• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus Diabetes & Endocrinology Clinical Trials

• Hyperglycemia/Hypoglycemia
• Diabetes Mellitus
• Endocrinology
• Diabetes & Metabolic Syndrome
• Diabetes & Endocrinology Clinical Trials

Pratik Choudhary, MD, King's College London, London, United Kingdom, presented data showing that men with type 1 diabetes mellitus (T1DM) with impaired hypoglycemia awareness (HA) have different brain activation patterns than do patients with intact HA. Patients with T1DM who are unable to sense that they are hypoglycemic have less activation of brain regions involved in the stress response, autonomic activation, and emotional salience.

Hypoglycemia is a huge burden for patients with T1DM. Epidemiologic and cross-sectional studies suggest that 25% to 40% of patients with T1DM have impaired HA, and the incidence increases as the disease duration increases [Choudhary P et al. Diabet Med 2010]. Impaired HA increases the risk of severe hypoglycemia by 3 to 6 times [Choudhary P et al. Diabet Med 2010] and is associated with counterregulatory hormonal and symptomatic responses to subsequent hypoglycemia.

Dr. Choudhary and his colleagues previously published findings on the evolution of brain responses to acute hypoglycemia in nondiabetic healthy volunteers using water positron-emission tomography (PET) imaging, showing that different regions of the brain were engaged in response to different stressors [Teh MM et al. Neuroimage 2010]. The objective of the current study was to compare regional brain activation during experimental hypoglycemia in people with T1DM and intact or impaired HA, using radiolabeled water PET scanning. The researchers used hyperinsulinemic clamping to achieve a succession of glycemic states: euglycemia (90 mg/dL), hypoglycemia (46.8 mg/dL for 50 minutes), and recovery (90 mg/dL). Scans were performed at 10-minute intervals before, during, and up to 40 minutes after hypoglycemia.

In total, 27 right-handed men were studied (17 men with T1DM with > 5 years' duration of diabetes, of whom 8 had impaired HA, and 10 healthy controls). The patients with T1DM were older and heavier than were the healthy volunteers, although those with intact and impaired HA were well matched (Table 1). A Clarke score ≥ 4 indicates impaired HA.

Among T1DM subjects with impaired HA compared with subjects with intact HA or healthy volunteers, acute hypoglycemia resulted in deactivation or lack of activation in brain regions involved in stress responses, autonomic activation, and emotional salience of stressful stimuli. Impaired HA resulted in activation or a lack of deactivation in areas of the brain involved in interoception, executive function, and reward and hedonic perception and in the resting state network. After recovery from hypoglycemia, there was persistent activation or lack of deactivation in reward networks in patients with impaired HA compared to those with intact HA. The investigators concluded that emotional and motivational responses to hypoglycemia, including the emotional memory of each event, are likely barriers to hypoglycemia avoidance and are potential targets for restoring HA.

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