Gut microbiota of Type 1 diabetes patients with good glycaemic control and high physical fitness is similar to people without diabetes: an observational study.

AIM: Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes. METHODS: Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units. RESULTS: Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group. CONCLUSIONS: We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes.

Breakfast consumption and exercise interact to affect cognitive performance and mood later in the day. A randomized controlled trial.

The current study assessed the interactive effect of breakfast and exercise on cognition and mood. Twelve active males completed four trials; no breakfast-rest, breakfast-rest, no breakfast-exercise or breakfast-exercise in a randomized, cross-over design. The trials consisted of; breakfast or fast, a 2h rest, exercise (treadmill run) or equivalent rest, a chocolate milk drink, a 90 min rest and an ad libitum lunch. Cognitive performance and mood were recorded frequently throughout each trial. Data was analysed as pre-exercise/rest, during and immediately post exercise/rest and post-drink. No effects were found prior to consumption of the drink. Post-drink, fasting before exercise increased mental fatigue compared to consuming breakfast before exercise and fasting before rest. Tension increased when breakfast was consumed at rest and when exercise was undertaken fasted compared to omitting breakfast before rest. Breakfast before rest decreased rapid visual information processing task speed and impaired Stroop performance. Breakfast omission improved Four Choice Reaction Time performance. To conclude, breakfast before exercise appeared beneficial for post-exercise mood even when a post-exercise snack was consumed. Exercise reversed post-breakfast cognitive impairment in active males.

Acute and chronic effects of multivitamin/mineral supplementation on objective and subjective energy measures.

BACKGROUND: Vitamins and minerals play an essential role within many cellular processes including energy production and metabolism. Previously, supplementation with a multivitamin/mineral (MVM) for ≥28 days resulted in improvements to cognition and subjective state. We have also demonstrated shifts in metabolism during cognitively demanding tasks following MVM in females, both acutely and following 8-week supplementation. The current study aimed to assess these effects further in males and females using metabolically challenging exercise and cognitive tasks. METHODS: The current randomised, placebo-controlled, parallel groups study investigated the effects of a MVM complex in 82 healthy young (18-35y) exercisers. Subjective ratings and substrate metabolism were assessed during 30 min each of increasingly effortful incremental exercise and demanding cognitive tasks. Assessments took place on acute study days following a single dose (Day 1) of MVM, containing 3 times recommended daily allowance of water-soluble vitamins plus CoQ10, and following 4-week supplementation (Day 28). RESULTS: Energy expenditure (EE) was increased during cognitive tasks following MVM across Day 1 and Day 28, with greater effects in males. In males, MVM also increased carbohydrate oxidation and energy expenditure during exercise across Day 1 and Day 28. In females, mental tiredness was lower during exercise; increases in physical tiredness following 30 min of exercise were attenuated; and stress ratings following cognitive tasks were reduced following MVM. In males, MVM only lowered mental tiredness following 10 min of exercise. These effects were apparent irrespective of day, but effects on mental tiredness were greater on Day 28. Ferritin levels were also higher on Day 28 in those receiving MVM. CONCLUSION: These findings extend on existing knowledge, demonstrating increased carbohydrate oxidation and increased energy expenditure in males following MVM supplementation for the first time. Importantly, they show modulation of energy expenditure and subjective tiredness following a single dose, providing further evidence for acute effects of MVM. Differential effects in men and women suggest that sex may play an important role in the effects of MVM on energy metabolism and should be considered in future research. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03003442. Registered 22nd November 2016 - retrospectively registered.

Protein for Life: Towards a focussed dietary framework for healthy ageing.

'Ageing well' has been highlighted as an important research area by the World Health Organization. In the UK, healthy ageing has been identified as a priority research area by multiple Research Councils and is a key NHS priority. Sarcopaenia, the decline of muscle mass/strength and a key component of healthy ageing, can have a major impact on quality of life and is associated with premature mortality. Increasing protein intake at all stages of the life course may help to reduce the rate of muscle decline and the onset of associated health conditions. However, there is a lack of understanding of the social, demographic and psychological drivers of food choices surrounding protein intake. This report describes the multidisciplinary approach that has been adopted by the Protein for Life project to create a framework for the development of palatable, cost-effective higher-protein foods suitable for an ageing population.

The influence of calcium supplementation on substrate metabolism during exercise in humans: a randomized controlled trial.

BACKGROUND/OBJECTIVES: High calcium intakes enhance fat loss under restricted energy intake. Mechanisms explaining this may involve reduced dietary fat absorption, enhanced lipid utilization and (or) reductions in appetite. This study aimed to assess the impact of 2 weeks of calcium supplementation on substrate utilization during exercise and appetite sensations at rest. SUBJECTS/METHODS: Thirteen physically active males completed two 14-d supplemental periods, in a double-blind, randomized crossover design separated by a ⩾4-week washout period. During supplementation, a test-drink was consumed daily containing 400 and 1400 mg of calcium during control (CON) and high-calcium (CAL) periods, respectively. Cycling-based exercise tests were conducted before and after each supplemental period to determine substrate utilization rates and circulating metabolic markers (non-esterified fatty acid, glycerol, glucose and lactate concentrations) across a range of exercise intensities. Visual analog scales were completed in the fasting, rested state to determine subjective appetite sensations. RESULTS: No significant differences between supplements were observed in lipid or carbohydrate utilization rates, nor in circulating metabolic markers (both P>0.05). Maximum rates of lipid utilization were 0.47±0.05 and 0.44±0.05 g/min for CON and CAL, respectively, prior to supplementation and 0.44±0.05 and 0.42±0.05 g/min, respectively, post-supplementation (main effects of time, supplement and time x supplement interaction effect all P>0.05). Furthermore, no significant differences were detected in any subjective appetite sensations (all P>0.05). CONCLUSIONS: Two weeks of calcium supplementation does not influence substrate utilization during exercise in physically active males.

Effect of calcium intake on fat oxidation in adults: a meta-analysis of randomized, controlled trials.

Calcium intake is likely to increase body fat loss during energy restriction. Part of this effect may be explained by increased fat oxidation in the presence of a similar energy balance, yet studies have not provided a conclusive answer. Therefore a meta-analysis was performed to determine whether chronic or acute high calcium intake increases fat oxidation. Randomized controlled trials of high calcium intake in human adults where measures of fat oxidation were taken were included. A random-effects meta-analysis was performed on outcomes expressed as standardized mean differences. Chronic high calcium intake increased fat oxidation by a standardized mean difference of 0.42 (95% confidence intervals: 0.14, 0.69; P= 0.003; estimated to correspond to an 11% increase), displaying low heterogeneity (I(2) = 18%), which was more prominent when habitual calcium intake was low (<700 mg d(-1) ). Acute high calcium intake increased fat oxidation by a standardized mean difference of 0.41 (0.04, 0.77; P = 0.03), with low heterogeneity (I(2) = 19%), yet sensitivity analysis revealed that this effect was relatively weak. In conclusion, chronic high calcium intake is likely to increase rates of fat oxidation. The effects of acute high calcium intake appear to point in the same direction, but further work is needed to permit a greater degree of certainty.

Effect of breakfast glycemic index on metabolic responses during rest and exercise in overweight and non-overweight adolescent girls.

BACKGROUND/OBJECTIVES: The metabolic responses to mixed breakfast meals with different glycemic indexes (GI) and their effects on substrate metabolism during exercise in adolescent girls have not been examined. The interaction with weight status also warrants investigation. This study investigated the effect of mixed breakfast meals containing high GI (HGI) or low GI (LGI) carbohydrates on metabolic responses and fat oxidation during rest and exercise in overweight (OW) and non-overweight (NO) adolescent girls. SUBJECTS/METHODS: A total of 8 OW and 12 NO adolescent girls consumed an isoenergetic HGI (GI=73) or LGI (GI=44) breakfast 120 min before completing a 30-min treadmill walk at 50% \[Vdot]O(2peak). RESULTS: Peak blood glucose concentration was higher for HGI compared with LGI in OW (P=0.023), but not NO (P>0.05) girls. Blood glucose total area under the curve (TAUC) was 13% higher in HGI compared with LGI in OW (P=0.006), but only 4% higher in NO (P=0.072) girls. Plasma insulin data were log(e) transformed (lninsulin). Plasma lninsulin concentrations were not different between HGI and LGI (P>0.05). Peak plasma lninsulin concentration (P=0.016) and TAUC (P=0.001) were greater in OW than NO girls. Fat oxidation during postprandial rest and exercise was not different between breakfasts (P>0.05). CONCLUSIONS: The elevated glycemic response in HGI compared with LGI was more pronounced in OW girls, suggesting a reduced ability to cope with the metabolic demands of the HGI, but not LGI, breakfast. Manipulation of breakfast GI did not alter fat oxidation during rest or subsequent moderate intensity exercise in OW and NO adolescent girls.

Dietary glycemic index influences lipid oxidation but not muscle or liver glycogen oxidation during exercise.

The glycemic index (GI) of dietary carbohydrates influences glycogen storage in skeletal muscle and circulating nonesterified fatty acid (NEFA) concentrations. We hypothesized that diets differing only in GI would alter intramuscular lipid oxidation and glycogen usage in skeletal muscle and liver during subsequent exercise. Endurance-trained individuals (n = 9) cycled for 90 min at 70% Vo(2peak) and then consumed either high- or low-GI meals over the following 12 h. The following day after an overnight fast, the 90-min cycle was repeated. (1)H and (13)C magnetic resonance spectroscopy was used before and after exercise to assess intramuscular lipid and glycogen content of the vastus muscle group and liver. Blood and expired air samples were collected at 15-min intervals throughout exercise. NEFA availability was reduced during exercise in the high- compared with the low-GI trial (area under curve 44.5 +/- 6.0 vs. 38.4 +/- 7.30 mM/h, P < 0.05). Exercise elicited an approximately 55% greater reduction in intramyocellular triglyceride (IMCL) in the high- vs. low-GI trial (1.6 +/- 0.2 vs. 1.0 +/- 0.3 mmol/kg wet wt, P < 0.05). There was no difference in the exercise-induced reduction of the glycogen pool in skeletal muscle (76 +/- 8 vs. 68 +/- 5 mM) or in liver (65 +/- 8 vs. 71 +/- 4 mM) between the low- and high-GI trials, respectively. High-GI recovery diets reduce NEFA availability and increase reliance on IMCL during moderate-intensity exercise. Skeletal muscle and liver glycogen storage or usage are not affected by the GI of an acute recovery diet.

Identification of weight-bearing-responsive elements in the skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) gene.

The skeletal muscle sarco(endo)plasmic reticulum calcium ATPase (SERCA1) gene is transactivated as early as 2 days after the removal of weight-bearing (Peters, D. G., Mitchell-Felton, H., and Kandarian, S. C. (1999) Am. J. Physiol. 276, C1218-C1225), but the transcriptional mechanisms are elusive. Here, the rat SERCA1 5' flank and promoter region (-3636 to +172 base pairs) was comprehensively examined using in vivo somatic gene transfer into rat soleus muscles (n = 804) to identify region(s) that are both necessary and sufficient for sensitivity to weight-bearing. In all, 40 different SERCA1 reporter plasmids were constructed and tested. Several different regions of the SERCA1 5' flank were sufficient to confer a transcriptional response to 7 days of muscle unloading when placed upstream of a heterologous promoter. Two of these regions were analyzed further because they were necessary for the unloading response of -3636 to +172, as demonstrated using internal deletion constructs. Deletion analysis of these regions (-1373 to -1158 and -330 to +172) suggested that unloading responsiveness corresponded to CACC sites and E-boxes. Mutagenesis of cis-elements in the first region showed that a specific CACC box (-1262) was involved in SERCA1 transactivation and a nearby E-box (-1248) was also implicated. Constructs containing trimerized CACC sites and E-boxes showed that the presence of both elements is required to activate transcription. This is the first identification of specific cis-elements required for the regulation of a Ca(2+) handling gene by changes in muscle loading condition.

The calcineurin-NFAT pathway and muscle fiber-type gene expression.

To test for a role of the calcineurin-NFAT (nuclear factor of activated T cells) pathway in the regulation of fiber type-specific gene expression, slow and fast muscle-specific promoters were examined in C2C12 myotubes and in slow and fast muscle in the presence of calcineurin or NFAT2 expression plasmids. Overexpression of active calcineurin in myotubes induced both fast and slow muscle-specific promoters but not non-muscle-specific reporters. Overexpression of NFAT2 in myotubes did not activate muscle-specific promoters, although it strongly activated an NFAT reporter. Thus overexpression of active calcineurin activates transcription of muscle-specific promoters in vitro but likely not via the NFAT2 transcription factor. Slow myosin light chain 2 (MLC2) and fast sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) reporter genes injected into rat soleus (slow) and extensor digitorum longus (EDL) (fast) muscles were not activated by coinjection of activated calcineurin or NFAT2 expression plasmids. However, an NFAT reporter was strongly activated by overexpression of NFAT2 in both muscle types. Calcineurin and NFAT protein expression and binding activity to NFAT oligonucleotides were different in slow vs. fast muscle. Taken together, these results indicate that neither calcineurin nor NFAT appear to have dominant roles in the induction and/or maintenance of slow or fast fiber type in adult skeletal muscle. Furthermore, different pathways may be involved in muscle-specific gene expression in vitro vs. in vivo.