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MASLD, hepatic steatosis and fibrosis are associated with the prevalence of chronic kidney disease and retinopathy in adults with type 1 diabetes mellitus - 20/11/23

Doi : 10.1016/j.diabet.2023.101497 
Alessandro Mantovani 1, Mario Luca Morieri 2, Raffaella Aldigeri 3, Luisa Palmisano 4, Maria Masulli 4, Katia Bonomo 5, Marco Giorgio Baroni 6, 7, Efisio Cossu 8, Flavia Agata Cimini 9, Gisella Cavallo 9, Raffaella Buzzetti 9, Carmen Mignogna 9, Frida Leonetti 10, Simonetta Bacci 11, Roberto Trevisan 2, 12, Riccardo Maria Pollis 2, Alessandra Dei Cas 3, 13, Saula Vigili de Kreutzenberg 2, Giovanni Targher 1, 14,
1 Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy 
2 Metabolic Diseases, Department of Medicine, University of Padua, Padua, Italy 
3 Department of Medicine and Surgery, University of Parma, Parma, Italy 
4 Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy 
5 Diabetes and Metabolic Diseases Unit, San Luigi Gonzaga University Hospital, Turin, Italy 
6 Department of Clinical Medicine, Life, Health & Environmental Sciences, University of Aquila, L'Aquila, Italy 
7 Neuroendocrinology and Metabolic Diseases, IRCCS Neuromed, Pozzilli, Italy 
8 Diabetology Unit, Policlinico Universitario of Cagliari, Cagliari, Italy 
9 Department of Experimental Medicine, Sapienza University, Rome, Italy 
10 Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University, Rome, Italy 
11 Section of Endocrinology, Department of Medicine, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy 
12 Department of Medicine and Surgery, University of Milan Bicocca, Milan, Italy 
13 Division of Nutritional and Metabolic Sciences, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy 
14 IRCCS Sacro Cuore - Don Calabria Hospital, Negrar di Valpolicella, Italy 

Correspondence: Prof. Giovanni Targher, MD, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata, Piazzale Stefani, 1, 37126 Verona, ItalySection of Endocrinology, Diabetes and Metabolism, Department of MedicineUniversity and Azienda Ospedaliera Universitaria IntegrataPiazzale Stefani, 1Verona37126Italy
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HIGHLIGHTS

Little is known about the association between MASLD and risk of CKD and diabetic retinopathy in people with type 1 diabetes.
In adults with type 1 diabetes MASLD with and without coexisting significant fibrosis was associated with an increased risk of prevalent CKD and retinopathy.
This association remained significant after adjusting for multiple renal risk factors.

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ABSTRACT

Aim

We examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM).

Methods

We performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants.

Results

Patients with MASLD and significant fibrosis (n=93) had a remarkably higher prevalence of CKD and diabetic retinopathy than their counterparts with MASLD without fibrosis (n=578) and those without steatosis (n=738). After adjustment for sex, diabetes duration, hemoglobin A1c, hypertension, and use of antihypertensive or lipid-lowering medications, patients with SLD and significant fibrosis had a higher risk of prevalent CKD (adjusted-odds ratio 1.76, 95% confidence interval 1.05-2.96) than those without steatosis. Patients with MASLD without fibrosis had a higher risk of prevalent retinopathy (adjusted-odds ratio 1.49, 95% CI 1.13-1.46) than those without steatosis.

Conclusion

This is the largest cross-sectional study showing that MASLD with and without coexisting significant fibrosis was associated, independently of potential confounders, with an increased risk of prevalent CKD and retinopathy in adults with T1DM.

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Keywords : Chronic kidney disease, CKD, Diabetic retinopathy, Metabolic dysfunction-associated steatotic liver disease, Nonalcoholic fatty liver disease, Steatotic liver disease, Type 1 diabetes

Abbreviations : MASLD, NAFLD, SLD, T1DM, CKD, BMI, AST, ALT, GGT, eGFR, ACR, CKD-EPI, HSI, FIB-4


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