Are there sex differences in the variability of fasting metabolism?

There is evidence across species and across many traits that males display greater between-individual variance. In contrast, (premenopausal) females display large within-individual variance in sex hormone concentrations, which can increase within-individual variance in many other parameters. The latter may contribute to the lower representation of females in metabolic research. This study is a pooled secondary analysis of data from seven crossover studies to investigate the between-individual and the within-individual variance in fasting plasma metabolites, resting metabolic rate (RMR), and body mass. Females demonstrated higher within-individual variability of plasma 17ß-estradiol [coefficient of variation (CV): 15 ± 15% for males vs. 38 ± 34% for females, P < 0.001] and progesterone concentrations (CV: 13 ± 11% for males vs. 52 ± 51% for females, P < 0.001) but there were no meaningful differences in the variability of plasma glucose (CV: 4 ± 3% for males vs. 5 ± 5% for females), insulin, lactate, triglycerides (CV: 15 ± 9% for males vs. 15 ± 10% for females), and esterified fatty acid concentrations or in RMR and body mass (CV: 0.43 ± 0.34% for males vs. for 0.42 ± 0.33% females; P > 0.05 for all outcomes). Males displayed higher between-individual variance in RMR compared with females (SD: 224 kcal·day-1 for males vs. 151 kcal·day-1 for females). In conclusion, these data do not provide evidence that females show greater within-individual variability in many fasting metabolic variables, RMR, or body mass compared with males. We conclude that including females in metabolic research is unlikely to introduce greater within-individual variance when using the recruitment and control procedures described in these studies.NEW & NOTEWORTHY To investigate the within-individual variability in metabolic parameters in males and females, we performed a pooled secondary analysis of fasting blood samples, resting metabolic rate, and body mass from seven crossover studies. We found a greater day-to-day variation in 17ß-estradiol and progesterone in females compared with males but no meaningful difference in within-individual variability of fasting plasma glucose, insulin, lactate, triglycerides, NEFA, resting metabolic rate, or body mass between females and males.

Are all sugars equal? Role of the food source in physiological responses to sugars with an emphasis on fruit and fruit juice.

High (free) sugar intakes can increase self-reported energy intake and are associated with unfavourable cardiometabolic health. However, sugar source may modulate the effects of sugars due to several mechanisms including the food matrix. The aim of this review was to assess the current state of evidence in relation to food source effects on the physiological responses to dietary sugars in humans relevant to cardiometabolic health. An additional aim was to review potential mechanisms by which food sources may influence such responses. Evidence from meta-analyses of controlled intervention trials was used to establish the balance of evidence relating to the addition of sugars to the diet from sugar-sweetened beverages, fruit juice, honey and whole fruit on cardiometabolic outcomes. Subsequently, studies which have directly compared whole fruit with fruit juices, or variants of fruit juices, were discussed. In summary, the sources of sugars can impact physiological responses, with differences in glycaemic control, blood pressure, inflammation, and acute appetite. Longer-term effects and mechanisms require further work, but initial evidence implicates physical structure, energy density, fibre, potassium and polyphenol content, as explanations for some of the observed responses.

Postprandial Metabolic Mesponses to High-fat Feeding in Healthy Adults Following Ingestion of Oolong Tea-Derived Polymerized Polyphenols: A Randomized, Double-blinded, Placebo-controlled Crossover Study.

BACKGROUND: Polymerized polyphenols (PP) found in oolong tea can inhibit pancreatic lipase activity in vitro, and pilot work indicates that this may reduce postprandial lipemia. Since tea contains caffeine and catechins, the interactions between these ingredients and PP warrant investigation. OBJECTIVES: To assess whether PP ingested alone or with caffeine and catechins lowers postprandial lipemia. METHODS: Fifty healthy adults [mean (SD) age: 26 (7) y; BMI (in kg/m2): 24.0 (2.7); female: n = 16] completed 4 oral lipid tolerance tests in a placebo-controlled randomized, crossover design. Participants ingested 40 g of fat with either 1) placebo, 2) 100 mg PP, 3) 150 mg PP, or 4) 100 mg PP plus 50 mg caffeine and 63 mg catechins (PP + CC). Blood was sampled for 3 h postprandially to assess concentrations of serum and plasma triacylglycerol and plasma markers of lipid (NEFA; glycerol; LDL and HDL cholesterol; and ApoA-I, A-II, B, C-II, C-III, and E) and glucose metabolism (glucose, insulin, and C-peptide). RESULTS: Serum and plasma triacylglycerol concentrations and lipid metabolism variables generally increased following any test drink ingestion (main effect of time, p < 0.001). Nevertheless, for the lipid metabolism responses, there were no statistically significant condition-time interactions and no statistically significant differences in incremental or total area under the curve between conditions, apart from HDL cholesterol (p = 0.021). Ingesting 100 mg PP + CC lowered peak plasma glucose, insulin, and C-peptide concentrations compared with all other conditions 30 min postingestion (p < 0.001), with persistent alterations in glucose concentrations observed for 90 min compared with placebo and 100 mg PP conditions. CONCLUSIONS: PP ingested at doses ≤150 mg does not clearly alter early-phase postprandial triacylglycerol concentrations in healthy adults, irrespective of the presence or absence of caffeine and catechins. Nevertheless, caffeine and catechins added to PP lowered postprandial glucose and insulin concentrations. This trial was registered in ClinicalTrials.gov as NCT03324191 (https://clinicaltrials.gov/ct2/show/NCT03324191).

Perspective: Is the Response of Human Energy Expenditure to Increased Physical Activity Additive or Constrained?

The idea that increasing physical activity directly adds to TEE in humans (additive model) has been challenged by the energy constrained hypothesis (constrained model). This model proposes that increased physical activity decreases other components of metabolism to constrain TEE. There is a logical evolutionary argument for trade-offs in metabolism, but, to date, evidence supporting constraint is subject to several limitations, including cross-sectional and correlational studies with potential methodological issues from extreme differences in body size/composition and lifestyle, potential statistical issues such as regression dilution and spurious correlations, and conclusions drawn from deductive inference rather than direct observation of compensation. Addressing these limitations in future studies, ideally, randomized controlled trials should improve the accuracy of models of human energy expenditure. The available evidence indicates that in many scenarios, the effect of increasing physical activity on TEE will be mostly additive although some energy appears to "go missing" and is currently unaccounted for. The degree of energy balance could moderate this effect even further.

Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women.

PURPOSE: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h. METHODS: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning. RESULTS: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d-1; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d-1; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01). CONCLUSION: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes. CLINICAL TRIALS REGISTRATION ID: NCT03509610, https://clinicaltrials.gov/show/NCT03509610.

Addition of Fructose to a Carbohydrate-Rich Breakfast Improves Cycling Endurance Capacity in Trained Cyclists.

It was previously demonstrated that postexercise ingestion of fructose-glucose mixtures can lead to superior liver and equal muscle glycogen synthesis as compared with glucose-based carbohydrates (CHOs) only. After an overnight fast, liver glycogen stores are reduced, and based on this we hypothesized that addition of fructose to a glucose-based breakfast would lead to improved subsequent endurance exercise capacity. In this double-blind cross-over randomized study (eight males, peak oxygen uptake: 62.2 ± 5.4 ml·kg-1·min-1), participants completed two experimental trials consisting of two exercise bouts. In the afternoon of Day 1, they completed a cycling interval training session to normalize glycogen stores after which a standardized high-CHO diet was provided for 4 hr. On Day 2, in the morning, participants received 2 g/kg of CHOs in the form of glucose and rice or fructose and rice, both in a CHO ratio of 1:2. Two hours later they commenced cycling exercise session at the intensity of the first ventilatory threshold until task failure. Exercise capacity was higher in fructose and rice (137.0 ± 22.7 min) as compared with glucose and rice (130.06 ± 19.87 min; p = .046). Blood glucose and blood lactate did not differ between the trials (p > .05) and neither did CHO and fat oxidation rates (p > .05). However, due to the duration of exercise, total CHO oxidation was higher in fructose and rice (326 ± 60 g vs. 298 ± 61 g, p = .009). Present data demonstrate that addition of fructose to a glucose-based CHO source at breakfast improves endurance exercise capacity. Further studies are required to determine the mechanisms and optimal dose and ratio.

Dietary Inorganic Nitrate as an Ergogenic Aid: An Expert Consensus Derived via the Modified Delphi Technique.

INTRODUCTION: Dietary inorganic nitrate is a popular nutritional supplement, which increases nitric oxide bioavailability and may improve exercise performance. Despite over a decade of research into the effects of dietary nitrate supplementation during exercise there is currently no expert consensus on how, when and for whom this compound could be recommended as an ergogenic aid. Moreover, there is no consensus on the safe administration of dietary nitrate as an ergogenic aid. This study aimed to address these research gaps. METHODS: The modified Delphi technique was used to establish the views of 12 expert panel members on the use of dietary nitrate as an ergogenic aid. Over three iterative rounds (two via questionnaire and one via videoconferencing), the expert panel members voted on 222 statements relating to dietary nitrate as an ergogenic aid. Consensus was reached when > 80% of the panel provided the same answer (i.e. yes or no). Statements for which > 80% of the panel cast a vote of insufficient evidence were categorised as such and removed from further voting. These statements were subsequently used to identify directions for future research. RESULTS: The 12 panel members contributed to voting in all three rounds. A total of 39 statements (17.6%) reached consensus across the three rounds (20 yes, 19 no). In round one, 21 statements reached consensus (11 yes, 10 no). In round two, seven further statements reached consensus (4 yes, 3 no). In round three, an additional 11 statements reached consensus (5 yes, 6 no). The panel agreed that there was insufficient evidence for 134 (60.4%) of the statements, and were unable to agree on the outcome of the remaining statements. CONCLUSIONS: This study provides information on the current expert consensus on dietary nitrate, which may be of value to athletes, coaches, practitioners and researchers. The effects of dietary nitrate appear to be diminished in individuals with a higher aerobic fitness (peak oxygen consumption [V̇O2peak] > 60 ml/kg/min), and therefore, aerobic fitness should be taken into account when considering use of dietary nitrate as an ergogenic aid. It is recommended that athletes looking to benefit from dietary nitrate supplementation should consume 8-16 mmol nitrate acutely or 4-16 mmol/day nitrate chronically (with the final dose ingested 2-4 h pre-exercise) to maximise ergogenic effects, taking into consideration that, from a safety perspective, athletes may be best advised to increase their intake of nitrate via vegetables and vegetable juices. Acute nitrate supplementation up to ~ 16 mmol is believed to be safe, although the safety of chronic nitrate supplementation requires further investigation. The expert panel agreed that there was insufficient evidence for most of the appraised statements, highlighting the need for future research in this area.

Interrupting Prolonged Sitting with Intermittent Walking Increases Postprandial Gut Hormone Responses.

INTRODUCTION: Continuous exercise can increase postprandial gut hormone such as glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) responses, but it is unknown whether interrupting prolonged sitting with intermittent walking elicits this effect. METHOD: Ten participants with central overweight/obesity (7 men and 3 postmenopausal women, 51 ± 5 yr; mean ± SD) completed a randomized crossover study in which they consumed breakfast and lunch in the laboratory while either sitting continuously for the entire 5.5-h period (SIT) or the prolonged sitting interrupted every 20 min by walking briskly (6.4 km·h-1) for 2 min (BREAKS). Blood samples were collected at regular intervals to examine postprandial plasma GLP-1, PYY, and glucose-dependent insulinotropic polypeptide concentrations. Adipose tissue samples were collected at baseline and at the end of the trials to examine changes in net dipeptidyl peptidase 4 secretion from primary explants. RESULTS: Mean (95% confidence interval) postprandial GLP-1 and PYY incremental area under curve values were elevated by 26% and 31% in the BREAKS trial versus SIT (8.4 [0.7, 16.1] vs 6.7 [-0.8, 14.2], P = 0.001, and 26.9 [8.1, 45.6] vs 20.4 [5.1, 35.8] nmol·330 min·L-1, P = 0.024, respectively) but without any such effect on glucose-dependent insulinotropic polypeptide (P = 0.076) or net adipose tissue dipeptidyl peptidase 4 secretion (P > 0.05). CONCLUSIONS: Interrupting prolonged sitting with regular short bouts of brisk walking increases postprandial GLP-1 and PYY concentrations in healthy middle-age men and women with central adiposity.

Primary, Secondary, and Tertiary Effects of Carbohydrate Ingestion During Exercise.

The purpose of this current opinion paper is to describe the journey of ingested carbohydrate from 'mouth to mitochondria' culminating in energy production in skeletal muscles during exercise. This journey is conveniently described as primary, secondary, and tertiary events. The primary stage is detection of ingested carbohydrate by receptors in the oral cavity and on the tongue that activate reward and other centers in the brain leading to insulin secretion. After digestion, the secondary stage is the transport of monosaccharides from the small intestine into the systemic circulation. The passage of these monosaccharides is facilitated by the presence of various transport proteins. The intestinal mucosa has carbohydrate sensors that stimulate the release of two 'incretin' hormones (GIP and GLP-1) whose actions range from the secretion of insulin to appetite regulation. Most of the ingested carbohydrate is taken up by the liver resulting in a transient inhibition of hepatic glucose release in a dose-dependent manner. Nonetheless, the subsequent increased hepatic glucose (and lactate) output can increase exogenous carbohydrate oxidation rates by 40-50%. The recognition and successful distribution of carbohydrate to the brain and skeletal muscles to maintain carbohydrate oxidation as well as prevent hypoglycaemia underpins the mechanisms to improve exercise performance.

Effect of carbohydrate-protein supplementation on endurance training adaptations.

PURPOSE: To examine the influence of post-exercise protein feeding upon the adaptive response to endurance exercise training. METHODS: In a randomised parallel group design, 25 healthy men and women completed 6 weeks of endurance exercise training by running on a treadmill for 30-60 min at 70-75% maximal oxygen uptake (VO2max) 4 times/week. Participants ingested 1.6 g per kilogram of body mass (g kg BM-1) of carbohydrate (CHO) or an isocaloric carbohydrate-protein solution (CHO-P; 0.8 g carbohydrate kg BM-1 + 0.8 g protein kg BM-1) immediately and 1 h post-exercise. Expired gas, blood and muscle biopsy samples were taken at baseline and follow-up. RESULTS: Exercise training improved VO2max in both groups (p ≤ 0.001), but this increment was not different between groups either in absolute terms or relative to body mass (0.2 ± 0.2 L min-1 and 3.0 ± 2 mL kg-1 min-1, respectively). No change occurred in plasma albumin concentration from baseline to follow-up with CHO-P (4.18 ± 0.18 to 4.23 ± 0.17 g dL-1) or CHO (4.17 ± 0.17 to 4.12 ± 0.22 g dL-1; interaction: p > 0.05). Mechanistic target of rapamycin (mTOR) gene expression was up-regulated in CHO-P (+ 46%; p = 0.025) relative to CHO (+ 4%) following exercise training. CONCLUSION: Post-exercise protein supplementation up-regulated the expression of mTOR in skeletal muscle over 6 weeks of endurance exercise training. However, the magnitude of improvement in VO2max was similar between groups.

The day-to-day reliability of peak fat oxidation and FATMAX.

PURPOSE: Prior studies exploring the reliability of peak fat oxidation (PFO) and the intensity that elicits PFO (FATMAX) are often limited by small samples. This study characterised the reliability of PFO and FATMAX in a large cohort of healthy men and women. METHODS: Ninety-nine adults [49 women; age: 35 (11) years; [Formula: see text]O2peak: 42.2 (10.3) mL·kg BM-1·min-1; mean (SD)] completed two identical exercise tests (7-28 days apart) to determine PFO (g·min-1) and FATMAX (%[Formula: see text]O2peak) by indirect calorimetry. Systematic bias and the absolute and relative reliability of PFO and FATMAX were explored in the whole sample and sub-categories of: cardiorespiratory fitness, biological sex, objectively measured physical activity levels, fat mass index (derived by dual-energy X-ray absorptiometry) and menstrual cycle status. RESULTS: No systematic bias in PFO or FATMAX was found between exercise tests in the entire sample (- 0.01 g·min-1 and 0%[Formula: see text]O2peak, respectively; p > 0.05). Absolute reliability was poor [within-subject coefficient of variation: 21% and 26%; typical errors: ± 0.06 g·min-1 and × / ÷ 1.26%[Formula: see text]O2peak; 95% limits of agreement: ± 0.17 g·min-1 and × / ÷ 1.90%[Formula: see text]O2peak, respectively), despite high (r = 0.75) and moderate (r = 0.45) relative reliability for PFO and FATMAX, respectively. These findings were consistent across all sub-groups. CONCLUSION: Repeated assessments are required to more accurately determine PFO and FATMAX.

Physiological responses to maximal eating in men.

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

Frequent Carbohydrate Ingestion Reduces Muscle Glycogen Depletion and Postpones Fatigue Relative to a Single Bolus.

The timing of carbohydrate ingestion and how this influences net muscle glycogen utilization and fatigue has only been investigated in prolonged cycling. Past findings may not translate to running because each exercise mode is distinct both in the metabolic response to carbohydrate ingestion and in the practicalities of carbohydrate ingestion. To this end, a randomized, cross-over design was employed to contrast ingestion of the same sucrose dose either at frequent intervals (15 × 5 g every 5 min) or at a late bolus (1 × 75 g after 75 min) during prolonged treadmill running to exhaustion in six well-trained runners (V˙O2max 61 ± 4 ml·kg-1·min-1). The muscle glycogen utilization rate was lower in every participant over the first 75 min of running (Δ 0.51 mmol·kg dm-1·min-1; 95% confidence interval [-0.02, 1.04] mmol·kg dm-1·min-1) and, subsequently, all were able to run for longer when carbohydrate had been ingested frequently from the start of exercise compared with when carbohydrate was ingested as a single bolus toward the end of exercise (105.6 ± 3.0 vs. 96.4 ± 5.0 min, respectively; Δ 9.3 min, 95% confidence interval [2.8, 15.8] min). A moderate positive correlation was apparent between the magnitude of glycogen sparing over the first 75 min and the improvement in running capacity (r = .58), with no significant difference in muscle glycogen concentrations at the point of exhaustion. This study indicates that failure to ingest carbohydrates from the outset of prolonged running increases reliance on limited endogenous muscle glycogen stores-the ergolytic effects of which cannot be rectified by subsequent carbohydrate ingestion late in exercise.

Co-ingestion of whey protein hydrolysate with milk minerals rich in calcium potently stimulates glucagon-like peptide-1 secretion: an RCT in healthy adults.

PURPOSE: To examine whether calcium type and co-ingestion with protein alter gut hormone availability. METHODS: Healthy adults aged 26 ± 7 years (mean ± SD) completed three randomized, double-blind, crossover studies. In all studies, arterialized blood was sampled postprandially over 120 min to determine GLP-1, GIP and PYY responses, alongside appetite ratings, energy expenditure and blood pressure. In study 1 (n = 20), three treatments matched for total calcium content (1058 mg) were compared: calcium citrate (CALCITR); milk minerals rich in calcium (MILK MINERALS); and milk minerals rich in calcium plus co-ingestion of 50 g whey protein hydrolysate (MILK MINERALS + PROTEIN). In study 2 (n = 6), 50 g whey protein hydrolysate (PROTEIN) was compared to MILK MINERALS + PROTEIN. In study 3 (n = 6), MILK MINERALS was compared to the vehicle of ingestion (water plus sucralose; CONTROL). RESULTS: MILK MINERALS + PROTEIN increased GLP-1 incremental area under the curve (iAUC) by ~ ninefold (43.7 ± 11.1 pmol L-1 120 min; p < 0.001) versus both CALCITR and MILK MINERALS, with no difference detected between CALCITR (6.6 ± 3.7 pmol L-1 120 min) and MILK MINERALS (5.3 ± 3.5 pmol L-1 120 min; p > 0.999). MILK MINERALS + PROTEIN produced a GLP-1 iAUC ~ 25% greater than PROTEIN (p = 0.024; mean difference: 9.1 ± 6.9 pmol L-1 120 min), whereas the difference between MILK MINERALS versus CONTROL was small and non-significant (p = 0.098; mean difference: 4.2 ± 5.1 pmol L-1 120 min). CONCLUSIONS: When ingested alone, milk minerals rich in calcium do not increase GLP-1 secretion compared to calcium citrate. Co-ingesting high-dose whey protein hydrolysate with milk minerals rich in calcium increases postprandial GLP-1 concentrations to some of the highest physiological levels ever reported. Registered at ClinicalTrials.gov: NCT03232034, NCT03370484, NCT03370497.

An additional bolus of rapid-acting insulin to normalise postprandial cardiovascular risk factors following a high-carbohydrate high-fat meal in patients with type 1 diabetes: A randomised controlled trial.

AIM: To evaluate an additional rapid-acting insulin bolus on postprandial lipaemia, inflammation and pro-coagulation following high-carbohydrate high-fat feeding in people with type 1 diabetes. METHODS: A total of 10 males with type 1 diabetes [HbA1c 52.5 ± 5.9 mmol/mol (7.0% ± 0.5%)] underwent three conditions: (1) a low-fat (LF) meal with normal bolus insulin, (2), a high-fat (HF) meal with normal bolus insulin and (3) a high-fat meal with normal bolus insulin with an additional 30% insulin bolus administered 3-h post-meal (HFA). Meals had identical carbohydrate and protein content and bolus insulin dose determined by carbohydrate-counting. Blood was sampled periodically for 6-h post-meal and analysed for triglyceride, non-esterified-fatty acids, apolipoprotein B48, glucagon, tumour necrosis factor alpha, fibrinogen, human tissue factor activity and plasminogen activator inhibitor-1. Continuous glucose monitoring captured interstitial glucose responses. RESULTS: Triglyceride concentrations following LF remained similar to baseline, whereas triglyceride levels following HF were significantly greater throughout the 6-h observation period. The additional insulin bolus (HFA) normalised triglyceride similarly to low fat 3-6 h following the meal. HF was associated with late postprandial elevations in tumour necrosis factor alpha, whereas LF and HFA was not. Fibrinogen, plasminogen activator inhibitor-1 and tissue factor pathway levels were similar between conditions. CONCLUSION: Additional bolus insulin 3 h following a high-carbohydrate high-fat meal prevents late rises in postprandial triglycerides and tumour necrosis factor alpha, thus improving cardiovascular risk profile.

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.

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.

Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation.

The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1 h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 ± 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1ß and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1ß and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation.

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.