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.

A Rare Presentation of New-Onset Type 1 Diabetes Mellitus in a Developmentally Delayed Child With an Overlap of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State.

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are serious complications associated with diabetes mellitus (DM). HHS is a common diagnosis in adults but rare in children. DKA is a usual presentation for new-onset type 1 DM, although HHS is rarely a manifestation of new-onset type 1 DM. Diagnosis and management of HHS are challenging in pediatric patients, especially if they present with a mixed picture of HHS and DKA. We report an adolescent female with a new onset of type 1 DM presented as mixed DKA and HHS. Treatment included meticulous management of fluids and continuous insulin drip with the resolution of acidosis within 24 hours and hyperosmolar state at 96 hours of admission. Early differentiation of these two entities and meticulous fluid management improves the outcome and decreases the risk of complications such as cerebral edema, renal failure, and thrombosis, among others.

A Pilot randomized trial to examine effects of a hybrid closed-loop insulin delivery system on neurodevelopmental and cognitive outcomes in adolescents with type 1 diabetes.

Type 1 diabetes (T1D) is associated with lower scores on tests of cognitive and neuropsychological function and alterations in brain structure and function in children. This proof-of-concept pilot study (ClinicalTrials.gov Identifier NCT03428932) examined whether MRI-derived indices of brain development and function and standardized IQ scores in adolescents with T1D could be improved with better diabetes control using a hybrid closed-loop insulin delivery system. Eligibility criteria for participation in the study included age between 14 and 17 years and a diagnosis of T1D before 8 years of age. Randomization to either a hybrid closed-loop or standard diabetes care group was performed after pre-qualification, consent, enrollment, and collection of medical background information. Of 46 participants assessed for eligibility, 44 met criteria and were randomized. Two randomized participants failed to complete baseline assessments and were excluded from final analyses. Participant data were collected across five academic medical centers in the United States. Research staff scoring the cognitive assessments as well as those processing imaging data were blinded to group status though participants and their families were not. Forty-two adolescents, 21 per group, underwent cognitive assessment and multi-modal brain imaging before and after the six month study duration. HbA1c and sensor glucose downloads were obtained quarterly. Primary outcomes included metrics of gray matter (total and regional volumes, cortical surface area and thickness), white matter volume, and fractional anisotropy. Estimated power to detect the predicted treatment effect was 0.83 with two-tailed, α = 0.05. Adolescents in the hybrid closed-loop group showed significantly greater improvement in several primary outcomes indicative of neurotypical development during adolescence compared to the standard care group including cortical surface area, regional gray volumes, and fractional anisotropy. The two groups were not significantly different on total gray and white matter volumes or cortical thickness. The hybrid closed loop group also showed higher Perceptual Reasoning Index IQ scores and functional brain activity more indicative of neurotypical development relative to the standard care group (both secondary outcomes). No adverse effects associated with study participation were observed. These results suggest that alterations to the developing brain in T1D might be preventable or reversible with rigorous glucose control. Long term research in this area is needed.

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.

Impact of Type 1 Diabetes in the Developing Brain in Children: A Longitudinal Study.

OBJECTIVE: To assess whether previously observed brain and cognitive differences between children with type 1 diabetes and control subjects without diabetes persist, worsen, or improve as children grow into puberty and whether differences are associated with hyperglycemia. RESEARCH DESIGN AND METHODS: One hundred forty-four children with type 1 diabetes and 72 age-matched control subjects without diabetes (mean ± SD age at baseline 7.0 ± 1.7 years, 46% female) had unsedated MRI and cognitive testing up to four times over 6.4 ± 0.4 (range 5.3-7.8) years; HbA1c and continuous glucose monitoring were done quarterly. FreeSurfer-derived brain volumes and cognitive metrics assessed longitudinally were compared between groups using mixed-effects models at 6, 8, 10, and 12 years. Correlations with glycemia were performed. RESULTS: Total brain, gray, and white matter volumes and full-scale and verbal intelligence quotients (IQs) were lower in the diabetes group at 6, 8, 10, and 12 years, with estimated group differences in full-scale IQ of -4.15, -3.81, -3.46, and -3.11, respectively (P < 0.05), and total brain volume differences of -15,410, -21,159, -25,548, and -28,577 mm3 at 6, 8, 10, and 12 years, respectively (P < 0.05). Differences at baseline persisted or increased over time, and brain volumes and cognitive scores negatively correlated with a life-long HbA1c index and higher sensor glucose in diabetes. CONCLUSIONS: Detectable changes in brain volumes and cognitive scores persist over time in children with early-onset type 1 diabetes followed longitudinally; these differences are associated with metrics of hyperglycemia. Whether these changes can be reversed with scrupulous diabetes control requires further study. These longitudinal data support the hypothesis that the brain is a target of diabetes complications in young children.

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.

COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multicenter Surveillance Study.

CONTEXT: Diabetes mellitus is associated with increased COVID-19 morbidity and mortality, but there are few data focusing on outcomes in people with type 1 diabetes. OBJECTIVE: The objective of this study was to analyze characteristics of adults with type 1 diabetes for associations with COVID-19 hospitalization. DESIGN: An observational multisite cross-sectional study was performed. Diabetes care providers answered a 33-item questionnaire regarding demographics, symptoms, and diabetes- and COVID-19-related care and outcomes. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between glycated hemoglobin (HbA1c), age, and comorbidities and hospitalization. SETTING: Cases were submitted from 52 US sites between March and August 2020. PATIENTS OR OTHER PARTICIPANTS: Adults over the age of 19 with type 1 diabetes and confirmed COVID-19 infection were included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospitalization for COVID-19 infection. RESULTS: A total of 113 cases were analyzed. Fifty-eight patients were hospitalized, and 5 patients died. Patients who were hospitalized were more likely to be older, to identify as non-Hispanic Black, to use public insurance, or to have hypertension, and less likely to use continuous glucose monitoring or insulin pumps. Median HbA1c was 8.6% (70 mmol/mol) and was positively associated with hospitalization (odds ratio 1.42, 95% confidence interval 1.18-1.76), which persisted after adjustment for age, sex, race, and obesity. CONCLUSIONS: Baseline glycemic control and access to care are important modifiable risk factors which need to be addressed to optimize care of people with type 1 diabetes during the worldwide COVID-19 pandemic.

Altered expression of SIRPγ on the T-cells of relapsing remitting multiple sclerosis and type 1 diabetes patients could potentiate effector responses from T-cells.

Factors regulating self-antigen directed immune-responses in autoimmunity are poorly understood. Signal regulatory protein gamma (SIRPγ) is a human T-cell specific protein with genetic variants associated with type 1 diabetes (T1D). SIRPγ's function in the immune system remains unclear. We show that T1D and relapsing remitting multiple sclerosis (RRMS) subjects have significantly greater frequency of rs2281808 T genetic variant, that correlates with reduced SIRPγ-expression in T-cells. Importantly, reduced SIRPγ-expression in RRMS and T1D subjects was not restricted to T variant, suggesting SIRPγ-expression is also regulated by disease specific factors in autoimmunity. Interestingly, increased frequencies of SIRPγlow T-cells in RRMS and T1D positively correlated with proinflammatory molecules from T-cells. Finally, we show that SIRPγlow T-cells have enhanced pathogenecity in vivo in a GVHD model. These findings suggest that decreased-SIRPγ expression, either determined by genetic variants or through peripherally acquired processes, may have a mechanistic link to autoimmunity through induction of hyperactive T-cells.

Brain Function Differences in Children With Type 1 Diabetes: A Functional MRI Study of Working Memory.

Glucose is a primary fuel source to the brain, yet the influence of dysglycemia on neurodevelopment in children with type 1 diabetes remains unclear. We examined brain activation using functional MRI in 80 children with type 1 diabetes (mean ± SD age 11.5 ± 1.8 years; 46% female) and 47 children without diabetes (control group) (age 11.8 ± 1.5 years; 51% female) as they performed a visuospatial working memory (N-back) task. Results indicated that in both groups, activation scaled positively with increasing working memory load across many areas, including the frontoparietal cortex, caudate, and cerebellum. Between groups, children with diabetes exhibited reduced performance on the N-back task relative to children in the control group, as well as greater modulation of activation (i.e., showed greater increase in activation with higher working memory load). Post hoc analyses indicated that greater modulation was associated in the diabetes group with better working memory function and with an earlier age of diagnosis. These findings suggest that increased modulation may occur as a compensatory mechanism, helping in part to preserve working memory ability, and further, that children with an earlier onset require additional compensation. Future studies that test whether these patterns change as a function of improved glycemic control are warranted.

Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Participants: A Multicenter Prospective Study.

CONTEXT: Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking. OBJECTIVE: To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor. DESIGN: Multicenter, prospective study. SETTING: Twelve centers within the T1D Exchange Clinic Network. PATIENTS OR PARTICIPANTS: Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index. INTERVENTION: Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days. MAIN OUTCOME MEASURES: CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. RESULTS: A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d). CONCLUSION: By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies.

Metformin Improves Peripheral Insulin Sensitivity in Youth With Type 1 Diabetes.

CONTEXT: Type 1 diabetes in adolescence is characterized by insulin deficiency and insulin resistance (IR), both thought to increase cardiovascular disease risk. We previously demonstrated that adolescents with type 1 diabetes have adipose, hepatic, and muscle IR, and that metformin lowers daily insulin dose, suggesting improved IR. However, whether metformin improves IR in muscle, hepatic, or adipose tissues in type 1 diabetes was unknown. OBJECTIVE: Measure peripheral, hepatic, and adipose insulin sensitivity before and after metformin or placebo therapy in youth with obesity with type 1 diabetes. DESIGN: Double-blind, placebo-controlled clinical trial. SETTING: Multi-center at eight sites of the T1D Exchange Clinic Network. PARTICIPANTS: A subset of 12- to 19-year-olds with type 1 diabetes (inclusion criteria: body mass index ≥85th percentile, HbA1c 7.5% to 9.9%, insulin dosing ≥0.8 U/kg/d) from a larger trial (NCT02045290) were enrolled. INTERVENTION: Participants were randomized to 3 months of metformin (N = 19) or placebo (N = 18) and underwent a three-phase hyperinsulinemic euglycemic clamp with glucose and glycerol isotope tracers to assess tissue-specific IR before and after treatment. MAIN OUTCOME MEASURES: Peripheral insulin sensitivity, endogenous glucose release, rate of lipolysis. RESULTS: Between-group differences in change in insulin sensitivity favored metformin regarding whole-body IR [change in glucose infusion rate 1.3 (0.1, 2.4) mg/kg/min, P = 0.03] and peripheral IR [change in metabolic clearance rate 0.923 (-0.002, 1.867) dL/kg/min, P = 0.05]. Metformin did not impact insulin suppression of endogenous glucose release (P = 0.12). Adipose IR was not assessable with traditional methods in this highly IR population. CONCLUSIONS: Metformin appears to improve whole-body and peripheral IR in youth who are overweight/obese with type 1 diabetes.

Individual glucose responses to prolonged moderate intensity aerobic exercise in adolescents with type 1 diabetes: The higher they start, the harder they fall.

OBJECTIVE: To evaluate the pattern of change in blood glucose concentrations and hypoglycemia risk in response to prolonged aerobic exercise in adolescents with type 1 diabetes (T1D) that had a wide range in pre-exercise blood glucose concentrations. METHODS: Individual blood glucose responses to prolonged (~60 minutes) moderate-intensity exercise were profiled in 120 youth with T1D. RESULTS: The mean pre-exercise blood glucose concentration was 178 ± 66 mg/dL, ranging from 69 to 396 mg/dL, while the mean change in glucose during exercise was -76 ± 55 mg/dL (mean ± SD), ranging from +83 to -257 mg/dL. Only 4 of 120 youth (3%) had stable glucose levels during exercise (ie, ± ≤10 mg/dL), while 4 (3%) had a rise in glucose >10 mg/dL, and the remaining (93%) had a clinically significant drop (ie, >10 mg/dL). A total of 53 youth (44%) developed hypoglycemia (≤70 mg/dL) during exercise. The change in glucose was negatively correlated with the pre-exercise glucose concentration (R2 = 0.44, P < 0.001), and tended to be greater in those on multiple daily insulin injections (MDI) vs continuous subcutaneous insulin infusion (CSII) (-98 ± 15 vs -65 ± 7 mg/dL, P = 0.05). No other collected variables appeared to predict the change in glucose including age, weight, height, body mass index, disease duration, daily insulin dose, HbA1c , or sex. CONCLUSION: Youth with T1D have variable glycemic responses to prolonged aerobic exercise, but this variability is partially explained by their pre-exercise blood glucose levels. When no implementation strategies are in place to limit the drop in glycemia, the incidence of exercise-associated hypoglycemia is ~44% and having a high pre-exercise blood glucose concentration is only marginally protective.

Autoimmunity-associated intronic SNP (rs2281808) detected by a simple phenotypic assay: Unique case or broader opportunity?

Multiple genome-wide association studies have shown that the single-nucleotide polymorphism (SNP) rs2281808 TT variant, present within the signal regulatory protein gamma (SIRPG) gene, is associated with autoimmune diseases, such as type 1 diabetes. SIRPγ is the only SIRP expressed on T cells. The role of SIRPγ in human T-cells or the effect of the TT variant are poorly understood. In this short report, we demonstrate the rather unusual finding that this intronic SNP is associated with a reduction of SIRPγ expression on T cells, both in healthy subjects as well as patients with type 1 diabetes. Using this information, we propose that a simple flow cytometric detection of SIRPγ could be a potential diagnostic testing approach for the presence of SNP in the appropriate clinical context.

An autoimmune disease risk SNP, rs2281808, in SIRPG is associated with reduced expression of SIRPγ and heightened effector state in human CD8 T-cells.

Multiple GWAS studies have shown that the SNP rs2281808 TT variant, present within the SIRPG gene, is associated with autoimmune diseases, such as type 1 diabetes. However, the role of SIRPγ in human T-cells is not known, neither is the functional significance of TT variant. Here we investigated SIRPG genotypes and their effects on the fate and function of human T-cells. We found that the presence of T variant resulted in reduction of SIRPγ expression on T-cells. Functionally, SIRPγlow CD8 T-cells in CT and TT individuals existed in a heightened effector state with lower activation threshold and had greater expression of genes and molecules associated with migratory and cytotoxic potential. Further, SIRPγlow CD8 T-cells were deficient in transcription factors associated with long-term functional memory formation. Our study reveals biological consequences of the SNP rs2281808 and provides novel insights into the potential mechanisms by which SIRPγ might regulate human immune responses.

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.

Vitamin D Toxicity: A 16-Year Retrospective Study at an Academic Medical Center.

BACKGROUND: Interest in vitamin D has increased during the past 2 decades, with a corresponding increase in laboratory testing of 25-hydroxyvitamin D [25(OH)D]. The vast majority of specimens tested display normal or deficient levels of 25(OH)D; concentrations rarely fall in the potentially toxic range. METHODS: We performed a retrospective investigation of elevated 25(OH)D levels during a 16-year period at the University of Iowa Hospitals and Clinics (UIHC), a 734-bed tertiary-/quaternary-care academic medical center in the midwestern United States. Detailed medical-record review was performed for patients with serum/plasma 25(OH)D concentrations higher than 120 ng per mL. RESULTS: A total of 127,932 serum/plasma 25(OH)D measurements were performed on 73,779 unique patients. Of these patients, 780 (1.05%) had results that exceeded 80 ng per mL and 89 patients (0.12%) had results that exceeded 120 ng per mL. Only 4 patients showed symptoms of vitamin D toxicity. Three of these cases involved inadvertent misdosing of liquid formulations. CONCLUSIONS: Symptomatic vitamin D toxicity is uncommon, and elevated levels of 25(OH)D do not strongly correlate with clinical symptoms or total serum/plasma calcium levels. Our study highlights the potential risks of the liquid formulation of vitamin D.

Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months.

OBJECTIVES: Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. METHODS: A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. RESULTS: Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. CONCLUSIONS: The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.

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.