Postprandial Glucose Concentrations Research Articles

Pulse consumption improves indices of glycemic control in adults with and without type 2 diabetes: a systematic review and meta-analysis of acute and long-term randomized controlled trials

PurposeFindings from randomized controlled trials (RCTs) evaluating the effect of pulse intake on glycemic control are inconsistent and conclusive evidence is lacking. The aim of this study was to systematically review the impact of pulse consumption on post-prandial and long-term glycemic control in adults with and without type 2 diabetes (T2D).MethodsDatabases were searched for RCTs, reporting outcomes of post-prandial and long-term interventions with different pulse types on parameters of glycemic control in normoglycemic and T2D adults. Effect size (ES) was calculated using random effect model and meta-regression was conducted to assess the impact of various moderator variables such as pulse type, form, dose, and study duration on ES.ResultsFrom 3334 RCTs identified, 65 studies were eligible for inclusion involving 2102 individuals. In acute RCTs, pulse intake significantly reduced peak post-prandial glucose concentration in participants with T2D (ES – 2.90; 95%CI – 4.60, – 1.21; p ≤ 0.001; I2 = 93%) and without T2D (ES – 1.38; 95%CI – 1.78, – 0.99; p ≤ 0.001; I2 = 86%). Incorporating pulse consumption into long-term eating patterns significantly attenuated fasting glucose in normoglycemic adults (ES – 0.06; 95%CI – 0.12, 0.00; p ≤ 0.05; I2 = 30%). Whereas, in T2D participants, pulse intake significantly lowered fasting glucose (ES – 0.54; 95%CI – 0.83, – 0.24; p ≤ 0.001; I2 = 78%), glycated hemoglobin A1c (HbA1c) (ES – 0.17; 95%CI – 0.33, 0.00; p ≤ 0.05; I2 = 78) and homeostatic model assessment of insulin resistance (HOMA-IR) (ES – 0.47; 95%CI – 1.25, – 0.31; p ≤ 0.05; I2 = 79%).ConclusionPulse consumption significantly reduced acute post-prandial glucose concentration > 1 mmol/L in normoglycemic adults and > 2.5 mmol/L in those with T2D, and improved a range of long-term glycemic control parameters in adults with and without T2D.PROSPERO registry number(CRD42019162322).

Meal-induced inflammation: postprandial insights from the Personalised REsponses to DIetary Composition Trial (PREDICT) study in 1000 participants

ABSTRACTBackgroundMeal-induced metabolic changes trigger an acute inflammatory response, contributing to chronic inflammation and associated diseases.ObjectivesWe aimed to characterize variability in postprandial inflammatory responses using traditional (IL-6) and novel [glycoprotein acetylation (GlycA)] biomarkers of inflammation and dissect their biological determinants with a focus on postprandial glycemia and lipemia.MethodsPostprandial (0–6 h) glucose, triglyceride (TG), IL-6, and GlycA responses were measured at multiple intervals after sequential mixed-nutrient meals (0 h and 4 h) in 1002 healthy adults aged 18–65 y from the PREDICT (Personalised REsponses to DIetary Composition Trial) 1 study, a single-arm dietary intervention study. Measures of habitual diet, blood biochemistry, gut microbiome composition, and visceral fat mass (VFM) were also collected.ResultsThe postprandial changes in GlycA and IL-6 concentrations were highly variable between individuals. Participants eliciting an increase in GlycA and IL-6 (60% and 94% of the total participants, respectively) had mean 6-h increases of 11% and 190%, respectively. Peak postprandial TG and glucose concentrations were significantly associated with 6-h GlycA (r = 0.83 and r = 0.24, respectively; both P < 0.001) but not with 6-h IL-6 (both P > 0.26). A random forest model revealed the maximum TG concentration was the strongest postprandial TG predictor of postprandial GlycA and structural equation modeling revealed that VFM and fasting TG were most strongly associated with fasting and postprandial GlycA. Network Mendelian randomization demonstrated a causal link between VFM and fasting GlycA, mediated (28%) by fasting TG. Individuals eliciting enhanced GlycA responses had higher predicted cardiovascular disease risk (using the atherosclerotic disease risk score) than the rest of the cohort.ConclusionsThe variable postprandial increases in GlycA and their associations with TG metabolism highlight the importance of modulating TG in concert with obesity to reduce GlycA and associated low-grade inflammation–related diseases.This trial was registered at clinicaltrials.gov as NCT03479866.

Glucose-Responsive Polyelectrolyte Complexes Based on Dendritic Mesoporous Silica for Oral Insulin Delivery.

The postprandial glycemic regulation is essential for diabetic patients to reduce the risk of long-term microvascular and macrovascular complications. Herein, we designed a glucose-responsive oral insulin delivery system based on polyelectrolyte complexes (PECs) for controlling the increasing postprandial glucose concentrations. Briefly, alginate-g-3-aminophenylboronic acid (ALG-g-APBA) and chitosan-g-3-fluoro-4-carboxyphenylboronic acid (CS-g-FPBA) were wrapped on mesoporous silica (MSN) to form the negative charged ALG-g-APBA@MSN and the positive charged CS-g-FPBA@MSN nanoparticles, with an optimum insulin loading capacity of 124 mg/g and 295 mg/g, respectively. ALG-g-APBA@MSN was further cross-linked with CS-g-FPBA@MSN to form PECs through electrostatic interaction and borate esters. The dense polyelectrolyte network wrapped on MSN was capable of preventing insulin from diffusion and regulating its release. The in vitro insulin release of PECs demonstrated an obvious glucose response profile in different glucose concentrations (0 mg/mL, 2 mg/mL, 5 mg/mL) and presented a switch "on" and "off" release regulation at hyperglycemic or normal state. The CCK-8 assay showed that none of the MSN, ALG-g-APBA@MSN, CS-g-FPBA@MSN, and PECs possessed cytotoxicity to Caco-2 cells. For in vivo tests, the oral PECs exhibited a significant hypoglycemic effect and maintained in the euglycemic levels up to approximately 12 h on diabetic rats. Overall, the PECs directly triggered by postprandial glucose in the intestine have a good potential to be applied in intelligent insulin delivery by the oral route.

An algorithm mimicking pancreas pulsatile behavior improves artificial pancreas performance.

Artificial pancreas design using subcutaneous insulin infusion without pre-meal feed-forward boluses often induces an over-response leading to hypoglycemia due to the increase of blood insulin concentration sustained in time. The objective of this work was to create an algorithm for controlling the function of insulin pumps in closed-loop systems to improve blood glucose management in type 1 diabetic patients by mimicking the pulsatile behaviour of the pancreas. A controller tuned in a pulsatile way promotes damped oscillations of blood insulin concentration injected through an insulin pump. We tested it in a simulated environment, using nine 'in silica' subjects. The control algorithm is founded on feedback linearization where through a change of variables, the nonlinear system turns into an equivalent linear system, suitable for implementing through a PID controller. We compared the results obtained 'in silica' with the volume injected by an insulin pump controlled by this algorithm. The use of this algorithm resulted in a pulsatile control of postprandial blood glucose concentration, avoiding hypoglycaemic episodes. The results obtained 'in silica' were replicated in a real pump 'in vitro'. With this proposed linear system, an appropriate control input can be designed. The controller works with a damped pulsatile pattern making the insulin infusion from the pump and blood insulin concentration pulsatile. This operational would improve the performance of an artificial pancreas.

Correlation of fasting and postprandial dyslipidemia with macrovascular complications of diabetes mellitus

: The most prevalent form of the disease, type 2 Diabetes Mellitus is often asymptomatic in the early stages and it may remain undiagnosed for many years.The insulin resistance in the liver leads to failure of the hyperinsulinaemia to suppress the gluconeogenesis, which increases fasting glucose levels and decreases Postprandial hypertriglyceridemia results in a proatherogenic environment which leads to atherosclerosis and macrovascular complications in type 2 diabetes mellitus. It is believed that atherosclerosis is a postprandial phenomenon with respect to lipids, as we are in the postprandial state for most of the day. Increased glucose production in the liver occurs early in the course of diabetes, and it is likely in skeletal muscles after the onset of the insulin secretory abnormalities and the insulin resistance Due to the insulin resistance in the adipose tissue and obesity, the free fatty acid (FFA) flux from the adipocytes is increased, which in turn leads to an increase in lipid [very low-density lipoprotein (VLDL) and triglycerides] synthesis in the hepatocytes. This is responsible for the dyslipidaemia which is found in type2 diabetes mellitus [elevated triglycerides, reduced HDL, and increased low-density lipoprotein (LDL) particle.Individuals with type 2 diabetes mellitus are at increased risk of developing microvascular and macrovascular complications. Increased postprandial glucose (PPG) concentrations contribute to suboptimal glycemic control. : To correlate fasting and postprandial dyslipidemia with macrovascular complications of diabetes.: This is a cross-sectional study, wherein written informed consent was taken after giving detailed information to the participants regarding the study. Patients who were in the age group of 35-65 years, admitted in the Department of Medicine, RRMCH from November 2017 for next 18 months with Diabetes Mellitus who met a predefined inclusion and exclusion criteria were studied. The study was initiated after obtaining clearance from the institution's ethical committee.: IHD changes were found in 8 cases and 3 controls, LVH by voltage criteria was found in 15 cases and 8 controls. IHD changes found in cases and controls are 16% and 6% respectively. LVH changes found in cases and controls are 30% and 16% respectively.Abnormal 2D Echo findings in our study were mainly IHD and LVH. The occurrence of IHD was more in cases compared to controls with statistical significance(p&amp;#60;0.05).Peripheral vascular disease in our study was found in 25 patients i.e.25% of the study group. In cases, it was found in 20 patients and in controls, it was found in 5 patients i.e. 40% and 10% respectively. The occurrence of PVD was more in cases compared to controls with statistical significance(p&amp;#60;0.05).Stroke in our study is found in 7 patients i.e. 7% of the study group. In cases, it was found in 6 patients and in controls, it was found in 1 patient i.e. 12% and 2% respectively. : It could be said that there is an increase in the occurrence of postprandial dyslipidemia with increasing age, irregular treatment, increase in HbA1c, FBS ,PPBS and with the past history of HTN, CVA, PVD and IHD.All macrovascular complications (IHD, CVA, PVD) were found more in the case compared to controls with statistical significance. So it could be said that there is an increase in the occurrence of macrovascular complications with an increase in postprandial dyslipidemia.

203-LB: Boosted Beta-Cell Function with Selective Deletion of the Adaptor Protein Mig6

Type 1 and type 2 diabetes (T1D and T2D) are characterized by absolute and relative insulin deficiency, respectively. Thus, fortifying functional beta cell mass is essential for preventing or reversing either form of diabetes. We have investigated the impact of the adaptor protein mitogen inducible gene 6 (Mig6), a feedback inhibitor of epidermal growth factor receptor (EGFR) signaling induced in the diabetic milieu, on functional beta cell mass in the context of T1D and T2D. Given the importance of EGFR signaling in establishing and maintaining functional beta cell mass, we hypothesized that a selective loss of Mig6 in beta cells would increase functional beta cell mass. To this end, we generated mice lacking Mig6 in beta cells (BKO) using Mig6 floxed and Ins1-Cre knock-in mice and conducted extensive phenotyping, including quantifying beta cell function in vivo with hyperglycemic clamps. Compared to control littermates (CON), BKO mice had comparable beta cell mass, glucose tolerance, and post-prandial blood glucose or insulin concentrations when fed a standard chow diet. Mice underwent surgical catheterization of a carotid artery and jugular vein, and were allowed to recover for 4 days. Following a 5-h fast, mice were administered a primed and subsequent variable glucose infusion designed to clamp blood glucose at 15 mM (270 mg/dl). Target glycemia was achieved by 60 min and remained constant for the duration of the experiment. During the clamp, blood glucose or glucose infusion rates were not different between groups. Whereas beta cell mass was not different between groups, BKO had enhanced beta cell function in vivo, as exhibited by increased insulin secretion; compared to CON, the cumulative circulating insulin during the clamp in BKO was substantially larger (AUC: 340 ± 24 vs. 545 ± 70 ng/ml*120 min). Thus, a loss of Mig6 in beta cells enhances functional beta cell mass by increasing beta cell insulin secretory capacity in vivo. Therefore, Mig6 should be considered as a therapeutic target for diabetes. Disclosure B. M. Bauer: None. E. A. Bloom-saldana: None. J. M. Irimia-dominguez: None. P. T. Fueger: Consultant; Self; Protomer Technologies. Funding National Institutes of Health (R01DK099311)

In vitro α amylase and amyloglucosidase inhibitory activities of selected underutilized cereals, yams and root crops

Diabetes is one of the most challenging global health problems. Currently, reducing postprandial blood glucose concentration by inhibiting carbohydrate hydrolyzing enzymes is recognized as an effective treatment against diabetes. In this study, in vitro α-amylase and amyloglucosidase inhibitory effect of selected, underutilized and locally grown cereals (P. miliaceum, P. scrobiculatum and S. italica), yams (D. alata and D. esculenta) and root crops (L. spinosa and N. nucifera) were evaluated related to their dietary fiber contents. Results showed that the inhibitory effect of selected food crops has a positive correlation with their dietary fiber contents. L. spinosa with higher dietary fiber content generally had higher α-amylase (78.0%) and amyloglucosidase (71.28%) enzyme inhibitory percentages among yams and root crops. Significantly highest (p<0.05) dietary fiber content was in S. italic among three cereal varieties and it showed the highest inhibition activity against α-amylase (67.8%) and amyloglucosidase (59.40%) activity. These tested food crops are considerable sources of dietary fiber and are having α-amylase and amyloglucosidase enzyme inhibitory actions against starch hydrolysis.

Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults.

Background: Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described.Objective: To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance.Design: Ninety-five non-diabetic Chinese subjects (43 females) underwent a mixed-meal tolerance test; blood biomarkers including BCAAs (leucine, isoleucine, valine) were measured for 6 h. Fasting and postprandial insulin secretion rates (ISR) and insulin clearance were determined by oral minimal modeling of glucose and C-peptide.Results: Fasting and postprandial plasma BCAA correlated strongly with each other (ρ = 0.796, P < 0.001), and both were positively associated with basal ISR (ρ = 0.45/0.36, P < 0.001), total postprandial ISR AUC (ρ = 0.37/0.45, P < 0.001), and negatively with insulin clearance (ρ = −0.29/−0.29, P < 0.01), after adjusting for sex and body mass index. These relationships largely persisted after adjusting further for insulin resistance and postprandial glucose. Compared with subjects in the middle and lowest tertiles for fasting or postprandial plasma BCAA, subjects in the highest tertile had significantly greater postprandial glucose (by 7–10%) and insulin (by 74–98%) concentrations, basal ISRs (by 34–53%), postprandial ISR AUCs (by 41–49%), and lower insulin clearance rates (by 17–22%) (all P < 0.05).Conclusions: Fasting and postprandial plasma BCAA levels are associated with greater fasting and postprandial insulin secretion and reduced insulin clearance in healthy Chinese subjects. These observations potentially highlight an additional layer of involvement of BCAA in the regulation of glucose homeostasis.

Gut Microbiome Prolongs an Inhibitory Effect of Korean Red Ginseng on High-Fat-Diet-Induced Mouse Obesity.

Although the anti-obesity effect of Korean red ginseng (Panax ginseng Meyer) has been revealed, its underlying mechanisms are not clearly understood. Here, we demonstrate an involvement of gut microbiome in the inhibitory effect of Korean red ginseng on high-fat-diet (HFD)-induced mouse obesity, and further provides information on the effects of saponin-containing red ginseng extract (SGE) and saponin-depleted red ginseng extract (GE). Mice were fed with either SGE or GE every third day for one month, and their food intakes, fat weights, plasma glucose, and insulin and leptin levels were measured. Immunofluorescence assays were conducted to measure pancreatic islet size. Stools from the mice were subjected to metagenomic analysis. Both SGE and GE attenuated HFD-induced gain of body weight, reducing HFD-induced increase of food intakes and fat weights. They also reduced HFD-increased plasma glucose, insulin, and leptin levels, decreased both fasting and postprandial glucose concentrations, and improved both insulin resistance and glucose intolerance. Immunofluorescence assays revealed that they blocked HFD-induced increase of pancreatic islet size. Our pyrosequencing of the 16S rRNA gene V3 region from stools revealed that both SGE and GE modulated HFD-altered composition of gut microbiota. Therefore, we conclude that Korean red ginseng inhibits HFD-induced obesity and diabetes by altering gut microbiome.

Effects of energy source in milk replacer on glucose metabolism of neonatal dairy calves

Milk replacers (MR) formulated to contain more lactose than whole milk could potentially reduce insulin sensitivity in dairy calves. This study evaluated how partially replacing lactose in MR with fat on a weight/weight basis affects glucose-insulin kinetics in neonatal dairy calves fed high quantities of MR. Thirty-four Holstein bull calves were blocked by dam parity (1.6 ± 0.3) and randomly assigned to 1 of 2 treatments (n = 17): a high-lactose MR (HL; 46.1% lactose, 18.0% crude fat, and 23.9% crude protein on a dry matter basis) or a high fat MR (HF; 39.9% lactose, 24.6% crude fat, and 24.0% crude protein on a dry matter basis). Calves were individually housed and fed pooled colostrum at 1.5 h and 12 h postnatal at 18 and 9% of metabolic body weight (BW0.75), respectively. From 24 h postnatal until the end of the study (d 7), calves were transitioned to MR (prepared at 150 g/L) at 18% of BW0.75 twice daily at 0700 and 1900 h. On d 4, an insulin-modified intravenous glucose tolerance test was conducted 8 h after the morning meal by intravenous infusion of glucose (0.54 g/kg of BW0.75, min 0) and insulin (3.9 µg/kg of BW0.75, min 20). During postprandial sampling on d 6, abomasal emptying was assessed by dosing acetaminophen (0.13 g/kg of BW0.75) with MR and measuring its appearance within plasma. Sequential blood samples were collected and analyzed for plasma glucose, insulin, and acetaminophen concentrations. Calves were killed on d 7 and liver and pancreatic tissues were collected for histomorphological analysis. Partially replacing lactose in MR with fat increased body weight gain (679.6 vs. 462.0 ± 69.68 g/d) and gain:metabolizable energy intake (186.6 vs. 120.5 ± 20.21 g of body weight/Mcal) compared with feeding HL MR. Furthermore, abomasal emptying rate was reduced in calves fed HF MR. Calculated variables based on postprandial glucose and insulin concentrations, such as maximum concentration or area under the curve, were or tended to be lower in HF than in HL calves. Postprandial insulin sensitivity tended to be reduced in HL compared with HF, although insulin sensitivity estimated from the insulin-modified intravenous glucose tolerance test was not different. Calves fed HF MR showed enhanced glucose-stimulated insulin secretion. In conclusion, partially replacing lactose in MR with fat resulted in smaller fluctuations in postprandial glucose and insulin concentrations and tended to increase postprandial but not fasting insulin sensitivity in neonatal dairy calves.

A Practical Perspective for a Conservative Estimate of Blood Glucose Level during Restaurant Dining and Supermarket Shopping.

Foods today are so diverse and enjoyable, making healthy choices difficult. In this perspective, an in vitro-in silico approach for obtaining a conservative estimate of the postprandial blood glucose concentration, which is a realistic estimate nevertheless, after intake of a certain portion of meals is proposed. The rationales and feasibilities of the approach are described and discussed to an extent. The key idea is to first measure the maximum amount of glucose released in an in vitro test under standardized conditions from a specified serving size of a meal or dish or a packaged product sold in a supermarket. The value can then be translated by a literate consumer to the highest estimate of blood glucose rise prior to purchasing or eating through an established in silico blood glucose prediction model in the medical field. The strategy proposed here would help health conscious (diabetics included) and other life quality conscious individuals to make quantitative decisions on consuming the portions of different foods of desire. This strategy may be more effective in reality compared to the conventional GI (Glycemic Index) and GL (Glycemic Load) concepts.

Long limb compared with standard limb Roux-en-Y gastric bypass for type 2 diabetes and obesity: the LONG LIMB RCT

Background Roux-en-Y gastric bypass is recognised as a standard of care in the treatment of diabetes mellitus and obesity. However, the optimal length of the Roux-en-Y gastric bypass limbs remains controversial, with substantial variation in practice. Specifically, a longer biliopancreatic limb length of 150 cm (‘long limb’) has been hypothesised to be better for the treatment of diabetes mellitus because it increases the postprandial secretion of gut hormones, such as glucagon-like peptide 1, and increases insulin sensitivity, compared with the Roux-en-Y gastric bypass utilising a standard biliopancreatic limb length of 50 cm (‘standard limb’). Objective To evaluate the mechanisms, clinical efficacy and safety of long limb versus the standard limb Roux-en-Y gastric bypass in patients undergoing metabolic surgery for obesity and diabetes mellitus. Design A double-blind, mechanistic randomised controlled trial was conducted to evaluate the mechanisms, clinical efficacy and safety of the two interventions. Setting Imperial College London, King’s College London and their associated NHS trusts. Participants Patients with obesity and type 2 diabetes mellitus who were eligible for metabolic surgery. Interventions Participants were randomly assigned (1 : 1) to 150-cm (long limb) or 50-cm (standard limb) biliopancreatic limb Roux-en-Y gastric bypass with a fixed alimentary limb of 100 cm. The participants underwent meal tolerance tests to measure glucose excursions, glucagon-like peptide 1 and insulin secretion, and hyperinsulinaemic–euglycaemic clamps with stable isotopes to measure insulin sensitivity preoperatively, at 2 weeks after the surgery and at matched 20% total body weight loss. Clinical follow-up continued up to 1 year. Main outcome measures Primary – postprandial peak of active glucagon-like peptide 1 concentration at 2 weeks after intervention. Secondary – fasting and postprandial glucose and insulin concentrations, insulin sensitivity, glycaemic control and weight loss at 12 months after surgery, and safety of participants. Results Of the 53 participants randomised, 48 completed the trial. There were statistically significant decreases in fasting and postprandial glucose concentrations, increases in insulin, glucagon-like peptide 1 secretion and insulin sensitivity, and reductions in the levels of glycated haemoglobin (i.e. HbA1c) and weight in both long and standard limb groups. However, there were no significant differences between trial groups in any of these parameters. Limitations The main limitations of this trial include the relatively short follow-up of 12 months and elongation of the biliopancreatic limb to a fixed length of 150 cm. Conclusion Patients undergoing both types of Roux-en-Y gastric bypass benefited metabolically from the surgery. The results have not demonstrated that elongation of the biliopancreatic limb of the Roux-en-Y gastric bypass from 50 to 150 cm results in superior metabolic outcomes in terms of glucose excursions, insulin and incretin hormone secretion, and insulin sensitivity, when assessed at up to 12 months after surgery. Future work Continued longitudinal follow-up of the long and standard limb cohorts will be necessary to evaluate any differential effects of the two surgical procedures on patients’ metabolic trajectories. Trial registration Current Controlled Trials ISRCTN15283219. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 3. See the NIHR Journals Library website for further project information. The section in the report on endocrinology and investigative medicine is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award and a FP7-HEALTH-2009-241592 EuroCHIP grant. This section is also supported by the NIHR Biomedical Research Centre Funding Scheme.

Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance

Hyperuricemia is an independent risk factor for the metabolic syndrome and cardiovascular disease. We hypothesized that asymptomatic carriers for hereditary fructose intolerance (OMIM 22960) would have increased uric acid and altered component of the metabolic syndrome when exposed to fructose overfeeding. Six heterozygotes for HFI (hHFI) and 6 controls (Ctrl) were studied in a randomized, controlled, crossover trial. Participants ingested two identical test meals containing 0.7gkg-1 glucose and 0.7gkg-1 fructose according to a cross-over design, once after a 7-day on a low fructose diet (LoFruD, <10g/d) and on another occasion after 7 days on a high fructose diet (HiFruD, 1.4gkg-1day-1 fructose+0.1gkg-1day-1 glucose). Uric acid, glucose, and insulin concentrations were monitored in fasting conditions and over 2h postprandial, and insulin resistance indexes were calculated. HiFruD increased fasting uric acid (p<0.05) and reduced fasting insulin sensitivity estimated by the homeostasis model assessment (HOMA) for insulin resistance (p<0.05), in both groups. Postprandial glucose concentrations were not different between hHFI and Ctrl. However HiFruD increased postprandial plasma uric acid, insulin and hepatic insulin resistance index (HIRI) in hHFI only (all p<0.05). Seven days of HiFruD increased fasting uric acid and slightly reduced fasting HOMA index in both groups. In contrast, HiFruD increased postprandial uric acid, insulin concentration and HIRI in hHFI only, suggesting that heterozygosity for pathogenic Aldolase B variants may confer an increased susceptibility to the effects of dietary fructose on uric acid and hepatic insulin sensitivity. This trial was registered at the U.S. Clinical Trials Registry as NCT03545581.

Metabolic, hormonal and performance effects of isomaltulose ingestion before prolonged aerobic exercise: a double-blind, randomised, cross-over trial

BackgroundIsomaltulose has been discussed as a low glycaemic carbohydrate but evidence concerning performance benefits and physiological responses has produced varying results. Therefore, we primarily aimed to investigate the effects of isomaltulose ingestion compared to glucose and maltodextrin on fat and carbohydrate oxidation rates, blood glucose levels and serum hormone concentrations of insulin and glucose-dependent insulinotropic polypeptide (GIP). As secondary aims, we assessed running performance and gastrointestinal discomfort.MethodsTwenty-one male recreational endurance runners performed a 70-min constant load trial at 70% maximal running speed (Vmax), followed by a time to exhaustion (TTE) test at 85% Vmax after ingesting either 50 g isomaltulose, maltodextrin or glucose. Fat and carbohydrate oxidation rates were calculated from spiroergometric data. Venous blood samples for measurement of GIP and insulin were drawn before, after the constant load trial and after the TTE. Capillary blood samples for glucose concentrations and subjective feeling of gastrointestinal discomfort were collected every 10 min during the constant load trial.ResultsNo between-condition differences were observed in the area under the curve analysis of fat (p = 0.576) and carbohydrate oxidation rates (p = 0.887). Isomaltulose ingestion led to lower baseline postprandial concentrations of blood glucose compared to maltodextrin (percent change [95% confidence interval], − 16.7% [− 21.8,-11.6], p < 0.001) and glucose (− 11.5% [− 17.3,-5.7], p = 0.001). Similarly, insulin and GIP concentrations were also lower following isomaltulose ingestion compared to maltodextrin (− 40.3% [− 50.5,-30.0], p = 0.001 and − 69.1% [− 74.3,-63.8], p < 0.001, respectively) and glucose (− 32.6% [− 43.9,-21.2], p = 0.012 and − 55.8% [− 70.7,-40.9], p < 0.001, respectively). Furthermore, glucose fluctuation was lower after isomaltulose ingestion compared to maltodextrin (− 26.0% [− 34.2,-17.8], p < 0.001) and glucose (− 17.4% [− 29.1,-5.6], p < 0.001). However, during and after exercise, no between-condition differences for glucose (p = 0.872), insulin (p = 0.503) and GIP (p = 0.244) were observed. No between-condition differences were found for TTE (p = 0.876) or gastrointestinal discomfort (p = 0.119).ConclusionIsomaltulose ingestion led to lower baseline postprandial concentrations of glucose, insulin and GIP compared to maltodextrin and glucose. Consequently, blood glucose fluctuations were lower during treadmill running after isomaltulose ingestion, while no between-condition differences were observed for CHO and fat oxidation rates, treadmill running performance and gastrointestinal discomfort. Further research is required to provide specific guidelines on supplementing isomaltulose in performance and health settings.

Effect of cacao polyphenol-rich chocolate on postprandial glycemia, insulin, and incretin secretion in healthy participants

ObjectivesThere is substantial interest in using dark chocolate to prevent postprandial hyperglycemia. We investigated the effects of cacao polyphenol-rich chocolate on postprandial glycemic and insulinemic responses and whether cacao polyphenol-rich chocolate increases glucagon-like peptide-1 (GLP-1) secretion. MethodsIn a stratified, randomized, crossover study, 48 healthy participants ingested either water (W) or cacao polyphenol-rich chocolate plus water (C) 15 min before a 50 g oral glucose tolerance test (OGTT). Pre- and postprandial concentrations of blood glucose, insulin, free fatty acid, glucagon, and GLP-1 were evaluated. ResultsPeak plasma glucose concentrations did not differ significantly between groups W and C; however, plasma glucose concentrations at 120 min in group C were significantly lower than those in group W (P < .01). Postprandial serum insulin and plasma GLP-1 concentrations and incremental serum insulin and plasma GLP-1 area under the curve (AUC)–15–180 min for group C were significantly higher than those for group W (P < .05). When comparing the changes after the OGTT, the incremental plasma glucose AUC0–180 min for group C was significantly lower than that for group W (P < .05), but the incremental serum insulin and plasma GLP-1 AUC0–180 min did not differ significantly between groups W and C. ConclusionsThis study indicated that the intake of cacao polyphenol-rich chocolate before a 50 g OGTT could enhance early insulin and GLP-1 secretion in healthy participants, and illustrates the potential of cacao polyphenol-rich chocolate in managing postprandial glucose excursions.

Computational modelling of self-reported dietary carbohydrate intake on glucose concentrations in patients undergoing Roux-en-Y gastric bypass versus one-anastomosis gastric bypass

Objectives Our aim was to investigate in a real-life setting the use of machine learning for modelling the postprandial glucose concentrations in morbidly obese patients undergoing Roux-en-Y gastric bypass (RYGB) or one-anastomosis gastric bypass (OAGB). Methods As part of the prospective randomized open-label trial (RYSA), data from obese (BMI ≥35 kg/m2) non-diabetic adult participants were included. Glucose concentrations, measured with FreeStyle Libre, were recorded over 14 preoperative and 14 postoperative days. During these periods, 3-day food intake was self-reported. A machine learning model was applied to estimate glycaemic responses to the reported carbohydrate intakes before and after the bariatric surgeries. Results Altogether, 10 participants underwent RYGB and 7 participants OAGB surgeries. The glucose concentrations and carbohydrate intakes were reduced postoperatively in both groups. The relative time spent in hypoglycaemia increased regardless of the operation (RYGB, from 9.2 to 28.2%; OAGB, from 1.8 to 37.7%). Postoperatively, we observed an increase in the height of the fitted response curve and a reduction in its width, suggesting that the same amount of carbohydrates caused a larger increase in the postprandial glucose response and that the clearance of the meal-derived blood glucose was faster, with no clinically meaningful differences between the surgeries. Conclusions A detailed analysis of the glycaemic responses using food diaries has previously been difficult because of the noisy meal data. The utilized machine learning model resolved this by modelling the uncertainty in meal times. Such an approach is likely also applicable in other applications involving dietary data. A marked reduction in overall glycaemia, increase in postprandial glucose response, and rapid glucose clearance from the circulation immediately after surgery are evident after both RYGB and OAGB. Whether nondiabetic individuals would benefit from monitoring the post-surgery hypoglycaemias and the potential to prevent them by dietary means should be investigated. KEY MESSAGES The use of a novel machine learning model was applicable for combining patient-reported data and time-series data in this clinical study. Marked increase in postprandial glucose concentrations and rapid glucose clearance were observed after both Roux-en-Y gastric bypass and one-anastomosis gastric bypass surgeries. Whether nondiabetic individuals would benefit from monitoring the post-surgery hypoglycaemias and the potential to prevent them by dietary means should be investigated.

Effects of Concord grape juice flavor intensity and phenolic compound content on glycemia, appetite and cognitive function in adults with excess body weight: a randomized double-blind crossover trial.

Background & aims: Concord grape (Vitis lambrusca) juice (CGJ) contains a unique combination of polyphenolic compounds with diverse effects on human health. It also has an intense sensory profile that may modify food choice. Daily consumption of CGJ over 8 weeks reduced fasting blood glucose. However, the impact on 24h-postprandial glucose response from CGJ is still not clear. The purpose of this study was to assess the effect of CGJ flavor intensity and phenolic content on 24 h postprandial glucose concentrations, appetitive sensations, and cognitive function in adults with excess body weight when consumed alone or with a meal. Methods: In a randomized, double-blind, crossover design study, participants consumed three types of beverages: 100% CGJ, a polyphenol-free grape flavored drink with the same flavor essence (LP) or a polyphenol-free grape flavored drink with reduced flavor essence (LPF) either without (trial I) or with (trial II) a meal. 24 h glucose was measured through continuous glucose monitoring. Phenolic metabolite excretion was assessed in 24 h urine samples. Appetite (hunger, thirst, fullness, desire to eat, and prospective consumption) and cognitive function (alertness, energetic, strength, calmness, and relaxation) were assessed hourly through visual analog scales. Results: Thirty-four adults completed trial I and 34 adults completed trial II. When consumed with a meal, beverages with customary flavor essence (CGJ and LP) reduced hunger, desire to eat, and prospective consumption and consumption of the polyphenol-free reduced flavor essence beverage was associated with higher 24 h glucose tAUC. No consistent effects were observed for cognitive outcomes. When consumed alone, CGJ was related to lower glycemic responses by those excreting a higher concentration of the phenolic metabolite iso/ferulic-3'-O-glucuronide, but in beverages without CG phenolics and reduced flavor essence, glycemia was higher among those excreting higher concentrations of caffeic acid-O-sulfate. Conclusions: Both natural phenolics and flavor essence of CGJ may help to moderate appetite and glycemia. Clinical Trials registered at http://www.clinicaltrials.gov: NCT03409484 (trial I) and NCT03409497 (trial II).

Incretin Hormones and Type 2 Diabetes-Mechanistic Insights and Therapeutic Approaches.

Simple SummaryWhen we ingest a meal, our intestine secretes hormones that are released into the bloodstream. Amongst these hormones are the incretins hormones which stimulate the release of insulin from the pancreas which is essential for the regulation of in particular postprandial glucose concentrations. In patients with type 2 diabetes, the effect of the incretins is diminished. This is thought to contribute importantly to the pathophysiology of the disease. However, in pharmacological amounts, the incretins may still influence insulin secretion and metabolism. Much research has therefore been devoted to the development of incretin-based therapies for type 2 diabetes. These therapies include compounds that strongly resemble the incretins, hereby stimulating their effects as well as inhibitors of the enzymatic degradation of the hormones, thereby increasing the concentration of incretins in the blood. Both therapeutic approaches have been implemented successfully, but research is still ongoing aimed at the development of further optimized therapies. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the gut upon nutrient stimulation and regulate postprandial metabolism. These hormones are known as classical incretin hormones and are responsible for a major part of postprandial insulin release. The incretin effect is severely reduced in patients with type 2 diabetes, but it was discovered that administration of GLP-1 agonists was capable of normalizing glucose control in these patients. Over the last decades, much research has been focused on the development of incretin-based therapies for type 2 diabetes. These therapies include incretin receptor agonists and inhibitors of the incretin-degrading enzyme dipeptidyl peptidase-4. Especially the development of diverse GLP-1 receptor agonists has shown immense success, whereas studies of GIP monotherapy in patients with type 2 diabetes have consistently been disappointing. Interestingly, both GIP-GLP-1 co-agonists and GIP receptor antagonists administered in combination with GLP-1R agonists appear to be efficient with respect to both weight loss and control of diabetes, although the molecular mechanisms behind these effects remain unknown. This review describes our current knowledge of the two incretin hormones and the development of incretin-based therapies for treatment of type 2 diabetes.

Commercial Vinegar Tablets Do Not Display the Same Physiological Benefits for Managing Postprandial Glucose Concentrations as Liquid Vinegar

Objective Research evidence suggests that vinegar may effectively reduce postprandial glucose in both healthy adults and those with type 2 diabetes. There is heightened consumer interest in commercially available vinegar tablets; however, it is not known whether these products lower postprandial glycemia to the same extent as liquid vinegar. This crossover trial examined the impact of liquid vinegar versus commercial vinegar tablet ingestion at the start of a meal on the 60-minute glucose excursion postmeal in healthy adults. Methods Twelve young men and women (22.6 ± 0.6 y; 21.2 ± 1.2 kg/m2) completed this 4-arm Latin square crossover trial. Testing was separated by one week and consisted of a test meal (64 g carbohydrate) consumed immediately following one of the four oral treatments: CON, 60 g water (control treatment); VIN, 25 g liquid vinegar (5% acidity; 1.25 g acetic acid) diluted with 35 g water; PILL, four vinegar tablets (1.50 g acetic acid) swallowed whole with 60 g water; and PILL-c, four crushed vinegar tablets dissolved in 60 g water. Capillary blood glucose was tested in the fasted state and at 30 and 60 minutes postmeal. Results The 60-minute glucose excursion varied significantly by treatment (iAUC: 4.9 ± 0.6, 3.4 ± 0.4, 4.9 ± 0.6, and 4.1 ± 0.5 mmol˖h/l for CON, VIN, PILL, and PILL-c, respectively; F (3, 33) = 3.037, p = 0.043; repeated measures ANOVA). Post hoc analysis revealed a 31% reduction in the glucose postmeal excursion for VIN in comparison to CON and PILL (p = 0.040 and p = 0.049, respectively). Conclusions These data suggest that commercial vinegar tablets taken whole at mealtime are not as effective as liquid vinegar for reducing the postmeal glucose excursion in young, healthy adults.

Role of Fluid Milk in Attenuating Postprandial Hyperglycemia and Hypertriglyceridemia.

Postprandial plasma glucose and triglyceride concentrations are predictive of relative cardiovascular disease (CVD) risk, and the pathogenesis of both insulin resistance and atherosclerosis has been attributed to acute states of hyperglycemia and hypertriglyceridemia. Postprandial lipemia and hyperglycemia suppress vascular reactivity and induce endothelial dysfunction. Epidemiological studies suggest that chronically-high consumption of milk and milk products is associated with a reduced risk of type 2 diabetes, metabolic syndrome, and CVD. The addition of dairy products to meals high in carbohydrates and fat may lessen these risks through reductions in postprandial glucose and triglyceride responses. Purported mechanisms include dairy proteins and bioactive compounds, which may explain the inverse relationship between dairy consumption and cardiometabolic diseases. The current review evaluates the available literature describing the relationships between metabolic dysfunction, postprandial metabolism, and vascular dysfunction and discusses the potential role of milk and dairy products in attenuating these impairments.