Intervening on Metabolic Dysfunction-Associated Steatotic Liver Disease in Latino/a and Black Patients with Diabetes: A Feasibility Pilot

Abstract

Introduction

Patients with type 2 diabetes (T2D), particularly those from historically marginalized racial and ethnic groups, are at high risk of poor outcomes from metabolic dysfunction-associated steatotic liver disease (MASLD). Evidence-based management (EBM) of MASLD can prevent its progression to cirrhosis and poor outcomes, yet rates of EBM of MASLD are low in T2D.

Methods

In this pilot study of ten participants, we examined the feasibility and acceptability of a telehealth intervention that delivered EBM of MASLD in Latino/a and Black patients with T2D in the Duke Healthcare System. The intervention included: (a) MASLD education; (b) diet/lifestyle counseling; (c) T2D medication adjustment (i.e., to promote liver health) and (d) ordering of clinically indicated tests and referrals. This 3-month intervention was delivered by an endocrinologist over three virtual study visits. Phone interviews were conducted at study conclusion. We examined rates of recruitment, retention, T2D medication adjustment, and ordering of clinically indicated tests/referrals.

Results

The median age of our cohort was 54.0 (44.0, 59.0); six and four participants self-identified as Latino/a ethnicity and Black race, respectively. Retention rate in this study was 100% (n = 10/10), and all scheduled visits were completed (n = 30/30). Recruitment occurred over one month, and the rate was 25.8% (n = 8/31) by telephone call and 10% (n = 2/20) by electronic health record message. The intervention was highly acceptable based on a median Treatment Acceptability and Preferences score of 4.0 (4.0, 4.0). In exit interviews, all participants reported improved understanding of MASLD and its link to diabetes. All participants received T2D medication adjustment (n = 5/10) and/or clinically indicated testing/referral (n = 10/10) for the purpose of improving MASLD.

Conclusions

We demonstrated that a telehealth intervention designed to proactively deliver EBM of MASLD was feasible and acceptable in a cohort of Latino/a and Black patients with T2D. Opportunities existed to better align each participants’ care with guideline-based care of MASLD.

Key Summary Points

Why carry out this study?

Patients with diabetes—especially those of historically marginalized racial/ethnic groups—are at high risk of poor outcomes from metabolic liver disease (MASLD).

Very few patients with diabetes (< 12%) receive guideline-based care of MASLD to prevent cirrhosis and poor liver outcomes.

We assessed the feasibility and acceptability of a telehealth intervention that proactively delivered evidence-based care of MASLD in Latino/a and Black patients with diabetes.

What was learned from the study?

In this pilot study, we found a telehealth intervention that combined behavioral and physician-led care components for MASLD to be feasible to implement in patients with diabetes, with good recruitment (25% over 1 month) and retention (100%) rates.

Participants found the intervention to be highly acceptable, as assessed by surveys and interviews, and there were opportunities for each participant’s care of MASLD to be improved.

Future larger studies are needed to test the clinical effectiveness of this intervention.

Introduction

Patients with type 2 diabetes (T2D), especially those from historically marginalized racial and ethnic groups, are at high risk of poor outcomes from metabolic dysfunction-associated steatotic liver disease (MASLD) [1]. Compared to non-Latino/a White patients, Latino/a patients are at 24% higher risk of having metabolic dysfunction-associated steatohepatitis than White patients [2], which is the precursor to cirrhosis. Further, Latino/a patients with MASLD experience faster progression to cirrhosis and liver cancer than White patients [1]. Black patients are also at heightened risk of poor MASLD outcomes, with more than a two-fold higher risk of mortality compared to White patients with MASLD [1, 3]. Early detection and evidence-based management (EBM) of MASLD are key to preventing progression to advanced, irreversible forms of liver disease in these high-risk groups. EBM of MASLD in T2D includes: (a) education about MASLD and liver protective measures; (b) lifestyle counseling to promote healthy weight loss and cardiometabolic health; (c) prioritization of T2D medications known to benefit MASLD, with reduction in obesogenic agents (i.e., insulin, sulfonylureas) when possible; and d) ordering of tests and hepatology referral based on risk of advanced liver fibrosis, i.e., using the fibrosis-4 (FIB-4) index [4].

Currently, rates of EBM of MASLD are low among those with T2D (11.4%), and racial disparities in care persist [5]. Approaches are needed to improve EBM of MASLD in T2D, and to do so in a manner that promotes health equity. The objective of this pilot study was to evaluate the feasibility and acceptability of a telehealth intervention that delivers all components of EBM of MASLD in Latino/a and Black patients with T2D. We chose to focus on Latino/a and Black patients to maximize acquisition of feasibility and acceptability data in these groups, and to understand how intervention content may be adapted to optimize their engagement in future studies.

Methods

This single-arm, 3-month study enrolled ten adult participants with T2D from the Duke University Healthcare System (DUHS) who self-identified as Latino, Latina, or Black, and who had an elevated alanine aminotransferase (ALT) level within the preceding 12 months (ALT ≥ 40 U/l in men, ≥ 31 U/l in women). Patients without a primary care provider or endocrinologist in DUHS were excluded, as were those with a history of hepatitis B or C infection, alcohol overuse, and/or chemotherapy use. We used a self-service electronic health record (EHR) tool called DEDUCE to generate a list of eligible patients based on the above criteria in the DUHS EHR. A list of eligible patients was extracted from DEDUCE and placed into a protected Duke analytics network, and this list included patient phone numbers and basic demographic data to facilitate balanced recruitment across race/ethnicities. Recruitment was conducted via telephone call and EHR messaging by the study coordinator and the study endocrinologist.

Eligible and interested patients were sent a link to an e-consent form via Duke REDCap, a secure web-based platform used for building and managing online surveys and databases. All participants provided informed consent to participate in this study, and they provided consent for data from this study to be published. This study was approved by the Duke Health Institutional Review Board (protocol number Pro00113239) and was registered on ClinicalTrials.gov (NCT05844137) before study initiation. This study was performed in accordance with the Helsinki Declaration of 1964, and its later amendments.

All participants had at minimum of three study visits during the intervention (Table 1), during which participants received: (a) MASLD education; (b) diet/lifestyle counseling; (c) T2D medication adjustment to improve MASLD; and (d) ordering of clinically indicated tests and referrals [4]. Table 1 provides additional detail regarding study components. All study visits were conducted with a board-certified endocrinologist via Zoom, or via telephone when participants had difficulty connecting to Zoom. Surveys were conducted at baseline and 3 months, and phone interviews were conducted at study conclusion by the study coordinator. Participants were reimbursed a total of $100 for their time to complete surveys at baseline ($50) and 3 months ($50). At study completion, each participant’s T2D care was transferred back to their usual provider, and the study endocrinologist sent a message to each T2D provider with advice on annual FIB-4 testing, MASLD risk stratification, and continued diet/lifestyle efforts.

Table 1. Details of the intervention

Intervention component	Content	Timing
MASLD education	Overview of MASLD physiology and its link to diabetes; rates of MASLD progression to cirrhosis; review of screening and diagnosis of MASLD; racial/ethnic disparities in MASLD; management of MASLD; diabetes medications with evidence for improving MASLD; liver protective measures (e.g., minimizing alcohol, hepatitis vaccinations)	Single, 30-min session at study initiation
Diet/lifestyle counseling	Module 1: Diet in MASLD and diabetes Module 2: Diet and healthy weight loss in MASLD and diabetes Module 3: Diet and exercise in MASLD and diabetes Each module consisted of questions, individualized goal setting and review of relevant content and tips for improving metabolic health	Monthly 20–45 min per session
Diabetes medication management	Prioritization (and intensification of) glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors as appropriate, as well as pioglitazone when more severe MASLD was suspected	At study initiation and monthly as indicated
Clinically indicated testing and referrals	In order to ensure an updated FIB-4 score within the preceding year, participants that did not have paired liver enzymes (AST, ALT) and platelets within the preceding 12 months had these labs updated. Patients with no prior hepatitis A, B, and C serologies in the healthcare system had these updated. Patients with repeated ALT levels 2 × the upper limit of normal were offered liver ultrasound to rule out other etiology of ALT elevation. Hepatology referrals were considered in cases of persistently elevated ALT, based on history. Participants with indeterminate-risk FIB-4 (> 1.3) would have been referred for transient elastography (note: no participants met these criteria in this study)	Initiated at study onset as indicated, and continued throughout the study

MASLD metabolic dysfunction-associated steatotic liver disease, FIB-4 fibrosis-4, AST aspartate aminotransferase, ALT alanine aminotransferase

Primary outcomes were: (a) feasibility, as measured by recruitment rates (eligible patients contacted/enrolled), retention rates (participants enrolled/completed) and visit completion rates (visits scheduled/completed); and (b) acceptability, assessed using the Treatment Acceptability and Preferences (TAP) measure [6] (maximum score of four, higher score indicates greater acceptability), and individual phone interview. In accordance with best practices for feasibility pilots [7], we used only descriptive statistics to summarize our data.

Results

Among the ten participants, median age was 54.0 (44.0, 59.0) and five were female. Six participants self-identified as Latino/a ethnicity and four as Black race. Median body mass index and hemoglobin A1c were 35 kg/m² (32, 42) and 6.4% (6.1, 7.7), respectively (Table 2). Most participants (n = 7/10) had adequate health literacy, yet half (n = 5/10) reported low confidence in their knowledge of MASLD, and the majority (n = 7/10) were unaware of a link between MASLD and T2D. In terms of the baseline T2D regimen, most participants were prescribed metformin (n = 9/10) and glucagon-like peptide-1 receptor agonists (n = 6/10). The median FIB-4 score was 0.9 (0.8, 1.1); all participants were in the low-risk FIB-4 category (Supplementary Material).

Table 2. Participant characteristics

Baseline characteristics	All participants N = 10
Demographics
Age, years
Median (Q1, Q3)	54.0 (44.0, 59.0)
Mean (SD)	51.1 (9.6)
Female sex, n (%)	5 (50)
Latino/a ethnicity, n (%)	6 (60)
Black race, n (%)	4 (40)
Comorbidities, n (%)
Obesity	9 (90)
Hypertension	6 (60)
Hyperlipidemia	3 (30)
Obstructive sleep apnea	3 (30)
Atherosclerotic cardiovascular disease	2 (20)
Chronic kidney disease	1 (10)
Frequency of alcohol use, n (%)
Never	4 (40)
Monthly or less	4 (40)
2–4 times per month	1 (10)
2–3 times per week	1 (10)
Smoking status, n (%)
Never smoker	7 (77.8)
Prior smoker	2 (22.2)
Missing	1
Social determinants of health, n (%)
Food insecurity	1 (10)
Housing insecurity	1 (10)
Transportation barriers	0 (0)
Health literacy level (by NVS), n (%)
Adequate health literacy	7 (70)
Possibly limited health literacy	2 (20)
Likely limited health literacy	1 (10)
Psychosocial measures, mean (SD)a Median (Q1, Q3) Mean (SD)
SEMCD (self-efficacy)	8.4 (7.2, 9.7) 8.3 (1.4)
HCCQ (perceived autonomy support)	4.7 (4.0, 5.0) 4.5 (0.5)
SF-12, physical-health related quality of life	43.5 (42.2, 54.2) 45.7 (9.0)
SF-12, mental-health related quality of life	54.5 (50.1, 56.0) 52.0 (6.2)
Low confidence in knowledge, n (%)
Of MASLD	5 (50)
Of link between MASLD and T2D	7 (70)
BMI, kg/m2 mean (SD)
Median (Q1, Q3)	35.0 (32.0, 42.0)
Mean (SD)	36 (5.6)
Diabetes duration, years, mean (SD)
Median (Q1, Q3)	3.0 (3.0, 12.0)
Mean (SD)	7.2 (7.7)
Diabetes medication use, n (%)b
Metformin	9 (90)
GLP-1 receptor agonist	6 (60)
SGLT2 inhibitors	4 (40)
DPP4 inhibitors	1 (10)
Insulin	1 (10)
Non-adherence to diabetes medications, n (%)b
Non-insulin	2/9 (22.2)
Insulin	1/1 (100)
Laboratory values, mean (SD)  Median (Q1, Q3)  Mean (SD)
Hemoglobin A1c, %	6.4 (6.1, 7.7) 6.9 (1.2)
ALT, mean, U/l	55.5 (42.0, 67.0) 58.1 (17.6)
AST, mean, U/l	37.5 (34.0, 50.0) 41.8 (14.7)
Platelet count, mean × 109/l (SD)	295 (261.8, 354.8) 313 (76.1)
FIB-4 scorec
Median (Q1, Q3)	0.9 (0.8, 1.1)
Mean (SD)	0.9 (0.2)
T2D medications adjusted to improve MASLDd	5 (50)
Clinically indicated tests and referrals ordered during studyd
Labs ordered	7 (70)
Liver ultrasound ordered	2 (20)
Hepatology referral	1 (10)
Hep A/B immunization recommended	5 (50)

NVS newest vital sign measure, SEMCD self-efficacy for managing chronic diseases scale, HCCQ healthcare climate questionnaire, SF-12 12-item short form survey, MASLD metabolic dysfunction-associated steatotic liver disease, T2D type 2 diabetes, BMI body mass index, DPP4 dipeptidyl peptidase-4, SGLT2 sodium-glucose cotransporter-2, GLP-1 glucagon-like peptide-1, ALT alanine e aminotransferase, AST aspartate aminotransferase, FIB-4 fibrosis-4

^aSEMCD is a measure of self-efficacy (max score of 10, higher score indicates better self-efficacy); HCCQ is a measure of perceived support in autonomy (maximum score of 5, higher score indicates greater perceived support); SF-12 is a measure of quality of life (max score 60, higher score indicates better quality of life)

^bOne participant was not on T2D medications at enrollment

^cFIB-4 is a highly validated non-invasive test for stratifying patients into low (<1.3), indeterminate (1.3–2.67) and high risk (> 2.67) of advanced liver fibrosis. It is the recommended approach for initial risk stratification in patients with T2D [4], and is calculated using the following formula: (age × AST)/(platelets × √(ALT) [15]. It is not validated in patients < 35 years, so it was not calculated for one participant who was < 35 years of age.

^dThese columns describe changes that occurred during the study (vs. all other columns describe baseline data)

The retention rate in this study was 100% and all scheduled visits were completed (n = 30/30). All participants were recruited over 1 month, and the rate of recruitment was 25.8% (n = 8/31) by telephone call and 10% (n = 2/20) by electronic health record message. The median TAP score was 4.0 (4.0, 4.0), indicating high intervention acceptability. In exit interviews conducted by the study coordinator, all participants felt the intervention was acceptable and reported improved awareness and understanding of MASLD and its link to T2D.

During the study, all participants had either clinically indicated labs ordered (n = 7/10) and/or T2D medications adjusted (n = 5/10) for the purpose of improving MASLD. Only two participants had liver ultrasound ordered during the study, both of whom were found to have hepatic steatosis. One participant was referred to Hepatology for ALT > 100 U/l, and additional laboratory testing was recommended. Five participants were non-immune to viral hepatitis A and/or B and were thus advised to receive these vaccinations for liver protection (Supplementary Material). Psychosocial measures (e.g., self-efficacy, quality of life) did not meaningfully change during the study (Table 3).

Table 3. Change in psychosocial measures

Score Median (Q1, Q3) Mean (SD)	Baseline	3 months	Change (3 months—baseline)
SEMCD (self-efficacy)	8.4 (7.2, 9.7) 8.3 (1.4)	9.0 (7.8, 10.0) 8.7 (1.4)	0.1 (− 0.7, 1.7) 0.4 (1.1)
HCCQ (autonomy support)	4.7 (4.0, 5.0) 4.5 (0.5)	4.9 (4.0, 5.0) 4.4 (1.0)	0.0 (− 0.2, 0.0) − 0.1 (0.7)
SF-12, physical health	43.5 (42.2, 54.2) 45.7 (9.0)	50.9 (47.9, 53.9) 49.2 (6.7)	2.4 (0.5, 5.7) 3.0 (3.0)
SF-12, mental health	54.5 (50.1, 56.0) 52.0 (6.2)	51.3 (50.1, 59.3) 53.4 (6.4)	0.5 (− 0.4, 1.9) 0.5 (2.7)

Meaningful changes defined a priori as change in: ≥ 1 for SEMCD, ≥ 1 for HCCQ, ≥ 10 for SF-12

SEMCD self-efficacy for managing chronic diseases scale, HCCQ healthcare climate questionnaire, SF-12 12-item short form survey

Discussion

Patients with T2D are disproportionately impacted by poor MASLD outcomes [1]. Given the high prevalence (> 10%) of advanced MASLD in T2D [8], multiple professional societies now advocate for risk stratification and initiation of MASLD care in primary care and endocrinology settings for patients with T2D [4, 9, 10–11]. Unfortunately, uptake of these recommendations has been low, leading to many missed cases of advanced MASLD. Further, current evidence suggests that racial disparities exist in receipt of EBM [5], which is highly problematic given patients of historically marginalized races and ethnicities are at especially high risk of poor MASLD outcomes [1]. It is therefore imperative that interventions are developed to improve rates of EBM of MASLD, and these approaches should be designed to assure engagement and improved outcomes of those at highest risk, i.e., high-risk racial and ethnic groups with T2D.

In this study, our telehealth approach to delivering EBM of MASLD was feasible and acceptable to a small cohort of Latino/a and Black patients with T2D, and there were opportunities to better align each participant’s care with current guidelines. We were able to recruit all participants over a 1-month period, with recruitment rates that were on par, and in some instances, even higher than other diabetes studies. For instance, in one lifestyle-based clinical trial that used the EHR to recruit patients with diabetes, recruitment rates for Latino/a and Black patients were reported at 20% and 21.4% [12], respectively; similar to our recruitment rate by EHR messaging. In another lifestyle-based trial in diabetes, recruitment rates by telephone call were very low at 1.2% [13] (versus 25% in our study). In both of these clinical trials, direct referrals from providers led to higher rates of recruitment of approximately 27% [12, 13], which were similar to our recruitment rate by telephone call in this study.

While each component of our intervention is based solidly in guidelines and best practice recommendations, combining these components into a telehealth intervention to improve MASLD care is novel, and has the potential to reach populations that are not engaging in clinic-based care. To date, no interventions have combined recommended T2D medication strategies for MASLD [4] with other aspects of guideline-based care to ensure high-quality EBM of MASLD in T2D. While multidisciplinary clinics have been developed for the management of MASLD, many are outside the U.S. [14], and programs designed to systematically, and equitably, deliver EBM of MASLD outside of the traditional clinic-based setting are lacking.

This study is limited by small sample size. Further, larger studies will be necessary to examine the effectiveness of this approach—across broader racial and ethnic identities—and to determine the effectiveness of this intervention (versus usual care) on clinically relevant outcomes, such as FIB-4 and steatosis on imaging. The implementation of this intervention would also need to be tested beyond a single academic hospital.

Conclusions

In summary, we demonstrated feasibility and acceptability of a telehealth intervention designed to deliver EBM of MASLD in a small cohort of Latino/a and Black patients with T2D. Future studies are needed to test this approach in a larger cohort of patients, and to examine its clinical effectiveness for improving liver health and preventing MASLD complications in T2D.

Author Contributions

Anastasia-Stefania Alexopoulos, Bryan. C. Batch, Cynthia A. Moylan and Matthew J. Crowley contributed to study conception and design. Anastasia-Stefania Alexopoulos and Susanne Danus contributed to data collection. Anastasia-Stefania Alexopoulos, Alice Parish and Maren K. Olsen contributed to data analysis. The first draft of the manuscript was written by Anastasia-Stefania Alexopoulos, and all authors provided edits to the manuscript and read and approved the final manuscript. Susanne Danus and Connie R. Thacker contributed to regulatory oversight of this study.

Funding

The study was funded by the Duke Clinical and Translational Science Institute (CTSI) under award number KL2TR002554, as was the Rapid Service Fee. Dr. Crowley acknowledges funding from the National Institutes of Health (1R01NR019594), the Veterans Affairs Quality Enhancement Research Initiative (VA QUE 20-012), and the Veterans Affairs Office of Rural Health. We wish to acknowledge support from the Biostatistics, Epidemiology and Research Design (BERD) Methods Core funded through Grant Award Number UL1TR002553 from the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the Duke CTSI or the NIH.

Data Availability

All data generated or analyzed during this study are included in this published article/as supplementary information files.

Declarations

Conflict of Interest

Cynthia A. Moylan has consulted for NovoNordisk and has served on the advisory board for Boehringer Ingelheim, Inc. Cynthia A. Moylan has also received grants from GlaxoSmithKline, Exact Sciences, and Madrigal to conduct research at Duke University. Anastasia-Stefania Alexopoulos, Susanne Danus, Alice Parish, Maren K. Olsen, Connie R. Thacker, Bryan C. Batch and Matthew J. Crowley have no competing interests for this work.

Ethical Approval

This study was approved by the Duke Health Institutional Review Board (protocol number Pro00113239) and was registered on ClinicalTrials.gov (NCT05844137) before study initiation. Written informed consent was obtained from all participants in this study for: (a) participation in the study; and (b) publication of data. This study was performed in accordance with the Helsinki Declaration of 1964, and its later amendments.

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