Diabetes Mellitus, Type 2
Conditions
Brief summary
Type 2 diabetes mellitus (T2DM) is the most expensive chronic disease in the U.S. Lifestyle modification is central to T2DM management, but long-term adherence to dietary recommendations is difficult. A key challenge is the difficulty of coping with cravings for high carbohydrate or sugar-laden foods in an environment where these foods are tempting and widely available. One mechanism by which mindfulness may increase long-term dietary adherence is by better equipping individuals with skills to experience food cravings and difficult emotions without eating in response. Such approaches seek to strengthen abilities to be non-judgmentally aware of, tolerate, and respond skillfully to food cravings and difficult emotions without reacting impulsively or maladaptively. The investigators hypothesize that improved ability to manage food cravings and emotional eating is a key mechanism through which mindfulness-enhancements can improve dietary adherence. The study will test a mindfulness-based intervention (MBI) for improving dietary adherence. Although the particular diet employed is not the focus of this study, the study will use a diet with about 10% of calories from carbohydrate as: (1) it induces a low level of ketone production, which will be used as a biomarker for dietary adherence; (2) prior studies suggest it improves metabolic parameters in T2DM, including glycemic control.
Detailed description
The study will use ecological momentary assessment (EMA) methods to measure eating in response to difficult emotions and/or food cravings. In the R61 phase, the team will ensure this measure is appropriate for further testing and assess the impact of the MBI components on our hypothesized behavioral mechanisms in N=60 persons with T2DM. The study plans 3 waves of 20 persons each with 12 weekly sessions. All participants will attend an in-person group course providing education on basic behavioral strategies for diet and physical activity. Participants will be randomized to receive this education alone (Ed) or this same material with added MBI components (Ed+MBI). The team will also pilot test two levels of intensity of maintenance phase intervention (monthly group meetings alone or supplemented by individualized attention) to prepare them for R33 testing. the investigators plan an R33 phase trial in which 120 persons with T2DM will be randomized (using a 1:2 ratio) to Ed or Ed+MBI conditions and followed for 12 months, including a 9-month maintenance phase. The study will test the robustness of the effect of MBI components on our proposed behavioral mechanisms, and on dietary adherence, as well as preliminary effect sizes on weight and glycemic control. The study will use an innovative adaptive intervention design to optimize maintenance phase intensity, which the investigators believe may be key to augment the MBI effects. The R33 phase will be registered and reported in a separate clinicaltrials.gov record.
Interventions
BEHAVIORALCarbohydrate-restricted diet
Education for carbohydrate-restricted diet
BEHAVIORALMindfulness
Mindful eating app-use and instruction
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Blood tests at LabCorp and 24-hour dietary recall interviews are done by research assistants blinded to treatment assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. History of T2DM mellitus. If taking insulin, screening labs will include C-Peptide to rule out T1DM. 2. HbA1c \>= 6.5% and \< 12.0% at screening. 3. Experience food-related cravings most days of the week and eat in response to these cravings regularly. 4. Aged 18 years old and older. 5. Able to engage in light physical activity. 6. Willing and able to participate in the interventions. Must be interested in following a carbohydrate- restricted diet, willing to learn about mindful eating and behavioral strategies for following prescribed diets, have sufficient control over their food intake so that they can follow either diet, and otherwise be able and willing to participate in the intervention. Intervention content must be practiced to evaluate whether it is effective. 7. Have smartphone and are willing to use it on a regular basis for data collection. 8. Ability to speak English.
Exclusion criteria
1. Unable to provide informed consent. 2. A substance abuse, mental health, or medical condition that, in the opinion of investigators, will make it difficult for the potential participant to participate in the intervention or that may need immediate changes in medical management that will affect study outcome measures. Such conditions may include cancer, liver failure, renal failure, untreated hypo or hyperthyroidism, or history of serious bulimia. Some other serious medical conditions that may alter key study outcomes or require other important diet modifications, including untreated hypothyroidism, renal failure, cirrhosis, and conditions requiring oral or parenteral glucocorticoid treatment. 3. Pregnant or planning to get pregnant in the next 6 months, breastfeeding or less than 6 months post-partum. 4. Current use of weight loss medications, such as Alli or amphetamine-based drugs that may affect weight. 5. Planned weight-loss (bariatric) surgery or bariatric surgery within the past 18 months. 6. Currently enrolled in a weight loss program, such as Weight Watchers or a self-help group such as Overeaters Anonymous, or have unalterable plans to enroll in one of these programs in the next year. 7. Vegan or vegetarian. 8. Unwilling to do home ketone monitoring.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Eating in Response to Cravings (Primary Mechanistic Outcome) | change from baseline to 6 months | Percent of ecological momentary assessment (EMA) opportunities in which participants reported eating in response to food cravings over a 3 day period. EMA measures were delivered to cell phones 3 times each day. The final EMA measure each day included a second question about whether there were any instances of craving related eating not already reported earlier during the day. Thus there was an opportunity to report eating in response to cravings on 4 different EMA questions each day, a total of 12 potential measures over 3 days. The percent here uses the number of EMA responses received as the denominator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Emotion-related Eating (Secondary Mechanistic Outcome) | change from baseline to 6 months | Change in emotion-related eating as measured by the Coping subscale of the Palatable Eating Motives Scale (PEMS). The Coping subscale is comprised of 4 items rated on a scale from 1 (almost never/never) to 5 (almost always/always), with possible scores ranging from 4-20. Higher scores reflect worse coping/greater emotional eating. Thus, decreases over time reflect improved coping/decreased emotional eating. |
| Stress-related Eating (Secondary Mechanistic Outcome) | change from baseline to 6 months | Change in stress-related eating as measured by two questions about stress-related eating from the MIDUS study. Possible scores range from 2-8. Higher scores reflect worse outcomes/greater eating in response to stress. Thus, decreases over time reflect improved outcomes/decreased stress-related eating. |
| Glycemic Control, Using HbA1c | change from baseline to 6 months | Change in hemoglobin A1c (HbA1c) from baseline to 6 months by study arm |
| Fasting Glucose | change from baseline to 6 months | Change in plasma fasting glucose from baseline to 6 months by study arm |
| Change in Impulsivity as Measured by Delayed Discounting Score | change from baseline to 6 months | The 5-trial adaptation of the Delayed Discounting (DD; Koffarnus & Bickel, 2014) is a decision-making exercise where individuals choose between a smaller, immediate reward and a larger, delayed reward. The task measures an individual's discount rate, or how much they devalue a future reward compared to an immediate one, which is a a key aspect of impulsivity and self-control. Respondents choose between $100 delivered after a delay, or $50 available immediately. To derive estimates of discount rate, we used Mazur's hyperbolic discounting model (V=A/ (1+kD)18, wherein V is the discounted value of the delayed option, A is its objective amount, D is its delay, and k indexes the discount rate. We calculated values of k for each participant as the inverse of the indifference delay (1/ED50). We log transformed these values prior to analysis. Higher values of K indicate greater discounting, which reflects greater impulsivity. |
| Weight Change(Secondary Clinical Outcome) | change from baseline to 6 months | kilograms |
| Adherence to Diet as Measured by Fingerstick Blood Ketones | 6 months | Adherence to diet as measured by average proportion of fingerstick blood ketones at or above 0.3 mmol/L at 24 weeks. |
| Diet Adherence by Mean Grams of Non-fiber Carbohydrate Consumed Per Day | change from baseline to 6 months | Diet Adherence Between Intervention Arms as Measured by Mean Grams of Non-fiber Carbohydrate Consumed Per Day From 24- Hour Diet Recall |
| Perceived Stress | change from baseline to 6 months | Perceived Stress Scale (PPS-10) total score. Scores can range from 0 to 40 with higher scores indicated greater perceived stress. |
| HOMA-2IR Index of Insulin Resistance (Secondary Clinical Outcome) | change from baseline to 6 months | Insulin resistance estimated from the Homeostatic model assessment (HOMA) model 2 index of insulin resistance. The basic formula is: (glucose × insulin) / 22.5, where glucose is measured in mmol/L and insulin in mU/L. The computer assisted re-calibration in model 2 addresses variations in the glucose resistance of the peripheral tissue and liver, increases in the insulin secretion curve for glucose \> 180 mg/dL, and contribution of circulating pro-insulin. Higher values indicate more insulin resistance (worse outcome). The Oxford University HOMA-2IR calculator was used (https://process.innovation.ox.ac.uk/software/p/2112/homa2-calculator/1). HOMA index values \< 2.0 are generally considered normal and indicate adequate sensitivity of cells to insulin. HOMA index values between 2.0 and 2.5 may indicate borderline changes in insulin sensitivity. HOMA index values \> 2.5 clearly indicate insulin resistance. |
Countries
United States
Participant flow
Recruitment details
Recruitment conducted 12/2016-9/2018 via several sources including: flyers posted in and outreach to providers in UCSF clinics (e.g., Diabetes Clinic, General Internal Medicine Clinic); letters mailed to potentially eligible participants in the UCSF system who had previously consented to be contacted about research studies for which they may be eligible; flyers posted in the community as on social media including Facebook, Nextdoor, and Craigslist. First participant was consented 2/17/2017.
Participants by arm
| Arm | Count |
|---|---|
| Diet Education All participants will receive instruction in the carbohydrate-restricted diet (CR).The study diet has approximately 10% of kcal coming from carbohydrate, typically 50 grams/day or fewer, not including fiber. Participants will be encouraged to eat a normal amount of protein, typically about 80-100 grams/day (about 20-25% of calories), and the rest of their calories from fat. Foods that are encouraged include green leafy and other non-starchy vegetables, nuts, seeds, oils (especially olive oil), fish, poultry, tofu, and avocados. Other foods consistent with the diet include berries (in modest amounts), meats, eggs, and cheese. Key foods to minimize include any sugar-sweetened foods or beverages, bread, pasta, potatoes, highly processed packaged foods, and other starchy foods.
Carbohydrate-restricted diet: Education for carbohydrate-restricted diet | 28 |
| Diet Education + Mindfulness In addition to the carbohydrate-restricted diet described above, the Ed+MBI group will receive mindfulness training consisting of two integrated components: 1) use of a mindful eating app at home to learn and practice mindfulness skills for food-cravings and eating, and 2) in-person group-based meetings to discuss and troubleshoot how the mindfulness practices are working. Key mindfulness content includes helping people improve their relationship with food and control food cravings and using mindful eating approaches including paying attention, noticing habit loops, understanding brain science and food/sugar addiction, disrupting emotional and stress eating, cultivating acceptance and curiosity, lovingkindness, detaching from thoughts, using healthy restraint, and maintaining motivation.
Carbohydrate-restricted diet: Education for carbohydrate-restricted diet
Mindfulness: Mindful eating app-use and instruction | 30 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Diet Education | Diet Education + Mindfulness | Total |
|---|---|---|---|
| Age, Continuous | 58.3 years STANDARD_DEVIATION 10.9 | 59.0 years STANDARD_DEVIATION 11.2 | 58.7 years STANDARD_DEVIATION 10.9 |
| Education 4-year college degree | 13 participants | 7 participants | 20 participants |
| Education Advanced degree | 9 participants | 9 participants | 18 participants |
| Education Declined to report | 0 participants | 1 participants | 1 participants |
| Education High school or less | 1 participants | 1 participants | 2 participants |
| Education Some college | 5 participants | 12 participants | 17 participants |
| Race/Ethnicity, Customized Asian or Pacific Islander | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Black/African-American | 3 Participants | 3 Participants | 6 Participants |
| Race/Ethnicity, Customized Latino/Hispanic | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Non-hispanic White | 14 Participants | 15 Participants | 29 Participants |
| Race/Ethnicity, Customized Other/more than 1 race | 0 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 20 Participants | 17 Participants | 37 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 30 |
| other Total, other adverse events | 12 / 28 | 11 / 30 |
| serious Total, serious adverse events | 0 / 28 | 0 / 30 |
Outcome results
Primary
Frequency of Eating in Response to Cravings (Primary Mechanistic Outcome)
Percent of ecological momentary assessment (EMA) opportunities in which participants reported eating in response to food cravings over a 3 day period. EMA measures were delivered to cell phones 3 times each day. The final EMA measure each day included a second question about whether there were any instances of craving related eating not already reported earlier during the day. Thus there was an opportunity to report eating in response to cravings on 4 different EMA questions each day, a total of 12 potential measures over 3 days. The percent here uses the number of EMA responses received as the denominator.
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Frequency of Eating in Response to Cravings (Primary Mechanistic Outcome) | -20.39 % of EMAs with craving related eating |
| Diet Education + Mindfulness | Frequency of Eating in Response to Cravings (Primary Mechanistic Outcome) | -25.27 % of EMAs with craving related eating |
Secondary
Adherence to Diet as Measured by Fingerstick Blood Ketones
Adherence to diet as measured by average proportion of fingerstick blood ketones at or above 0.3 mmol/L at 24 weeks.
Time frame: 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Adherence to Diet as Measured by Fingerstick Blood Ketones | 0.46 proportion of measurements >= 0.3 mmol/L |
| Diet Education + Mindfulness | Adherence to Diet as Measured by Fingerstick Blood Ketones | 0.60 proportion of measurements >= 0.3 mmol/L |
Secondary
Change in Impulsivity as Measured by Delayed Discounting Score
The 5-trial adaptation of the Delayed Discounting (DD; Koffarnus & Bickel, 2014) is a decision-making exercise where individuals choose between a smaller, immediate reward and a larger, delayed reward. The task measures an individual's discount rate, or how much they devalue a future reward compared to an immediate one, which is a a key aspect of impulsivity and self-control. Respondents choose between $100 delivered after a delay, or $50 available immediately. To derive estimates of discount rate, we used Mazur's hyperbolic discounting model (V=A/ (1+kD)18, wherein V is the discounted value of the delayed option, A is its objective amount, D is its delay, and k indexes the discount rate. We calculated values of k for each participant as the inverse of the indifference delay (1/ED50). We log transformed these values prior to analysis. Higher values of K indicate greater discounting, which reflects greater impulsivity.
Time frame: change from baseline to 6 months
Population: Intent to treat; note 2 participants in each arm had impulsivity data excluded due to nonsystematic Delayed Discounting data at baseline
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Diet Education | Change in Impulsivity as Measured by Delayed Discounting Score | 87.17 % change |
| Diet Education + Mindfulness | Change in Impulsivity as Measured by Delayed Discounting Score | 6.42 % change |
Secondary
Diet Adherence by Mean Grams of Non-fiber Carbohydrate Consumed Per Day
Diet Adherence Between Intervention Arms as Measured by Mean Grams of Non-fiber Carbohydrate Consumed Per Day From 24- Hour Diet Recall
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Diet Adherence by Mean Grams of Non-fiber Carbohydrate Consumed Per Day | -91.43 grams |
| Diet Education + Mindfulness | Diet Adherence by Mean Grams of Non-fiber Carbohydrate Consumed Per Day | -116.92 grams |
Secondary
Emotion-related Eating (Secondary Mechanistic Outcome)
Change in emotion-related eating as measured by the Coping subscale of the Palatable Eating Motives Scale (PEMS). The Coping subscale is comprised of 4 items rated on a scale from 1 (almost never/never) to 5 (almost always/always), with possible scores ranging from 4-20. Higher scores reflect worse coping/greater emotional eating. Thus, decreases over time reflect improved coping/decreased emotional eating.
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Emotion-related Eating (Secondary Mechanistic Outcome) | -0.62 scores on a scale |
| Diet Education + Mindfulness | Emotion-related Eating (Secondary Mechanistic Outcome) | -0.90 scores on a scale |
Secondary
Fasting Glucose
Change in plasma fasting glucose from baseline to 6 months by study arm
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Fasting Glucose | -30.21 mg/dL |
| Diet Education + Mindfulness | Fasting Glucose | -25.92 mg/dL |
Secondary
Glycemic Control, Using HbA1c
Change in hemoglobin A1c (HbA1c) from baseline to 6 months by study arm
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Glycemic Control, Using HbA1c | -1.32 % of hemaglobin with glucose (HbA1C) |
| Diet Education + Mindfulness | Glycemic Control, Using HbA1c | -0.87 % of hemaglobin with glucose (HbA1C) |
Secondary
HOMA-2IR Index of Insulin Resistance (Secondary Clinical Outcome)
Insulin resistance estimated from the Homeostatic model assessment (HOMA) model 2 index of insulin resistance. The basic formula is: (glucose × insulin) / 22.5, where glucose is measured in mmol/L and insulin in mU/L. The computer assisted re-calibration in model 2 addresses variations in the glucose resistance of the peripheral tissue and liver, increases in the insulin secretion curve for glucose \> 180 mg/dL, and contribution of circulating pro-insulin. Higher values indicate more insulin resistance (worse outcome). The Oxford University HOMA-2IR calculator was used (https://process.innovation.ox.ac.uk/software/p/2112/homa2-calculator/1). HOMA index values \< 2.0 are generally considered normal and indicate adequate sensitivity of cells to insulin. HOMA index values between 2.0 and 2.5 may indicate borderline changes in insulin sensitivity. HOMA index values \> 2.5 clearly indicate insulin resistance.
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | HOMA-2IR Index of Insulin Resistance (Secondary Clinical Outcome) | -0.45 units on a scale |
| Diet Education + Mindfulness | HOMA-2IR Index of Insulin Resistance (Secondary Clinical Outcome) | -0.85 units on a scale |
Secondary
Perceived Stress
Perceived Stress Scale (PPS-10) total score. Scores can range from 0 to 40 with higher scores indicated greater perceived stress.
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Perceived Stress | -1.09 score on a scale |
| Diet Education + Mindfulness | Perceived Stress | -2.04 score on a scale |
Secondary
Stress-related Eating (Secondary Mechanistic Outcome)
Change in stress-related eating as measured by two questions about stress-related eating from the MIDUS study. Possible scores range from 2-8. Higher scores reflect worse outcomes/greater eating in response to stress. Thus, decreases over time reflect improved outcomes/decreased stress-related eating.
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Stress-related Eating (Secondary Mechanistic Outcome) | -1.62 units on a scale |
| Diet Education + Mindfulness | Stress-related Eating (Secondary Mechanistic Outcome) | -1.73 units on a scale |
Secondary
Weight Change(Secondary Clinical Outcome)
kilograms
Time frame: change from baseline to 6 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diet Education | Weight Change(Secondary Clinical Outcome) | -4.96 kilograms |
| Diet Education + Mindfulness | Weight Change(Secondary Clinical Outcome) | -4.43 kilograms |