Monovalent SARS-CoV-2 mRNA Vaccine Does not Boost Omicron-Specific Immune Response in Diabetic and Control Pediatric Patients.

While the immunogenicity of SARS-CoV-2 vaccines has been well described in adults, pediatric populations have been less studied. In particular, children with type 1 diabetes are generally at elevated risk for more severe disease after infections, but are understudied in terms of COVID-19 and SARS-CoV-2 vaccine responses. We investigated the immunogenicity of COVID-19 mRNA vaccinations in 35 children with type 1 diabetes (T1D) and 23 controls and found that these children develop levels of SARS-CoV-2 neutralizing antibody titers and spike protein-specific T cells comparable to nondiabetic children. However, in comparing the neutralizing antibody responses in children who received 2 doses of mRNA vaccines (24 T1D; 14 controls) with those who received a third, booster dose (11 T1D; 9 controls), we found that the booster dose increased neutralizing antibody titers against ancestral SARS-CoV-2 strains but, unexpectedly, not Omicron lineage variants. In contrast, boosting enhanced Omicron variant neutralizing antibody titers in adults.

Diabetes Device Downloading: Benefits and Barriers Among Youth With Type 1 Diabetes.

BACKGROUND: The majority of youth with type 1 diabetes (T1D) fail to meet glycemic targets despite increasing continuous glucose monitoring (CGM) use. We therefore aimed to determine the proportion of caregivers who review recent glycemic trends ("retrospective review") and make ensuant insulin adjustments based on this data ("retroactive insulin adjustments"). We additionally considered that fear of hypoglycemia and frequency of severe hypoglycemia would be associated with performing retrospective review. METHODS: We conducted a cross-sectional survey of caregivers of youth with T1D, collecting demographics, diabetes technology usage, patterns of glucose data review/insulin dose self-adjustment, and Hypoglycemia Fear Survey (HFS). RESULTS: Nineteen percent of eligible caregivers (191/1003) responded. Performing retrospective review was associated with younger child age (12.2 versus 15.4, P = .0001) and CGM use (92% versus 73%, P = .004), but was not associated with a significant improvement in child's HbA1c (7.89 versus 8.04, P = .65). Retrospective reviewers had significantly higher HFS-behavior scores (31.9 versus 27.7, P = .0002), which remained significantly higher when adjusted for child's age and CGM use (P = .005). Linear regression identified a significant negative association between HbA1c (%) and number of retroactive insulin adjustments (0.24 percent lower mean HbA1c per additional adjustment made, P = .02). CONCLUSIONS: Retrospective glucose data review is associated with improved HbA1c when coupled with data-driven retroactive insulin adjustments. Barriers to data downloading existed even in this cohort of predominantly CGM-using T1D families.

Hypoglycemia secondary to insulinoma masking the onset of type 1 diabetes in an adolescent.

Type 1 diabetes and insulinoma can co-occur in pediatric patients and may present with episodes of hypo- and hyperglycemia, significant glycemic variability, and weight gain. Surgical resection leads to development of fulminant diabetes.

The Evolution of Insulin Administration in Type 1 Diabetes.

Insulin has been utilized in the treatment of type 1 diabetes (T1D) for 100 years. While there is still no cure for T1D, insulin administration has undergone a remarkable evolution which has contributed to improvements in quality of life and life expectancy in individuals with T1D. The advent of faster-acting and longer-acting insulins allowed for the implementation of insulin regimens more closely resembling normal insulin physiology. These improvements afforded better glycemic control, which is crucial for limiting microvascular complications and improving T1D outcomes. Suspension of insulin delivery in response to actual and forecasted hypoglycemia has improved quality of life and mitigated hypoglycemia without compromising glycemic control. Advances in continuous glucose monitoring (CGM) and insulin pumps, efforts to model glucose and insulin kinetics, and the application of control theory to T1D have made the automation of insulin delivery a reality. This review will summarize the past, present, and future of insulin administration in T1D.

Longitudinal assessment of hippocampus structure in children with type 1 diabetes.

The extant literature finds that children with type 1 diabetes mellitus (T1D) experience mild cognitive alterations compared to healthy age-matched controls. The neural basis of these cognitive differences is unclear but may relate in part to the effects of dysglycemia on the developing brain. We investigated longitudinal changes in hippocampus volume in young children with early-onset T1D. Structural magnetic resonance imaging data were acquired from 142 children with T1D and 65 age-matched control subjects (4-10 years of age at study entry) at 2 time points, 18 months apart. The effects of diabetes and glycemic exposure on hippocampal volume and growth were examined. Results indicated that although longitudinal hippocampus growth did not differ between children with T1D and healthy control children, slower growth of the hippocampus was associated with both increased exposure to hyperglycemia (interval HbA1c) and greater glycemic variability (MAGE) in T1D. These observations indicate that the current practice of tolerating some hyperglycemia to minimize the risk of hypoglycemia in young children with T1D may not be optimal for the developing brain. Efforts that continue to assess the factors influencing neural and cognitive development in children with T1D will be critical in minimizing the deleterious effects of diabetes.

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.

Cross-Validation of Single-Stage Treadmill Tests for Predicting Aerobic Fitness in Adolescents with Type I Diabetes.

PURPOSE: Determining fitness is important when assessing adolescents with type 1 diabetes mellitus (T1DM). Submaximal tests estimate fitness, but none have been validated in this population. This study cross-validates the Ebbeling and Nemeth equations to predict fitness (VO2max (ml/kg/min)) in adolescents with T1DM. METHODS: Adolescents with T1DM (n = 20) completed a maximal treadmill test using indirect calorimetry. Participants completed one 4-min stage between 2.0 and 4.5 mph and 5% grade (Ebbeling/Nemeth protocol). Speed and grade were then increased until exhaustion. Predicted VO2max was calculated using the Ebbeling and Nemeth equations and compared with observed VO2max using paired t tests. Pearson correlation coefficients, 95% confidence intervals, coefficients of determination (R²), and total error (TE) were calculated. RESULTS: The mean observed VO2max was 47.0 ml/kg/min (SD = 6.9); the Ebbeling and Nemeth mean predictions were 42.4 (SD = 9.4) and 43.5 ml/kg/min (SD = 6.9), respectively. Paired t tests resulted in statistically significant (p < .01) mean differences between observed and predicted VO2max for both predictions. The association between the Ebbeling prediction and observed VO2max was r = .90 (95% CI = 0.76, 0.96), R² = .81, and TE = 6.5 ml/kg/ min. The association between the Nemeth prediction and observed VO2max was r = .81 (95% CI = 0.57, 0.92), R² = .66, and TE = 5.6 ml/kg/min. CONCLUSION: The Nemeth submaximal treadmill protocol provides a better estimate of fitness than the Ebbeling in adolescents with T1DM.

Effects of moderate-to-vigorous intensity physical activity on overnight and next-day hypoglycemia in active adolescents with type 1 diabetes.

OBJECTIVE: Physical activity (PA) provides many benefits to adolescents with type 1 diabetes; however, these individuals tend to have lower fitness and PA levels than their disease-free counterparts. The purpose of this study was to examine the acute temporal associations between moderate-to-vigorous intensity PA (MVPA) and hypoglycemia (continuous glucose monitor [CGM] reading ≤70 mg/dL). RESEARCH DESIGN AND METHODS: Nineteen participants (53% females) 14-20 years old with type 1 diabetes were recruited. Participant fitness was evaluated via indirect calorimetry using a maximal exercise test; body composition was measured using air displacement plethysmography. An accelerometer was worn continuously (3-5 days) and acceleration data used to estimate MVPA (minutes per day). Blood glucose values were simultaneously tracked using CGM. Controlling for sex, percent body fat (%BF), fitness, and concurrent MVPA, the likelihood of nighttime and next-day hypoglycemia due to MVPA was examined using logistic regression. RESULTS: Participants were of average fitness (females: 43.9 mL/kg/min; males: 49.8 mL/kg/min) and adiposity (females: 26.2%; males: 19.2%); 63.2% met the U.S. federal guideline of accumulating 60 min/day of MVPA. Hypoglycemia was 31% more likely in those who accumulated 30 min/day more MVPA in the previous afternoon than those with less (95% CI 1.05-1.63; P = 0.017). CONCLUSIONS: The results suggest that participating in afternoon MVPA increases the risk of overnight and next-day hypoglycemia, independent of sex, %BF, fitness, and concurrent MVPA. While promoting PA as a healthy behavior, it is important to educate adolescents with type 1 diabetes on prevention of hypoglycemia following PA.

Factors associated with microalbuminuria in 7,549 children and adolescents with type 1 diabetes in the T1D Exchange clinic registry.

OBJECTIVE: To examine factors associated with clinical microalbuminuria (MA) diagnosis in children and adolescents in the T1D Exchange clinic registry. RESEARCH DESIGN AND METHODS: T1D Exchange participants <20 years of age with type 1 diabetes ≥ 1 year and urinary albumin-to-creatinine ratio (ACR) measured within the prior 2 years were included in the analysis. MA diagnosis required all of the following: 1) a clinical diagnosis of sustained MA or macroalbuminuria, 2) confirmation of MA diagnosis by either the most recent ACR being ≥ 30 mg/g or current treatment with an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 3) no known cause for nephropathy other than diabetes. Logistic regression was used to assess factors associated with MA. RESULTS: MA was present in 329 of 7,549 (4.4%) participants, with a higher frequency associated with longer diabetes duration, higher mean glycosylated hemoglobin (HbA1c) level, older age, female sex, higher diastolic blood pressure (BP), and lower BMI (P ≤ 0.01 for each in multivariate analysis). Older age was most strongly associated with MA among participants with HbA1c ≥ 9.5% (≥ 80 mmol/mol). MA was uncommon (<2%) among participants with HbA1c <7.5% (<58 mmol/mol). Of those with MA, only 36% were receiving ACEI/ARB treatment. CONCLUSIONS: Our results emphasize the importance of good glycemic and BP control, particularly as diabetes duration increases, in order to reduce the risk of nephropathy. Since age and diabetes duration are important nonmodifiable factors associated with MA, the importance of routine screening is underscored to ensure early diagnosis and timely treatment of MA.

Variants of the dopamine D2 receptor gene and risperidone-induced hyperprolactinemia in children and adolescents.

OBJECTIVE: To investigate the association between hyperprolactinemia and variants of the dopamine D2 receptor (DRD2) gene in children and adolescents in long-term treatment with risperidone. METHODS: Medically healthy 7 to 17-year-old patients chronically treated with risperidone but receiving no other antipsychotics were recruited in a cross-sectional study. Four DRD2 variants were genotyped and prolactin concentration was measured. Medication history was obtained from the medical records. The effect of the TaqIA variants of the DRD2 on the risk of risperidone-induced hyperprolactinemia was the primary outcome measure. RESULTS: Hyperprolactinemia was present in 50% of 107 patients (87% males) treated with risperidone for an average of 2.9 years. Age, stage of sexual development, and the dose of risperidone independently predicted a higher prolactin concentration, whereas the dose of psychostimulants was negatively correlated with it. However, these four predictors became nonsignificant when risperidone serum concentration was entered into the model. Adverse events potentially related to hyperprolactinemia were more common in participants with elevated prolactin concentration and in girls (45%) compared with boys (10%). After controlling for risperidone concentration and the dose of psychostimulants, the TaqIA A1 and the A-241G alleles were associated with higher prolactin concentration, whereas the -141C Ins/Del and C957T variants had no significant effect. In addition, adverse events potentially related to hyperprolactinemia were four times more common in TaqIA A1 allele carriers. CONCLUSION: Prolactin concentration is closely related to central DRD2 blockade, as reflected by risperidone serum concentration. Furthermore, the TaqIA and A-241G variants of the DRD2 gene could be useful in predicting the emergence of hyperprolactinemia and its potential adverse events.

Evaluation of factors affecting CGMS calibration.

BACKGROUND: The optimal number/timing of calibrations entered into the CGMS (Medtronic MiniMed, Northridge, CA) continuous glucose monitoring system have not been previously described. METHODS: Fifty subjects with Type 1 diabetes mellitus (10-18 years old) were hospitalized in a clinical research center for approximately 24 h on two separate days. CGMS and OneTouch Ultra meter (LifeScan, Milpitas, CA) data were obtained. The CGMS was retrospectively recalibrated using the Ultra data varying the number and timing of calibrations. Resulting CGMS values were compared against laboratory reference values. RESULTS: There was a modest improvement in accuracy with increasing number of calibrations. The median relative absolute deviation (RAD) was 14%, 15%, 13%, and 13% when using three, four, five, and seven calibration values, respectively (P < 0.001). Corresponding percentages of CGMS-reference pairs meeting the International Organisation for Standardisation criteria were 66%, 67%, 71%, and 72% (P < 0.001). Nighttime accuracy improved when daytime calibrations (pre-lunch and pre-dinner) were removed leaving only two calibrations at 9 p.m. and 6 a.m. (median difference, -2 vs. -9 mg/dL, P < 0.001; median RAD, 12% vs. 15%, P = 0.001). Accuracy was better on visits where the average absolute rate of glucose change at the times of calibration was lower. On visits with average absolute rates <0.5, 0.5 to <1.0, 1.0 to <1.5, and >or=1.5 mg/dL/min, median RAD values were 13% versus 14% versus 17% versus 19%, respectively (P = 0.05). CONCLUSIONS: Although accuracy is slightly improved with more calibrations, the timing of the calibrations appears more important. Modifying the algorithm to put less weight on daytime calibrations for nighttime values and calibrating during times of relative glucose stability may have greater impact on accuracy.

The effects of aerobic exercise on glucose and counterregulatory hormone concentrations in children with type 1 diabetes.

OBJECTIVE: To examine the acute glucose-lowering effects of aerobic exercise in children and adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifty children and adolescents with type 1 diabetes (ages 10 to <18 years) were studied during exercise. The 75-min exercise session consisted of four 15-min periods of walking on a treadmill to a target heart rate of 140 bpm and three 5-min rest periods. Blood glucose and plasma glucagon, cortisol, growth hormone, and norepinephrine concentrations were measured before, during, and after exercise. RESULTS: In most subjects (83%), plasma glucose concentration dropped at least 25% from baseline, and 15 (30%) subjects became hypoglycemic (< or = 60 mg/dl) or were treated for low glucose either during or immediately following the exercise session. The incidence of hypoglycemia and/or treatment for low glucose varied significantly by baseline glucose, occurring in 86 vs. 13 vs. 6% of subjects with baseline values <120, 120-180, and >180 mg/dl, respectively (P < 0.001). Exercise-induced increases in growth hormone and norepinephrine concentrations were marginally higher in subjects whose glucose dropped < or = 70 mg/dl. Treatment of hypoglycemia with 15 g of oral glucose resulted in only about a 20-mg/dl rise in glucose concentrations. CONCLUSIONS: In youth with type 1 diabetes, prolonged moderate aerobic exercise results in a consistent reduction in plasma glucose and the frequent occurrence of hypoglycemia when preexercise glucose concentrations are <120 mg/dl. Moreover, treatment with 15 g of oral glucose is often insufficient to reliably treat hypoglycemia during exercise in these youngsters.

Accuracy of the modified Continuous Glucose Monitoring System (CGMS) sensor in an outpatient setting: results from a diabetes research in children network (DirecNet) study.

OBJECTIVE: We previously reported the results of an inpatient accuracy study in children with type 1 diabetes using the Continuous Glucose Monitoring System (CGMS, Medtronic MiniMed, Northridge, CA). During the course of that study, a new process was implemented for manufacturing the CGMS sensor. Accuracy from the resulting modified sensor used by only 14 children was significantly better than the original version [median relative absolute difference (RAD), 11% vs. 19%; P < 0.001]. Baseline data from a subsequent outpatient study provide an opportunity to further assess the accuracy of the modified sensor in a much larger sample of children with type 1 diabetes. RESEARCH DESIGN AND METHODS: As part of a randomized trial to assess the utility of the GlucoWatch G2 Biographer (Cygnus, Inc., Redwood City, CA), 200 children with type 1 diabetes were instructed to wear a CGMS for 48-72 h in an outpatient setting at baseline. Glucose measurements from a OneTouch UltraSmart (Lifescan, Inc., Milpitas, CA) home glucose meter were downloaded and used as reference values to calculate accuracy measures. RESULTS: The overall median RAD was 12%. Accuracy was better during hyperglycemia than during hypoglycemia (median RAD, 10% vs. 20%; P < 0.001) and on optimal versus non-optimal days but did not vary significantly by the number of calibrations entered. CONCLUSIONS: These data confirm the improved accuracy previously reported for the modified version of the CGMS sensor.

A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients.

This report details the 26- and 36-yr outcomes of 116 patients under the age of 20 yr with Graves' disease who were treated with radioiodine between 1953 and 1973. Contacted by telephone and mail in 1991-1992, 107 of them supplied personal historical data, and their physicians furnished interval histories, physical examinations, and laboratory data. This was repeated in 2001-2002, with 98 of them being contacted. At the time of treatment, the patients' ages ranged between 3 yr, 7 months and 19 yr, 9 months. Six were less than 6 yr of age, 11 were between 6 and 11 yr, 45 were between 11 and 15 yr, and 45 were between 16 and 19 yr. The average length of follow-up in 1991-1992 was 26.1 yr; that in 2001-2002 was 36.2 yr. None of the patients developed cancer of the thyroid or leukemia. Early on, when the objective of treatment was euthyroidism, the dose of radioiodine was low, and retreatment was frequently needed. Later, the doses used were increased. Over time, all but two patients became hypothyroid. Pregnancies did not result in an unusual number of congenital anomalies or spontaneous abortions. Treating young people with Graves' disease with radioiodine is safe and effective over the long term.