Fabio A. Almeida

Mitochondrial alteration in type 2 diabetes and obesity: An epigenetic link

The growing epidemic of type 2 diabetes mellitus (T2DM) and obesity is largely attributed to the current lifestyle of over-consumption and physical inactivity. As the primary platform controlling metabolic and energy homeostasis, mitochondria show aberrant changes in T2DM and obese subjects. While the underlying mechanism is under extensive investigation, epigenetic regulation is now emerging to play an important role in mitochondrial biogenesis, function, and dynamics. In line with lifestyle modifications preventing mitochondrial alterations and metabolic disorders, exercise has been shown to change DNA methylation of the promoter of PGC1α to favor gene expression responsible for mitochondrial biogenesis and function. In this article we discuss the epigenetic mechanism of mitochondrial alteration in T2DM and obesity, and the effects of lifestyle on epigenetic regulation. Future studies designed to further explore and integrate the epigenetic mechanisms with lifestyle modification may lead to interdisciplinary interventions and novel preventive options for mitochondrial alteration and metabolic disorders.

Methods for the cultural adaptation of a diabetes lifestyle intervention for Latinas: an illustrative project.

Because Latinas experience a high prevalence of type 2 diabetes and its complications, there is an urgent need to reach them with interventions that promote healthful lifestyles. This article illustrates a sequential approach that took an effective multiple-risk-factor behavior-change program and adapted it for Latinas with type 2 diabetes. Adaptation stages include (a) information gathering from literature and focus groups, (b) preliminary adaptation design, and (c) preliminary adaptation test. In this third stage, a pilot study finds that participants were highly satisfied with the intervention and showed improvement across diverse outcomes. Key implications for applications include the importance of a model for guiding cultural adaptations, and the value of procedures for obtaining continuous feedback from staff and participants during the preliminary adaptation test.

Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans

BackgroundMitochondrial alterations have been observed in subjects with metabolic disorders such as obesity and diabetes. Studies on animal models and cell cultures suggest aberrant glucose and lipid levels, and impaired insulin signaling might lead to mitochondrial changes. However, the molecular mechanism underlying mitochondrial aberrance remains largely unexplored in human subjects.ResultsHere we show that the mitochondrial DNA copy number (mtDNAn) was significantly reduced (6.9-fold lower, p < 0.001) in the leukocytes from obese humans (BMI >30). The reduction of mtDNAn was strongly associated with insulin resistance (HOMA-IR: −0.703, p < 0.05; fasting insulin level: −0.015, p < 0.05); by contrast, the correlation between fasting glucose or lipid levels and mtDNAn was not significant. Epigenetic study of the displacement loop (D-loop) region of mitochondrial genome, which controls the replication and transcription of the mitochondrial DNA as well as organization of the mitochondrial nucleoid, revealed a dramatic increase of DNA methylation in obese (5.2-fold higher vs. lean subjects, p < 0.05) and insulin-resistant (4.6-fold higher vs. insulin-sensitive subjects, p < 0.05) individuals.ConclusionsThe reduction of mtDNAn in obese human subjects is associated with insulin resistance and may arise from increased D-loop methylation, suggesting an insulin signaling-epigenetic-genetic axis in mitochondrial regulation.

Move More: Translating an efficacious group dynamics physical activity intervention into effective clinical practice

The purpose of this study was to describe the effectiveness of a practical group dynamics-based physical activity (PA) intervention and determine the mechanisms of PA change. Participants (n =115) were randomly assigned to the three-month Move More intervention or Enhanced Standard Care control. Self-reported PA and proposed mediators were assessed at baseline, three and nine months. Participants from both conditions increased their PA during the initial three months, F(2,67) = 24.67, p < .01. A significant time by condition interaction, F(2,67) = 4.25, p < .05, demonstrated that participants in the group dynamics condition sustained or further increased PA at nine months while those in the Enhanced Standard Care did not. Change in self-efficacy, outcome expectation-satisfaction, PA goals, and institutional support, significantly predicted increases in PA (p < .05) at three months, but not at nine months. These findings demonstrate the potential of adopting efficacious group dynamics principles from intensive PA interventions into a practical and effective clinical model.

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.

The Effectiveness and Cost of Lifestyle Interventions Including Nutrition Education for Diabetes Prevention: A Systematic Review and Meta-Analysis

BACKGROUND Type 2 diabetes is a significant public health concern. With the completion of the Diabetes Prevention Program, there has been a proliferation of studies attempting to translate this evidence base into practice. However, the cost, effectiveness, and cost-effectiveness of these adapted interventions is unknown. OBJECTIVE The purpose of this systematic review was to conduct a comprehensive meta-analysis to synthesize the effectiveness, cost, and cost-effectiveness of lifestyle diabetes prevention interventions and compare effects by intervention delivery agent (dietitian vs non-dietitian) and channel (in-person vs technology-delivered). METHODS English and full-text research articles published up to July 2015 were identified using the Cochrane Library, PubMed, Education Resources Information Center, CAB Direct, Science Direct, and Google Scholar. Sixty-nine studies met inclusion criteria. Most employed both dietary and physical activity intervention components (four of 69 were diet-only interventions). Changes in weight, fasting and 2-hour blood glucose concentration, and hemoglobin A1c were extracted from each article. Heterogeneity was measured by the I2 index, and study-specific effect sizes or mean differences were pooled using a random effects model when heterogeneity was confirmed. RESULTS Participants receiving intervention with nutrition education experienced a reduction of 2.07 kg (95% CI 1.52 to 2.62; P<0.001; I2=90.99%, 95% CI 88.61% to 92.87%) in weight at 12 months with effect sizes over time ranging from small (0.17, 95% CI 0.04 to 0.30; P=0.012; I2= 86.83%, 95% CI 80.42% to 91.14%) to medium (0.65, 95% CI 0.49 to 0.82; P<0.001; I2=98.75%, 95% CI 98.52% to 98.94). Effect sizes for 2-hour blood glucose and hemoglobin A1c level changes ranged from small to medium. The meta-regression analysis revealed a larger relative weight loss in dietitian-delivered interventions than in those delivered by nondietitians (full sample: -1.0 kg; US subsample: -2.4 kg), and did not find statistical evidence that the delivery channel was an important predictor of weight loss. The average cost per kilogram weight loss ranged from

Who participates in internet-based worksite weight loss programs?

34.06 over 6 months to

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

1,005.36 over 12 months. The cost of intervention per participant delivered by dietitians was lower than interventions delivered by non-dietitians, although few studies reported costs. CONCLUSIONS Lifestyle interventions are effective in reducing body weight and glucose-related outcomes. Dietitian-delivered interventions, compared with those delivered by other personnel, achieved greater weight reduction. No consistent trend was identified across different delivery channels.

The Influence of Health Literacy on Reach, Retention, and Success in a Worksite Weight Loss Program.

BackgroundThe 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.MethodsA 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.ResultsThe 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 (ps < .01).ConclusionsWorksite weight loss programs should include targeted marketing strategies to engage employees with lower income, education, and health literacy.

Does Successful Weight Loss in an Internet-Based Worksite Weight Loss Program Improve Employee Presenteeism and Absenteeism?

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.