Serum growth differentiation factor 15 level is associated with muscle strength and lower extremity function in older patients with cardiometabolic disease

Abstract

Aims: Sarcopenia is a serious problem because of its poor prognosis. Growth differentiation factor 15 (GDF15) is associated with mitochondrial dysfunction, inflammation, insulin resistance and oxidative stress, which may play crucial roles for the development of sarcopenia. We aimed to examine whether serum GDF15 level is associated with muscle mass, strength and lower extremity function in older patients with cardiometabolic disease. Methods: Serum GDF15 levels were measured in 257 patients with cardiometabolic diseases (including 133 patients with diabetes) who had visited the frailty clinic, using a latex turbidimetric immunoassay. Appendicular skeletal muscle index, handgrip strength, timed-upand-go test and gait speed were evaluated. Power, speed, balance and total scores based on the sit-to-stand test were calculated to assess lower extremity function. Results: The highest tertile of serum GDF15 was independently associated with low handgrip strength, low gait speed, long timed-up-and-go time and scores of lower extremity function but not an appendicular skeletal muscle index in multiple logistic regression analyses after adjustment for covariates. Patients in the highest tertile of GDF15 were at the risk of having three to nine times lower grip strength, three times lower gait speed, five to six times lower mobility and five to 11 times reduction in lower extremity function as compared with those in the lowest GDF15 tertile dependent on the models. Conclusions: Elevated serum GDF15 level was independently associated with low muscle strength and lower extremity function in older patients with cardiometabolic disease. Serum GDF15 could be one of the biomarkers for muscle weakness and low physical performance.

Associations Between Plasma Growth and Differentiation Factor-15 with Aging Phenotypes in Muscle, Adipose Tissue, and Bone

“…Our results are consistent with several studies that have found associations between elevated serum GDF-15 levels and a sarcopenic phenotype [7][8][9][10][11][12][13]. However, there are some notable inconsistencies in the associations between serum GDF-15 levels and ASM in human studies: there are reports of a significant association between GDF-15 levels with ASM before and after adjustment for confounders [8,11], no association, [12], and non-significant associations after adjustment for confounders [9,10,12,13]. Although we could not explain inconsistencies in the associations reported in previous studies [8][9][10][11][12][13], age-related increases in plasma GDF-15 (γ = 0.556) might be responsible for the inconsistencies.…”

“…However, there are some notable inconsistencies in the associations between serum GDF-15 levels and ASM in human studies: there are reports of a significant association between GDF-15 levels with ASM before and after adjustment for confounders [8,11], no association, [12], and non-significant associations after adjustment for confounders [9,10,12,13]. Although we could not explain inconsistencies in the associations reported in previous studies [8][9][10][11][12][13], age-related increases in plasma GDF-15 (γ = 0.556) might be responsible for the inconsistencies. The present study shows significant associations between GDF-15 levels and BMI-adjusted ASM and sarcopenia, not only in the unadjusted model, but also in the adjusted model.…”

“…Growth and differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β cytokine superfamily. Several studies have shown that higher serum GDF-15 levels are associated with a sarcopenic phenotype [7][8][9][10][11][12][13], obesity [14][15][16], and advanced osteolytic bone disease resulting from increased osteoclast activity in multiple myeloma patients [17]. GDF-15 is one of the circulating proteins most strongly correlated with chronological age [18,19].…”

High serum concentrations of growth differentiation factor-15 in male Crohn’s disease patients with low skeletal muscle index

“…The inverse correlation between muscle mass and circulating GDF-15 levels is not speci c to CD and has been reported in patients with chronic obstructive pulmonary disease [22], pulmonary arterial hypertension [23], and preoperative cardiovascular disease [24]. Moreover, an inverse association between GDF-15 and MS or function has also been reported in patients with cardiometabolic disease [25] and cancer [26], and in healthy community-dwelling adults [27]. Although the exact mechanisms of serum GDF-15 elevation in CD patients with low SMI remain unknown, some evidence suggests that GDF-15 may promote muscle wasting.…”

Role of Growth Differentiation Factor 15 in Lung Disease and Senescence: Potential Role Across the Lifespan

“…Low body mass index (BMI) is a risk factor for exaggerated decline in the lung function, and is an independent predictor of the overall mortality in COPD (64), and is a bad prognostic indicator in the BODE index; which is used to predict the mortality risk among COPD patients (65). Elevated levels of GDF15 are associated with low muscle mass and strength, in aging patients (66,67). In COPD patients, it was associated with a sedentary lifestyle and cognitive risk (68).…”