Effect of hypoglycemia on brain structure in people with type 2 diabetes: epidemiological analysis of the ACCORD-MIND MRI trial

Zhang Z, Lovato J, Battapady H, et al. Effect of hypoglycemia on brain structure in people with type 2 diabetes: epidemiological analysis of the ACCORD-MIND MRI trial. Diabetes Care. 2014;37(12):3279-3285.

The relationship between treatment-related hypoglycemia and cognition remains unclear. Brain atrophy is a sensitive and powerful correlate of cognitive function and decline. Abnormal white matter (AWM) tissue volume suggests diffuse and focal ischemic, demyelinating, and inflammatory processess related to small vessel disease. Increased AWM is associated with diabetes and impaired cognition. This MRI cohort study1 of ACCCORD MIND2 determined whether severe symptomatic hypoglycemia events in treated subjects with type 2 diabetes are associated with chronic brain changes.

Participants in ACCORD MIND were randomly assigned to an intensive strategy, aiming to achieve A1C < 6.0%, or to a standard strategy, aiming to maintain an A1C 7.0-7.9% Brain MRI scans were performed at baseline and 40 months after randomization. The exposure of interest was severe hypoglycemia requiring assistance. The primary endpoints were changes in total brain volume (TBV) and AWM volume.

In ACCORD-MIND MRI, serious hypoglycemic events were defined as a blood glucose concentration of <50 mg/dL (<2.8 mmol/L) or recovery with carbohydrate treatment in which the participant reported receiving medical care or assistance from another individual. A total of 28 participants reported having at least one episode of severe hypoglycemia before the 40-month MRI exam, and six reported coma during the severe hypoglycemic episode. A total of 19 (68%) had one episode, five (18%) had two episodes, two (7%) had three episodes, and two (7%) had five episodes. The median time between serious hypoglycemic events and the 40-month MRI scans was 28 months.

Subjects who experienced serious hypoglycemic events had marginally significantly less atrophy (less decrease of total brain volume) from baseline to the 40-month follow-up compared with patients without serious hypoglycemic events: difference = -9.554 (95% CI, -15.21 to -3.903) vs -15.38 (95% CI, -16.64 to -14.12); P=0.051. There was no significant difference in the changes of abnormal white matter volume from baseline to the 40-month follow-up: ratio =2.06 (95% CI, 1.71-2.49) for serious hypoglycemic events vs 1.84 (95% CI, 1.76-1.91) for no serious hypoglycemic events (P=0.247). There were no significant differences between patients with and without serious hypoglycemic episodes in secondary outcomes from baseline to 40 months:

  • Total gray matter volume: difference = -17.13 (95% CI, -24.87 to -9.395 vs -19.61 (95% CI, -21.34 to -17.89); P=0.544
  • Total white volume matter: difference = 1.017 (95% CI, 1.000-1.034) vs 1.009 (95% CI, 1.006-1.013); P=0.414
  • Abnormal deep gray/white matter volume: ratio = 1.46 (95% CI, 1.22-1.76) vs 1.33 (95% CI, 1.27-1.38); P=0.303

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 ACCORD-MIND MRI Hypoglycemia Related to Type 2 Diabetes Treatment Does Not Accentuate Brain Pathology  



  • In ACCORD-MIND MRI, there was no evidence of additional brain injury among subjects with type 2 diabetes who experienced serious hypoglycemic events
  • Subjects with serious hypoglycemic events showed the same general pattern of brain atrophy and abnormal white matter as those without. Subanalysis of the intensive glycemic control group showed similar results.
  • The absence of incremental brain volume loss suggest good future cognitive function in subjects who experience serious hypoglycemia

All slides available for download in the Slide Library.

ACCORD=Action to Control Cardiovascular Risk in Diabetes

For more on ACCORD and ACCORD-MIND, click here. 


Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

November 2014 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

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