Improving Detection and Evidence-based Care of NAFLD in Latinx and Black Patients With Type 2 Diabetes (NAFLD-DM): A Pilot Study
Phase: NA
Conditions: NAFLD, Diabetes Mellitus
Sponsor: Duke University

 
 
Official Title:  Improving Detection and Evidence-based Care of NAFLD in Latinx 
and Black Patients With Type 2 Diabetes (NAFLD-DM): A Pilot Study     
 
NCT:  NCT05844137 
 
IRB Document Date:  5/31/2024 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 1 of 7 
Version 2: May 31, 2024 
 
Background: NAFLD is a critically overlooked T2D complication, and T2D accelerates NAFLD progression to 
poor outcomes, such as cirrhosis, liver cancer and death.1, 2 As with other T2D complications, racial and 
ethnic disparities exist in detection and care of NAFLD, although the drivers of these disparities are poorly 
understood, especially in the context of T2D care.3 Based on my prior work published in Hepatology,4 there are 
racial/ethnic disparities in who receives liver biopsy to diagnose NAFLD. For instance, of the 350 patients with 
T2D who underwent liver biopsy for NAFLD between 2007-2019 in DUHS, only 1.7% and 13% of patients were 
Latinx and Black, respectively.4 This is striking when considering that these underrepresented minority groups 
are disproportionately impacted by T2D complications and poor liver outcomes due to NAFLD.3 Because T2D 
imparts higher risk of poor liver outcomes due to NAFLD,1, 2 and because underrepresented minority 
groups are likewise at higher risk of these outcomes, Latinx and Black patients with T2D should be 
prioritized for proactive detection and intensive management of NAFLD.5, 6  
 
Diabetes care guidelines specifically call for further evaluation of NAFLD in T2D in the presence of 
abnormal liver enzymes, or when imaging has revealed hepatic steatosis.6 Detection of high-risk forms of 
NAFLD is critical in T2D, not only because of the elevated risk of poor NAFLD outcomes in T2D, but also 
because we can use T2D approaches to effectively treat NAFLD.5, 7, 8 In a recently published study,9 we 
showed that T2D medications that prevent NAFLD progression are vastly underutilized in high-risk patients 
with T2D. Currently, disparities in the detection and treatment of NAFLD in patients with T2D are poorly 
characterized; however, given known racial and ethnic disparities in biopsy rates and NAFLD 
outcomes, we urgently need to understand disparities in NAFLD detection and care in T2D. Such data 
could directly inform the development of interventions to foster the equitable management of T2D and 
NAFLD. To address these critical issues, I propose a KL2 program of research that will characterize health 
disparities in NAFLD detection and care in T2D, and then develop and pilot a culturally-competent 
 intervention that will improve recognition and management of Latinx and Black patients with T2D and NAFLD.  
 
Significance: NAFLD-related liver disease and mortality are high – based on 2015 data, 16.5 million 
Americans have NASH (i.e., high-risk NAFLD) and mortality in patients with NAFLD is up to 1.27 million 
annually.10 These rates are projected to increase by over 130% in the next 10 years.10 This increased clinical 
burden will result in direct medical and societal costs of over $300 billion/year.11, 12 Efforts to prevent this rise in 
NAFLD complications and costs should focus on populations at highest risk for poor outcomes; thus, this 
proposal’s focus on T2D and high-risk racial/ethnic groups is highly significant. Furthermore, given known 
health disparities in NAFLD detection, and in T2D care in general, our emphasis on addressing disparities is 
crucial. This proposal will generate a patient-facing intervention that will improve evidence-based care of 
NAFLD in T2D, with a focus on reaching Latinx and Black patients who are disproportionately impacted by T2D 
complications,13 especially NAFLD.3 This work is critically urgent as the U.S. burden of NAFLD is rising, and 
several drugs for NAFLD in T2D will come to market soon; this proposal will support equitable use of current 
and emerging therapies for NAFLD, assuring that those with the greatest need are able to access effective 
treatment. Because current services are already struggling to reach rising numbers of patients with NAFLD, a 
major strength of this proposal is its support of multidisciplinary efforts to tackle this public health threat.  
 
Innovation: This proposal is novel in multiple ways. First, the drivers underlying health disparities in NAFLD 
detection are poorly understood, and this proposal will address this gap. Second, there are no existing 
interventions to promote detection and management of NAFLD as part of T2D care, and certainly none to 
address disparities in these areas. Third, I am proposing an innovative intervention development approach that 
will leverage community engagement resources at Duke and maximize intervention relevance and feasibility 
through use of stakeholder input. No studies have queried minority communities to understand how best to 
design/deliver an intervention to improve outcomes in NAFLD and T2D. Notably, this proposal will proactively 
improve the care of an exceedingly high-risk, high-cost group through a joint T2D/NAFLD intervention. To our 
knowledge, this will be the first intervention geared towards intensively co-managing these linked conditions.  
 
Research Strategy/Approach 
This project will assess the feasibility and acceptability of an intervention for improved detection and 
evidence-based care of NAFLD in Latinx and Black patients with T2D.  
 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 2 of 7 
Version 2: May 31, 2024 
 
Rationale: Below is a conceptual framework that has guided the design, and will inform the execution, of our 
intervention. This framework includes features of the Health Belief Model (HBM)14 to highlight patient-level 
strategies for disease prevention, and the Chronic Care Model (CCM)15 to highlight the system-level 
components aimed at improving the care of NAFLD. As depicted in the Figure below, this intervention 
represents an innovative approach to redesigning care and using available EHR to promote equitable 
detection of NAFLD (right side of figure). Once detected, we will engage patients with NAFLD and T2D in 
strategies to promote their overall health and halt, or even reverse their NAFLD. These patient-level 
approaches will consider how to alter patient perceptions (i.e., perceived threat of NAFLD, perceived 
benefits & barriers) and understand patient cues to action, to promote patient engagement with the care 
plan (left side of Figure). The ultimate objective of this project is to lead to productive interactions between 
patients and the care teams (center of Figure) that will ultimately lead to better detection and care of NAFLD in 
those at highest risk. Prior work has helped us develop this intervention in a culturally-appropriate manner to 
allow us to reach high-risk racial/ethnic groups with T2D and NAFLD. This will be a feasibility pilot.  
 
 
Figure: Conceptual framework guiding intervention design and execution 
 
 
 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 3 of 7 
Version 2: May 31, 2024 
 
Intervention content and design: The first intervention component will involve proactive detection of NAFLD in 
Latinx/Black patients with T2D using DEDUCE; this EHR-based approach will allow us to identify eligible study 
participants in DUHS based on our inclusion/exclusion criteria listed below. The next intervention component 
will focus on delivery of evidence-based care, which will rely on a proactive care team that is knowledgeable 
about NAFLD and can intervene, as well as an informed and activated patient who wants to engage with care.  
Once identified, patients will receive the following guideline-concordant content as part of the intervention: 
a) diet/lifestyle support, with counseling on hypocaloric diet and moderate-intensity exercise;5 b) NAFLD 
education;5 c) medication management, with proactive use of T2D medications known to be protective against 
NAFLD progression (pioglitazone, GLP-1RA, SGLT2i);5, 7, 16 and d) clinically-indicated liver testing and care 
based on guidelines.5 The content of this intervention will be delivered remotely via telehealth approaches.  In 
order to ensure feasibility within the proposed KL2 timeline, we have limited the pilot duration to 3 months. This 
will allow time to observe change in liver enzymes, as well as HbA1c. Table 1  
shows when intervention content will be delivered throughout the  
 
Study population: We will enroll 10-15 Latinx/Hispanic and 10-15 Black patients with T2D and NAFLD, based 
on elevated ALT and exclusion of other liver diseases (e.g., viral hepatitis, alcohol abuse).  
 
Research activity:  
Detection of NAFLD in T2D: The Duke DEDUCE tool will be used to generate a report of potentially eligible 
Latinx and Black patients with an ICD code for T2D (E11.xx) and at least one ALT >40 IU/mL in males or > 31 
IU/mL in females17 in the preceding 12 months. For this feasibility pilot, we will also restrict eligibility to patients 
who have a PCP or Endocrinologist in DUHS to facilitate communication regarding T2D medication changes 
during the study period. We anticipate >2,000 patient will meet our inclusion and exclusion criteria. A report will 
be exported from DEDUCE and I will review the charts of potentially eligible patients to exclude individuals with 
liver dysfunction likely due to an etiology other than NAFLD. We will not exclude patients with an ICD-10 code 
for NASH (K75.81), as long as they are not medically optimized (i.e. on pioglitazone and GLP-1RA), since 
these individuals serve to benefit from the intervention.  
The first 50 patients who meet eligibility will be mailed a letter or sent a MyChart message with opt-out 
instructions. Patients who do not opt out will be contacted by phone and, if interested, they will sign an e-
consent form via REDCap. In parallel 
to the above recruitment approach, we 
will also advertise this study in the 
community with the help of community 
partners that had assisted us in the 
design of the intervention, i.e., Latin-19 
group and the AME Zion partnership. 
An IRB-approved flyer (with brief 
inclusion/exclusion criteria) will be 
created and placed in community 
spaces with the help of our community 
partners. Community members who 
are interested in the study, and who 
are also part of DUHS, will be provided with a study contact number to let us know of their interest. We will use 
the EHR to determine their eligibility, and if eligible, consent will be obtained as above. 
Baseline surveys will be conducted by phone or completed online via Duke REDCap. For participants 
completing surveys by phone, we will ensure that a copy of the survey is mailed or emailed in advance, in case 
participants prefer to review content in advance. We will survey: self-efficacy,18 and quality of life surveys19). 
The most recent BMI in the EHR will be used for the purpose of characterizing the participant population – if 
there is no BMI documented within 1 year of enrollment, we will count BMI data as missing. For HbA1c, if there 
is no documented HbA1c within 3 months of enrollment to the study, or ALT and ALT within 6 months of 
enrollment, we will order these tests to be completed at baseline.  
 
Table 1: NAFLD-DM study visits and timing 
Months 
0 
1 
2 
3 
Enrollment, consent review (~20 min, remote visit) 
x 
 
 
 
Surveys (~20-30 min, online or on phone) 
x 
 
 
x 
NAFLD education (~30 min, remotely) 
x 
 
 
 
Diet and lifestyle support (~30 min each, remotely) 
x 
x 
x 
 
Medication changes (~20 min, remotely) * 
o 
o 
o o 
If indicated, ordering tests and referrals * 
o 
o 
o o 
Interviews (~30 min, remotely) 
 
 
 
x 
*Timing of med changes and ordering of tests/referrals will vary by participant. 
x Visits that will occur for all participants. 
o Visits that may or may not occur and are dependent upon individual needs. 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 4 of 7 
Version 2: May 31, 2024 
 
Evidence-based care of NAFLD in T2D: Intervention content will include: 1) NAFLD education; 2) 
diet/lifestyle support; 3) T2D medication management; and 4) clinically-indicated liver testing and care. Dr. 
Alexopoulos (PI) and the Clinical Research Coordinator (CRC) will deliver NAFLD education and diet/lifestyle 
support content. Dr. Alexopoulos (PI) will conduct medication management, which will involve review of 
glycemic trends, assessment of hypoglycemia and adjustment of the T2D regimen to accommodate initiation of 
pioglitazone, GLP-1RA and/or SGLT2i. The order in which these medications are considered will depend on 
clinical judgement, patient preference and cost, but GLP-1RA will be prioritized as appropriate, since this class 
has potent weight loss effects.16 Also, at baseline (and as indicated throughout the study), Dr. Alexopoulos (PI) 
will review clinical data and order clinically-indicated liver testing based on guidelines. Surveys and clinical 
evaluation will be repeated at study conclusion. A treatment acceptability measure (TAP) 20 will be 
administered at conclusion to gauge intervention acceptability. A detailed summary of data collection and 
outcome measures can be seen in Table 3. 
 
Table 3: Detailed summary of data collection 
and outcomes 
Method 
Timing 
Primary outcomes 
Feasibility 
System-level NAFLD detection  
Patients who met criteria for NAFLD 
after chart review / total number of 
potentially-eligible patients based 
on our EHR criteria 
3 months 
Recruitment rate* 
Patients eligible and sent letter or 
MyChart message / Patients 
enrolled  
3 months 
Retention rate 
Patients enrolled / Patients 
completed study 
3 months 
Visit completion rate 
Total study visits completed / total 
study visits scheduled 
3 months 
Acceptability 
 
TAP measure20 
3 months 
 
Qualitative interviews 
3 months 
Secondary outcomes of interest 
Medication changes made during the study 
 
Study visit notes in EHR 
0, 3 months 
Proportion of patients in whom clinically-
indicated tests were ordered (e.g. labs, referral, 
imaging).   
Study visit notes in HER 
0, 3 months 
Psychosocial constructs 
Self-efficacy 
Autonomy support 
Quality of life 
 
6-item SEMCD21 
HCCQ Diabetes18 
SF-1219 
 
0,3 months 
Descriptive data to characterize population 
Social and demographic 
Age, sex, race/ethnicity, marital status, 
education, employment, tobacco use, 
alcohol use, SDOH screen (food 
insecurity, housing instability, lack of 
transportation) 
Self-reported surveys 
0 months 
Health literacy/numeracy 
NVS 
0 months 
Medication adherence 
VMNQ22 
0 months 
Clinical 
Baseline knowledge of NAFLD, years 
with diabetes, medical history, 
medication use 
Self-reported surveys 
0 months 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 5 of 7 
Version 2: May 31, 2024 
 
Labs: HbA1c, AST, ALT 
Use from EHR if collected within 3 
months of baseline visit. Otherwise, 
research labs collected in DUHS at 
specified time points. 
 
0 months 
Biomedical 
Height, weight, BMI 
From EHR (last recorded values) 
0 months 
*We will also track the number of participants who expressed interest in the study based on our recruitment flyer, and 
examine the recruitment rate via this approach (i.e., patients who expressed interest / patients enrolled. Abbreviations: 
TAP=Treatment Acceptability & Preferences; SDOH=social determinates of health; NAFLD=nonalcoholic fatty liver 
disease; BMI=body mass index; HER=electronic health record; SEMCD=Self-efficacy to Manage Chronic Disease 
Scale; VMNQ=Voils Medication Non-Adherence Questionnaire; NVS=Newest Vital Sign; HCCQ=Healthcare Climate 
Questionnaire.  
Participant interviews: At study conclusion, individual 30-minute virtual interviews will be conducted with all 
study participants. The primary purpose will be to assess intervention acceptability and to gain specific 
feedback about intervention content. Thematic saturation is expected by 12 interviews.22  
 
Quantitative analysis: Intervention feasibility will be evaluated by examining recruitment rates, retention rates, 
and  study visit completion rates. For the TAP measure, mean score and standard deviation will be calculated. 
This feasibility pilot will not be powered to examine changes in clinical measures (e.g., HbA1c, ALT).  
 
Qualitative analysis: All interviews will be digitally recorded and transcribed. Transcripts will be analyzed with 
direct content analysis.23  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 6 of 7 
Version 2: May 31, 2024 
 
References 
 
1. 
Younossi ZM, Stepanova M, Rafiq N, et al. Nonalcoholic steatofibrosis independently predicts mortality in 
nonalcoholic fatty liver disease. Hepatol Commun. Jul 2017;1(5):421-428. doi:10.1002/hep4.1054 
2. 
Diabetes Mellitus. Federal Practitioner. 2017; 
3. 
Samji NS, Snell PD, Singal AK, Satapathy SK. Racial Disparities in Diagnosis and Prognosis of Nonalcoholic Fatty 
Liver Disease. Clin Liver Dis (Hoboken). Aug 2020;16(2):66-72. doi:10.1002/cld.948 
4. 
Alexopoulos AS, Crowley MJ, Wang Y, et al. Glycemic Control Predicts Severity of Hepatocyte Ballooning and 
Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease. Hepatology. Mar 16 2021;doi:10.1002/hep.31806 
5. 
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: 
Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. Jan 2018;67(1):328-357. 
doi:10.1002/hep.29367 
6. 
American Diabetes A. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of 
Medical Care in Diabetes-2021. Diabetes Care. Jan 2021;44(Suppl 1):S40-S52. doi:10.2337/dc21-S004 
7. 
Newsome PN, Buchholtz K, Cusi K, et al. A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic 
Steatohepatitis. N Engl J Med. Mar 25 2021;384(12):1113-1124. doi:10.1056/NEJMoa2028395 
8. 
Raj H, Durgia H, Palui R, et al. SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes 
mellitus: A systematic review. World J Diabetes. Feb 15 2019;10(2):114-132. doi:10.4239/wjd.v10.i2.114 
9. 
Alexopoulos AS, Duffy R, Kobe EA, et al. Underrecognition of nonalcoholic fatty liver disease in poorly-controlled 
diabetes: A call to action in diabetes care. J Endocr Soc (In Press). 2021; 
10. 
Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease 
demonstrates an exponential increase in burden of disease. Hepatology. Jan 2018;67(1):123-133. 
doi:10.1002/hep.29466 
11. 
Shetty A, Syn WK. Health and Economic Burden of Nonalcoholic Fatty Liver Disease in the United States and Its 
Impact on Veterans. Fed Pract. Jan 2019;36(1):14-19.  
12. 
Younossi ZM, Blissett D, Blissett R, et al. The economic and clinical burden of nonalcoholic fatty liver disease in 
the United States and Europe. Hepatology. Nov 2016;64(5):1577-1586. doi:10.1002/hep.28785 
13. 
Haw JS, Shah M, Turbow S, Egeolu M, Umpierrez G. Diabetes Complications in Racial and Ethnic Minority 
Populations in the USA. Curr Diab Rep. Jan 9 2021;21(1):2. doi:10.1007/s11892-020-01369-x 
14. 
MH B. The Health Belief Model and personal health behavior. Health Education Monographs. 1974;2:324–508.  
15. 
EH W. Chronic disease management: What will it take to improve care for chronic illness? Effective Clinical 
Practice. 1998;1(1):2-4.  
16. 
American Diabetes A. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in 
Diabetes-2021. Diabetes Care. Jan 2021;44(Suppl 1):S111-S124. doi:10.2337/dc21-S009 
17. 
Kanwal F, Kramer JR, Mapakshi S, et al. Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver 
Disease. Gastroenterology. Dec 2018;155(6):1828-1837 e2. doi:10.1053/j.gastro.2018.08.024 
18. 
Williams GC, Freedman ZR, Deci EL. Supporting autonomy to motivate patients with diabetes for glucose control. 
Diabetes Care. Oct 1998;21(10):1644-51. doi:10.2337/diacare.21.10.1644 
19. 
Ware J, Jr., Kosinski M, Keller SD. A 12-Item Short-Form Health Survey: construction of scales and preliminary 
tests of reliability and validity. Med Care. Mar 1996;34(3):220-33. doi:10.1097/00005650-199603000-00003 
20. 
Sidani S, Epstein DR, Bootzin RR, Moritz P, Miranda J. Assessment of preferences for treatment: validation of a 
measure. Res Nurs Health. Aug 2009;32(4):419-31. doi:10.1002/nur.20329 
21. 
Ritter PL, Lorig K. The English and Spanish Self-Efficacy to Manage Chronic Disease Scale measures were 
validated using multiple studies. J Clin Epidemiol. Nov 2014;67(11):1265-73. doi:10.1016/j.jclinepi.2014.06.009 
22. 
G. G, A. B, Johnson L. How Many Interviews Are Enough?: An Experiment with Data Saturation and Variability. 
Field Methods. 2006;18(1):59-82.  
23. 
Hsieh HF, Shannon SE. Three approaches to qualitative content analysis. Qual Health Res. Nov 2005;15(9):1277-
88. doi:10.1177/1049732305276687 

Improving detection and evidence-based care of NAFLD in Latinx and Black patients with type 2 
diabetes (NAFLD-DM): A pilot study  
PI: Anastasia-Stefania Alexopoulos, MD 
 
Page 7 of 7 
Version 2: May 31, 2024