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  • Review Article
  • Published:

Metabolic neuroimaging of the brain in diabetes mellitus and hypoglycaemia

Nature Reviews Endocrinology volume 8, pages 588–597 (2012)Cite this article

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Abstract

Functional neuroimaging techniques can be used to study changes in regional brain activation, using changes in surrogate markers such as regional cerebral perfusion and rates of glucose uptake or metabolism. These approaches are shedding new light on two major health problems: the increasing burden of type 2 diabetes mellitus (T2DM), which is driven by the rising prevalence of insulin resistance and obesity; and recurrent intractable problematic hypoglycaemia, which is driven by the cognitive impairment that can occur in association with iatrogenic hypoglycaemic episodes. Some patients with diabetes mellitus lose awareness of being hypoglycaemic, which puts them at risk of severe hypoglycaemia as they are unlikely to take action to prevent the condition worsening. Involvement of corticolimbic brain and centres serving higher executive functions as well as the hypothalamus has been demonstrated in both situations and has implications for therapy. This Review describes the relevant principles of functional neuroimaging techniques and presents data supporting the notion that the dysregulation of central pathways involved in metabolic regulation, reward and appetite could contribute to problematic hypoglycaemia during therapy for diabetes mellitus and to insulin-resistant obesity and T2DM. Understanding these dysregulations could enable the development of novel clinical interventions.

Key Points

  • Functional neuroimaging shows brain regions that are activated during task performance or in response to stimuli by detecting changes in markers showing, for example, perfusion, nutrient uptake or metabolism

  • Functional neuroimaging has been used to study therapy-related hypoglycaemia in patients with diabetes mellitus and the increasing prevalence of type 2 diabetes mellitus (T2DM), which is driven by obesity

  • Patients with acute hypoglycaemia demonstrate extensive activation of the cortex, putative glucose-sensing brain regions and stress pathways; these features are altered in patients with counter-regulatory deficits and hypoglycaemia unawareness

  • In patients with hypoglycaemia unawareness, altered responses of reward and memory pathways might prevent long-term restoration of awareness

  • Growing evidence from functional neuroimaging studies indicates that dysfunction of reward and motivational pathways occurs in individuals with obesity or T2DM

  • Increased understanding of the cortical components of these alterations in patients with T2DM, obtained from neuroimaging studies, could lead to development of effective therapeutic interventions

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Figure 1: A schematic representation of the principles of functional neuroimaging.
Figure 2: Principles of glucose PET.
Figure 3: Water PET study showing the evolution of regional brain activation patterns observed during an episode of controlled hypoglycaemia induced in a group of healthy men.

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Acknowledgements

The authors acknowledge grant support from the Wellcome Trust; Juvenile Diabetes Research Foundation; the Comprehensive Biomedical Research Centre of Guy's and St Thomas' NHS Foundation Trust, and King's College London and the King's College Hospital Charity.

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  1. Diabetes Research Group, Weston Education Centre, Denmark Hill Campus, King's College London, 10 Cutcombe Road, London, SE5 9RJ, UK

    Yee-Seun Cheah & Stephanie A. Amiel

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Y.-S. Cheah and S. A. Amiel contributed equally to researching the data for the article, discussions of its content, writing the article, and reviewing and/or editing of the manuscript before submission.

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Correspondence to Stephanie A. Amiel.

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Cheah, YS., Amiel, S. Metabolic neuroimaging of the brain in diabetes mellitus and hypoglycaemia. Nat Rev Endocrinol 8, 588–597 (2012). https://doi.org/10.1038/nrendo.2012.97

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