Influence of hormonal levels on atherosclerotic risk markers and platelet activation related to diabetic complications in patients with type 1 diabetes

BACKGROUND AND AIMS: Patients with childhood-onset type 1 diabetes (T1D) are at increased risk of developing microvascular complications, including neuropathy and nephropathy. Hormonal dysregulation and markers of atherosclerotic plaque instability and platelet activation may play key roles in the pathogenesis of these complications. The aim of this study was to investigate the impact of hormonal levels on atherosclerotic risk markers and platelet function, as well as to explore the association between diabetic neuropathy and nephropathy in individuals with childhood-onset type 1 diabetes. METHODS: In this cross-sectional analysis of a longitudinal cohort, 34 individuals with childhood-onset type 1 diabetes (mean age 27.6 ± 4.2 years; diabetes duration 8.2 ± 5.6 years) were examined. S-IGF-I, long-term HbA1c, micro/macroalbuminuria, triiodothyronine and thyroxine, S-Cortisol, P-ACTH, P-Renin, sP-Selectin, P-MMP-9, P-TIMP-1, P-Adiponectin, and platelet adhesion to albumin, collagen, and fibrinogen were assessed. An abnormality in nerve conduction tests was defined as diabetic neuropathy. RESULTS: S-IGF-I was negatively correlated with age (r = -0.36, p = 0.007), and with long-term HbA1c (r = -0.426, p = 0.019, corrected for age). IGF-I levels in patients diagnosed with clinical neuropathy (n = 6) were lower (123 ± 38 µg/L) than in patients without neuropathy (n = 26, 178 ± 56 µg/L, p = 0.029). S-IGF-I levels were also lower in patients with nephropathy (n = 7, 122 ± 28 µg/L) compared with patients without nephropathy (n = 27, 180 ± 60 µg/L, p = 0.02). S-IGF-I was negatively correlated with P-TIMP-1 (r = -0.44, p = 0.009), sP-Selectin (r = -0.53, p = 0.001), and positively correlated with platelet adhesion to fibrinogen (r = 0.38, p = 0.035). S-free-Triiodothyronine correlated negatively with P-MMP-9, (r = -0.46, p = 0.005), and P-MMP-/P-TIMP-1 ratio (r = -0.40, p = 0.018), and P-Adiponectin (r = -0.49, p = 0.018). P-Renin correlated negatively with P-Adiponectin (r = -0.34, p = 0.045). CONCLUSIONS: Low serum IGF-I levels were associated with the presence of diabetic neuropathy and nephropathy in young adults with type 1 diabetes. Additionally, both IGF-I and S-free-Triiodothyronine levels were linked to changes in platelet activation and atherosclerotic markers, suggesting that hormonal dysregulation may contribute to early vascular complications in this population.