CARDIA sleep ancillary study: study design and methods.

Sleep and circadian disturbances are common and are experienced more often by Black compared to White individuals. We conducted an observational study of sleep that was ancillary to an ongoing cohort study, Coronary Artery Disease in Young Adults (CARDIA). The goal of the ancillary study will be to examine potential determinants of sleep/circadian disparities between Black and White adults in future analyses. Herein we describe the study design and methodology. Our ancillary study coincided with the Year 35 examination of the CARDIA study and was conducted in two phases (due to the SARS-COV-2 pandemic). Phase 1 involved only questionnaires to assess chronotype, restless legs syndrome, and the household sleep environment. Phase 2 involved three additional questionnaires to assess sleep quality, daytime sleepiness and insomnia symptoms, as well as two sleep devices. Participants wore a wrist activity monitor to assess sleep-wake patterns and light levels for 7 days and a home sleep apnea test for 1 night. A subset also had devices objectively record light, temperature, and sound levels in their bedrooms for 7 days. Sample sizes ranged based on assessment from 2200 to 2400, completing Phase 1 questionnaires, 899 with valid wrist actigraphy data, and 619 with a valid sleep apnea test. The data will be part of the full CARDIA dataset, which is available to researchers.

Time-Restricted Eating Versus Daily Calorie Restriction: Effect on Sleep in Adults with Obesity over 12 Months.

Objective: The aim of this secondary analysis was to compare the effects of time-restricted eating (TRE) versus daily calorie restriction (CR) on sleep quality, duration, insomnia severity, and risk of obstructive sleep apnea in adults with obesity over one year. Methods: A total of 90 participants were randomized to one of three groups for 12 months: 8 h TRE (eating only between 12 p.m. and 8 p.m.); CR (25% daily calorie restriction) or a no-intervention control group. Results: By the end of the study, weight loss was 4.61 kg (95% CI; 7.37 to 1.85 kg; p ≤ 0.01) for the TRE group and 5.42 kg (CI; 9.13 to 1.71 kg; p ≤ 0.01) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI; 3.07 to 4.69]; p = 0.68]). Self-reported sleep quality, sleep duration, insomnia severity, and risk of obstructive sleep apnea did not change in the TRE or CR groups versus controls by month 12. Conclusions: These findings suggest that the weight loss produced by TRE and CR does not have any impact on various sleep parameters in adults with obesity over one year.

Gender-specific associations between sleep stages and cardiovascular risk factors.

STUDY OBJECTIVES: Sleep characteristics are associated with cardiovascular disease (CVD) risk and both sleep and CVD risk vary by gender. Our objective was to examine associations between polysomnographic sleep characteristics and CVD risk after excluding moderate-severe sleep apnea, and whether gender modifies these associations. METHODS: This was a cross-sectional study with at-home polysomnography in adults in Brazil (n= 1,102 participants with apnea-hypopnea index (AHI)<15 events/hour). Primary exposures were N3, REM, wake after sleep onset (WASO), arousal index (AI) and AHI, and outcomes were blood pressure (BP) and lipid levels. RESULTS: Associations between sleep and BP varied by gender. In women, more N3 was associated with lower systolic BP (-0.40 mmHg per 10 minutes, 95%CI -0.71, -0.09), lower diastolic BP (-0.29 mmHg per 10 minutes, 95%CI -0.50, -0.07), and lower odds of hypertension (OR 0.94, 95%CI 0.89, 0.98). In men, more WASO was associated with higher systolic BP (0.41 mmHg per 10 minutes, 95%CI 0.08, 0.74) and higher odds of hypertension (OR 1.07, 95%CI 1.01, 1.14). No interactions by gender were observed for lipids. More WASO was associated with lower total cholesterol (-0.71 per 10 minutes, 95%CI -1.37, -0.05). Higher AHI was associated with higher total cholesterol (+0.97 per event/hour, 95%CI 0.24, 1.70) and higher LDL (+0.84 per event/hour, 95%CI 0.04, 1.64). CONCLUSIONS: N3 is more strongly associated with BP in women, which is consistent with other studies demonstrating gender differences in BP control and CVD risk and adds a novel risk factor. Longitudinal and interventional studies are required to determine whether changes in N3 result in BP changes.

Proteomic Risk Score of Increased Respiratory Susceptibility: A Multi-Cohort Study.

RATIONALE: Accelerated decline in lung function is associated with incident COPD, hospitalizations and death. However, identifying this trajectory with longitudinal spirometry measurements is challenging in clinical practice. OBJECTIVE: To determine whether a proteomic risk score trained on accelerated decline in lung function can assess risk of future respiratory disease and mortality. METHODS: In CARDIA, a population-based cohort starting in young adulthood, longitudinal measurements of FEV1 percent predicted (up to six timepoints over 30 years) were used to identify accelerated and normal decline trajectories. Protein aptamers associated with an accelerated decline trajectory were identified with multivariable logistic regression followed by LASSO regression. The proteomic respiratory susceptibility score was derived based on these circulating proteins and applied to the UK Biobank and COPDGene studies to examine associations with future respiratory morbidity and mortality. MEASUREMENTS AND RESULTS: Higher susceptibility score was independently associated with all-cause mortality (UKBB: HR 1.56, 95%CI 1.50-1.61; COPDGene: HR 1.75, 95%CI 1.63-1.88), respiratory mortality (UKBB: HR 2.39, 95% CI 2.16-2.64; COPDGene: HR 1.83, 95%CI 1.33-2.51), incident COPD (UKBB: HR 1.84, 95%CI 1.71-1.98), incident respiratory exacerbation (COPDGene: OR 1.11, 95%CI 1.03-1.20), and incident exacerbation requiring hospitalization (COPDGene: OR 1.18, 95%CI 1.08-1.28). CONCLUSIONS: A proteomic signature of increased respiratory susceptibility identifies people at risk of respiratory death, incident COPD, and respiratory exacerbations. This susceptibility score is comprised of proteins with well-known and novel associations with lung health and holds promise for the early detection of lung disease without requiring years of spirometry measurements.

Effect of Time-Restricted Eating on Sleep in Type 2 Diabetes.

The aim of this secondary analysis was to compare the effects of time-restricted eating (TRE) versus calorie restriction (CR) and controls on sleep in adults with type 2 diabetes (T2D). Adults with T2D (n = 75) were randomized to 1 of 3 interventions for 6 months: 8 h TRE (eating only between 12 and 8 pm daily); CR (25% energy restriction daily); or control. Our results show that TRE has no effect on sleep quality, duration, insomnia severity, or risk of obstructive sleep apnea, relative to CR and controls, in patients with T2D over 6 months.

Longitudinal associations of screen time, physical activity, and sleep duration with body mass index in U.S. youth.

BACKGROUND: Youth use different forms of screen time (e.g., streaming, gaming) that may be related to body mass index (BMI). Screen time is non-independent from other behaviors, including physical activity and sleep duration. Statistical approaches such as isotemporal substitution or compositional data analysis (CoDA) can model associations between these non-independent behaviors and health outcomes. Few studies have examined different types of screen time, physical activity, and sleep duration simultaneously in relation to BMI. METHODS: Data were baseline (2017-2018) and one-year follow-up (2018-2019) from the Adolescent Brain Cognitive Development Study, a multi-site study of a nationally representative sample of U.S. youth (N = 10,544, mean [SE] baseline age = 9.9 [0.03] years, 48.9% female, 45.4% non-White). Participants reported daily minutes of screen time (streaming, gaming, socializing), physical activity, and sleep. Sex-stratified models estimated the association between baseline behaviors and follow-up BMI z-score, controlling for demographic characteristics, internalizing symptoms, and BMI z-score at baseline. RESULTS: In females, isotemporal substitution models estimated that replacing 30 min of socializing (ß [95% CI] = -0.03 [-0.05, -0.002]), streaming (-0.03 [-0.05, -0.01]), or gaming (-0.03 [-0.06, -0.01]) with 30 min of physical activity was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing (-0.03 [-0.05, -0.01]), streaming (-0.02 [-0.03, -0.01]), or gaming (-0.02 [-0.03, -0.01]) with 30 min of sleep was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing with 30 min of gaming was associated with a lower follow-up BMI z-score (-0.01 [-0.03, -0.0001]). CoDA estimated that in males, a greater proportion of time spent in baseline socializing, relative to the remaining behaviors, was associated with a higher follow-up BMI z-score (0.05 [0.02, 0.08]). In females, no associations between screen time and BMI were observed using CoDA. CONCLUSIONS: One-year longitudinal associations between screen time and BMI may depend on form of screen time, what behavior it replaces (physical activity or sleep), and participant sex. The alternative statistical approaches yielded somewhat different results. Experimental manipulation of screen time and investigation of biopsychosocial mechanisms underlying the observed sex differences will allow for causal inference and can inform interventions.

Urinary Incontinence in Primary Care-The Gap Between Recommendations and Real World.

IMPORTANCE: Routine screening for urinary incontinence (UI) by primary care providers (PCPs) is recommended. OBJECTIVES: We aimed to describe the rate of incident UI diagnosed at annual PCP visits, the prevalence of UI in a large primary care population, and estimate the rate of screening for UI during primary care preventive and annual wellness visits. Secondary aims were to describe PCP knowledge and behavior as they relate to UI screening and diagnosis. STUDY DESIGN: The electronic health record was used to abstract the number of adult female patients seen by PCPs within a regional health system with a diagnosis of UI before our study period and with a new diagnosis over a 2-year period. Additional new diagnoses and screening practices were found on chart review of an additional 824 representative charts. Primary care providers within the health system were surveyed about their screening practices and knowledge about UI. RESULTS: There were 192,053 women primary care patients seen over 2 years. A total of 5.7% had a UI diagnosis preceding the study period and 3.4% had a UI diagnosis during the study period. A total of 42% of PCPs reported that they screen for UI at least half the time and none were completely satisfied with their ability to screen for UI. Sixteen percent of annual wellness visits had any documentation of screening for UI. CONCLUSION: In a large primary care population, screening for and detection of UI in women was low.

The longitudinal association of adipose-to-lean ratio with incident cardiometabolic morbidity: The CARDIA study.

AIM: To assess the association of adipose-to-lean ratio (ALR) with incident type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia in middle adulthood. METHOD: Black and White Coronary Artery Risk Development in Young Adults participants without T2DM, hypertension, or dyslipidemia in 2005-06 (baseline) were included. Baseline adipose and lean mass were assessed via dual-energy X-ray absorptiometry. ALR was calculated as adipose divided by lean mass and then standardized within sex strata. Single time-point incident morbidity was assessed every five years from baseline through 2016. Cox proportional hazards regression was used to estimate hazard ratios (HR) for morbidity over 10 years per 1-SD increment in ALR adjusted for cardiovascular risk factors. RESULT: The cumulative incidence of T2DM was 7.9 % (129 events/N = 1643; 16,301 person-years), 26.7 % (485 events/N = 1819; 17,895 person-years) for hypertension, and 49.1 % (435 events/N = 855, 8089 person-years) for dyslipidemia. In the adjusted models, ALR was positively associated with a risk of T2DM (HR [95 % CI]; 1.69 [1.31, 2.19]) and hypertension (1.23 [1.08, 1.40]). There was no significant interaction between ALR and sex for any morbidity. CONCLUSION: ALR in middle adulthood is associated with incident T2DM and hypertension. The extent to which localized body composition measures might inform morbidity risk merits further investigation.

The association between timing of dietary macronutrient and sodium consumption and sleep duration and quality.

Study Objective: The objective of this study was to examine the association between the timing of dietary macronutrients and sodium intake and sleep quantity and quality. Methods: This was a cross-sectional study that included 34 adults between 21 and 50 years of age. The main outcome measures were objective sleep measures assessed from three nights of wrist actigraphy including sleep duration, fragmentation, and wake after sleep onset (WASO), and one night of polysomnography (PSG), including rapid eye movement (REM) sleep, non-REM stage 2 (N2), stage 3 (N3), and WASO. Multiple linear regression models and linear mixed models were used to estimate the associations between sleep measures and dietary measures (carbohydrates, fats, saturated fats, proteins, and sodium). Dietary timing was examined in two ways: (1) the average amount of each nutrient consumed within 3 hours of sleep start, and (2) the interval between the final intake of each nutrient and sleep. Results: Average fat intake within 3 hours of sleep was associated with greater WASO from PSG (ß = 4.48, p = 0.01). No other associations were found between the macronutrients or sodium intake (p > 0.05) within 3 hours of sleep and the sleep parameters from PSG or actigraphy. Similarly, no associations were found between any of the PSG or actigraphy sleep measures and the interval between final nutrient intakes and sleep with sleep duration. Conclusions: The study suggests that greater fat but not carbohydrate, protein, saturated fat, or sodium intake close to sleep may be associated with greater sleep disruption; however, no other associations were observed.

Altered sleep architecture in diabetes and prediabetes: findings from the Baependi Heart Study.

STUDY OBJECTIVES: People with diabetes and prediabetes are more likely to have sleep-disordered breathing (SDB), but few studies examined sleep architecture in people with diabetes or prediabetes in the absence of moderate-severe SDB, which was the aim of our cross-sectional study. METHODS: This cross-sectional sample is from the Baependi Heart Study, a family-based cohort of adults in Brazil. About 1074 participants underwent at-home polysomnography (PSG). Diabetes was defined as fasting glucose >125 mg/dL or HbA1c > 6.4 mmol/mol or taking diabetic medication, and prediabetes was defined as HbA1c ≥ 5.7 & <6.5 mmol/mol or fasting glucose ≥ 100 & ≤125 mg/dl. We excluded participants with an apnea-hypopnea index (AHI) ≥ 30 in primary analyses and ≥ 15 in secondary analysis. We compared sleep stages among the 3 diabetes groups (prediabetes, diabetes, neither). RESULTS: Compared to those without diabetes, we found shorter REM duration for participants with diabetes (-6.7 min, 95%CI -13.2, -0.1) and prediabetes (-5.9 min, 95%CI -10.5, -1.3), even after adjusting for age, gender, BMI, and AHI. Diabetes was also associated with lower total sleep time (-13.7 min, 95%CI -26.8, -0.6), longer slow-wave sleep (N3) duration (+7.6 min, 95%CI 0.6, 14.6) and higher N3 percentage (+2.4%, 95%CI 0.6, 4.2), compared to those without diabetes. Results were similar when restricting to AHI < 15. CONCLUSIONS: People with diabetes and prediabetes had less REM sleep than people without either condition. People with diabetes also had more N3 sleep. These results suggest that diabetes and prediabetes are associated with differences in sleep architecture, even in the absence of moderate-severe sleep apnea.

Study protocol for a longitudinal observational study of disparities in sleep and cognition in older adults: the DISCO study.

INTRODUCTION: Cognitive dysfunction, a leading cause of mortality and morbidity in the USA and globally, has been shown to disproportionately affect the socioeconomically disadvantaged and those who identify as black or Hispanic/Latinx. Poor sleep is strongly associated with the development of vascular and metabolic diseases, which correlate with cognitive dysfunction. Therefore, sleep may contribute to observed disparities in cognitive disorders. The Epidemiologic Study of Disparities in Sleep and Cognition in Older Adults (DISCO) is a longitudinal, observational cohort study that focuses on gathering data to better understand racial/ethnic sleep disparities and illuminate the relationship among sleep, race and ethnicity and changes in cognitive function. This investigation may help inform targeted interventions to minimise disparities in cognitive health among ageing adults. METHODS AND ANALYSIS: The DISCO study will examine up to 495 individuals aged 55 and older at two time points over 24 months. An equal number of black, white and Hispanic/Latinx individuals will be recruited using methods aimed for adults traditionally under-represented in research. Study procedures at each time point will include cognitive tests, gait speed measurement, wrist actigraphy, a type 2 home polysomnography and a clinical examination. Participants will also complete self-identified assessments and questionnaires on cognitive ability, sleep, medication use, quality of life, sociodemographic characteristics, diet, substance use, and psychological and social health. ETHICS AND DISSEMINATION: This study was approved by the Northwestern University Feinberg School of Medicine Institutional Review Board. Deidentified datasets will be shared via the BioLINCC repository following the completion of the project. Biospecimen samples from the study that are not being analysed can be made available to qualified investigators on review and approval by study investigators. Requests that do not lead to participant burden or that conflict with the primary aims of the study will be reviewed by the study investigators.

Effect of Time-Restricted Eating on Weight Loss in Adults With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Time-restricted eating (TRE) has become increasingly popular, yet longer-term randomized clinical trials have not evaluated its efficacy and safety in patients with type 2 diabetes (T2D). Objective: To determine whether TRE is more effective for weight reduction and glycemic control than daily calorie restriction (CR) or a control condition in adults with T2D. Design, Setting, and Participants: This 6-month, parallel-group, randomized clinical trial was performed between January 25, 2022, and April 1, 2023, at the University of Illinois Chicago. Participants were aged 18 to 80 years with obesity and T2D. Data analysis was based on intention to treat. Interventions: Participants were randomized to 1 of 3 groups: 8-hour TRE (eating 12 to 8 pm only, without calorie counting), CR (25% energy restriction daily), or control. Main Outcomes and Measures: The primary outcome measure was change in body weight by month 6. Secondary outcomes included changes in hemoglobin A1c (HbA1c) levels and metabolic risk factors. Results: Seventy-five participants were enrolled with a mean (SD) age of 55 (12) years. The mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39 (7) and the mean (SD) HbA1c level was 8.1% (1.6%). A total of 53 participants (71%) were women. One participant (1%) was Asian, 30 (40%) were Hispanic White, 40 (53%) were non-Hispanic Black, and 4 (5%) were non-Hispanic White. Participants in the TRE group were adherent with their eating window on a mean (SD) of 6.1 (0.8) days per week, and 17 (68%) in the CR group were adherent with their prescribed calorie goals over 6 months. The mean (SD) reduction in energy intake was -313 (509) kcal/d for TRE, -197 (426) kcal/d for CR, and -16 (439) kcal/d for controls. By month 6, body weight decreased significantly in the TRE group (-3.56% [95% CI, -5.92% to -1.20%]; P = .004) but not the CR group (-1.78% [95% CI, -3.67% to 0.11%]; P = .06), relative to controls. Levels of HbA1c decreased in the TRE (-0.91% [95% CI, -1.61% to -0.20%]) and CR (-0.94% [95% CI, -1.59% to -0.30%]) groups, relative to controls, with no differences between the TRE and CR groups. Time in euglycemic range, medication effect score, blood pressure, and plasma lipid levels did not differ among groups. No serious adverse events were reported. Conclusions and relevance: This randomized clinical trial found that a TRE diet strategy without calorie counting was effective for weight loss and lowering of HbA1c levels compared with daily calorie counting in a sample of adults with T2D. These findings will need to be confirmed by larger RCTs with longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT05225337.

Effect of Time-Restricted Eating versus Daily Calorie Restriction on Mood and Quality of Life in Adults with Obesity.

The purpose of this secondary analysis is to compare the effects of two popular weight loss regimens, time-restricted eating (TRE) and daily calorie restriction (CR), on mood and quality-of-life measures in adults with obesity. Ninety participants were randomized to one of three interventions for 12 months: 8 h TRE (eating only between 12:00 and 8:00 p.m., with no calorie counting); CR (25% energy restriction daily); or no-intervention control group. Questionnaires were administered to measure mood (Beck Depression Inventory-II (BDI-II), and Profile of Mood States (POMS)) and quality of life (Rand 36-Item Short Form) at baseline and month 12. Body weight decreased in the TRE group (-4.87%, 95%CI: -7.61, -2.13) and CR group (-5.30%, 95%CI: -9.06, -1.54) versus controls, with no difference between TRE and CR. The BDI-II depression score did not change in the TRE or CR group, versus controls, by month 12. Likewise, there were no changes in any of the POMS subscales (tension, depression, anger, fatigue, anger, confusion, or vigor) or the total mood disturbance score in the TRE or CR group versus controls. As for quality of life, there were no significant changes in the SF-36 constructs of mental health, bodily pain, and general physical health in the TRE or CR group versus controls. However, there was a trend towards increased vitality in the TRE group (7.77 [95% CI: 0.15, 15.39] p = 0.05) relative to controls. There were no associations between changes in body weight, physical activity, mood, and quality of life in any group by the end of the study. These findings suggest that TRE and CR produce similar degrees of weight loss, but impact neither mood nor quality of life in adults with obesity over 12 months. Future well-powered studies will be needed to confirm these findings.

Time-Restricted Eating Without Calorie Counting for Weight Loss in a Racially Diverse Population : A Randomized Controlled Trial.

BACKGROUND: Time-restricted eating (TRE), without calorie counting, has become a popular weight loss strategy, yet long-term randomized trials evaluating its efficacy are limited. OBJECTIVE: To determine whether TRE is more effective for weight control and cardiometabolic risk reduction compared with calorie restriction (CR) or control. DESIGN: 12-month randomized controlled trial. (ClinicalTrials.gov: NCT04692532). SETTING: University of Illinois Chicago from January 2021 to September 2022. PARTICIPANTS: 90 adults with obesity. INTERVENTION: 8-hour TRE (eating between noon and 8:00 p.m. only, without calorie counting), CR (25% energy restriction daily), or control (eating over a period of 10 or more hours per day). Participants were not blinded. MEASUREMENTS: Change in body weight, metabolic markers, and energy intake by month 12. RESULTS: Seventy-seven persons completed the study. Mean age was 40 years (SD, 11), 33% were Black, and 46% were Hispanic. Mean reduction in energy intake was -425 kcal/d (SD, 531) for TRE and -405 kcal/d (SD, 712) for CR. Compared with the control group, weight loss by month 12 was -4.61 kg (95% CI, -7.37 to -1.85 kg; P ≤ 0.01) (-4.87% [CI, -7.61% to -2.13%]) for the TRE group and -5.42 kg (CI, -9.13 to -1.71 kg; P ≤ 0.01) (-5.30% [CI, -9.06% to -1.54%]) for the CR group, with no statistically significant difference between TRE and CR (0.81 kg [CI, -3.07 to 4.69 kg; P = 0.68]) (0.43% [CI, -3.48% to 4.34%]). LIMITATION: Not blinded, not powered to detect relatively large differences in weight loss, and lack of adjustment for multiple comparisons. CONCLUSION: Time-restricted eating is more effective in producing weight loss when compared with control but not more effective than CR in a racially diverse population. PRIMARY FUNDING SOURCE: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Altered sleep architecture in diabetes and prediabetes: findings from the Baependi Heart Study.

Objective: People with diabetes are more likely to have obstructive sleep apnea, but there are few studies examining sleep architecture in people with diabetes, especially in the absence of moderate-severe sleep apnea. Therefore, we compared sleep architecture among people with diabetes, prediabetes or neither condition, whilst excluding people with moderate-severe sleep apnea. Research design and methods: This sample is from the Baependi Heart Study, a prospective, family-based cohort of adults in Brazil. 1,074 participants underwent at-home polysomnography (PSG). Diabetes was defined as 1) FBG>125 OR 2) HbA1c>6.4 OR 3) taking diabetic medication, and prediabetes was defined as 1) [(5.7≤HbA1c≤6.4) OR (100≤FBG≤125)] AND 2) not taking diabetic medication. We excluded participants that had an apnea-hypopnea index (AHI)>30 from these analyses to reduce confounding due to severe sleep apnea. We compared sleep stages among the 3 groups. Results: Compared to those without diabetes, we found shorter REM duration for participants with diabetes (-6.7min, 95%CI -13.2, -0.1) or prediabetes (-5.9min, 95%CI -10.5, -1.3), even after adjusting for age, gender, BMI, and AHI. Diabetes was also associated with lower total sleep time (-13.7min, 95%CI -26.8, -0.6), longer slow-wave sleep (N3) duration (+7.6min, 95%CI 0.6, 14.6) and higher N3 percentage (+2.4%, 95%CI 0.6, 4.2), compared to those without diabetes. Conclusions: People with diabetes and prediabetes had less REM sleep after taking into account potential confounders, including AHI. People with diabetes also had more N3 sleep. These results suggest that diabetes is associated with different sleep architecture, even in the absence of moderate-severe sleep apnea.

Effect of alternate day fasting combined with aerobic exercise on non-alcoholic fatty liver disease: A randomized controlled trial.

Innovative non-pharmacological lifestyle strategies to treat non-alcoholic fatty liver disease (NAFLD) are critically needed. This study compared the effects of alternate day fasting (ADF) combined with exercise to fasting alone, or exercise alone, on intrahepatic triglyceride (IHTG) content. Adults with obesity and NAFLD (n = 80, 81% female, age: 23-65 years) were randomized to 1 of 4 groups for 3 months: combination of ADF (600 kcal/2,500 kJ "fast day" alternated with an ad libitum intake "feast day") and moderate-intensity aerobic exercise (5 session per week, 60 min/session); ADF alone; exercise alone; or a no-intervention control group. By month 3, IHTG content was significantly reduced in the combination group (-5.48%; 95% CI, -7.77% to -3.18%), compared with the exercise group (-1.30%; 95% CI, -3.80% to 1.20%; p = 0.02) and the control group (-0.17%; 95% CI, -2.17% to 1.83%; p < 0.01) but was not significantly different versus the ADF group (-2.25%; 95% CI, -4.46% to -0.04%; p = 0.05). Body weight, fat mass, waist circumference, and alanine transaminase (ALT) levels significantly decreased, while insulin sensitivity significantly increased in the combination group compared with the control group. Lean mass, aspartate transaminase (AST), HbA1c, blood pressure, plasma lipids, liver fibrosis score, and hepatokines (fetuin-A, FGF-21, and selenoprotein P) did not differ between groups. Combining intermittent fasting with exercise is effective for reducing hepatic steatosis in patients with NAFLD but may offer no additional benefit versus fasting alone.

Assessing intervention effects in a randomized trial within a social network.

Studies of social networks provide unique opportunities to assess the causal effects of interventions that may impact more of the population than just those intervened on directly. Such effects are sometimes called peer or spillover effects, and may exist in the presence of interference, that is, when one individual's treatment affects another individual's outcome. Randomization-based inference (RI) methods provide a theoretical basis for causal inference in randomized studies, even in the presence of interference. In this article, we consider RI of the intervention effect in the eX-FLU trial, a randomized study designed to assess the effect of a social distancing intervention on influenza-like-illness transmission in a connected network of college students. The approach considered enables inference about the effect of the social distancing intervention on the per-contact probability of influenza-like-illness transmission in the observed network. The methods allow for interference between connected individuals and for heterogeneous treatment effects. The proposed methods are evaluated empirically via simulation studies, and then applied to data from the eX-FLU trial.