Postprandial Plasma Glucose Levels Research Articles

Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Internet-Based Interventions for Preventing Premature Birth Among Pregnant Women: Systematic Review.

Premature birth rates have slightly increased globally, making its prevention critical for both short-term and long-term health outcomes. Various interventions have been developed in response to the multifaceted risk factors for premature birth, including internet-based programs. These programs offer accessibility and enhanced engagement; however, their overall efficacy in preventing premature births requires thorough evaluation. This systematic review aims to identify the study designs and assess the effectiveness of internet-based interventions in preventing premature birth among pregnant women. A comprehensive search of the MEDLINE, Embase, CINAHL, and Cochrane Library databases was conducted to identify randomized trials and quasi-experimental studies evaluating internet-based interventions for premature birth prevention in pregnant women. The search was inclusive, with no restrictions based on language or geographical location, allowing for a comprehensive global perspective. The time frame for the inclusion of studies extended until February 2023. The risk of bias (RoB) in each study was independently assessed by 3 authors forming pairs, using the revised Cochrane RoB tool (RoB 2) for randomized trials, as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Owing to heterogeneity in populations, measurements, and interventions, a meta-analysis was not conducted. This review included 26 articles, comprising 12 intention-to-treat and 14 per-protocol studies. The overall RoB was high in most intention-to-treat studies and of some concern in most per-protocol studies. The target populations varied, including nonspecific pregnant women, those with gestational diabetes mellitus (GDM) or those at risk of GDM, individuals with anxiety or depression, and those experiencing preterm labor. Psychosocial, physiological, and wellness health outcomes were evaluated. Internet-based interventions effectively reduced stress/distress in nonspecific pregnant women but not in those experiencing preterm labor. Their effectiveness in reducing anxiety and depression varied, with inconsistent results among different groups. In women with GDM or those at risk of GDM, interventions successfully controlled fasting plasma glucose and 2-hour postprandial plasma glucose levels but did not consistently manage glycated hemoglobin levels. These interventions did not reduce the incidence of premature births across the various populations studied. The effectiveness of these internet-based interventions in addressing substance or alcohol abuse and insomnia also varied. Internet-based interventions show promise in improving psychosocial health and managing blood sugar to prevent premature birth, highlighting variability in effectiveness across different risk factors. Further research, including clinical trials, is vital for developing, evaluating, and disseminating effective, safe internet-based interventions. Establishing standardized measurement tools and rigorous evaluation processes is crucial for enhancing these interventions' effectiveness and reliability in clinical practice, significantly contributing to preventing premature births and improving maternal health outcomes. PROSPERO CRD42021278847; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278847.

Taraxacum officinale Extracts Alleviate Anhedonia and Depression by Inhibiting Uprmt and Mitophagy in the Hippocampi of T2dm Rats

<i>Taraxacum officinale</i> Extracts Alleviate Anhedonia and Depression by Inhibiting Upr^mt and Mitophagy in the Hippocampi of T2dm Rats

Glycaemic Variability in Diabetes

Glycemic variability GV pertains to the variations in blood glucose levels throughout a period. In diabetes it specifically refers to the wide swings in blood sugar levels experienced by diabetic patients. Normally blood glucose levels vary during the day in reaction to various factors including food consumption physical activity stress and hormone release. Nevertheless individuals with poorly managed blood sugar levels often encounter more substantial and frequent fluctuations in their glucose levels a phenomenon prevalent in both type 1 and type 2 diabetes. The assessment of glucose variability GV involves various methods encompassing short term measures such as within-day and between-day variations as well as long-term GV typically determined by sequential measurements over an extended period incorporating values such as HbA1c fasting and postprandial plasma glucose levels. Strategies to address glycaemic variability in individuals with diabetes include lifestyle adjustments medication continuous glucose monitoring CGM insulin pump therapy and diabetes education and support.

A retrospective electronic medical record-based study of insulin usage and outcomes in insulin-naive Indian adults with T2DM: The REALITY study

Abstract Objective This retrospective longitudinal study analyzed the demographic profile, insulin usage pattern, and outcomes of insulin-naive adults with type 2 diabetes mellitus (T2DM) who initiated insulin glargine. Methods The study included 1006 insulin naive T2DM individuals aged ≥ 18 years, treated with any insulin type between January 2016 and December 2018, using electronic medical records. Results Majority of participants were men (55.8%) with a mean age of 59.8 ± 11.9 years and average T2DM duration of 12.0 ± 6.6 years. Insulin glargine was the most commonly used insulin (66.9%), followed by insulin aspart (16.4%), insulin degludec (15.1%), human insulin (11.1%), and insulin isophane (9.2%). At baseline, the mean glycated hemoglobin (HbA1c) was 8.9 ± 1.9%, mean fasting plasma glucose (FPG) was 190 ± 59 mg/dL, and mean post-prandial plasma glucose (PPG) was 264 ± 78 mg/dL. In the insulin glargine group, baseline HbA1c was 9.0 ± 1.7%, FPG was 196 ± 62 mg/dL, and PPG was 283 ± 81 mg/dL. Throughout the study, there was an improvement in HbA1c, FPG, and PPG levels in the insulin glargine group. Body weight remained relatively stable, and the number of hypoglycemic events was minimal and non-life-threatening. Conclusion The REALITY study in India demonstrated that initiating basal insulin treatment in insulin-naive individuals with T2DM led to improved glycemic parameters over a 12-month period.

Efficacy and Safety of a Fixed-Dose Combination of Vildagliptin and Pioglitazone in Indian Patients With Type 2 Diabetes Mellitus: A Randomized, Open-Label, Comparative, Phase III Study.

Background Type 2 diabetes mellitus (T2DM) arises due to a range of pathological abnormalities, necessitating a combination therapy to achieve optimal glycemic control. Vildagliptin, an effective and selective DPP-4 inhibitor, and pioglitazone, an insulin sensitizer, offerdistinct mechanisms of action. Hence, the integration of these medications represents a logical and justified therapeutic strategy Objective To compare the efficacy, safety, and tolerability of vildagliptin and pioglitazone 50 mg/15 mgfixed-dose combination (FDC) tablets with individual monotherapy vildagliptin 50 mg and pioglitazone 15 mg tablets in Indian T2DM patients who were inadequately controlled on metformin monotherapy. Methods This was a randomized, open-label, comparative, multicenter, phase III study involving 195 T2DM patients with inadequate glycemic control on metformin ≥ 1000 mg/day. Patients were randomly assigned in a 1:1:1 ratio to the test product group (n=65) (vildagliptin 50 mg + pioglitazone 15 mg FDC tablets), reference product group 1 (n=65) (vildagliptin 50 mg tablet), or reference product group 2 (n=65) (pioglitazone 15 mg tablet reference product). The primary endpoint was the mean change in HbA1c levels from baseline to end of the study visit (12 weeks (84 days ±2)). The secondary endpoints were the mean change in fasting plasma glucose (FPG) and 2-hr postprandial plasma glucose (2-hr PPG) levels. Safety parameters were assessed till the end of the study. Results A total of 178 patients completed the study. At 12 weeks, the mean HbA1c level in the test group reduced to 6.85 ± 1.27%, in the reference product 1 group to 7.56 ± 1.72%, and in the reference product 2 groups to 7.37 ± 1.59%. The mean change in Hb1Ac from baseline in the test group was statistically significant compared to the reference groups (p=0.037). Similarly, the mean changes in the FPG and 2hr-PPG with the test product were statistically significant compared to reference products (p=0.041). The adverse events were comparable across all the treatment groups. Conclusion In Indian T2DM patients inadequately controlled on a daily maximum dose of metformin, treatment with vildagliptin and pioglitazone FDC showed better glycemic control than either vildagliptin or pioglitazone along with a good tolerability profile.

New Insights into the Latest Advancement in α-Amylase Inhibitors of Plant Origin with Anti-Diabetic Effects.

The rising predominance of type 2 diabetes, combined with the poor medical effects seen with commercially available anti-diabetic medications, has motivated the development of innovative treatment approaches for regulating postprandial glucose levels. Natural carbohydrate digestion enzyme inhibitors might be a viable option for blocking dietary carbohydrate absorption with fewer side effects than manufactured medicines. Alpha-amylase is a metalloenzyme that facilitates digestion by breaking down polysaccharides into smaller molecules such as maltose and maltotriose. It also contributes to elevated blood glucose levels and postprandial hyperglycemia. As a result, scientists are being urged to target α-amylase and create inhibitors that can slow down the release of glucose from carbohydrate chains and prolong its absorption, thereby resulting in lower postprandial plasma glucose levels. Natural α-amylase inhibitors derived from plants have gained popularity as safe and cost-effective alternatives. The bioactive components responsible for the inhibitory actions of various plant extracts have been identified through phytochemical research, paving the way for further development and application. The majority of the findings, however, are based on in vitro investigations. Only a few animal experiments and very few human investigations have confirmed these findings. Despite some promising results, additional investigation is needed to develop feasible anti-diabetic drugs based on plant-derived pancreatic α-amylase inhibitors. This review summarizes the most recent findings from research on plant-derived pancreatic α-amylase inhibitors, including plant extracts and plant-derived bioactive compounds. Furthermore, it offers insights into the structural aspects of the crucial therapeutic target, α-amylases, in addition to their interactions with inhibitors.

Adding empagliflozin to sitagliptin plus metformin vs. adding sitagliptin to empagliflozin plus metformin as triple therapy in Egyptian patients with type 2 diabetes: a 12-week open trial.

This study aimed to compare 12.5 mg empagliflozin effectiveness and safety vs. 50 mg sitagliptin twice daily as an add-on triple medication in Egyptians with type 2 diabetes. Patients with hemoglobin A1c (HbA1c) between 53 and 86 mmol/mol after receiving open-label either sitagliptin 50 mg (n = 85) or empagliflozin 12.5 mg (n = 85) twice daily for 12 weeks were afterward taken into account for the administration of open-label empagliflozin 12.5 mg (n = 40) and sitagliptin 50 mg (n = 28) respectively twice daily for another 12 weeks of treatment as an added-on triple therapy. Both groups of patients kept taking metformin and empagliflozin 12.5 mg or sitagliptin 50 mg twice daily as prescribed. The HbA1c change from baseline after 12 weeks of triple-added-on therapy was the main endpoint. The sitagliptin group receiving empagliflozin saw a substantial drop in HbA1c, fasting and postprandial plasma glucose levels, body weight, and blood pressure compared to the starting point. As opposed to that, adding sitagliptin to the empagliflozin group non-significantly reduced HbA1c, fasting, and postprandial plasma glucose levels, and systolic blood pressure from baseline but significantly reduced body weight and diastolic blood pressure. Comparing the two groups, adding empagliflozin significantly reduced HbA1c, fasting, and postprandial plasma glucose levels (p < 0.001 for all except fasting plasma glucose level, p = 0.002). While the patient's weight and blood pressure were not significantly affected. Empagliflozin was superior to sitagliptin in relation to glycemic control, weight, and systolic/diastolic blood pressure reduction.

111-OR: Effect of Dulaglutide plus Calorie-Restricted Diet vs. Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome—A Randomized Controlled Trial

This study investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits compared with the CRD regimen alone in overweight or obese women with PCOS. This single-center, randomized, controlled, open-label clinical trial was conducted between May 2021 and May 2022. Overall, 243 patients were screened, of which 68 overweight or obese women with PCOS were randomly assigned to receive dulaglutide combined with CRD treatment (n=35) or CRD treatment alone (n=33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. The mean time to achieve 7% weight loss was significantly shorter in the dulaglutide+CRD group than in the CRD group. There was no significant between-group difference in the change in VAT reduction (-0.97 cm2, 95% confidence interval, -14.36-12.42; P=0.884). Compared to CRD alone, dulaglutide+CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. Results of analyses of changes in menstrual frequency, other metabolic profiles, hormonal parameters, liver fat, and body composition were not significantly different between the two groups. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These findings support the importance of dietary intervention as first-line management in women with PCOS, and glucagon-like peptide 1 receptor agonist (GLP-1 RA) therapy offers an effective and generally tolerable adjunct therapy to aid in achieving weight target based on dietary therapy in overweight/obese women with PCOS. Disclosure Y.Zhang: None. X.Shao: None. M.Cai: None. D.Dilimulati: None. S.Qu: None. M.Zhang: None. Funding National Natural Science Foundation of China (81601269)

Effects of the Consumption of Low to Medium Glycemic Index–based Rice on the Rate of Insulin Initiation in Patients with Gestational Diabetes: A Triple-blind, Randomized, Controlled Trial

IntroductionMedical nutritional therapy is vital in patients with diabetes. A low glycemic index (GI) is generally advised in the management of women with gestational diabetes mellitus (GDM). However, the efficacy of this advice has not been systematically examined. The purpose of this study was to determine whether recommending a low to moderate GI rice (RD43 rice; GI = 56.9) in women with GDM would reduce the number of women requiring insulin, compared with rice of high GI (Thai Hom Mali [THM] rice; GI = 80.1). MethodsNinety-six participants with GDM were randomly assigned to receive either RD43 rice or THM rice. ResultsThe mean ± SD ages in the RD43 and THM groups were 33.1 ± 13.1 and 33.6 ± 4.1 years, respectively. The mean gestational ages at the sampling in the RD43 and THM groups were 23.3 ± 5.9 and 23.5 ± 5.4 weeks. Both groups had comparable baseline characteristics, including age, gestational age, body mass index prior to pregnancy and at enrollment, baseline postprandial (oral glucose tolerance test) plasma glucose level, and hemoglobin A1c. Of the 48 women assigned to the RD43 group, 3 (6.3%) required insulin; in the THM group, 11 (22.9%) met the criteria for insulin therapy (P = 0.017). However, 10 of these 11 women were able to avoid insulin use by changing to the low to moderate GI rice. ConclusionUsing a low to moderate GI rice in GDM effectively reduced the number of patients requiring insulin therapy. Thai Clinical Trials Registry ID: TCTR20210524007.

The impacts of physical properties of extruded feed on the digestion kinetics, gastrointestinal emptying and stomach water fluxes of spotted seabass (Lateolabrax maculatus)

This study investigated the effect of extruded feed physical pellet quality (PPQ) on the physiological response of spotted seabass (Lateolabrax maculatus). Two batches of pellets with the same formula but contrasting PPQ were produced by extrusion. The contrast in PPQ was created by applying two levels of water (14% versus 20%) into the feed mixture prior to extrusion. This resulted in a low-water addition treatment (LW) with a short pellet hydration time versus a high-water addition treatment (HW) with a long pellet hydration time. Fish (average weight, 159 g) were fed to satiation twice daily for 48 days. Faeces were collected during the experimental period for digestibility measurements. At the end of the experiment, chyme was collected from the stomach and intestine at 0.5, 2, 4, 6, 8, 10, 12, 16 and 24 h after the last meal during which fish were also fed to satiation. Chyme dry matter, crude protein, and inert marker (Y2O3) content were analysed for the calculation of gastrointestinal evacuation, kinetics of digestion and water fluxes. A significantly larger stomach water influx led to a lower stomach DM content at 2 h postprandial in the LW-pellets compared to the HW-pellets. During the last meal, fish fed LW-pellets consumed more feed and had a higher plasma α-melanocyte stimulating hormone concentration at postprandial 2 h. On a fresh basis, LW-pellets generated a faster stomach digesta evacuation, while on a DM basis stomach emptying was similar for both treatments. Fish fed LW-pellets had a lower feed conversion ratio, a higher protein efficiency ratio, hepatosomatic index and postprandial plasma glucose level than fish fed HW-pellets. Nevertheless, PPQ did not statistically influence on the stomach digestion kinetics, faecal digestibility values and feed intake during the experimental period. Our results show that the PPQ can alter stomach water fluxes and digesta evacuation rate in spotted seabass. Additionally, it is suggested that PPQ, particularly hydration time, can affect fish's feed intake regulation and metabolic responses.

Direct comparison two fixed-ratio combination glucagon-like peptide receptor agonist and basal insulin on glycemic and non glycemic parameters in type 2 diabetes

BackgroundTwo types of fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1RA) have been approved for use in type 2 diabetes. One is insulin degludec/liraglutide (iDergLira), and the other is insulin glargine/lixisenatide (iGlarLixi). Direct comparisons between these two combination is not available.MethodsThe retrospective study included 186 patients with type 2 diabetes mellitus (DM) with inadequate glycemic control on metformin and basal insulin (degludec, glargine 100, glargine 300) who were switched to fixed-ratio combination GLP-1 RA and basal insulin. Patients were divided into two groups based on the basal insulin before study: group I (n = 86) treated with degludec were switched to iDegLira and patients group II (n = 99), treated with glargine were switched to iGlarLixi. The aim of this study was to directly compare the effects between two fixed – ratio combination on glycemic parameters and non glycemic parameters. Follow up was 6 months.ResultsMean HbA1c decreased similarly (− 1.2% vs.-1.1%). Higher percentage patients in iDegLira group had reached the HbA1c < 7% after 6 months (22% vs. 18.2%, p < 0.05). The mean change in fasting plasma glucose (FPG) was comparable for the two groups, while mean decrease postprandial plasma glucose (PPG) level were lower in iGlarLixi group (2 vs 1.8 mmol/l, p > 0.05). Change in body weight was significant in iDegLira group (1.8 kg vs. 0.7 kg, p < 0.001). At the end of the study patients showed decrease in total cholesterol (TC) and low-density lipoprotein (LDL) for 0.2 mmol/L in iDegLira, 0.1 mmol/l in iGlarLixi, triglycerides decreased 0.3 mmol/l in both groups, high-density lipoprotein(HDL) increased 0.1 mm/l in iGlarLixi.ConclusionOur results showed that more patients with iDegLira had HbA1c less than 7% and these combination had better effect on weight loss. There was no difference observed in FPG and PPG, lipid profile and rate of hypoglycemia.

Effects of a Dulaglutide plus Calorie-Restricted Diet versus a Calorie-Restricted Diet on Visceral Fat and Metabolic Profiles in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial.

The effects of dulaglutide and a calorie-restricted diet (CRD) on visceral adipose tissue (VAT) and metabolic profiles in polycystic ovary syndrome (PCOS) have not been extensively investigated. In this study, we investigated whether dulaglutide combined with CRD could further reduce VAT and promote clinical benefits as compared with a CRD regimen alone in overweight or obese PCOS-affected women. Between May 2021 and May 2022, this single-center, randomized, controlled, open-label clinical trial was conducted. Overall, 243 participants with PCOS were screened, of which 68 overweight or obese individuals were randomly randomized to undergo dulaglutide combined with CRD treatment (n = 35) or CRD treatment alone (n = 33). The duration of intervention was set as the time taken to achieve a 7% weight loss goal from baseline body weight, which was restricted to 6 months. The primary endpoint was the difference in the change in VAT area reduction between the groups. The secondary endpoints contained changes in menstrual frequency, metabolic profiles, hormonal parameters, liver fat, and body composition. As compared with the CRD group, the dulaglutide + CRD group had a considerably shorter median time to achieve 7% weight loss. There was no significant between-group difference in area change of VAT reduction (-0.97 cm2, 95% confidence interval from -14.36 to 12.42, p = 0.884). As compared with CRD alone, dulaglutide + CRD had significant advantages in reducing glycated hemoglobin A1c and postprandial plasma glucose levels. The results of the analyses showed different changes in menstruation frequency, additional metabolic profiles, hormonal markers, liver fat, and body composition between the two groups did not differ significantly. Nausea, vomiting, constipation, and loss of appetite were the main adverse events of dulaglutide. These results emphasize the value of dietary intervention as the first line of treatment for PCOS-affected women, while glucagon-like peptide 1 receptor agonist therapy provides an efficient and typically well tolerated adjuvant therapy to aid in reaching weight targets based on dietary therapy in the population of overweight/obese PCOS-affected women.

Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome.

Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics.

Recent Updates on Phytoconstituent Alpha-Glucosidase Inhibitors: An Approach towards the Treatment of Type Two Diabetes.

Diabetes is a common metabolic disorder marked by unusually high plasma glucose levels, which can lead to serious consequences such as retinopathy, diabetic neuropathy and cardiovascular disease. One of the most efficient ways to reduce postprandial hyperglycemia (PPHG) in diabetes mellitus, especially insulin-independent diabetes mellitus, is to lower the amount of glucose that is absorbed by inhibiting carbohydrate hydrolyzing enzymes in the digestive system, such as α-glucosidase and α-amylase. α-Glucosidase is a crucial enzyme that catalyzes the final stage of carbohydrate digestion. As a result, α-glucosidase inhibitors can slow D-glucose release from complex carbohydrates and delay glucose absorption, resulting in lower postprandial plasma glucose levels and control of PPHG. Many attempts have been made in recent years to uncover efficient α-glucosidase inhibitors from natural sources to build a physiologic functional diet or lead compound for diabetes treatment. Many phytoconstituent α-glucosidase inhibitors have been identified from plants, including alkaloids, flavonoids, anthocyanins, terpenoids, phenolic compounds, glycosides and others. The current review focuses on the most recent updates on different traditional/medicinal plant extracts and isolated compounds’ biological activity that can help in the development of potent therapeutic medications with greater efficacy and safety for the treatment of type 2 diabetes or to avoid PPHG. For this purpose, we provide a summary of the latest scientific literature findings on plant extracts as well as plant-derived bioactive compounds as potential α-glucosidase inhibitors with hypoglycemic effects. Moreover, the review elucidates structural insights of the key drug target, α-glucosidase enzymes, and its interaction with different inhibitors.

TCF7L2 gene associated postprandial triglyceride dysmetabolism- a novel mechanism for diabetes risk among Asian Indians.

Aim TCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk.MethodsPostprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot.ResultsT allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (p<0.01), TgAUC (p<0.01), peakTg (p<0.01) as well as higher postprandial plasma glucose (p=.006) levels and HOMA-IR (p=0.03) and significantly lower adiponectin levels (p=0.02) as compared to CC genotype. The expression of TCF7L2 gene in VAT was 11-fold higher in prediabetes group as compared to NGT (P<0.01) and 5.7-fold higher in T2DM group as compared to NGT group(P=0.003) and was significantly associated with PPTg and glucose levels.ConclusionThere is significant PPTg dysmetabolism associated with the risk allele of rs7903146 polymorphism as well as adipocyte expression of TCF7L2 gene. Significant upregulation of TCF7L2 gene expression in VAT that correlates with PPTg and glycaemia is also seen in Asian Indians with glucose intolerance. Modulation of PPTg metabolism by TCF7L2 gene and the resultant PPHTg may be a novel mechanism that contributes to its diabetes risk in them.

Effects of Persimmon Fruit Polyphenols on Postprandial Plasma Glucose Elevation in Rats and Humans.

Persimmon is a fruit rich in polyphenols (proanthocyanidins or condensed tannins). Using rats and humans, the effects of Kaki-tannin (Nara-type), persimmon polyphenols prepared using a new method, on postprandial plasma glucose levels were investigated in this study. Kaki-tannin (Nara-type) comprised mainly proanthocyanidins, composed of epicatechin : epicatechin gallate : epigallocatechin : epigallocatechin gallate in a ratio of 1 : 1 : 2 : 2 with a molecular weight of approximately 8,000 Da, with epicatechin gallate as a terminal unit. These polyphenols inhibited amylolytic enzymes, such as α-amylase, maltase, sucrase, and α-glucosidase in vitro, and sodium-dependent glucose transporter 1 in Caco-2 cells. These results suggested that the polyphenols suppressed digestion and absorption in the intestinal tract. The ingestion of 250 mg/kg body weight of the polyphenols significantly suppressed increased blood glucose levels after carbohydrate (2 g/kg body weight of glucose or maltose) loading in rats. In a human trial, 1.88 g of Kaki-tannin (Nara-type) significantly delayed increased plasma glucose levels after carbohydrate (150 kcal of maltooligosaccharides) loading. Thus, Kaki-tannin (Nara-type) holds promise to be developed as a food material that potentially improve blood glucose elevation after meals.

Viscoelastic or Viscoplastic Glucose Theory (VGT #80): Applying VGT Energy Theories to Study the Residual Effect on Body Weight and Postprandial Plasma Glucose by Comparing Two Different Periods of Rich and Heavy Meals and Hyperglycemic Meals Based on GH-Method: Math-Physical Medicine (No. 670)

The author celebrated his birthday with a lunch party on 1/16/2022, where he consumed 20% of a large cake slice. His finger-pierced postprandial plasma glucose (PPG) level reached 171 mg/dL after that luncheon. Over several days, he noticed that his overall PPG levels were persistently higher. Out of curiosity regarding the possible extent of the residual effect on his PPG due to a single hyperglycemic meal, he then queried his ~5000 meals database for the high carbs/sugar meals with hyperglycemic PPG (hyper-PPG) levels above 170 mg/dL. He identified 20 independent hyper-PPG meals over 4 years, Y2018 - Y2022. Next, he grouped his extracted PPG and carbs/sugar data into two separate periods: the period containing 10 days of PPG data before the hyper-PPG day and the post-period containing 10 days of PPG data including the hyper-PPG day. He conducted his research work regarding the special hyper-PPG phenomenon and wrote paper No. 586, VGT#7. Its conclusion is that during these 4 years, any single hyper-PPG meal had a residual effect of approximately 10 days. This phenomenon would eventually dissipate with considerable effort. Since 1/1/2021, the author has maintained his body weight (BW) below 170 lbs. (BMI below 25) for ~1.5 years. On 4/5/2022, he traveled to a different city where he consumed his favorite local meals (rich and heavy) for a couple of days. This incident pushed his BW to 171.4 lbs. with a BMI of 25.3 on 4/7/2022. During the following 40 days, he has tried many weight-reduction techniques, including intermittent fasting, low-calorie meals, reduced food portions, increased exercise level, and good quality sleep to decrease his BW. Finally, on 5/16/2022, he successfully reduced his weight to 169.2 lbs. with a BMI of 24.3 (see figure below). This long, arduous process took 40 days which indicates the hyper-weight scenario had a residual effect of around 40 days. Therefore, he decides to conduct another VGT energy analysis of this hyper-weight scenario to make a direct comparison against his previous hyper-PPG scenario study. In this article, he selected BW values as the strain (ε) and the BW change rate as the strain rate (dε/dt), multiplied by his average food quantity amount (m9a) i.e., viscosity factor (η), as his stress (σ), to construct the desired stress-strain diagram. He used the following defined VGT energy equation from the disciplines of engineering and physics to address this unique “time-dependency characteristic” of biomedical symptoms and causes to establish stress-strain diagrams (i.e. cause-symptom diagram) in a space domain (SD):

Viscoelastic and Viscoplastic Glucose Theory (VGT #31): Applying VGT with Two Different CGM Sensor Measured 2-Hour Postprandial Plasma Glucose (PPG) values from 240 Liquid Egg Meals and 191 Solid Egg Meals as the Strain, along with the PPG Change Rate Multiplied by a Viscosity Factor of Average Carbs/ Sugar Amounts for Each Egg Meal Type as the Stress, and then

The author has studied strength of materials and theory of elasticity through his undergraduate courses at the University of Iowa. He also conducted research work and earned a master’s degree in Biomechanics under Professor James Andrews. In 1970-1971, he used a combined spring and dashpot model to simulate the behaviors of human joints, bones, muscles, and tendons in order to investigate the human-weapon interactions during the Vietnam war era. Later, he went to MIT to pursue his PhD study under Professor Norman Jones, who taught him theory of plasticity and dynamic plastic behaviors of various structure elements. To further his education, he took additional graduate courses in various fields of fluid dynamics, thermodynamics, bridge design using energy absorption pad, and soil mechanics under earthquake influences which have dealt with “time-dependency” issues. Since then, many advancements have been made in the biomechanics branch, especially with human body live tissues that possess certain viscoelastic characteristics, such as bones, muscles, cartilages, tendons (connect bone to muscle), ligaments (connect bone to bone), fascia, and skin. For example, the author suffered plantar fasciitis for many years. He understood that the night splint dorsiflexes forefoot, at the back of the foot, increases plantar fascia tension to offer stress-relief for the pain. This model where muscles and tendons connect the lower leg and foot is a form of viscoelastic study for medical problem solving. When dealing with human internal organs, it is not easy to conduct live experiments to obtain accurate measurements for the biomedical material properties. Blood itself is a viscous material (time-dependent) and its viscosity factor may fall between water, honey, syrup, or gel. But, the author’s research focus is on “glucose” where the blood sugar amount is produced by the liver and carried by red blood cells, not the blood itself. The postprandial plasma glucose (PPG) is strongly influenced by both energy input via carbs/sugar intake amount (~60%) and energy output via postmeal exercise level (~40%). Fundamentally, the PPG level is also dependent on the individual's health conditions in regard to liver cells and pancreatic beta cells, which produce glucose and release insulin to control the glucose level in blood. Therefore, it is nearly impossible to measure the material geometry or material properties to determine the viscosity of “glucose” like in engineering research work. As a result, the best the author could do is to apply the “concept” of viscoelasticity and/or viscoplasticity” to construct an analogy model of time-dependent glucose behaviors.

Viscoelastic and Viscoplastic Glucose Theory (VGT #30): Applying VGT with Two Different CGM Sensor Measured 3-Hour Postprandial Plasma Glucose (PPG) Values from 240 Liquid Egg Meals and 191 Solid Egg Meals as the Strain, Along with the PPG Change Rate Multiplied by a Viscosity Factor of Average Carbs/Sugar Amounts for Each Egg Meal Type as the Stress, and then Applying

The author has studied strength of materials and theory of elasticity through his undergraduate courses at the University of Iowa. He also conducted research work on UI campus to earn a master’s degree in Biomechanics under Professor James Andrews. At that time, he used a combined spring and dashpot model to simulate the behaviors of human joints, bones, muscles, and tendons in order to investigate the human-weapon interactions during the Vietnam war era. Later, he went to MIT to pursue his PhD study under Professor Norman Jones, who taught him theory of plasticity and dynamic plastic behaviors of various structure elements. He also took additional graduate courses in the field of fluid dynamics and thermodynamics along the way of his schooling years. Since then, many advancements have been made in the biomechanics branch, especially with human body tissues that possess certain viscoelastic characteristics, such as bones, muscles, cartilages, tendons (connect bone to muscle), ligaments (connect bone to bone), fascia, and skin. For example, the author suffered plantar fasciitis for many years. He understood that the night splint dorsiflexes forefoot, at the back of the foot, increases plantar fascia tension to offer stress-relief for the pain. This model where muscles and tendons connect the lower leg and foot is a form of viscoelastic study for medical problem solving. When dealing with human internal organs, it is not easy to conduct live experiments to obtain accurate measurements for the biomedical material properties. Blood itself is a viscous material (time-dependent) and its viscosity factor may fall between water, honey, syrup, or gel. The author’s research focuses on “glucose” where the blood sugar amount is produced by the liver and carried by red blood cells, not the blood itself. The postprandial plasma glucose (PPG) is strongly influenced by both energy input via carbs/sugar intake amount (~60%) and energy output via post-meal exercise level (~40%). Fundamentally, the PPG level is also dependent on the individual's health conditions in regard to liver cells and pancreatic beta cells, which produce glucose and release insulin to control the glucose level in blood. Therefore, it is nearly impossible to measure the material geometry or material properties to determine the viscosity of “glucose” like in engineering research work. As a result, the best the author could do is to apply the “concept” of viscoelasticity and/or viscoplasticity” to construct an analogy model of time-dependent glucose behaviors.