MO446: The Prevalence of Mafld in Subjects With Normoglycaemia, Prediabetes and Type 2 Diabetes Without Evidence of Chronic Kidney Disease and its Association With Glomerular Hyperfiltration

Abstract BACKGROUND AND AIMS Whereas metabolic dysfunction-associated fatty liver disease (MAFLD) reflects multisystem disorders [1], many aspects of the association between MAFLD and extra-hepatic diseases are the issues to study. Glomerular hyperfiltration (GHF) is an early manifestation of kidney damage in diabetic patients and predicts its further progression. Recently it was reported that an initial increase of plasma glucose in subjects with prediabetes is an independent risk for incident GHF [2]. However, it remains unknown whether GHF could also occur in subjects with normoglycaemia and whether it is associated with MAFLD. The study aimed to compare the prevalence of MAFLD in subjects with normoglycaemia, prediabetes and type 2 diabetes mellitus without evidence of chronic kidney disease (CKD) and then explore its association with GHF in the study groups. METHOD A cohort of 125 070 people aged 18–65 years, without CKD [(estimated glomerular filtration rate (eGFR) ≥60 mL/min], belonging to a large Spanish database of routine occupational health visits (January 2008–December 2010), has been explored. Subjects were divided into three groups according to their fasting plasma glucose (FPG) levels—subjects with normoglycaemia (FPG < 100 mg/dL), prediabetes (FPG ≥ 100–≤125 mg/dL) and type 2 diabetes mellitus (FPG ≥ 126 mg/d or use of antidiabetic drugs), according to the American Diabetes Association criteria. The presence of MAFLD was defined according to the new criteria of an international expert consensus statement [1]. Liver steatosis was determined by the validated Fatty liver index (FLI) with a cut-off value of ≥ 60 [3]. eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [4], deindexed for body surface area (BSA) to avoid underestimation in patients with obesity [5]. Hyperfiltration was defined as an eGFR above the age- and gender-specific 95th percentile. The association between MAFLD and GHF was evaluated by multivariable logistic regression. RESULTS The overall prevalence of subjects with MAFLD was 19.3% (n = 24 112) and it significantly increased from 14.7% (n = 14 809) to 33.2% (n = 5697) and 48,9% (n = 3606), in subjects with normoglycaemia, prediabetes and diabetes, respectively (Table 1), (P < 0.001 between all paired groups). By definition, the overall presence of hyperfiltration was 5% (n = 6249) and it significantly increased from 4.5% (n = 4553) to 5.7% (n = 978) and 9.7% (n = 718) in subjects with normoglycaemia, prediabetes and diabetes, respectively (P < 0.001 between all paired groups). In multivariable logistic regressions, along with age, gender, overweight, obesity (common risk factors in the three groups), the presence of MAFLD was independently associated with GHF, ​after adjusting for the following confounding variables—age, gender, overweight, obesity, FPG, mean arterial pressure, triglycerides, gamma-glutamyl transferase, presence of arterial hypertension, drug therapy and smoking status: adjusted odds ratio (OR), 1.96; 95% confidence interval (CI), 1.78–2.15, P < 0.001; adjusted OR, 2.83; 95% CI, 2.31–3.47, P < 0.001 and adjusted OR, 2.05; 95% CI, 1.58–2.66, P < 0.001 for the subjects with normoglycaemia, prediabetes and diabetes, respectively (Table 2). CONCLUSION The increase of FPG levels in subjects with normoglycaemia, prediabetes and diabetes is accompanied by an increase of the prevalence of MAFLD, which in turn, raises a possible independent early risk marker of GHF in the three study groups, together with other metabolic risk factors. Timely identifying subjects with MAFLD might be helpful to early setup calorie restriction and lifestyle modification strategies. Longitudinal studies are needed to investigate whether and to which extent MAFLD is associated with an increased risk of a future kidney function decline among subjects with normoglycaemia and prediabetes.