Non-Alcoholic Fatty Liver Disease in a Saudi Cohort With Type 2 Diabetes Mellitus (CORDIAL)

The global rise in the prevalence of obesity paved the way for the increased prevalence of yet another obesity-related complication significant enough to be considered within the roster of major public health threats: non-alcoholic fatty liver disease (NAFLD). In this follow-up study, the investigators will attempt to decipher the natural history of hepatic steatosis among patients with type 2 diabetes mellitus (T2DM) using state-of-the-art methods in a well-characterized Saudi cohort. The investigators aim also to validate existing biomarkers of disease severity and explore the pathogenesis of progressive disease using metabolic profiling technologies. A total of 1000 adult Saudi patients (males and females) with T2DM will be recruited. Those with co-morbidities, including hepatic decompensation, will be excluded. Participants will be followed three times for a total of 10 years/patient (Year 2, Year 5, and Year 10), and measures such as dietary evaluations, anthropometrics, and urine, stool, and blood examinations will be performed. Patients who develop NAFLD will be noted, and patterns/changes in the metabolic profile will be examined. For this specific grant (the first 2 years of the whole project), the investigators will be able to recruit the study cohort, do the baseline anthropometric, imaging, and biochemical measurements, and report the prevalence of NAFLD among patients with T2DM. This information will be the basis of subsequent follow-up and allow for validating potential diagnostic and prognostic biomarkers. This project will be of high importance at the national level since it will create awareness in the local medical community of the current severity status of NAFLD in the kingdom and will be used as a tool to promote public health awareness in the community.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus; Nonalcoholic Fatty Liver Disease

Detailed Description

The increased prevalence of obesity in both the developed and developing worlds paved the way to the increased prevalence of yet another obesity-related complication significant enough to be considered within the roster of major public health threats: non-alcoholic fatty liver disease (NAFLD). It has been estimated that approximately 20% to 30% of the adult population harbors NAFLD. It is also the most common liver pathology among children of developed countries. Unfortunately, despite the alarming figures, NAFLD remains largely underdiagnosed, probably because of its less aggressive nature and benign presentation compared with other liver diseases. Thus, it is apparent that NAFLD, being a precursor to more serious liver conditions such as cirrhosis and hepatocellular carcinoma, should be given equal, if not greater, clinical significance.

Accumulating evidence has pointed to parallel clinical similarities between NAFLD and metabolic syndrome (MetS), the clustering of cardiovascular risk factors with insulin resistance as the common unifying factor. It is well established that persons with MetS are at greater risk of progressing to major chronic non-communicable diseases such as coronary artery disease and type 2 diabetes mellitus (T2DM). Consequently, patients with T2DM are more likely to develop NAFLD. Obesity is acknowledged as one of the common denominators linking NAFLD, MetS, and T2DM, making dietary and lifestyle modifications the gold standard for the treatment of these clinical entities aside from pharmacotherapy that aims to improve insulin sensitivity. Therefore, it is important to better understand the intricate pathophysiology of NAFLD among patients with T2DM so that future interventions will be aimed at reversing complications.

Our current knowledge of NAFLD in terms of prognosis and treatment is promising yet inconclusive, which means that further investigations using prospective approaches are required. Only recently was a consensus design for clinical trials and endpoints for non-alcoholic steatohepatitis (NASH) reported. In this follow-up study, the investigators attempt to decipher the natural history of hepatic steatosis among patients with T2DM using state-of-the-art methods in a well-characterized Saudi cohort. Diabetes, and its related medical complications, have been identified as one of the priority areas of the National Plan for Science and Technology in the Kingdom of Saudi Arabia (KSA).

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Assim A Alfadda, MD; Phone Number: 0557021171; Email: aalfadda@ksu.edu.sa
• Study Contact Backup: Name: Rukhsana Gul, MD; Phone Number: 0501387295; Email: Rgul@ksu.edu.sa

Study Locations

• Saudi Arabia
  • Select A State Or Province
    • Riyadh, Select A State Or Province, Saudi Arabia, 11525
      • Recruiting
      • King Fahad Medical City

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The study population included patients who participated in the Cohort of Non-alcoholic Fatty Liver Disease with T2DM (the CORDIAL Study). This prospective cohort study started in 2015 and recruited patients from King Fahad Medical City (KFMC) and affiliated Primary Care Centers in Riyadh, Saudi Arabia. The patients will be prospectively followed up for 10 years for hepatic, metabolic, renal, and cardiovascular complications.

Description

Inclusion Criteria:

• Subject has provided informed consent prior to screening
• Men and women aged 18 to 60 years
• T2DM

Exclusion Criteria:

• Evidence of hepatic decompensation (ascites, clinical jaundice-bilirubin ≥ 40 µmol/L, encephalopathy)
• Preexisting hepatocellular carcinoma
• Other preexisting hepatic or extrahepatic malignancy
• Previous overt ischemic heart disease (myocardial infarction or acute coronary syndrome) or cerebrovascular disease (stroke or transient ischemic attack)
• Previous coronary artery bypass grafting, angioplasty, or stenting
• Any other issues that, in the opinion of the investigators, may preclude satisfactory completion of the study protocol

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of hepatic steatosis in T2DM	Fatty liver will be assessed by USS and FibroScan in patients with T2DM	15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression of hepatic steatosis to advanced liver disease will be assessed by USS and FibroScan.	Assessment of hepatic steatosis progression to advanced liver disease by USS and FibroScan.	15 years
Pathogenesis of progressive disease	Untargeted metabolomics using a high-throughput proton NMR metabolomics approach for the screening of novel metabolites to understand the pathogenesis of progressive disease	15 years

Collaborators and Investigators

• Sponsor: King Saud University
• Collaborators: King Fahad Medical City
• Investigators: Principal Investigator: Assim Alfadda, MD, King Saud University

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2015
• Primary Completion (Estimated): April 23, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: January 5, 2023
• First Submitted That Met QC Criteria: January 15, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: NAFLD; T2DM; Fatty Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CORDIAL KSU

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: was not including in protocol and consent form