Type-2 diabetes mellitus reduces cortical thickness and decreases oxidative metabolism in sensorimotor regions after stroke

Abstract

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with stroke and diabetes had lower cortical thickness bilaterally in the primary somatosensory cortex, and primary and secondary motor cortices. Individuals with stroke and diabetes also showed reduced creatine levels bilaterally in the sensorimotor cortex. Contralesional primary and secondary motor cortex thicknesses were negatively related to sensorimotor outcomes in the paretic upper-limb in the stroke and diabetes group such that those with thinner primary and secondary motor cortices had better motor function. These data suggest that type-2 diabetes alters cerebral energy metabolism, and is associated with thinning of sensorimotor cortex after stroke. These factors may influence motor outcomes after stroke.

Keywords: Chronic stroke; creatine; magnetic resonance imaging; magnetic resonance spectroscopy; volumetrics.

Figure 1.

Example MRS voxel placement and MRS spectra on a participant with cortical involvement of the lesion. Voxels were placed bilaterally over the ‘hand knob’ region of primary motor cortex. Panel (a) shows voxel placement and MRS spectral fit from LC model for the contralesional hemisphere; Panel (b) shows voxel placement and spectral fit for the ipsilesional hemisphere. MRS metabolites of interest are marked on example LC model output. Glx: glutamate; mI: myo-inositol; Cho: choline; Cre: creatine; NAA: N-acetylaspartate.

Figure 2.

Gross cortical grey and white matter volumes in individuals with chronic stroke, comparing the impact of diabetes. There was no significant main effect of diabetes status on grey or white matter volumes. Across the stroke cohort, there was a significant main effect of Hemisphere with lower brain volumes in the ipsilesional hemisphere relative to the contralesional hemisphere. Grey and white matter volumes are normalized values expressed as total hemispheric volume/estimated total intracranial volume. DCS: diabetes with chronic stroke; NDCS: no diabetes with chronic stroke. Significance set to p < 0.05; error bars are SEM; **p < 0.01.

Figure 3.

Regional cortical thickness in sensorimotor regions in individuals with chronic stroke, comparing the impact of diabetes. The diabetes group showed significantly lower cortical thickness in sensorimotor regions, compared with the non-diabetes group. Across the entire stroke cohort, there was significantly thinner sensorimotor cortex in the ipsilesional hemisphere, relative to the contralesional hemisphere. M1: primary motor cortex; BA6: Brodmann area 6 (secondary motor cortex); S1: primary somatosensory cortex; DCS: diabetes with chronic stroke; NDCS: no diabetes with chronic stroke. Significance set to p < 0.05; error bars are SEM; *p < 0.05.

Figure 4.

Cerebral metabolite profiles in sensorimotor cortex in individuals with chronic stroke, comparing the impact of diabetes. The diabetes group showed significantly lower creatine bilaterally. Across the stroke cohort, NAA was significantly lower in the ipsilesional hemisphere relative to the contralesional hemisphere. There were no significant effects of Group or Hemisphere on myo-inositol levels. NAA: N-acetylaspartate; DCS: diabetes with chronic stroke; NDCS: no diabetes with chronic stroke; significance set to p < 0.05; error bars are SEM; *p < 0.05.

Figure 5.

(a,b) Motor function (indexed by mean WMFT rate) was negatively correlated with (a) contralesional M1 (p = 0.047) and (b) BA6 thickness (p = 0.004) in the DCS group only. (c) Motor impairment (indexed by Fugl-Meyer (FM) score) was negatively correlated with contralesional BA6 thickness (p = 0.015) in the DCS group only.