Background: MicroRNA-378a (MiR-378a) has been identified as a key regulator of glucose homeostasis and emerging as a promising target for the improvement of glycemic dysregulation including type 2 diabetes. Hypothesis: We assessed associations of circulating miR-378a-5p with improvements in insulin sensitivity and glucose metabolism in a 2-year dietary intervention trial.

Methods: Circulating miR-378a-5p levels were measured at baseline and 6 months among 5participants with overweight or obesity. Outcome measurements including fasting glucose, hemoglobin A1c (HbA1c) , fasting insulin, and homeostasis model assessment-of-insulin resistance (HOMA-IR) were assessed at baseline, 6 and 24 months.

Results: Higher level of miR-378a-5p was associated with greater fasting glucose (p =0.031) at baseline. Greater decrease in miR-378a-5p was significantly associated with greater improvements in fasting insulin (p =0.012) and HOMA-IR (p =0.017) over 6 months. The initial (6-months) decrease of miR-378a-5p was also significantly related to long-term (24-months) improvements in glucose, insulin, and HOMA-IR (p <0.for all) . Individuals in the lowest tertile group of the baseline miR-378a-5p showed consistently improved fasting insulin and HOMA-IR over 2 years, as compared to those with higher levels of miR-378a-5p (ptime*miR-378a-5p =0.015 and 0.007, respectively) . We also found significant interactions between baseline miR-378a-5p and dietary fat in the 6-months change in HbA1c (p = 0.003) ; a lower level of baseline miR-378a-5p showed a greater reduction of HbA1c at 6 months among participants who consumed a low-fat diet.

Conclusions: In conclusion, decreased circulating miR-378a-5p levels were related to significant improvements in insulin sensitivity and glucose metabolism in response to dietary weight-loss interventions; and dietary fat intake modified such associations.


Q.Xue: None. Y.Heianza: None. X.Li: None. H.Deng: None. J.Rood: None. G.Bray: None. F.Sacks: None. L.Qi: None.


National Heart, Lung, and Blood Institute (HL071981, HL034594, and HL126024) ;National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, and DK100383) ;Fogarty International Center (TW010790)

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