A study of serum growth differentiation factor 15 in Indian women with and without gestational diabetes mellitus in the third trimester of pregnancy and its association with pro-inflammatory markers and glucose metabolism

Abstract

The pathogenesis of gestational diabetes mellitus (GDM) is multifactorial and it shares many features with type 2 diabetes mellitus. Growth differentiation factor 15 (GDF-15), a member of transforming growth factor-β superfamily, is expressed in a high amount in the placenta in addition to other organs. This cross-sectional study was performed to assess the difference of GDF-15 and pro-inflammatory cytokines between pregnant women with or without GDM, and to explore the possible association of GDF-15 with the parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60 min, and 120 min post-75 gm oral glucose plasma glucose levels) and inflammation (IL-6 and TNF-α) in women with GDM at 24-28 weeks of gestation. Thirty-five women with GDM and 30 age-matched non-diabetic pregnant control (NDPC) subjects were recruited for the study. Mean serum GDF-15, IL-6, and TNF-α levels were significantly higher in GDM in comparison to the NDPC population. These differences persisted even after adjusting for the possible confounders like maternal age and BMI. GDF-15 level showed a positive correlation with parameters of dysglycemia (Serum insulin, HOMA-IR, fasting, 60 min, and 120 min post-75 gm oral glucose plasma glucose levels) but a variable correlation with the markers of inflammation. In conclusion, our study provides evidence that, in Indian women, serum GDF-15 level is higher in GDM in comparison to age-matched pregnant subjects without GDM in the early third trimester pregnancy. Moreover, in third trimester, GDF-15 level increases with increase in plasma glucose and insulin resistance.

Keywords: Diabetes; Gestational; Growth differentiation factor 15; Pregnancy; Pro-inflammatory cytokines.

Fig. 1

Average GDF-15 level in GDM population was significantly higher than NDPC subjects. p ≤ 0.001

Fig. 2

Correlation of GDF-15 with different biochemical parameters. a Fasting plasma glucose (r = 0.318, p = 0.009), b post 60 min OGTT plasma glucose (r = 0.407, p = 0.001), c post 120 min OGTT plasma glucose (r = 0.298, p = 0.019), d fasting serum insulin (r = 0.466, p ≤ 0.001), e HOMA-IR (r = 0.464, p ≤ 0.001), f IL-6 (r = 0.298, p = 0.016), g TNF-α (r = 0.233, p = 0.061)