Exposure to gestational diabetes mellitus in utero impacts hippocampal functional connectivity in response to food cues in children

Abstract

Objectives: Intrauterine exposure to gestational diabetes mellitus (GDM) increases the risk of obesity in the offspring, but little is known about the underlying neural mechanisms. The hippocampus is crucial for food intake regulation and is vulnerable to the effects of obesity. The purpose of the study was to investigate whether GDM exposure affects hippocampal functional connectivity during exposure to food cues using functional magnetic resonance imaging (fMRI).

Methods: Participants were 90 children age 7-11 years (53 females) who underwent an fMRI-based visual food cue task in the fasted state. Hippocampal functional connectivity (FC) was examined using generalized psychophysiological interaction in response to food versus non-food cues. Hippocampal FC was compared between children with and without GDM exposure, while controlling for possible confounding effects of age, sex and waist-to-hip ratio. In addition, the influence of childhood and maternal obesity were investigated using multiple regression models.

Results: While viewing high caloric food cues compared to non-food cure, children with GDM exposure exhibited higher hippocampal FC to the insula and striatum (i.e., putamen, pallidum and nucleus accumbens) compared to unexposed children. With increasing BMI, children with GDM exposure had lower hippocampal FC to the somatosensory cortex (i.e., postcentral gyrus).

Conclusions: Intrauterine exposure to GDM was associated with higher food-cue induced hippocampal FC especially to reward processing regions. Future studies with longitudinal measurements are needed to clarify whether altered hippocampal FC may raise the risk of the development of metabolic diseases later in life.

Fig. 1. Masks of the hippocampus derived from the AAL atlas 3, overlaid on the average normalized T1 weighted image of the children.

Hippo, Hippocampus; L, left; R, right.

Fig. 2. Hippocampal functional connectivity during the food-cue task.

a Children with GDM exposure showed higher FC between bilateral hippocampus and left insula, left putamen/pallidum. b Children with GDM exposure showed higher FC between left hippocampus and the bilateral putamen, insula, and left NAcc. The cluster of the right putamen extended to the right insula. The cluster of left putamen extended to the left pallidum. Color map corresponds to T values (p < 0.001 uncorrected for display) overlaid on the normalized average T1 weighted image of the children. Hippo hippocampus, FC functional connectivity, GDM gestational diabetes mellitus, NAcc nucleus accumbens, L left, R right.

Fig. 3. Hippocampal functional connectivity in relation to BMI z-score in the GDM group.

a Children with GDM exposure showed lower FC between the left hippocampus and the right postcentral gyrus with higher BMI z-score. Color map corresponds to T values (Multiple regression analysis with BMI z-score; p < 0.001 uncorrected for display) overlaid on the normalized average T1 weighted image of the children. b Negative correlation between BMI z-score and the extracted cluster of the FC of the left hippocampus and the right postcentral gyrus in the GDM group. Error bars indicate 95% confidence interval. Hippo hippocampus, FC functional connectivity, GDM gestational diabetes mellitus, L left, R right.