Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-d-glucose PET study

Abstract

Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An Abstract Aims/hypothesis: Hypoglycaemia unawareness in type 1 diabetes increases the risk of severe hypoglycaemia and impairs quality of life for people with diabetes. To explore the central mechanisms of hypoglycaemia awareness, we used [ 11 C]-3-O-methyl-D-glucose (CMG) positron emission tomography (PET) to measure changes in global and regional brain glucose metabolism between euglycaemia and hypoglycaemia in aware and unaware diabetic subjects. Materials and methods: Twelve men with type 1 diabetes, of whom six were characterised as aware and six as unaware of hypoglycaemia, underwent two CMG-PET brain scans while plasma glucose was controlled by insulin and glucose infusion either at euglycaemia (5 mmol/l) or at hypoglycaemia (2.6 mmol/l) in random order. Results: With hypoglycaemia, symptoms and sweating occurred only in the aware group. Brain glucose content fell in both groups (p=0.0002; aware, 1.18± 0.45 to 0.02±0.2 mmol/l; unaware, 1.07±0.46 to 0.19±0.23 mmol/l), with a relative increase in tracer uptake in prefrontal cortical regions, including the anterior cingulate. No detectable differences were found between groups in global brain glucose transport parameters (K 1 , k 2 ). The cerebral metabolic rate for glucose (CMRglc) showed a relative rise in the aware subjects (11.839±2.432 to 13.958± 2.372) and a fall in the unaware subjects (from 12.457± 1.938 to 10.16±0.801 μmol 100 g −1 min −1 , p=0.043). Conclusions/interpretation: Hypoglycaemia is associated with reduced brain glucose content in aware and unaware subjects, with a relative preservation of metabolism in areas associated with sympathetic activation. The relative rise in global glucose metabolic rate seen in aware subjects during hypoglycaemia contrasted with the relative fall in the unaware subjects and suggests that cortical neuronal activation is a necessary correlate of the state of hypoglycaemia awareness.

Syncope and Hypoglycemia

“…Hypoglycemic syncope is reported as isolated experiences [7]. Metabolic syncope is comprising about 5% of all syncope.…”

“…Metabolic syncope is comprising about 5% of all syncope. Hypoglycemic syncope is the most common metabolic syncope, with a reported incidence of 0.6% in diabetic patients and 4% in diabetic patients who take insulin [7]. Instead, the true incidence of hypoglycemic syncope is unknown due to the lack of established diagnostic criteria.…”

Hypoglycemia-Induced Increases in Thalamic Cerebral Blood Flow are Blunted in Subjects with Type 1 Diabetes and Hypoglycemia Unawareness

“…We also observed a reduced activation in left temporal lobe white matter, splenium and body of the corpus callosum of controls as compared with patients. While the involvement of these white matter areas is potentially interesting, the significance of the difference between the groups disappeared in such regions when a large cluster equal to that of other investigators was used for analysis, 1,4,6,7,12 in contrast to what observed in the thalamus. This observation raises questions about the robustness of the findings in the white-matter regions.…”

Improving management of type 1 diabetes in the UK: the Dose Adjustment For Normal Eating (DAFNE) programme as a research test-bed. A mixed-method analysis of the barriers to and facilitators of successful diabetes self-management, a health economic analysis, a cluster randomised controlled trial of different models of delivery of an educational intervention and the potential of insulin pumps and additional educator input to improve outcomes

“…14 Meanwhile, working simultaneously on a different NIHR programme grant, the research group attached to the King's College Hospital DAFNE centre had continued to investigate the pathophysiology of impaired hypoglycaemia awareness and problematic hypoglycaemia resistant to intervention. Bingham et al 117 and Dunn et al…”