Higher fasting plasma glucose is associated with striatal and hippocampal shape differences: the 2sweet project

Abstract

Objective: Previous studies have demonstrated associations between higher normal fasting plasma glucose levels (NFG) (<6.1 mmol/L), type 2 diabetes (T2D) and hippocampal atrophy and other cerebral abnormalities. Little is known about the association between plasma glucose and the striatum despite sensorimotor deficits being implicated in T2D. This study aimed to investigate the relationship between plasma glucose levels and striatal and hippocampal morphology using vertex-based shape analysis.

Design: A population-based, cross-sectional study.

Setting: Canberra and Queanbeyan, Australia.

Participants: 287 cognitively healthy individuals (mean age 63 years, 132 female, 273 Caucasian) with (n=261) or without T2D (n=26), selected from 2551 participants taking part in the Personality & Total Health (PATH) Through Life study by availability of glucose data, MRI scan, and absence of gross brain abnormalities and cognitive impairment.

Outcome measures: Fasting plasma glucose was measured at first assessment, and MRI images were collected 8 years later. Shape differences indicating outward and inward deformation at the hippocampus and the striatum were examined with FMRIB Software Library-Integrated Registration and Segmentation Toolbox (FSL-FIRST) after controlling for sociodemographic and health variables.

Results: Higher plasma glucose was associated with shape differences indicating inward deformation, particularly at the caudate and putamen, among participants with NFG after controlling for age, sex, body mass index (BMI), hypertension, smoking and depressive symptoms. Those with T2D showed shape differences indicating inward deformation at the right hippocampus and bilateral striatum, but outward deformation at the left hippocampus, compared with participants with NFG.

Conclusions: These findings further emphasize the importance of early monitoring and management of plasma glucose levels, even within the normal range, as a risk factor for cerebral atrophy.

Keywords: Brain; Fasting Blood Glucose; MRI.

Figure 1

Three-dimensional summary images of results from shape analysis of hippocampus, caudate, putamen and globus pallidus from superior and inferior views, showing association between plasma glucose levels and shape differences among participants with normal fasting plasma glucose levels (NFG) (top rows) and with type 2 diabetes (T2D) (middle rows). Bottom rows show shape differences between participants with T2D and participants with NFG (diabetes vs NFG). The color bar indicates the t statistic values presented on the surface maps. Results are statistically significant (p<0.05) at t<−1.96 for inward deformation and t>1.96 for outward deformation associated with plasma glucose levels or classification of T2D. Results were adjusted for all covariates. Structures with significant (p<0.05) volumetric differences indicating smaller volume are marked with blue squares, while those with volumetric differences indicating greater volume are marked with red squares.