Serum Levels of Osteocalcin and Insulin Resistance in Patients with Impaired Glucose Tolerance or New-Onset Diabetes Mellitus After Liver Transplantation

Abstract

Liver transplantation (LT) patients are at high risk of developing new-onset diabetes after transplantation (NODAT). Osteocalcin has been proposed as a mediator between bone tissue and glucose metabolism, but its role in the pathogenesis of diabetes is not defined yet. Our objective was to assess the relationship between serum osteocalcin and glucose metabolism parameters in liver transplantation recipients. A total of 187 liver transplantation patients were cross-sectionally studied, 54 of them developed NODAT. None had been diagnosed of diabetes mellitus prior to transplant. In 133 nondiabetic patients, a 75 g oral glucose tolerance test (OGTT) was performed to assess blood glucose, insulin, and C-peptide levels at baseline and 120 min. Serum total osteocalcin was measured at baseline in all patients.After OGTT, 10.5% of LT patients had NODAT criteria, 51.9% showed impaired glucose tolerance, and 37.6% had normal glucose tolerance. Overall, NODAT prevalence was 36.3%. HOMA-IR was significantly higher in NODAT compared with impaired glucose tolerance and normal glucose tolerance groups (p<0.001). Osteocalcin was inversely correlated to HOMA-IR (r=- 0.16, p=0.05), BMI (r=- 0.27, p=0.000) and waist circumference (r=- 0.21, p=0.005). Patients in the lowest osteocalcin tertile (< 16.5 ng/ml) had significantly higher fasting plasma glucose and HOMA-IR index (p=0.029 and 0.037, respectively) than those in medium or highest tertiles. In multiple linear regression analysis, osteocalcin was negatively associated with fasting plasma glucose (standardized β coefficient-0.16; p=0.041) and 2-h insulin (standardized β coefficient-0.21; p=0.028). Prevalence of NODAT/impaired glucose tolerance is high in liver transplantation patients and is associated with insulin resistance. In these patients total osteocalcin is inversely associated with plasma glucose level and insulin resistance indexes.

Aerobic exercise regulates blood lipid and insulin resistance via the toll‑like receptor 4‑mediated extracellular signal‑regulated kinases/AMP‑activated protein kinases signaling pathway

“…Domingueti et al (9) demonstrated that the linkages between oxidative stress, inflammation, hypercoagulability, vascular complications and diabetes mellitus have been investigated, and inflammation and oxidative stress may be regarded as predictors for evaluating the risk of cardiovascular and renal complications in patients with diabetes mellitus. In addition, previous studies have investigated the insulin resistance and sensitivity in liver, adipose tissue, skeletal muscle and placenta samples (10)(11)(12). Furthermore, studies have indicated that diabetes mellitus may be a syndrome, which includes vascular dysfunction, insulin resistance, inflammatory responses and oxidative stress (13,14).…”

Hepatic steatosis and liver fat contents in liver transplant recipients are associated with serum adipokines and insulin resistance

“…Insulin resistance is prevalent among patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis 27 and other causes of liver cirrhosis 28 . A cross-sectional study showed that insulin resistance is highly prevalent and associated with new onset diabetes after liver transplantation 29 . None of these studies reported the impact of insulin resistance on the development of hepatic steatosis after liver transplantation.…”

Islet Identity in Transplantation Procedures: The Intersection of Cellular Maturity and Function

“…Importantly, Sanchez-Enriquez et al demonstrated a link between cardiovascular risk factors for patients with T2DM, including high BMI, high fasting plasma glucose, and high HDL, and low serum levels of uOC, suggesting that osteocalcin could have more physiological roles than previously expected [152]. In a different model, patients who underwent liver transplantation and subsequently became diabetic post-surgery demonstrated that total osteocalcin was, yet again, inversely associated with plasma glucose levels and insulin resistance [153].…”