Research Unit of Diabetes and Endocrine Diseases, Fondazione IRCCS Casa Sollievo Della Sofferenza, 71013, San Giovanni Rotondo, Foggia, Italy.
Department of Experimental Medicine, Sapienza University, 00161, Rome, Italy.
Acta Diabetol. 2024 Aug;61(8):1007-1013. doi: 10.1007/s00592-024-02280-7. Epub 2024 Apr 17.
Aim of this study was to investigate in type 2 diabetes whether expression level of GALNT2, a positive modulator of insulin sensitivity, is associated with a metabolic signature.
Five different metabolite families, including acylcarnitines, aminoacids, biogenic amines, phospholipids and sphingolipids were investigated in fasting serum of 70 patients with type 2 diabetes, by targeted metabolomics. GALNT2 expression levels were measured in peripheral white blood cells by RT-PCR. The association between GALNT2 expression and serum metabolites was assessed using false discovery rate followed by stepwise selection and, finally, multivariate model including several clinical parameters as confounders. The association between GALNT2 expression and the same clinical parameters was also investigated.
GALNT2 expression was independently correlated with HbA1c levels (P value = 0.0052), a finding that is the likely consequence of the role of GALNT2 on insulin sensitivity. GALNT2 expression was also independently associated with serum levels of the aminoacid glycine (P value = 0.014) and two biogenic amines phenylethylamine (P value = 0.0065) and taurine (P value = 0.0011). The association of GALNT2 expression with HbA1c was not mediated by these three metabolites.
Our data indicate that in type 2 diabetes the expression of GALNT2 is associated with several serum metabolites. This association needs to be further investigated to understand in depth its role in mediating the effect of GALNT2 on insulin sensitivity, glucose control and other clinical features in people with diabetes.
本研究旨在探讨 2 型糖尿病患者中，GALNT2（胰岛素敏感性的正调节剂）的表达水平是否与代谢特征有关。
通过靶向代谢组学方法，研究了 70 例 2 型糖尿病患者空腹血清中的 5 种不同代谢物家族，包括酰基肉碱、氨基酸、生物胺、磷脂和鞘脂。通过 RT-PCR 测量外周白细胞中的 GALNT2 表达水平。使用错误发现率（false discovery rate，FDR）进行逐步选择，最终包括几个混杂因素的多元模型，评估 GALNT2 表达与血清代谢物之间的关联。还研究了 GALNT2 表达与相同临床参数之间的关联。
GALNT2 表达与 HbA1c 水平独立相关（P 值=0.0052），这一发现可能是由于 GALNT2 对胰岛素敏感性的作用所致。GALNT2 表达还与血清中氨基酸甘氨酸（P 值=0.014）以及两种生物胺苯乙胺（P 值=0.0065）和牛磺酸（P 值=0.0011）的水平独立相关。GALNT2 表达与 HbA1c 的关联不受这三种代谢物的影响。
我们的数据表明，在 2 型糖尿病中，GALNT2 的表达与几种血清代谢物有关。需要进一步研究这种关联，以深入了解其在调节 GALNT2 对胰岛素敏感性、血糖控制和糖尿病患者其他临床特征的作用中的作用。
