Protocol for a randomized controlled trial comparing a very low-carbohydrate diet or moderate-carbohydrate plate-method diet for type 2 diabetes: the LEGEND (Lifestyle Education about Nutrition for Diabetes) trial.

BACKGROUND: Optimal carbohydrate intake is an important and controversial area in the nutritional management of type 2 diabetes. Some evidence indicates that reducing overall carbohydrate intake with a low- or very low-carbohydrate eating plan can improve glycemic control compared to following eating plans that involve greater carbohydrate intake. However, critical knowledge gaps currently prevent clear recommendations about carbohydrate intake levels. METHODS: The LEGEND (Lifestyle Education about Nutrition for Diabetes) Trial aims to compare a very low-carbohydrate diet to a moderate-carbohydrate plate-method diet for glycemic control in adults with type 2 diabetes. This two-site trial plans to recruit 180 adults with type 2 diabetes. We will randomize participants to either a 20-session group-based diet and lifestyle intervention that teaches either a very low-carbohydrate diet or a moderate-carbohydrate plate-method diet. We will assess participants at study entry and 4 and 12 months later. The primary outcome is HbA1c, and secondary outcomes include inflammation (high sensitivity C-reactive protein), body weight, changes in diabetes medications, lipids (small particle LDL, HDL, triglycerides), skeletal metabolism (bone mineral density from dual-energy x-ray absorptiometry and bone turnover markers serum procollagen type I N propeptide and serum C-terminal telopeptide of type I collagen), and body composition (percent body fat, percent lean body mass). DISCUSSION: The LEGEND trial is a randomized controlled trial to assess optimal carbohydrate intake in type 2 diabetes by evaluating the effects of a very low-carbohydrate diet vs. a moderate-carbohydrate plate-method diet over a year-long period. The research addresses important gaps in the evidence base for the nutritional management of type 2 diabetes by providing data on potential benefits and adverse effects of different levels of carbohydrate intake. TRIAL REGISTRATION: ClinicalTrials.gov NCT05237128. Registered on February 11, 2022.

Focus on the Breath: Brain Decoding Reveals Internal States of Attention During Meditation.

Meditation practices are often used to cultivate interoception or internally-oriented attention to bodily sensations, which may improve health via cognitive and emotional regulation of bodily signals. However, it remains unclear how meditation impacts internal attention (IA) states due to lack of measurement tools that can objectively assess mental states during meditation practice itself, and produce time estimates of internal focus at individual or group levels. To address these measurement gaps, we tested the feasibility of applying multi-voxel pattern analysis (MVPA) to single-subject fMRI data to: (1) learn and recognize internal attentional states relevant for meditation during a directed IA task; and (2) decode or estimate the presence of those IA states during an independent meditation session. Within a mixed sample of experienced meditators and novice controls (N = 16), we first used MVPA to develop single-subject brain classifiers for five modes of attention during an IA task in which subjects were specifically instructed to engage in one of five states [i.e., meditation-related states: breath attention, mind wandering (MW), and self-referential processing, and control states: attention to feet and sounds]. Using standard cross-validation procedures, MVPA classifiers were trained in five of six IA blocks for each subject, and predictive accuracy was tested on the independent sixth block (iterated until all volumes were tested, N = 2,160). Across participants, all five IA states were significantly recognized well above chance (>41% vs. 20% chance). At the individual level, IA states were recognized in most participants (87.5%), suggesting that recognition of IA neural patterns may be generalizable for most participants, particularly experienced meditators. Next, for those who showed accurate IA neural patterns, the originally trained classifiers were applied to a separate meditation run (10-min) to make an inference about the percentage time engaged in each IA state (breath attention, MW, or self-referential processing). Preliminary group-level analyses demonstrated that during meditation practice, participants spent more time attending to breath compared to MW or self-referential processing. This paradigm established the feasibility of using MVPA classifiers to objectively assess mental states during meditation at the participant level, which holds promise for improved measurement of internal attention states cultivated by meditation.

Lipid findings from the Diabetes Education to Lower Insulin, Sugars, and Hunger (DELISH) Study.

BACKGROUND: A carbohydrate-restricted (CR) diet can improve glycemic control in people with type 2 diabetes mellitus (T2DM). There are concerns, however, that the high dietary fat content of CR diets can increase low-density lipoprotein cholesterol (LDL-C), thus increasing cardiovascular disease (CVD) risk. Quantifying CVD risk associated with changes in LDL-C in the context of CR diets is complicated by the fact that LDL-C reflects heterogeneous lipids. For example, small LDL particle number (sLDL-P) is more closely associated with CVD risk than is total LDL-C, and CR diets tend to decrease the proportion of sLDL-C in LDL-C, which standard lipid measures do not indicate. Advanced lipoprotein assays, such as nuclear magnetic resonance (NMR) testing, can subfractionate lipoproteins by size and density and may better depict the effects of CR diets on CVD risk. METHODS: Adults (N = 58) with T2DM (n = 37 women; baseline HbA1c ≥ 6.5%) completed a 6-month group-based CR diet intervention. We obtained a standard lipid panel, advanced lipoprotein assays (NMR testing), and two 24-h diet recalls at baseline and post-intervention (6 months). Participants also completed home-based blood ketone testing (a biological index of dietary adherence) during the final five weeks of the intervention. RESULTS: From baseline to post-intervention, participants had increased mean HDL-C, decreased triglycerides and triglyceride/HDL ratio, decreased mean sLDL-P, and increased LDL size, which reflect reductions in CVD risk (ps < 0.05). Participants did not have statistically significant changes in total cholesterol, non-HDL-C cholesterol, LDL-P, or HDL-P. Twelve participants (23.1%) had a ≥ 5% increase in sLDL-P. Exploratory analyses revealed that participants with sLDL-P increases of ≥ 5% reported larger increases in servings of red meat than participants without sLDL-P increases of ≥ 5% (+ 0.69 vs - 0.29 servings; p = 0.033). Changes in saturated fat intake were not associated with changes in sLDL-P. CONCLUSIONS: Among most participants, we observed changes in several lipid measures consistent with decreased CVD risk. Approximately one in four participants evidenced increases in sLDL-P. Further research should clarify whether individuals with increased sLDL-P after implementing a CR diet can reverse observed increases by limiting red meat consumption. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03207711, Registered 6/11/2017. Retrospectively registered.

A Randomized Controlled Trial of a Mindfulness-Based Weight Loss Intervention on Cardiovascular Reactivity to Social-Evaluative Threat Among Adults with Obesity.

OBJECTIVE: Mindfulness-based interventions have been found to reduce psychological and physiological stress reactivity. In obesity, however, stress reactivity is complex, with studies showing both exaggerated and blunted physiological responses to stressors. A nuanced view of stress reactivity is the "challenge and threat" framework, which defines adaptive and maladaptive patterns of psychophysiological stress reactivity. We hypothesized that mindfulness training would facilitate increased challenge-related appraisals, emotions, and cardiovascular reactivity, including sympathetic nervous system activation paired with increased cardiac output (CO) and reduced total peripheral resistance (TPR) compared to a control group, which would exhibit an increased threat pattern of psychophysiological reactivity to repeated stressors. METHODS: Adults (N=194) with obesity were randomized to a 5.5-month mindfulness-based weight loss intervention or an active control condition with identical diet-exercise guidelines. Participants were assessed at baseline and 4.5 months later using the Trier Social Stress Task. Electrocardiogram, impedance cardiography, and blood pressure were acquired at rest and during the speech and verbal arithmetic tasks to assess pre-ejection period (PEP), CO, and TPR reactivity. RESULTS: Mindfulness participants showed significantly greater maintenance of challenge-related emotions and cardiovascular reactivity patterns (higher CO and lower TPR) from pre to post-intervention compared to control participants, but groups did not differ in PEP. Findings were independent of changes in body mass index. CONCLUSIONS: Mindfulness training may increase the ability to maintain a positive outlook and mount adaptive cardiovascular responses to repeated stressors among persons with obesity though findings need to be replicated in other populations and using other forms of mindfulness interventions.

Correction to: Lipid findings from the Diabetes Education to Lower Insulin, Sugars, and Hunger (DELISH) Study.

[This corrects the article DOI: 10.1186/s12986-019-0383-2.].

Twelve-month outcomes of a randomized trial of a moderate-carbohydrate versus very low-carbohydrate diet in overweight adults with type 2 diabetes mellitus or prediabetes.

Dietary treatment is important in management of type 2 diabetes or prediabetes, but uncertainty exists about the optimal diet. We randomized adults (n = 34) with glycated hemoglobin (HbA1c) > 6.0% and elevated body weight (BMI > 25) to a very low-carbohydrate ketogenic (LCK) diet (n = 16) or a moderate-carbohydrate, calorie-restricted, low-fat (MCCR) diet (n = 18). All participants were encouraged to be physically active, get sufficient sleep, and practice behavioral adherence strategies based on positive affect and mindful eating. At 12 months, participants in the LCK group had greater reductions in HbA1c levels (estimated marginal mean (EMM) at baseline = 6.6%, at 12 mos = 6.1%) than participants in MCCR group (EMM at baseline = 6.9%, at 12 mos = 6.7%), p = .007. Participants in the LCK group lost more weight (EMM at baseline = 99.9 kg, at 12 mos = 92.0 kg) than participants in the MCCR group (EMM at baseline = 97.5 kg, at 12 mos = 95.8 kg), p < .001. The LCK participants experienced larger reductions in diabetes-related medication use; of participants who took sulfonylureas or dipeptidyl peptidase-4 inhibitors at baseline, 6/10 in the LCK group discontinued these medications compared with 0/6 in the MCCR group (p = .005). In a 12-month trial, adults with elevated HbA1c and body weight assigned to an LCK diet had greater reductions in HbA1c, lost more weight, and reduced more medications than those instructed to follow an MCCR diet.

An Online Intervention Comparing a Very Low-Carbohydrate Ketogenic Diet and Lifestyle Recommendations Versus a Plate Method Diet in Overweight Individuals With Type 2 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Type 2 diabetes is a prevalent, chronic disease for which diet is an integral aspect of treatment. In our previous trial, we found that recommendations to follow a very low-carbohydrate ketogenic diet and to change lifestyle factors (physical activity, sleep, positive affect, mindfulness) helped overweight people with type 2 diabetes or prediabetes improve glycemic control and lose weight. This was an in-person intervention, which could be a barrier for people without the time, flexibility, transportation, social support, and/or financial resources to attend. OBJECTIVE: The aim was to determine whether an online intervention based on our previous recommendations (an ad libitum very low-carbohydrate ketogenic diet with lifestyle factors; "intervention") or an online diet program based on the American Diabetes Associations' "Create Your Plate" diet ("control") would improve glycemic control and other health outcomes among overweight individuals with type 2 diabetes. METHODS: In this pilot feasibility study, we randomized overweight adults (body mass index ≥25) with type 2 diabetes (glycated hemoglobin [HbA1c] 6.5%-9.0%) to a 32-week online intervention based on our previous recommendations (n=12) or an online diet program based around a plate method diet (n=13) to assess the impact of each intervention on glycemic control and other health outcomes. Primary and secondary outcomes were analyzed by mixed-effects linear regression to compare outcomes by group. RESULTS: At 32 weeks, participants in the intervention group reduced their HbA1c levels more (estimated marginal mean [EMM] -0.8%, 95% CI -1.1% to -0.6%) than participants in the control group (EMM -0.3%, 95% CI -0.6% to 0.0%; P=.002). More than half of the participants in the intervention group (6/11, 55%) lowered their HbA1c to less than 6.5% versus 0% (0/8) in the control group (P=.02). Participants in the intervention group lost more weight (EMM -12.7 kg, 95% CI -16.1 to -9.2 kg) than participants in the control group (EMM -3.0 kg, 95% CI -7.3 to 1.3 kg; P<.001). A greater percentage of participants lost at least 5% of their body weight in the intervention (10/11, 90%) versus the control group (2/8, 29%; P=.01). Participants in the intervention group lowered their triglyceride levels (EMM -60.1 mg/dL, 95% CI -91.3 to -28.9 mg/dL) more than participants in the control group (EMM -6.2 mg/dL, 95% CI -46.0 to 33.6 mg/dL; P=.01). Dropout was 8% (1/12) and 46% (6/13) for the intervention and control groups, respectively (P=.07). CONCLUSIONS: Individuals with type 2 diabetes improved their glycemic control and lost more weight after being randomized to a very low-carbohydrate ketogenic diet and lifestyle online program rather than a conventional, low-fat diabetes diet online program. Thus, the online delivery of these very low-carbohydrate ketogenic diet and lifestyle recommendations may allow them to have a wider reach in the successful self-management of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01967992; https://clinicaltrials.gov/ct2/show/NCT01967992 (Archived by WebCite at http://www.webcitation.org/6o0fI9Mkq).

Effects of a mindfulness-based weight loss intervention in adults with obesity: A randomized clinical trial.

OBJECTIVE: To determine whether adding mindfulness-based eating and stress management practices to a diet-exercise program improves weight loss and metabolic syndrome components. METHODS: In this study 194 adults with obesity were randomized to a 5.5-month program with or without mindfulness training and identical diet-exercise guidelines. Intention-to-treat analyses with multiple imputation were used for missing data. The primary outcome was 18-month weight change. RESULTS: Estimated effects comparing the mindfulness to control arm favored the mindfulness arm in (a) weight loss at 12 months, -1.9 kg (95% CI: -4.5, 0.8; P = 0.17), and 18 months, -1.7 kg (95% CI: -4.7, 1.2; P = 0.24), though not statistically significant; (b) changes in fasting glucose at 12 months, -3.1 mg/dl (95% CI: -6.3, 0.1; P = 0.06), and 18 months, -4.1 mg/dl (95% CI: -7.3, -0.9; P = 0.01); and (c) changes in triglyceride/HDL ratio at 12 months, -0.57 (95% CI: -0.95, -0.18; P = 0.004), and 18 months, -0.36 (95% CI: -0.74, 0.03; P = 0.07). Estimates for other metabolic risk factors were not statistically significant, including waist circumference, blood pressure, and C-reactive protein. CONCLUSIONS: Mindfulness enhancements to a diet-exercise program did not show substantial weight loss benefit but may promote long-term improvement in some aspects of metabolic health in obesity that requires further study.

Feasibility and Preliminary Efficacy of a Novel RDoC-Based Treatment Program for Adolescent Depression: "Training for Awareness Resilience and Action" (TARA)-A Pilot Study.

BACKGROUND: The novel group treatment program Training for Awareness, Resilience, and Action (TARA) was developed to target specific mechanisms based on neuroscience findings in adolescent depression and framed within the National Institute of Mental Health Research Domain Criteria. TARA contains training of autonomic and emotional self-regulation, interoceptive awareness, relational skills, and value-based committed action. METHODS: We performed a single-arm trial to test the feasibility and preliminary efficacy of TARA in reducing depression and anxiety levels and assessed whether the specific targeted domains of function reflected the hypothesized symptom change. Twenty-six adolescents (14-18 years old, 7 males and 19 females) participated in the 12-week group program. Assessment was performed before (T0), immediately after (T1), and 3 months after the end of TARA (T2). RESULTS: Significant improvement was seen in depression symptoms (Reynolds Adolescent Depression Scale Second Edition) between T0-T1 (t-value = -3.56, p = 0.002, CI = -6.64, -1.77) and T0-T2 (t-value = -4.17, p < 0.001, CI = -11.20, -3.75) and anxiety symptoms (Multidimensional Anxiety Scale for Children) between T0-T1 (t-value = -2.26, p = 0.033, CI = -4.61, -0.21) and T0-T2 (t-value = -3.06, p = 0.006, 95% confidence interval = -9.02, -1.73). Significant improvements in psychological flexibility, sleep, and mindfulness skills were also found between T0 and T2. LIMITATIONS: The sample size was small without a control condition. The pilot design did not allow for testing the hypothesized brain changes and effect of TARA on relevant systemic biomarkers. CONCLUSION: TARA is feasible in a sample of clinically depressed and/or anxious adolescents and preliminary efficacy was demonstrated by reduced depression and anxiety symptoms. The specific symptom and behavioral outcomes corresponded well with the hypothesized mechanisms of change.

Training in ChiRunning to reduce blood pressure: a randomized controlled pilot study.

BACKGROUND: People with prehypertension (120-130/80-90 mmHg) are at increased risk of progressing to hypertension. Recommendations for prehypertension include engaging in regular physical activity. We aimed to assess feasibility and acceptability and collect preliminary outcome data on ChiRunning for people with elevated blood pressure. ChiRunning is a commercially available running program based on the mindful movements of Tai Chi, which is aimed at decreasing injury by both increasing body awareness and modifying running form. METHODS: We enrolled adults with elevated systolic (130-150 mmHg) or diastolic (80-100 mmHg) blood pressure in a 12-week pilot trial. Participants were randomized 2:1:1 to 8 weeks of: 1) intervention-a trainer-led ChiRunning group (n = 10); 2) active control-a trainer-led running group (n = 6); or 3) educational control-a self-directed running group (n = 6) and followed for 4 more weeks. The active control and educational control groups were combined for analysis. RESULTS: This study was feasible, meeting recruitment, retention and adherence goals, and acceptable to participants. Systolic and diastolic blood pressure did not change significantly over the study for either the ChiRunning or control groups. Changes in BMI over time were significantly different from zero in the ChiRunning group (p = 0.04) but not in the control group (slope for ChiRunning -0.05 [-0.1 to -0.002] vs. control -0.01 [-0.06 to 0.04], between slope difference, p = 0.22). Self-reported running-related injury (i.e. discomfort leading to a decrease in running) was similar between groups (ChiRunning, 4 [1.2 to 8.4] vs. control, 3 [0.7 to 7.1] injuries per 100 h of running, p = 0.72) although self-reported running-related discomfort (i.e. discomfort that does not lead to changes in running) trended higher in the ChiRunning group (ChiRunning, 10 [5.4 to 16.8] vs. control, 4 [1.5 to 9] reports of discomfort per 100 h of running, p = 0.06). CONCLUSION: ChiRunning appears to be a feasible and acceptable exercise program for people with elevated blood pressure. We did not find that ChiRunning had a significant impact on blood pressure or self reported injury, but did see a positive change in BMI over time. ChiRunning warrants further investigation in a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01587183.

Effects of Form-Focused Training on Running Biomechanics: A Pilot Randomized Trial in Untrained Individuals.

OBJECTIVE: To investigate the changes in running biomechanics after training in form-focused running using ChiRunning versus not-form focused training and self-directed training in untrained individuals. DESIGN: Pilot study-randomized controlled trial. SETTING: Research institution with tertiary care medical center. PARTICIPANTS: Seventeen subjects (9 men, 8 women) with prehypertension. METHODS: Twenty-two participants were randomized to 3 study arms but 17 completed the study. The study arms were: (1) group-based Form-Focused running using ChiRunning (enrolled, n = 10; completed, n = 7); (2) group-based conventional running (enrolled, n = 6; completed, n = 4); and (3) self-directed training with educational materials (enrolled, n = 6; completed, n = 6). The training schedule was prescribed for 8 weeks with 4 weeks of follow-up. All subjects completed overground running motion analyses before and after training. ClinicalTrials.gov identifier for this study is NCT0158718. OUTCOMES: Ankle, knee, hip joint peak moments, and powers; average vertical loading rate (AVLR); impact peak; cadence; stride length; strike index; and stride reach. Paired t tests were used to compare differences within groups over time. RESULTS: Form-focused group reduced their Stride Reach (P = .047) after the training but not the other groups. Form-focused group showed a close to significant reduction in knee adduction moment (P = .051) and a reduction in the peak ankle eversion moment (P = .027). Self-directed group showed an increase in the running speed (P = .056) and increases in ankle and knee joint powers and moments. CONCLUSIONS: There are differences in the changes in running biomechanics between individuals trained in running form that emphasizes mid-foot strike, greater cadence, and shorter stride compared with those not trained in the these techniques. These differences may be associated with reduced lower extremity stress in individuals trained in this running form, but more studies are needed to confirm these findings in larger samples.

A randomized pilot trial of a moderate carbohydrate diet compared to a very low carbohydrate diet in overweight or obese individuals with type 2 diabetes mellitus or prediabetes.

We compared the effects of two diets on glycated hemoglobin (HbA1c) and other health-related outcomes in overweight or obese adults with type 2 diabetes or prediabetes (HbA1c>6%). We randomized participants to either a medium carbohydrate, low fat, calorie-restricted, carbohydrate counting diet (MCCR) consistent with guidelines from the American Diabetes Association (n = 18) or a very low carbohydrate, high fat, non calorie-restricted diet whose goal was to induce nutritional ketosis (LCK, n = 16). We excluded participants receiving insulin; 74% were taking oral diabetes medications. Groups met for 13 sessions over 3 months and were taught diet information and psychological skills to promote behavior change and maintenance. At 3 months, mean HbA1c level was unchanged from baseline in the MCCR diet group, while it decreased 0.6% in the LCK group; there was a significant between group difference in HbA1c change favoring the LCK group (-0.6%, 95% CI, -1.1% to -0.03%, p = 0.04). Forty-four percent of the LCK group discontinued one or more diabetes medications, compared to 11% of the MCCR group (p = 0.03); 31% discontinued sulfonylureas in the LCK group, compared to 5% in the MCCR group (p = 0.05). The LCK group lost 5.5 kg vs. 2.6 kg lost in MCCR group (p = 0.09). Our results suggest that a very low carbohydrate diet coupled with skills to promote behavior change may improve glycemic control in type 2 diabetes while allowing decreases in diabetes medications. This clinical trial was registered with ClinicalTrials.gov, number NCT01713764.