Adiponectin and Leptin—Considerations in Adult Patients with Spinal Muscular Atrophy Type 3

Background: Spinal muscular atrophy (SMA) is a severe neuromuscular disorder characterized by the degeneration of alpha motor neurons in the spinal cord, leading to progressive proximal muscle weakness and paralysis. SMA is clinically categorized into four phenotypes based on age of onset and motor function achieved. Patients with SMA type 3 (juvenile, Kugelberg-Welander disease) initially have the ability to walk unaided, but experience a gradual decline in motor abilities over time. However, their lifespan is not affected by the presence of the disease. Leptin, a cytokine-like hormone secreted by adipocytes, has receptors widely distributed in musculoskeletal tissues. Several studies suggest that adiponectin deficiency contributes to the development of insulin resistance, with lower adiponectin levels closely associated with greater insulin resistance and hyperinsulinemia. However, the role of adiponectin in different types of sarcopenia and its connection to insulin sensitivity remains controversial. The purpose of this study was to measure leptin and adiponectin levels in patients with SMA type 3 and explore their association with markers of insulin sensitivity. Methods: This cross-sectional study included 23 adult patients with SMA type 3 (SMA group) and 18 community-based healthy volunteers (control group), conducted from July 2020 to September 2024. Anthropometric parameters, body composition, body fat percentage, surrogate markers of insulin sensitivity (Homeostasis model assessment of insulin resistance index-HOMA-IR and ISI Matsuda), and circulating levels of leptin and adiponectin were measured in all participants. Results: Insulin resistance was present in 91.3% of patients with SMA type 3, as determined by HOMA-IR and ISI Matsuda insulin sensitivity markers. In the control group, 64.7% had insulin resistance (IR) according to HOMA-IR, while 44.4% met the ISI Matsuda criterion for IR, showing a significant difference in peripheral insulin sensitivity between groups. A significant difference in serum adiponectin levels was observed between patients with SMA type 3 and the control group, whereas there was no significant difference in serum leptin concentrations. High adiponectin levels were observed in 50% of patients with SMA type 3. In the healthy control group, adiponectin levels positively correlated with ISI Matsuda and negatively correlated with HOMA-IR, confirming the insulin-sensitizing role of adiponectin. However, this correlation was not observed in patients with SMA type 3. Conclusions: Our results suggest that in this specific type of hereditary neuromuscular disease, the interplay between sarcopenia and insulin leads to adiponectin resistance, challenging the canonical narrative between insulin sensitivity and adiponectin, and indicating a need for further research.