Clinical trial NCT04664036: Prevalence, Incidence and Characteristics of NAFLD/NASH in Type 1 Diabetes Mellitus
Official title: Prevalence, Incidence and Characteristics of NAFLD/NASH in Type 1 Diabetes Mellitus Obtained Via a Non-invasive Screening Protocol
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: NAFLD
Type 1 Diabetes
Cardiovascular Diseases
Keywords: NAFLD
type 1 diabetes
cardiovascular disease
insulin resistance
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
First posted: 2020-12-11
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult type 1 diabetes patients followed in the outpatient diabetes clinic of the Antwerp University Hospital

Brief summary: Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by intrahepatic fat accumulation. It is closely related to insulin resistance. To date, it remains unclear whether NAFLD is common in patients with type 1 diabetes or if NAFLD translates into an increased health burden in this population. Screening for NAFLD is challenging due to the limitations of non-invasive diagnostic tools.

Liver biopsy remains the gold standard but is not suited for routine screening or clinical studies. Therefore, there is a great demand for accurate non-invasive screening tools that can not only diagnose but also stage NAFLD. This study aims to generate a large cohort of thoroughly characterized type 1 diabetes patients screened for NAFLD using multiple non-invasive tools including MRI, ultrasound, controlled attenuation parameter, and score panels. We aim to generate a biobank to promote a research collaboration network in the field of non-invasive diagnosis of NAFLD.

A secondary endpoint is to investigate the potential correlation between the presence of NAFLD and the occurrence of micro-or macrovascular complications in patients with diabetes.

Detailed description: This study aims to characterize and follow a thoroughly characterized cohort of adult type 1 diabetes patients free from secondary liver disease due to excessive alcohol usage, viral hepatitis, alfa-1 antitrypsin deficiency, Wilson's disease or steatogenic or hepatotoxic drug use.

The investigators will screen for NAFLD and fibrosis using multiple non-invasive techniques including

* ultrasound
* controlled attenuation parameter
* fatty liver index
* human steatosis index
* transient elastography
* FIB-4
* NAFLD fibrosis score
* NASH algorithm based on multiple parameters

Subjects will be screened for microvascular and microvascular complications with:

* ECG
* microfilament examination
* 24hour urine collection for microalbuminuria
* serum kidney test (creatinine, eGFR)
* fundoscopy
* peripheral arterial pulsation palpation

The investigators will subsequently thoroughly characterize various metabolic and anthropometric parameters and document any microvascular or macrovascular complications.

The patients will be annually rescreened for both NAFLD-related as cardiovascular variables. Therefore this study will assess the correlation between NAFLD, cardiovascular risk, and type 1 diabetes in a prospective manner.

Eligibility criteria: Inclusion Criteria:

* Type 1 diabetes
* Adult age
* Informed consent given

Exclusion Criteria:

* Secondary liver disease
* Excess alcohol usage
* Pregnancy
* Use of steatogenic medication
* Active cancer or oncological treatment
* History of organ transplantation

Primary outcomes:
measure: Prevalence of NAFLD in type 1 diabetes: percentage of patients with indices of liver steatosis and/or NASH and/or fibrosis.
timeFrame: one year
measure: Incidence of NAFLD in type 1 diabetes.
timeFrame: five years
measure: correlation of NAFLD with microvascular and macrovascular complications in type 1 diabetes mellitus: odds ratio to have prevalent complications in NAFLD and diabetes compared to diabetes without NAFLD
timeFrame: one year
measure: Association of NAFLD with microvascular and macrovascular complications in type 1 diabetes mellitus: odds ratio to develop in NAFLD and diabetes compared to diabetes without NAFLD in subjects with no prior complications
timeFrame: five years
Secondary outcomes:
measure: Diagnostic accuracy of non-invasive tools for NAFLD in type 1 diabetes: comparison of AUROC and diagnostic accuracy
timeFrame: five years
measure: Natural history of NAFLD in type 1 diabetes
timeFrame: five years
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerp
Study officials:
affiliation: Universiteit Antwerpen
name: Christophe De Block, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universiteit Antwerpen
name: Sven Francque, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: de Vries M, Westerink J, Kaasjager KHAH, de Valk HW. Prevalence of Nonalcoholic Fatty Liver Disease (NAFLD) in Patients With Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2020 Dec 1;105(12):3842-53. doi: 10.1210/clinem/dgaa575.
citation: Tana C, Ballestri S, Ricci F, Di Vincenzo A, Ticinesi A, Gallina S, Giamberardino MA, Cipollone F, Sutton R, Vettor R, Fedorowski A, Meschi T. Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications. Int J Environ Res Public Health. 2019 Aug 26;16(17):3104. doi: 10.3390/ijerph16173104.
citation: European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. No abstract available.
citation: Ismaiel A, Dumitrascu DL. Cardiovascular Risk in Fatty Liver Disease: The Liver-Heart Axis-Literature Review. Front Med (Lausanne). 2019 Sep 13;6:202. doi: 10.3389/fmed.2019.00202. eCollection 2019.
citation: De Block CEM, Shivalkar B, Goovaerts W, Brits T, Carpentier K, Verrijken A, Van Hoof V, Parizel PM, Vrints C, Van Gaal LF. Coronary artery calcifications and diastolic dysfunction versus visceral fat area in type 1 diabetes: VISCERA study. J Diabetes Complications. 2018 Mar;32(3):271-278. doi: 10.1016/j.jdiacomp.2017.11.008. Epub 2017 Nov 28.
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