A High-Fat Compared with a High-Carbohydrate Breakfast Enhances 24-Hour Fat Oxidation in Older Adults.

Background: The ability to oxidize fat is associated with a lower risk of chronic metabolic disease. Preclinical data in mice showed that a high-fat "breakfast" increased 24-h fat oxidation relative to a high-carbohydrate breakfast. Objectives: The objectives of this study were to determine whether the timing of macronutrient intake in humans affects daily fuel utilization and to examine associations between fuel utilization and metabolic indexes. Methods: Participants were 29 healthy sedentary men and women (aged 55-75 y) with a body mass index (kg/m2) between 25 and 35. Participants were randomly assigned to receive either a high-fat breakfast (FB; 35% carbohydrate, 20% protein, 45% fat; n = 13) or a high-carbohydrate breakfast (CB; 60% carbohydrate, 20% protein, 20% fat; n = 16) for 4 wk while consuming a "neutral" lunch and dinner. Twenty-four-hour and postprandial respiratory quotients (RQs) were measured by whole-room indirect calorimetry. Insulin and glucose measures including insulin sensitivity were determined by an oral-glucose-tolerance test. Measures were taken at baseline and after the 4-wk intervention. Group-by-time interactions were determined by 2-factor repeated-measures mixed-model ANOVA. Pearson's correlation analyses were used to determine associations of 24-h RQs with metabolic measures after the intervention. Results: There was a significant group-by-time interaction for change in the 24-h RQ [FB (mean ± SD): 0.88 ± 0.02 to 0.86 ± 0.02; CB: 0.88 ± 0.02 for both; P < 0.05], breakfast RQ (FB: 0.88 ± 0.03 to 0.86 ± 0.03; CB: 0.89 ± 0.02 to 0.90 ± 0.02; P < 0.01), and lunch RQ (FB: 0.089 ± 0.03 to 0.85 ± 0.03; CB: 0.89 ± 0.03 for both; P < 0.01). In the CB group at follow-up, 24-h RQ was positively associated with fasting glucose (r = 0.66, P < 0.05), glucose area under the curve (AUC) (r = 0.51, P < 0.05), and insulin AUC (r = 0.52, P < 0.05) and inversely associated with insulin sensitivity (r = -0.51, P < 0.05). Conclusions: The macronutrient composition of breakfast affects substrate utilization throughout the day in older adults. The consumption of a high-fat, lower-carbohydrate breakfast may reduce the risk of metabolic disease. This trial was registered at www.clinicaltrials.gov as NCT03164200.

Erratum to: Baseline insulin sensitivity affects response to high-amylose maize resistant starch in women: a randomized, controlled trial.

[This corrects the article DOI: 10.1186/s12986-016-0062-5.].

Baseline insulin sensitivity affects response to high-amylose maize resistant starch in women: a randomized, controlled trial.

BACKGROUND: Resistant starch (RS) is a type of dietary fiber that can improve glucose metabolism, but its effects may be modulated by sex or baseline insulin sensitivity. This study was designed to examine the effect of high-amylose maize resistant starch (HAM-RS2) on insulin sensitivity (SI) in women, and to determine if SI status affects the response to RS. METHODS: This was a randomized, placebo-controlled, double-blind, cross-over study. Participants were 40 healthy, non-diabetic women aged 22-67 years in the normal-weight to obese BMI range (20.6-47.4 kg/m(2)). Two doses of HAM-RS2 were tested, 15 and 30 g per day, administered in the form of cookies. Participants were randomized to the order in which they received the experimental and placebo product. Each arm was 4 weeks, with a 4-week wash-out period in between. SI was assessed at the end of each 4-week arm of product consumption by frequently-sampled, insulin-modified, intravenous glucose tolerance test and minimal modeling. Participants were categorized as being insulin resistant (IR; SI < 7.8) or insulin sensitive (IS; SI ≥ 7.8) based on Gaussian analysis. The effect of treatment arm on SI was examined by mixed-model analysis within IR and IS sub-groups, using all available data. In addition, SI was examined by ANOVA among just those women who completed all three arms of the study with valid SI results. RESULTS: Among IR participants, SI was on average ~16 % higher after the 30 g arm when compared to the control arm by mixed-model analysis (n = 40, P < 0.05), and tended to be 23 % higher by ANOVA among women who completed all arms (n = 23, P = 0.06). HAM-RS2 did not affect SI in IS women. CONCLUSION: Consumption of HAM-RS2 at 30 g/day in the form of a snack food item was associated with improved insulin sensitivity in women with insulin resistance. CLINICAL TRIALS REGISTRY NUMBER: NCT0152806.

High Intensity Interval- vs Moderate Intensity- Training for Improving Cardiometabolic Health in Overweight or Obese Males: A Randomized Controlled Trial.

PURPOSE: To compare the effects of six weeks of high intensity interval training (HIIT) vs continuous moderate intensity training (MIT) for improving body composition, insulin sensitivity (SI), blood pressure, blood lipids, and cardiovascular fitness in a cohort of sedentary overweight or obese young men. We hypothesized that HIIT would result in similar improvements in body composition, cardiovascular fitness, blood lipids, and SI as compared to the MIT group, despite requiring only one hour of activity per week compared to five hours per week for the MIT group. METHODS: 28 sedentary overweight or obese men (age, 20 ± 1.5 years, body mass index 29.5 ± 3.3 kg/m2) participated in a six week exercise treatment. Participants were randomly assigned to HIIT or MIT and evaluated at baseline and post-training. DXA was used to assess body composition, graded treadmill exercise test to measure cardiovascular fitness, oral glucose tolerance to measure SI, nuclear magnetic resonance spectroscopy to assess lipoprotein particles, and automatic auscultation to measure blood pressure. RESULTS: A greater improvement in VO2peak was observed in MIT compared to HIIT (11.1% vs 2.83%, P = 0.0185) in the complete-case analysis. No differences were seen in the intention to treat analysis, and no other group differences were observed. Both exercise conditions were associated with temporal improvements in % body fat, total cholesterol, medium VLDL, medium HDL, triglycerides, SI, and VO2peak (P < 0.05). CONCLUSION: Participation in HIIT or MIT exercise training displayed: 1) improved SI, 2) reduced blood lipids, 3) decreased % body fat, and 4) improved cardiovascular fitness. While both exercise groups led to similar improvements for most cardiometabolic risk factors assessed, MIT led to a greater improvement in overall cardiovascular fitness. Overall, these observations suggest that a relatively short duration of either HIIT or MIT training may improve cardiometabolic risk factors in previously sedentary overweight or obese young men, with no clear advantage between these two specific regimes (Clinical Trial Registry number NCT01935323). TRIAL REGISTRATION: ClinicalTrials.gov NCT01935323.

The Risk for Cardiovascular Events Associated with Hyperlipdemia among Patients with and Without Rheumatoid Arthritis.

OBJECTIVES: To determine, using data from a real-world setting, the overall and sex-specific risk of cardiovascular (CV) events in patients with rheumatoid arthritis (RA), with or without comorbid hyperlipidemia, relative to those in a non-RA cohort. METHODS: This retrospective cohort study using claims data from a US commercial health plan (2005-2011) included patients with RA and a matched non-RA cohort. Cox proportional hazards regression model determined the hazard ratio (HR) for CV events (myocardial infarction, stroke, revascularization procedures), using the presence of RA and hyperlipidemia as the independent variables, controlling for other covariates (age, sex, diabetes, and hypertension). RESULTS: The incidence of CV events per 1000 person-years was 10.19 for the RA cohort and 6.41 for the non-RA cohort (crude rate ratio [RR] =1.59). Within the RA cohort, incidence was 15.54 for patients with hyperlipidemia and 7.05 for patients without hyperlipidemia (crude RR=2.21); in the non-RA cohort, incidence was 10.55 and 3.82 for those with and without hyperlipidemia, respectively (crude RR=2.76). After controlling for covariates, the HR of CV events among RA patients was 1.68 (95% CI: 1.50, 1.87) relative to non-RA patients. After multivariable adjustment, hyperlipidemia conferred a significant risk of CV events in both RA and non-RA patients; the interaction between RA and hyperlipidemia was not significant (p=0.13). CONCLUSION: This real-world analysis demonstrates that patients with RA have an increased risk of CV events. Similar to a non-RA cohort, CV event rates were incrementally higher for those patients with hyperlipidemia. SIGNIFICANCE: Cardiovascular disease is an increasingly visible topic of concern in the rheumatoid arthritis community. However, there are only limited data that informs both the absolute and relative rates of CVD events, and the contribution of various risk factors such as hyperlipidemia, compared to non-RA populationsThe 'lipid paradox' hypothesis in RA suggests that elevated LDL cholesterol has a negligible effect on CVD risk in RA, unlikely in the general population where it is a well-accepted CVD risk factorThe incidence of CVD events in RA patients was 10/1000 patient years, a 1.6 fold greater risk compared to non-RA patientsThe contribution of hyperlipidemia to CVD risk was associated with comparable or greater absolute increases in the rate of CV events compared to non RA patients, a finding that does not support the lipid paradox.

Pet-1 deficiency alters the circadian clock and its temporal organization of behavior.

The serotonin and circadian systems are two important interactive regulatory networks in the mammalian brain that regulate behavior and physiology in ways that are known to impact human mental health. Previous work on the interaction between these two systems suggests that serotonin modulates photic input to the central circadian clock (the suprachiasmatic nuclei; SCN) from the retina and serves as a signal for locomotor activity, novelty, and arousal to shift the SCN clock, but effects of disruption of serotonergic signaling from the raphe nuclei on circadian behavior and on SCN function are not fully characterized. In this study, we examined the effects on diurnal and circadian behavior, and on ex vivo molecular rhythms of the SCN, of genetic deficiency in Pet-1, an ETS transcription factor that is necessary to establish and maintain the serotonergic phenotype of raphe neurons. Pet-1⁻/⁻ mice exhibit loss of rhythmic behavioral coherence and an extended daily activity duration, as well as changes in the molecular rhythms expressed by the clock, such that ex vivo SCN from Pet-1⁻/⁻ mice exhibit period lengthening and sex-dependent changes in rhythmic amplitude. Together, our results indicate that Pet-1 regulation of raphe neuron serotonin phenotype contributes to the period, precision and light/dark partitioning of locomotor behavioral rhythms by the circadian clock through direct actions on the SCN clock itself, as well as through non-clock effects.