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Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.

ABSTRACT: Background:Exercise improves glycemic control but the magnitude, and in some cases, the direction of this effect is variable. Ambient hyperglycemia has been implicated in this exercise response heterogeneity. The current study investigated whether pre-exercise hyperglycemia directly impacts the effect of exercise on glycemic control. Methods:Twelve healthy normal glucose-tolerant males completed four trials in a randomized, crossover design. Each trial consisted of 24-h pre-intervention monitoring, a 7-h intervention, and 24-h post-intervention monitoring. Glycemic control was measured throughout the study by continuous glucose monitoring. The four interventions were no exercise (CON) or 45 min of cycling exercise (70%HRmax) preceded by 3.5 h of either normoglycemia (NG-Ex), steady-state hyperglycemia induced by constant glucose infusion (HG-Ex) or fluctuating glycemia induced by repeated glucose bolus infusions (FG-Ex). Results:Physical activity and diet were similar between trials, and energy expenditure during exercise was matched between exercise trials (all P > 0.05). Mean glucose during the 3.5 h ± infusion period was higher in HG-Ex (mean ± SEM; 7.2 ± 0.4 mmol/L) and FG-Ex (7.3 ± 0.3 mmol/L) compared to CON (4.8 ± 0.2 mmol/L) and NG-Ex (5.0 ± 0.2 mmol/L) trials (P < 0.01). Glycemic variability was greatest in FG-Ex (P < 0.01). Following the interventions, the postprandial glucose response (iAUC) was reduced by exercise in NG-Ex compared to CON (321.1 ± 38.6 vs. 445.5 ± 49.7 mmol/L.8h, P < 0.05, d=0.81). This benefit was blunted when exercise was preceded by steady-state (HG-Ex, 425.3 ± 45.7 mmol/L.8h) and fluctuating (FG-Ex, 465.5 ± 39.3 mmol/L.8h) hyperglycemia (both P > 0.05 vs. CON). Conclusion:Pre-exercise hyperglycemia blunted the glucoregulatory benefits of acute exercise upon postprandial glucose response, suggesting that exposure to hyperglycemia contributes to exercise response heterogeneity. Clinical Trial Registration:ClinicalTrials.gov, identifier NCT03284216.

SUBMITTER: Carter S

PROVIDER: S-EPMC7593662 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.

Carter Steven S Solomon Thomas P J TPJ

Frontiers in endocrinology 20201015

<h4>Background</h4>Exercise improves glycemic control but the magnitude, and in some cases, the direction of this effect is variable. Ambient hyperglycemia has been implicated in this exercise response heterogeneity. The current study investigated whether pre-exercise hyperglycemia directly impacts the effect of exercise on glycemic control.<h4>Methods</h4>Twelve healthy normal glucose-tolerant males completed four trials in a randomized, crossover design. Each trial consisted of 24-h pre-interv ...[more]

PMID: 33178135

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Project description:Introduction: Fatty acids are a major nutrient in dietary fat, some of which are ligands of long-chain fatty acid receptors, including G-protein-coupled receptor (GPR) 40 and GPR120. Pretreatment with GPR40 agonists enhanced the secretion of insulin in response to elevating blood glucose levels after glucose load in a diabetes model, but pretreatment with GPR120 agonist did not ameliorate postprandial hyperglycemia. This study examined whether oral administration of linoleic acid (LA), a GPR40 and GPR120 agonist, immediately before glucose load would affect the elevation of postprandial blood glucose levels in rats. Methods: Male rats and rats with type 1 diabetes administered streptozocin were orally administered LA, trilinolein, α-linolenic acid (α-LA), oleic acid, TAK-875, or TUG-891 immediately before glucose load. Blood glucose levels were measured before, then 15, 30, 60 and 120 min after glucose load. CACO-2 cells were used to measure the uptake of [14C] α-MDG for 30 min with or without LA. Gastric content from rats administered LA was collected 15 and 30 min after glucose load, and blood samples were collected for measurement of glucagon-like peptide 1 (GLP-1) and cholecystokinin concentrations. Results: The elevation of postprandial blood glucose levels was slowed by LA but not by trilinolein in rats without promotion of insulin secretion, and this effect was also observed in rats with type 1 diabetes. The uptake of α-MDG, an SGLT-specific substrate, was, however, not inhibited by LA. Gastric emptying was slowed by LA 15 min after glucose load, and GLP-1, but not cholecystokinin, level was elevated by LA 15 min after glucose load. TUG-891, a GPR120 agonist, ameliorated postprandial hyperglycemia but TAK-875, a GPR40 agonist, did not. Pretreatment with AH7614, a GPR120 antagonist, partially canceled the improvement of postprandial hyperglycemia induced by LA. α-LA, which has high affinity with GPR120 as well as LA, slowed the elevation of postprandial blood glucose levels, but oleic acid, which has lower affinity with GPR120 than LA, did not. Conclusion: Oral administration of LA immediately after glucose load ameliorated postprandial hyperglycemia due to slowing of gastric emptying via promotion of GLP-1 secretion. The mechanisms may be associated with GPR120 pathway.

Project description:Aims/hypothesisExercise is recommended for the treatment and prevention of type 2 diabetes. However, the most effective time of day to achieve beneficial effects on health remains unknown. We aimed to determine whether exercise training at two distinct times of day would have differing effects on 24 h blood glucose levels in men with type 2 diabetes.MethodsEleven men with type 2 diabetes underwent a randomised crossover trial. Inclusion criteria were 45-68 years of age and BMI between 23 and 33 kg/m2. Exclusion criteria were insulin treatment and presence of another systemic illness. Researchers were not blinded to the group assignment. The trial involved 2 weeks of either morning or afternoon high-intensity interval training (HIIT) (three sessions/week), followed by a 2 week wash-out period and a subsequent period of the opposite training regimen. Continuous glucose monitor (CGM)-based data were obtained.ResultsMorning HIIT increased CGM-based glucose concentration (6.9 ± 0.4 mmol/l; mean ± SEM for the exercise days during week 1) compared with either the pre-training period (6.4 ± 0.3 mmol/l) or afternoon HIIT (6.2 ± 0.3 mmol/l for the exercise days during week 1). Conversely, afternoon HIIT reduced the CGM-based glucose concentration compared with either the pre-training period or morning HIIT. Afternoon HIIT was associated with elevated thyroid-stimulating hormone (TSH; 1.9 ± 0.2 mU/l) and reduced T4 (15.8 ± 0.7 pmol/l) concentrations compared with pre-training (1.4 ± 0.2 mU/l for TSH; 16.8 ± 0.6 pmol/l for T4). TSH was also elevated after morning HIIT (1.7 ± 0.2 mU/l), whereas T4 concentrations were unaltered.Conclusions/interpretationAfternoon HIIT was more efficacious than morning HIIT at improving blood glucose in men with type 2 diabetes. Strikingly, morning HIIT had an acute, deleterious effect, increasing blood glucose. However, studies of longer training regimens are warranted to establish the persistence of this adverse effect. Our data highlight the importance of optimising the timing of exercise when prescribing it as treatment for type 2 diabetes.

Dataset Information

Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.

Publications

Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.

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