NAFLD, Type 1 Diabetes, Cardiovascular Diseases
Conditions
Keywords
NAFLD, type 1 diabetes, cardiovascular disease, insulin resistance
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.
Interventions
DIAGNOSTIC_TESTultrasound
ultrasound to check for NAFLD according to Saverymuttu criteria
DIAGNOSTIC_TESTelastography
elastography to compare liver stiffness indices
DIAGNOSTIC_TESTcontrolled attenuation parameter (CAP)
CAP is a non-invasive additive on Fibroscan (trademark) which can quantify hepatic steatosis
DIAGNOSTIC_TESTFLI
the FLI is a score panel designed to screen for NAFLD
DIAGNOSTIC_TESTFIB-4
the FIB-4 is a score panel designed to screen for significant fibrosis
DIAGNOSTIC_TESTNFS
the NFS is a score panel designed to screen for significant fibrosis
Sponsors
University Hospital, Antwerp
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of NAFLD in type 1 diabetes: percentage of patients with indices of liver steatosis and/or NASH and/or fibrosis. | one year | Determination of the cross-sectional prevalence of NAFLD in a cohort of type 1 diabetes patient (population size approximately 1000 subjects) according to ultrasound criteria, FLI≥60, HSI≥36, controlled attenuation parameter \>215dB/m (M-probe) or ≥250 dB/m (XL probe) and MRI-PDFF \>5% hepatocyte steatosis (reference method). All measures will be performed in a combined and standardized protocol to explore their diagnostic accuracy (see outcome 4). |
| Incidence of NAFLD in type 1 diabetes. | five years | Incidence of NAFLD in type 1 diabetes determined by new cases of NAFLD according to ultrasound criteria, FLI≥60, HSI≥36, controlled attenuation parameter \>215dB/m (M-probe) or ≥250 dB/m (XL probe) or MRI-PDFF \>5% hepatocyte fat infiltration (reference method) |
| 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 | one year | The correlation between indices of microvascular (neuropathy assessed by microfilament test, nephropathy assessed by microalbuminuria rate and retinopathy assessed by fundoscopic criteria) or macrovascular (non-fatal ischemic coronary disease, non-fatal cerebrovascular disease, non-fatal peripheral artery disease, or mortality due to cardiovascular disease) complications will be compared between groups with and without NAFLD as determined by the abovementioned screening tools. |
| 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 | five years | The association between indices of microvascular (neuropathy assessed by microfilament test, nephropathy assessed by microalbuminuria rate and retinopathy assessed by fundoscopic criteria) or macrovascular (non-fatal ischemic coronary disease, non-fatal cerebrovascular disease, non-fatal peripheral artery disease or mortality due to cardiovascular disease) complications will be assessed between groups with and without NAFLD, but all without prior micro- or macrovascular disease as determined by the abovementioned screening tools. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Diagnostic accuracy of non-invasive tools for NAFLD in type 1 diabetes: comparison of AUROC and diagnostic accuracy | five years | The investigators will compare the abovementioned non-invasive tools to diagnose and grade liver steatosis and fibrosis with the predefined gold standard (MRI-PDFF for steatosis and magnetic resonance elastography for fibrosis). Correlations and agreement statistics will be performed for each index. Using regression analysis, a new specific algorithm will be developed based on cohort-specific cutoffs. Using longitudinal data, a prediction score will be determined to predict NAFLD occurrence or NAFLD progression. |
| Natural history of NAFLD in type 1 diabetes | five years | Timewise description of the progression of quantitative indices of liver steatosis and fibrosis on the abovementioned tools (ultrasound, score systems, elastography) to assess the natural evolution of NAFLD. Every year this assay will be performed. MRI-PDFF will be performed in 5 years as a reference method to mark the five-year follow-up window |
Countries
Belgium
Contacts
Primary ContactJonathan Mertens, M.D.
Backup ContactRie Braspenning, nurse
Outcome results
None listed