Bone Turnover Markers in Patients with Non-Alcoholic Fatty Liver Disease and/or Type 2 Diabetes during Oral Glucose and Isoglycemic iv Glucose

Context: Non-alcoholic fatty liver disease (NAFLD) is associated with type 2 diabetes (T2D) and vice versa, and both conditions are associated with an increased risk of fractures and altered bone turnover. While NAFLD patients typically suffer from decreased bone mineral density (BMD), T2D is associated with normal to high BMD. The pathophysiology is uncertain, but may involve the gut-bone axis.

Objective: We investigated the influence of the gut on glucose-induced changes in plasma bone turnover markers in healthy controls and patients with T2D and/or biopsy-verified NAFLD.

Design: Cross-sectional cohort study.

Patients: NAFLD patients with normal glucose tolerance, NAFLD patients with T2D, T2D patients without liver disease and healthy controls.

Interventions: 4-hour 50g oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose infusion (IIGI).

Main Outcome Measures: Collagen type 1 C-telopeptide (CTX), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP) and parathyroid hormone (PTH).

Results: Plasma glucose levels achieved during OGTTs were successfully matched on corresponding IIGI days. Patients with NAFLD+T2D exhibited similar CTX suppression during the two glucose challenges (P = 0.46) and pronounced suppression of P1NP during IIGI compared with OGTT. Conversely, remaining groups showed greater (P < 0.05) CTX suppression during OGTT and similar suppression of bone formation markers during IIGI and OGTT.

Conclusions: OGTT-induced CTX suppression seems to be impaired in patients with NAFLD+T2D, but preserved in patients with either NAFLD or T2D, suggesting that coexistence of T2D and NAFLD may affect gut-bone axis.