Ingestion Of Mixed Meal Research Articles

Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study

South Asians (SAs) develop type 2 diabetes at lower body mass index values than white Europeans (WEs). This basic human experimental study aimed to compare the metabolic consequences of weight gain in SA and WE men without overweight or obesity. Fourteen SAs and 21 WEs had assessments of body composition, metabolic responses to mixed-meal ingestion, cardiorespiratory fitness and physical activity, and a subcutaneous abdominal adipose tissue biopsy, before and after 4–6 weeks of overfeeding to induce 5–7% weight gain. Here we show that body mass index and whole-body adipose tissue volume increases similarly between ethnic groups, but SAs gain less lean tissue. SAs experience a substantially greater decrease in insulin sensitivity compared with WEs (38% versus 7% decrease, P = 0.009), have fewer small (37.1% versus 60.0%, P = 0.003) and more large (26.2% versus 9.1%, P = 0.005) adipocytes at baseline and have a smaller decrease in very small adipocytes with weight gain (−0.1% versus −1.9%, P < 0.0001). Ethnic differences in adipocyte morphology are associated with SA’s greater adverse metabolic changes with weight gain. ClinicalTrials.gov registration: NCT02399423.

Differential effect of endogenous glucagon-like peptide-1 on prandial glucose counterregulatory response to hypoglycaemia in humans with and without bariatric surgery.

To determine the effect of endogenous glucagon-like peptide 1 (GLP-1) on prandial counterregulatory response to hypoglycaemia after gastric bypass (GB). Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion, were compared during a hyperinsulinaemic-hypoglycaemic (~3.2 mmol/L) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) infusion in non-diabetic patients who had previously undergone GB compared to matched participants who had previously undergone sleeve gastrectomy (SG) and non-surgical controls. Exendin-(9-39) infusion raised prandial endogenous glucose production (EGP) response to insulin-induced hypoglycaemia in the GB group but had no consistent effect on EGP response among the SG group or non-surgical controls (p < 0.05 for interaction). The rates of systemic appearance of ingested glucose or prandial glucose utilization did not differ among the three groups or between studies with and without exendin-(9-39) infusion. Blockade of GLP-1R had no effect on insulin secretion or insulin action but enhanced prandial glucagon in all three groups. These results indicate that impaired post-meal glucose counterregulatory response to hypoglycaemia after GB is partly mediated by endogenous GLP-1, highlighting a novel pathogenic mechanism of GLP-1 in developing hypoglycaemia in this population.

Relationships among Postprandial Plasma Active GLP-1 and GIP Excursions, Skeletal Muscle Mass, and Body Fat Mass in Patients with Type 2 Diabetes Treated with Either Miglitol, Sitagliptin, or Their Combination: A Secondary Analysis of the MASTER Study.

We previously conducted a pilot randomized controlled trial "the MASTER study" and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear. We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients. SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated. Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass.

Muscle fiber type-specific autophagy responses following an overnight fast and mixed meal ingestion in human skeletal muscle

The aim of the present study was to investigate the fiber type-specific abundance of autophagy-related proteins after an overnight fast and following ingestion of a mixed meal in human skeletal muscle. Twelve overweight, healthy young male volunteers underwent a 3-h mixed meal tolerance test following an overnight fast. Blood samples were collected in the overnight-fasted state and throughout the 180-min postmeal period. Skeletal muscle biopsies were collected in the fasted state, and at 30 and 90 min after meal ingestion. Protein content of key autophagy markers and upstream signaling responses were measured in whole muscle and pooled single fibers using immunoblotting. In the fasted state, type I fibers displayed lower LC3B-I but higher LC3B-II abundance and higher LC3B-II/LC3B-I ratio compared with type II fibers (P < 0.05). However, there were no fiber type differences in p62/SQSTM1, unc-51 like autophagy activating kinase (ULK1), ATG5, or ATG12 (P > 0.05). Compared with the fasted state, there was a reduction in LC3B-II abundance, indicative of lower autophagosome content, in whole muscle and in both type I and type II fibers following meal ingestion (P < 0.05). This reduction in autophagosome content occurred alongside similar increases in p-AktS473 and p-mTORS2448 in both type I and type II muscle fibers (P < 0.05). In human skeletal muscle, type I fibers have a greater autophagosome content than type II fibers in the overnight-fasted state despite comparable abundance of other key upstream autophagy proteins. Autophagy is rapidly inhibited in both fiber types following the ingestion of a mixed meal.NEW & NOTEWORTHY This study examined the fiber type-specific content of key autophagy proteins in human muscle. We showed that markers of autophagosome content are higher in type I fibers in the overnight-fasted state, whereas autophagy is rapidly inhibited in both type I and type II fibers after the ingestion of a mixed meal.

Stimulated UCPCR Levels Are Lower in People With Type 1 Diabetes Than in Other Diabetes Types in Sub-Saharan Africa: Results From a Preliminary Cross-Sectional Study.

BackgroundThe clinical utility of Urinary C-Peptide to Creatinine Ratio (UCPCR) is well understood in people with different types of diabetes in Caucasian populations, but studies are lacking in African populations. We, therefore, aimed to examine Urinary C-Peptide to Creatinine Ratio levels among groups of people with different types of diabetes in a sub-Saharan African population.MethodsA total of 47 adults with diabetes; 10 with type 1 diabetes, 26 with type 2 diabetes, 11 with ketosis-prone diabetes, and 22 healthy control individuals, were recruited from Yaoundé Central Hospital in Cameroon. Fasting blood glucose and C-peptide were measured in venous blood and urine. Stimulated Urinary C-Peptide to Creatinine Ratio was determined in all subjects after ingestion of a standardized mixed meal. We compared the stimulated Urinary C-peptide to Creatinine Ration concentration in subjects with type 1 diabetes to the other groups.ResultsThe basal C-peptide and HOMA-β were lower in T1D than in the T2D group [median 57 (34, 69) vs. 398 (335, 502) pmol/l; p ≤ 0.001] and [median 3.0 (1.63, 5.25) vs. 30.6 (17.94, 45.03); p < 0.001] respectively. Also, basal C-peptide and HOMA-β were lower in T1D than in those with KPD [median 57 (34, 69) vs. 330 (265, 478) pmol/l; p = 0.003] and [median 3.0 (1.63, 5.25) vs. 47.1 (16.2, 63.1), p = 0.001] respectively. Basal C-peptide was not different between participants with T2D and KPD; 398 (335, 502) vs. 330 (265, 478) pmol/l, p = 0.19. Stimulated UCPCR was lower in T1D compared to T2D, KPD and control participants; [median 0.29 (0.14, 0.68) vs. 0.89 (0.40, 1.69) nmol/moll; p = 0.009], [median 0.29 (0.14, 0.68) vs. 1.33 (0.84, 1.59) nmol/mol; p = 0.006] and [median 0.29 (0.14, 0.68) vs. 1.21 (0.85, 1.21) nmol/mol; p = 0.005] respectively. However, stimulated UCPCR was similar between the T2D and KPD study participants; 0.89 (0.40, 1.69) vs. 1.33 (0.84, 1.59) nmol/mol, p = 0.36.ConclusionsStimulated Urinary C-Peptide to Creatinine Ratio (UCPCR) is lower in participants with type 1 diabetes compared to those with other types of diabetes in this population. This means stimulated UCPCR could potentially differentiate type 1 diabetes from other diabetes types among people with diabetes in sub-Saharan Africa.

Prandial hepatic glucose production during hypoglycemia is altered after gastric bypass surgery and sleeve gastrectomy

Aims/hypothesisRoux-en Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) alter prandial glucose metabolism, producing lower nadir glucose values and predisposing susceptible individuals to prandial hypoglycemia. The glycemic phenotype of GB or SG is associated with prandial hyperinsulinemia and hyperglucagonemia along with an increased influx of ingested glucose. Following insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production (HGP). It is unclear whether prandial hyperglucagonemia after GB or SG changes HGP under hyperinsulinemic hypoglycemia conditions. This study examined the hypothesis that prandial glucose production is reduced after GB and SG during hypoglycemia. MethodsGlucose kinetics and islet-cell and gut hormone secretion during hyperinsulinemic (120 mU.m−2.min−1) hypoglycemic clamp (~3.2 mM) were measured before and after mixed meal ingestion in 9 non-diabetic subjects with GB, 7 with SG, and 5 matched non-operated controls (CN). ResultsSystemic appearance of ingested glucose was faster in GB compared to SG, and in SG compared to CN (p < 0.05). Subjects with GB and SG had greater plasma glucagon levels after eating (AUCGlucagon) compared to CN (p < 0.05). But prandial HGP response during insulin-induced hypoglycemia (AUCHGP) was smaller and shorter in duration in surgical groups (p < 0.05). In the absence of meal stimuli, however, glucose counterregulatory response to hypoglycemia was comparable among the 3 groups during hyperinsulinemic clamp. ConclusionAfter bariatric surgery, prandial glucose counterregulatory response to hypoglycemia is impaired. Considering post-meal hyperglucagonemia after GB or SG the blunted HGP response suggests a lower sensitivity of liver to glucagon that can predispose to hypoglycemia in this population.

Ghrelin, glucagon-like peptide-1, and peptide YY secretion in patients with and without weight regain during long-term follow-up after bariatric surgery: a cross-sectional study.

IntroductionWeight loss after bariatric surgery is attributed, at least in part, to the altered gastrointestinal (GI) hormone secretion, which is thought to be responsible for a number of beneficial metabolic effects.Material and methodsWe conducted a cross-sectional study. Twelve patients who underwent laparoscopic sleeve gastrectomy (SG) and 20 patients who underwent a variant of biliopancreatic diversion with Roux-en-Y gastric bypass and long limbs (BPD/RYGB-LL) were evaluated ≥ 7 years postoperatively. Ghrelin, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) secretion were compared between patients with successful weight loss maintenance (WM group) and patients with weight regain (WR group).ResultsIn both types of surgery, standard liquid mixed meal (SLMM) ingestion did not result in significant changes in fasting GI hormone levels. Fasting ghrelin levels did not differ between the WM group and the WR group in both types of surgery. In SG patients, SLMM ingestion elicited greater suppression of ghrelin levels in the WM group (p = 0.032). No difference in GLP-1 secretion was observed between the 2 groups of patients in both types of surgery. When patients were examined, regardless of the type of bariatric surgery they had undergone, postprandial PYY levels were lower in the WM group (p < 0.05), while fasting and postprandial PYY levels were correlated positively with an increase in body mass index (BMI) in the evaluation (Spearman’s rho ≥ 0.395, p < 0.03).ConclusionsOur data do not support the hypothesis that long-term weight regain after bariatric surgery is associated with an unfavourable GI hormone secretion pattern.

The Change in Glucagon Following Meal Ingestion Is Associated with Glycemic Control, but Not with Incretin, in People with Diabetes.

Background: We aimed to investigate the changes in glucagon levels in people with diabetes after the ingestion of a mixed meal and the correlations of variation in glucagon levels with incretin and clinico-biochemical characteristics. Methods: Glucose, C-peptide, glucagon, intact glucagon-like peptide 1 (iGLP-1), and intact glucose-dependent insulinotropic polypeptide (iGIP) were measured in blood samples collected from 317 people with diabetes before and 30 min after the ingestion of a standard mixed meal. The delta (Δ) is the 30-min value minus the basal value. Results: At 30 min after meal ingestion, the glucagon level showed no difference relative to the basal value, whereas glucose, C-peptide, iGLP-1, and iGIP levels showed a significant increase. In univariate analysis, Δglucagon showed not only a strong correlation with HbA1c but also a significant correlation with fasting glucose, Δglucose, and estimated glomerular filtration rate. However, Δglucagon showed no significant correlations with ΔiGLP-1 and ΔiGIP. In the hierarchical multiple regression analysis, HbA1c was the only variable that continued to show the most significant correlation with Δglucagon. Conclusions: People with diabetes showed no suppression of glucagon secretion after meal ingestion. Patients with poorer glycemic control may show greater increase in postprandial glucagon level, and this does not appear to be mediated by incretin.

Acute hyperglycaemia enhances both vascular endothelial function and cardiac and skeletal muscle microvascular function in healthy humans.

Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may themselves alter vascular function. No prior studies have examined the effect of acute hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations. Macrovascular and microvascular functional responses to euglycaemia and hyperglycaemia were compared. Octreotide was infused throughout both protocols to prevent endogenous insulin release. Acute hyperglycaemia (induced by intravenous glucose) enhanced brachial artery flow-mediated dilatation, increased skeletal muscle microvascular blood volume and flow, and expanded cardiac muscle microvascular blood volume. Compared to other published findings, the results suggest that vascular responses to acute hyperglycaemia differ based on the study population (i.e. normal weight vs. overweight/obese) and/or glucose delivery method (i.e. intravenous vs. oral glucose). High glucose concentrations acutely provoke endothelial cell oxidative stress and are suggested to trigger diabetes-related macro- and microvascular injury in humans. Multiple clinical studies report that acute hyperglycaemia (induced by mixed meal or oral glucose) decreases arterial vascular function in healthy humans. Feeding, however, impacts autonomic output, blood pressure, and insulin and incretin secretion, which may each independently alter vascular function and obscure the effect of acute hyperglycaemia per se. Surprisingly, no studies have examined the acute effects of intravenous glucose-induced hyperglycaemia on both macro- and microvascular function while controlling plasma insulin concentrations. In this randomized study of healthy young adults, we compared macrovascular (i.e. brachial artery flow-mediated dilatation, carotid-femoral pulse wave velocity and post-ischaemic brachial artery flow velocity) and microvascular (heart and skeletal muscle perfusion by contrast-enhanced ultrasound) functional responses to euglycaemia and hyperglycaemia. Octreotide was infused throughout both protocols to prevent endogenous insulin release. Acute intravenous glucose-induced hyperglycaemia enhanced brachial artery flow-mediated dilatation (P=0.004), increased skeletal muscle microvascular blood volume and flow (P=0.001), and expanded cardiac muscle microvascular blood volume (P=0.014). No measure of vascular function changed during octreotide-maintained euglycaemia. Our findings suggest that unlike meal-provoked acute hyperglycaemia, 4h of intravenous glucose-induced hyperglycaemia enhances brachial artery flow-mediated dilatation, provokes cardiac and skeletal muscle microvascular function, and does not impair aortic stiffness. Previous findings of acute large artery vascular dysfunction during oral glucose or mixed meal ingestion may be due to differences in study populations and meal-induced humoral or neural factors beyond hyperglycaemia per se. (ClinicalTrials.gov number NCT03520569.).

Impact of glucagon response on early postprandial glucose excursions irrespective of residual β-cell function in type 1 diabetes: A cross-sectional study using a mixed meal tolerance test.

Aims/IntroductionControlling postprandial glucose levels in patients with type 1 diabetes is challenging even under the adequate treatment of insulin injection. Recent studies showed that dysregulated glucagon secretion exacerbates hyperglycemia in type 2 diabetes patients, but little is known in type 1 diabetes patients. We investigated whether the glucagon response to a meal ingestion could influence the postprandial glucose excursion in patients with type 1 diabetes.Materials and MethodsWe enrolled 34 patients with type 1 diabetes and 23 patients with type 2 diabetes as controls. All patients underwent a liquid mixed meal tolerance test. We measured levels of plasma glucose, C‐peptide and glucagon at fasting (0 min), and 30, 60 and 120 min after meal ingestion. All type 1 diabetes patients received their usual basal insulin and two‐thirds of the necessary dose of the premeal bolus insulin.ResultsThe levels of plasma glucagon were elevated and peaked 30 min after the mixed meal ingestion in both type 1 diabetes and type 2 diabetes patients. The glucagon increments from fasting to each time point (30, 60 and 120 min) in type 1 diabetes patients were comparable to those in type 2 diabetes patients. Among the type 1 diabetes patients, the glucagon response showed no differences between the subgroups based on diabetes duration (<5 vs ≥5 years) and fasting C‐peptide levels (<0.10 vs ≥0.10 nmol/L). The changes in plasma glucose from fasting to 30 min were positively correlated with those in glucagon, but not C‐peptide, irrespective of diabetes duration and fasting C‐peptide levels in patients with type 1 diabetes.ConclusionsThe dysregulated glucagon likely contributes to postprandial hyperglycemia independent of the residual β‐cell functions during the progression of type 1 diabetes.

Skeletal muscle anabolic and insulin sensitivity responses to a mixed meal in adult patients with active Crohn's disease.

We have previously shown reduced protein balance in response to nutrition in paediatric Crohn's disease (CD) in remission, associated with reduced lean mass (sarcopenia) and reduced protein intake in males. We aim to compare skeletal muscle metabolic response to feeding in adult active CD and healthy volunteers. Eight CD participants with active disease (41.3±4.5yrs; BMI 26.9±1.5kg/m2) and eight matched healthy volunteers (Con) (41.2±4.3yrs; BMI 25.1±1.1kg/m2) were recruited. Participants had a dual energy X-ray absorptiometry scan, handgrip dynamometer test, wore a pedometer and completed a food diary. Arterialized hand and venous forearm blood samples were collected concurrently and brachial artery blood flow measured at baseline and every 20mins for 2hrs after the ingestion of a standardized mixed liquid meal. Net balance of branched chain amino acids (BCAA), glucose and free fatty acids across the forearm were derived. No differences in muscle BCAA, glucose or FFA net balance were found between CD and Con. Neither were differences in muscle mass and function, physical activity or diet found. CD did not differ from Con in whole body insulin and lipid responses, or in energy expenditure and fuel oxidation. Skeletal muscle mass, function, dietary protein intake and response to a test meal in an adult CD cohort with active disease is similar to that seen in healthy volunteers. Combining these results with our previous findings in paediatric patients suggests that age of onset and/or disease burden over time, as well as daily protein intake, may be significant in the development of sarcopenia in CD. Longitudinal studies investigating these factors are required.

Muscle Protein Synthesis and Whole-Body Protein Turnover Responses to Ingesting Essential Amino Acids, Intact Protein, and Protein-Containing Mixed Meals with Considerations for Energy Deficit.

Protein intake recommendations to optimally stimulate muscle protein synthesis (MPS) are derived from dose-response studies examining the stimulatory effects of isolated intact proteins (e.g., whey, egg) on MPS in healthy individuals during energy balance. Those recommendations may not be adequate during periods of physiological stress, specifically the catabolic stress induced by energy deficit. Providing supplemental intact protein (20–25 g whey protein, 0.25–0.3 g protein/kg per meal) during strenuous military operations that elicit severe energy deficit does not stimulate MPS-associated anabolic signaling or attenuate lean mass loss. This occurs likely because a greater proportion of the dietary amino acids consumed are targeted for energy-yielding pathways, whole-body protein synthesis, and other whole-body essential amino acid (EAA)-requiring processes than the proportion targeted for MPS. Protein feeding formats that provide sufficient energy to offset whole-body energy and protein-requiring demands during energy deficit and leverage EAA content, digestion, and absorption kinetics may optimize MPS under these conditions. Understanding the effects of protein feeding format-driven alterations in EAA availability and subsequent changes in MPS and whole-body protein turnover is required to design feeding strategies that mitigate the catabolic effects of energy deficit. In this manuscript, we review the effects, advantages, disadvantages, and knowledge gaps pertaining to supplemental free-form EAA, intact protein, and protein-containing mixed meal ingestion on MPS. We discuss the fundamental role of whole-body protein balance and highlight the importance of comprehensively assessing whole-body and muscle protein kinetics when evaluating the anabolic potential of varying protein feeding formats during energy deficit.

The gut hormone secretin triggers a gut-brown fat-brain axis in the control of food intake.

What is the topic of this review? Brown fat's role in meal-associated thermogenesis and the related consequences for energy balance regulation with a focus on the gut hormone secretin, which has been identified as the endocrine molecular mediator of meal-associated brown fat thermogenesis. What advances does it highlight? The finding of the secretin-induced gut-brown fat-brain axis creates new opportunities to manipulate brown fat and thereby energy balance in a natural way while living in a thermoneutral environment. The role of brown fat as a mere catabolic heater organ needs to be revised and more attention should be directed towards the regulatory role of brown fat beyond energy expenditure. Brown fat research concentrates on the energy expenditure function of this heating organ, whereas previous evidence for a role of brown fat in regulating energy intake has been mostly neglected. Ingestion of a single mixed meal activates human brown fat thermogenesis to the same degree as cold. In mice, activation of brown fat thermogenesis with a β3 -adrenergic receptor agonist inhibits food intake. Pharmacological β-blockade, however, inhibits neither meal-associated thermogenesis nor food intake. We recently identified the gut hormone secretin as a non-adrenergic activator of brown fat. In vivo, secretin treatment acutely increases energy expenditure and inhibits food intake in wild-type, but not in uncoupling protein 1 (UCP1)-knockout (KO) mice, which lack thermogenic brown fat function. Concurrently, secretin alters gene expression of melanocortinergic peptides of hypothalamic neurons in wild-type mice, but not UCP1-KO. Blocking endogenous secretin with a neutralizing antibody attenuates brown fat thermogenesis during refeeding, increases food intake of mice, and alters ad libitum feeding behaviour. Taken together, these findings demonstrate that secretin triggers an endocrine gut-brown adipose tissue-brain axis in the control of satiation. We hypothesize that meal-associated activation of brown adipose tissue thermogenesis induced by secretin results in a rise in brain temperature and increased melanocortinergic signalling. Taken together, brown fat is not a mere heating organ dissipating excess calories but also involved in gut-brain communication in the control of food intake.

The Impact of Disuse and High-Fat Overfeeding on Forearm Muscle Amino Acid Metabolism in Humans.

Anabolic resistance is mechanistically implicated in muscle disuse atrophy. The objective of this study is to assess whether anabolic resistance is associated with reduced postprandial amino acid uptake or exacerbated by excess lipid availability. Twenty men underwent 7 days of forearm immobilization while consuming a eucaloric (CON; n = 11) or high-fat overfeeding (HFD; n = 9; 50% excess energy as fat) diet (parallel design) within our Nutritional Physiology Research Unit. Preimmobilization and postimmobilization we measured forearm muscle cross-sectional area (aCSA), and postabsorptive and postprandial (3-hour postingestion of a liquid, protein-rich, mixed meal) forearm amino acid metabolism using the arterialized venous-deep venous balance method and infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine. Immobilization did not affect forearm muscle aCSA in either group, but tended to reduce postabsorptive phenylalanine (P = .07) and leucine (P = .05) net balances equivalently in CON and HFD. Mixed-meal ingestion switched phenylalanine and leucine net balances from negative to positive (P < .05), an effect blunted by immobilization (P < .05) and to a greater extent in HFD than CON (P < .05). Preimmobilization, meal ingestion increased leucine rates of disappearance (Rd; P < .05), with values peaking at 191% (from 87 ± 38 to 254 ± 60 µmol·min-1·100 mL forearm volume-1) and 183% (from 141 ± 24 to 339 ± 51 µmol·min-1·100 mL-1) above postabsorptive rates in CON and HFD, respectively, with meal-induced increases not evident postimmobilization in either group (P > .05). Disuse impairs the ability of a protein-rich meal to promote positive muscle amino acid balance, which is aggravated by dietary lipid oversupply. Moreover, disuse reduced postprandial forearm amino acid uptake; however, this is not worsened under high-fat conditions.

Short-Communication: Ingestion of a Nucleotide-Rich Mixed Meal Increases Serum Uric Acid Concentrations but Does Not Affect Postprandial Blood Glucose or Serum Insulin Responses in Young Adults.

Circulating uric acid concentrations have been linked to various metabolic diseases. Consumption of large boluses of nucleotides increases serum uric acid concentrations. We investigated the effect of a nucleotide-rich mixed meal on postprandial circulating uric acid, glucose, and insulin responses. Ten healthy adults participated in a randomised, controlled, double-blind, crossover trial in which they consumed a mixed-meal containing either nucleotide-depleted mycoprotein (L-NU) or high-nucleotide mycoprotein (H-NU) on two separate visits. Blood samples were collected in the postabsorptive state and throughout a 24 h postprandial period, and were used to determine circulating uric acid, glucose, and insulin concentrations. Mixed meal ingestion had divergent effects on serum uric acid concentrations across conditions (time x condition interaction; P < 0.001), with L-NU decreasing transiently (from 45 to 240 min postprandially) by ~7% (from 279 ± 16 to 257 ± 14 µmol·L−1) and H-NU resulting in a ~12% increase (from 284 ± 13 to 319 ± 12 µmol·L−1 after 210 min), remaining elevated for 12 h and returning to baseline concentrations after 24 h. There were no differences between conditions in blood glucose or serum insulin responses, nor in indices of insulin sensitivity. The ingestion of a nucleotide-rich mixed-meal increases serum uric acid concentrations for ~12 h, but does not influence postprandial blood glucose or serum insulin concentrations.

Effects of a whole diet approach on metabolic flexibility, insulin sensitivity and postprandial glucose responses in overweight and obese adults - A randomized controlled trial.

Metabolic flexibility is the ability to adapt fuel oxidation to fuel availability. Metabolic inflexibility has been associated with obesity, the metabolic syndrome and insulin resistance, and can be improved by exercise or weight loss. Dietary changes can modulate metabolic flexibility; however, the effect of a whole diet approach on metabolic flexibility has never been studied. Therefore, our objective was to assess the effect of a healthy diet (HD), as compared to a typical Western diet (WD), on several fasting and postprandial markers of metabolic flexibility and insulin sensitivity. In this parallel randomized trial, overweight or obese men and women (50-70 years; BMI 25-35kg/m2) consumed a healthy diet (HD; high in fruits and vegetables, pulses, fibers, nuts, fatty fish, and low in high-glycemic carbohydrates; n=19) or a typical Western diet (WD; n=21) for six weeks, following a two-week run-in period. The change in respiratory quotient upon insulin stimulation (ΔRQ), and insulin sensitivity, expressed as the M-value, were both determined with a hyperinsulinemic euglycemic clamp. Additionally, other fasting and postprandial markers of metabolic flexibility were assessed during a 5-h high-fat high-glycemic mixed meal challenge. ΔRQ (p=0.730) and insulin sensitivity (p=0.802) were not significantly affected by diet. Postprandial RQ did also not show significant differences (p=0.610), whereas postprandial glucose excursions were significantly higher in the HD group at T30 (p=0.014) and T45 (p=0.026) after mixed meal ingestion (p=0.037). Fasting glucose (p=0.530) and HbA1c (p=0.124) remained unchanged, whereas decreases in fasting insulin (p=0.038) and the HOMA-IR (p=0.050) were significantly more pronounced with the HD. A healthy diet for six weeks, without further life-style changes, did not improve metabolic flexibility and whole-body insulin sensitivity, when compared to a Western-style diet. It remains to be determined whether the short time increase in postprandial glucose is physiologically relevant or detrimental to metabolic health. This trial was registered at clinicaltrials.gov as NCT02519127.

Associations Among Indices of Insulin Resistance and Vascular Reactivity in Older, Obese Adults

Insulin resistance (IR), estimated by calculating the homeostasis model assessment of IR (HOMA-IR), independently predicts incident cardiovascular disease (CVD) events. Further, HOMA-IR is inversely associated with brachial artery flow-mediated dilation (FMD) in non-diabetics, suggesting that IR may contribute to vascular dysfunction that increases CVD risk. PURPOSE: We sought to determine associations among indices of IR/glucose control and vascular reactivity in older, obese adults. We hypothesized that brachial artery FMD and hyperemic shear rate area under the curve (AUC) would be inversely associated with indices of IR/glucose control. METHODS: Preliminary data are from older, obese adults [n = 20 (16 women); age = 64.2 ± 4.8 y; BMI = 35.3 ± 5.3 kg/m2] participating in an ongoing clinical study. Brachial artery FMD and hyperemic shear rate AUC were assessed by a trained technician using high-resolution ultrasonography following an overnight fast. Additionally, fasting blood glucose (FBG) and serum insulin concentrations, HOMA-IR, hemoglobin (Hb)A1c, and postprandial blood glucose responses (i.e., 2 h AUC) to mixed meal ingestion (0.3 g protein/kg lean body mass + 0.5 g glucose/kg lean body mass) were measured to assess IR/glucose control. Partial correlations (controlling for age and sex) were used to examine associations among these variables. RESULTS: Participants were insulin resistant (HOMA-IR = 3.7 ± 2.2) but not diabetic (FBG = 99.5 ± 9.5 mg/dL, HbA1c = 5.5 ± 0.2%). Fasting brachial artery FMD (3.4 ± 1.6%) was not correlated (all P≥0.44) with FBG (r = -0.18) or serum insulin (14.2 ± 7.5 μIU/ml; r = -0.07), HOMA-IR (r = -0.13), HbA1c (r = -0.19), or 2 h blood glucose AUC (13,430 ± 2,298 mg/min/dL; r = -0.23). Hyperemic shear rate AUC was not correlated with indices of IR/glucose control (all P≥0.11). CONCLUSIONS: Preliminary data from our ongoing clinical study show that indices of IR/glucose control are not associated with vascular reactivity in older, obese adults. Continued recruitment of participants will more definitely determine the potential contribution of IR to vascular dysfunction and CVD risk. Supported by National Institute on Aging (1R15AG055923-01).

SUN-145 Factors Related to Blood Intact Incretin Levels in Patients with Type 2 Diabetes

We performed this study to identify factors related to intact incretin levels in patients with type 2 diabetes (T2D).We cross-sectionally analyzed 336 patients with T2D. Intact glucagon-like peptide 1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 min after ingestion of a standard mixed meal. The differences between 30 and 0 min iGLP-1 and iGIP levels were indicated as ΔiGLP-1 and ΔiGIP.After ingestion of a mixed meal, iGLP-1 (5.5±3.0 to 10.4±7.0 pmol/L; p<0.001) and iGIP (3.8±3.8 to 21.5±7.1 pmol/L; p<0.001) levels increased by 190% and 570%, respectively. In simple correlation analyses, fasting iGLP-1 was positively correlated with glucose (r=0.199; p<0.001), C-peptide (r=0.137; p<0.05), creatinine (r=0.124; p<0.05) and triglyceride (r=0.112; p<0.05) levels, and negatively correlated with eGFR (r=-0.139; p<0.05). ΔiGLP-1 was positively correlated only with ΔC-peptide levels (r=0.194; p<0.001). Fasting iGIP showed positive correlations with HbA1c (r=0.146; p<0.01), fasting glucose (r=0.126; p<0.05) and C-peptide (r=0.153; p<0.01) levels, and negative correlations with ΔC-peptide (r=-0.183; p<0.01) and HDL cholesterol (r=-0.124; p<0.05) levels. ΔiGIP was negatively correlated with diabetes duration (r=-0.118; p<0.05) and HbA1c (r=-0.196; p<0.001) levels, and positively correlated with ΔGlucose (r=0.210; p<0.001) and ΔC-peptide (r=0.238; p<0.01) levels. In multivariate analyses adjusting for age, sex, and covariates, fasting iGLP-1 levels were significantly related to fasting glucose (β=0.189, p<0.01) and creatinine (β=0.158, p<0.05) levels, ΔiGLP-1 levels were positively related to ΔC-peptide levels (β=0.194, p<0.001), fasting iGIP levels were related to fasting C-peptide levels (β=0.160, p<0.01) and female sex (β=0.124, p<0.05), and ΔiGIP levels were positively related to ΔC-peptide (β=0.165, p<0.01) and Δglucose (β=0.138, p<0.05) levels.Taken together, intact incretin levels are primarily related to C-peptide and glucose levels. This result suggests that glycemia and insulin secretion are the main factors associated with intact incretin levels in T2D patients.

Factors Related to Blood Intact Incretin Levels in Patients with Type 2 Diabetes Mellitus.

BackgroundWe performed this study to identify factors related to intact incretin levels in patients with type 2 diabetes mellitus (T2DM).MethodsWe cross-sectionally analyzed 336 patients with T2DM. Intact glucagon-like peptide 1 (iGLP-1) and intact glucose-dependent insulinotropic polypeptide (iGIP) levels were measured in a fasted state and 30 minutes after ingestion of a standard mixed meal. The differences between 30 and 0 minute iGLP-1 and iGIP levels were indicated as ΔiGLP-1 and ΔiGIP.ResultsIn simple correlation analyses, fasting iGLP-1 was positively correlated with glucose, C-peptide, creatinine, and triglyceride levels, and negatively correlated with estimated glomerular filtration rate. ΔiGLP-1 was positively correlated only with ΔC-peptide levels. Fasting iGIP showed positive correlations with glycosylated hemoglobin (HbA1c) and fasting glucose levels, and negative correlations with ΔC-peptide levels. ΔiGIP was negatively correlated with diabetes duration and HbA1c levels, and positively correlated with Δglucose and ΔC-peptide levels. In multivariate analyses adjusting for age, sex, and covariates, fasting iGLP-1 levels were significantly related to fasting glucose levels, ΔiGLP-1 levels were positively related to ΔC-peptide levels, fasting iGIP levels were related to fasting C-peptide levels, and ΔiGIP levels were positively related to ΔC-peptide and Δglucose levels.ConclusionTaken together, intact incretin levels are primarily related to C-peptide and glucose levels. This result suggests that glycemia and insulin secretion are the main factors associated with intact incretin levels in T2DM patients.

Duration-Response of Light-Intensity Physical Activity and Glucose Dynamics in Older Adults.

Older adults spend 30% of their day in light-intensity physical activity (LPA). This study was designed to determine if increasing the proportion of time spent in LPA would affect glucose control. Older adults (N = 9) completed four 3-hour treatment conditions consisting of a seated control and 3 randomized conditions: (1)20% time spent in continuous LPA, 80% seated; (2)40% time spent in continuous LPA, 60% seated; and (3)60% time spent in continuous LPA, 40% seated. Energy expenditure was measured continuously, and glucose was measured prior to mixed-meal ingestion and hourly thereafter. Glucose area under the curve was compared between conditions using Friedman test. There was a significant difference in glucose area under the curve by time spent in LPA (P < .001); specifically, between the seated and 60% LPA (mean difference = 35.0 [24.6]mg/dL, P = .01), seated and 40% LPA (mean difference = 25.2 [11.8]mg/dL, P = .03), seated and 20% LPA (mean difference = 17.8 [22.5]mg/dL, P = .03), 20% LPA and 60% LPA (mean difference = 17.2 [22.5]mg/dL, P = .01), and 40% LPA and 60% LPA (mean difference = 9.8 [7.3]mg/dL, P = .01). These results provide experimental evidence to the importance LPA has on metabolic health. If older adults who already spend, on average, about 3hours per day in LPA, further increase their LPA, they could see benefit to glucose control.