The metabolic recovery of marathon runners: an untargeted 1H-NMR metabolomics perspective.

Introduction: Extreme endurance events may result in numerous adverse metabolic, immunologic, and physiological perturbations that may diminish athletic performance and adversely affect the overall health status of an athlete, especially in the absence of sufficient recovery. A comprehensive understanding of the post-marathon recovering metabolome, may aid in the identification of new biomarkers associated with marathon-induced stress, recovery, and adaptation, which can facilitate the development of improved training and recovery programs and personalized monitoring of athletic health/recovery/performance. Nevertheless, an untargeted, multi-disciplinary elucidation of the complex underlying biochemical mechanisms involved in recovery after such an endurance event is yet to be demonstrated. Methods: This investigation employed an untargeted proton nuclear magnetic resonance metabolomics approach to characterize the post-marathon recovering metabolome by systematically comparing the pre-, immediately post, 24, and 48 h post-marathon serum metabolite profiles of 15 athletes. Results and Discussion: A total of 26 metabolites were identified to fluctuate significantly among post-marathon and recovery time points and were mainly attributed to the recovery of adenosine triphosphate, redox balance and glycogen stores, amino acid oxidation, changes to gut microbiota, and energy drink consumption during the post-marathon recovery phase. Additionally, metabolites associated with delayed-onset muscle soreness were observed; however, the mechanisms underlying this commonly reported phenomenon remain to be elucidated. Although complete metabolic recovery of the energy-producing pathways and fuel substrate stores was attained within the 48 h recovery period, several metabolites remained perturbed throughout the 48 h recovery period and/or fluctuated again following their initial recovery to pre-marathon-related levels.

The Postprandial Glycaemic and Hormonal Responses Following the Ingestion of a Novel, Ready-to-Drink Shot Containing a Low Dose of Whey Protein in Centrally Obese and Lean Adult Males: A Randomised Controlled Trial.

Purpose: Elevated postprandial glycaemia [PPG] increases the risk of cardiometabolic complications in insulin-resistant, centrally obese individuals. Therefore, strategies that improve PPG are of importance for this population. Consuming large doses of whey protein [WP] before meals reduces PPG by delaying gastric emptying and stimulating the secretion of the incretin peptides, glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide 1 [GLP-1]. It is unclear if these effects are observed after smaller amounts of WP and what impact central adiposity has on these gastrointestinal processes. Methods: In a randomised-crossover design, 12 lean and 12 centrally obese adult males performed two 240 min mixed-meal tests, ~5-10 d apart. After an overnight fast, participants consumed a novel, ready-to-drink WP shot (15 g) or volume-matched water (100 ml; PLA) 10 min before a mixed-nutrient meal. Gastric emptying was estimated by oral acetaminophen absorbance. Interval blood samples were collected to measure glucose, insulin, GIP, GLP-1, and acetaminophen. Results: WP reduced PPG area under the curve [AUC0-60] by 13 and 18.2% in the centrally obese and lean cohorts, respectively (both p <0.001). In both groups, the reduction in PPG was accompanied by a two-three-fold increase in GLP-1 and delayed gastric emptying. Despite similar GLP-1 responses during PLA, GLP-1 secretion during the WP trial was ~27% lower in centrally obese individuals compared to lean (p = 0.001). In lean participants, WP increased the GLP-1ACTIVE/TOTAL ratio comparative to PLA (p = 0.004), indicative of reduced GLP-1 degradation. Conversely, no treatment effects for GLP-1ACTIVE/TOTAL were seen in obese subjects. Conclusion: Pre-meal ingestion of a novel, ready-to-drink WP shot containing just 15 g of dietary protein reduced PPG in lean and centrally obese males. However, an attenuated GLP-1 response to mealtime WP and increased incretin degradation might impact the efficacy of nutritional strategies utilising the actions of GLP-1 to regulate PPG in centrally obese populations. Whether these defects are caused by an individual's insulin resistance, their obese state, or other obesity-related ailments needs further investigation. Clinical Trial Registration: ISRCTN.com, identifier [ISRCTN95281775]. https://www.isrctn.com/.

Type 1 diabetes patients increase CXCR4+ and CXCR7+ haematopoietic and endothelial progenitor cells with exercise, but the response is attenuated.

Exercise mobilizes angiogenic cells, which stimulate vascular repair. However, limited research suggests exercise-induced increase of endothelial progenitor cell (EPCs) is completely lacking in type 1 diabetes (T1D). Clarification, along with investigating how T1D influences exercise-induced increases of other angiogenic cells (hematopoietic progenitor cells; HPCs) and cell surface expression of chemokine receptor 4 (CXCR4) and 7 (CXCR7), is needed. Thirty T1D patients and 30 matched non-diabetes controls completed 45 min of incline walking. Circulating HPCs (CD34+, CD34+CD45dim) and EPCs (CD34+VEGFR2+, CD34+CD45dimVEGFR2+), and subsequent expression of CXCR4 and CXCR7, were enumerated by flow cytometry at rest and post-exercise. Counts of HPCs, EPCs and expression of CXCR4 and CXCR7 were significantly lower at rest in the T1D group. In both groups, exercise increased circulating angiogenic cells. However, increases was largely attenuated in the T1D group, up to 55% lower, with CD34+ (331 ± 437 Δcells/mL vs. 734 ± 876 Δcells/mL p = 0.048), CD34+VEGFR2+ (171 ± 342 Δcells/mL vs. 303 ± 267 Δcells/mL, p = 0.006) and CD34+VEGFR2+CXCR4+ (126 ± 242 Δcells/mL vs. 218 ± 217 Δcells/mL, p = 0.040) significantly lower. Exercise-induced increases of angiogenic cells is possible in T1D patients, albeit attenuated compared to controls. Decreased mobilization likely results in reduced migration to, and repair of, vascular damage, potentially limiting the cardiovascular benefits of exercise.Trial registration: ISRCTN63739203.

A small dose of whey protein co-ingested with mixed-macronutrient breakfast and lunch meals improves postprandial glycemia and suppresses appetite in men with type 2 diabetes: a randomized controlled trial.

Background: Large doses of whey protein consumed as a preload before single high-glycemic load meals has been shown to improve postprandial glycemia in type 2 diabetes. It is unclear if this effect remains with smaller doses of whey co-ingested at consecutive mixed-macronutrient meals. Moreover, whether hydrolyzed whey offers further benefit under these conditions is unclear. Objective: The aim of this study was to investigate postprandial glycemic and appetite responses after small doses of intact and hydrolyzed whey protein co-ingested with mixed-nutrient breakfast and lunch meals in men with type 2 diabetes. Design: In a randomized, single-blind crossover design, 11 men with type 2 diabetes [mean ± SD age: 54.9 ± 2.3 y; glycated hemoglobin: 6.8% ± 0.3% (51.3 ± 3.4 mmol/mol)] attended the laboratory on 3 mornings and consumed 1) intact whey protein (15 g), 2) hydrolyzed whey protein (15 g), or 3) placebo (control) immediately before mixed-macronutrient breakfast and lunch meals, separated by 3 h. Blood samples were collected periodically and were processed for insulin, intact glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), leptin, peptide tyrosine tyrosine (PYY3-36), and amino acid concentrations. Interstitial glucose was measured during and for 24 h after each trial. Subjective appetite was assessed with the use of visual analog scales. Results: Total postprandial glycemia area under the curve was reduced by 13% ± 3% after breakfast following the intact whey protein when compared with control (P < 0.05). Hydrolyzed whey attenuated early glucose after breakfast when compared with control (P < 0.05). Glycemia was improved postlunch after the intact whey protein only when compared with control (P < 0.05). Greater satiety was observed after the intact whey protein only after both meals when compared with control (P < 0.05). Insulin concentrations increased after both the intact and hydrolyzed whey protein, showing strong positive correlations with increases in valine and isoleucine (P < 0.05). Incretin and appetite regulatory hormone responses were similar across trials (P > 0.05). Conclusions: The consumption of a small 15-g dose of intact whey protein immediately before consecutive mixed-macronutrient meals improves postprandial glycemia, stimulates insulin release, and increases satiety in men with type 2 diabetes. This trial was registered at www.clinicialtrials.gov as NCT02903199.

The role of whey protein in postprandial glycaemic control.

Epidemiological studies demonstrate that poor glycaemic control is an independent risk factor for CVD. Postprandial glycaemia has been demonstrated as a better predictor of glycated Hb, the gold standard of glycaemic control, when compared with fasting blood glucose. There is a need for more refined strategies to tightly control postprandial glycaemia, particularly in those with type 2 diabetes, and nutritional strategies around meal consumption may be effective in enhancing subsequent glycaemic control. Whey protein administration around meal times has been demonstrated to reduce postprandial glycaemia, mediated through various mechanisms including an enhancement of insulin secretion. Whey protein ingestion has also been shown to elicit an incretin effect, enhancing the secretion of glucose-dependent insulinotropic peptide and glucagon-like peptide-1, which may also influence appetite regulation. Acute intervention studies have shown some promising results however many have used large dosages (50-55 g) of whey protein alongside high-glycaemic index test meals, such as instant powdered potato mixed with glucose, which does not reflect realistic dietary strategies. Long-term intervention studies using realistic strategies around timing, format and amount of whey protein in relevant population groups are required.

A pilot study investigating reactive oxygen species production in capillary blood after a marathon and the influence of an antioxidant-rich beetroot juice.

We report that reactive oxygen species (ROS), as measured in capillary blood taken from the finger-tip, increased after a marathon (+128% P < 0.01; effect size = 1.17), indicating that this collection method might be useful for measuring ROS in field settings. However, mitochondrial DNA damage remained unchanged. Beetroot juice, taken before and after exercise, was unable to mitigate exercise-induced ROS production, questioning its use an antioxidant-rich food.

A comparison of isomaltulose versus maltodextrin ingestion during soccer-specific exercise.

PURPOSE: The performance and physiological effects of isomaltulose and maltodextrin consumed intermittently during prolonged soccer-specific exercise were investigated. METHODS: University soccer players (n = 22) performed 120 min of intermittent exercise while consuming 8% carbohydrate-electrolyte drinks (equivalent to ~ 20 g h-1) containing maltodextrin (Glycaemic Index: 90-100), isomaltulose (Glycaemic Index: 32) or a carbohydrate-energy-free placebo in a manner replicating the practices of soccer players (i.e., during warm-up and half-time). Physical (sprinting, jumping) and technical (shooting, dribbling) performance was assessed. RESULTS: Blood glucose and plasma insulin (both P < 0.001) concentrations varied by trial with isomaltulose maintaining > 13% higher blood glucose concentrations between 75 and 90 min versus maltodextrin (P < 0.05). A decline in glycaemia at 60 min in maltodextrin was attenuated with isomaltulose (-19 versus -4%; P = 0.015). Carbohydrates attenuated elevations in plasma epinephrine concentrations (P < 0.05), but isomaltulose proved most effective at 90 and 120 min. Carbohydrates did not attenuate IL-6 increases or reductions in physical or technical performances (all P > 0.05). Ratings of abdominal discomfort were influenced by trial (P < 0.05) with lower values for both carbohydrates compared to PLA from 60 min onwards. CONCLUSIONS: Although carbohydrates (~ 20 g h-1) did not attenuate performance reductions throughout prolonged soccer-specific exercise, isomaltulose maintained higher blood glucose at 75-90 min, lessened the magnitude of the exercise-induced rebound glycaemic response and attenuated epinephrine increases whilst maintaining similar abdominal discomfort values relative to maltodextrin. When limited opportunities exist to consume carbohydrates on competition-day, low-glycaemic isomaltulose may offer an alternative nutritional strategy for exercising soccer players.

Minimal muscle damage after a marathon and no influence of beetroot juice on inflammation and recovery.

This study examined whether beetroot juice (BTJ) would attenuate inflammation and muscle damage following a marathon. Using a double blind, independent group design, 34 runners (each having completed ca. ∼16 previous marathons) consumed either BTJ or an isocaloric placebo (PLA) for 3 days following a marathon. Maximal isometric voluntary contractions (MIVC), countermovement jumps (CMJ), muscle soreness, serum cytokines, leucocytosis, creatine kinase (CK), high sensitivity C-reactive protein (hs-CRP), and aspartate aminotransferase (AST) were measured pre, post, and 2 days after the marathon. CMJ and MIVC were reduced after the marathon (P < 0.05), but no group differences were observed (P > 0.05). Muscle soreness was increased in the day after the marathon (BTJ; 45 ± 48 vs. PLA; 46 ± 39 mm) and had returned to baseline by day 2, irrespective of supplementation (P = 0.694). Cytokines (interleukin-6; IL-6, interleukin-8, tumour necrosis factor-α) were increased immediately post-marathon but apart from IL-6 had returned to baseline values by day 1 post. No interaction effects were evident for IL-6 (P = 0.213). Leucocytes increased 1.7-fold after the race and remained elevated 2 days post, irrespective of supplement (P < 0.0001). CK peaked at 1 day post marathon (BTJ: 965 ± 967, and PLA: 1141 ± 979 IU·L-1) and like AST and hs-CRP, was still elevated 2 days after the marathon (P < 0.05); however, no group differences were present for these variables. Beetroot juice did not attenuate inflammation or reduce muscle damage following a marathon, possibly because most of these indices were not markedly different from baseline values in the days after the marathon.

The plasma bioavailability of nitrate and betanin from Beta vulgaris rubra in humans.

PURPOSE: To evaluate the plasma bioavailability of betanin and nitric oxide (NOx) after consuming beetroot juice (BTJ) and whole beetroot (BF). BTJ and BF were also analysed for antioxidant capacity, polyphenol content (TPC) and betalain content. METHODS: Ten healthy males consumed either 250 ml of BTJ, 300 g of BF or a placebo drink, in a randomised, crossover design. Venous plasma samples were collected pre (baseline), 1, 2, 3, 5 and 8 h post-ingestion. Betanin content in BTJ, BF and plasma was analysed with reverse-phase high-performance liquid chromatography (HPLC) and mass spectrometry detection (LCMS). Antioxidant capacity was estimated using the Trolox equivalent antioxidant capacity (TEAC) and polyphenol content using Folin-Ciocalteu colorimetric methods [gallic acid equivalents (GAE)] and betalain content spectrophotometrically. RESULTS: TEAC was 11.4 ± 0.2 mmol/L for BTJ and 3.4 ± 0.4 µmol/g for BF. Both BTJ and BF contained a number of polyphenols (1606.9 ± 151 mg/GAE/L and 1.67 ± 0.1 mg/GAE/g, respectively), betacyanins (68.2 ± 0.4 mg/betanin equivalents/L and 19.6 ± 0.6 mg/betanin equivalents/100 g, respectively) and betaxanthins (41.7 ± 0.7 mg/indicaxanthin equivalents/L and 7.5 ± 0.2 mg/indicaxanthin equivalents/100 g, respectively). Despite high betanin contents in both BTJ (~194 mg) and BF (~66 mg), betanin could not be detected in the plasma at any time point post-ingestion. Plasma NOx was elevated above baseline for 8 h after consuming BTJ and 5 h after BF (P < 0.05). CONCLUSIONS: These data reveal that BTJ and BF are rich in phytonutrients and may provide a useful means of increasing plasma NOx bioavailability. However, betanin, the major betalain in beetroot, showed poor bioavailability in plasma.

Antioxidant-rich beetroot juice does not adversely affect acute neuromuscular adaptation following eccentric exercise.

This study examined the effects of beetroot juice on the repeated bout effect (RBE) to eccentric exercise. Twenty-nine recreationally active males performed two bouts of 100-drop jumps, separated by 14-21 days. Using a double-blind, independent groups design, participants consumed either a higher dose beetroot juice (H-BT; 250 ml, n = 10), a lower dose beetroot juice (L-BT; 125 ml, n = 9) or an isocaloric placebo (PLA; 250 ml, n = 10) for 3 days after bout 1; no drinks were consumed after bout 2. Maximal isometric voluntary contraction (MIVC), countermovement jump (CMJ), pressure-pain threshold (PPT) and creatine kinase (CK) were measured pre, post, 24, 48 and 72 h following both bouts. In bout 2, CMJ and MIVC recovered quicker and CK activity was attenuated (versus bout 1) (P < 0.05) in all groups, demonstrating an RBE. At 24 h post bout 1, MIVC was 84.1 ± 16.1, 83.6 ± 11.6, 79.7 ± 15.1% relative to baseline values in the H-BT, L-BT and PLA groups, respectively; at 24 h post bout 2, MIVC recovered to 90.7 ± 13.7, 92.9 ± 6.9, 87.8 ± 6.9, in the H-BT, L-BT and PLA groups, respectively. These findings suggest that supplementation with antioxidant-rich beetroot juice does not adversely affect acute adaptations to a bout of eccentric exercise.

The effects of beetroot juice supplementation on indices of muscle damage following eccentric exercise.

PURPOSE: Foods rich in antioxidant and anti-inflammatory phytochemicals might attenuate skeletal muscle damage; thus, the present study investigated whether consuming an antioxidant rich beetroot juice would attenuate the muscle-damaging effects of eccentric exercise. METHODS: Using a double blind, independent groups design, 30 recreationally active males were allocated to consume a high dose of beetroot juice (H-BT; 250 ml), a lower dose of beetroot juice (L-BT; 125 ml), or an isocaloric placebo (PLA; 250 ml) immediately (×3 servings), 24 (×2 servings) and 48 h (×2 servings) following completion of 100-drop jumps. Maximal isometric voluntary contractions (MIVC), countermovement jumps (CMJ), pressure pain threshold (PPT), creatine kinase (CK), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) were measured pre, post, 2 (blood indices only), 24, 48 and 72 h following the drop jumps. RESULTS: CMJ performance recovered quicker (relative to baseline) in H-BT vs. PLA at 48 (91.7 ± 12.2 vs. 74.4 ± 17.3%; P = 0.009, ES = 1.00) and 72 h postexercise (93.4 ± 7.7 vs. 86 ± 5.9%; P = 0.046, ES = 1.25). PPT was greater in both the H-BT and L-BT vs. PLA at 24, 48 and 72 h postexercise (P < 0.001); PPT had returned to baseline in H-BT and L-BT at 72 h postexercise, but was still reduced in PLA (80.1 ± 28.9% of baseline values). MIVC, CK, IL-6, TNF-α and IL-8 were unaffected by beetroot juice (P > 0.05). CONCLUSIONS: Acute beetroot juice supplementation attenuated muscle soreness and decrements in CMJ performance induced by eccentric exercise; further research on the anti-inflammatory effects of beetroot juice are required to elucidate the precise mechanisms.

The inflammation, vascular repair and injury responses to exercise in fit males with and without Type 1 diabetes: an observational study.

BACKGROUND: Type 1 diabetes is associated with raised inflammation, impaired endothelial progenitor cell mobilisation and increased markers of vascular injury. Both acute and chronic exercise is known to influence these markers in non-diabetic controls, but limited data exists in Type 1 diabetes. We assessed inflammation, vascular repair and injury at rest and after exercise in physically-fit males with and without Type 1 diabetes. METHODS: Ten well-controlled type 1 diabetes (27 ± 2 years; BMI 24 ± 0.7 kg.m(2); HbA1c 53.3 ± 2.4 mmol/mol) and nine non-diabetic control males (27 ± 1 years; BMI 23 ± 0.8 kg.m(2)) matched for age, BMI and fitness completed 45-min of running. Venous blood samples were collected 60-min before and 60-min after exercise, and again on the following morning. Blood samples were processed for TNF-α using ELISA, and circulating endothelial progenitor cells (cEPCs; CD45(dim)CD34(+)VEGFR2(+)) and endothelial cells (cECs; CD45(dim)CD133(-)CD34(+)CD144(+)) counts using flow-cytometry. RESULTS: TNF-α concentrations were 4-fold higher at all-time points in Type 1 diabetes, when compared with control (P < 0.001). Resting cEPCs were similar between groups; after exercise there was a significant increase in controls (P = 0.016), but not in Type 1 diabetes (P = 0.202). CEPCs peaked the morning after exercise, with a greater change in controls vs. Type 1 diabetes (+139 % vs. 27 %; P = 0.01). CECs did not change with exercise and were similar between groups at all points (P > 0.05). Within the Type 1 diabetes group, the delta change in cEPCS from rest to the following morning was related to HbA1c (r = -0.65, P = 0.021) and TNF-α (r = -0.766, P = 0.005). CONCLUSIONS: Resting cEPCs and cECs in Type 1 diabetes patients with excellent HbA1c and high physical-fitness are comparable to healthy controls, despite eliciting 4-fold greater TNF-α. Furthermore, Type 1 diabetes patients appear to have a blunted post-exercise cEPCs response (vascular repair), whilst a biomarker of vascular injury (cECs) remained comparable to healthy controls.

Insulin therapy and dietary adjustments to normalize glycemia and prevent nocturnal hypoglycemia after evening exercise in type 1 diabetes: a randomized controlled trial.

INTRODUCTION: Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. METHODS: Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, ß-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. RESULTS: Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. CONCLUSIONS: Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances. CLINICAL TRIALS NUMBER: NCT02204839, ClinicalTrials.gov.

Recovery facilitation with Montmorency cherries following high-intensity, metabolically challenging exercise.

The impact of Montmorency tart cherry (Prunus cerasus L.) concentrate (MC) on physiological indices and functional performance was examined following a bout of high-intensity stochastic cycling. Trained cyclists (n = 16) were equally divided into 2 groups (MC or isoenergetic placebo (PLA)) and consumed 30 mL of supplement, twice per day for 8 consecutive days. On the fifth day of supplementation, participants completed a 109-min cycling trial designed to replicate road race demands. Functional performance (maximum voluntary isometric contraction (MVIC), cycling efficiency, 6-s peak cycling power) and delayed onset muscle soreness were assessed at baseline, 24, 48, and 72 h post-trial. Blood samples collected at baseline, immediately pre- and post-trial, and at 1, 3, 5, 24, 48, and 72 h post-trial were analysed for indices of inflammation (interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor alpha, high-sensitivity C-reactive protein (hsCRP)), oxidative stress (lipid hydroperoxides), and muscle damage (creatine kinase). MVIC (P < 0.05) did not decline in the MC group (vs. PLA) across the 72-h post-trial period and economy (P < 0.05) was improved in the MC group at 24 h. IL-6 (P < 0.001) and hsCRP (P < 0.05) responses to the trial were attenuated with MC (vs. PLA). No other blood markers were significantly different between MC and PLA groups. The results of the study suggest that Montmorency cherry concentrate can be an efficacious functional food for accelerating recovery and reducing exercise-induced inflammation following strenuous cycling exercise.

Calcium ingestion suppresses appetite and produces acute overcompensation of energy intake independent of protein in healthy adults.

BACKGROUND: Prior evidence suggests that high-calcium intake influences postprandial appetite and insulinemia, possibly due to elevated incretins. In vitro and ex vivo models demonstrate that extracellular calcium and protein synergistically enhance secretion of incretins. This is yet to be shown in humans. OBJECTIVE: This study was designed to assess energy intake compensation in response to protein and calcium ingestion. METHODS: Twenty healthy adults (13 men; 7 women) completed 4 trials in a randomized, double-blind crossover design separated by ≥48 h. During the trials, each participant consumed a low-calcium and low-protein control preload [(CON); 4 g and 104 mg, respectively], a high-protein preload (PRO; 29 g), a high-calcium preload (CAL; 1170 mg), or a high-protein and high-calcium preload (PROCAL). Blood samples were collected at baseline and 15, 30, 45, and 60 min after preload ingestion to determine insulin and incretin hormone concentrations. Energy intake was assessed by a homogenous test meal 60 min after the preload. Visual analog scales were completed immediately before blood sampling to assess subjective appetite sensations. RESULTS: Relative to the CON, the PRO produced 100% (95% CI: 85%, 115%) energy compensation, whereas the CAL produced significant overcompensation [118% (95% CI: 104%, 133%)], which was significantly more positive than with the PRO (P < 0.05). The PROCAL resulted in energy compensation of 109% (95% CI: 95%, 123%), which tended to be greater than with the PRO (P = 0.06). The mean difference in appetite sensations relative to the CON was not significantly different between the PRO (-3 mm; 95% CI: -8, 3 mm), CAL (-5 mm; 95% CI: -9, 0 mm), and PROCAL (-5 mm; 95% CI: -10, -1 mm) (P > 0.05). CONCLUSIONS: The addition of protein to a preload results in almost perfect energy compensation, whereas the addition of calcium, with or without protein, suppresses appetite and produces overcompensation of subsequent energy intake. The role of circulating insulin and incretin concentrations in these responses, however, remains unclear. This trial was registered at clinicaltrials.gov as NCT01986036.

Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial.

AIM: To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients. METHODS: This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l-1) treated with insulin's glargine and aspart, or lispro attended the laboratory on two mornings at ∼08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kg-1BM; 380±10 kcal) and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660±21 kcal) and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, ß-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α concentrations were measured for 180 minutes post-meal. RESULTS: All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p<0.05) resulting in 75% of patients experiencing hyperglycaemia (blood glucose ≥8.0 mmol.l-1; 50% n = 6, Full n = 3). ß-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = -0.484, p = 0.017). CONCLUSIONS: Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive running exercise may cause hyperglycaemia, but does not augment ketonaemia, raise inflammatory cytokines TNF-α and IL-6 above fasting levels, or cause other adverse metabolic or hormonal disturbances. TRIAL REGISTRATION: ClinicalTrials.gov NCT01531855.

A low-glycemic index meal and bedtime snack prevents postprandial hyperglycemia and associated rises in inflammatory markers, providing protection from early but not late nocturnal hypoglycemia following evening exercise in type 1 diabetes.

OBJECTIVE: To examine the influence of the glycemic index (GI) of foods consumed after evening exercise on postprandial glycemia, metabolic and inflammatory markers, and nocturnal glycemic control in type 1 diabetes. RESEARCH DESIGN AND METHODS: On two evenings (∼1700 h), 10 male patients (27 ± 5 years of age, HbA1c 6.7 ± 0.7% [49.9 ± 8.1 mmol/mol]) were administered a 25% rapid-acting insulin dose with a carbohydrate bolus 60 min before 45 min of treadmill running. At 60 min postexercise, patients were administered a 50% rapid-acting insulin dose with one of two isoenergetic meals (1.0 g carbohdyrate/kg body mass [BM]) matched for macronutrient content but of either low GI (LGI) or high GI (HGI). At 180 min postmeal, the LGI group ingested an LGI snack and the HGI group an HGI snack (0.4 g carbohdyrate/kg BM) before returning home (∼2300 h). Interval samples were analyzed for blood glucose and lactate; plasma glucagon, epinephrine, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α); and serum insulin, cortisol, nonesterified fatty acid, and ß-hydroxybutyrate concentrations. Interstitial glucose was recorded for 20 h postlaboratory attendance through continuous glucose monitoring. RESULTS: Following the postexercise meal, an HGI snack induced hyperglycemia in all patients (mean ± SD glucose 13.5 ± 3.3 mmol/L) and marked increases in TNF-α and IL-6, whereas relative euglycemia was maintained with an LGI snack (7.7 ± 2.5 mmol/L, P < 0.001) without inflammatory cytokine elevation. Both meal types protected all patients from early hypoglycemia. Overnight glycemia was comparable, with a similar incidence of nocturnal hypoglycemia (n = 5 for both HGI and LGI). CONCLUSIONS: Consuming LGI food with a reduced rapid-acting insulin dose following evening exercise prevents postprandial hyperglycemia and inflammation and provides hypoglycemia protection for ∼8 h postexercise; however, the risk of late nocturnal hypoglycemia remains.

Calcium co-ingestion augments postprandial glucose-dependent insulinotropic peptide(1-42), glucagon-like peptide-1 and insulin concentrations in humans.

PURPOSE: This study determined whether calcium co-ingestion potentiates postprandial GIP(1-42) and GLP-1 concentrations in humans and the concomitant impact on insulin, appetite sensations and substrate metabolism. METHODS: Ten healthy males consumed two energy- and macronutrient-matched meals in a double-blind, randomized, crossover design. The calcium content of the control meal was 3 mg/kg body mass, which was increased to 15 mg/kg body mass with calcium co-ingestion. Circulating concentrations of GIP(1-42), GLP-1 and insulin were determined over a 180-min postprandial period, followed by 60 min of exercise. Visual analogue scales were used to determine subjective appetite sensations. Rates of energy expenditure and substrate (lipid and carbohydrate) oxidation were estimated using indirect calorimetry. RESULTS: Calcium co-ingestion resulted in a 47% increase in GIP(1-42), a 22% increase in GLP-1 and a 19% increase in insulin areas under the curve for the 120 min following consumption (all P < 0.05). Furthermore, appetite sensations were suppressed by calcium co-ingestion by 12% (P = 0.034). No differences, however, were observed in substrate metabolism (P > 0.05). CONCLUSION: Ingestion of a high-calcium meal potentiates postprandial GIP(1-42), GLP-1 and insulin concentrations in humans. Subjective appetite is also temporarily suppressed, although substrate metabolism is unaffected.