ABSTRACT
BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) plays a crucial role in breaking down various substrates. It also has effects on the insulin signaling pathway, contributing to insulin resistance, and involvement in inflammatory processes like obesity and type 2 diabetes mellitus. Emerging effects of DPP-4 on bone metabolism include an inverse relationship between DPP-4 activity levels and bone mineral density, along with an increased risk of fractures. MAIN BODY: The influence of DPP-4 on bone metabolism occurs through two axes. The entero-endocrine-osseous axis involves gastrointestinal substrates for DPP-4, including glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptides 1 (GLP-1) and 2 (GLP-2). Studies suggest that supraphysiological doses of exogenous GLP-2 has a significant inhibitory effect on bone resorption, however the specific mechanism by which GLP-2 influences bone metabolism remains unknown. Of these, GIP stands out for its role in bone formation. Other gastrointestinal DPP-4 substrates are pancreatic peptide YY and neuropeptide Y-both bind to the same receptors and appear to increase bone resorption and decrease bone formation. Adipokines (e.g., leptin and adiponectin) are regulated by DPP-4 and may influence bone remodeling and energy metabolism in a paracrine manner. The pancreatic-endocrine-osseous axis involves a potential link between DPP-4, bone, and energy metabolism through the receptor activator of nuclear factor kappa B ligand (RANKL), which induces DPP-4 expression in osteoclasts, leading to decreased GLP-1 levels and increased blood glucose levels. Inhibitors of DPP-4 participate in the pancreatic-endocrine-osseous axis by increasing endogenous GLP-1. In addition to their glycemic effects, DPP-4 inhibitors have the potential to decrease bone resorption, increase bone formation, and reduce the incidence of osteoporosis and fractures. Still, many questions on the interactions between DPP-4 and bone remain unanswered, particularly regarding the effects of DPP-4 inhibition on the skeleton of older individuals. CONCLUSION: The elucidation of the intricate interactions and impact of DPP-4 on bone is paramount for a proper understanding of the body's mechanisms in regulating bone homeostasis and responses to internal stimuli. This understanding bears significant implications in the investigation of conditions like osteoporosis, in which disruptions to these signaling pathways occur. Further research is essential to uncover the full extent of DPP-4's effects on bone metabolism and energy regulation, paving the way for novel therapeutic interventions targeting these pathways, particularly in older individuals.
ABSTRACT
BACKGROUND: The aim of this study was to compare the prevalence of low muscle mass and sarcopenia in patients with type 2 diabetes mellitus (T2DM) versus paired controls (control group, CG) and the association between sarcopenia and chronic diabetes complications. METHODS: Men and women ≥50 years with T2DM (T2DM group, T2DMG) were recruited during routine outpatient visits. Total body densitometry and handgrip strength (HGS) were evaluated in the T2DMG and CG, while the T2DMG was also evaluated for the physical performance using the gait speed (GS) test. Sarcopenia was diagnosed according to the criteria of the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). RESULTS: The study included 177 individuals in the T2DMG and 146 in the CG. The mean HGS value was lower in the T2DMG (24.4 ± 10.3 kg) compared with the CG (30.9 ± 9.15 kg), p < 0.001, with low HGS in 46 (25.9%) and 10 (9%) in the T2DMG and CG, respectively (p < 0.001). The prevalence of sarcopenia defined according to the FNIH criteria was higher in the T2DMG 23 (12.9%) compared with the CG 8 (5.4%), p < 0.03. The presence of albuminuria increased the odds of sarcopenia (odds ratio (OR) 2.84, 95% confidence interval (CI) 1.07-7.68, p=0.04) and osteoporosis (OR 3.38, 95% CI 1.12-9.89, p=0.03), even in patients with mild to moderate nephropathy. The body composition analysis showed increased odds of sarcopenia with increased percentage of total fat (%TF) in women (OR 1.18, 95% CI, 1.03-1.43, p=0.03) and men (OR 1.31, 95% CI, 1.10-1.75, p=0.01). CONCLUSION: Patients with T2DM presenting with albuminuria, osteoporosis, and increased %TF were more likely to have sarcopenia. This finding emphasizes the need for patients with T2DM to be evaluated for sarcopenia to allow for early implementation of measures to prevent or treat this disorder.