Non Alcoholic Fatty Liver Disease and Coronary Heart Disease in Type 2 Diabetes Patients
Non Alcoholic Fatty Liver Disease and Coronary Heart Disease in Type 2 Diabetes Patients
To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and
 advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the
 hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to
 estimate hepatic stiffness.
This is a prospective cohort study consisting of a one-time visit by diabetic patients with
 optional following liver biopsy. The aim of the study is to evaluate whether liver fat
 fraction and liver stiffness, as determined by magnetic resonance imaging, are associated
 with subclinical cardiovascular disease, as evaluated by coronary artery calcium scan in
 diabetics. During the visit, patients will undergo review of medical history, vitals
 (including body mass index, blood pressure), physical exam, blood work, urine collection,
 ECG, magnetic resonance imaging (MRI), including MR proton density fat fraction (MRI-PDFF)
 and MR elastography, ultrasound using acoustic radiation force impulse (ARFI) imaging, and
 computed tomography (CT) scan for coronary artery calcium scoring. Blood work will be sent
 for labs relevant to traits of metabolic syndrome including markers for diabetes (hemoglobin
 A1C, fasting glucose) and hyperlipidemia (lipid panel). Serum, plasma and whole blood will be
 stored for future studies. Results from history, physical exam, and radiographic imaging will
 be analyzed and if they indicate the presence of nonalcoholic steatohepatitis, patients will
 be offered an optional liver biopsy for further assessment. All patients will be invited to
 continue in the study and have follow-up visits every two years for a total duration of the
 study of 5 years.
Inclusion criteria:

 -  Adults, age 21 or above, with diagnosis of T2DM according to the American Diabetes
 Association (ADA) clinical practice recommendations.

 -  T2DM is defined according to American Diabetes Association (ADA) clinical practice
 recommendations if one of the following criteria is met:

 -  Diabetes symptoms (polyuria, polydipsia, polyphagia, increased fatigue, weight
 loss, blurred vision) exist and casual plasma glucose ≥200 mg/dl (11.1 mmol/l) OR

 -  Fasting plasma glucose (FPG) ≥126 mg/dl (7.0 mmol/l); OR

 -  Plasma glucose ≥200 mg/dl (11.1 mmol/l) during a 75-g oral glucose tolerance test
 (OGTT) (25).

 -  If any of these test results occur, testing should be repeated on a different day to
 confirm the diagnosis. OR

 -  hemoglobin A1C (HbA1C) ≥6.5% (26).

 -  The subject is fully informed and willing and able to perform all the procedures
 specified in the protocol and signed a written informed consent to participate

 Exclusion criteria:

 -  Documented history of cardiovascular disease (CVD), such as acute coronary syndrome
 (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable
 angina), stable angina, history of angioplasty or stent placement, cerebrovascular
 disease (ischemic or hemorrhagic stroke), and peripheral vascular disease.

 -  History of congestive heart failure

 -  Evidence of other causes of chronic liver disease

 -  Hepatitis B as defined as presence of hepatitis B surface antigen (HBsAg).

 -  Previous or current infection with Hepatitis C as defined by presence of
 hepatitis C virus Ab in serum (anti-HCV Ab).

 -  Autoimmune hepatitis as defined by anti-nuclear antibody (ANA) of 1:160 or
 greater and liver histology consistent with autoimmune hepatitis or previous
 response to immunosuppressive therapy.

 -  Autoimmune cholestatic liver disorders as defined by elevation of alkaline
 phosphatase and anti-mitochondrial antibody of greater than 1:80 or liver
 histology consistent with primary biliary cirrhosis or elevation of alkaline
 phosphatase and liver histology consistent with sclerosing cholangitis.

 -  Wilson disease as defined by ceruloplasmin below the limits of normal and liver
 histology consistent with Wilson disease.

 -  Alpha-1-antitrypsin deficiency as defined by alpha-1-antitrypsin level less than
 normal and liver histology consistent with alpha-1-antitrypsin deficiency.

 -  Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy
 and homozygosity for C282Y or compound heterozygosity for C282Y/H63D.

 -  Drug-induced liver disease as defined on the basis of typical exposure and
 history.

 -  Bile duct obstruction as shown by imaging studies.

 -  History of gastrointestinal bypass surgery or ingestion of medications known to
 produce steatosis, such as corticosteroids, high-dose estrogen, tamoxifen,
 methotrexate, amiodarone or tetracycline in the previous 6 months.

 -  Evidence of cirrhosis or previously known cirrhosis based on the results from previous
 liver biopsy or history of portal hypertension presented by ascites, hepatic
 encephalopathy or varices

 -  Absence of regular and/or excessive use of alcohol(defined as >30g/day for males and
 >15g/day for females) for a period longer than 2 years at any times in the last 10
 years

 -  Serum creatinine> 1.5 mg/dL

 -  The subject is a pregnant or nursing female

 -  Contraindications to computed tomography (CT) or magnetic resonance imaging (MRI):

 -  The subject has any contraindication to MR imaging, such as patients with cardiac
 pacemaker or defibrillator, neurostimulator, intravascular stents, coils, valves,
 surgical clips, implanted electronic infusion pump, ferromagnetic foreign body or
 other conditions that would preclude proximity to a strong magnetic field.

 -  The subject has a history of extreme claustrophobia.

 -  The subject cannot fit inside the MRI or CT machine