High serum concentrations of growth differentiation factor-15 and their association with Crohn’s disease and a low skeletal muscle index

Abstract

Sarcopenia comprises a low skeletal muscle index (SMI) and low muscle strength (MS) or low physical function. Many sarcopenia biomarkers have been reported. With Crohn’s disease (CD), a low SMI is predictive of intestinal complications. Therefore, many CD studies have reported that sarcopenia is defined by SMI alone. This study investigated the sarcopenia frequency by assessing the SMI and MS of Japanese patients with CD and biomarkers predicting a low SMI. We evaluated the SMI using a bioelectrical impedance analysis, handgrip strength, and C-reactive protein, albumin, interleukin-6, tumor necrosis factor-α, growth differentiation factor (GDF)-8, and GDF-15 levels as biomarker candidates for 78 CD patients at our hospital. Sarcopenia and a low SMI were observed in 7.7% and 42.3% of the patients, respectively. There was a significant difference in the GDF-15 levels of the low SMI group and normal group according to the multivariate analysis (P = 0.028; odds ratio [OR], 1.001; 95% confidence interval [CI] 1.000–1.002). When evaluated by sex, males exhibited a negative correlation between the GDF-15 level and SMI (Pearson’s r = − 0.414; P = 0.0031), and the multivariate analysis indicated a significant difference in the GDF-15 levels (P = 0.011; OR, 1.001; 95% CI 1.000–1.002). GDF-15 levels may indicate a low SMI with CD.

Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskel

“…Target same receptors as myostatin [163] Limited number of studies [163] Unknown Muscle protein turnover GDF-15 Increased Correlate with muscle mass and performance tests [42][43][44] Limited number of studies [163] Increased with renal insufficiency [49] Muscle protein turnover Not modified by exercise in long-term interventional studies [32,35] Irisin Decreased Associated with muscle mass and strength [56,164] No interventional studies [80] Unknown…”

“…Several cohorts have shown increased GDF-15 expression in sarcopenic participants [40,41]. GDF-15 was also sometimes, but not systematically, associated with handgrip strength, skeletal muscle index (SMI) [42][43][44] and physical performance tests [45,46]. Myostatin and follistatin expression is induced upon acute physical exercise [47].…”

Accelerated ageing of skeletal muscle and the immune system in patients with chronic liver disease.

“…GDF-15 has recently gained recognition as a key age-associated cytokine, with elevated serum concentrations positively correlated with all-cause mortality (46, 47), multimorbidity (48), frailty (49,50) and sarcopenia (51)(52)(53), while recent work by Kim-Muller et al demonstrated that GDF-15 neutralisation restored both muscle mass and function in mice (54). In line with these data and consistent with other reports in CLD (55, 56), we observed signi cantly greater circulating levels of GDF-15 in CLD patients, which were positively associated with muscle epigenetic age acceleration, further supporting an aged phenotype of the skeletal muscle in CLD patients.…”

Role of growth differentiation factor 15 in cancer cachexia (Review)

“…As GDF15 is a myokine, its circulating levels are negatively correlated with muscle mass in numerous diseases, including COPD, intensive care unit-acquired weakness (ICUAW), Crohn's disease, pulmonary hypertension (PH) and CC (30,(55)(56)(57)(58). Muscle atrophy, including that of skeletal, chest, diaphragm and cardiac muscle, is a hallmark of CC and a major cause of mortality in patients with cancer (4,59).…”