Modification of the diabetes prevention program for the treatment of nonalcoholic fatty liver disease: A pilot study
Abstract
Objective
The Diabetes Prevention Program (DPP) is the gold standard lifestyle modification program that reduces incident type 2 diabetes mellitus. Patients with prediabetes and patients with non-alcoholic fatty liver disease (NAFLD) often share metabolic features; we hypothesized that the DPP could be adapted and used to improve outcomes in patients with NAFLD.
Methods
NAFLD patients were recruited into a 1 year modified DPP. Demographics, medical comorbidities, and clinical laboratory values were collected at baseline, 6 and 12 months. The primary endpoint was change in weight at 12 months. Secondary endpoints were changes in hepatic steatosis, metabolic comorbidities, and liver enzymes (per-protocol basis) and retention at 6 and 12 months.
Results
Fourteen NAFLD patients enrolled; three dropped out before 6 months. From baseline to 12 months, hepatic steatosis (p = 0.03), alanine aminotransferase (p = 0.02), aspartate aminotransferase (p = 0.02), high-density lipoprotein (p = 0.01) and NAFLD fibrosis score (p < 0.001) improved, but low-density lipoprotein worsened (p = 0.04).
Conclusion
Seventy-nine percent of patients completed the modified DPP. Patients lost weight and had improvements in five out of six indicators of liver injury and lipid metabolism.
Clinical Trial Registry Number
NCT04988204.
1 INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions including hepatic steatosis and non-alcoholic steatohepatitis (NASH).1 In parallel with increases in obesity and type 2 diabetes mellitus (T2DM), the prevalence of NAFLD is rising and is projected to involve 33.5% of individuals 15 years of age and older by 2030.2 Nearly all (98%) patients with non-cirrhotic NAFLD die of non-liver related causes: cardiovascular disease, T2DM complications and malignancy.3 Thus, optimal care of patients with NAFLD should utilize interventions that reduce cardiovascular disease, cancer, and diabetes, as well as liver-related morbidity and mortality.
Weight loss promotes favorable histological changes in NAFLD.4 The American Association for the Study of Liver Diseases (AASLD) recommends reducing daily caloric intake by 500–1000 kcal and instituting a moderate-intensity exercise regimen.1 More recently, a guidance statement endorsed by the American Gastroenterology Association (AGA) was published on lifestyle interventions for the management of NAFLD.5 To date however, no approved standardized lifestyle programs are widely accepted, available, or well-studied.6
The Diabetes Prevention Program (DPP) achieves weight loss in patients with prediabetes mellitus (preDM). A multicenter clinical trial randomized 3234 individuals with preDM to placebo, metformin (850 mg twice daily), or lifestyle intervention (i.e., DPP). Patients were followed for an average of 2.8 years. The DPP reduced incident T2DM by 58% (95% Confidence Interval [CI]: 48%–66%). The impact was more dramatic in individuals over 60 years of age (71% [95% CI: 51%–83%]).7 The Centers for Medicare and Medicaid Services (CMS) began covering the DPP since 1 July 2018 and is a reimbursable service for participants with a diagnosis of preDM. The DPP is conducted in a group setting led by certified lifestyle coaches and health workers targeting weight loss and behavior change to prevent the development of T2DM. Formally accredited by the Center for Disease Control and Prevention (CDC), there are over 1773 CDC-recognized organizations as of 1 October 2018 for preDM.8 Because patients with preDM and patients with NAFLD share several anthropometric (high body mass index and central obesity) and endocrine-related abnormalities (insulin resistance [IR]), the hypothesis was that a modified version of the DPP might benefit patients with NAFLD. The aim of the study was to determine the feasibility and impact of the DPP on NAFLD by assessing changes in weight, liver enzymes and metabolic parameters.
2 METHODS
2.1 Study design and characteristics of the participants
In this prospective, open-label trial, patients with NAFLD were recruited at an urban liver clinic in New York, NY and enrolled in a 1 year modified DPP conducted in-person by a DPP-certified coach. The program was conducted in a conference room at one of Mount Sinai Healthcare System sites.
All patients had a diagnosis of NAFLD, defined by the presence of hepatic steatosis with vibration controlled transient elastography (VCTE) controlled attenuation parameter (CAP) measurement over 240 dB/m, or liver biopsy showing macrovesicular steatosis in ≥5% of hepatocytes. Patients were 18 years and older, fluent in English (the program could only be conducted in English by the DPP-certified coach), able to meet program scheduling requirements, and able to participate in physical activity. Patients with additional causes of liver diseases such as viral hepatitis, biliary obstruction, hepatocellular carcinoma, Wilson's disease, Budd Chiari Syndrome, autoimmune hepatitis, alcoholic liver disease or alcohol use (>20 g/day women, >30 g/day men), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values > 300 U/L, using steatogenic medications (amiodarone, methotrexate, tamoxifen, and corticosteroids), history of liver transplantation and pregnancy were excluded.
Participants (n = 42) with an interest in participating in a non-pharmacological or lifestyle intervention for NAFLD were approached in person or by telephone. Participants able to commit to the 1 year duration of the study were seen in person to obtain informed written consent. A set target of a total of 20 participants was considered the maximum number of participants in one group with one coach, modeled after the initial DPP.7 Only 14 could be recruited and enrolled based on the 1 year time commitment and chosen day and time of the week. The primary endpoint of the study was changes in weight at 12 months. Secondary endpoints were retention, changes in aminotransferases, lipid profile, comorbidities, and liver stiffness (LS) at 6 and 12 months.
The 1 year program spanned from October 2018 to October 2019. The program included 16 weekly core sessions followed by 12 maintenance sessions that took place at biweekly to monthly intervals. Attendance was taken at the start of every session and weight was measured on a standard scale. Data were collected at baseline, at 6 months, and at 12 months; it included demographics, severity of NAFLD determined by VCTE (stage of fibrosis estimated from measurement of LS and steatosis grade estimated from CAP scores), and factors associated with metabolic comorbidities, for example, weight, body mass index (BMI), ALT, AST, alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), glycated hemoglobin A1C (HbA1c), HDL, LDL, and triglycerides (TG). During the study, participants continued to meet with primary liver specialist for standard of care visits (at enrollment, 6 months, and 12 months). At each of the visits, patients underwent a structured history and physical examination, review of medications, physical examination, laboratory collection, and VCTE to measure LS and hepatic steatosis. All test results were discussed with the patient by the primary hepatologist. Participants were compensated a total of $100 in $50 installments at 6 and 12 months.
The study was approved by the Institutional Review Board of the Icahn School of Medicine at Mount Sinai (IF# 2441442) and was in accord with the Helsinki agreement. Informed and written consent was obtained from all participants. Minors were not included in the study. The authors confirm that all ongoing and related trials for this drug/intervention are registered (NCT04988204).
2.2 Description of the modified DPP
The modified DPP focused on NAFLD instead of preDM or T2DM (Table 1); however, it used handouts from the PreventT2 CDC curriculum (accessible at: https://www.cdc.gov/diabetes/prevention/resources/curriculum.html). It provided information about the benefits of following a healthy diet and maintaining an exercise regimen, and included guidance about stress reduction, sleep, and self-motivation techniques. The DPP does not recommend a specific diet, instead the curriculum focuses on understanding caloric counts with an emphasis on overall caloric reduction, mindfulness and accountability for food choices. To help participants achieve these goals, participants were advised to keep a food log and to share the log with the lifestyle coach. The MyPlate method was employed for the assessment of food intake over 24 h: apportion each meal into 50% fruits and vegetables, 25% protein, and 25% carbohydrate.8 In the sixth session, the group was introduced to exercise with the goal of building toward 150 min per week of exercise and asked to submit a weekly log of activity minutes. The DPP was modified to focus on elements central to NAFLD treatment (Table 1).
| Modified DPP for NAFLD | Original DPP |
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| Design | Design |
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Goal |
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| Goal | |
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| ο Retention in program at 6 months | |
| ο Changes in weight, BMI, CAP, LS, HbA1c, aminotransferases, HDL, LDL, TG, NAFLD activity indices |
- Abbreviations: BMI, body mass index; CAP, controlled attenuated parameter; DPP, Diabetes Prevention Program; HbA1c, glycated hemoglobin A1C; HDL, high density lipoprotein; HFCS, high fructose corn syrup; LS, liver stiffness; LDL, low density lipoprotein; NAFLD, nonalcoholic fatty liver disease; T2DM, type 2 diabetes mellitus; TG, triglycerides; TG, triglycerides.
During the first 6 months, sessions occurred every week and during the second 6 months, sessions occurred every other week, or monthly. The lifestyle coach contacted the participants via weekly email with information ranging from general health advice to news articles and relevant studies on NAFLD to maintain engagement. Up to 2 sessions could be missed per 6 month period, and any additional absences had to be made up in-person or by telephone. During the make-up sessions, weight, and number of minutes of exercise was obtained by the lifestyle coach and communicated to the research team.
2.3 Statistical analysis
Descriptive statistics were used to define the demographics of the study population. Paired t tests were performed to assess change in mean baseline lab data to data collected at both 6 and 12 month follow-up visits for normally distributed data and Wilcoxon signed-rank test for non-normal data. These tests were utilized instead of analysis of variance as the primary outcome of interest is whether there were improvements from baseline to 12 month follow-up, and as a secondary outcome if those improvements were also significant at 6 months. All analyses were run at an alpha of 0.05 with 95% confidence using SPSS v. 26. Dedoose was used to perform a thematic analysis of program reflections patients shared.
3 RESULTS
Fourteen patients with NAFLD were enrolled in the program. Three dropped out prior to the 6 month follow-up visit: two of the three did not attend any session due to scheduling conflicts, and one stopped at 4 months citing discomfort with the group-setting format. The three patients were excluded from the per-protocol analysis of outcomes. There was no difference in baseline characteristics noted between the three participants who dropped out and the 11 who completed the program. Baseline demographics of patients that remained enrolled in the program are presented in Table 2. The mean age of the 11 participants was 48 (13.9) years, 73% were female, 45% self-identified as Hispanic, 55% as non-Hispanic white. At baseline, the median CAP was 354 dB/m (interquartile range [IQR] 365, 379.5), consistent with severe steatosis, ≥S3 steatosis and the median LS was 8.5 kPa (IQR 5.75, 9.75), consistent with moderate fibrosis, ≥F2 fibrosis.9, 10 The mean BMI was 35.8 kg/m2. Nine (82%) had BMI ≥30 kg/m2 indicating obesity, five (45%) had hypertriglyceridemia, five (45%) had hypertension, six (55%) had preDM and two (18%) had T2DM (defined by the American Diabetes Association criteria,11 or prior diagnosis on currently therapy) and three (27%) had low HDL (Table 2).
| Characteristic | Number (%) of active |
|---|---|
| Participants | |
| N = 11 | |
| Gender | |
| Male | 3 (27%) |
| Female | 8 (73%) |
| Ethnicity | |
| Hispanic | 5 (45%) |
| Non-Hispanic black | 6 (55%) |
| Non-Hispanic black | 0 (0%) |
| Smoker | |
| Never | 8 (73%) |
| Former | 3 (27%) |
| Current | 0 (0%) |
| CAP score, dB/m | |
| 240–270 (S1) | 1 (9%) |
| 270–299 (S2) | 1 (9%) |
| ≥300 (S3) | 9 (82%) |
| Mean CAP score | 346 dB/m |
| Liver stiffness, kPa | |
| >0 < 7.5 (F0-1) | 4 (36%) |
| ≥7.5 < 10 (F2) | 5 (45%) |
| ≥10 < 14 (F3) | 0 (0%) |
| ≥14 (F4) | 2 (18%) |
| Mean LS score | 8.8 kPa |
| Obesity class by BMI, kg/m2 | |
| 25.0–29.9 (overweight) | 2 (18.2%) |
| 30.0–34.9 (Class I) | 4 (36.3%) |
| 35.0–39.9 (Class II) | 2 (18.2%) |
| ≥40.0 (Class III) | 3 (27.3%) |
| Mean BMI | 35.8 kg/m2 |
| Hypertension | 5 (45%) |
| Glycemic status | |
| Normal (HbA1c < 5.7%) | 3 (27%) |
| Prediabetes (HbA1c 5.7%–6.4%) | 6 (55%) |
| Type 2 diabetes (HbA1c ≥ 6.5%) | 2 (18%) |
| Hypertriglyceridemia (>150 mg/dl) | 5 (45%) |
| Low HDL (<35 mg/dl) | 3 (21%) |
- Abbreviations: BMI, body mass index; CAP, controlled attenuated parameter; HbA1c, glycated hemoglobin A1C; HDL, high density lipoprotein; LS, liver stiffness.
Overall, 79% of the enrolled patients were active participants in the modified DPP at 6 and 12 months, higher than that observed in other lifestyle programs.12, 13 The average attendance for the in-person group sessions was 72.4% for the 11 participants who completed the program. All sessions that were missed were made up with the lifestyle coach on an individual basis (majority were completed in person prior to scheduled meeting).
Among the 11 participants who completed the program, the mean percentage weight loss from baseline to 12 months was 5%, 4.9 kg (95% CI: 2.65–7.29, p = 0.001). The greatest mean percentage weight loss was noted at 6 months, 7%; 6.8 kg (95% CI: 0.71–5.75, p = 0.016).
Body mass index did not change significantly. LS decreased by a mean of 2.5 ± 3.2 kPa from baseline to 6 months (95% CI: 0.4, 4.7; p = 0.03) and by 2.2 ± 3.3 kPa (95% CI: −0.05, 4.4; p = 0.05) baseline to 12 months, suggesting that fibrosis may have decreased by one or more stage in some participants. There was a significant decrease in hepatic steatosis (CAP score) from baseline to 12 months of 43 ± 54.2 dB/m (95% CI: 6.5, 79.3; p = 0.025). From baseline to 12 months, there was a mean improvement in Fibrosis-4 (FIB-4) scores approaching significance (0.26 ± 0.38, 95% CI: 0.003,5.12; p = 0.05) and true significant improvement in mean NFS (2.78 ± 0.92, 95% CI: 2.16, 3.40; p < 0.001).
Of the 11 patients who completed the program, eight patients had ALT above the upper limit of normal (ALT ≥30 IU/ml) at baseline. ALT decreased in seven of the patients; the mean decrease in the seven patients was 31 ± 43.4 IU/ml (95% CI: 1.9, 60.3; p = 0.04). ALT normalized in three of the eight participants and increased by 25 IU/ml in one. ALT remained in the normal range in the three participants with normal values at baseline. The mean LDL remained unchanged from baseline to 6 months (116 mg/dl) but rose to 125 mg/dl at 12 months (p = 0.04). The mean HDL increased over the course of 12 months, from 53 ± 11 mg/dl to 60 ± 11.4 mg/dl at 12 months (p = 0.01). TG declined during the 12 month course, with a mean 33 ± 53.5 mg/dl decrease at 12 months, but the change was not statistically significant (p = 0.11). Similarly, Hg1Ac decreased by 0.4% baseline to 12 months, but the change was not statistically significant (p = 0.67). None of the preDM patients developed T2DM over the 12 months (Table 3).
| Patient characteristics | Baseline | 6 month follow-up | Baseline to 6 months | 12 month follow-up | Baseline to 12 months |
|---|---|---|---|---|---|
| N = 11 | N = 11 | p-value* | N = 11 | p-value* | |
| mean, (range) | mean, (range) | mean, (range) | |||
| Weight (kg) | 99.5 (76.0–130.8) | 92.7 (72.3–115) | 0.31 | 94.6 (71.2–125.6) | 0.06 |
| BMI | 35.8 (27.8–49) | 35.1 (28.2–44.8) | 0.03 | 34.4 (26.8–44.3) | 0.05 |
| CAP (dB/m) | 346 (244–400) | 314.6 (219–393) | 0.13 | 303 (240–399) | 0.03 |
| LS (kPa) | 8.78 (4.1–17.5 | 6.3 (2.7–8.6) | 0.10 | 6.6 (3.6–8.9) | 0.04 |
| ALT | 67.45 (15–172) | 45.6 (10–162) | 0.04** | 36 (10–96) | 0.02** |
| AST | 52.1 (18–179) | 32.1 (18–70) | 0.02** | 28 (16–53) | 0.02** |
| ALP | 78.55 (50–120) | 75.5 (47–113) | 0.17 | 79 (47–155) | 0.12 |
| GGT | 51 (20–151) | 36 (19–79) | 0.03** | 34 (17–66) | 0.04** |
| HbA1c % | 6.4 (5.2–11.4) | 6.02 (5.4–7.3) | 0.66** | 6.0 (5.5–7.0) | 0.67** |
| HDL mg/DL | 53.1 (35–67) | 54.6 (42–65) | 0.46 | 60 (44–76) | 0.01 |
| LDL mg/dL | 115.8 (52–167) | 117.9 (65–181) | 0.76 | 125 (65–167) | 0.04 |
| TG mg/dL | 170.6 (88–365) | 148.2 (94–234) | 0.66** | 138 (102–221) | 0.11** |
| FIB–4 | 1.08 (0.44–2.17) | 0.89 (0.43–1.64) | 0.15 | 0.83 (0.48–1.6) | 0.05 |
| NFS | 1.12 ( −1.85 – 3.15) | 0.66 (−2.8–2.7) | 0.13 | −1.66 (−3.0 to −0.1) | <0.001 |
- Abbreviations: ALT, alanine transferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; BMI, body mass index; CAP, controlled attenuated parameter; FIB-4, fibrosis -4; GGT, gamma-glutamyl transferase; HbA1c, glycated hemoglobin A1C; HDL, high density lipoprotein; LS, liver stiffness; LDL, low density lipoprotein; NFS, Nonalcoholic fatty liver disease fibrosis score; TG, triglycerides.
- *p-values presented for paired t-tests. **p-values presented for Wilcoxon signed-rank test.
At baseline, majority of the study participants were not exercising regularly. Toward the end of the program, weekly activity ranged from 30 to 980 min. Both compliance with weekly logging and achievement of activity goal (above 150 min per week) increased over the course of the program. During the first 10 weeks only 39% of the requested logs were submitted, with 70% reaching the exercise goal, while during the final 10 weeks 53% of the requested logs were submitted, with 81% reaching the exercise goal.
Medications were reviewed throughout the duration of the study. At baseline, two participants were on statin therapy, three were on metformin, one was on a Dipeptidyl peptidase-4 inhibitor, one was on a sodium-glucose transport protein 2 inhibitor, none was on insulin. None of the patients were on vitamin E therapy. LDL did not change in the two participants on statin therapy, but HDL rose by 13 mg/dl in one (and remained unchanged in the other). The most likely explanation for favorable increase in HDL is increased exercise. Two of the three participants discontinued metformin during the study due to improvement in their HbA1c values, which decreased from 7.2% to 6.1% and from 11.4% to 7%. These participants lost 7.9% and 10.4% of their baseline weight, likely promoting the decrease in HbA1c.
Feedback was provided by six participants. Responses mentioned the following themes: learning about diet or disease process, expressing continuity of learned behaviors after the program ends, expressing increased accountability personally or by others and lastly improved attitudes toward exercise. Females were more likely than males to report learning more about diet and the effects of weight management on their overall disease process. Overall, participants reported increased accountability and mindfulness about overall health as well as being likely to continue the behaviors post completion of the program. Specifically, one participant reported ‘When I told my family I had NAFLD we stopped stocking soda in the house and added vegetables to every meal. Instead of spending weekends watching TV on the couch we all joined the gym together’.
4 DISCUSSION
To our knowledge, this is the first study to modify the DPP for use in NAFLD and the first to test the impact of a structured lifestyle program for NAFLD in the US. Typically, goals for weight loss, diet and exercise are not easily achieved likely due to lack of standardized programs and resources and lack of expertise in how to actually achieve successful lifestyle interventions.1 Variations in the designs of studies aiming to improve lifestyle in NAFLD make it difficult to reach firm conclusions about optimal diet and exercise regimen.14
There are a few studies that highlight the promise in structured lifestyle interventions as a treatment for NAFLD. A randomized control trial of 31 NASH patients reported significant reduction in NAFLD activity score (NAS) score of 2.4 points on post liver biopsy after a 48 week lifestyle intervention program including moderate-intensity exercise with a goal of >200 min per week, reduced calorie diet, and behavioral guidance.15 Still, in this and other lifestyle intervention studies for NAFLD, less than 50% of patients achieved weight loss of at least 7%.15, 16 A recent study assigned 716 patients with NAFLD to either a structured program conducted in person (five weekly meetings, n = 438) or web-based (n = 278) with the primary outcome of at least 10% weight loss over 2 years. This target was only reached in 15% in the in-person group and 20% in the web-based group.17 In our study, all participants were able to achieve weight loss, with 27% achieving 7% weight loss or more.
Our modified DPP is unique in that it employed a well-validated, established program that has shown success in persons with preDM and adapted it to focus on NAFLD by providing direction on weight loss, diet and exercise. One of the strengths of the DPP is that it is tailored to the needs of the group instead of focusing on a ‘diet.’ The DPP stresses the value of making mindful choices about food, avoiding carbohydrates and sugars, and adhering to portion control. Caloric reduction of at least 750 kcal/day has the strongest evidence for improvement in IR and hepatic steatosis in NAFLD.14, 18 Caloric restriction allows for success in the long-term and prevents short-term gratifications achieved by typical noncommercial and commercially available ‘diets.’19, 20 The unique element of our program was additional insight into the link between the detrimental impact of sugar and caloric intake on NAFLD, particularly high fructose corn syrup.21
Exercise is another element of lifestyle change that is recommended by society guidelines.1, 5, 6 In a retrospective analysis, over half (54%) of adult patients with biopsy proven NAFLD, self-reported being physically inactive.22 Our program introduced exercise with the goal of achieving 150 min a week, on par with and 2008 US Department of Health and Human Services Physical Activity Guidelines for Americans23 and DPP targets. We stressed participating in some form of exercise and again tailored to the individual and physical abilities if needed. Among our participants completing the program, 49% of requested weekly activity logs were received. Of those logs submitted, 75% self-reported achieving a goal of ≥150 weekly activity minutes.
There was a 79% retention achieved at the end of the program, which is almost double that observed in the traditional DPP.24, 25 At completion, all 11 active participants achieved some degree of weight loss from 0.4% to 10.6% of their baseline weight (0.5–11.6 kg). Weight loss remained statistically significant throughout the course of the program. Three patients (27%) accomplished weight loss of 7% or higher. While the impact of the program on weight loss may appear to be limited, similar outcomes were observed in the initial DPP trial where 50% of participants in the lifestyle intervention arm achieved this goal at 24 weeks.7 Notably, at the time of transition from the core weekly sessions to maintenance bimonthly to monthly sessions (i.e., approximately week 18) a rebound weight gain was observed in 6 of 11 participants (range +0.4 kg, +2.4 kg from prior session), 4 of whom surpassed initial weight. This highlights the importance of providing ongoing support and empowering participants with coping strategies to maintain weight loss goals. One of the methods we employed to continue to engage our participants was providing weekly email alerts to engage participants.
One of the unexpected outcomes observed was an increase in LDL at the end of the study in the presence of amelioration of other lipid parameters (TG and HDL). This might be a reflection of how dietary changes were discussed during the program and will need to be addressed in future studies. The direct improvement in HDL and decrease in TG can be explained by the increased uptake of physical activity and weight loss achieved by the participants.
While this pilot study shows promising results and a possible platform to develop large scale lifestyle programs for NAFLD, it has several limitations. The initial aim was to recruit 20 participants for proof of concept, which to the authors' dismay was difficult to recruit given a wealth of NAFLD patients in the healthcare system. This was primary driven by the time commitment to participate in, in-person sessions for a year long. Spanish–speaking patients were also excluded as the language of instruction of the sessions were conducted in English. Despite an even distribution of Hispanic and Non-Hispanic Caucasians in the study, the recruitment demographics were limited or void of persons of Asian or African American background. In addition, there was a predominance of women represented in the sample, like other weight loss programs and intervention trials.26, 27 The representation of men was 27%, like other weight loss program studies.26, 27 The demographics of the study partially represents a larger population in terms of majority women and equal distribution of Hispanic and non-Hispanic Caucasians as observed in lifestyle programs. The study did not include a control arm by which to judge the success of the program compared to standard follow up for NAFLD. The feedback received on improvements on quality of life and other associated comorbidities was anecdotal instead of being captured in a standardized method. Further understanding of the barrier to recruitment and study retention should be investigated. However, given the feasibility of the DPP, reputable track record and its existing establishment across the United States, the results of this study provide solid framework to expand the modified-DPP to a larger scale study, with potential to conduct in different languages and virtually (telehealth platforms).
5 CONCLUSIONS
The 1 year adapted DPP is the first program in the United States that shows promise in providing a structured, reproducible lifestyle intervention for patients with NAFLD. At the end of 12 months, the retention rate was 79%. From baseline, there were noteworthy improvements in BMI, hepatic steatosis, aminotransferases, and HDL. There was a promising improvement also observed in liver fibrosis which will need to be further explored. The data from this pilot study demonstrates a feasible program outline for targeting sustained lifestyle modification in NAFLD and will enable the design of expanded clinical trials.
AUTHOR CONTRIBUTIONS
Melissa Hershman: study design, interpretation of data, writing-original draft. Karen Torbjornsen: study design, interpretation of data, critical revision of manuscript. Daniel Pang: data management, interpretation of data, review, editing and revision of manuscript. Brooke Wyatt: data management, interpretation of data, statistical analysis, editing and revision of manuscript. Douglas T. Dieterich: review, editing and critical revision of manuscript. Ponni V. Perumalswami: study design and concept, interpretation of data, critical revision of manuscript. Andrea D. Branch: study design and concept, interpretation of data, critical revision of manuscript. Amreen M Dinani: study concept and design, interpretation of data, writing-original draft, review, editing and critical revision of manuscript. All authors approved the final draft submitted.
ACKNOWLEDGMENTS
We acknowledge the patients who participated in the program.
CONFLICT OF INTEREST
The authors declare no other conflict of interest.
