Hippocampal volume reduction is associated with direct measure of insulin resistance in adults

Abstract

Hippocampal integrity is highly susceptible to metabolic dysfunction, yet its mechanisms are not well defined. We studied 126 healthy individuals aged 23-61 years. Insulin resistance (IR) was quantified by measuring steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Body mass index (BMI), adiposity, fasting insulin, glucose, leptin as well as structural neuroimaing with automatic hippocampal subfield segmentation were performed. Data analysis using unsupervised machine learning (k-means clustering) identified two subgroups reflecting a pattern of more pronounced hippocampal volume reduction being concurrently associated with greater adiposity and insulin resistance; the hippocampal volume reductions were uniform across subfields. Individuals in the most deviant subgroup were predominantly women (79 versus 42 %) with higher BMI [27.9 (2.5) versus 30.5 (4.6) kg/m²], IR (SSPG concentration, [156 (61) versus 123 (70) mg/dL] and leptinemia [21.7 (17.0) versus 44.5 (30.4) μg/L]. The use of person-based modeling in healthy individuals suggests that adiposity, insulin resistance and compromised structural hippocampal integrity behave as a composite phenotype; female sex emerged as risk factor for this phenotype.

Keywords: Adiposity; Hippocampal volume; Insulin resistance.

Fig. 1.

Relationship of hippocampal volume subfields with direct measure of insulin resistance (SSPG) and clinical and metabolic measures – Move to supplement. Spearman correlation coefficients amongst hippocampal subfields and direct measure of insulin resistance (SSPG), fasting insulin, fasting glucose, BMI, WC, leptin, and cortisol. All measures were adjusted for age and sex. Positive correlations are presented in blue colors and negative correlations in red. SSPG, indicates steady-state-plasma glucose; FPI, fasting plasma insulin; FPG, fasting plasma glucose; BMI, body mass index; and WC, waist circumference; HATA, hippocampal amygdala transition area (HATA and GC granule cell layer of the dentate gyrus. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).

Fig. 2.

Violin plots depicting cluster differences in total hippocampal volume. The box plots represent the median and interquartile range; the lower and upper points of the plots represent the lower and upper adjustment values.