Postprandial Hyperglycemia Research Articles

Prognostic value of 1,5-anhydro-D-glucitol incorporating syntax score in acute coronary syndrome.

The utility of adding information on 1,5-anhydro-D-glucitol (1,5-AG), a marker for postprandial hyperglycemia, to a pre-existing scoring system in acute coronary syndrome (ACS) patients is unknown. This retrospective cohort study included 266 ACS patients. The end point was major adverse cardiac and cerebral events (MACCE) through 5years of follow-up. To evaluate incremental benefits of combining 1,5-AG with the syntax score, we applied time-dependent receiver operating curve (ROC) analysis, net reclassification improvement (NRI), integrated discrimination improvement (IDI) and decision curve analysis (DCA). Temporal changes to the area under time-dependent ROC curves showed that addition of 1,5-AG parameters to syntax score did not provide any incremental value (area under the curve for syntax alone, 0.673 (95% confidence interval (CI), 0.599-0.747) vs. with 1,5-AG combined, 0.671 (95%CI 0.596-0.746; Delong p = 0.65). Incorporating 1,5-AG into syntax score yielded a significant NRI of 0.291 (95%CI 0.015-0.567) and IDI of 0.055 (95%CI 0.018-0.093), while DCA analysis showed the limited net benefit in combination with 1,5-AG and syntax score. 1,5-AG values exhibited significant discriminatory utility for detecting MACCE within the ACS population. However, 1,5-AG levels contributed limited utility beyond syntax score based on time-dependent ROC and DCA analyses.Trial registration: UMIN000023837.

In Vitro Combined Effect of Annona Senegalensis and Piliostigma Thonningii Leaf Extracts on Alpha Amylase Activity

Background: Diabetes mellitus (DM), a group of metabolic disorders characterised by hyperglycaemia, has been attributed to increased activity of α-amylase, one of the key enzymes in carbohydrate metabolism. Alpha amylase inhibition can potentially control postprandial hyperglycaemia, hence significant in the management of diabetes mellitus, especially type 2. Acarbose, the proven α-amylase inhibitor, has been associated with several side effects. Plants used in traditional medicine represent a valuable source in the search for an alternative. The study aimed at determining the combined effect of Piliostigma thonningii and Annona senegalensis leaf extracts on alpha amylase activity. Methodology: Mortar and pestle were used to crush the leaves into powder. The fine powder was dispensed in distilled water. Percolation was used to filter the crude extract, evaporated in a water bath at 65 0C to concentrate the extract then reconstituted. Spectrophotometric assay method was used for alpha amylase activity at 540 nm. Results: The results of the study showed that A. senegalensis inhibited α-amylase by 27%, 32% and 34% at 15, 30 and 45 minutes respectively. P. thonningii exhibited inhibitory effects on α-amylase by 25%, 27% and 37% at 15, 30 and 45 minutes respectively. The combined inhibitory effects of A. senegalensis and P. thonningii on α-amylase were 28%, 37% and 62% at 15, 30 and 45 minutes respectively which are significantly different (p <0.05) from that of the positive control, acarbose (71% at 45 minutes) Conclusion: This study revealed the increased strength to inhibit alpha amylase enzyme by a combination of A. senegalensis and P. thonningii and a proportional increase in the inhibitory effect with increase in incubation time than their individual potential to inhibit alpha amylase.

In vitro antidiabetic activity of Peperomia pellucida extract and fraction by alpha-amylase inhibition pathway

The development of type 2 diabetes is influenced by the important role of post-prandial blood glucose management. One strategy in controlling post-prandial hyperglycemia can be done by inhibiting the digestion of dietary carbohydrates through inhibition of alpha amylase enzyme. Natural alpha amylase enzyme inhibition strategy that utilizes natural ingredients is an important alternative in the development of antidiabetic drugs. One of the plants that has the potential to be developed as an antidiabetic is Peperomia pellucida . This study aims to examine the effects of antidiabetic extracts and fractions of Peperomia pellucida in inhibiting alpha amylase enzyme. The research was conducted by determining the total flavonoid using quercetin standard. Antidiabetic studies were carried out by looking at the activity of extracts and fractions of Peperomia pellucida in inhibiting alpha amylase enzyme using visible spectrophotometry method. Data analysis was performed by entering the absorbance value into the standard quercetin curve, while the IC50 value of in vitro antidiabetic activity was determined by entering the value 50 on the curve between the sample concentration and % inhibition of the alpha amylase enzyme. The results showed that the total flavonoid values of the ethanol extract and the ethyl acetate fraction of the herb were 88.24 mg QE/g extract and 80.45 mg QE/g fraction, respectively. Based on the results, the inhibition of alpha amylase enzyme showed that the ethanol extract and the ethyl acetate fraction of the herbs had inhibitory activity with the IC50 value of the ethanol extract 1065.54 g/mL and the ethyl acetate fraction 906.53 g/mL. While the control of acarbose showed an IC50 value of 379.45 g/mL. The ethanol extract and the ethyl acetate fraction of Peperomia pellucida herbs have the potential to be developed as antidiabetic agents with the mechanism of action of inhibiting the activity of the alpha amylase enzyme.

Polyphenol-enriched extract from pearl millet (Pennisetum glaucum) inhibits key enzymes involved in post prandial hyper glycemia (α-amylase, α-glucosidase) and regulates hepatic glucose uptake

Inhibition of carbohydrate digestion and modulation of glucose uptake are the major mechanisms of anti-hyperglycemic potential known to be played by phenolics; but the role of archaeologically relevant staple pearl millet (Pennisetum glaucum; PM), is still much unknown. A combined approach using in vitro inhibitory data and in silico docking of PM phenolics against key players of glucose homeostasis (salivary α-amylase: SA; pancreatic α-amylase: PA; α-glucosidase, maltase-glucoamylase: MGAM and GLUT2) were carried out. Observed notable inhibition with HHB299 having the most relevant effect (IC50: 73.06 ± 0.37 μg/mL for α-amylase; IC50: 73.80 ± 0.12 μg/mL for α-glucosidase). The role of phenolics on basal glucose uptake into hepatocytes, revealed a maximum of 241.25% in PC612 and the least of 198.1% in HHB67imp. Virtual screening via docking found that 3, 4-Di-OMe luteolin, acacetin as the major flavonoids while salicylic acid, melilotic acid as the key phenolic acids contributing towards the observed anti-diabetic effect. Further, structure-activity relationship (SAR) identified the critical functional groups required for the protein-phenolic molecular interactions. This report validates the role of PM phenolics in inhibiting carbolytic enzymes and regulating GLUT and thus probes the link towards the anti-diabetic potential.

Post-transplant Diabetes Mellitus: What Physicians Need to Know.

Post-transplant diabetes mellitus (PTDM) is a common problem among solid organ transplant recipients contributing to morbidity and affecting patient as well as graft survival adversely. It can occur at any period following transplantation, but maximum incidence is observed in the first few months, with a second peak after a few years after transplantation. The pathogenesis is complex and poorly understood, however, it is associated with both dysfunctional beta-cells and insulin resistance. Both nonpharmacologic and antidiabetic therapies are important for adequate glycemic control. This point of view article provides a short review on PTDM in solid organ transplantation (SOT) recipients from a general physician's perspective.

Alpha-glucosidase and Alpha-amylase Inhibition Activity of Avocado Fruit of Nepalese Origin

Background: Diabetes has become a major health problem due to its high prevalence, morbidity, and mortality rate. Reducing postprandial hyperglycemia has become the main target in the treatment of diabetes mellitus. So, developing new drugs with fewer side effects has been a major priority. Objective: The main objective of this study is to investigate total phenolic and flavonoid content, antioxidant activity, α-glucosidase, and α-amylase inhibition activity of Persea Americana Mill (avocado) pulp and seed. Methods: The α-glucosidase and α-amylase inhibition activity were performed using substrates PNPG and CNPG3, respectively. DPPH free radical scavenging assay was used to perform the antioxidant activity. The total phenolic content was estimated using folin-ciocalu’s reagent. Likewise, the aluminium trichloride method was applied to find out the total flavonoid content. Results: The crude methanolic extract of avocado seed revealed potent α-glucosidase inhibition activity with an IC50 1.959±0.93μg/mL followed by the avocado pulp 308±2.36μg/mL. Similarly, the IC50 for the α-amylase inhibition activity of avocado seed was found to be 120.3±1.382μg/mL. In addition, the avocado pulp and seed revealed a significant antioxidant activity with IC50 values of 75.01±0.72μg/mL and 6.445±0.62μg/mL, respectively, compared to the standard quercetin 1.525±0.5μg/mL. The total phenolic content of avocado pulp and the seed was reported as 7.031±2.87 mg of GAE/g, and 142.96±1.589 mg of GAE/g, respectively. Similarly, the total flavonoid content of avocado pulp and the seed was found to be 6.313±1.301 mg of QE/g and 48.696±0.110 mg of GAE/g, respectively. Conclusions: The avocado seed of Nepali origin was found to inhibit the digestive enzyme significantly. These findings indicate that avocado fruit of Nepali origin has the potential to develop as an alternative food therapy for diabetic patients. Further research is required to find out the inhibitor compounds.

1,5-Anhydroglucitol as a Marker of Acute Hyperglycemia in Cardiovascular Events.

1,5-anhydroglucitol (1,5-AG) is a biomarker of acute hyperglycemia in diabetology and also in cardiodiabetology. It is used to monitor fluctuating glucose levels. 1,5-AG is a monosaccharide that is biochemically similar to D-glucose and originates from the nutrition. The presence of 1,5-AG in blood and tissue is nearly constant due to reabsorption in the renal proximal tubule. In acute hyperglycemia, renal reabsorption is inhibited by glucose and 1,5- AG is excreted in the urine, while its serum level decreases rapidly. 1,5-AG reflects glucose excursions over 1-3 days to 2 weeks. In this regard, low levels of serum 1,5-AG can be a clinical marker of short- term glycemic derangements such as postprandial hyperglycemia, which is an important risk factor for the pathogenesis of coronary artery disease (CAD) as low levels of 1,5-AG reflect severe plaque calcification in CAD and correlate with high-density lipoprotein cholesterol (HDL-C) levels. For these reasons, 1,5-AG may also be a marker for atherosclerosis; in fact an even better marker than HbA1c or fructosamine which are normally used. 1,5-AG may also be a predictor of cardiovascular disease, left ventricular dysfunction after acute coronary syndrome (ACS), and mortality after ACS. This articles reviews the current knowledge on 1,5-AG related to its use as predictor for cardiovascular events.

Effect of Different Nutritional Supplements on Glucose Response of Complete Meals in Two Crossover Studies.

Postprandial hyperglycemia is an important risk factor in the development and progression of type-2 diabetes and cardiometabolic diseases. Therefore, maintaining a low postprandial glucose response is key in preventing these diseases. Carbohydrate-rich meals are the main drivers of excessive glycemic excursions during the day. The consumption of whey protein premeals or mulberry leaf extract was reported to reduce postprandial glycemia through different mechanisms of action. The efficacy of these interventions was shown to be affected by the timing of the consumption or product characteristics. Two randomised crossover studies were performed, aiming to identify the optimal conditions to improve the efficacy of these nutritional supplements in reducing a glycemic response. The acute postprandial glycemic response was monitored with a continuous glucose monitoring device. The first study revealed that a preparation featuring 10 g of whey protein microgel reduced the postprandial glucose response by up to 30% (p = 0.001) and was more efficient than the whey protein isolates, independently of whether the preparation was ingested 30 or 10 min before a complete 320 kcal breakfast. The second study revealed that a preparation featuring 250 mg mulberry leaf extract was more efficient if it was taken together with a complete 510 kcal meal (−34%, p < 0.001) rather than ingested 5 min before (−26%, p = 0.002). These findings demonstrate that the efficacy of whey proteins premeal and mulberry leaf extracts can be optimised to provide potential nutritional solutions to lower the risk of type-2 diabetes or its complications.

Association of polymorphism rs10841855 in the glycogen synthase 2 gene with hypercholesterolemia and type 2 diabetes mellitus

Background: Glycogen synthase 2 (GYS2) catalyzes a key step in glycogenesis in the liver. Loss-of-function mutations in the GYS2 gene are associated with type 0a glycogenosis with characteristic fasting hypoglycemia and postprandial hyperglycemia. The association of the single nucleotide polymorphism rs10841855 (G&gt;T) with the risk of type 2 diabetes mellitus (T2D) was first established in the European population, but data on the effect of this variant on the predisposition to T2D in the inhabitants of the Slavic ethnic group of Central Russia are not available in the literature. The aim of the study: To investigate the association of polymorphism rs10841855 (G&gt;T) GYS2 with the risk of T2D in residents of Central Russia. Materials and methods: The study included 2668 unrelated individuals of Slavic origin, including 1387 patients with T2D and 1281 healthy volunteers. Genotyping of the rs10841855 polymorphism of the GYS2 gene was performed by the MassArray Analyzer-4 genetic analyzer. SNPStats software was used for statistical analysis of the data. Results: Linear regression established an association of the alternative rs10841855-T allele (OR 1.25; 95% CI 1.09-1.43; P=0.001) and the rs10841855-G/T genotype (OR 1.37; 95% CI 1, 13-1.66; P=0.0064) of GYS2 with an increased risk of T2D. The sex- and BMI-stratified analysis showed that the association of the rs10841855-G/T genotype (OR 1.71; 95% CI 1.32-2.22; P=0.0001) occurred only in females with BMI&gt;25 kg/m2. In addition, carriage of the rs10841855-T allele was associated with a higher level of total cholesterol in the blood plasma of T2D patients (P=0.0068). According to the Roadmap Epigenomic Consortium, the rs10841855-T allele is associated with H3K4 histone methylation in the enhancer and promoter regions of the GYS2 gene in the liver. Conclusion: The association of rs10841855 of the GYS2 gene with an increased risk of T2D in residents of Central Russia was validated for the first time. The association may be explained by the low transcriptional activity of the glycogen synthase 2 gene in the carriers of the alternative allele of this polymorphism.

Controlling Effect of Ethyl-acetate and n-Butanol Fractions fromPunica granatumL. Peel on Postprandial Hyperglycemia In Vivo, and Its Potent α-Amylase Inhibitory

Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and has been proposed as an independent risk factor for cardiovascular diseases. Herbal medicine has been used for many years by different cultures around the world for the treatment of diabetes.Punica granatumis one of the traditional remedies used for that reason. In this study, we investigated the effects of organic extracts (ethyl acetate andn-butanol) fromPunica granatumpeel on postprandial hyperglycemiain vivocaused by glucose, sucrose, maltose, or starch loading. Oral administration ofPunica granatumpeel extracts (400 mg/kg b.w.) markedly lowered plasma glucose levels in fasted normal rats. We examinedin vitrowhether the organic fractions ofPunica granatumpeel have an antidiabetic effect through α-amylase inhibitory action. Ethyl acetate andn-butanol fractions of aqueous/acetone crude extracts displayed a potent inhibitory effect on α-amylase activity (IC50 = 0.85 and 2.13 g/l, respectively). These results suggest that inhibitory activity ofPunica granatumpeel extracts may contribute to delay in carbohydrate digestion and glucose absorption and improves postprandial hyperglycemia in type 2 diabetes by inhibiting intestinal αamylase and disaccharidases activity.

A pilot study on the effect of d-allulose on postprandial glucose levels in patients with type 2 diabetes mellitus during Ramadan fasting

BackgroundDuring Ramadan fasting, postprandial hyperglycemia is commonly observed after iftar (break of fast at sunset) meal. d-allulose is a rare sugar and is reported to have several health benefits, including the suppression of increase in postprandial glucose levels. This study investigates whether d-allulose (a C-3 epimer of d-fructose) improves the postprandial glucose in patients with type 2 diabetes mellitus (T2DM) during Ramadan.MethodsThis was a pilot, prospective single-arm study design that was conducted for 10 consecutive days; 5 days of control and 5 days of consumption. The primary outcome was postprandial peak glucose levels. During the consumption period, 8.5 g of d-allulose was consumed by the participants before iftar meal. Postprandial glucose was measured using a continuous glucose monitoring system.ResultsA total of 12 participants completed the study. Significant lower (p < 0.01) postprandial glucose values and the glucose incremental area under the curve (iAUC) were observed from 0 to 180 min during the consumption period compared to the control period. The consumption period demonstrated significantly higher percentages of time in which glucose values were found in the target range (p = 0.0032), and when the glucose levels above the target range were reduced (p = 0.0015).ConclusionsThe supplementation with d-allulose has the potential to improve postprandial hyperglycemia in patients with T2DM after iftar during Ramadan. Further studies are needed to confirm these findings.Trial registration ClinicalTrials.gov NCT05071950. Retrospectively registered, 8 October 2021.

Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches.

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.

A Pilot Study to Assess Glucose, Insulin, and Incretin Responses Following Novel High Resistant Starch Rice Ingestion in Healthy Men.

IntroductionA newly developed resistant starch (RS) rice line with double mutation of starch synthase IIIa and branching enzyme IIb (ss3a/be2b) exhibits a tenfold greater percentage RS value than the wild-type rice line. Currently, the effects of cooked rice with such high RS content on secretion and action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are unclear. Therefore, we conducted a pilot study to assess postprandial responses of GLP-1 and GIP along with glucose and insulin and also gastric emptying after ingestion of the high-RS cooked rice with ss3a/be2b in healthy subjects.MethodsIn a non-randomized crossover design, five healthy men ingested two test foods, control (low-RS) and high-RS cooked rice, with at least 1-week washout period between testing days. Plasma glucose, serum insulin, plasma total GLP-1, plasma total GIP, and also gastric emptying rate were measured after ingestion of each test food, and the incremental area under the curves (iAUC) was calculated for each biochemical parameter using the values from 0 to 180 min after ingestion.ResultsThe high-RS cooked rice ingestion tended to reduce iAUC-glucose (p = 0.06) and significantly reduced iAUC-insulin (p < 0.01) and iAUC-GLP-1 (p < 0.05) but not iAUC-GIP (p = 0.21) relative to control cooked rice ingestion. In addition, the high-RS cooked rice ingestion did not affect gastric emptying.ConclusionsThe present results indicate that the suppressive effects of the high-RS cooked rice ingestion on postprandial responses of glucose and insulin may be provided through attenuation in GLP-1 secretion along with its low digestibility into glucose. We suggest that the high-RS rice with ss3a/be2b may serve as a better carbohydrate source and also as a novel functional food for dietary interventions to improve postprandial hyperglycemia and hyperinsulinemia without both enhancing GLP-1 secretion and affecting gastric emptying in patients with diabetes.

Additional insulin dosing for fat and protein in children with type 1 diabetes using multiple daily injections

High-fat high-protein (HFHP) meals are associated with post-prandial hyperglycemia in type 1 diabetes (T1D), administration of additional insulin for such meals is recommended in order to optimize glucose levels. Optimal timing of additional insulin for HFHP meals in children and young people receiving multiple daily injections (MDI) remains unclear. To investigate the glycemic impact of additional insulin doses given before or after eating a HFHP meal in children with T1D using MDI. A randomized, controlled three period crossover trial of 27 participants aged 13 years (6.1-17.7) at two Pediatric Diabetes centers was conducted. Additional rapid-acting insulin for the fat-protein content of a standardized HFHP meal was given at three time points calculated using an algorithm extrapolated from current evidence base and clinical recommendations. Post-prandial glucose (PPG) parameters were calculated for 420minutes using continuous glucose monitoring. The primary outcome was mean PPG excursion. Secondary outcomes included peak glucose, time to peak and hypoglycemia incidence. There was no difference in post-prandial glucose parameters when additional HFHP insulin was administered at mean glucose excursion (mmol/L) (SE): 1.9(0.7), 1.2(0.7), 2.5(0.7); p= 0.5); mean peak glucose (mmol/L)(SE): 10.9(0.9), 11.5(0.8), 11.5(0.9); p= 0.9; time to peak glucose (mins)(SE): 82.3(35.4), 113.6(30.9), 95.1(32.1); p= 0.8. Mild hypoglycemia was common (55%) in all groups (p= 0.97). We found no benefit in giving additional insulin as a split dose for HFHP meals in children using MDI, mild hypoglycemia was common. Future studies would benefit from refinement of the insulin dose algorithm.

Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.

Insulin-stimulated glucose uptake in skeletal muscle is of fundamental importance to prevent postprandial hyperglycemia, and long-term deficits in insulin-stimulated glucose uptake underlie insulin resistance and type 2 diabetes. Skeletal muscle is responsible for ~80% of the peripheral glucose uptake from circulation via the insulin-responsive glucose transporter GLUT4. GLUT4 is mainly sequestered in intracellular GLUT4 storage vesicles in the basal state. In response to insulin, the GLUT4 storage vesicles rapidly translocate to the plasma membrane, where they undergo vesicle docking, priming, and fusion via the high-affinity interactions among the soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) exocytosis proteins and their regulators. Numerous studies have elucidated that GLUT4 translocation is defective in insulin resistance and type 2 diabetes. Emerging evidence also links defects in several SNAREs and SNARE regulatory proteins to insulin resistance and type 2 diabetes in rodents and humans. Therefore, we highlight the latest research on the role of SNAREs and their regulatory proteins in insulin-stimulated GLUT4 translocation in skeletal muscle. Subsequently, we discuss the novel emerging role of SNARE proteins as interaction partners in pathways not typically thought to involve SNAREs and how these atypical functions reveal novel therapeutic targets for combating peripheral insulin resistance and diabetes.

Nutritional strategies to attenuate postprandial glycemic response.

SummaryMaintaining good glycemic control to prevent complications is crucial in people with type 2 diabetes and in people with prediabetes and in the general population. Different strategies to improve glycemic control involve the prescription of blood glucose‐lowering drugs and the modulation of physical activity and diet. Interestingly, lifestyle intervention may be more effective in lowering hyperglycemia than pharmaceutical intervention. Regulation of postprandial glycemia is complex, but specific nutritional strategies can be applied to attenuate postprandial hyperglycemia. These strategies include reducing total carbohydrate intake, consuming carbohydrates with a lower glycemic index, the addition of or substitution by sweeteners and fibers, using food compounds which delay or inhibit gastric emptying or carbohydrate digestion, and using food compounds which inhibit intestinal glucose absorption. Nevertheless, it must be noted that every individual may respond differently to certain nutritional interventions. Therefore, a personalized approach is of importance to choose the optimal nutritional strategy to improve postprandial glycemia for each individual, but this requires a better understanding of the mechanisms explaining the differential responses between individuals.

Blood Glucose Response of a Low-Carbohydrate Oral Nutritional Supplement with Isomaltulose and Soluble Dietary Fiber in Individuals with Prediabetes: A Randomized, Single-Blind Crossover Trial.

A high-energy-type oral dietary supplement (ONS), with a low proportion of available carbohydrate (LC-ONS), which contains a slowly digestible carbohydrate, isomaltulose, and is fortified with soluble dietary fiber, was newly developed for individuals with diabetes or prediabetes. This study aimed to evaluate the impact of LC-ONS on blood glucose levels after ingestion in individuals with prediabetes. A single-blind, randomized crossover clinical trial was performed on 20 individuals with prediabetes. After overnight fasting, all subjects ingested one serving (200 kcal/125 mL) of either LC-ONS (40% energy proportion of available carbohydrates) or standard ONS (ST-ONS, 54% energy proportion of available carbohydrates) on two separate days. The incremental area under the curve of blood glucose levels for 120 min was significantly lower after LC-ONS ingestion compared to ST-ONS (2207 ± 391 mg/dL·min (least mean square value ± standard error) and 3735 ± 391 mg/dL·min, respectively; p < 0.001). The LC-ONS showed significantly lower blood glucose levels than the ST-ONS at all time points, except at baseline. Similarly, the incremental area under the curve of plasma insulin was significantly lower after LC-ONS ingestion. These results suggest that LC-ONS is useful as an ONS for energy supply in individuals with postprandial hyperglycemia.

Endothelial Dysfunction Is Associated with Decreased Nitric Oxide Bioavailability in Dysglycaemic Subjects and First-Degree Relatives of Type 2 Diabetic Patients.

Oxidative stress plays an important role in the pathogenesis of diabetes. We investigated oxidative stress and nitrite/nitrate concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDRs) of diabetic patients with normal oral glucose tolerance test (OGTT) results, 40 subjects with abnormal OGTT results (dysglycaemic) and 20 subjects with normal OGTT results (normoglycaemic). Malondialdehyde (MDA), protein carbonyls (PCs), nitrite/nitrate plasma levels, the perfused boundary region (PBR—Glycocheck) of the sublingual microvessels, a marker of glycocalyx integrity, coronary flow reserve (CFR) and left ventricular global longitudinal strain (GLS) were assessed at 0 and 120 min of the OGTT. Insulin sensitivity was evaluated using Matsuda and the insulin sensitivity index (ISI). In all subjects, there were no significant changes in MDA or PC after the OGTT (p > 0.05). Compared with normoglycaemic subjects, FDRs and dysglycaemic subjects had significantly decreased nitrite/nitrate levels (−3% vs. −24% vs. −30%, respectively), an increased PBR and reduced CFR and GLS at 120 min (p < 0.05). The percent reduction in nitrite/nitrate was associated with abnormal Matsuda and ISI results, reversely related with the percent increase in PBR (r = −0.60) and positively related with the percent decrease in CFR (r = 0.39) and GLS (r = 0.48) (p < 0.05). Insulin resistance is associated with reduced nitric oxide bioavailability and coronary and myocardial dysfunction in FDRs and dysglycaemic subjects.

SGLT2 Inhibition with Empagliflozin as a Possible Therapeutic Option for Postprandial Hypoglycemia After Bariatric Surgery

Since SGLT2 inhibitors may reduce postprandial hyperglycemia, this study aimed to evaluated whether empagliflozin might be useful in the treatment of postprandial hypoglycemia (PPH) postbariatric surgery (BS). Fourteen patients who underwent BS, nine without type 2 diabetes and five with diabetes before surgery and in remission after surgery, were included. Seven of them presented symptoms of PPH (hypoglycemic group; HG) and seven were asymptomatic (nonhypoglycemic group (NHG)). A meal tolerance test was performed before and after administration of a daily dose of empagliflozin (EMPA) 25mg for 3days. Plasma glucose and serum insulin levels were measured. In HG, compared with NHG, in the basal test, the area under the curve (AUC) of plasma glucose levels (AUCgly) was smaller (158.3 ± 25.3 vs 276.6 ± 79.2mgh dL-1; p = 0.001) while the AUC of insulin levels (AUCins) did not differ, leading to a higher AUCins/AUCgly ratio (0.79 ± 0.46 vs 0.38 ± 0.20; p = 0.055) and a lower HOMA-IR (0.92 ± 0.22 vs 1.75 ± 0.77; p = 0.030). The HG after EMPA, but not the NHG, showed significant increases in glycemia leading to greater AUCgly (158.0 ± 25.3 to 197.2 ± 51.6mgh dL-1; p = 0.043) without significant changes in AUCins. HOMA-IR increased only in the HG (0.92 ± 0.20 vs 1.61 ± 0.30; p = 0.025) and, when both groups were analyzed together, both before and post EMPA, a significant correlation was found between HOMA-IR and AUCgly values (r = 0.594; p = 0.002). Our results suggest that empagliflozin increased glycemic levels in patients with PPH possibly through increases in hepatic glucose production.

Photoacoustic imaging reveals mechanisms of rapid-acting insulin formulations dynamics at the injection site

ObjectiveUltra-rapid insulin formulations control postprandial hyperglycemia; however, inadequate understanding of injection site absorption mechanisms is limiting further advancement. We used photoacoustic imaging to investigate the injection site dynamics of dye-labeled insulin lispro in the Humalog® and Lyumjev® formulations using the murine ear cutaneous model and correlated it with results from unlabeled insulin lispro in pig subcutaneous injection model. MethodsWe employed dual-wavelength optical-resolution photoacoustic microscopy to study the absorption and diffusion of the near-infrared dye-labeled insulin lispro in the Humalog and Lyumjev formulations in mouse ears. We mathematically modeled the experimental data to calculate the absorption rate constants and diffusion coefficients. We studied the pharmacokinetics of the unlabeled insulin lispro in both the Humalog and Lyumjev formulations as well as a formulation lacking both the zinc and phenolic preservative in pigs. The association state of insulin lispro in each of the formulations was characterized using SV-AUC and NMR spectroscopy. ResultsThrough experiments using murine and swine models, we show that the hexamer dissociation rate of insulin lispro is not the absorption rate-limiting step. We demonstrated that the excipients in the Lyumjev formulation produce local tissue expansion and speed both insulin diffusion and microvascular absorption. We also show that the diffusion of insulin lispro at the injection site drives its initial absorption; however, the rate at which the insulin lispro crosses the blood vessels is its overall absorption rate-limiting step. ConclusionsThis study provides insights into injection site dynamics of insulin lispro and the impact of formulation excipients. It also demonstrates photoacoustic microscopy as a promising tool for studying protein therapeutics. The results from this study address critical questions around the subcutaneous behavior of insulin lispro and the formulation excipients, which could be useful to make faster and better controlled insulin formulations in the future.