Mobile exergaming in Type 2 Diabetes mellitus – innovative ways to overcome physical inactivity and increase exercise adherence

Background Type 2 diabetes has developed into a worldwide pandemic in recent years that is associated with vast comorbidity and mortality and has created an enormous financial strain on health care systems all around the globe. Physical inactivity is known to be one of the most important risk factors for the development of type 2 diabetes and responsible for much of the diabetes‐related comorbidity. An increase in regular physical activity is therefore an essential component of a successful type 2 diabetes treatment. However, despite the proven benefits of regular physical activity, the vast majority of patients with type 2 diabetes remain inactive – often due to low motivation and lack of physical activity enjoyment. A recent and promising approach to motivate sedentary individuals to be more physically active and sustainably adhere to regular physical activity is exergames. These games integrate physical activity and personal health information into a game or game‐like setting and thereby promote physical activity through playful and enjoyable challenges. Aims The aims of this Ph.D. project were: (1) to systematically review the current evidence for the effectiveness of exergaming in overweight and type 2 diabetes and (2) to evaluate the suitability of the Wii Fit Plus exergame to improve cardiorespiratory fitness in individuals with type 2 diabetes. The aim was further (3) to develop a behavior change technique‐based smartphone game that delivers individualized exercise and physical activity promotion with the intention to motivate inactive type 2 diabetes patients to become sustainably physically active and to plan a 24‐week randomized controlled trial evaluating the game’s effectiveness. In addition, it was aimed (4) to assess the accuracy of a commercial activity wristband and of iOS and Android smartphones to measure steps during various walking conditions as those devices were intended to be used to measure the primary outcome (steps per day) in the 24‐week randomized controlled trial. Finally, the aims were (5) to examine the effectiveness of the smartphone game to increase daily physical activity and improve glycemic control and aerobic capacity as well as (6) to evaluate the game’s suitability to increase the intrinsic physical activity motivation and elicit sustained improvements in physical activity adherence in inactive individuals with type 2 diabetes over a 24‐week period. Methods In this Ph.D. project, one systematic review and three studies were conducted. In the systematic review, electronic bibliographic databases (PubMed, Embase, Web of Science, OpenGrey, and the Cochrane Central Register of Controlled Trials) were searched up to March 2015. Randomized controlled trials and cross‐sectional studies published in English in peer‐reviewed journals were included. Included studies were required to have analyzed the effects of exergames on objectively measured intensity parameters of physical activity (oxygen uptake, energy expenditure, and heart rate) in overweight adults with and without type 2 diabetes. In study 1, data collected from a study conducted by Prof. Schmidt‐Trucksäss before the start of my Ph.D. was analyzed to evaluate the cardiorespiratory exertion (maximum and mean oxygen uptake) of 12 elderly individuals with type 2 diabetes during 10‐minute bouts of different Wii Fit Plus exercises. Oxygen uptake values were compared to the maximally reached values during a previously conducted cardiopulmonary exercise test on a treadmill. Correlations between oxygen uptake values reached during exergame activity and those reached during the all‐out exercise test were analyzed using Spearman’s rank correlation coefficient. Following this preparatory work and considering its results, I collaborated with an international team consisting of sports scientists, gamification researchers, professional game developers, and clinical professionals in developing an innovative smartphone game with the aim to encourage a healthier, more active lifestyle through gamified physical activity in inactive type 2 diabetes patients. To evaluate the effectiveness of the game to sustainably increase physical activity in the target group, I planned a 24‐week randomized controlled trial with daily physical activity (steps per day) as the primary outcome. To verify the validity of the devices used to measure the primary outcome (steps per day) in the 24‐week intervention study, I conducted a validation study in an additional investigation of this Ph.D. project. In the study, 20 participants were equipped with 3 iPhone SE smartphones (placed in pants pocket, shoulder bag, and backpack), 1 Samsung Galaxy S6 Edge (pants pocket), 1 Garmin Vivofit 2 wristband, and 2 ActiGraph wGTX+ devices (worn at wrist and hip) and instructed to walk for five minutes at four predefined walking speeds (1.6, 3.2, 4.8, and 6.0 km/h) and to complete an outdoor walking course. Video observation was used as gold standard. Validity was evaluated by comparing each device with the gold standard using mean absolute percentage errors. In the main study (ClinicalTrials.gov identifier NCT02657018) of this Ph.D. project, 36 inactive, overweight type 2 diabetes patients between 45 and 70 years of age were randomly assigned to either the intervention group or the control group. Participants in the intervention group received the self‐developed smartphone game, and participants in the control group were instructed to implement the recommendations from the baseline lifestyle counseling autonomously during the 24‐week intervention period. Before and after the intervention period, steps per day were objectively measured during six consecutive days. In addition, glycemic control (HbA1c) was measured by analysis of venous blood, and aerobic capacity (oxygen uptake at the first ventilatory threshold) was assessed during an all‐out exercise test on a bike ergometer. Intrinsic physical activity motivation was assessed with an abridged 12‐item version of the Intrinsic Motivation Inventory (IMI). In the intervention group, adherence to the game‐proposed physical activity recommendations during the intervention period was additionally assessed via the phonerecorded game usage data. Analyses of covariance with adjustment for the respective preintervention values were used to compare changes in outcome parameters (steps per day, HbA1c, oxygen uptake at the first ventilatory threshold, and IMI score) between the two groups. Correlations between game use (min) and change in steps per day as well as change in workload (W) at the first ventilatory threshold were analyzed using Spearman’s rank correlation coefficient, and a linear regression model was used to assess the relationship between total in‐game training (min) and change in IMI total score. Results Publication 1: Effects of Exergaming on Physical Activity in Overweight Individuals. [1] The systematic review showed that exergames are able to increase physical activity among overweight individuals. However, the magnitude of this increase as well as the intensity of the exergame‐related physical activity and consequently their suitability to offer a guidelineconcordant training is greatly dependent on the console and the game mode as well on the duration of play. The majority of the included studies were of poor or moderate methodological quality. No studies exist that objectively assess the effect of exergames on daily physical activity in type 2 diabetes, and the cross‐sectional nature of all included studies does not permit judgement on whether exergames are suitable to increase physical activity in the long term. A general lack of adequate individualization of the intensity and difficulty level was noted for all exergames, making most game modes unsuitable for an effective training and potentially unsafe for inactive individuals with chronic diseases and a likely reduced fitness level. Publication 2: Cardiorespiratory Exertion While Playing Video Game Exercises in Elderly Individuals With Type 2 Diabetes. [2] In elderly type 2 diabetes patients, carefully selected Wii Fit Plus exercises elicit peak values in oxygen uptake that correspond to 60% of the maximally reached values during an all‐out treadmill test. Mean values were just above 40% for all exercises and were thus in a range that corresponds to current exercise guidelines. A moderate‐to‐strong positive correlation between the peak oxygen uptake during exergame play and the maximal value reach during the exercise test was found, indicating that subjects with a higher fitness level were able to exercise at a higher intensity during exergame play than individuals with a lower fitness level. Publication 3: Mobile Exergaming for Health – Effects of a Serious Game Application for Smartphones on Physical Activity and Exercise Adherence in Type 2 Diabetes Mellitus – Study Protocol for a Randomized Controlled Trial. [3] The self‐developed and innovative game takes the proven motivational benefit of exergames into consideration and further extends them by integrating established behavior change techniques into an elaborate storyline. Shortcomings with regard to the suitability and effectiveness of the exercise regimen of current exergames are addressed by offering a fitness level‐adjusted training with an individualized rate of intensity progression that is based on the performance in established and in‐game‐conducted exercise tests. Publication 4: Validity of Activity Trackers, Smartphones, and Phone Applications to Measure Steps in Various Walking Conditions. [4] The Garmin Vivofit 2 and iPhone SE showed good accuracy for treadmill walking ≥3.2 km/h (<3% deviation from video recordings) and for free walking thus being suitable to measure steps at normal, fast, and even slow walking speeds. The Samsung Galaxy S6 Edge showed good accuracy (<3% deviation from video recordings) for treadmill walking ≥4.8 km/h and for free walking, demonstrating suitability to measure steps during normal and fast walking. The good validity of the iPhone SE was found independently of the phone’s position (pants pocket, backpack, shoulder bag), suggesting a broad versatility of the device for physical activity measurement in various settings. Publication 5: Publication 5 Behavior Change Technique‐based Smartphone Game Sustainably Increases Daily Physical Activity in Type 2 Diabetes Patients – A Randomized Controlled Trial. [5] In persistently inactive type 2 diabetes patients, a novel self‐developed smartphone game that follows a cognitive/behavioral approach and incorporates individualized exercise regimens and physical activity recommendations elicited significant and clinically meaningful increases in daily physical activity (+4,000 steps per day) over a 24‐week period, classifying the participants as sufficiently active post‐intervention (average of 9,782 steps per day). The increase in daily physical activity was accompanied by an increase in aerobic capacity with a significantly higher oxygen uptake and workload at the first ventilatory threshold. Total duration of in‐game training was positively correlated with the change in steps per day and the change in workload at the first ventilatory threshold. Glycemic control (HbA1c) did not change during the intervention period; however, as indicated by the significant adjusted difference in HbA1c of ‐0.9 percentage points in favor of the intervention group, there is reason to assume that regular use of the game supports the stabilization of glycemic control in medically well‐controlled patients. In the control group, none of the outcome parameters changed significantly during the intervention period. Publication 6: Effectiveness of a Behavior Change Technique‐based Smartphone Game to Improve Intrinsic Motivation and Physical Activity Adherence in Type 2 Diabetes Patients: A Randomized Controlled Trial. [6] The 24‐week randomized controlled trial further showed that participants in the intervention group significantly increased their IMI‐measured intrinsic physical activity motivation during the intervention period. Participants in the control group did not show any significant changes in their intrinsic physical activity motivation. The analysis of the usage data revealed that participants in the intervention group used the game for an average of 143.1 (SD 59.1) minutes of in‐game training per week, which underlines the game’s potential in motivating formerly inactive type 2 diabetes patients to meet and sustainably adhere to established physical activity recommendations. Conclusions A novel smartphone game that incorporates established motivational elements and personalized physical activity recommendations into an elaborate storyline elicits clinically relevant increases in daily physical activity and aerobic capacity and contributes to a medically well‐regulated glycemic control in persistently inactive type 2 diabetes patients. The game is therefore a suitable treatment option to motivate inactive individuals to increase daily physical activity that may be relevant for other inactive target groups with and without chronic diseases. Future research should further refine the game design as well as the motivational and physical activity‐related content to make it an even more comprehensive treatment tool for various target groups

Differential Impact of Biological and Behavioral Traits on Postexercise Energy Intake in Men andWomen

The energy intake response to exercise is highly variable and energy (over-) compensation via increased post-exercise energy intake occurs in some individuals but not others. In explorative analyses, we aimed to identify biological and behavioral predictors of post-exercise ad libitum energy intake and whether these predictors differ from ad libitum energy intake after rest. Conclusions:Post-exercise energy intake is associatedwithdifferent factors than energy intake after rest and behavioral and biological traits differentially affect post-exercise energy intake in men and women. In women, habitual exercise behavior seems to predict postexercise energy intake, protecting against compensatory eating. Inmen, appetite-regulating hormones play a role in the energy intake response to acute exercise. Our findings may help identify individuals who are likely to show post-exercise energy compensation and help explain why it occurs in some individuals but not others

Validation of a visually aides dietary assessment tool to estimate dietary intake in adult Swiss population

Background: Accurately assessing dietary intake is crucial in understanding how diet affects a person’s health. In large cohorts, paper-based Dietary Assessment Tools (DAT) such as food recalls or food frequency questionnaires have emerged as valid tools with a low burden for participants. Objective: To validate a visually aided DAT for use in studies with Swiss adults against the gold standard of a weighed 7-day food record (7d-FR). Design: Fifty-one subjects (n=24 women, n=27 males) participated in the study and were recruited within two age groups (20- 40y and 50-70 y). Each subject filled out the visually aided DAT, then the 7dFR. The DAT was compared to the 7d-FR for total energy intake, macronutrients, sugar, water, and portions of fruits and vegetables. Pearson correlation and Bland-Altman analyses were used for statistical analyses. Results: Total correlations ranged from 0.288 (sugar, p 0.5, whereas only water and protein reached those values in the young group. Both groups overestimated total calories in kcal (+14.0%), grams of protein (+44.6%), and fats (+36.3%), and portions of fruits and vegetables (+16.0%) but strongly underestimated sugar intake (-50.9%). Conclusions: This DAT showed that all macronutrients and total energy intake were estimated more accurately by the older age group and therefore might be adequate to capture dietary habits in older Swiss adults

Exercise-induced changes in central adiposity during a RCT: effect of exercise dose and associations with compensation

Context: Exercise can decrease central adiposity, but the effect of exercise dose and the relationship between central adiposity and exercise-induced compensation is unclear. Objective: Test the effect of exercise dose on central adiposity change and the association between central adiposity and exercise-induced weight compensation. Methods: In this ancillary analysis of a 6-month randomized controlled trial, 170 participants with overweight or obesity (mean±SD BMI: 31.5±4.7 kg/m2) were randomized to a control group or exercise groups that reflected exercise recommendations for health (8 kcal/kg/week [KKW]) or weight loss and weight maintenance (20 KKW). Waist circumference was measured, and dual-energy X-ray absorptiometry assessed central adiposity. Predicted weight change was estimated and weight compensation (weight change minus predicted weight change) was calculated. Results: Between-group change in waist circumference (control: 0.0 cm [95% CI: -1.0,1.0], 8 KKW: -0.7 cm [95% CI: -1.7,0.4], 20 KKW: -1.3 cm [95% CI: -2.4, -0.2]) and visceral adipose tissue (VAT; control: -0.02 kg [95% CI: -0.07,0.04], 8 KKW: -0.01 kg [95% CI: -0.07,0.04], 20 KKW: -0.04 kg [95% CI: -0.10,0.02]) was similar (P≥0.23). Most exercisers (82.6%) compensated (predicted weight change lower than actual weight change). Exercisers who compensated exhibited a 2.5 cm (95% CI: 0.8,4.2) and 0.23 kg (95% CI: 0.14,0.31) increase in waist circumference and VAT, respectively, versus those who did not (P&lt;0.01). Desire to eat predicted VAT change during exercise (β=0.21; P=0.03). Conclusions: In the presence of significant weight compensation, exercise at doses recommended for health and weight loss and weight maintenance leads to negligible changes in central adiposity

Racial variations in appetite-related hormones, appetite, and laboratory-based energy intake from the E-MECHANIC randomized clinical trial

African Americans (AAs) have a higher obesity risk than Whites; however, it is unclear if appetite-related hormones and food intake are implicated. We examined differences in appetite-related hormones, appetite, and food intake between AAs (n = 53) and Whites (n = 111) with overweight or obesity. Participants were randomized into a control group or into supervised, controlled exercise groups at 8 kcal/kg of body weight/week (KKW) or 20 KKW. Participants consumed lunch and dinner at baseline and follow-up, with appetite and hormones measured before and after meals (except leptin). At baseline, AAs had lower peptide YY (PYY; p &lt; 0.01) and a blunted elevation in PYY after lunch (p = 0.01), as well as lower ghrelin (p = 0.02) and higher leptin (p &lt; 0.01) compared to Whites. Despite desire to eat being lower and satisfaction being higher in AAs relative to Whites (p ≤ 0.03), no racial differences in food intake were observed. Compared to Whites, leptin increased in the 8 KKW group in AAs (p = 0.01), yet no other race-by-group interactions were evident. Differences in appetite-related hormones between AAs and Whites exist; however, their influence on racial disparities in appetite, food intake, and obesity within this trial was limited

How to conceptualize and implement a PhD program in health sciences - the Basel approach

Over the past decade, several excellent guidelines have been published on how to enhance the quality of PhD education in Europe. Aimed primarily at preparing students for innovative roles in their fields, they include variously structured approaches to curricular offerings, as well as other program components applicable across specialties (eg: supervisor support, scientific conduct, transferable skills). Since 2012, the interdisciplinary PhD Program in Health Sciences (PPHS) at the Faculty of Medicine of the University of Basel in Switzerland has focused on translating these guidelines into a 21st-century health sciences PhD program.; The PPHS started in 2012 based on the European Union (EU) guidelines for PhD education. This article describes the resulting interdisciplinary PhD program's conceptual underpinnings, rationale, structures, and 10 building blocks, like student portfolios, thematic training, interdisciplinary research seminars, student-initiated interdisciplinary activities, financial support of course participation, top-up and extension stipends, PhD supervision, research integrity, alumni follow-up network, and promotional tools including a dedicated website. Students enter from Clinical Research, Medicine Development, Nursing Science, Epidemiology and Public Health including Insurance Medicine, Sport Science (all from the Faculty of Medicine), and Epidemiology (Faculty of Science).; The Basel PPHS exemplifies state-of-the-art PhD education in Health Sciences based on European guidelines and offers guidance to other groups from conceptualization to rollout of an interdisciplinary health sciences PhD program

The Personalized Nutrition Study (POINTS): evaluation of a genetically informed weight loss approach, a randomized clinical trial

Weight loss (WL) differences between isocaloric high-carbohydrate and high-fat diets are generally small; however, individual WL varies within diet groups. Genotype patterns may modify diet effects, with carbohydrate-responsive genotypes losing more weight on high-carbohydrate diets (and vice versa for fat-responsive genotypes). We investigated whether 12-week WL (kg, primary outcome) differs between genotype-concordant and genotype-discordant diets. In this 12-week single-center WL trial, 145 participants with overweight/obesity were identified a priori as fat-responders or carbohydrate-responders based on their combined genotypes at ten genetic variants and randomized to a high-fat (n = 73) or high-carbohydrate diet (n = 72), yielding 4 groups: (1) fat-responders receiving high-fat diet, (2) fat-responders receiving high-carbohydrate diet, (3) carbohydrate-responders receiving high-fat diet, (4) carbohydrate-responders receiving high-carbohydrate diet. Dietitians delivered the WL intervention via 12 weekly diet-specific small group sessions. Outcome assessors were blind to diet assignment and genotype patterns. We included 122 participants (54.4 [SD:13.2] years, BMI 34.9 [SD:5.1] kg/m2, 84% women) in the analyses. Twelve-week WL did not differ between the genotype-concordant (−5.3 kg [SD:1.0]) and genotype-discordant diets (−4.8 kg [SD:1.1]; adjusted difference: −0.6 kg [95% CI: −2.1,0.9], p = 0.50). With the current ability to genotype participants as fat- or carbohydrate-responders, evidence does not support greater WL on genotype-concordant diets. ClinicalTrials identifier: NCT04145466

Investigating the circulating sphingolipidome response to a single high-intensity interval training session within healthy females and males in their twenties (SphingoHIIT): Protocol for a randomised controlled trial [version 2; peer review: 2 approved]

Introduction: Growing scientific evidence indicates that sphingolipids predict cardiometabolic risk, independently of and beyond traditional biomarkers such as low-density lipoprotein cholesterol. To date, it remains largely unknown if and how exercise, a simple, low-cost, and patient-empowering modality to optimise cardiometabolic health, influences sphingolipid levels. The SphingoHIIT study aims to assess the response of circulating sphingolipid species to a single session of high-intensity interval training (HIIT). Methods: This single-centre randomised controlled trial (RCT) will last 11 days per participant and aim to include 32 young and healthy individuals aged 20-29 (50% females). Participants will be randomly allocated to the HIIT (n= 16) or control groups (physical rest, n= 16). Participants will self-sample fasted dried blood spots for three consecutive days before the intervention (HIIT versus rest) to determine baseline sphingolipid levels. Dried blood spots will also be collected at five time points (2, 15, 30, 60min, and 24h) following the intervention (HIIT versus rest). To minimise the dietary influence, participants will receive a standardised diet for four days, starting 24 hours before the first dried blood sampling. For females, interventions will be timed to fall within the early follicular phase to minimise the menstrual cycle's influence on sphingolipid levels. Finally, physical activity will be monitored for the whole study duration using a wrist accelerometer. Ethics and dissemination: The Ethics Committee of Northwest and Central Switzerland approved this protocol (ID 2022–00513). Findings will be disseminated in scientific journals and meetings. Trial Registration The trial was registered on www.clinicaltrials.gov (NCT05390866, https://clinicaltrials.gov/ct2/show/NCT05390866) on May 25, 2022

Behavioural determinants of physical activity across the life course: a "Determinants of Diet and Physical Activity" (DEDIPAC) umbrella literature review

Background Low levels of physical activity (PA) are a global concern and increasing PA engagement is becoming a priority in current public health policies. Despite the large number of studies and reviews available, the evidence regarding the behavioral determinants of PA is still inconclusive. Thus, the aim of this umbrella systematic literature review (SLR) was to summarize the evidence on the behavioral determinants of PA across the life course. Methods A systematic online search was conducted on MEDLINE, ISI Web of Science, Scopus, and SPORTDiscus databases. The search was limited to studies published in English from January, 2004 to April, 2016. SLRs and meta-analyses (MAs) of observational studies that investigated the behavioral determinants of PA were considered eligible. The extracted data were assessed based on the importance of the determinants, the strength of evidence, and the methodological quality. The full protocol is available from PROSPERO (PROSPERO 2014:CRD42015010616). Results Seventeen reviews on 35 behavioral determinants of PA were eligible for this umbrella SLR. Regardless of age, the most investigated determinants were those related with ‘screen use’ and ‘smoking’. For youth, probable positive evidence emerged for ‘previous PA’ and ‘independent mobility and active transport’ among children and adolescents. For the adult population, ‘transition to university’ and ‘pregnancy/having a child’ showed probable negative associations. Conclusions Although the majority of the evidence was limited and most of the determinants were not associated with PA, this umbrella SLR provided a comprehensive overview of the associations between behavioral determinants and PA. Youth should be physically active in the early years and increase active transportation to/from school, independent mobility, and ‘free-range activities’ without adult supervision, whilst adult PA behaviors are mostly influenced by the life events. Finally, more research is needed that incorporates prospective study designs, standardized definitions of PA, objective measurement methods of PA assessment, and the use of interactionist and mediational approaches for the evaluation of different behavioral determinants influencing PA behaviors

ViennaRNA Package 2.0

<p>Abstract</p> <p>Background</p> <p>Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties.</p> <p>Results</p> <p>The <monospace>ViennaRNA</monospace> Package has been a widely used compilation of RNA secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the <it>Turner 2004 </it>parameters, the pervasive use of multi-core CPUs, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying <monospace>RNAlib</monospace> and the interactive user programs. New features include an expanded repertoire of tools to assess RNA-RNA interactions and restricted ensembles of structures, additional output information such as <it>centroid </it>structures and <it>maximum expected accuracy </it>structures derived from base pairing probabilities, or <it>z</it>-<it>scores </it>for locally stable secondary structures, and support for input in <monospace>fasta</monospace> format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions.</p> <p>Conclusions</p> <p>The <monospace>ViennaRNA Package 2.0</monospace>, supporting concurrent computations <monospace>via OpenMP</monospace>, can be downloaded from <url>http://www.tbi.univie.ac.at/RNA</url>.</p