Reversibility of brain glucose kinetics in type 2 diabetes mellitus

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 HbA_1c 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 HbA_1c 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 HbA_1c 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 HbA_1c (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 registrationClinicalTrials.gov NCT03469492. Graphical abstract: [Figure not available: see fulltext.]