Prevalence, Incidence and Characteristics of NAFLD/NASH in Type 1 Diabetes Mellitus (NAFLDIA1)
3 mars 2022 mis à jour par: 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.
Aperçu de l'étude
Statut
Recrutement
Les conditions
Description détaillée
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.
Type d'étude
Observationnel
Inscription (Anticipé)
700
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Coordonnées de l'étude
- Nom: Jonathan Mertens, M.D.
- Numéro de téléphone: +328217304
- E-mail: jonathan.mertens@uza.be
Sauvegarde des contacts de l'étude
- Nom: Rie Braspenning, nurse
- E-mail: rie.braspenning@uza.be
Lieux d'étude
-
-
Antwerp
-
Edegem, Antwerp, Belgique, 2650
- Recrutement
- Antwerp University Hospital
-
Contact:
- Jonathan Mertens, M.D.
- Numéro de téléphone: +328217304
- E-mail: jonathan.mertens@uza.be
-
-
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
Adult type 1 diabetes patients followed in the outpatient diabetes clinic of the Antwerp University Hospital
La description
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 d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
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
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Prevalence of NAFLD in type 1 diabetes: percentage of patients with indices of liver steatosis and/or NASH and/or fibrosis.
Délai: 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.
Délai: 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
Délai: 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
Délai: 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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Diagnostic accuracy of non-invasive tools for NAFLD in type 1 diabetes: comparison of AUROC and diagnostic accuracy
Délai: 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
Délai: 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
|
Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Chercheur principal: Christophe De Block, M.D., PhD, Universiteit Antwerpen
- Chercheur principal: Sven Francque, M.D., PhD, Universiteit Antwerpen
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- 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.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude (Réel)
17 septembre 2018
Achèvement primaire (Anticipé)
30 juillet 2023
Achèvement de l'étude (Anticipé)
30 juillet 2025
Dates d'inscription aux études
Première soumission
4 novembre 2020
Première soumission répondant aux critères de contrôle qualité
10 décembre 2020
Première publication (Réel)
11 décembre 2020
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
4 mars 2022
Dernière mise à jour soumise répondant aux critères de contrôle qualité
3 mars 2022
Dernière vérification
1 mars 2022
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 18/32/361
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Description du régime IPD
monocentric study
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produit fabriqué et exporté des États-Unis.
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