (IV) injection of normal saline (Group A, the placebo group), preoperative IV injection of 10 mg DEX (Group B), and preoperative IV injection of 20 mg DEX (Group C). Postoperative fasting BG (FBG) levels were designated as the primary outcome, while postoperative postprandial BG (PBG) levels were assigned as the secondary outcome. The incidence of complications was recorded. We also investigated the risk factors for FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL. RESULTS: The FBG levels were higher in Groups B and C than in Group A on postoperative days (PODs) 0 and 1. The PBG levels were lower for Groups A and B compared to Group C on POD 1. No differences in FBG or PBG were detected beyond POD 1. Elevated preoperative glycosylated hemoglobin A1c levels increased the risk of FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL, respectively. However, preoperative IV injection of DEX was not associated with FBG ≥ 140 mg/dL or PBG ≥ 180 mg/dL. No differences were found in postoperative complications among the three groups. CONCLUSIONS: The preoperative IV administration of 10 or 20 mg DEX in patients who do not have diabetes showed transient effects on postoperative BG after total joint arthroplasty. The preoperative glycosylated hemoglobin A1c level threshold (regardless of the administration or dosage of DEX) that increased the risk for the occurrence of FBG ≥ 140 mg/dL and PBG ≥ 180 mg/dL was 5.75 and 5.85%, respectively.

Sucralose regulates postprandial blood glucose in mice through intestinal sweet taste receptors Tas1r2/Tas1r3.

BACKGROUND: Non-nutritive sweeteners (such as sucralose) bind to sweet receptors Tas1r2/Tas1r3 on intestinal endocrine L cells after diets to upregulate blood glucose. However, the mechanism by which sucralose regulates postprandial blood glucose (PBG) has not been clarified to date. We hypothesized that the gut sweet taste receptor was one of the targets for sucralose to regulate PBG. The aim of this study was to examine the effect of sucralose on PBG based on the gut sweet taste receptor signaling pathway and to explore the mechanism. Therefore, we examined PBG, genes, and proteins associated with the gut sweet receptor pathway in sucralose-exposed mice. RESULTS: The results showed that after 12 weeks of sucralose exposure the PBG of mice increased significantly, and the expression of intestinal sweet taste receptors increased correspondingly. Within the concentration range of this experiment, a significant increase of PBG was observed in mice fed on sucralose with a concentration equal to or higher than 0.33 g L-1 . CONCLUSION: Long-term consumption of sucralose may increase body weight and the risk of elevated PBG, resulting in overexpression of sweetness receptors and glucose transporters. The mechanism of these effects might be the result of non-nutritive sweeteners binding to sweetness receptors Tas1r2/Tas1r3 in gut endocrine cells and upregulating Slc5a1 and Slc2a2. But we cannot rule out that the rise in PBG is the result of a combination of sweet receptors and gut microbes. Therefore, the effect of gut microbes on PBG needs to be studied further. © 2023 Society of Chemical Industry.

Synthesis, biological evaluation and action mechanism of 7H-[1,2,4] triazolo [3,4-b] [1,3,4] thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors.

In our work, several 7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine-phenylhydrazone derivatives as α-glucosidase inhibitors (α-GIs) were synthesized and characterized by 1H NMR, 13C NMR, and HRMS spectrum. Then, their bio-activity against the α-glucosidase (α-Glu) was further evaluated. Among them, almost all compounds displayed better bio-activity with IC50 from 31.23 ± 0.89 to 213.50 ± 4.19 µM than acarbose (IC50 = 700.20 ± 10.55 µM). In particular, compound 5o showed the best potency to inhibit α-Glu in a mixed manner. Moreover, the action mechanisms of 5o were further clarified including fluorescence quenching, circular dichroism spectra, three-dimensional fluorescence spectra, molecular docking, etc. All mechanism studies revealed that 5o could arouse the changed secondary structure of α-Glu to hinder enzyme catalytic activity. It was observed from an in vivo study that 5o of 20 mg/kg could significantly decrease by 24.45 % postprandial blood glucose in mice vs. the control. Meanwhile, 5o had low drug-drug interaction potential and was likely to be an orally active compound. Moreover, 5o was observed to be no obvious cytotoxicity to HEK-293 cells. In summary, compound 5o exhibited one potential to be further applied as an antidiabetic drug.

Inhibitory activities and rules of plant gallotannins with different numbers of galloyl moieties on sucrase, maltase and α-amylase in vitro and in vivo.

BACKGROUND: α-Glucosidase inhibitors could effectively reduce postprandial blood glucose (PBG) levels and control the occurrence of complications of diabetes. Gallotannins (GTs) in plants have attracted much attention due to their significant α-glucosidase inhibitory activities in vitro. However, there is still a lack of systematic comparative studies to further elucidate inhibitory activities in vivo and in vitro of these compounds against α-glucosidase, especially for mammalian sucrase and maltase, and analyze their structure-activity relationship. PURPOSE: Determine the in vitro and in vivo inhibitory activities of five GTs with different number of galloyl moieties (GMs) on sucrase, maltase and α-amylase, and elucidate the relationship between α-glucosidase inhibitory activities and the number and connection mode of GMs. METHODS: Molecular docking and dynamics were used to study the binding mode and binding ability of five GTs against sucrase, maltase and α-amylase. Then, the inhibitory activities and inhibitory mechanisms of these compounds on sucrase, maltase and α-amylase in vitro were studied using inhibitory assay and enzyme inhibition kinetics. Further, the hypoglycemic effects in vivo of these compounds were demonstrated by three polysaccharides tolerance experiments on diabetes model mice. RESULTS: The results of molecular docking showed that these compounds could bind to enzymes through hydrogen bonds, hydrophobic interactions, etc. In addition, the α-glucosidase inhibition comparative studies in vitro and in vivo demonstrated that the inhibitory activities of these compounds on all three sucrase, maltase and α-amylase were ranked as TA ≈ PGG > TeGG > TGG > 1GG, and their inhibitory activities increases with the increase in the number of GMs. Moreover, the hypoglycemic effects of 1,2,3,4,6-pentagalloylglucose (PGG) and tannic acid (TA) in vitro and in vivo were also confirmed to be equivalent to or even stronger than that of acarbose. CONCLUSION: α-Glucosidase inhibitory activities in vitro and in vivo of GTs were positively correlated with the number of GTs, and the more the number, the stronger the activity. However, PGG with five GTs and TA with ten GTs showed almost identical α-glucosidase inhibitory activities, possibly due to the reduced binding force with the enzyme caused by spatial hindrance.

Effects of Quinine on the Glycaemic Response to, and Gastric Emptying of, a Mixed-Nutrient Drink in Females and Males.

Intraduodenal quinine, in the dose of 600 mg, stimulates glucagon-like peptide-1 (GLP-1), cholecystokinin and insulin; slows gastric emptying (GE); and lowers post-meal glucose in men. Oral sensitivity to bitter substances may be greater in women than men. We, accordingly, evaluated the dose-related effects of quinine on GE, and the glycaemic responses to, a mixed-nutrient drink in females, and compared the effects of the higher dose with those in males. A total of 13 female and 13 male healthy volunteers received quinine-hydrochloride (600 mg ('QHCl-600') or 300 mg ('QHCl-300', females only) or control ('C'), intraduodenally (10 mL bolus) 30 min before a drink (500 kcal, 74 g carbohydrates). Plasma glucose, insulin, C-peptide, GLP-1, glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin were measured at baseline, for 30 min after quinine alone, and then for 2 h post-drink. GE was measured by 13C-acetate breath-test. QHCl-600 alone stimulated insulin, C-peptide and GLP-1 secretion compared to C. Post-drink, QHCl-600 reduced plasma glucose, stimulated C-peptide and GLP-1, and increased the C-peptide/glucose ratio and oral disposition index, while cholecystokinin and GIP were less, in females and males. QHCl-600 also slowed GE compared to C in males and compared to QHCl-300 in females (p < 0.05). QHCl-300 reduced post-meal glucose concentrations and increased the C-peptide/glucose ratio, compared to C (p < 0.05). Magnitudes of glucose lowering and increase in C-peptide/glucose ratio by QHCl-600 were greater in females than males (p < 0.05). We conclude that quinine modulates glucoregulatory functions, associated with glucose lowering in healthy males and females. However, glucose lowering appears to be greater in females than males, without apparent differential effects on GI functions.

Utilizing bio-affinity ultrafiltration combined with UHPLC Q-Exactive Plus Orbitrap HRMS to detect potential α-glucosidase inhibitors in Oxalis corniculate L.

Oxalis corniculate L. (O. corniculate) was used to treat diabetes in Chinese folk as a popular tea drink. In this work, 31 compounds from O. corniculate were screened and identified as potential α-Glucosidase inhibitors (α-GIs). Among them, 6 compounds displayed stronger inhibitory activity than acarbose (IC50 = 212.9 ± 5.98 µg/mL). Especially, the most effective compounds quercetin (Qu, IC50 = 4.70 ± 0.40 µg/mL) and luteolin (Lu, IC50 = 15.72 ± 0.75 µg/mL) inhibited α-Glu in competitive and mixed manners, respectively. Moreover, fluorescence quenching, circular dichroism (CD), and molecular docking study revealed that they can arouse the changes in the secondary structure and hydrophobic micro-environment of the enzyme mainly through a hydrophobic binding. Furthermore, it was observed that oral administration of Qu (20 mg/kg) can significantly reduce postprandial blood glucose (PBG) levels in mice vs. the control group. To sum up, the above research confirmed that O. corniculate could prevent and treat postprandial hyperglycemia as a good tea drink, and the plant was an excellent source to obtain natural α-GIs.

Physicochemical characterizations, α-amylase inhibitory activities and inhibitory mechanisms of five bacterial exopolysaccharides.

Inhibiting pancreatic α-amylase activity can decrease the release rate of glucose, thereby delaying postprandial blood glucose. This study aimed to investigate the physicochemical properties and porcine pancreatic α-amylase (PPA) inhibitory activities of five bacterial exopolysaccharides (EPSs). We also aimed to analyze the differences of their inhibitory activities, exploring the inhibition mechanism between EPSs and PPA. Five EPSs had a low molecular weight (55-66 kDa), which were mainly composed of mannose and glucose with total content exceeding 86 %. The IC50 values of five EPSs (0.162-0.431 mg/mL) were significantly lower than that of acarbose (0.763 mg/mL), indicating that the inhibitory effects of five EPSs on PPA were stronger than acarbose, especially the EPS from Bacillus subtilis STB22 (BS-EPS). Moreover, BS-EPS was a mixed-type inhibitor, whereas other EPSs were noncompetitive inhibitors of PPA. Five EPSs quenched the fluorophore of PPA by the mixed quenching or apparent static quenching. Interestingly, BS-EPS showed stronger binding affinity to PPA than other EPSs. It can be speculated that EPSs with low molecular weight, high carboxylic acid content, and α-glycosidic bond exhibited high PPA inhibitory activity. These results suggest that BS-EPS can effectively inhibit PPA activity and has potential applications in reducing postprandial hyperglycemia.

A Pilot Study on the Efficacy of a Diabetic Diet Containing the Rare Sugar D-Allulose in Patients with Type 2 Diabetes Mellitus: A Prospective, Randomized, Single-Blind, Crossover Study.

High sugar consumption increases the risk of diabetes, obesity, and cardiovascular diseases. Regarding the diet of patients with diabetes, artificial sweeteners are considered a safe alternative to sugar; however, there is also a risk that artificial sweeteners exacerbate glucose metabolism. D-allulose (C-3 isomer of d-fructose), which is a rare sugar, has been reported to have antidiabetic and antiobesity effects. In this study, the efficacy of a diabetic diet containing D-allulose was investigated in patients with type 2 diabetes using an intermittently scanned continuous glucose monitoring system (isCGM). This study was a validated, prospective, single-blind, randomized, crossover comparative study. Comparison of peak postprandial blood glucose (PPG) levels after consumption of a standard diabetic diet and a diabetic diet containing 8.5 g of D-allulose was the primary endpoint. A D-allulose-containing diabetic diet improved PPG levels in type two diabetes patients compared with a strictly energy-controlled diabetic diet. The results also showed a protective effect on endogenous pancreatic insulin secretory capacity owing to reduced insulin requirement. In patients with type two diabetes mellitus, diabetic diets containing 8.5 g D-allulose were effective in improving PPG levels.

White-skinned sweet potato (Ipomoea batatas L.) acutely suppresses postprandial blood glucose elevation by improving insulin sensitivity in normal rats.

Long-term administration of Ipomoea batatas L. (white-skinned sweet potato, WSSP) has been reported to help manage type 2 diabetes mellitus (T2DM) in humans and animals; however, the mechanisms of blood glucose regulation by WSSP remain unclear. Therefore, we aimed to investigate the acute effects of WSSP on blood glucose homeostasis under normal conditions and the underlying mechanisms. Three fractions of WSSP (≤10, 10-50, and >50 kDa) were obtained via ultracentrifugation. Rats were subjected to an oral glucose tolerance test (OGTT) after a single administration of WSSP. The insulin tolerance test (ITT) and pyruvate tolerance test (PTT) were performed to evaluate insulin sensitivity and gluconeogenesis, respectively. Single WSSP administration markedly reduced blood glucose levels as revealed by the OGTT. Serum insulin levels were not increased by WSSP treatment. Blood glucose levels during ITT were significantly reduced due to WSSP treatment. WSSP treatment activated the phosphorylation of Akt, thereby activating insulin signaling in the skeletal muscles and liver. The ≤10 kDa fraction considerably reduced blood glucose levels per the OGTT and ITT. In contrast, gluconeogenesis in PTT and the expression of key enzymes in hepatocytes were suppressed by the >50 kDa fraction. This study demonstrated that WSSP acutely reduced postprandial blood glucose levels by improving insulin sensitivity in skeletal muscles in normal rats, which was attributed to constituents with a molecular weight of ≤10 kDa. Moreover, WSSP treatment suppressed gluconeogenesis in the liver, for which constituents of >50 kDa were responsible. Thus, WSSP can acutely regulate blood glucose homeostasis via multiple mechanisms. Since postprandial hyperglycemia leads to the onset of T2DM, WSSP, as a functional food, may possess potential active compounds that prevent T2DM.

Eating Vegetables First Regardless of Eating Speed Has a Significant Reducing Effect on Postprandial Blood Glucose and Insulin in Young Healthy Women: Randomized Controlled Cross-Over Study.

People with fast eating habits have been reported to have an increased risk of diabetes and obesity. To explore whether the speed of eating a test meal (tomato, broccoli, fried fish, and boiled white rice) influences postprandial blood glucose, insulin, triglyceride, and free fatty acid levels, 18 young, healthy women consumed a 671 kcal breakfast at fast speed (10 min) and slow speed (20 min) with vegetables first and slow speed (20 min) with carbohydrate first on three separate days. This study was conducted using a within-participants cross-over design in which all participants consumed identical meals of three different eating speeds and food orders. Significant ameliorations of both fast and slow eating with vegetables first regimen on postprandial blood glucose and insulin levels at 30 and 60 min were observed compared with those of slow eating with carbohydrates first. In addition, the standard deviation, large amplitude of excursion, and incremental area under the curve for blood glucose and insulin in both fast and slow eating with vegetables first were all significantly lower than those of slow eating with carbohydrate first. Interestingly, there was no significant difference between fast and slow eating on postprandial blood glucose and insulin levels as long as vegetables were consumed first, although postprandial blood glucose at 30 min was significantly lower in slow eating with vegetables first than that of fast eating with the same food order. These results suggest that food order with vegetables first and carbohydrate last ameliorates postprandial blood glucose and insulin concentrations even if the meal was consumed at fast speed.

Determinants of blood glucose concentrations following a high carbohydrate meal in type 2 diabetes: A multiple linear regression analysis.

This study showed that in relatively well-controlled type 2 diabetes blood glucose levels after a high carbohydrate meal were associated positively with fasting blood glucose, but also positively with gastric emptying in the first hour and negatively with the increments in plasma glucagon-like peptide-1 (GLP-1) in the later postprandial phase.

A Review on Experimental Models to Test Medicinal Plants on Postprandial Blood Glucose in Diabetes.

Due to the gravity of postprandial hyperglycemia in the development of microvascular and macrovascular diseases in diabetics, many medicinal plants are tested to determine their effectiveness in glycemic control and the mechanisms of action of the products. Consequently, various diabetic models have been developed and enhanced over the years. The objective of this review is to describe some of the experimental models to study the effect of medicinal plants used to control postprandial hyperglycemia. Data was collected from PubMed, ScienceDirect, Scopus, and Google scholar (1953-2021). Fiftyseven (57) studies were included in this review article. Ten models were identified and described. For each model, we described the targets involved and their roles in postprandial blood glucose control. The experimental design and procedures described the targets such as an α-glucosidase enzyme, SGLT1, GLUT2, DPP-IV, Na+/K+ ATPase pump, or intestinal motility in the models, experiment design and procedures were described. This review will facilitate the selection of the most appropriate model for studying agents used to investigate postprandial blood glucose.

Identification of a novel α-glucosidase inhibitor from Melastoma dodecandrum Lour. fruits and its effect on regulating postprandial blood glucose.

Melastoma dodecandrum Lour. (MDL) extracts have shown potent α-glucosidase inhibitory activity, suggesting MDL might be a good source of α-glucosidase inhibitors. The aim of the study was to identify compounds in MDL extracts with α-glucosidase inhibitory activities and evaluate their effect on postprandial blood glucose as well as elucidating the underlying mechanisms of inhibition. A total of 34 polyphenols were identified in MDL fruits, among which 10 anthocyanins and three proanthocyanidin derivatives were discovered for the first time. Dosing mice with MDL extracts (100 mg/kg body weight, by gavage) was associated with a significantly decrease in postprandial blood glucose concentrations after oral administration of maltose. The most potent α-glucosidase inhibitor was identified as casuarictin (IC50 of 0.21 µg/mL). Casuarictin bound competitively to α-glucosidase, occupying not only the catalytic site but also forming strong hydrogen bonds with α-glucosidase residues. Therefore, casuarictin derived from MDL fruits might be used as novel α-glucosidase inhibitor in functional foods or other dietary products.

The Effect of Alpha-Cyclodextrin on Postprandial Glucose Excursions: a Systematic Meta-Analysis.

Alpha-cyclodextrin (αCD) is a bacterial product that is widely used as a food ingredient. In the European Union (EU), αCD is regulated as a dietary fiber with an authorized health claim "for contributing to the reduction of postprandial glycemic responses." In the US, αCD is generally recognized as save (GRAS), but on April 25, 2022, the U.S. Food and Drug Administration (FDA) rejected the inclusion of αCD in the list of dietary fibers because "the strength of the scientific evidence does not support a finding of a beneficial effect of αCD on postprandial blood glucose …" To evaluate the strength of this scientific evidence, this meta-analysis reviews clinical trials conducted to test the effect of αCD on the rise of blood glucose and insulin levels during three hours after consumption of a meal comprising carbohydrates, fats, and proteins. Several issues related to the standardization of the outcomes, the choice of the statistical methods in the cross-over studies conducted, and the choice of methods for the aggregation of P-values are discussed. It is concluded that the administration of αCD not only reduces the postprandial glycemic responses, but the absence of an increase in insulin levels suggests that αCD acts independently of increasing insulin production and, thus, the beneficial effect of αCD is not affected by insulin resistance.

Chalcone-1-Deoxynojirimycin Heterozygote Reduced the Blood Glucose Concentration and Alleviated the Adverse Symptoms and Intestinal Flora Disorder of Diabetes Mellitus Rats.

Chalcone-1-deoxynojirimycin heterozygote (DC-5), a novel compound which was designed and synthesized in our laboratory for diabetes treatment, showed an extremely strong in vitro inhibitory activity on α-glucosidase in our previous studies. In the current research, its potential in vivo anti-diabetic effects were further investigated by integration detection and the analysis of blood glucose concentration, blood biochemical parameters, tissue section and gut microbiota of the diabetic rats. The results indicated that oral administration of DC-5 significantly reduced the fasting blood glucose and postprandial blood glucose, both in diabetic and normal rats; meanwhile, it alleviated the adverse symptoms of elevated blood lipid level and lipid metabolism disorder in diabetic rats. Furthermore, DC-5 effectively decreased the organ coefficient and alleviated the pathological changes of the liver, kidney and small intestine of the diabetic rats at the same time. Moreover, the results of 16S rDNA gene sequencing analysis suggested that DC-5 significantly increased the ratio of Firmicutes to Bacteroidetes and improved the disorder of gut microbiota in diabetic rats. In conclusion, DC-5 displayed a good therapeutic effect on the diabetic rats, and therefore had a good application prospect in hypoglycemic drugs and foods.

Clinical Utility of a Digital Therapeutic Intervention in Indian Patients With Type 2 Diabetes Mellitus: 12-Week Prospective Single-Arm Intervention Study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) having elevated levels of blood glucose and glycated hemoglobin (HbA1c) are at higher risk of macro- and microvascular complications. Nonetheless, the goal of achieving glycemic control cannot be met with the use of pharmacotherapy alone. The recent emergence of digital therapeutic tools has shown the possibility of improving the modifiable risk factors and self-management of diabetes. OBJECTIVE: The aim of this study was to examine the clinical utility of a digital therapeutic intervention as an add-on therapy to achieve glycemic control in patients with T2DM. METHODS: This was a 12-week prospective, single-arm digital intervention study in patients with T2DM receiving regular antidiabetic treatment. The eligibility criteria included male and female patients with HbA1c≥6.5%, functional English literacy, and a mobile phone capable of running the intervention app. Outcome measures of the study were mean changes in HbA1c, fasting blood glucose (FBG), postprandial blood glucose (PPBG), BMI, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index at the end of 12 weeks. RESULTS: A total of 128 participants completed the study period of 12 weeks. There were 54.7% (70/128) men and 45.3% (58/128) women with a mean age of 48.48 years (SD 10.27). At the end of 12 weeks, the mean change in HbA1c, FBG, PPBG, and BMI for the overall study population was -0.84% (P<.001), -8.39 mg/dl (P=.02), -14.97 mg/dl (P<.001), and -0.24 kg/m2 (P=.06), respectively. Among the participants showing improvement in the HbA1c value at the end of 12 weeks (responders), the mean change in HbA1c, FBG, PPBG, and BMI was -1.24% (P<.001), -12.42 mg/dl (P=.003), -21.45 mg/dl (P<.001), and -0.34 kg/m2 (P=.007), respectively. There was an increase in HOMA-IR values for the overall study population (0.54, P=.29). HbA1c response showed a significant association with a baseline HbA1c level ≥7.5%, no prior history of smoking, and no prior COVID-19 infection, as well as with higher levels of program engagement. CONCLUSIONS: A digital therapeutic intervention when used alongside standard medications significantly reduces HbA1c, FBG, and PPBG levels in patients with T2DM.

Acute Flaxseed Intake Reduces Postprandial Glycemia in Subjects with Type 2 Diabetes: A Randomized Crossover Clinical Trial.

Background: Postprandial glycemic excursions are associated with impairment control of diabetes mellitus. Long-term consumption of flaxseed can lower blood glucose levels; however, its effects on the postprandial glycemic response remain unknown. Therefore, this study aimed to evaluate the acute effects of raw flaxseed consumption on the 2 h postprandial glycemic curve in men with type 2 diabetes mellitus (T2DM). Methods: This was a randomized crossover clinical trial. Nineteen men with T2DM were randomly assigned a standardized breakfast without (control) or with a previous intake of 15 g of ground raw golden flaxseed (flax). Glycemia was measured at fasting and postprandial at 15, 30, 45, 60, 90, and 120 min. Palatability markers (visual appeal, smell, and pleasantness of taste) and taste intensity (sweetness, saltiness, bitterness, sourness, and creaminess) were evaluated. Results: The peak glucose rise and the 2 h AUC glycemic response reduced in the flax group by 17% (p = 0.001) and 24% (p < 0.001), respectively. The glucose peak time, palatability, and taste parameters did not differ between the two groups. Conclusions: Ingestion of 15 g of ground raw golden flaxseed before breakfast decreases the 2 h postprandial glycemic response in men with T2DM.