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

Active, not recruiting
Conditions
Nonalcoholic Steatohepatitis
Cirrhosis, Liver
Nonalcoholic Fatty Liver
Type 1 Diabetes
Fibrosis, Liver
Interventions
Device: Transient Elastography
Registration Number
NCT04595474
Lead Sponsor
Joslin Diabetes Center
Brief Summary

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

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
533
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Study CohortTransient Elastography533 adult subjects with type 1 diabetes with no secondary causes of fatty liver
Primary Outcome Measures
NameTimeMethod
Proportion of subjects with NAFLDBaseline (one time point evaluation)

Controlled Attenuation Parameter (CAP) will be used to define the presence of NAFLD

Proportion of subjects with advanced fibrosisBaseline (one time point evaluation)

Transient elastography will be used to define the presence of fibrosis

Secondary Outcome Measures
NameTimeMethod
AnthropometricsBaseline (one time point evaluation)

Association with BMI and waist circumference

Proportion of subjects with advanced fibrosis per Fibrosis-4 (FIB-4) indexBaseline (one time point evaluation)

FIB-4 will be calculated using the following formula:

FIB-4 = Age (years)×AST (U/L)/\[PLT(109/L)×√ALT(U/L)\]

HbA1cBaseline (one time point evaluation)

Association with level of diabetes control as reflected in percentage HbA1c

Proportion of subjects with advanced fibrosis per NAFLD fibrosis score-NFSBaseline (one time point evaluation)

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).

Lipid profileBaseline (one time point evaluation)

Association with lipid parameters (LDL, HDL, TG)

Trial Locations

Locations (1)

Joslin Diabetes Center

🇺🇸

Boston, Massachusetts, United States

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