Tanya M. Halliday

The effect of prebiotic supplementation with inulin on cardiometabolic health: Rationale, design, and methods of a controlled feeding efficacy trial in adults at risk of type 2 diabetes

Prediabetes is associated with low-grade chronic inflammation that increases the risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). An elevated lipopolysaccharide concentration, associated with dysbiosis of the intestinal microbiota, has been implicated in the development of both T2D and CVD. Selective modulation of the intestinal microbiota with prebiotics reduces intestinal permeability and endotoxin concentrations, inflammation, and metabolic dysfunction in rodents. The effect of prebiotic supplementation on cardio-metabolic function in humans at risk for T2D is not known. The primary aim of this trial is to determine the influence of prebiotic supplementation with inulin on insulin sensitivity and skeletal muscle metabolic flexibility in adults at risk for T2D. We hypothesize that prebiotic supplementation with inulin will improve insulin sensitivity and skeletal muscle metabolic flexibility. We will randomize 48 adults (40-75 yrs) with prediabetes or a score ≥ 5 on the American Diabetes Association (ADA) risk screener to 6 weeks of prebiotic supplementation with inulin (10 g/day) or placebo. Subjects will be provided with all food for the duration of the study, to avoid potential confounding through differences in dietary intake between individuals. Intestinal permeability, serum endotoxin concentrations, insulin sensitivity, skeletal muscle metabolic flexibility, endothelial function, arterial stiffness, and fecal bacterial composition will be measured at baseline and following treatment. The identification of prebiotic supplementation with inulin as an efficacious strategy for reducing cardio-metabolic risk in individuals at risk of T2D could impact clinical practice by informing dietary recommendations and increasing acceptance of prebiotics by the scientific and medical community.

Resist diabetes: A randomized clinical trial for resistance training maintenance in adults with prediabetes

Objective To determine whether a social cognitive theory (SCT)-based intervention improves resistance training (RT) maintenance and strength, and reduces prediabetes prevalence. Research design and methods Sedentary, overweight/obese (BMI: 25–39.9 kg/m2) adults aged 50–69 (N = 170) with prediabetes participated in the 15-month trial. Participants completed a supervised 3-month RT (2×/wk) phase and were randomly assigned (N = 159) to one of two 6-month maintenance conditions: SCT or standard care. Participants continued RT at a self-selected facility. The final 6-month period involved no contact. Assessments occurred at baseline and months 3, 9, and 15. The SCT faded-contact intervention consisted of nine tailored transition (i.e., supervised training to training alone) and nine follow-up sessions. Standard care involved six generic follow-up sessions. Primary outcomes were prevalence of normoglycemia and muscular strength. Results The retention rate was 76%. Four serious adverse events were reported. After 3 months of RT, 34% of participants were no longer prediabetic. This prevalence of normoglycemia was maintained through month 15 (30%), with no group difference. There was an 18% increase in the odds of being normoglycemic for each % increase in fat-free mass. Increases in muscular strength were evident at month 3 and maintained through month 15 (P<0.001), which represented improvements of 21% and 14% for chest and leg press, respectively. Results did not demonstrate a greater reduction in prediabetes prevalence in the SCT condition. Conclusions Resistance training is an effective, maintainable strategy for reducing prediabetes prevalence and increasing muscular strength. Future research which promotes RT initiation and maintenance in clinical and community settings is warranted. Trial Registration ClinicalTrials.gov NCT01112709.

Resistance training is associated with spontaneous changes in aerobic physical activity but not overall diet quality in adults with prediabetes

BACKGROUND Aerobic exercise interventions have been shown to result in alterations to dietary intake and non-exercise physical activity (PA). To date, the ability for resistance training (RT) to influence other health-related behaviors has not been examined. This study aimed to determine if initiation and maintenance of RT is associated with spontaneous changes in dietary quality and non-RT PA in adults with prediabetes. METHODS Overweight/obese adults (n=170, BMI=32.9±3.8kg·m2, age=59.5±5.5years, 73% female) with prediabetes were enrolled in the 15-month Resist Diabetes trial. Participants completed a supervised 3-month RT initiation phase followed by a 6-month maintenance phase and a 6-month no-contact phase. Participants were not encouraged to change eating or non-RT PA behaviors. At baseline, and months 3, 9, and 15, three 24-hour diet recalls were collected to evaluate dietary intake and quality, the Aerobics Institute Longitudinal Study Questionnaire was completed to evaluate non-RT PA, and body mass, body composition (DXA), and muscular strength were measured. At months 3, 9, and 15 social cognitive theory (SCT) constructs were assessed with a RT Health Beliefs Questionnaire. Mixed effects models were used to assess changes in dietary intake and non-RT PA over the 15-month study period. RESULTS Energy and carbohydrate intake decreased with RT initiation and maintenance phases (baseline to month 9: β=-87.9, p=0.015 and β=-16.3, p<0.001, respectively). No change in overall dietary quality (Healthy Eating Index [HEI]-2010 score: β=-0.13, p=0.722) occurred, but alterations in HEI-2010 sub-scores were detected. Maintenance of RT was accompanied by an increase in MET-min/week of total non-RT PA (month 3 to month 9: β=146.2, p=0.01), which was predicted by increased self-regulation and decreased negative outcome expectancies for RT (β=83.7, p=0.014 and β=-70.0, p=0.038, respectively). CONCLUSIONS Initiation and maintenance of RT may be a gateway behavior leading to improvements in other health-related behaviors. These results provide rationale for single-component lifestyle interventions as an alternative to multi-component interventions, when resources are limited.

Skeletal muscle autophagy and mitophagy in endurance-trained runners before and after a high-fat meal

Objective We tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). Methods Muscle biopsies were collected to determine differences in autophagy and mitophagy protein markers and metabolic flexibility under fasting conditions and 4 h following a HFM between endurance-trained male runners (n = 10) and sedentary, non-obese controls (n = 9). Results Maximal oxygen consumption (ml·kg·min−1) was approximately 50% higher (p < 0.05) in endurance-trained runners compared with sedentary controls (65.8 ± 2.3 and 43.1 ± 3.4, respectively). Autophagy markers were similar between groups. Mitophagy and mitochondrial dynamics protein markers were significantly higher in skeletal muscle of endurance-trained runners compared with sedentary controls in the fasted state, although unaffected by the HFM. Skeletal muscle metabolic flexibility was similar between groups when fasted (p > 0.05), but increased in response to the HFM in endurance-trained athletes only (p < 0.005). Key mitophagy markers, phospho-Pink1Thr257 and phospho-ParkinS65 (r = 0.64, p < 0.005), and phospo-ParkinSer65 and phospho-Drp1Ser616 (r = 0.70, p < 0.05) were correlated only within the endurance-trained group. Autophagy and mitophagy markers were not correlated with metabolic flexibility. Conclusion In summary, mitophagy may be enhanced in endurance-trained runners based on elevated markers of mitophagy and mitochondrial dynamics. The HFM did not alter autophagy or mitophagy in either group. The absence of a relationship between mitophagy markers and metabolic flexibility suggests that mitophagy is not a key determinant of metabolic flexibility in a healthy population, but further investigation is warranted.

Sodium Intake and Blood Pressure: New Controversies, New Labels . . . New Guidelines?

H YPERTENSION AND PREHYPERTENSION ARE highly prevalent; these conditions are present in 29% and 36% of US adults aged 18 and older, respectively. Among adults aged 60 years and older, hypertension prevalence rises to about two-thirds of US adults (ie, 65%). Of individuals with hypertension, only about half (ie, 52%) have their blood pressure adequately controlled to 4,945 mg/day). The authors reported a U-shaped relation, meaning that the lowest risk of mortality and cardiovascular events was associated with the usual sodium intake level, which is above the US recommended intake of 2,300 mg/day. The American Heart Association issued a response, stating “Reduced salt intake critical,” and called the review by Graudal and colleagues flawed, in that study populations were not representative of the general population, but rather those with poor health, and that unreliable measurements of sodium intake (eg, self-reported dietary intake, spot urine secretions) were used. Within weeks, He and colleagues published results from the Health Survey for England, which attributed significant reductions in blood pressure, stroke, and ischemic heart disease mortality during an 8-year period to a 15% reduction in salt intake during this time period. Salt intake was assessed using an objective indicator (ie, biomarker) of sodium intake, 24-hour urinary sodium excretion, which was verified for completeness using para-aminobenzoic acid. Despite this strength, a limitation of

Urinary Excretion of Sodium, Nitrogen, and Sugar Amounts Are Valid Biomarkers of Dietary Sodium, Protein, and High Sugar Intake in Nonobese Adolescents

Background: Objective indicators of dietary intake (e.g., biomarkers) are needed to overcome the limitations of self-reported dietary intake assessment methods in adolescents. To our knowledge, no controlled feeding studies to date have evaluated the validity of urinary sodium, nitrogen, or sugar excretion as dietary biomarkers in adolescents.Objective: This investigation aimed to evaluate the validity of urinary sodium, nitrogen, and total sugars (TS) excretion as biomarkers for sodium, protein, and added sugars (AS) intake in nonobese adolescents.Methods: In a crossover controlled feeding study design, 33 adolescents [12-18 y of age, 47 ± 25th percentile (mean ± SD) of body mass index (BMI; in kg/m2) for age] consumed 5% AS [low added sugars (LAS)] and 25% AS [high added sugars (HAS)] isocaloric, macronutrient-matched (55% carbohydrate, 30% fat, and 15% protein) diets for 7 d each, in a randomly assigned order, with a 4-wk washout period between diets. On the final 2 d of each diet period, 24-h urine samples were collected. Thirty-two adolescents completed all measurements (97% retention).Results: Urinary sodium was not different from the expected 90% recovery (mean ± SD: 88% ± 18%, P = 0.50). Urinary nitrogen was correlated with protein intake (r = 0.69, P < 0.001), although it was below the 80% expected recovery (62% ± 7%, P < 0.001). Urinary TS values were correlated with AS intake during the HAS diet (r = 0.77, P < 0.001) and had a higher R2 value of 0.28 than did AS intake (R2 = 0.36). TS excretion differed between LAS (0.226 ± 0.09 mg/d) and HAS (0.365 ± 0.16 mg/d) feeding periods (P < 0.001).Conclusions: Urinary sodium appears to be a valid biomarker for sodium intake in nonobese adolescents. Urinary nitrogen is associated with protein intake, but nitrogen excretion rates were less than previously reported for adults, possibly owing to adolescent growth rates. TS excretion reflects AS at 25% AS intake and was responsive to the change in AS intake. Thus, urinary biomarkers are promising objective indicators of dietary intake in adolescents, although larger-scale feeding trials are needed to confirm these findings. This trial was registered at clinicaltrials.gov as NCT02455388.

Dietary Intake, Body Composition, and Menstrual Cycle Changes during Competition Preparation and Recovery in a Drug-Free Figure Competitor: A Case Study

Physique competitions are events in which competitors are judged on muscular appearance and symmetry. The purpose of this retrospective case study was to describe changes in dietary intake, body mass/composition, and the menstrual cycle during the 20-week competition preparation (PREP) and 20-week post competition recovery (REC) periods of a drug-free amateur female figure competitor (age = 26–27, BMI = 19.5 kg/m2). Dietary intake (via weighed food records) and body mass were assessed daily and averaged weekly. Body composition was estimated via Dual-energy X-ray absorptiometry (DXA) and 7-site skinfold measurements. Energy intake, body mass and composition, and energy availability decreased during the 20-week PREP period (changes of ~298 kcals, 5.1 kg, 6.5% body fat, and 5.4 kcal/kg fat free mass, respectively) and returned to baseline values by end of the 20-week REC period. Menstrual cycle irregularity was reported within the first month of PREP and the last menstruation was reported at week 11 of PREP. Given the potentially adverse health outcomes associated with caloric restriction, future, prospective cohort studies on the physiological response to PREP and REC are warranted in drug-free, female physique competitors.

Short-term changes in added sugar consumption by adolescents reflected in the carbon isotope ratio of fingerstick blood:

Background: Consumption of added sugars (AS) and sugar-sweetened beverages (SSB) may adversely affect adolescents’ weight and cardiovascular disease risk. Reliance on self-reported dietary assessment methods is a common research limitation, which could be overcome by dietary intake biomarkers. Aim: The investigation was a proof-of-concept study to evaluate the proposed carbon isotope ratio (δ13C) biomarker of AS intake in adolescents, using a controlled feeding design. Methods: Participants (n = 33, age 15.3 years, 53% female) underwent two seven-day controlled feeding periods in a randomly assigned order. Diets were matched in composition except for AS content (5% or 25% of total energy). Fasting fingerstick blood samples were collected daily during each diet period. Results: Fingerstick δ13C values changed from day 1 to 8 by –0.05 ± 0.071‰ on 5% AS, and +0.03 ± 0.083‰ on 25% AS (p ≤ 0.001). Reliability was demonstrated between day 7 and 8 δ13C values on the 5% (ICC = 0.996, p ≤ 0.001) and 25% (ICC = 0.997, p ≤ 0.001) AS diets. Conclusions: Larger scale investigations are warranted to determine if this technique could be applied to population-level research in order to help assess the effectiveness of interventions aimed at reducing the consumption of AS or SSB intake.