Background: We aimed to evaluate irisin and SREBP-1c levels in serum, colostrum and mature breast milk in women with and without gestational diabetes (GDM); and to relate them with maternal glucose, lipid profile and weight status of babies. Methods: GDM positive women (n = 33) and normal glucose tolerant women (NGT) (n = 33) were recruited. Maternal blood samples were collected at 28th week of gestation and later at 6-week post-partum while breast milk samples of the lactating mothers were collected within 72 hours of birth (colostrum) and at 6 weeks post-partum (mature milk). Irisin and SREBP-1c levels were analyzed by commercially available ELISA kits for all maternal samples. Results: Lower levels of irisin were seen in serum, colostrum and mature breast milk of GDM females (p < .01). SREBP-1c profile showed a similar trend of low serum levels in GDM, however, they were undetectable in colostrum and mature breast milk. Weak to moderate correlations of serum irisin with BMI (r = 0.439; p < .001), GTT 0 hours (r = 0.403; p = .01), HbA1c (r = -0.312; p = .011), Fasting blood glucose (r = 0.992; p = .008), and baby weight at birth (r = 0.486; p < .001). Colostrum and mature breast milk irisin showed positive associations with baby weight at 6 weeks (r = 0.325; p = .017; r = 0.296; p = .022, respectively). Serum SREBP-1c at 6 weeks correlated with random blood glucose (r = 0.318; p = .009), and HbA1c (r= -0.292; p = .011). All correlations were lost once we adjusted for maternal BMI. Conclusions: Low irisin and SREBP1-c levels may favor development of GDM in pregnant subjects. Further, low mature breast milk levels may act as a continued stressor from fetal to infant life as long as breast-feeding is continued. Further studies are required to identify the mechanistic relationship between these biomarkers and GDM.

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