Prevalence, Incidence and Characteristics of NAFLD/NASH in Type 1 Diabetes Mellitus (NAFLDIA1)
3 de marzo de 2022 actualizado por: Christophe De Block, University Hospital, Antwerp
Prevalence, Incidence and Characteristics of NAFLD/NASH in Type 1 Diabetes Mellitus Obtained Via a Non-invasive Screening Protocol
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.
Descripción general del estudio
Estado
Reclutamiento
Condiciones
Descripción detallada
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.
Tipo de estudio
De observación
Inscripción (Anticipado)
700
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Estudio Contacto
- Nombre: Jonathan Mertens, M.D.
- Número de teléfono: +328217304
- Correo electrónico: jonathan.mertens@uza.be
Copia de seguridad de contactos de estudio
- Nombre: Rie Braspenning, nurse
- Correo electrónico: rie.braspenning@uza.be
Ubicaciones de estudio
-
-
Antwerp
-
Edegem, Antwerp, Bélgica, 2650
- Reclutamiento
- Antwerp University Hospital
-
Contacto:
- Jonathan Mertens, M.D.
- Número de teléfono: +328217304
- Correo electrónico: jonathan.mertens@uza.be
-
-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Método de muestreo
Muestra no probabilística
Población de estudio
Adult type 1 diabetes patients followed in the outpatient diabetes clinic of the Antwerp University Hospital
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / Cohorte |
Intervención / Tratamiento |
|---|---|
|
NAFLD + type 1 diabetes
type 1 diabetes patient with NAFLD on screening
|
ultrasound to check for NAFLD according to Saverymuttu criteria
elastography to compare liver stiffness indices
CAP is a non-invasive additive on Fibroscan (trademark) which can quantify hepatic steatosis
the FLI is a score panel designed to screen for NAFLD
the FIB-4 is a score panel designed to screen for significant fibrosis
the NFS is a score panel designed to screen for significant fibrosis
|
|
noNAFLD + type 1 diabetes
type 1 diabetes patient without NAFLD on screening
|
ultrasound to check for NAFLD according to Saverymuttu criteria
elastography to compare liver stiffness indices
CAP is a non-invasive additive on Fibroscan (trademark) which can quantify hepatic steatosis
the FLI is a score panel designed to screen for NAFLD
the FIB-4 is a score panel designed to screen for significant fibrosis
the NFS is a score panel designed to screen for significant fibrosis
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Prevalence of NAFLD in type 1 diabetes: percentage of patients with indices of liver steatosis and/or NASH and/or fibrosis.
Periodo de tiempo: 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).
|
one year
|
|
Incidence of NAFLD in type 1 diabetes.
Periodo de tiempo: 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)
|
five years
|
|
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
Periodo de tiempo: 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.
|
one year
|
|
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
Periodo de tiempo: 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.
|
five years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Diagnostic accuracy of non-invasive tools for NAFLD in type 1 diabetes: comparison of AUROC and diagnostic accuracy
Periodo de tiempo: 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.
|
five years
|
|
Natural history of NAFLD in type 1 diabetes
Periodo de tiempo: 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
|
five years
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Christophe De Block, M.D., PhD, Universiteit Antwerpen
- Investigador principal: Sven Francque, M.D., PhD, Universiteit Antwerpen
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- 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.
- 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.
- 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.
- 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.
- 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.
- Hampson SJ. Nursing interventions for the first three postpartum months. J Obstet Gynecol Neonatal Nurs. 1989 Mar-Apr;18(2):116-22. doi: 10.1111/j.1552-6909.1989.tb00474.x.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
17 de septiembre de 2018
Finalización primaria (Anticipado)
30 de julio de 2023
Finalización del estudio (Anticipado)
30 de julio de 2025
Fechas de registro del estudio
Enviado por primera vez
4 de noviembre de 2020
Primero enviado que cumplió con los criterios de control de calidad
10 de diciembre de 2020
Publicado por primera vez (Actual)
11 de diciembre de 2020
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
4 de marzo de 2022
Última actualización enviada que cumplió con los criterios de control de calidad
3 de marzo de 2022
Última verificación
1 de marzo de 2022
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Digestivo
- Trastornos del metabolismo de la glucosa
- Enfermedades metabólicas
- Enfermedades del sistema inmunológico
- Enfermedades autoinmunes
- Enfermedades del sistema endocrino
- Enfermedades del HIGADO
- Hígado graso
- Enfermedades cardiovasculares
- Diabetes mellitus
- Diabetes Mellitus, Tipo 1
- Enfermedad del hígado graso no alcohólico
Otros números de identificación del estudio
- 18/32/361
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Descripción del plan IPD
monocentric study
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Sí
producto fabricado y exportado desde los EE. UU.
No
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