Postprandial Hyperglycemia Research Articles

Natural Sweetener, Glycyrrhetinic Acid 3-O-Mono-beta-d-glucuronide, for Postprandial Hyperglycemia Management.

This study examines the inhibitory effects of a range of sweeteners on α-glucosidase. Our findings revealed that only one natural sweetener, namely, glycyrrhetinic acid 3-O-mono-beta-d-glucuronide (GAMG), derived from licorice, exhibited a mixed-type inhibition against α-glucosidase with a IC50 value of 0.73 ± 0.05 mg/mL. The fluorescence intensity of α-glucosidase was quenched by GAMG in the formation of an α-glucosidase-GAMG complex. GAMG has been shown to induce conformational changes in α-glucosidase, likely through hydrogen bonding, van der Waals force, and alkyl-alkyl interactions with amino acid residues, including Arg 281, Leu 283, Trp 376, Asp 404, Asp 443, Trp 481, Asp 518, Phe 525, Ala 555, and Asp 616. Additional animal validation experiments demonstrated that GAMG slowed starch digestion, thereby attenuating the postprandial glycemic response. Taken together, these findings provide evidence that GAMG is a natural sweetener with potent inhibitory activity that selectively targets α-glucosidase. This study supports the use of GAMG as a natural sweetener, which holds a high biological value and may be beneficial for managing postprandial hyperglycemia.

Regular Intermittent Aerobic Exercise Reduces Arterial Stiffness Associated with Postprandial Hyperglycemia in Middle-Aged and Older Individuals

Hardening of arterial walls associated with elevated postprandial blood glucose levels increases the risk of cardiovascular disease; however, the impact of intermittent aerobic training on reducing arterial stiffness is unknown. The aim of this study was to examine the chronic effects of intermittent aerobic exercise on arterial stiffness during hyperglycemia in middle-aged adults: 30 healthy middle-aged adults were randomly assigned to an 8-week intermittent aerobic training group (n = 15, jogging or running, 30 min/run, 3 times/week, 65% reserve heart rate) and a control group (n = 15, no training). Pulse wave velocity (PWV) of carotid-femoral (cf) and brachial-ankle (ba), heart rate, blood pressure, and blood glucose was measured before a 75 g oral glucose tolerance test (OGTT) and 30, 60, and 90 min after the test, before the exercise intervention, and 4 and 8 weeks after intervention. The baPWV and blood glucose levels before the intervention were elevated at 30, 60, and 90 min in both groups compared to levels before the 75 g OGTT (p < 0.01). The baPWV and blood glucose levels after 4 and 8 weeks of intervention were unchanged in the training group compared to that before the 75 g OGTT, but increased at 30, 60, and 90 min in the control group compared to that before the 75 g OGTT (p < 0.01). The baPWV and blood glucose levels at 30 and 60 min after the 75 g OGTT after 4 and 8 weeks of intervention were lower in the training group than in the control group (p < 0.01). These results indicate that intermittent aerobic exercise training may reduce the acute increase in arterial stiffness after hyperglycemia.

Evaluating the relationship between hepatitis B viral activity and gestational diabetes mellitus: A prospective cohort study.

Hepatitis B infection has been associated with the development of gestational diabetes but the underlying mechanism is not known. To examine associations between viral activity, gestational diabetes mellitus (GDM), and insulin resistance in pregnant people with chronic hepatitis B infection (HBV). Prospective cohort study across three tertiary maternity centres in Melbourne, Australia, between May 2021 and April 2023. Participants were followed prospectively through pregnancy to evaluate subsequent GDM diagnosis. Demographics, pregnancy outcomes, and markers of viral activity were compared between those with GDM versus those without. Logistic regression analysis was performed pre- and post-adjustment for known confounders. Sub-group analysis of participants from South East Asia (SEA) was performed. Outcome measures included GDM diagnosis, insulin resistance (Homeostatic Model Assessment Insulin Resistance score (HOMA-IR) score), HBV activity as measured by liver function tests, HBV viral load, hepatitis B e antigen, and quantitative hepatitis B surface antigen (quantHBsAg). A total of 113 women were recruited. One third (38/112, 33.9%) developed GDM, mostly diagnosed on isolated postprandial hyperglycaemia (25/38, 65.8%). Over half were born in SEA (66/113, 58.4%). Mean quantHBsAg was significantly lower in those with GDM (p = 0.044). No other associations were identified between GDM or HOMA-IR and markers of hepatic activity on multivariate logistic regression analysis and on sub-group analysis of those born in SEA. QuantHBsAg was significantly lower in those with GDM; otherwise, no association between GDM and measures of HBV viral activity was found. QuantHBsAg may be useful as an early pregnancy marker for GDM risk and warrants further research.

Curcuma longa extract reduces serum inflammatory markers and postprandial hyperglycemia in healthy but borderline participants with overweight and glycemia in the normal/prediabetes range: a randomized, double-blind, and placebo-controlled trial.

The spice turmeric, which has the Latin name Curcuma longa (C. longa), has various physiological effects. This study evaluated the effects of a hot water mixture with supercritical carbon dioxide C. longa extracts, CLE, and the potential active components of C. longa, turmeronols A and B and bisacurone on inflammation and glucose metabolism. First, we investigated the effect of CLE and the potential active components of C. longa on lipopolysaccharide-induced inflammation in RAW264.7 macrophages. We found a significant decrease in the production of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide with CLE, turmeronol A, and bisacurone, Significant inhibition of each of these substances was also observed, except for TNF-α with turmeronol B. The second part of our work was a 12-week randomized, double-blind, placebo-controlled study in healthy but borderline adults aged 40 to 69 years with overweight and normal/prediabetes glycemia. We compared blood inflammatory and glycometabolic markers in the CLE (n = 55) and placebo groups (n = 55). We found significantly lower serum high-sensitivity C-reactive protein and hemoglobin A1c levels in the CLE group. This group also showed significant improvements in postprandial hyperglycemia and insulin sensitivity indices. Our findings indicate that CLE may reduce low-grade inflammation and thus improve insulin sensitivity and postprandial hyperglycemia. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000051492, UMIN-CTR, UMIN000045106.

Two Prenylated Chalcones, 4-Hydroxyderricin, and Xanthoangelol Prevent Postprandial Hyperglycemia by Promoting GLUT4 Translocation via the LKB1/AMPK Signaling Pathway in Skeletal Muscle Cells.

Stimulation of glucose uptake in the skeletal muscle is crucial for the prevention of postprandial hyperglycemia. Insulin and certain polyphenols enhance glucose uptake through the translocation of glucose transporter 4 (GLUT4) in the skeletal muscle. The previous study reports that prenylated chalcones, 4-hydroxyderricin (4-HD), and xanthoangelol (XAG) promote glucose uptake and GLUT4 translocation in L6 myotubes, but their underlying molecular mechanism remains unclear. This study investigates the mechanism in L6 myotubes and confirms antihyperglycemia by 4-HD and XAG. In L6 myotubes, 4-HD and XAG promote glucose uptake and GLUT4 translocation through the activation of adenosine monophosphate-activated protein kinase (AMPK) and liver kinase B1 (LKB1) signaling pathway without activating phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and Janus kinases (JAKs)/signal transducers and activators of transcriptions (STATs) pathways. Moreover, Compound C, an AMPK-specific inhibitor, as well as siRNA targeting AMPK and LKB1 completely canceled 4-HD and XAG-increased glucose uptake. Consistently, oral administration of 4-HD and XAG to male ICR mice suppresses acute hyperglycemia in an oral glucose tolerance test. In conclusion, LKB1/AMPK pathway and subsequent GLUT4 translocation in skeletal muscle cells are involved in Ashitaba chalcone-suppressed acute hyperglycemia.

Inhibitory mechanism of chrysin and diosmetin to α-glucosidase: insights from kinetics, multispectroscopy and molecular docking investigations

Inhibition of α-glucosidase activity is a promising method to prevent postprandial hyperglycemia. The inhibitory effect and interaction of chrysin and diosmetin on α-glucosidase were studied in this study. The results of inhibition kinetics showed that chrysin and diosmetin reversibly inhibited α-glucosidase activity with IC50 value of 26.445 ± 1.406 μmol L−1 and 18.380 ± 1.264 μmol L−1, respectively. Further research revealed that chrysin exhibited a mixed-type inhibitory pattern against α-glucosidase, while diosmetin was noncompetitive inhibitory with Ki value of (2.6 ± 0.04) ×10−4 mol L−1. Fluorescence spectroscopy showed that both chrysin and diosmetin could quench the intrinsic fluorescence of α-glucosidase, the maximum emission wavelength of tyrosine (Tyr) and tryptophan (Trp) were not moved by chrysin, but red shifted by diosmetin. UV-Vis, fourier transform infrared spectroscopy (FT-IR) and circular dichroism (CD) measurements showed that the secondary structure and microenvironment of α-glucosidase were changed by chrysin and diosmetin. Further analysis of molecular docking showed that chrysin and diosmetin could bind with α-glucosidase and might cause the decrease of α-glucosidase activity. The results of molecular dynamics (MD) simulation showed that the stability of chrysin (or diosmetin)-α-glucosidase complex system was changed during binding process. In conclusion, chrysin and diosmetin are good α-glucosidase inhibitors. Communicated by Ramaswamy H. Sarma

How to descript a clinical case correctly: For inquiry scientists and demanding doctors

The article presents step by step international CARE guidelines (CAse REport), which regulate the structure of the description of a clinical case and include a checklist of 13 points. This form of presentation of the material does not create any difficulties in understanding, does not require a long period of time to prepare a publication for the author, demonstrating a unique personalized experience and informing the medical community about interesting clinical manifestations, diagnostic or therapeutic approaches within a particular nosology, as well as describing rare or newly reported side effects of drugs or features of their prescription. Below as an example presented a clinical observation of a young man with diabetes mellitus of complex origin, which was diagnosed after the initial diagnosis of type 2 diabetes mellitus, which was later supplemented with recurrent pancreatitis, pancreatic cyst development and alcohol abuse with underlying severe hypertriglyceridemia (up to 67 mmol/l). Given the limited choice of glucose-lowering therapy, inability to prescribe metformin, glucagon-like peptide-1 agonists, infeasibility to use dipeptidyl peptidase 4 inhibitors and gliflozins (history of episodes of balanoposthitis), after a detailed discussion with the patient, a decision was made to prescribe a combination insulin drug – biphasic Lispro (RinLis Mix 25, Geropharm, Russia), which, together with fundamental lifestyle changes, strong alcohol avoidance, and regular medical follow-ups, allowed him to achieve glycemic targets and reduce plasma triglyceride levels, which once again supported the versatility of insulin as hypoglycemic agent, easiness to use and comprehensive glycemic control, if pre-mixed ultra-fast-acting insulin analogue and its protaminized analogue are prescribed. The prescription of insulin premix in this case is also justified in terms of clinical guidelines, as the man led a regular lifestyle, had low physical activity, an HbA1c level greater than 1.5% of the target value, as well as fasting and postprandial hyperglycemia.

Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose-stimulated insulin secretion.

Postprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated. LPLAT10 expression is low in the liver, the main organ that regulates metabolism, under normal conditions. Here, we investigated whether overexpression of LPLAT10 in the liver leads to improved glucose metabolism. For overexpression, we generated an LPLAT10-expressing adenovirus (Ad) vector (Ad-LPLAT10) using an improved Ad vector. Postprandial hyperglycemia was suppressed by the induction of glucose-stimulated insulin secretion in Ad-LPLAT10-treated mice compared with that in control Ad vector-treated mice. Hepatic and serum levels of phosphatidylcholine 40:7, containing C18:1 and C22:6, were increased in Ad-LPLAT10-treated mice. Serum from Ad-LPLAT10-treated mice showed increased glucose-stimulated insulin secretion in mouse insulinoma MIN6 cells. These results indicate that changes in hepatic phosphatidylcholine species due to liver-specific LPLAT10 overexpression affect the pancreas and increase glucose-stimulated insulin secretion. Our findings highlight LPLAT10 as a potential novel therapeutic target for T2DM.

Discovery of a new tannin compound as an α‐glucosidase inhibitor from Carya cathayensis Sarg. kernels and its inhibitory kinetics

SummaryInhibition of α‐glucosidases is recognised as an effective approach towards managing postprandial hyperglycaemia. This study aimed to identify a specific compound in Carya cathayensis Sarg. kernels (CCSKs) exhibiting strong inhibitory activities against α‐glucosidase and elucidate the inhibitory kinetic mechanism. Employing a bioassay‐guided approach, an α‐glucosidase inhibitor was isolated from CCSKs through sequential chromatography protocol involving AB‐8 macroporous adsorptive resin, Sephadex LH‐20 and C18‐reversed phase silica gel. The resulting inhibitor was a novel tannin compound, identified as rugosin C ethyl ester. Rugosin C ethyl ester displayed superior inhibitory activity (IC50 of 2.60 μg/mL) compared to acarbose (IC50 of 105.95 μg/mL). The kinetic analysis indicated that rugosin C ethyl ester had a mixed‐type reversible inhibition against α‐glucosidase. The inhibition constants (Ki and Kis) were determined to be 3.119 and 0.856 μg/mL, respectively. The findings indicated that rugosin C ethyl ester might serve as a promising functional ingredient in low‐glycemic index foods.

Rapid adaptation of the rainbow trout intestinal microbiota to the use of a high-starch 100% plant-based diet.

Short-term adaptation of the microbiota could promote nutrient degradation and the host health. While numerous studies are currently undertaking feeding trials using sustainable diets for the aquaculture industry, the extent to which the microbiota adapts to these novel diets is poorly described. The incorporation of carbohydrates (CHO) within a 100% plant-based diet could offer a novel, cost-effective energy source that is readily available, potentially replacing the protein component in the diets. In this study, we investigated the short-term (3 weeks) effects of a high CHO, 100% plant-based diet on the mucosal and digesta associated microbiota diversity and composition, as well as several metabolic parameters in rainbow trout. We highlighted that the mucosa is dominated by Mycoplasma (44.86%). While the diets did not have significant effects on the main phyla (Proteobacteria, Firmicutes, and Actinobacteria), after 3 weeks, a lower abundance of Bacillus genus, and higher abundances of four lactic-acid bacteria were demonstrated in digesta. In addition, no post-prandial hyperglycemia was observed with high carbohydrate intake. These results provide evidence for the rapid adaptation of the gut microbiota and host metabolism to high CHO in combination with 100% plant ingredients in rainbow trout.

Diphenolic boldine, an aporphine alkaloid: inhibitory effect evaluation on α-glucosidase by molecular dynamics integrating enzyme kinetics

Screening α-glucosidase inhibitors with novel structures is an important field in the development of anti-diabetic drugs due to their application in postprandial hyperglycemia control. Boldine is one of the potent natural antioxidants with a wide range of pharmacological activities. Virtual screening and biochemical inhibition kinetics combined with molecular dynamics simulations were conducted to verify the inactivation function of boldine on α-glucosidase. A series of inhibition kinetics and spectrometry detections were conducted to analyze the α-glucosidase inhibition. Computational simulations of molecular dynamics/docking analyses were conducted to detect boldine docking sites’ details and evaluate the key binding residues. Boldine displayed a typical reversible and mixed-type inhibition manner. Measurements of circular dichroism and fluorescence spectrum showed boldine changed the secondary structure and loosened the tertiary conformation of target α-glucosidase. The computational molecular dynamics showed that boldine could block the active pocket site through close interaction with binding key residues, and two phenolic hydroxyl groups of boldine play a core function in α-glucosidase inhibition via ligand binding. This investigation reveals the boldine function on interaction with the α-glucosidase active site, which provides a new inhibitor candidate. Communicated by Ramaswamy H. Sarma

Investigation on the inhibition mechanism and binding behavior of cryptolepine to α-glucosidase and its hypoglycemic activity by multi-spectroscopic method

Cryptolepine, one important active ingredient of Cryptolepis sanguinolenta (Lour), exhibits various beneficial pharmacological activities. But its anti-α-glucosidase and hypoglycemic activities are still not cleared. Thence, in this study, we investigated its inhibitory effects on α-glucosidase by a multi-spectroscopic method and in vivo hypoglycemic activity by the oral glucose tolerance test (OGTT). The results showed that cryptolepine is a reversible mixed-type α-glucosidase inhibitor with IC50 value of 0.44 ± 0.05 mM, ∼ 2-fold stronger than positive control acarbose (IC50: 0.72 ± 0.02 mM). Fluorescence quenching confirmed cryptolepine could quench the endogenous fluorescence of α-glucosidase in a static process. Fluorescence quenching, synchronous fluorescence, CD spectra, and 3D fluorescence results showed that the binding of cryptolepine with α-glucosidase caused chromophore microenvironment and conformation changes of α-glucosidase, consequently inhibiting its catalytic activity. Molecular docking revealed the detailed binding interactions between cryptolepine and α-glucosidase. Furthermore, oral administration of cryptolepine could improve the glucose tolerance in mice to reduce the postprandial hyperglycemia. These findings provide a solid foundation for understanding the inhibitory effects on α-glucosidase and hypoglycemic activity of cryptolepine.

Euclea natalensis Suppresses Postprandial Hyperglycemia in Rats via the Inhibition of α-Glucosidase: In vitro, in vivo, and Molecular Docking Studies

Background:: Postprandial hyperglycemia is a key factor in type 2 diabetes, and its management is critical in alleviating the deleterious consequences of diabetes and its associated micro and macrovascular complications. Objective:: The current study aims to determine the effect of Euclea natalensis leaf extracts on α- glucosidase inhibition in vitro and postprandial hyperglycemia in vivo in rats. Methods:: Sequentially extracted leaf extracts of Euclea natalensis were evaluated for their inhibitory effects on α-glucosidase in vitro and the suppression of postprandial hyperglycemia in normoglycemic rats. The extracts were fingerprinted using a Fourier-transform infrared spectrophotometer (FTIR), and the bioactive compounds were evaluated by molecular docking for their interaction with α-glucosidase. Results:: FTIR fingerprinting of the extracts showed that they contain functional groups of important bioactive phytochemicals. The extracts inhibited α-glucosidase in vitro, with the methanol extract (1 mg/mL) showing the highest inhibitory effect of 93.52 ± 1.50% compared to 69.62% ± 1.45 of the standard drug acarbose (0.05 mg/mL). The extracts also reduced postprandial hyperglycemia in rats in a sucrose tolerance test, where the hexane and methanol extracts performed similarly to Acarbose. Molecular docking studies showed that 20(29)-lupene-3β- isoferulate 3 is the most potent α-glucosidase inhibitor with the lowest binding energy of -10.79 kcal/mol, 2 hydrogen bonds with residues ASP1526 and ASP1157, and numerous Van der Waal interactions with amino acids in the binding pocket of α-glucosidase. Conclusion:: Euclea natalensis leaf extracts were found to suppress postprandial hyperglycemia by inhibiting α-glucosidase activity; thus, it has a promising potential for use as an antidiabetic agent.

Manipulation of Post-Prandial Hyperglycaemia in Type 2 Diabetes: An Update for Practitioners.

This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose "excursions" being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins - prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise.

Dietary flaxseed oil suppresses hyperglycemia and hyperinsulinemia through increasing in α-linolenic acid content in the muscle.

Types of fats and oils affect the onset of lifestyle diseases. In this study, we investigated the relationship between the postprandial hyperglycemia and fatty acids content in the skeletal muscle of C57BL/6 mice given 20% lard, palm oil, corn oil, safflower oil, and flaxseed oil for 16 weeks. Lard increased plasma glucose and insulin levels at the end of feeding period, whereas flaxseed oil did not. It was noteworthy that there is a positive correlation between palmitic acid content in the muscle and postprandial hyperglycemia, and a negative correlation between α-linolenic acid content and hyperglycemia. Alternatively, mice were given 30% lard for 16 weeks. When lard was partially substituted with flaxseed oil (10-50% substitution), flaxseed oil dose-dependently prevented lard-induced hyperglycemia and hyperinsulinemia. In conclusion, flaxseed oil prevents the adverse effects of lard through increasing in α-linolenic acid content in the muscle.

Successful treatment of dumping syndrome with diazoxide in an infant with hypoplastic left heart syndrome.

Dumping syndrome is a rare but potentially serious condition that causes inappropriate postprandial hyperinsulinemia leading to hypoglycemia in children following gastrointestinal surgeries. While dietary modifications are often the first line of treatment, severe cases may require pharmacological intervention to prevent severe hypoglycemia. We present a case of successful treatment of dumping syndrome with diazoxide. A 2-month-old infant with left hypoplastic heart syndrome who underwent single ventricle palliation pathway and developed feeding intolerance that required Nissen fundoplication. Postprandial hypoglycemia was detected following the procedure, with glucose level down to 12 mg/dL, and the diagnosis of dumping syndrome was established. The patient was successfully managed with diazoxide, which effectively resolved postprandial hypoglycemia without any major adverse events. The patient was eventfully weaned off the medication at the age of 5 months. This case highlights the potential role of diazoxide in the management of pediatric patients with postprandial hyperinsulinemic hypoglycemia secondary to dumping syndrome. Dumping syndrome is a possible complication of gastrointestinal surgeries and should be suspected in children with abnormal glucose levels. Postprandial hyperglycemia should be monitored closely for significant subsequent hypoglycemia. Diazoxide might be considered as part of the treatment plan for dumping syndrome.

Влияние фиксированной комбинации алоглиптина и пиоглитазона на факторы риска возникновения сердечно-сосудистых заболеваний у пациентов сахарным диабетом 2 типа

Objective: to study the dynamics of carbohydrate and lipid metabolism and markers of visceral obesity (VO) in patients with type 2 diabetes mellitus (T2DM) and obesity when using a fixed combination of alogliptin and pioglitazone. Material and methods. 30 patients with T2DM and obesity were examined. Indicators of carbohydrate and lipid metabolism and markers of VO (conicity index, index of lipid products accumulation, waist circumference to height ratio) were assessed initially and over time 6 months after the start of using alogliptin 25 mg and pioglitazone 30 mg. Results. When taking alogliptin and pioglitazone, patients with T2DM and obesity showed a compensation of fasting and postprandial hyperglycemia, an effective reduction in glycated hemoglobin and insulin resistance of peripheral tissues, and favorable changes in lipid metabolism with a positive effect on the calculated VO indices. Conclusions. The combination of alogliptin and pioglitazone can be recommended as a reliable and safe treatment regimen for patients with T2DM and obesity with the ability to correct major cardiovascular risk factors.

Study of Glycemic Variability in Well-controlled Type 2 Diabetic Patients Using Continuous Glucose Monitoring System.

The world has changed tremendously for patients suffering from diabetes mellitus with the development of cutting-edge technologies like continuous glucose monitoring and flash glucose monitoring systems. Now, the details of constant fluctuations of glucose in their blood can be monitored not only by medical professionals but also by patients, and this is called glycemic variability (GV). Traditional metrics of glycemic control measurement, such as glycated hemoglobin (HbA1c), fail to reflect various short-term glycemic changes like postprandial hyperglycemia and hypoglycemic episodes, paving the way to the occurrence of various diabetic complications even in asymptomatic, well-controlled diabetic patients. This need for advanced management of diabetes and effective monitoring of these swings in blood glucose can be met by using a continuous glucose monitoring system (CGMS). To evaluate the extent of GV in well-controlled type 2 diabetes mellitus (T2DM) patients using a flash CGMS and to assess the correlation between GV and HbA1c. A hospital-based prospective observational study was carried out from May 2020 to Oct 2021 at the Department of Medicine, SMS Hospital, Jaipur, Rajasthan (India), after approval from the Ethics Committee of the institution. A total of 30 patients with well-controlled T2DM (HbA1c was ≥6.5, but ≤7.5) were included in the study using simple random techniques after written informed consent from patients. Patients were studied for glycemic excursions over a period of 7 days by using FreeStyle® Libre Pro™, which is a flash glucose monitoring system. The CGM sensor was attached to the left upper arm of the patient on day 0 and removed on day 7. The data recorded in the sensor was then retrieved using pre-installed computer software and analyzed using standard CGM metrics like standard deviation (SD), percentage coefficient of variation (%CV), time above range (TAR), time below range (TBR), and time in range (TIR), out of which %CV was used to quantify GV. %CV has been used to cluster patients into four cohorts from best to worst, namely: best/low CV ≤ 10%, intermediate CV from 10 to 20%, high CV from 20 to 30%, and very high CV of >30%. Scatterplots are used to establish correlations between various parameters. Data from a total of 30 patients were analyzed using CGMS and thus used for calculating standard CGM metrics; glucose readings every 15 minutes were recorded consecutively for 7-day periods, making it a total of 672 readings for each patient. Interpreting the CGM data of all 30 patients, the following results were found: the mean blood glucose of all cases is 134.925 ± 22.323 mg/dL, the mean SD of blood glucose of all cases is 35.348 ± 9.388 mg/dL, the mean of %CV of all cases is 26.376 ± 6.193%. CGM parameters of time are used in the form of percentages, and the following results were found: the mean of TAR, TBR, and TIR is 14.425 ± 13.211, 5.771 ± 6.808, and 82.594 ± 12.888%, respectively. Clustering the patients into cohorts, the proportion of patients exhibiting best/low %CV (10%) is 0, intermediate %CV (10-20%) is 16.67% (five out of 30 patients), high %CV (20-30%) is 50% (15 out of 30 patients) and very high %CV (>30%) is 33.33% (10 out of 30 patients). Also, there is no significant correlation found between HbA1c and %CV (ρ = 0.076, p-value = 0.690); a significant negative correlation was found between %CV and TIR (ρ = -0.604, p < 0.001S); a positive correlation of %CV with TAR and TBR is significant (ρ = 0.816, p-value of <0.001). Using a flash CGMS device and considering %CV as the parameter and primary measure of GV, the study demonstrated the overall instability of a person's glycemic control, making note of unrecognized events of hypoglycemia and hyperglycemia in asymptomatic well-controlled T2DM patients, revealing the overall volatile glycemic control. The most important finding of this study is that even those diabetics who are considered well-controlled experience a great degree of GV as assessed by CGM-derived metrics. This study also demonstrated that there is no significant correlation between HbA1c and GV, suggesting that patients may not have optimal control of their diabetes despite having "normal HbA1c" values; hence, GV can be considered an HbA1c-independent danger factor, having more harmful effects than sustained hyperglycemia in the growth of diabetic complications. So, by using CGM-derived metrics, the measurement of GV has the potential to complement HbA1c data. In this manner, a more comprehensive assessment of glycemic excursions can be provided for better treatment decisions, thereby facilitating optimal glycemic control, which is essential for reducing overall complications and promoting good quality of life.

Water solubility differentiates the impact of tea polyphenols and rutin on the postprandial glycemic response to cooked maize starch.

Postprandial hyperglycemia is an independent risk factor for cardiovascular diseases, and the impact of tea polyphenols (TP) and rutin, representative phenolic compounds with different water solubilities, on the postprandial glycemic response to cooked normal corn starch (CCS) was investigated. Comparatively, TP (DPPH50 = 0.12 mmol L-1) are more potent than rutin (DPPH50 = 0.50 mmol L-1) in scavenging the free radicals of DPPH, but both TP and rutin inhibited the activity of porcine pancreatic α-amylase (PPA), the major enzyme in starch digestion, with an IC50 of 4.09 mmol L-1 and 2.71 mmol L-1, respectively. However, an in vivo study showed that a significant reduction in postprandial blood glucose was only observed in the presence of rutin, and TP had no effect on the glycemic response to CCS. To find out the underlying mechanism, fluorescence spectroscopy and molecular docking were carried out and they showed that, compared to TP, rutin bound to the active site of PPA with higher affinity and a lower free energy (ΔG) driven by hydrogen bonds and π-stacking, and rutin also greatly increased the viscosity of starch. Collectively, water-soluble TP have a higher antioxidant property and a lower potency to inhibit PPA compared to water-insoluble rutin, and the weaker interaction between TP and PPA, and starch as well might synergistically contribute to TP's ineffectiveness in lowering the postprandial glycemic response, and water solubility linking the molecular structures and functions of phenolic compounds might be the fundamental basis for the observed difference in their biological functions, and water solubility can also be used to enrich specific phenolic compounds for desired functions.

From waste to bioactive compounds: A response surface methodology approach to extract antioxidants from Pistacia vera shells for postprandial hyperglycaemia management

Pistacia vera shells, an abundant agricultural by-product, are a rich source of undiscovered bioactive compounds. This study employed a response surface methodology (RSM) approach to optimize the microwave-assisted extraction of antioxidants. The highest total phenolic content, and antioxidant activity were achieved under the optimized extraction conditions (20 % ethanol, 1000 W, 135 s, and solvent-to-solid ratio of 27 mL/g). The resulting extract (OPVS-E) included gallic acid derivatives, hydrolysable tannins, flavonoids, fatty acids, and anacardic acids. Remarkably, OPVS-E displayed potent inhibitory activity against α-amylase (IC50 = 2.05 μg/mL) and α-glucosidase (IC50 = 41.07 μg/mL), by far more powerful than the anti-diabetic drug acarbose, OPVS-E exhibited a strong antiradical capacity against reactive oxygen species (ROS) without causing toxicity in intestinal cells (HT29-MTX and Caco-2). These findings introduce OPVS-E as a potential novel dual-action nutraceutical ingredient, able to mitigate postprandial hyperglycemia and counteract the ROS overproduction occurring in type 2 diabetes mellitus.