Prevalence of NAFLD and Advanced Fibrosis in Patients With Type 1 Diabetes

Assessing the Prevalence of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in Patients With Type 1 Diabetes Using Vibration-Controlled Transient Elastography and Noninvasive Scores

The aim of this study is to assess the prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 1 diabetes receiving care at Joslin clinic using noninvasive imaging and serum-based methods with the goal of identifying high-risk patients with advanced fibrosis who should be prioritized for specialty referral

Study Overview

• Status: Active, not recruiting
• Conditions: Type 1 Diabetes; Fibrosis, Liver; Nonalcoholic Steatohepatitis; Cirrhosis, Liver; Nonalcoholic Fatty Liver
• Intervention / Treatment: Device: Transient Elastography

Detailed Description

This is a prospective cohort, single-center, single-arm study screening adult subjects with type 1 diabetes from the Joslin Diabetes Center outpatient clinic mainly through physician referrals for NAFLD and advanced fibrosis. Subjects will undergo a one-time screening which will last for about 30 minutes.

The following procedures will be conducted during the study visit:

1. Blood draw for metabolic measurements (HbA1c, lipid panel, ALT, AST, serum albumin, complete blood count-CBC)
2. FibroScan Measurements (LSM and CAP)
3. Anthropometric measurements (weight, height, BMI calculation, waist, and hip circumference)
4. Systolic and diastolic blood pressure

Blood Draw:

Samples of blood taken during the trial for laboratory testing will include the following metabolic measurements: AST, ALT, Platelets, percentage A1C, and lipid parameters (TC, LDL, HDL, TG).

Fibroscan: Vibration controlled transient elastography (VCTE) or FibroScan® (EchoSens, Paris, France) is a simple aid to diagnose adult patients with chronic liver diseases. FibroScan provides a fast and reliable alternative to hepatic needle biopsy. In this 5-7 minute test, the investigator induces a mild amplitude shear wave into liver tissue from a small mechanical vibrator at the end of the FibroScan probe. VCTE evaluates a representative volume of the liver that is 100-fold greater than needle biopsy and the liver stiffness measurement (LSM) is expressed in kilopascals (kPa) with values >9.8 kPa being consistent with the presence of advanced fibrosis/cirrhosis. Typically, 10 successful VCTE measurements with a median interquartile range/median ration of less than 30% are needed to have a reliable LSM.

FIB-4 Index: This is a noninvasive surrogate biomarker of advanced fibrosis that is calculated using the following formula:

FIB-4 = Age (years)×AST (U/L)/[PLT(109/L)×√ALT(U/L)] (Sterling, Lissen et al. 2006) FIB-4>2.67 is consistent with the presence of advanced fibrosis with 80% PPV.

NAFLD Fibrosis Score (NFS): This is a noninvasive surrogate biomarker of advanced fibrosis that is calculated using the following formula:

NFS= -1.675 + 0.037 - age (years) + 0.094 - BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet count (×109/l) - 0.66 × albumin (g/dl).

NFS>0.676 is consistent with the presence of advanced fibrosis

Anthropometric measurements: These include weight, height, BMI calculation, waist, and hip measurements. Measurements will be done using standardized anthropometric techniques.

Follow up may be required for High-risk patients with advanced fibrosis. If patient consents, referring or treating physicians will be notified and provided with fibroscan results for possible referral to hepatologists for further evaluation and intervention.

• Study Type: Observational
• Enrollment (Estimated): 533

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will include subjects with type 1 diabetes receiving care at Joslin Diabetes Center. Addiotnal subjects from the broader Boston area may be recruited for the study.

Description

Inclusion Criteria:

1. Subject is male or female
2. Subject age between 18-75 years old
3. Subject with an established diagnosis of T1D for at least three months prior to screening

Exclusion Criteria:

1. Subject is pregnant or lactating
2. Subject has an active malignancy

4.Subject with secondary causes of fatty liver including history of any of the following:

• Hepatitis B or C virus infection
• Wilson's disease
• Lipodystrophy
• Abetalipoproteinemia
• Current or previous use of any of the following medication: amiodarone, tamoxifen, methotrexate,corticosteroids (e.g. Prednisone), or Valproate
• Male subject consuming >30 g of alcohol per day or female subject consuming >20 g of alcohol perday

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Study Cohort; 533 adult subjects with type 1 diabetes with no secondary causes of fatty liver	Device: Transient Elastography; Transient elastography is a noninvasive imaging modality used to assess NAFLD and advanced fibrosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with NAFLD	Controlled Attenuation Parameter (CAP) will be used to define the presence of NAFLD	Baseline (one time point evaluation)
Proportion of subjects with advanced fibrosis	Transient elastography will be used to define the presence of fibrosis	Baseline (one time point evaluation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with advanced fibrosis per NAFLD fibrosis score-NFS	NFS will be calculated using the following formula: NFS= -1.675 + 0.037 - age (years) + 0.094 - BMI (kg/m2) + 1.13 × IFG/diabetes (yes = 1, no = 0) + 0.99 × AST/ALT ratio - 0.013 × platelet count (×109/l) - 0.66 × albumin (g/dl).	Baseline (one time point evaluation)
Proportion of subjects with advanced fibrosis per Fibrosis-4 (FIB-4) index	FIB-4 will be calculated using the following formula: FIB-4 = Age (years)×AST (U/L)/[PLT(109/L)×√ALT(U/L)]	Baseline (one time point evaluation)
HbA1c	Association with level of diabetes control as reflected in percentage HbA1c	Baseline (one time point evaluation)
Anthropometrics	Association with BMI and waist circumference	Baseline (one time point evaluation)
Lipid profile	Association with lipid parameters (LDL, HDL, TG)	Baseline (one time point evaluation)

Collaborators and Investigators

• Sponsor: Joslin Diabetes Center
• Investigators: Principal Investigator: Osama Hamdy, MD PhD, Joslin Diabetes Center

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2021
• Primary Completion (Actual): August 19, 2022
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: October 13, 2020
• First Submitted That Met QC Criteria: October 19, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Screening; Type 1 Diabetes; Nonalcoholic fatty liver disease (NAFLD); Nonalcoholic steatohepatitis (NASH); Advanced fibrosis
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Liver Diseases; Fibrosis; Fatty Liver; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 1; Liver Cirrhosis
• Other Study ID Numbers: STUDY00000092

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No