Ren Qian, Han Xueyao, Gong Siqian, Zhang Simin, Ba Tianhao, Zhao Yilin, Li Yating, Wang Yan'ai, Zhou Xianghai, Li Yufeng, Ji Linong
Endocr Connect. 2024 Dec 13;14(1). doi: 10.1530/EC-24-0409. Print 2025 Jan 1.
To test whether postprandial hypoglycaemia is an extreme and repeatable phenotype of glucose metabolism. We also explored the genetic determinants of this phenotype.
We conducted this study using data from the Pinggu Metabolic Disease Study database (n = 3,345). We selected subjects after an oral glucose tolerance test (OGTT) (2 h glucose < 3 mmol/L) and compared their clinical features with those of subjects with normal glucose tolerance (NGT). In addition, we selected 75 subjects as a super-healthy control group. Whole-exome sequencing (WES) was performed on subjects with postprandial hypoglycaemic and super-healthy controls. We also evaluated several candidate genes believed to be important in pancreatic hypoglycaemia.
We found 13 participants (0.39%) who had an OGTT (2 h glucose < 3 mmol/L). Ten of these patients were men (76.9%). All 13 participants had insulin >3 μU/mL when postprandial blood glucose levels were <3 mmol/L. WES analysis identified one gene, paternally expressed 3 (PEG3), which had three rare mutations in four patients (30.8%). Minor allele frequencies of rare PEG3 mutations were significantly higher in subjects with postprandial hypoglycaemia than in super-healthy controls. Among the four subjects with PEG3 gene mutations, 71.4% were men, and their body mass index was significantly lower than that of the NGT group.
Postprandial hypoglycaemia is an extreme and reproducible phenotype in the general population. PEG3 mutations may represent a potential genetic aetiology for postprandial hypoglycaemia. Further research with larger and more diverse populations and a broader genetic focus is needed to understand the genetic basis of postprandial hypoglycaemia.
检验餐后低血糖是否为葡萄糖代谢的一种极端且可重复的表型。我们还探究了该表型的遗传决定因素。
我们利用平谷代谢病研究数据库（n = 3345）中的数据开展本研究。我们在口服葡萄糖耐量试验（OGTT）后（2小时血糖<3 mmol/L）选择受试者，并将他们的临床特征与糖耐量正常（NGT）的受试者进行比较。此外，我们选择75名受试者作为超级健康对照组。对餐后低血糖受试者和超级健康对照组进行全外显子组测序（WES）。我们还评估了几个被认为在胰腺性低血糖中很重要的候选基因。
我们发现13名参与者（0.39%）OGTT（2小时血糖<3 mmol/L）异常。其中10名患者为男性（76.9%）。当餐后血糖水平<3 mmol/L时，所有13名参与者的胰岛素水平均>3 μU/mL。WES分析鉴定出一个基因，父源表达3（PEG3），4名患者（30.8%）中有3个罕见突变。餐后低血糖受试者中罕见PEG3突变的次要等位基因频率显著高于超级健康对照组。在4名有PEG3基因突变的受试者中，71.4%为男性，且他们的体重指数显著低于NGT组。
餐后低血糖是普通人群中一种极端且可重复的表型。PEG3突变可能是餐后低血糖的潜在遗传病因。需要对更大、更多样化的人群进行进一步研究，并扩大基因研究范围，以了解餐后低血糖的遗传基础。
