Higher β cell death in pregnant women, measured by DNA methylation patterns of cell-free DNA, compared to new-onset type 1 and type 2 diabetes subjects: a cross-sectional study

Diabetes is a metabolic disorder of glucose homeostasis in which beta cell destruction occurs silently and is detected mainly when symptoms appear. In the last few years, it has emerged a great interest in developing markers capable of detecting pancreatic beta cell death focused on improving early diagnosis and getting a better treatment response, mainly in type 1 diabetes. But other types of diabetes would also benefit from early detection of beta cell death. Differentially methylated circulating DNA is being studied as minimally invasive biomarker of cell death. We aimed to explore whether the unmethylated/methylated ratio of the insulin and amylin genes might be a good biomarker of beta cell death in different types of diabetes. A lower index Delta Ct indicates a higher rate of beta-cell death. Plasma samples from subjects without diabetes, pregnant women, pregnant with gestational diabetes (GDM), type 1 diabetes and type 2 diabetes were analyzed. A qPCR reaction with specific primers for both methylated and unmethylated fragments of insulin and amylin genes were carried out. Pregnant women, GDM and non-GDM, showed a higher beta-cell death for both markers (Delta INS = 3.8 +/- 2.1 and Delta Amylin = 8.5 +/- 3.6), whereas T1D presented lower rate (Delta INS = 6.2 +/- 2.1 and Delta Amylin = 10.7 +/- 2.9) comparable to healthy subjects. The insulin methylation index was associated with the newborn birth weight (r = 0.46; p = 0.033) and with insulin resistance (r = -0.533; p = 0.027) in the GDM group. The higher rate of beta-cell death was observed in pregnant women independently of their metabolic status. These indexes could be a good indicator of beta cell death in processes caused by defects on insulin secretion, insulin action, or both.

Automated summary

There is increasing interest in developing markers for detecting pancreatic beta cell death to improve early diagnosis and treatment response in diabetes, particularly in type 1 diabetes. Early detection of beta cell death would also benefit other types of diabetes.