Steatosis, Glycation and Liver Fibrosis in Patients with Diabetes

Abstract

Introduction: Non Alcoholic Fatty Liver Disease (NAFLD) is frequent and progresses to fibrosis among patients with diabetes. The roles of hepatic steatosis and of the accumulation of Advanced Glycation Endproducts (AGEs) can now be analyzed by new non-invasive methods. Patients and methods:Among hospitalized patients with diabetes, we assessed liver fibrosis by liver stiffness measurement (LSM), steatosis by the attenuation coefficient of an ultrasonic wave (CAP) and AGE accumulation by skin autofluorescence (sAF). The patients with severe fibrosis were compared to the others by ANOVA and Chi-2, and the relations between fibrosis, steatosis, and skin AF were studied by regression analysis.Results: 178 patients were included: 60% male, age 59 ± 11 years, BMI 31 ± 6 kg/m 2 , 79% with Type 2 Diabetes (T2D), poorly controlled (HbA1C 9.0 ± 2.4%). sAF were available in all patients, LSM in 139 and CAP in 93 subjects. Severe fibrosis (LSM>8.7 kPa) was evidenced in 32 (23%) patients, mainly T2D (n=31/32), with higher BMI and waist circumference (p<0.0001). They had higher CAP: 319 ± 53 dB/m (No fibrosis: 268 ± 59, p<0.005), whereas their sAF did not differ. LSM was correlated to the CAP (r=0.40, p<0.0001) and the waist circumference (r=0.46, p<0.0001), but not to sAF. CAP was related to waist circumference and triglycerides level (r=0.70 in multivariate analysis). Conclusion:More steatosis and similar skin autofluorescence in patients with diabetes and severe liver fibrosis support that steatosis promotes fibrosis, and suggests that AGEs do not accelerate this progression. Steatosis, Glycation and Liver Fibrosis in Patients with Diabetes IntroductionNon Alcoholic Fatty Liver Diseases (NAFLD) causes serious hepatic damage and can lead to fibrosis, cirrhosis and liver cancer [1]. Their natural history includes two phases: first the accumulation of triglycerides due to insulin resistance makes a vulnerable steatotic liver, and then a second hit, involving oxidative stress, leads to inflammation and fibrosis [2] . These events are not clinically apparent, and diagnosis is delayed. NAFLD is a cause of "cryptogenetic" cirrhosis [3]. A direct histological follow-up is rarely performed because the liver biopsy is an invasive procedure, indicated only when advanced lesions are suspected, whereas a simple steatosis is benign [4]. Whether triglycerides by themselves are toxic for the liver is even uncertain, some reports suggest that their accumulation may be a mechanism of defense against liver injury [5,6]. Noninvasive procedures of evaluation of liver fibrosis and steatosis, by Fibroscan (Liver Stiffness Measurement LSM and Controlled Attenuation Parameter CAP) seem adapted to study early stages of NAFLD in high risk populations, like patients with diabetes [7]. Are the levels of steatosis high in patients with diabetes and hepatic fibrosis? NAFLD are especially frequent among patients with diabetes [8]; mainly Type 2, but Type 1 Diabetes is also concerned [9]. They progress more to liver fibrosis, rates of severe fibr...