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 registrationClinicalTrials.gov NCT03469492. Graphical abstract

Pathophysiology and management of hypoglycemia in diabetes

“…Recently, our group has reported in a pilot study that improvement of glycemic control over 12 weeks can improve brain glucose levels toward normal controls (but not completely). 182 Moreover, the degree of improvement in brain glucose correlated with the degree of glucose improvement and the duration of diabetes. 182 These findings suggest that, in principle, glucose transport can be modulated with changes in glycemic control.…”

“…182 Moreover, the degree of improvement in brain glucose correlated with the degree of glucose improvement and the duration of diabetes. 182 These findings suggest that, in principle, glucose transport can be modulated with changes in glycemic control. Whether avoidance of hypoglycemia can restore brain glucose in the other direction remains an active area of investigation.…”

“…Whether changes in brain glucose transport and metabolism are reversible remains unclear. Recently, our group has reported in a pilot study that improvement of glycemic control over 12 weeks can improve brain glucose levels toward normal controls (but not completely) 182 . Moreover, the degree of improvement in brain glucose correlated with the degree of glucose improvement and the duration of diabetes 182 .…”