Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)+ compared with AAb− relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb+ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.

中文翻译：

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1 型糖尿病诊断前后的胰岛素样生长因子失调

胰岛素样生长因子 (IGF)，特别是 IGF1 和 IGF2，可促进葡萄糖代谢，其可用性受 IGF 结合蛋白 (IGFBP) 的调节。我们假设 IGF1 和 IGF2 水平或其生物利用度在 1 型糖尿病发展过程中降低。在 1 型糖尿病进展的不同阶段，在年龄匹配的横断面队列中测量总血清 IGF1、IGF2 和 IGFBP1-7 水平。与 1 型糖尿病受试者的 AAb- 亲属相比，自身抗体 (AAb)+ 中的 IGF1 和 IGF2 水平显着降低。大多数高亲和力 IGFBP 在 1 型糖尿病前期患者中没有变化，这表明总 IGF 水平可能反映了生物活性。我们还测量了一组禁食的 1 型糖尿病患者的血清 IGF。IGF1 水平随着疾病持续时间显着降低，同时伴随着β细胞功能的下降。此外，在一个 AAb+ 队列中每月评估血浆 IGF 水平，持续一年。IGF1 和 IGF2 在单个 AAb + 受试者中显示出纵向稳定性，但 IGF1 水平在具有多个 AAb 的受试者和进展为 1 型糖尿病的受试者中随时间下降，尤其是在诊断后。总之，IGFs 在 1 型糖尿病临床诊断前后均失调，可作为新的生物标志物来改善疾病预测。