Using Integrated Research-Practice Partnerships to Move Evidence-Based Principles Into Practice.

The implementation of evidence-based physical activity interventions is improved when integrated research-practice partnerships are used. These partnerships consider both research- and practice-based evidence that moves beyond only assessing program efficacy. Our novel hypothesis is that integrated research-practice partnerships may lead to interventions that are practical and effective, reach more participants, and are more likely to be sustained in practice.

A Quasi-Experiment to Assess the Impact of a Scalable, Community-Based Weight Loss Program: Combining Reach, Effectiveness, and Cost.

BACKGROUND: Primary care addresses obesity through physician oversight of intensive lifestyle interventions or referral to external programs with demonstrated efficacy. However, limited information exists on community program reach, effectiveness, and costs across different groups of participants. OBJECTIVE: To evaluate a scalable, community weight loss program using reach, effectiveness, and cost metrics. DESIGN: Longitudinal pre-post quasi-experiment without control. PARTICIPANTS: Enrolled participants in Weigh and Win (WAW), a community-based weight loss program. INTERVENTION: A 12-month program with daily social cognitive theory-based email and/or text support, online access to health coaches, objective weight assessment through 83 community-based kiosks, and modest financial incentives to increase program reach. MAIN MEASURES: Number of participants, representativeness, weight loss achievement (3%, 5% of initial weight lost), and cost of implementation. KEY RESULTS: A total of 40,308 adults (79% women; 73% white; BMI = 32.3 ± 7.44, age = 43.9 ± 13.1 years) enrolled in WAW. Women were more likely than men to enroll in the program and continue engagement beyond an initial weigh-in (57% vs. 53%). Based on census data, African Americans were over-represented in the sample. Among participants who engaged in the program beyond an initial weigh-in (n = 19,029), 47% and 34% of participants lost 3% and 5% of their initial body weight, respectively. The average duration for those who achieved 5% weight loss was 1.7 ± 1.3 years. African American participants were more likely to achieve 5% weight loss and remain enrolled in the program longer compared to non-African American participants (2.0 ± 1.3 vs. 1.6 ± 1.2 years). Implementation costs were $2,822,698. Cost per clinically meaningful weight loss for African Americans ($257.97/3% loss; $335.96/5% loss) was lower than that for Hispanics ($318.62; $431.10) and Caucasians ($313.65; $441.87), due to the higher success rate of that subgroup of participants. CONCLUSIONS: Weigh and Win is a scalable technology-supported and community-based weight loss program that reaches a large number of participants and may contribute to reducing health disparities.

Cost effectiveness and return on investment of a scalable community weight loss intervention.

This study assessed the lifetime health and economic consequences of an efficacious scalable community weight loss program for overweight and obese adults. We applied a state-transition Markov model to project lifetime economic outcome (US dollar) and the degree of disease averted as a result of a weight loss intervention, compared with no intervention, from a payer perspective. Effect sizes of the intervention on weight loss, by sex, race and ethnicity, and body mass index (BMI) of participants, were derived from a 12-month community program. Relative risk of diseases across BMI levels and other parameters were informed by the literature. A return on investment (ROI) analysis was conducted to present the overall cost-benefit of the program. Simulation results showed that among 33,656 participants and at a cost of $2.88 million, the program was predicted to avert (with a corresponding estimated medical costs saved of) 78 cases of coronary heart disease ($28 million), 9 cases of strokes ($971,832), 92 cases of type 2 diabetes ($24 million), 1 case of colorectal cancer ($357,022), and 3 cases of breast cancer ($483,259) over the participant lifetime. The estimated medical costs saved per participant was $1403 ($1077 of African American men and $1532 of Hispanic men), and the ROI was $16.7 ($12.8 for African American men and $18.3 for Hispanic men) for every $1 invested. We concluded that a scalable efficacious community weight loss program provides a cost-effective approach with significant ROI, which will assist informed decisions for future adoption and dissemination.

An Interactive Computer Session to Initiate Physical Activity in Sedentary Cardiac Patients: Randomized Controlled Trial.

BACKGROUND: Physical activity (PA) improves many facets of health. Despite this, the majority of American adults are insufficiently active. Adults who visit a physician complaining of chest pain and related cardiovascular symptoms are often referred for further testing. However, when this testing does not reveal an underlying disease or pathology, patients typically receive no additional standard care services. A PA intervention delivered within the clinic setting may be an effective strategy for improving the health of this population at a time when they may be motivated to take preventive action. OBJECTIVE: Our aim was to determine the effectiveness of a tailored, computer-based, interactive personal action planning session to initiate PA among a group of sedentary cardiac patients following exercise treadmill testing (ETT). METHODS: This study was part of a larger 2x2 randomized controlled trial to determine the impact of environmental and social-cognitive intervention approaches on the initiation and maintenance of weekly PA for patients post ETT. Participants who were referred to an ETT center but had a negative-test (ie, stress tests results indicated no apparent cardiac issues) were randomized to one of four treatment arms: (1) increased environmental accessibility to PA resources via the provision of a free voucher to a fitness facility in close proximity to their home or workplace (ENV), (2) a tailored social cognitive intervention (SC) using a "5 As"-based (ask, advise, assess, assist, and arrange) personal action planning tool, (3) combined intervention of both ENV and SC approaches (COMBO), or (4) a matched contact nutrition control (CON). Each intervention was delivered using a computer-based interactive session. A general linear model for repeated measures was conducted with change in PA behavior from baseline to 1-month post interactive computer session as the primary outcome. RESULTS: Sedentary participants (n=452; 34.7% participation rate) without a gym membership (mean age 58.57 years; 59% female, 78% white, 12% black, 11% Hispanic) completed a baseline assessment and an interactive computer session. PA increased across the study sample (F1,441=30.03, P<.001). However, a time by condition interaction (F3,441=8.33, P<.001) followed by post hoc analyses indicated that SC participants exhibited a significant increase in weekly PA participation (mean 45.1, SD 10.2) compared to CON (mean -2.5, SD 10.8, P=.004) and ENV (mean 8.3, SD 8.1, P<.05). Additionally, COMBO participants exhibited a significant increase in weekly PA participation (mean 53.4, SD 8.9) compared to CON (P<.001) and ENV (P=.003) participants. There were no significant differences between ENV and CON or between SC and COMBO. CONCLUSIONS: A brief, computer-based, interactive personal action planning session may be an effective tool to initiate PA within a health care setting, in particular as part of the ETT system. TRIAL REGISTRATION: Clinicaltrials.gov NCT00432133, http://clinicaltrials.gov/ct2/show/NCT00432133 (Archived by WebCite at http://www.webcitation.org/6aa8X3mw1).

Physical activity promotion in Latin American populations: a systematic review on issues of internal and external validity.

The purpose of this review was to determine the degree to which physical activity interventions for Latin American populations reported on internal and external validity factors using the RE-AIM framework (reach & representativeness, effectiveness, adoption, implementation, maintenance). We systematically identified English (PubMed; EbscoHost) and Spanish (SCIELO; Biblioteca Virtual en Salud) language studies published between 2001 and 2012 that tested physical activity, exercise, or fitness promotion interventions in Latin American populations. Cross-sectional/descriptive studies, conducted in Brazil or Spain, published in Portuguese, not including a physical activity/fitness/exercise outcome, and with one time point assessment were excluded. We reviewed 192 abstracts and identified 46 studies that met the eligibility criteria (34 in English, 12 in Spanish). A validated 21-item RE-AIM abstraction tool was used to determine the quality of reporting across studies (0-7 = low, 8-14 = moderate, and 15-21 = high). The number of indicators reported ranged from 3-14 (mean = 8.1 ± 2.6), with the majority of studies falling in the moderate quality reporting category. English and Spanish language articles did not differ on the number of indicators reported (8.1 vs. 8.3, respectively). However, Spanish articles reported more across reach indicators (62% vs. 43% of indicators), while English articles reported more across effectiveness indicators (69% vs 62%). Across RE-AIM dimensions, indicators for reach (48%), efficacy/effectiveness (67%), and implementation (41%) were reported more often than indicators of adoption (25%) and maintenance (10%). Few studies reported on the representativeness of participants, staff that delivered interventions, or the settings where interventions were adopted. Only 13% of the studies reported on quality of life and/or potential negative outcomes, 20% reported on intervention fidelity, and 11% on cost of implementation. Outcomes measured after six months of intervention, information on continued delivery and institutionalization of interventions, were also seldom reported. Regardless of language of publication, physical activity intervention research for Latin Americans should increase attention to and measurement of external validity and cost factors that are critical in the decision making process in practice settings and can increase the likelihood of translation into community or clinical practice.

A randomized controlled trial to test the effectiveness of two technology-enhanced diabetes prevention programs in primary care: The DiaBEAT-it study.

Objective: To evaluate the effectiveness of two technology-enhanced interventions for diabetes prevention among adults at risk for developing diabetes in a primary care setting. Methods: The DiaBEAT-it study employed a hybrid 2-group preference (Choice) and 3-group randomized controlled (RCT) design. This paper presents weight related primary outcomes of the RCT arm. Patients from Southwest Virginia were identified through the Carilion Clinic electronic health records. Eligible participants (18 and older, BMI ≥ 25, no Type 2 Diabetes) were randomized to either Choice (n = 264) or RCT (n = 334). RCT individuals were further randomized to one of three groups: (1) a 2-h small group class to help patients develop a personal action plan to prevent diabetes (SC, n = 117); (2) a 2-h small group class plus automated telephone calls using an interactive voice response system (IVR) to help participants initiate weight loss through a healthful diet and regular physical activity (Class/IVR, n = 110); or (3) a DVD with same content as the class plus the same IVR calls over a period of 12 months (DVD/IVR, n = 107). Results: Of the 334 participants that were randomized, 232 (69%) had study measured weights at 6 months, 221 (66%) at 12 months, and 208 (62%) at 18 months. Class/IVR participants were less likely to complete weight measures than SC or DVD/IVR. Intention to treat analyses, controlling for gender, race, age and baseline BMI, showed that DVD/IVR and Class/IVR led to reductions in BMI at 6 (DVD/IVR -0.94, p < 0.001; Class/IVR -0.70, p < 0.01), 12 (DVD/IVR -0.88, p < 0.001; Class/IVR-0.82, p < 0.001) and 18 (DVD/IVR -0.78, p < 0.001; Class/IVR -0.58, p < 0.01) months. All three groups showed a significant number of participants losing at least 5% of their body weight at 12 months (DVD/IVR 26.87%; Class/IVR 21.62%; SC 16.85%). When comparing groups, DVD/IVR were significantly more likely to decrease BMI at 6 months (p < 0.05) and maintain the reduction at 18 months (p < 0.05) when compared to SC. There were no differences between the other groups. Conclusions: The DiaBEAT-it interventions show promise in responding to the need for scalable, effective methods to manage obesity and prevent diabetes in primary care settings that do not over burden primary care clinics and providers. Registration: https://clinicaltrials.gov/ct2/show/NCT02162901, identifier: NCT02162901.

Effects of a digital diabetes prevention program on cardiovascular risk among individuals with prediabetes.

OBJECTIVE: To examine changes in cardiovascular disease (CVD) risk outcomes of overweight/obese adults with prediabetes. METHODS: Using data from a randomized control trial of digital diabetes prevention program (d-DPP) with 599 participants. We applied the atherosclerotic CVD (ASCVD) risk calculator to predict 10-year CVD risk for d-DPP and small education (comparison) groups. Between-group risk changes at 4 and 12 months were compared using a repeated measures linear mixed-effect model. We examined within-group differences in proportion of participants over time for specific CVD risk factors using generalized estimating equations. RESULTS: We found no differences between baseline 10-year ASCVD risk. Relative to the comparison group, the d-DPP group experienced greater reductions in predicted 10-year ASCVD risk at each follow-up visit and a significant group difference at 4 months (-0.96%; 95% confidence interval: -1.58%, -0.34%) (but not at 12 months). Additionally, we observed that the d-DPP group experienced a decreased proportion of individuals with hyperlipidemia (18% and 16% from baseline to 4 and 12 months), high-risk total cholesterol (8% from baseline to 12 months), and being insufficiently active (26% and 22% from baseline to 4 and 12 months at follow-up time points. CONCLUSIONS: Our findings suggest that a digitally adapted DPP may promote the prevention of cardiometabolic disease among overweight/obese individuals with prediabetes. However, given the lack of maintenance of effect on ASCVD risk at 12 months, there may also be a need for additional interventions to sustain the effect detected at 4 months.

Effects of a Digital Diabetes Prevention Program: An RCT.

INTRODUCTION: In light of the need to expand the reach and access of clinically proven digital Diabetes Prevention Programs (d-DPPs) and the need for rigorous evidence of effectiveness, the purpose of this study was to determine the effectiveness of a digital Diabetes Prevention Program for improving weight, HbA1c, and cardiovascular risk factors among people with prediabetes compared to enhanced standard care plus waitlist control. STUDY DESIGN: This was a single-blind RCT among participants at risk of developing type 2 diabetes and included 12 months of follow-up. SETTING/PARTICIPANTS: A total of 599 volunteer patients with prediabetes were recruited primarily through electronic medical records and primary care practices. INTERVENTION: Participants were randomized to either a d-DPP (n=299) or a single-session small-group diabetes-prevention education class (n=300) focused on action planning for weight loss. The d-DPPs consisted of 52 weekly sessions, lifestyle coaching, virtual peer support, and behavior tracking tools. MAIN OUTCOME MEASURES: The primary outcome was a change in HbA1c from baseline to 12 months using intent-to-treat analyses. On the basis of multiple comparisons of endpoints, 95% CIs are presented and 2-sided p<0.025 was required for statistical significance. Secondary outcomes included body weight and cardiovascular disease risk factors. RESULTS: Among 599 randomized participants (mean age=55.4 years, 61.4% women), 483 (80%) completed the study. The d-DPPs produced significantly greater reductions in HbA1c (0.08%, 95% CI= -0.12, -0.03) and percentage change in body weight (-5.5% vs -2.1%, p<0.001) at 12 months. A greater proportion of the d-DPPs group achieved a clinically significant weight loss ≥5% (43% vs 21%, p<0.001), and more participants shifted from prediabetes to normal HbA1c range (58% vs 48%, p=0.04). Engagement in d-DPPs was significantly related to improved HbA1c and weight loss. CONCLUSIONS: This d-DPPs demonstrated clinical effectiveness and has significant potential for widespread dissemination and impact, particularly considering the growing demand for telemedicine in preventive healthcare services. TRIAL REGISTRATION: This study is registered at www. CLINICALTRIALS: gov (ClinicalTrials.gov Identifier: NCT03312764).

Who participates in internet-based worksite weight loss programs?

BACKGROUND: The reach and representativeness are seldom examined in worksite weight loss studies. This paper describes and illustrates a method for directly assessing the reach and representativeness of a internet-based worksite weight loss program. METHODS: A brief health survey (BHS) was administered, between January 2008 and November 2009, to employees at 19 worksites in Southwest Virginia. The BHS included demographic, behavioral, and health questions. All employees were blinded to the existence of a future weight loss program until the completion of the BHS. RESULTS: The BHS has a participation rate of 66 percent and the subsequent weight loss program has a participation rate of 30 percent. Employees from higher income households, with higher education levels and health literacy proficiency were significantly more likely to participate in the program (p's < .01). CONCLUSIONS: Worksite weight loss programs should include targeted marketing strategies to engage employees with lower income, education, and health literacy.

Building a multiple modality, theory-based physical activity intervention: The development of CardiACTION!

OBJECTIVES: Despite the widely acknowledged benefits of regular physical activity (PA), specific goals for increased population levels of PA, and strongly recommended strategies to promote PA, there is no evidence suggesting that the prevalence of PA is improving. If PA intervention research is to be improved, theory should be used as the basis for intervention development, participant context or environment should be considered in the process, and intervention characteristics that will heighten the likelihood of translation into practice should be implemented (e.g., ease of implementation, low human resource costs). The purpose of this paper is to describe the implementation of the aforementioned concepts within the intervention development process associated with CardiACTION an ongoing randomized 2 × 2 factorial trial. METHODS: The Ecological Model of Physical Activity integrated with Protection Motivation Theory was used to inform the design of the interventions. This integrated model was selected to allow for the development of theory-based individual, environmental, and individually + environmentally targeted physical activity interventions. All intervention strategies were matched to proposed mediators of behavior change. Strategies were then matched to the most appropriate interactive technology (i.e., interactive computer session, automated telephone counseling, and tailored mailings) delivery channel. CONCLUSIONS: The potential implications of this study include determining the independent and combined influence of individual and environment mechanisms of behavior change on intervention effectiveness. In addition, all intervention models are developed to be scalable and disseminable to a broad audience at a low cost.

Psychometric assessment of the Brief Weight-Loss-Related Behavior Self-Efficacy Survey in adults with prediabetes.

Self-efficacy is a commonly examined cognitive determinant of behavior change in weight-loss trials, but there has been little uniformity in its measurement. To address this, a recently developed survey captures self-efficacy as it relates to three behavioral domains of interest to weight-loss interventionists: physical activity (PA), healthful eating, and weight loss. The purpose of this study was to test the psychometric properties of the Brief Weight-Loss-Related Behavior Self-Efficacy Scales in a large sample (n = 599) of adults with prediabetes. Participants completed the self-efficacy survey, as well as measures of PA, dietary intake, weight, and height. The factor structure was scrutinized using exploratory and confirmatory factor analysis, which supported a factor structure with three correlated first-order latent self-efficacy factors, specific to PA, healthful eating, and weight loss. This model is statistically equivalent to a hierarchical model including a second-order factor for overall behavioral weight-management self-efficacy. Measurement equivalence/invariance between relevant demographic groups was also supported by tests for equivalence of covariance matrices. Bivariate correlations between self-efficacy factors and measures of PA, dietary intake, and weight support the concurrent validity of score interpretations. Overall, these psychometric analyses support the validity of these scales' scores as independently reflective of self-efficacy for PA, healthful eating, and weight loss. This instrument is useful in clinical research to identify the cognitive drivers of weight loss and weight loss-inducing behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Using a population health management approach to enroll participants in a diabetes prevention trial: reach outcomes from the PREDICTS randomized clinical trial.

Population health management (PHM) strategies to address diabetes prevention have the potential to engage large numbers of at-risk individuals in a short duration. We examined a PHM approach to recruit participants to a diabetes prevention clinical trial in a metropolitan health system. We examined reach and representativeness and assessed differences from active and passive respondents to recruitment outreach, and participants enrolled through two clinical screening protocols. The PHM approach included an electronic health record (EHR) query, physician review of identified patients, letter invitation, and telephone follow-up. Data describe the reach and representativeness of potential participants at multiple stages during the recruitment process. Subgroup analyses examined proportional reach, participant differences based on passive versus active recruitment response, and clinical screening method used to determine diabetes risk status. The PHM approach identified 10,177 potential participants to receive a physician letter invitation, 60% were contacted by telephone, 2,796 (46%) completed telephone screening, 1,961 were eligible from telephone screen, and 599 were enrolled in 15 months. Accrual was unaffected by shifting clinical screening protocols despite the increase in participant burden. Relative to census data, study participants were more likely to be obese, female, older, and Caucasian. Relative to the patient population, enrolled participants were less likely to be Black and were older. Active respondents were more likely to have a higher income than passive responders. PHM strategies have the potential to reach a large number of participants in a relatively short period, though concerted efforts are needed to increase participant diversity.

Reach and effectiveness of a weight loss intervention in patients with prediabetes in Colorado.

INTRODUCTION: Although lifestyle interventions are effective in delaying the onset of diabetes, translating these lessons to routine health care settings remains a challenge. We investigated the effectiveness of a theory-based, brief, small-group weight loss intervention for diabetes prevention. A secondary purpose was to determine the potential reach of the intervention. METHODS: A total of 14,379 members of an integrated health care organization newly diagnosed with prediabetes were potentially eligible to participate in this matched cohort longitudinal study. Of this group, 1,030 attended a 90-minute, small-group session that targeted personal action planning for healthful eating, physical activity, and weight management. We accessed electronic medical records to select 1 to 2 controls (matched on impaired fasting glucose measurement, sex, age, and body mass index) for each member who attended the small-group session (n = 760). Weight change, as recorded in the medical record, was the primary outcome. Mixed models analyses were used to adjust for matching variables and covariates and to account for individual random effects over time. RESULTS: Small-group participants lost significantly more weight than did their matched controls. A significantly higher proportion of small-group participants lost at least 5% of their body weight compared with controls. CONCLUSION: A brief, small-group weight loss intervention was effective. However, it did not reach broadly into the population that was at risk for diabetes.

Preventing diabetes with digital health and coaching for translation and scalability (PREDICTS): A type 1 hybrid effectiveness-implementation trial protocol.

BACKGROUND: Diabetes prevention remains a top public health priority; digital approaches are potential solutions to existing scalability and accessibility challenges. There remains a gap in our understanding of the relationship between effectiveness, costs, and potential for sustained implementation of digital diabetes prevention strategies within typical healthcare settings. PURPOSE: To describe the methods and design of a type 1 hybrid effectiveness-implementation trial of a digital diabetes prevention program (DPP) using the iPARIHS and RE-AIM frameworks. METHODS: The trial will contrast the effects of two DPP interventions: (1) small group, in-person class, and (2) a digital DPP consisting of small group support, personalized health coaching, digital tracking tools, and weekly behavior change curriculum. Each intervention includes personal action planning with a focus on key elements of the lifestyle intervention from the CDC National DPP. Adults at risk for diabetes (BMI ≥25 and 5.7% ≤ HbA1c ≤ 6.4) will be randomly assigned to either the intervention group (n = 241) or the small group (n = 241). Assessment of primary (HbA1c) and secondary (weight loss, costs, cardiovascular risk factors) outcomes will occur at baseline, 4, and 12 months. Additionally, the trial will explore the potential for future adoption, implementation, and sustainability of the digitally-based intervention within a regional healthcare system based on key informant interviews and assessments of organizational administrators and primary care physicians. CONCLUSION: This trial of a digital DPP will allow the research team to determine the relationships between reach, effectiveness, implementation, and costs.

Translating efficacious behavioral principles for diabetes prevention into practice.

This case study describes the process of translating efficacy-based Diabetes Prevention Program principles into a practical format for delivery within a managed care organization. Using Rogers' innovation-decision process model, the authors tracked the adoption, implementation, and short-term effectiveness of a clinical program. Effectiveness was documented using a pre-post design to detect changes in physical activity and dietary habits. Participants (N = 298) were Kaiser Permanente of Colorado patients enrolled in diabetes-prevention classes. Changes were analyzed using paired-samples t tests and one-way analysis of variance. Participants significantly increased reported minutes of moderate (p < .001, mu = 84.52, CI: 58.44-110.61) and vigorous (t = 2.220, p = .028, mu = 19.05, CI: 2.10-36.00) physical activity and their daily servings of fruits and vegetables (p < .001, mu = 0.20, CI: 0.13-0.27). By identifying the underlying strategies that led to efficacy, professionals can implement sound diabetes-prevention programs that fit within their context.

Epigenetic reprogramming in metabolic disorders: nutritional factors and beyond.

Environmental factors (e.g., malnutrition and physical inactivity) contribute largely to metabolic disorders including obesity, type 2 diabetes, cardiometabolic disease and nonalcoholic fatty liver diseases. The abnormalities in metabolic activity and pathways have been increasingly associated with altered DNA methylation, histone modification and noncoding RNAs, whereas lifestyle interventions targeting diet and physical activity can reverse the epigenetic and metabolic changes. Here we review recent evidence primarily from human studies that links DNA methylation reprogramming to metabolic derangements or improvements, with a focus on cross-tissue (e.g., the liver, skeletal muscle, pancreas, adipose tissue and blood samples) epigenetic markers, mechanistic mediators of the epigenetic reprogramming, and the potential of using epigenetic traits to predict disease risk and intervention response. The challenges in epigenetic studies addressing the mechanisms of metabolic diseases and future directions are also discussed and prospected.

Estradiol signaling mediates gender difference in visceral adiposity via autophagy.

Excessive adiposity (particularly visceral fat mass) increases the risks of developing metabolic syndrome. Women have lower deposit of visceral fat than men, and this pattern becomes diminished postmenopausally, but the underlying mechanism remains largely unknown. Here, we show that the gender difference in visceral fat distribution is controlled by an estradiol-autophagy axis. In C57BL/6J and wild-type control mice, a higher visceral fat mass was detected in the males than in the females, which was associated with lower expression of estrogen receptor α (ERα) and more active autophagy in males vs. females. However, deletion of ERα normalized autophagy activity and abolished the gender difference in visceral adiposity. In line with the adiposity-reducing effect of the ERα-autophagy axis, we found that downregulation of ERα and increased autophagy activity were required for adipogenesis, while induction of estradiol signaling dampened autophagy and drastically prevented adipogenesis. Mechanistically, the estradiol-ERα signaling activated mTOR, which phosphorylated and inhibited ULK1, thereby suppressing autophagy and adipogenesis. Together, our study suggests that the lower visceral adiposity in the females (vs. the males) arises from a more active estradiol-ERα signaling, which tunes down autophagy and adipogenesis.

Improving physical activity program adoption using integrated research-practice partnerships: an effectiveness-implementation trial.

Integrated research-practice partnerships (IRPPs) may improve adoption of evidence-based programs. The aim of this study is to compare adoption of an IRPP-developed physical activity (PA) program (Fit Extension, FitEx) to a typical efficacy-effectiveness-dissemination pipeline model program (Active Living Every Day, ALED). Guided by the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework, a randomized controlled trial assigned health educators (HEs) to FitEx (n = 18) or ALED (n = 18). Fourteen HEs adopted FitEx, while two HEs adopted ALED (χ 2 = 21.8; p < 0.05). FitEx HEs took less time to deliver (p < 0.05), stated greater intentions for continued program delivery (p < 0.05), and reached more participants (n = 1097 total; 83 % female; 70 % Caucasian; M age = 44 ± 11.8) per HE than ALED (n = 27 total; 60 % female; 50 % Caucasian; M age = 41 ± 11.3). No significant difference existed in FitEx or ALED participants' increased PA (M increase = 9.12 ±29.09  min/day; p > 0.05). IRPP-developed programs may improve PA program adoption, implementation, and maintenance and may also result in programs that have higher reach-without reducing effectiveness.

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator.

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention.

FoxO1 antagonist suppresses autophagy and lipid droplet growth in adipocytes.

Obesity and related metabolic disorders constitute one of the most pressing heath concerns worldwide. Increased adiposity is linked to autophagy upregulation in adipose tissues. However, it is unknown how autophagy is upregulated and contributes to aberrant adiposity. Here we show a FoxO1-autophagy-FSP27 axis that regulates adipogenesis and lipid droplet (LD) growth in adipocytes. Adipocyte differentiation was associated with upregulation of autophagy and fat specific protein 27 (FSP27), a key regulator of adipocyte maturation and expansion by promoting LD formation and growth. However, FoxO1 specific inhibitor AS1842856 potently suppressed autophagy, FSP27 expression, and adipocyte differentiation. In terminally differentiated adipocytes, AS1842856 significantly reduced FSP27 level and LD size, which was recapitulated by autophagy inhibitors (bafilomycin-A1 and leupeptin, BL). Similarly, AS1842856 and BL dampened autophagy activity and FSP27 expression in explant cultures of white adipose tissue. To our knowledge, this is the first study addressing FoxO1 in the regulation of adipose autophagy, shedding light on the mechanism of increased autophagy and adiposity in obese individuals. Given that adipogenesis and adipocyte expansion contribute to aberrant adiposity, targeting the FoxO1-autophagy-FSP27 axis may lead to new anti-obesity options.