Bone Turnover Markers and Probable Advanced Nonalcoholic Fatty Liver Disease in Middle-Aged and Elderly Men and Postmenopausal Women With Type 2 Diabetes

Abstract

Objective: Type 2 diabetic patients have a higher incidence of nonalcoholic steatohepatitis (NASH) and advanced stages of fibrosis, and nonalcoholic fatty liver disease (NAFLD) is associated with impaired bone health. We aimed to investigate whether bone turnover is associated with the probable presence of NASH and fibrosis.Methods: In total, 4,937 diabetic participants from Shanghai, China were enrolled in 2018. Subjects with NAFLD were categorized into simple NAFLD and probable NASH groups based on the presence of a metabolic syndrome. The NAFLD fibrosis score was used to identify patients with a higher likelihood of advanced fibrosis.Results: In postmenopausal women, large N-mid fragment of osteocalcin (N-MID osteocalcin) was negatively associated with probable NASH (P for trend < 0.001). β-C-terminal cross-linked telopeptides of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP) were positively associated with the probable presence of significant fibrosis in postmenopausal women (P for trend 0.015 and <0.001). However, in men, N-MID osteocalcin and β-CTX were negatively associated with the probable presence of significant fibrosis (P for trend 0.029 and 0.027).Conclusions: Significant associations among N-MID osteocalcin, β-CTX and P1NP, and probable advanced NAFLD were observed. Further prospective and animal studies are warranted to understand the causal relationship and underlying mechanism.

Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes

“…However, similar studies focusing on T2DM population have been scarce and controversial so far. A study in a cohort of 4937 subjects by Wang et al 22 reported that N-mid fragment of OCN was negatively associated with advanced NAFLD status including nonalcoholic steatohepatitis and significant fibrosis in middle-aged and elderly men and postmenopausal women with T2DM. Nonetheless, another study in postmenopausal women with T2DM and impaired glucose regulation presented a positive correlation of serum OCN levels and NAFLD fibrosis score, a non-invasive test evaluating the severity of hepatic fibrosis caused by NAFLD.…”

“… 21 Additionally, few studies have investigated the correlation between serum OCN levels and MAFLD in T2DM patients, and the findings from different studies are inconsistent. For example, Wang et al 22 reported that serum OCN levels were negatively associated with advanced NAFLD status in middle-aged and elderly men and postmenopausal women with T2DM. However, another study in postmenopausal women with either T2DM or impaired glucose regulation presented a contrary result, in which a positive correlation between OCN levels and NAFLD fibrosis score was observed.…”

Metformin and Bone Metabolism in Endogenous Glucocorticoid Excess: An Exploratory Study

“…Whether metformin treatment is associated with a reduced risk of fractures remains controversial ( 26 ). Furthermore, metformin was shown to improve liver metabolism during GC excess ( 5 ), which in turn could have positive effects on bone health ( 27 , 28 ).…”

Biologic Treatment in Combination with Lifestyle Intervention in Moderate to Severe Plaque Psoriasis and Concomitant Metabolic Syndrome: Rationale and Methodology of the METABOLyx Randomized Controlled Clinical Trial

“…Low-grade inflammation mediated by these factors may also influence bone metabolism in obese patients [ 24 ]. Procollagen-1 N-terminal peptide (P1NP), a marker of bone and osteoporosis risk, may also be altered in patients with metabolic syndrome, and also in the inflammatory context of non-alcoholic fatty liver disease (NAFLD) [ 26 , 27 ]. However, little is known of the pathophysiological mechanisms and consequences of P1NP dysregulation in psoriasis.…”