Regional Brain Volume Differences Associated With Hyperglycemia and Severe Hypoglycemia in Youth With Type 1 Diabetes

Abstract

OBJECTIVE -Despite interest in the effects of type 1 diabetes on the developing brain, structural brain volumes in youth with this disease have not previously been examined. This study is the first to quantify regional brain volume differences in a large sample of youth with diabetes. RESEARCH DESIGN AND METHODS -Magnetic resonance images (MRIs)were acquired from youth with diabetes (n ϭ 108) and healthy sibling control subjects (n ϭ 51) aged 7-17 years. History of severe hypoglycemia was assessed by parent interview and included seizure, loss of consciousness, or requiring assistance to treat. A1C values since diagnosis were obtained from medical records; median A1C was weighted by duration of disease. Voxel-based morphometry was used to determine the relationships of prior hypo-and hyperglycemia to regional grey and white matter volumes across the whole brain.RESULTS -No significant differences were found between diabetic and healthy control groups in grey or white matter. However, within the diabetic group, a history of severe hypoglycemia was associated with smaller grey matter volume in the left superior temporal region. Greater exposure to hyperglycemia was associated with smaller grey matter volume in the right cuneus and precuneus, smaller white matter volume in a right posterior parietal region, and larger grey matter volume in a right prefrontal region.CONCLUSIONS -Qualitatively different relationships were found between hypo-and hyperglycemia and regional brain volumes in youth with type 1 diabetes. Future studies should investigate whether these differences relate to cognitive function and how these regions are affected by further exposure. Diabetes Care 30:2331-2337, 2007T ype 1 diabetes is known to have cumulative deleterious effects on the body, most notably on the retina, kidney, nerves, and blood vessels (1,2).The effects of diabetes on central nervous system structure and function are less well understood. A number of studies associate exposure to hypo-and hyperglycemia during childhood with deficits in specific cognitive domains (3,4). These findings suggest that during development, exposure to glycemic extremes may alter the structure or function of specific pathways or regions in the brain. Recent brain imaging studies in diabetic adults have reported differences in grey or white matter integrity associated with prior hypo-or hyperglycemia (5,6). However, the effects of diabetes on the developing brain have not been assessed in any largescale study to date (7). Assessing brain integrity earlier in the course of brain development and diabetes, followed by prospective monitoring, would be essential to determine when differences may emerge. Such knowledge could shed light on the neural basis of observed cognitive effects in children and adults with diabetes and determine whether there are developmental time periods during which the brain may be particularly vulnerable to the negative effects of hypoglycemia or hyperglycemia.The present study is the first to examine the structural integrity of t...

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