Serum IGF-1 and IGF-2 levels in idiopathic parkinson's disease and their comparison with disease stages

Introduction: Idiopathic Parkinson's disease is a chronic, progressive, neurodegenerative disease diagnosed typically based on clinical examination. It arises due to diseases of the basal ganglia and is characterized by four main features: tremor, rigidity, akinesia, and postural instability, appearing in various combinations. The pathogenesis of Parkinson's disease is not yet fully understood, but the fundamental mechanisms causing nigral dopaminergic cell death have been identified. Among these mechanisms, many proteins affecting the lysosomal autophagy system, responsible for the degradation of intracellular proteins, have been shown to influence neuroinflammation. Previous limited studies have suggested that IGF-1 (insulin-like growth factor-1) and IGF-2 (insulin-like growth factor-2) might be among these proteins. There is currently no biomarker to assist clinicians in diagnosing Parkinson's disease or supporting the preliminary diagnosis. With this study, we aimed to identify the levels of IGF-1 and IGF-2 in the blood of patients with idiopathic Parkinson's disease and their relationship with disease stages, if any, to determine their potential as biomarkers and enhance methods for clinical monitoring and diagnosis. Materials and Methods: The study included 84 individuals (43 patients and 41 controls) followed and treated at the Duzce University Research Hospital Neurology Department Parkinson and Movement Disorders clinic, who were diagnosed with Idiopathic Parkinson's Disease according to the United Kingdom Brain Bank Criteria, gave written consent for participation, were aged 18-79, had a Hoehn & Yahr scale between 1-3, and did not have a diagnosis of dementia. Disease stages were recorded using the Hoehn & Yahr score and the motor and non-motor sections of the Unified Parkinson's Disease Rating Scale . Fasting serum IGF-1 and IGF-2 levels of patients and controls were measured using commercial IGF-1 and IGF-2 kits with the ELISA method. Results: The study included 43 Parkinson's patients under follow-up in our Parkinson and Movement Disorders clinic and 41 healthy individuals with similar sociodemographic distribution. Of our patients, 62.8% were male, and 37.2% were female, with an average age of 65.14 years. Patients were grouped according to their stages and scores using the Hoehn and Yahr Scale and the motor and non-motor parts of the Unified Parkinson's Disease Rating Scale . The average disease duration for Idiopathic Parkinson's disease patients was 6 years, with 39.5% at stage 1, 37.2% at stage 2, and 23.3% at stage 3 according to the Hoehn and Yahr Scale system. Fasting serum IGF-1 and IGF-2 levels were measured using the ELISA method in patients and healthy volunteers. A significant difference was observed between the serum IGF-2 values of the patient and control groups (p = 0.006). When comparing serum IGF-1 and serum IGF-2 ratios according to Hoehn & Yahr scale stages in the patient group, no significant difference was observed between the stages (p = 0.140 and p = 0.089). When compared according to initial symptoms, no significant difference was found between serum IGF-1 and IGF-2 levels, but the IGF-2 value was relatively significant in patients whose symptoms started on the right side (n = 23) (p = 0.008). A significant relationship was found between disease duration and median serum IGF-1 and IGF-2 values (p = 0.044 and p = 0.008, respectively), and a weak inverse correlation was detected between them. No statistically significant relationship was found between the patients' Unified Parkinson's Disease Rating Scale motor and non-motor scores and median serum IGF-1 and IGF-2 values (motor p = 0.149 and p = 0.254; non-motor p = 0.108 and p = 0.526). No correlation was found between them. Conclusion: This study contributes to efforts to develop biomarkers that can aid in the early recognition of Idiopathic Parkinson's Disease and relate to its prognosis. When comparing the fasting serum levels of IGF-1 and IGF-2 in patients with mild-to-moderate stage Parkinson's disease with their Unified Parkinson's Disease Rating Scale motor and non-motor scores, stages, disease durations, and levodopa-dopamine agonist treatment, it was observed that serum IGF-1 and IGF-2 levels increased especially in stage 2 according to the Hoehn & Yahr scale scale, but the difference was not significant. It was also found that IGF-1 and IGF-2 levels negatively correlated with Unified Parkinson's Disease Rating Scale motor and non-motor scales, though this was not statistically significant. Comparing serum IGF-1 levels of patients and healthy individuals, no significant difference was detected; however, serum IGF-2 levels were significantly increased in the patient group. The roles of IGF-1 and IGF-2 in Idiopathic Parkinson's disease and their involvement in neuroinflammation remain unclear, indicating a need for further studies. Keywords: IGF-1, IGF-2, Parkinson, UPDRS, Hoehn&Yahr