Larry A. Fox

Comparison of fingerstick hemoglobin A1c levels assayed by DCA 2000 with the DCCT/EDIC central laboratory assay: results of a Diabetes Research in Children Network (DirecNet) Study.

Abstract:  Background:  The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) high‐performance liquid chromatography (HPLC) method for measuring hemoglobin A1c (HbA1c) serves as a reference standard against which other assays are compared. The DCA 2000® + Analyzer (Bayer Inc., Tarrytown, NY, USA), which uses an immunoassay, is a very popular device for measuring HbA1c levels in pediatric diabetes practices.

Continuous Glucose Monitoring in Youth with Type 1 Diabetes: 12-Month Follow-Up of the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Randomized Trial

BACKGROUND The use of continuous glucose monitoring (CGM) in the pediatric population is not well characterized. We have evaluated the use of CGM over a 12-month interval in youth with type 1 diabetes (TID) and have provided a description of CGM use. METHODS Eighty subjects 8-17 years old with T1D and baseline hemoglobin A1c (HbA1c) >or=7.0% used CGM as part of a 6-month randomized trial and subsequent 6-month extension study. Outcomes included frequency of CGM use, HbA1c levels, rate of severe hypoglycemia, and a CGM satisfaction scale. RESULTS Seventy-six (95%) of 80 subjects were using CGM after 6 months (median use = 5.5 days/week) compared with 67 (84%) after 12 months (median use = 4.0 days/week). The 17 subjects using CGM >or=6 days/week in month 12 had substantially greater improvement from baseline in HbA1c than did the 63 subjects using CGM <6 days/week in month 12 (mean change - 0.8 +/- 0.6% vs. +0.1 +/- 0.7%, P < 0.001). They also reported greater satisfaction with use of CGM (P = 0.001). The incidence of severe hypoglycemic events was low during the 12 months of the study irrespective of the amount of CGM use. CONCLUSIONS In youth with T1D, frequency of use decreases over time. Individuals who use CGM on a near-daily basis can have substantial improvement in glycemic control.

Variation of interstitial glucose measurements assessed by continuous glucose monitors in healthy, nondiabetic individuals.

OBJECTIVE To characterize glucose levels during daily living using continuous glucose monitors (CGMs) in nondiabetic individuals. RESEARCH DESIGN AND METHODS Seventy-four healthy children, adolescents, and adults aged 9–65 years with normal glucose tolerance used a blinded CGM device for 3 to 7 days. RESULTS Sensor glucose concentrations were 71–120 mg/dl for 91% of the day. Sensor values were ≤60 or >140 mg/dl for only 0.2% and 0.4% of the day, respectively. Sensor glucose concentrations were slightly higher in children than adults (P = 0.009) and were slightly lower during the night than day (95 vs. 99 mg/dl, P < 0.001). CONCLUSIONS Glucose values ≤60 and >140 mg/dl, measured with CGM, are uncommon in healthy, nondiabetic individuals. CGM may be useful to evaluate glucose tolerance in nondiabetic individuals over time. Furthermore, these data provide a basis for comparison for studies that use CGM to assess glucose control in subjects with diabetes.

Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children with Type 1 Diabetes: Association with Hyperglycemia

Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.

Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes

Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4–10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes.

Effects of glutamine on glycemic control during and after exercise in adolescents with type 1 diabetes a pilot study.

OBJECTIVE To investigate if oral glutamine ameliorates exercise and postexercise nighttime hypoglycemia in type 1 diabetic adolescents. RESEARCH DESIGN AND METHODS Ten adolescents (15.2 ± 1.4 years [SD], A1C 6.9 ± 0.9%) on insulin pumps were studied. The subjects were randomized to receive a glutamine or placebo drink pre-exercise and at bedtime (0.25 g/kg/dose). A 3:00 p.m. exercise session consisted of four 15-min treadmill/5-min rest cycles. Pre-exercise blood glucose was 140–150 mg/dl and was monitored throughout the night. Studies were randomized crossover over 3 weeks. RESULTS Blood glucose levels dropped comparably (52%) during exercise on both days. However, the overnight number of hypoglycemic events was higher on glutamine than placebo (≤70 mg/dl, P = 0.03 and ≤60, P = 0.05). The cumulative probability of nighttime hypoglycemia was increased on glutamine days (80%) versus placebo days (50%) (P = 0.02). CONCLUSIONS Glutamine increased the cumulative probability of postexercise overnight hypoglycemia compared with placebo in adolescents with type 1 diabetes. Whether glutamine may enhance insulin sensitivity postexercise requires further study in type 1 diabetes.

Effects of Glutamine on Glycemic Control During and After Exercise in Adolescents with Type 1 Diabetes Mellitus (T1DM): a Pilot Study

OBJECTIVE To investigate if oral glutamine ameliorates exercise and postexercise nighttime hypoglycemia in type 1 diabetic adolescents. RESEARCH DESIGN AND METHODS Ten adolescents (15.2 ± 1.4 years [SD], A1C 6.9 ± 0.9%) on insulin pumps were studied. The subjects were randomized to receive a glutamine or placebo drink pre-exercise and at bedtime (0.25 g/kg/dose). A 3:00 p.m. exercise session consisted of four 15-min treadmill/5-min rest cycles. Pre-exercise blood glucose was 140–150 mg/dl and was monitored throughout the night. Studies were randomized crossover over 3 weeks. RESULTS Blood glucose levels dropped comparably (52%) during exercise on both days. However, the overnight number of hypoglycemic events was higher on glutamine than placebo (≤70 mg/dl, P = 0.03 and ≤60, P = 0.05). The cumulative probability of nighttime hypoglycemia was increased on glutamine days (80%) versus placebo days (50%) (P = 0.02). CONCLUSIONS Glutamine increased the cumulative probability of postexercise overnight hypoglycemia compared with placebo in adolescents with type 1 diabetes. Whether glutamine may enhance insulin sensitivity postexercise requires further study in type 1 diabetes.