Hyperglycemia is clearly associated with the longterm risk of diabetes-related microvascular and macrovascular complications. Treatment to reduce hyperglycemia, as determined by hemoglobin A1c (HbA1c), reduces the occurrence and slows the progression of retinopathy, nephropathy, and neuropathy in adults [1] and adolescents [2,3] as well as the macrovascular complications [4]. Despite overall improved glycemic control from newer diabetes management technologies that have developed during the last three decades (insulin analogs, self-blood glucose monitoring, insulin pumps, and continuous glucose monitoring [CGM] sensors), hypoglycemia continues to be a limiting factor in achieving a euglycemic state in insulin-treated (type 1 and insulin-requiring type 2) diabetes mellitus [5]. Even today, with the best of technologies available, persons with type 1 diabetes mellitus (T1DM) spend a significant portion of each day hyperglycemic and/or hypoglycemic. This is clear from many studies, most notably from the JDRF CGM Study [6] in which an average of 395 min (6.5 hr) of the day were spent with blood glucoses (BG) >180 mg/dL, 101 min (1.7 hr) with BG >250 mg/dL and 60 min (1 hr) of the day with BGs 180 mg/dL, 268 min (4.5 hr) with BG >250 mg/dL and 47 min (0.8 hr) with BG <70 mg/dL. Nearly half the day, on average, was spent either hypoor hyperglycemic. In years past, when hypoglycemia was considered to be the major contributor to cognitive deficits in children with diabetes, we were satisfied with allowing a higher glycemic target in children so as to avoid hypoglycemia. Coupling the observations from the JDRF CGM study with the associated cognitive impairment in either hypoglycemic or hyperglycemic state leaves caregivers of patients with T1DM with an important challenge: What is the best range to target blood glucose to maximize the benefits of glycemic control for the prevention of the long-term vascular complications while minimizing the potential for cognitive and CNS complications associated with both hypoglycemia and hyperglycemia? In this issue of the Journal of Pediatric Neuroradiology, Kaufmann et al. report their findings from a crosssectional study using cognitive testing and brain MRI in 30 “pediatric patients” (6 20 years old) with T1DM and 19 similarly-aged non-diabetic controls. The T1DM subjects were analyzed in two groups, one (n = 15) with HbA1c < 8.0% (“low HbA1c group”) and the other with *Address for correspondence: Neil H. White, Division of Endocrinology & Diabetes, Co-Unit Leader, Patient-Oriented Research Unit (PORU), Director, Pediatric Clinical Research Unit (PCRU), Department of Pediatrics, 660 South Euclid Avenue, Box 8116, St. Louis, MO 63110, USA. Tel.: +1 314 286 1157; Fax: +1 314 286 1187; E-mail: white_n@kids.wustl.edu. Journal of Pediatric Neuroradiology 1 (2012) 3–5 DOI 10.3233/PNR-2012-002 IOS Press 3