Longitudinal Relationship of Asymptomatic Hypoglycemia to Cognitive Function in IDDM

Early-onset insulin-dependent diabetes mellitus (IDDM) is linked to subsequent learning deficits. To investigate the relationship of learning deficits to metabolic control, 23 children with IDDM (age at testing 71 ± 21 mo, age at diagnosis 35 ± 15 mo) diagnosed before 5 yr of age were followed for periods of 6–78 mo. Mean glycosylated hemoglobin (HbA,), episodes of severe hypoglycemia, and frequency of self-monitoring blood glucose (SMBG) measurements <2.8 mM (50 mg/dl, asymptomatic hypoglycemia) were recorded every 3 mo. Six subjects entered the study 12.3 ± 6.7 mo after diagnosis, and only severe hypoglycemia was present before entry. For the remaining 17 subjects, HbA, and severe and asymptomatic hypoglycemia were present from the time of diagnosis of diabetes. Mean HbA, level was 10.1 ± 1.0%, and mean severe hypoglycemic episodes per patient was 2.9, but the frequency was highly skewed; one patient had 37 episodes, and 14 had none. The mean percentage of SMBG readings <2.8 mM was 2.4 ± 2.1. On the revised Stanford-Binet Intelligence Scale there was no correlation between any subscale and severe hypoglycemia. However, the relative frequency of asymptomatic hypoglycemia correlated with scores on the abstract/visual reasoning scale (r = –.39, P = .037). This relationship was primarily accounted for by the relationship of asymptomatic hypoglycemia to performance on the copying subscale (r = –.42, P = .022). Children with frequent asymptomatic hypoglycemic episodes had lower mean copying scores and abstract reasoning scores than those with infrequent episodes. These findings are consistent with those of previous crosssectional studies of early-onset IDDM and extend previous results by suggesting that hypoglycemia, even if mild or asymptomatic, may be related to the neuropsychological changes previously described.