ObjectiveNon-alcoholic fatty liver disease (NAFLD) is prevalent in patients with type 2 diabetes. Here, we estimate the proportion of patients with type 2 diabetes that should be referred to hepatologists according to the 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) Guidelines and evaluate the association between non-invasive biomarkers of steatosis and fibrosis and diabetic complications.Research design and methodsThis is a retrospective analysis of type 2 diabetes patients who attended on a regular basis our diabetes clinic between 2013 and 2018 (n=2770). Steatosis was assessed using Fatty Liver Index (FLI), Hepatic Steatosis Index and NAFLD Ridge Score and fibrosis using NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) ratio. Outcome measures were altered albumin excretion rate (AER), chronic kidney disease (CKD) and cardiovascular disease (CVD).ResultsThe prevalence of advanced fibrosis varied from 1% (APRI) to 33% (NFS). The application of the guidelines using a sequential combination of FLI and FIB-4 would lead to referral of 28.3% of patients when using standard FIB-4 cut-offs, while this number dropped to 13.4% when age-adjusted FIB-4 thresholds were applied. A higher prevalence of altered AER was associated with liver steatosis (FLI: OR: 3.49; 95% CI 2.05 to 5.94, p<0.01), whereas liver fibrosis was associated with CKD (FIB-4: OR: 6.39; 95% CI 4.05 to 10.08, p<0.01) and CVD (FIB-4: OR: 2.62; 95% CI 1.69 to 4.04, p<0.01).ConclusionsWhile specific fibrosis scores identify different proportion of patients with advanced fibrosis, the use of age-adjusted FIB-4 cut-offs leads to a drop in gray-zone results, making referrals to hepatologists more sustainable. Interestingly non-invasive biomarkers were consistently associated with a different pattern of diabetic complications.

Background Few population-based studies investigated the association between body fat distribution and the risk of nonalcoholic fatty liver disease (NAFLD) and significant liver fibrosis. Objective To evaluate the relationship between total body fat and body fat distribution and NAFLD in the general US population. Methods This is a cross-sectional, population-based study based on the 2017-2018 cycle of the National Health and Nutrition Examination Survey. Participants aged 18-59 without known liver conditions or significant alcohol consumption were studied by dual energy x-ray absorptiometry (DXA) and vibration controlled transient elastography (VCTE) to assess body composition and liver steatosis and fibrosis, respectively. Multivariable logistic regression analysis was performed to evaluate the contribution of body mass index (BMI) and android/gynoid ratio (A/G ratio) on the prevalence of liver steatosis and fibrosis in males and females. Results Weighted prevalence of steatosis were 41.5% and 29.9% among the 1115 and 1113 males and females included in the study, whereas 7.0% of males and 4.0% of females had elastographic evidence of significant liver fibrosis. After adjustment for age, race-Hispanic origin, diabetes, cigarette smoke and BMI, a higher A/G ratio was associated with increased odds of steatosis in both males (odds ratio (OR) 1.79, 95% CI 1.07,2.99, p=0.029) and females (OR 1.95, 95% CI 1.11,3.41, p=0.023). Conversely, a significant association between A/G ratio and liver fibrosis was identified in females (OR 2.09, 95% CI 1.11,3.97, p=0.026), but not in males (OR 0.56, 95% CI 0.29,1.08, p=0.078). Conclusion Independently from BMI, an android fat deposition pattern is associated with increased prevalence of NAFLD in both sexes, while the effect on fibrosis was only evident in females.

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Context: Insulin resistance and diabetes may influence separately or in combination whole body energy metabolism. Objective: To assess the impact of insulin resistance and/or overt type 2 diabetes on resting energy expenditure (REE) in class 3 obese individuals. Design and Setting: Retrospective, cross-sectional analysis of a set of data about individuals attending the outpatients service of a single center of bariatric surgery between January 2015 and December 2017. Patients: We screened 382 patients in which abnormal thyroid function was excluded, and segregated them in three groups of subjects: patients with type 2 diabetes (T2DM; n=70), nondiabetic insulin-resistant patients with HOMA-IR ≥ 3 (n=236), non-diabetic insulin-sensitive patients with HOMA-IR < 3 (n=75). Main Outcome Measure: Resting energy expenditure (REE), body composition and insulin resistance assessed using indirect calorimetry, bioimpedance and HOMA-IR. Results: Non-diabetic insulin-sensitive patients resulted to be younger, with lower BMI and higher prevalence of female subjects; meanwhile, non-diabetic but insulin-resistant patients and T2DM patients were not different in terms of anthropometric parameters. REE was higher in T2DM than in non-diabetic insulin-resistant and insulin-sensitive individuals when expressed as percent of the predicted REE (based on Harris Benedict equation) (p<0.0001) or when adjusted for kg of free fat mass (p<0.0001) and was found to be higher also in insulinresistant vs insulin-sensitive patients (p<0.001). The respiratory quotient was different between groups (0.87±0.11, 0.86±0.12 and 0.91±0.14 in T2DM, insulin-resistant and insulinsensitive patients, respectively; p<0.03). Regression analysis confirmed that HOMA-IR was independently associated with the REE (R 2 =0.110, p<0.001). Conclusion: Class 3 obese patients with normal insulin sensitivity are characterized by reduced fasting REE in comparison to insulin-resistant obese patients and obese patients with short duration of diabetes supporting the hypothesis that down-regulation of nutrients' oxidative disposal may represent an adaptation of energy metabolism in obese individuals with preserved insulin sensitivity.

Context Growing evidence suggests that appropriate levothyroxine (LT4) replacement therapy may not correct the full set of metabolic defects afflicting individuals with hypothyroidism. Objective To assess whether obese subjects with primary hypothyroidism are characterized by alterations of the resting energy expenditure (REE). Design Retrospective analysis of a set of data about obese women attending the outpatients service of a single obesity center from January 2013 to July 2019. Patients A total of 649 nondiabetic women with body mass index (BMI) &gt; 30 kg/m2 and thyrotropin (TSH) level 0.4–4.0 mU/L were segregated into 2 groups: patients with primary hypothyroidism taking LT4 therapy (n = 85) and patients with normal thyroid function (n = 564). Main outcomes REE and body composition assessed using indirect calorimetry and bioimpedance. Results REE was reduced in women with hypothyroidism in LT4 therapy when compared with controls (28.59 ± 3.26 vs 29.91 ± 3.59 kcal/kg fat-free mass (FFM)/day), including when adjusted for age, BMI, body composition, and level of physical activity (P = 0.008). This metabolic difference was attenuated only when adjustment for homeostatic model assessment of insulin resistance (HOMA-IR) was performed. Conclusions This study demonstrated that obese hypothyroid women in LT4 therapy, with normal serum TSH level compared with euthyroid controls, are characterized by reduced REE, in line with the hypothesis that standard LT4 replacement therapy may not fully correct metabolic alterations related to hypothyroidism. We are not able to exclude that this feature may be influenced by the modulation of insulin sensitivity at the liver site, induced by LT4 oral administration.