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