Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes.

OBJECTIVE To examine the cross-sectional association between physical activity (PA) and hippocampal volume in middle-aged adults with childhood-onset type 1 diabetes (T1D), and whether hyperglycemia and insulin sensitivity contribute to this relationship. METHODS We analyzed neuroimaging and self-reported PA data from 79 adults with T1D from the Pittsburgh Epidemiology of Diabetes Complications Study (mean age 50 years, mean duration 41 years) and 122 similarly aged adults without T1D (mean age 48 years). Linear regression models, controlling for intracranial volume, sex, education, and age, tested associations between PA and gray matter volumes of hippocampi and total brain in the 2 groups. For the T1D group, models further controlled for hyperglycemia and glucose disposal rate, a measure of insulin sensitivity. RESULTS PA was significantly lower in the T1D than in the non-T1D group (median [interquartile range] 952 kcal [420-2,044] vs 1,614 kcal [588-3,091], respectively). Higher PA was significantly associated with larger hippocampi for T1D, but not for non-T1D (standardized β [p values] from regression models adjusted for intracranial volume, sex, age, and education: 0.270 [p < 0.001] and 0.098 [p = 0.12], respectively). Neither hyperglycemia nor glucose disposal rate substantially modified this association. Relationships between PA and total brain gray matter volume were similar. CONCLUSIONS A cross-sectional association between higher PA and larger hippocampi is already detectable by middle age for these patients with T1D, and it appears robust to chronic hyperglycemia and insulin sensitivity. Proof-of-concept studies should investigate whether increasing PA preserves hippocampal volume and the mechanisms underlying the effects of PA on hippocampal volume.