Abstract
Aim Determine the metabolic profile and identify risk factors of women transitioning from gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM). Methods 237 women diagnosed with GDM underwent an oral glucose tolerance test (OGTT), anthropometrics assessment, and completed lifestyle questionnaires six years after pregnancy. Blood was analysed for clinical variables (e.g., insulin, glucose, HbA1c, adiponectin, leptin, and lipid levels) and NMR metabolomics. Based on the OGTT, women were divided into three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. Results Six years after GDM, 19% of subjects had T2DM and 19% IGT. After BMI adjustment, the IGT group had lower HDL, higher leptin, and higher free fatty acid (FFA) levels, and the T2DM group higher triglyceride, FFA, and C-reactive protein levels than the NGT group. IGT and T2DM groups reported lower physical activity. NMR measurements revealed that levels of branched-chain amino acids (BCAAs) and the valine metabolite 3-hydroxyisobyturate were higher in T2DM and IGT groups and correlated with measures of insulin resistance and lipid metabolism. Conclusion In addition to well-known clinical risk factors, BCAAs and 3-hydroxyisobyturate are potential markers to be evaluated as predictors of metabolic risk after pregnancy complicated by GDM.
Highlights
Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy [1], occurs in up to 14% of pregnancies every year [2]
In most women glucose tolerance returns to normal after delivery, the frequency of GDM correlates with the prevalence of type 2 diabetes mellitus (T2DM), and women with GDM have increased risk for T2DM later in life
In the T2DM group, body mass index (BMI) at start of pregnancy was higher than in the normal glucose tolerance (NGT) group (Figure 1), GDM was diagnosed earlier, fasting glucose was higher at GDM diagnosis, and higher percentages required insulin during pregnancy or were non-Nordic
Summary
Gestational diabetes mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy [1], occurs in up to 14% of pregnancies every year [2]. The 10-year risk is ~40%, and the incidence is highest in the first 5 years after pregnancy [3]. In both GDM and T2DM, chronic insulin resistance and pancreatic β-cell dysfunction play crucial pathogenic roles. An inherently insulin-resistant state, may reveal a preexisting deficiency in insulin secretion and insulin sensitivity and relative β-cell failure. The stress of pregnancy may reveal a predisposition to T2DM and provide early signs useful for preventing chronic diseases
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