IGF-I/IGFBP3/ALS Deficiency in Sarcopenia: Low GHBP Suggests GH Resistance in a Subgroup of Geriatric Patients

Abstract

Context: Definition of etiological subgroups of sarcopenia may help to develop targeted treatments. insulin like growth factor-I (IGF-I), Insulinlike growth factor binding protein 3 (IGFBP3), and acid labile subunit (ALS) build a ternary complex that mediates growth hormone (GH) effects on peripheral organs, such as muscle. Low GH binding protein (GHBP) as a marker of GH receptor number would hint toward GH resistance. Objective: We aimed to analyze the association of IGF-I, IGFBP3, and ALS with sarcopenia. Study Participants and Setting: A total of 131 consecutively recruited patients of a geriatric ward were included in a single-center cross-sectional analysis; the nonsarcopenic patients served as controls. Methods: Measures included sarcopenia status by hand-grip strength measurement and Skeletal Muscle Index (SMI); IGF-I, IGFBP3, ALS, GH, GHBP; body mass index (BMI); Activity of Daily Living (ADL); Mini-Mental State Examination (MMSE); routine laboratory parameters; and statistical regression modeling. Results: Compared with controls, sarcopenic patients did not differ regarding age, sex, ADL, MMSE, C-reactive protein, glomerular filtration rate, and albumin serum concentrations. However, sarcopenic patients had significantly lower IGF-I, IGFBP3, and ALS. IGF-I and ALS associated significantly with sarcopenia and low hand-grip strength, even after adjustment for age, sex, BMI, and albumin, but not with low SMI. GHBP serum was low in sarcopenic patients, but normal in geriatric patients without sarcopenia. Over 60% of patients with IGF-I/ALS deficiency patients showed GH resistance. Conclusions: Our data suggest that in geriatric patients, low IGF-I/IGFBP3/ALS could be evaluated for causative connection of the sarcopenia spectrum. Low GHBP points toward potential GH resistance as one possible explanation of this deficiency.