Reversibility of brain glucose kinetics in type 2 diabetes mellitus

Abstract

Aims/hypothesis: We have previously shown that individuals with uncontrolled type 2 diabetes have a blunted rise in brain glucose levels measured by 1H magnetic resonance spectroscopy. Here, we investigate whether reductions in HbA1c normalise intracerebral glucose levels.

Methods: Eight individuals (two men, six women) with poorly controlled type 2 diabetes and mean ± SD age 44.8 ± 8.3 years, BMI 31.4 ± 6.1 kg/m2 and HbA1c 84.1 ± 16.2 mmol/mol (9.8 ± 1.4%) underwent 1H MRS scanning at 4 Tesla during a hyperglycaemic clamp (~12.21 mmol/l) to measure changes in cerebral glucose at baseline and after a 12 week intervention that improved glycaemic control through the use of continuous glucose monitoring, diabetes regimen intensification and frequent visits to an endocrinologist and nutritionist.

Results: Following the intervention, mean ± SD HbA1c decreased by 24.3 ± 15.3 mmol/mol (2.1 ± 1.5%) (p=0.006), with minimal weight changes (p=0.242). Using a linear mixed-effects regression model to compare glucose time courses during the clamp pre and post intervention, the pre-intervention brain glucose level during the hyperglycaemic clamp was significantly lower than the post-intervention brain glucose (p<0.001) despite plasma glucose levels during the hyperglycaemic clamp being similar (p=0.266). Furthermore, the increases in brain glucose were correlated with the magnitude of improvement in HbA1c (r = 0.71, p=0.048).

Conclusion/interpretation: These findings highlight the potential reversibility of cerebral glucose transport capacity and metabolism that can occur in individuals with type 2 diabetes following improvement of glycaemic control. Trial registration ClinicalTrials.gov NCT03469492.

Keywords: Brain glucose transport; Diabetes; Glucose kinetics.

© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Figures

Fig. 1

1H scanning of the brain. (a) Voxel placement, a 30 × 20 × 30 mm voxel was centred at the midline of the occiput. Localised shimming was obtained from an elliptical volume (green) around the selected voxel. The scale on the image is in (cm) centimeters (vertical axis). (b) Representative difference spectra at baseline (week 0, black) and after the intervention (week 12, red) from 1 participant. The glucose reference spectrum (phantom) is shown in green. The spectral window in which the glucose integration was performed is indicated

Fig. 2

Spectral processing for intracerebral glucose. An example using one representative participant of how an individual time point is calculated for change in brain glucose levels using difference spectra. The blue spectrum was obtained at baseline and the red spectrum was obtained 10 min later. The green spectrum underneath is the difference between the red and blue spectra

Fig. 3

Change in intracerebral glucose and plasma glucose levels. (a) Mean change in intracerebral glucose concentrations over time at week 0 and 12. (b) Mean plasma glucose levels over time. All eight participants were included in analysis. Data are presented as mean ± SEM

Fig. 4

Relationship between change in intracerebral glucose levels, reduction in HbA1c and duration of diabetes. All eight participants were included in the analysis. (a) Change in the average of brain glucose levels at steady state (time 60–120 min) correlated using a Pearson’s correlation with reduction of HbA1c (12 weeks vs 0 weeks). (b) Change in the average of brain glucose levels at steady state (time 60–120 min) correlated using a Pearson’s correlation with duration of diabetes