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.

Purpose The purpose of this study was to evaluate the impact of pre-existing diabetes on in-hospital mortality in patients admitted for Coronavirus Disease 2019 (COVID-19). Methods This is a single center, retrospective study conducted at Policlinico di Monza hospital, located in the Lombardy region, Northern Italy. We reviewed medical records of 373 consecutive adult patients who were hospitalized with COVID-19 between February 22 and May 15, 2020. Data were collected on diabetes status, comorbid conditions and laboratory findings. Multivariable logistic regression was performed to evaluate the effect of diabetes on in-hospital mortality after adjustment for potential confounding variables. Results Mean age of the patients was 72 ± 14 years (range 17-98), 244 (65.4%) were male and 69 (18.5%) had diabetes. The most common comorbid conditions were hypertension (237 [64.8%]), cardiovascular disease (140 [37.7%]) and malignant neoplasms (50 [13.6%]). In-hospital death occurred in 142 (38.0%) patients. In the multivariable model older age (Relative Risk [RR] 1.06 [1.04-1. 09] per year), diabetes (RR 1.56 [1.05-2.02]), chronic obstructive pulmonary disease (RR 1.82 [1.13-2.35]), higher values of lactic dehydrogenase and C-reactive protein were independently associated with in-hospital mortality. Conclusion In this retrospective single-center study, diabetes was independently associated with a higher in-hospital mortality. More intensive surveillance of patients with this condition is to be warranted.

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.

Context It is still debated whether nonalcoholic fatty liver disease (NAFLD) may be a risk factor for reduced bone mineral density (BMD), and it is not known whether liver fibrosis, which is the major predictor of future development of liver-related events in patients with NAFLD, has an influence on BMD. Objective To assess whether liver steatosis and fibrosis are associated with reduced BMD in the general US population. Design Cross-sectional analysis of the population-based 2017-2018 cycle of the National Health and Nutrition Examination Survey (NHANES), in which vibration controlled transient elastography (VCTE) and dual-energy x-ray absorptiometry (DXA) of the femoral neck were simultaneously available. Controlled attenuation parameter (CAP) ≥ 274 dB/m was considered indicative of liver steatosis, while a median liver stiffness measurement (LSM) ≥ 8 kPa indicated the presence of significant liver fibrosis. Patients We included all participants older than 50 with reliable VCTE and femoral neck DXA results (925 men and 859 women). Main Outcomes Femoral neck BMD values indicative of osteopenia or osteoporosis. Results Steatosis and significant fibrosis were highly prevalent in the studied population, being present in 53.1% and 9.6%of men and 44.2% and 8.0% of women, respectively. In univariate analysis, liver steatosis was associated with a lower prevalence of osteoporosis in both men and women, while no difference was noted according to the degree of liver fibrosis. After adjustment for potential confounders including age, BMI, race-ethnicity, cigarette smoke and diabetes, neither CAP, nor LSM were significantly associated with reduced BMD in both sexes. Conclusions Liver steatosis and fibrosis are not associated with femoral DXA-based diagnosis of osteopenia or osteoporosis in the US population older than 50 years.

Context Serum neurofilament light chain (sNfL) levels are biomarkers of neuro-axonal injury in multiple neurological diseases. Objective Given the paucity of data on the distribution of sNfL levels in the general population, in the present study we identified predictors of sNfL levels in a community setting and investigated the association between diabetes and sNfL. Methods sNfL levels were measured in 2070 people aged 20-75 years from the general U.S. population (275 with and 1795 without diabetes) that participated in the 2013-2014 cycles of the National Health and Nutrition Examination Survey. We evaluated the association between diabetes and sNfL levels after adjustment for age, sex, race-ethnicity, alcohol use and kidney function using a multivariable linear regression model. Cognitive function was evaluated in a subset of participants aged 60-75 years using the Consortium to Establish a Registry for Alzheimer’s Disease-Word Learning test, the Animal Fluency test and the Digit Symbol Substitution test. Results The weighted prevalence of diabetes was 10.4% (95% CI 9.0-11.9). In each age stratum, patients with diabetes exhibited higher sNfL levels compared with non-diabetic participants. Age, proportion of males, prevalence of diabetes and homeostatic model of insulin resistance (HOMA-IR) increased progressively across quartiles of sNfL levels in the overall population, while estimated glomerular filtration rate (eGFR) showed an opposite trend. In the multivariable model, age, sex, eGFR, alcohol use and diabetes were significantly associated with sNfL levels. Moreover, higher sNfL levels were associated with worse performance in all three cognitive function tests. Conclusion Diabetes is associated with higher sNfL. Further large-scale and prospective studies are needed to replicate our results and evaluate the ability of sNfL to predict the incidence of neuropathy and dementia in this patient population.