Department of Diabetology and Dysmetabolic Diseases, IRCCS MultiMedica, Milan, Italy.
Department of Molecular and Translational Medicine, University of Brescia, Brescia Italy.
PLoS One. 2017 Dec 4;12(12):e0188980. doi: 10.1371/journal.pone.0188980. eCollection 2017.
A major unmet medical need to better manage Type 2 Diabetes (T2D) is the accurate disease prediction in subjects who show glucose dysmetabolism, but are not yet diagnosed as diabetic. We investigated the possibility to predict/monitor the progression to T2D in these subjects by retrospectively quantifying blood circulating microRNAs in plasma of subjects with i) normal glucose tolerance (NGT, n = 9); ii) impaired glucose tolerance (IGT, n = 9), divided into non-progressors (NP, n = 5) and progressors (P, n = 4) based on subsequent diabetes occurrence, and iii) newly diagnosed T2D (n = 9). We found that impaired glucose tolerance associated with a global increase of plasma circulating microRNAs. While miR-148 and miR-222 were specifically modulated in diabetic subjects and correlated with parameters of glucose tolerance, the most accentuated microRNA dysregulation was found in NP IGT subjects, with increased level of miR-122, miR-99 and decreased level of let-7d, miR-18a, miR-18b, miR-23a, miR-27a, miR-28 and miR-30d in comparison with either NGT or T2D. Interestingly, several of these microRNAs significantly correlated with parameters of cholesterol metabolism. In conclusion, we observed the major perturbation of plasma circulating microRNA in NP pre-diabetic subjects and identified a unique microRNA profile that may become helpful in predicting diabetic development.
控制 2 型糖尿病（T2D）的主要医学需求尚未得到满足，即在尚未被诊断为糖尿病的葡萄糖代谢异常患者中准确预测疾病。我们通过对具有以下特征的受试者的血浆中循环 microRNA 进行回顾性定量分析，研究了在这些受试者中预测/监测进展为 T2D 的可能性：i）血糖正常（NGT，n = 9）；ii）葡萄糖耐量受损（IGT，n = 9），根据随后发生的糖尿病分为非进展者（NP，n = 5）和进展者（P，n = 4）；iii）新诊断的 T2D（n = 9）。我们发现，葡萄糖耐量受损与血浆循环 microRNA 的整体增加有关。miR-148 和 miR-222 特异性调节糖尿病患者的参数与葡萄糖耐量相关，而 NP IGT 受试者中发现的 microRNA 失调最严重，miR-122、miR-99 水平升高，let-7d、miR-18a、miR-18b、miR-23a、miR-27a、miR-28 和 miR-30d 水平降低，与 NGT 或 T2D 相比。有趣的是，其中一些 microRNAs 与胆固醇代谢参数显著相关。总之，我们观察到 NP 糖尿病前期患者血浆循环 microRNA 出现明显紊乱，并鉴定出一种独特的 microRNA 谱，可能有助于预测糖尿病的发展。
