Objective While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer-term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. Methods Cognitive testing was performed on children 7–17 years old with T1DM (n=66) within 3.5 months of diagnosis and siblings without T1DM (n=33). Overall intelligence, processing speed and memory (including a sensitive long-delay spatial memory test; Spatial Delayed Response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. Results Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p=0.006). In addition, within the group with T1DM higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p=0.027). Performance on the other cognitive tasks was not different across groups or subgroups. Conclusions DKA and degree of hyperglycemia exposure at diagnosis have implications for long delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function.

Alkaline phosphatase can be considered "our favorite enzyme" for reasons apparent to those who diagnose and treat metabolic bone diseases or who study skeletal biology. Few might know, however, that alkaline phosphatase likely represents the most frequently assayed enzyme in all of medicine. Elevated activity in the circulation is universally recognized as a marker for skeletal or hepatobiliary disease. Nevertheless, the assay conditions in many ways are nonphysiological. The term alkaline phosphatase emerged when it became necessary to distinguish "bone phosphatase" from the phosphatase in the prostate that features an acidic pH optimum. Beginning in 1948, studies of the inborn-error-of-metabolism hypophosphatasia would identify the natural substrates and establish the physiological role of alkaline phosphatase, including in biomineralization. Here, we recount the discovery in 1923 and then eventual naming of this enzyme that remains paramount in our field. © 2017 American Society for Bone and Mineral Research.

Objective Differences in cognition and brain structure have been found in youth with type 1 diabetes compared to controls, even after relatively short disease duration. To determine whether severity of clinical presentation contributes to these differences, we obtained structural MRI scans in youth ages 7–17 who were either newly diagnosed with type 1 diabetes (<3.5 months from diagnosis, n=46) or a sibling without diabetes (n=28). Research Design and Methods Severity of presentation was measured by the presence of diabetic ketoacidosis (DKA) and degree of hyperglycemia exposure (hemoglobin A1c (HbA1c)) at diagnosis. Magnetic resonance images were obtained using T1-weighted, T2-weighted, and Diffusion Weighted sequences. Results Within the group with type 1 diabetes, 12 subjects presented in DKA, and 34 did not. After controlling for age, sex and multiple comparisons, the type 1 diabetes group had lower volume in the left temporal-parietal-occipital cortex compared to controls. Within the type 1 diabetes group, DKA at presentation was associated with lower radial, axial and mean diffusivity throughout major white matter tracts and higher HbA1c was associated with lower hippocampal, thalamic, and cerebellar white matter volumes, lower right posterior parietal cortical thickness and greater right occipital cortical thickness. Conclusion These data suggest that severity of clinical presentation is an important factor in predicting brain structural differences in youth with type 1 diabetes approximately 3 months after diagnosis.

Objective Puberty‐induced insulin resistance is considered critical in the pathogenesis of type 2 diabetes (T2D) in youth. The development of T2D before puberty suggests distinct risk factors and pathophysiology but, because of its rarity, this has not been well studied. We aimed to describe the clinical characteristics of children with T2D diagnosed before the onset of puberty. Research design and methods We retrospectively studied all children with autoantibody‐negative T2D and available pubertal development assessment seen at our center between July 2016 and July 2019, and compared characteristics of those at Tanner stage I (prepubertal, n = 35) versus those at Tanner II–V of pubertal development (n = 341). Results At T2D diagnosis, prepubertal children compared with those at Tanner II–V had higher body mass index z‐score (p = 0.003) and higher C‐peptide (p = 0.003) (while glucose levels were not significantly different), with differences retaining significance after adjustment for glucose, race/ethnicity and sex. Dyslipidemia occurred in 100% of prepubertal children versus 89.7% of those diagnosed later (p = 0.036). Of the prepubertal children diagnosed under age 10 (n = 13), 69.2% were female, 100% racial/ethnic minority, 100% had obesity with history of dyslipidemia and none with diabetic ketoacidosis. Conclusions T2D, although rarely, can develop before puberty. Children with T2D diagnosed in the prepubertal period have more severe obesity, greater insulin resistance, and more frequent dyslipidemia than older youth. These findings suggest that children with prepubertal T2D are at increased risk for associated morbidity compared with older youth and underscore the significance of interventions to prevent and treat obesity in early childhood.