Evaluation of leukocyte SIRT1 expression in women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy

Abstract

Background. Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase, has been implicated as a key regulator of glucose/lipid metabolism, insulin secretion as well as adiponectin production and inflammation in metabolic disorders, including type 2 diabetes mellitus (T2DM). However, its role in gestational diabetes mellitus (GDM) remains widely unknown. Since GDM is associated with inflammation, the aim of this study was to determine whether leukocyte SIRT1 mRNA expression is alteredin GDM women in the third trimester of pregnancy, and whether this change is correlated with clinical characteristics of patients.

Methods. Leukocytes were isolated from the blood of GDM (n = 135) and normal glucose tolerant (NGT;n = 52) pregnant women. After extracting RNA from leukocytes, a quantitative real-time polymerase chain reaction (qRT-PCR) approach was performed to assess SIRT1 gene expression in these cells. Univariate regression analyses were applied to investigate correlations between SIRT1 expression and clinic parameters of patients.

Results. Leukocyte SIRT1 mRNA was increased 1.7-foldin the GDM vs. NGT subjects (p = 0.001) and it positively correlated with 2 h glucose concentration during oral glucose tolerance test (OGTT) in the whole studygroup and negatively correlated with pregnancy agein the GDM and NGT groups. The positive association was also observed between SIRT1 mRNA and plasma high density lipoprotein (HDL) cholesterol level in the NGT subjects.

Conclusions. GDM is accompanied by leukocyte SIRT1 mRNA over expression associated with hyperglycemia. Additionally, there is a close and beneficial relationship between enhanced leukocyte SIRT1 expression and increased plasma HDL-cholesterol level during normal pregnancy.