Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion.
ABSTRACT: Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281).
Project description:BACKGROUND:The previous meal modulates the postprandial glycemic responses to a subsequent meal; this is termed the second-meal phenomenon. OBJECTIVE:This study examined the effects of high-protein vs. high-carbohydrate breakfast meals on the metabolic and incretin responses after the breakfast and lunch meals. METHODS:Twelve type 2 diabetic men and women [age: 21-55 y; body mass index (BMI): 30-40 kg/m(2)] completed two 7-d breakfast conditions consisting of 500-kcal breakfast meals as protein (35% protein/45% carbohydrate) or carbohydrate (15% protein/65% carbohydrate). On day 7, subjects completed an 8-h testing day. After an overnight fast, the subjects consumed their respective breakfast followed by a standard 500-kcal high-carbohydrate lunch meal 4 h later. Blood samples were taken throughout the day for assessment of 4-h postbreakfast and 4-h postlunch total area under the curve (AUC) for glucose, insulin, C-peptide, glucagon, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide 1 (GLP-1). RESULTS:Postbreakfast glucose and GIP AUCs were lower after the protein (17%) vs. after the carbohydrate (23%) condition (P < 0.05), whereas postbreakfast insulin, C-peptide, glucagon, and GLP-1 AUCs were not different between conditions. A protein-rich breakfast may reduce the consequences of hyperglycemia in this population. Postlunch insulin, C-peptide, and GIP AUCs were greater after the protein condition vs. after the carbohydrate condition (second-meal phenomenon; all, P < 0.05), but postlunch AUCs were not different between conditions. The overall glucose, glucagon, and GLP-1 responses (e.g., 8 h) were greater after the protein condition vs. after the carbohydrate condition (all, P < 0.05). CONCLUSIONS:In type 2 diabetic individuals, compared with a high-carbohydrate breakfast, the consumption of a high-protein breakfast meal attenuates the postprandial glucose response and does not magnify the response to the second meal. Insulin, C-peptide, and GIP concentrations demonstrate the second-meal phenomenon and most likely aid in keeping the glucose concentrations controlled in response to the subsequent meal. The trial was registered at www.clinicaltrials.gov/ct2/show/NCT02180646 as NCT02180646.
Project description:Glucose-dependent insulinotropic polypeptide (GIP), unlike glucagon-like peptide (GLP)-1, lacks glucose-lowering properties in patients with type 2 diabetes. We designed this study to elucidate the underlying pathophysiology.Twenty-two insulin-naïve subjects with type 2 diabetes were given either synthetic human GIP (20 ng x kg(-1) x min(-1)) or placebo (normal saline) over 180 min, starting with the first bite of a mixed meal (plus 1 g of acetaminophen) on two separate occasions. Frequent blood samples were obtained over 6 h to determine plasma GIP, GLP-1, glucose, insulin, glucagon, resistin, and acetaminophen levels.Compared with placebo, GIP induced an early postprandial increase in insulin levels. Intriguingly, GIP also induced an early postprandial augmentation in glucagon, a significant elevation in late postprandial glucose, and a decrease in late postprandial GLP-1 levels. Resistin and acetaminophen levels were comparable in both interventions. By immunocytochemistry, GIP receptors were present on human and mouse alpha-cells. In alphaTC1 cell line, GIP induced an increase in intracellular cAMP and glucagon secretion. CONCLUSIONS; GIP, given to achieve supraphysiological plasma levels, still had an early, short-lived insulinotropic effect in type 2 diabetes. However, with a concomitant increase in glucagon, the glucose-lowering effect was lost. GIP infusion further worsened hyperglycemia postprandially, most likely through its suppressive effect on GLP-1. These findings make it unlikely that GIP or GIP receptor agonists will be useful in treating the hyperglycemia of patients with type 2 diabetes.
Project description:People with repeated rapid meal ingestion have been reported to have increased risk of insulin resistance, impaired glucose tolerance and obesity. To explore whether speed of eating a breakfast influences the postprandial rise of glucose, insulin and the incretin hormones, 24 healthy subjects (12 men and 12 women, mean age 62 years) ingested a standardized solid breakfast consisting of 524 kcal (60% from carbohydrate, 20% from protein, 20% from fat) over 5 or 12 minutes on separate days in random order. Breakfast ingestion increased circulating glucose and insulin with maximal levels seen at 30 minutes after start of meal ingestion with no significant difference in the two tests. Similarly, breakfast increased circulating levels of total (reflecting secretion) glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) with, again, no difference between the tests. Furthermore, gastric emptying, as revealed by the indirect paracetamol test, did not differ between the tests. We therefore conclude that the speed of breakfast ingestion does not affect the postprandial rise of glucose, insulin or incretin hormones in healthy subjects.
Project description:INTRODUCTION:To investigate canagliflozin-induced changes in postprandial total glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels in patients with type 2 diabetes mellitus (T2DM). METHODS:Forty-five patients with T2DM who had inadequate glycemic control (glycated hemoglobin???6.5%) with diet and exercise alone (n?=?15, drug naïve) and in combination with either a stable dose of the ?-glucosidase inhibitor acarbose (n?=?15) or metformin (n?=?15) received canagliflozin, a sodium-glucose cotransporter 2 inhibitor, at 100 mg once daily for 12 weeks. The primary endpoint was the change from baseline to week 12 in postprandial glucose and plasma levels of total GLP-1 and GIP during a meal tolerance test (MTT). RESULTS:Canagliflozin significantly reduced postprandial blood glucose (mean difference -?40.2 mg/mL at 60 min) and increased postprandial total GLP-1 (mean difference 1.8 pg/mL at 60 min) during an MTT. A transient reduction in the postprandial GIP level at only 30 min (mean difference -?80.3 pg/mL) during an MTT was observed. No changes in postprandial GLP-1 or GIP levels were seen after canagliflozin treatment as an add-on to acarbose in patients with T2DM. Acarbose treatment significantly decreased postprandial total GIP levels (P?<?0.05) and tended to increase postprandial total GLP-1 levels (P?=?0.07) compared to the other two treatments prior to canagliflozin. CONCLUSION:Canagliflozin 100 mg increased postprandial total GLP-1 levels in the absence of acarbose, suggesting that it may upregulate GLP-1 secretion through delayed glucose absorption in the upper intestine, as with the ?-glucosidase inhibitor. TRIAL REGISTRATION:University Hospital Medical Information Network, UMIN000018345. FUNDING:Mitsubishi Tanabe Pharma Corporation.
Project description:Postprandial hyperglycemia interferes with vascular reactivity and is a strong predictor of cardiovascular disease. Macronutrient preloads reduce postprandial hyperglycemia in subjects with impaired glucose tolerance (IGT) or type 2 diabetes (T2D), but the effect on endothelial function is unknown. Therefore, we examined whether a protein/lipid preload can attenuate postprandial endothelial dysfunction by lowering plasma glucose responses in subjects with IGT/T2D. Endothelial function was assessed by the reactive hyperemia index (RHI) at fasting, 60 min and 120 min during two 75 g oral glucose tolerance tests (OGTTs) preceded by either water or a macronutrient preload (i.e., egg and parmesan cheese) in 22 volunteers with IGT/T2D. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, free fatty acids, and amino acids were measured through each test. RHI negatively correlated with fasting plasma glucose. During the control OGTT, RHI decreased by 9% and its deterioration was associated with the rise in plasma glucose. The macronutrient preload attenuated the decline in RHI and markedly reduced postprandial glycemia. The beneficial effect of the macronutrient preload on RHI was proportional to the improvement in glucose tolerance and was associated with the increase in plasma GLP-1 and arginine levels. In conclusion, a protein/lipid macronutrient preload attenuates glucose-induced endothelial dysfunction in individuals with IGT/T2D by lowering plasma glucose excursions and by increasing GLP-1 and arginine levels, which are known regulators of the nitric oxide vasodilator system.
Project description:Glucose and lipids stimulate the gut-hormones glucagon-like peptide (GLP)-1, GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) but the effect of these on human postprandial lipid metabolism is not fully clarified.To explore the responses of GLP-1, GLP-2 and GIP after a fat-rich meal compared to the same responses after an oral glucose tolerance test (OGTT) and to investigate possible relationships between incretin response and triglyceride-rich lipoprotein (TRL) response to a fat-rich meal.Glucose, insulin, GLP-1, GLP-2 and GIP were measured after an OGTT and after a fat-rich meal in 65 healthy obese (BMI 26.5-40.2 kg/m(2)) male subjects. Triglycerides (TG), apoB48 and apoB100 in TG-rich lipoproteins (chylomicrons, VLDL1 and VLDL2) were measured after the fat-rich meal.Postprandial responses (area under the curve, AUC) for glucose, insulin, GLP-1, GLP-2, GIP in plasma, and TG, apoB48 and apoB100 in plasma and TG-rich lipoproteins.The GLP-1, GLP-2 and GIP responses after the fat-rich meal and after the OGTT correlated strongly (r = 0.73, p<0.0001; r = 0.46, p<0.001 and r = 0.69, p<0.001, respectively). Glucose and insulin AUCs were lower, but the AUCs for GLP-1, GLP-2 and GIP were significantly higher after the fat-rich meal than after the OGTT. The peak value for all hormones appeared at 120 minutes after the fat-rich meal, compared to 30 minutes after the OGTT. After the fat-rich meal, the AUCs for GLP-1, GLP-2 and GIP correlated significantly with plasma TG- and apoB48 AUCs but the contribution was very modest.In obese males, GLP-1, GLP-2 and GIP responses to a fat-rich meal are greater than following an OGTT. However, the most important explanatory variable for postprandial TG excursion was fasting triglycerides. The contribution of endogenous GLP-1, GLP-2 and GIP to explaining the variance in postprandial TG excursion was minor.
Project description:<h4>Background</h4>Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states.<h4>Methods</h4>Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR).<h4>Results</h4>The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia.<h4>Conclusions</h4>Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to 30% compared to no such changes after three 60%-carbohydrate meals, an effect that was independent of pre-meal exercise. The parallel timing and magnitude of postprandial insulin and GIP changes suggest their dependence on a delayed intestinal adaptation to a low-carbohydrate diet. Pre-meal exercise exacerbated glucose intolerance with both diets most likely due to impairment of insulin signaling by pre-meal elevation of FFAs.
Project description:BACKGROUND:Appetite and gastrointestinal hormones (GIHs) participate in energy homeostasis, feeding behavior and regulation of body weight. We demonstrated previously the superior effect of a hypocaloric diet regimen with lower meal frequency (B2) on body weight, hepatic fat content, insulin sensitivity and feelings of hunger compared to the same diet divided into six smaller meals a day (A6). Studies with isoenergetic diet regimens indicate that lower meal frequency should also have an effect on fasting and postprandial responses of GIHs. The aim of this secondary analysis was to explore the effect of two hypocaloric diet regimens on fasting levels of appetite and GIHs and on their postprandial responses after a standard meal. It was hypothesized that lower meal frequency in a reduced-energy regimen leading to greater body weight reduction and reduced hunger would be associated with decreased plasma concentrations of GIHs: gastric inhibitory peptide (GIP), glucagon-like peptide-1(GLP-1), peptide YY(PYY), pancreatic polypeptide (PP) and leptin and increased plasma concentration of ghrelin. The postprandial response of satiety hormones (GLP-1, PYY and PP) and postprandial suppression of ghrelin will be improved. METHODS:In a randomized crossover study, 54 patients suffering from type 2 diabetes (T2D) underwent both regimens. The concentrations of GLP-1, GIP, PP, PYY, amylin, leptin and ghrelin were determined using multiplex immunoanalyses. RESULTS:Fasting leptin and GIP decreased in response to both regimens with no difference between the treatments (p = 0.37 and p = 0.83, respectively). Fasting ghrelin decreased in A6 and increased in B2 (with difference between regimens p = 0.023). Fasting PP increased in B2with no significant difference between regimens (p = 0.17). Neither GLP-1 nor PYY did change in either regimen. The decrease in body weight correlated negatively with changes in fasting ghrelin (r = -0.4, p<0.043) and the postprandial reduction of ghrelin correlated positively with its fasting level (r = 0.9, p<0.001). The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. CONCLUSIONS:Both hypocaloric diet regimens reduced fasting leptin and GIP and postprandial response of GIP comparably. The postprandial responses of GIHs and appetite hormones were similar after both diet regimens. Eating only breakfast and lunch increased fasting plasma ghrelin more than the same caloric restriction split into six meals. The changes in fasting ghrelin correlated negatively with the decrease in body weight. These results suggest that for type 2 diabetic patients on a hypocaloric diet, eating larger breakfast and lunch may be more efficient than six smaller meals during the day.
Project description:Acute and sustained soluble dietary fibre (SDF) consumption are both associated with improved glucose tolerance in humans and animal models (e.g. porcine). However, the effects on glucose tolerance in grower pigs, adapted to diets with a combination of SDF have not been studied previously. In this experiment, cereal SDF wheat arabinoxylan (AX) and oat ?-glucan (BG) were fed individually and in combination to determine the effect on glucose tolerance in jugular vein catheterized grower pigs. Five groups of Large White male grower pigs were fed highly digestible diets containing either 10% AX, 10% BG, 5% AX with 5% BG, a model cereal whole wheat flour (WWF), or a control wheat starch diet (WS) with no SDF. Blood was collected via jugular vein catheters over 240 minutes following a feed challenge and an oral glucose tolerance test (OGTT) on two separate days. Postprandial blood samples were used to determine plasma glucose, insulin, non-esterified fatty acids (NEFA), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY), ghrelin, glucagon and cortisol concentrations. No dietary effects on glycaemic response were observed following the feed challenge or the OGTT as determined by the area under the curve (AUC). A biphasic glucose and insulin response was detected for all pigs following the OGTT. The current study showed male grower pigs have tight glycaemic control and glucose tolerance regardless of diet. In addition, pigs fed the combined SDF had a reduced GIP response and delayed insulin peak following the feed challenge. Incretin (GLP-1 and GIP) secretion appeared asynchronous reflecting their different enteroendocrine cell locations and response to nutrient absorption.
Project description:<h4>Introduction</h4>Both dipeptidyl peptidase-4 inhibitors and ?-glucosidase inhibitors (?-GI) have been reported to change the incretin and insulin secretion. To examine the effects of acarbose, miglitol, and sitagliptin on glucose metabolism and secretion of gut peptides, we conducted a crossover study in patients with type 2 diabetes mellitus (T2DM).<h4>Methods</h4>Eleven Japanese patients with T2DM underwent four meal tolerance tests with single administration of acarbose, miglitol, sitagliptin, or nothing. Fasting and postprandial plasma levels of glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), ghrelin, and des-acyl ghrelin were measured.<h4>Results</h4>Early-phase insulin secretion was reduced following acarbose and miglitol, and the areas under the curve (AUC) of insulin at 180 min following acarbose and miglitol were significantly lower than sitagliptin. AUC of plasma glucose at 180 min after acarbose, miglitol, and sitagliptin tended to be lower than in controls, and plasma glucose levels at 30-60 min following miglitol were significantly lower than in controls. Plasma glucagon, ghrelin, and des-acyl ghrelin levels did not differ among the four conditions. Postprandial plasma active GLP-1 levels and AUC of GLP-1 increased significantly in both the sitagliptin and miglitol groups compared to control. Postprandial plasma total GIP levels increased following sitagliptin but decreased after acarbose and miglitol. Changes in incretin levels tended to be greater with miglitol than acarbose.<h4>Conclusion</h4>These results showed that sitagliptin and ?-GIs, miglitol more so than acarbose, improved hyperglycemia in patients with T2DM after single administration, and had different effects on insulin and incretin secretion.<h4>Trial registration</h4>UMIN-CTR number, UMIN000009981.