Clinical features and search for genetic determinants of postprandial hypoglycemia.

Autor:	Ren Q; Q Ren, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China., Han X; X Han, Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China., Gong S; S Gong, 1. Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China., Zhang S; S Zhang, Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China., Ba T; T Ba, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China., Zhao Y; Y Zhao, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China., Li Y; Y Li, Department of Endocrinology and Metabolism, Peking University Diabetes Center, Beijing, China., Wang Y; Y Wang, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China., Zhou X; X Zhou, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China., Li Y; Y Li, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China., Ji L; L Ji, Endocrinology and metabolism department, Peking University People's Hospital, Beijing, China.
Jazyk:	angličtina
Zdroj:	Endocrine connections [Endocr Connect] 2024 Nov 01. Date of Electronic Publication: 2024 Nov 01.
DOI:	10.1530/EC-24-0409
Abstrakt:	Objective: To test whether postprandial hypoglycaemia is an extreme and repeatable phenotype of glucose metabolism. Secondly, we explored the genetic determinants of this phenotype. Design and Methods: We conducted this study using data from 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 clinical features with those of normal glucose tolerance (NGT). We additionally selected 75 subjects as super-healthy control group. Whole-exome sequencing (WES) was performed on postprandial hypoglycaemic and super-healthy controls. We also evaluated several candidate genes believed to be important in pancreatic hypoglycaemia. Results: We found 13 participants (0.39%) had an OGTT 2 h glucose <3 mmol/L. Ten patients were men (76.9%). All 13 participants had insulin > 3 uU/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 (MAF) of rare PEG3 mutations were significantly higher in subjects with postprandial hypoglycaemia than in super-healthy controls. Among all four subjects with PEG3 gene mutations, 71.4% were men, and their body mass index (BMI) was significantly lower than that of the NGT. Conclusions: 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.
Databáze:	MEDLINE
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