Elastographic parameters of liver steatosis and fibrosis predict independently the risk of incident chronic kidney disease and acute myocardial infarction in patients with type 2 diabetes mellitus.

AIMS: The aim of this prospective study was to examine the relationship between controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) with the risk of developing a composite endpoint inclusive of incident acute myocardial infarction (AMI), cerebrovascular insult (CVI) or chronic kidney disease (CKD) in people with type 2 diabetes mellitus (T2DM). METHODS: This study included 238 T2DM outpatients without chronic liver diseases. RESULTS: The patient population was followed for a median period of 7.6 years. Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the aforementioned composite outcome (P < 0.001 by the log-rank test), as well as CKD (P < 0.001) or AMI alone (P = 0.014) among those with elevated CAP values (≥238 dB/m) at baseline. Similarly, Kaplan-Meier survival analyses showed that there was a higher proportion of patients who developed the composite outcome (P < 0.001), as well as CKD (P < 0.001), or AMI alone (P < 0.001) among those with elevated LSM values (≥7.0/6.2 kPa). In multivariable regression analyses, the presence of elevated CAP (adjusted-hazard ratio 2.34, 95% CI 1.32-4.15) and elevated LSM (adjusted-hazard ratio 2.84, 95% CI 1.92-4.21), independently of each other, were associated with a higher risk of developing the composite outcome, as well as incident AMI or CKD alone after adjusting for traditional cardiovascular risk factors and diabetes-related variables. CONCLUSIONS: Our study shows that the elastographic parameters of liver steatosis and fibrosis independently predict the long-term risk of developing chronic vascular complications in T2DM patients.

Significant liver fibrosis, as assessed by fibroscan, is independently associated with chronic vascular complications of type 2 diabetes: A multicenter study.

AIMS: The aim of this study was to investigate whether controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), as assessed by vibration-controlled transient elastography (VCTE), are associated with chronic vascular complications of diabetes mellitus type 2 (T2DM). METHODS: We studied 442 outpatients with established T2DM, and who underwent VCTE and extensive assessment of chronic vascular complications of diabetes. RESULTS: A quarter of analyzed patients had a previous history of myocardial infarction and/or ischemic stroke, and about half of them had at least one microvascular complication (chronic kidney disease (CKD), retinopathy or polyneuropathy). The prevalence of liver steatosis (i.e., CAP ≥ 238 dB/m) and significant liver fibrosis (i.e., LSM ≥ 7.0/6.2 kPa) was 84.2% and 46.6%, respectively. Significant liver fibrosis was associated with an increased likelihood of having myocardial infarction (adjusted-odds ratio 6.61, 95%CI 1.66-37.4), peripheral polyneuropathy (adjusted-OR 4.55, 95%CI 1.25-16.6), CKD (adjusted-OR 4.54, 95%CI 1.24-16.6) or retinopathy (adjusted-OR 1.81, 95%CI 1.62-1.97), independently of cardiometabolic risk factors, diabetes-related variables, and other potential confounders. Liver steatosis was not independently associated with any macro-/microvascular diabetic complications. CONCLUSIONS: Significant liver fibrosis is strongly associated with the presence of macro-/microvascular complications in patients with T2DM. These results offer a new perspective on the follow-up of people with T2DM.

Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease.

BACKGROUND: Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis. METHODS: We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included. RESULTS: In the acute and chronic dextran sulphate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05). CONCLUSION: PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.

Screening for nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus using transient elastography - a prospective, cross sectional study.

AIM: To investigate the prevalence and severity of nonalcoholic fatty liver disease (NAFLD) in patients with diabetes mellitus type 2 (T2DM), based on increased controlled attenuation parameter (CAP) and liver stiffness measurements obtained by transient elastography. In addition, we aimed to identify parameters that correlate with increased elastographic parameters of steatosis and fibrosis to provide a better indication when a patient with T2DM should be screened for NAFLD. METHODS: We conducted prospective, cross-sectional study of 679 consecutive adult patients with diagnosed T2DM mean age 65.2±11.6. NAFLD was defined by transient elastography. In 105 patients a percutaneous liver biopsy (LB) was done. RESULTS: The prevalence of NAFLD based on transient elastography was 83.6%. Independent factors associated with increased CAP were higher body mass index, longer T2DM duration, higher serum triglyceride, lower levels of vitamin D, higher C-reactive protein, and higher HOMA-IR. The prevalence of moderate liver fibrosis was 26.9% and advanced liver fibrosis 12.6%. Independent factors associated with moderated fibrosis based on elastography were higher body mass index and higher levels of alanine aminotransferase (ALT), while independent factors associated with advanced fibrosis were female gender, higher body mass index, higher levels of ALT, gama-glutamil transferase and C-reactive protein. Sixty-four (60.9%) of 105 patients with LB had NAFLD activity score ≥5. Regarding the presence and stages of fibrosis based on LB, moderate fibrosis was found in 29.5% of patients, while 29.5% had advanced fibrosis and 6.7% cirrhosis. CONCLUSION: This study supports more aggressive screening for NAFLD and fibrosis in patients with T2DM.

Prospective evaluation of non-alcoholic fatty liver disease by elastographic methods of liver steatosis and fibrosis; controlled attenuation parameter and liver stiffness measurements.

AIMS: To examine the temporal changes of both controlled attenuation parameter (CAP) and liver stiffness measurements (LSM), assessed by Fibroscan, in a large sample of patients with non-alcoholic fatty liver disease (NAFLD). METHODS: In this prospective, observational study, we consecutively enrolled 507 adult individuals with Fibroscan-defined NAFLD who were followed for a mean period of 21.2 ±â€¯11.7 months. RESULTS: During the follow-up period, 84 patients (16.5%) had a progression of CAP of at least 20% with a median time of 39.93 months, while 201 (39.6%) patients had a progression of LSM of at least 20% with median time of 30.46 months. There were significant differences in the proportion of LSM progression across body mass index (BMI) categories, with obese patients having the highest risk of progression over the follow-up (hazard ratio 1.66; 95%CI 1.23-2.25). Multivariable regression analysis showed that BMI and serum creatinine levels were the strongest predictors for CAP progression in the whole population, while HOMA-estimated insulin resistance was an independent predictor of LSM progression over time in the subgroup of obese patients. CONCLUSION: This prospective study shows for the first time that the progression risk of both liver steatosis and fibrosis, detected non-invasively by Fibroscan, is relevant and shares essentially the same metabolic risk factors that are associated with NAFLD progression detected by other invasive methods.