Microvascular complications of type 2 diabetes with or without MASLD: the EPSOMIP study, a primary care cohort study

Bergram et al. BMC Primary Care (2025) 26:354 https://doi.org/10.1186/s12875-025-03096-2 BMC Primary Care Open Access RESEARCH Microvascular complications of type 2 diabetes with or without MASLD: the EPSOMIP study, a primary care cohort study Martin Bergram1* , Stergios Kechagias2, Fredrik Iredahl3,4, Wile Balkhed2, Markus Holmberg2, Nils Dahlström5,6, Peter Lundberg5,6,7, Patrik Nasr2,4,5, Mattias Ekstedt2,5 and Karin Rådholm8,9 Abstract Background Previous studies have shown inconsistent results for the microvascular complication risk in patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). In addition, many of these studies have been done in specialist care setting. We therefore aimed to explore the association between MASLD and chronic kidney disease, retinopathy, neuropathy, and diabetic foot ulcers in a primary care setting. Methods Participants with type 2 diabetes were recruited in primary care. Hepatic triglyceride content was assessed using magnetic resonance imaging with liver proton density fat fraction (MASLD ≥ 5%) or vibration-controlled transient elastography with controlled attenuation parameter (MASLD ≥ 248 dB/m), and hepatic fibrosis was assessed using vibration-controlled transient elastography (advanced fibrosis ≥ 10 kPa). Data on chronic kidney disease, retinopathy, neuropathy, and diabetic foot ulcers were collected from medical records. Results A total of 308 participants were included. The median duration of diabetes was 7 years (IQR 3–13). MASLD was present in 181 participants (58.8%). Of these, 161 (52.3%) showed no evidence of advanced fibrosis, while 20 (6.5%) were assessed as having advanced fibrosis. Neuropathy was present in 64 participants (20.8%), retinopathy in 60 (19.5%), chronic kidney disease in 59 (19.2%), and diabetic foot ulcers in 13 (4.2%). No significant differences in these complications were observed between participants with and without MASLD. However, participants with MASLD and a higher histopathological fibrosis stage had an increased risk of microvascular complications in our study. Conclusions Participants with type 2 diabetes and concomitant MASLD recruited in primary care, did not have an increased risk of chronic kidney disease, neuropathy, or retinopathy, supporting previous findings of risk variation across different ethnicities and geographic locations. Trial registration Clinical trial number NCT03864510 (registration date 2019-02-12). Keywords MASLD, Type 2 Diabetes, Diabetes Complications, Primary Care, Magnetic resonance imaging, Vibration Controlled Transient Elastography, Liver Biopsy *Correspondence: Martin Bergram Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Bergram et al. BMC Primary Care (2025) 26:354 Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in the world today. It is estimated to affect 38% of the global adult population [1]. The disease is heterogeneous, spanning from isolated steatosis, steatohepatitis, advanced fibrosis including cirrhosis, to hepatocellular carcinoma. Given the high prevalence, MASLD is likely common among patients in primary care. However, previous studies have shown that the number of undiagnosed cases in primary care is high, and knowledge of MASLD among general practitioners is low [2–7]. In Sweden, 85–90% of all patients with type 2 diabetes (T2D) receive their diabetes care in primary care [8]. MASLD and T2D are highly connected, with shared pathophysiology [9]. Individuals with MASLD have an increased risk of developing T2D [10]. In addition, the risk of macrovascular complications of diabetes is greater among patients with concomitant MASLD [11]. MASLD is more common among patients with T2D, and their risk of progression to steatohepatitis, advanced fibrosis, and hepatocellular carcinoma is elevated compared to individuals with MASLD without T2D [7, 12]. There is conflicting evidence on associations between MASLD and diabetic retinopathy as well as neuropathy [12–14]. Studies investigating the connection between MASLD and diabetic foot ulcers are few [15–17]. The risk of retinopathy in MASLD has been reported to be either higher, lower, or unchanged [12–14]. In a meta-analysis involving 7,170 patients, no association between MASLD and diabetic retinopathy was shown. However, there were geographic risk differences [13]. There are inconsistent results for diabetic neuropathy among patients with MASLD as well. Studies have reported both higher and lower risk [12, 14]. The risk of the microvascular diabetes complication chronic kidney disease (CKD) has been shown to be greater among patients with concomitant MASLD [18, 19]. Hospitalized patients with type 1 diabetes or T2D, with advanced fibrosis, more commonly have previous diabetic foot ulcers, and prevalent MASLD is associated with diabetic foot ulcer recurrence as well [15, 16]. Magnetic resonance imaging (MRI) techniques to determine MASLD have never been used in previous studies of retinopathy, neuropathy, and diabetic foot ulcers, despite their excellent diagnostic properties for steatosis quantification in MASLD [20]. Therefore, due to conflicting evidence on associations between MASLD and microvascular diabetes complications, the aim of this study was to examine the prevalence of microvascular complications of T2D among individuals with concomitant MASLD, with or without advanced fibrosis, compared with those without MASLD in a primary care setting. Page 2 of 11 Methods The cohort study Evaluating Prevalence and Severity Of MASLD In Primary Care (EPSOMIP) was combined with a retrospective review of medical records to identify microvascular disease. EPSOMIP study participants were recruited from the Region of Southeast Sweden at seven primary care centers located in urban and rural areas. The collection of clinical data, blood sampling, and imaging was conducted by research nurses at the Department of Gastroenterology and Hepatology, Linköping University Hospital; the Department of Internal Medicine, Vrinn (...truncated)