Glycemic Measures in Childhood as Predictors of Future Diabetes-Related Microvascular Complications in an Indigenous American Population.

OBJECTIVE: To examine the role of glycemic measures performed during childhood in predicting future diabetes-related nephropathy and retinopathy in a high-risk indigenous American cohort. RESEARCH DESIGN AND METHODS: We studied associations between glycated hemoglobin (HbA1c) and 2-h plasma glucose (PG), measured during childhood (age 5 to <20 years) in a longitudinal observational study of diabetes and its complications (1965-2007), and future albuminuria (albumin creatinine ratio [ACR] ≥30 mg/g), severe albuminuria (ACR ≥300 mg/g), and retinopathy (at least one microaneurysm or hemorrhage or proliferative retinopathy on direct ophthalmoscopy). Areas under the receiver operating characteristic curve (AUCs) for childhood glycemic measures when predicting nephropathy and retinopathy were compared. RESULTS: Higher baseline levels of HbA1c and 2-h PG significantly increased the risk of future severe albuminuria (HbA1c: hazard ratio [HR] 1.45 per %; 95% CI 1.02-2.05 and 2-h PG: HR 1.21 per mmol/L; 95% CI 1.16-1.27). When categorized by baseline HbA1c, children with prediabetes had a higher incidence of albuminuria (29.7 cases per 1,000 person-years [PY]), severe albuminuria (3.8 cases per 1,000 PY), and retinopathy (7.1 cases per 1,000 PY) than children with normal HbA1c levels (23.8, 2.4, and 1.7 cases per 1,000 PY, respectively); children with diabetes at baseline had the highest incidence of the three complications. No significant differences were observed between AUCs for models with HbA1c, 2-h PG, and fasting PG when predicting albuminuria, severe albuminuria, or retinopathy. CONCLUSIONS: In this study, higher glycemia levels ascertained by HbA1c and 2-h PG during childhood were associated with future microvascular complications; this demonstrates the potential utility of screening tests performed in high-risk children in predicting long-term health outcomes.

Adolescent Growth Spurt and Type 2 Diabetes Risk in Southwestern American Indians.

Early puberty onset is associated with higher risk of diabetes, but most studies have not accounted for childhood factors that may confound the association. Using data from a study conducted in an Indigenous community in Arizona (1965-2007), we examined associations of timing and velocity of the adolescent growth spurt with type 2 diabetes, and whether these associations are mediated by childhood body mass index and insulinemia. Adolescent growth parameters were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, for 861 participants with height measurements spanning the whole period of growth. In males, older age at take-off, age at peak velocity, and age at maturation were associated with decreased prevalence of diabetes (odds ratio (OR) = 0.43 per year, 95% confidence interval (CI): 0.27, 0.69; OR = 0.50, 95% CI: 0.35, 0.72; OR = 0.58, 95% CI: 0.41, 0.83, respectively), while higher velocity at take-off was associated with increased risk (OR = 3.47 per cm/year, 95% CI: 1.87, 6.42) adjusting for age, birth year, and maternal diabetes. Similar results were observed with incident diabetes. Our findings suggest that an early and accelerated adolescent growth spurt is a risk factor for diabetes, at least in males. These associations are only partially explained by measures of adiposity and insulinemia.

The utility of a type 2 diabetes polygenic score in addition to clinical variables for prediction of type 2 diabetes incidence in birth, youth and adult cohorts in an Indigenous study population.

AIMS/HYPOTHESIS: There is limited information on how polygenic scores (PSs), based on variants from genome-wide association studies (GWASs) of type 2 diabetes, add to clinical variables in predicting type 2 diabetes incidence, particularly in non-European-ancestry populations. METHODS: For participants in a longitudinal study in an Indigenous population from the Southwestern USA with high type 2 diabetes prevalence, we analysed ten constructions of PS using publicly available GWAS summary statistics. Type 2 diabetes incidence was examined in three cohorts of individuals without diabetes at baseline. The adult cohort, 2333 participants followed from age ≥20 years, had 640 type 2 diabetes cases. The youth cohort included 2229 participants followed from age 5-19 years (228 cases). The birth cohort included 2894 participants followed from birth (438 cases). We assessed contributions of PSs and clinical variables in predicting type 2 diabetes incidence. RESULTS: Of the ten PS constructions, a PS using 293 genome-wide significant variants from a large type 2 diabetes GWAS meta-analysis in European-ancestry populations performed best. In the adult cohort, the AUC of the receiver operating characteristic curve for clinical variables for prediction of incident type 2 diabetes was 0.728; with the PS, 0.735. The PS's HR was 1.27 per SD (p=1.6 × 10-8; 95% CI 1.17, 1.38). In youth, corresponding AUCs were 0.805 and 0.812, with HR 1.49 (p=4.3 × 10-8; 95% CI 1.29, 1.72). In the birth cohort, AUCs were 0.614 and 0.685, with HR 1.48 (p=2.8 × 10-16; 95% CI 1.35, 1.63). To further assess the potential impact of including PS for assessing individual risk, net reclassification improvement (NRI) was calculated: NRI for the PS was 0.270, 0.268 and 0.362 for adult, youth and birth cohorts, respectively. For comparison, NRI for HbA1c was 0.267 and 0.173 for adult and youth cohorts, respectively. In decision curve analyses across all cohorts, the net benefit of including the PS in addition to clinical variables was most pronounced at moderately stringent threshold probability values for instituting a preventive intervention. CONCLUSIONS/INTERPRETATION: This study demonstrates that a European-derived PS contributes significantly to prediction of type 2 diabetes incidence in addition to information provided by clinical variables in this Indigenous study population. Discriminatory power of the PS was similar to that of other commonly measured clinical variables (e.g. HbA1c). Including type 2 diabetes PS in addition to clinical variables may be clinically beneficial for identifying individuals at higher risk for the disease, especially at younger ages.

Lessons on Resilient Research: Adapting the Tribal Turning Point Study to COVID-19.

Tribal Turning Point (TTP) is a community-based randomized controlled trial of a lifestyle intervention to reduce risk factors for type 2 diabetes in Native youth. TTP began in 2018 and was interrupted by the COVID-19 pandemic in 2020. In this paper we aimed to understand 1) how the pandemic impacted TTP's operations, and how the TTP team successfully adapted to these impacts; 2) how the effects of COVID-19 and our adaptations to them were similar or different across TTP's research sites; and 3) lessons learned from this experience that may help other Native health research teams be resilient in this and future crises. Using a collaborative mixed methods approach, this report explored five a priori domains of adaptation: intervention delivery, participant engagement, data collection, analytic strategies, and team operations. We derived three lessons learned: 1) ensure that support offered is flexible to differing needs and responsive to changes over time; 2) adapt collaboratively and iteratively while remaining rooted in community; and 3) recognize that relationships are the foundation of successful research.

Increased Adiposity and Low Height-for-Age in Early Childhood Are Associated With Later Metabolic Risks in American Indian Children and Adolescents.

BACKGROUND: Growth abnormalities in childhood have been related to later cardiometabolic risks, but little is known about these associations in populations at high risk of type 2 diabetes. OBJECTIVES: We examined the associations of patterns of growth, including weight and height at ages 1-59 months, with cardiometabolic risk factors at ages 5-16 years. METHODS: We linked anthropometric data collected at ages 1-59 months to cardiometabolic data obtained from a longitudinal study in a southwestern American Indian population at high risk of diabetes. Analyses included 701 children with ≥1 follow-up examination at ages 5-16 years. We derived age- and sex-specific weight-for-height z-scores (WHZ) and height-for-age z-scores (HAZ) at ages 1-59 months. We selected the highest observed WHZ and the lowest observed HAZ at ages 1-59 months and analyzed associations of z-scores and categories of WHZ and HAZ with cardiometabolic outcomes at ages 5-16 years. We used linear mixed-effects models to account for repeated measures. RESULTS: Overweight/obesity (WHZ >2) at ages 1-59 months was significantly associated with increased BMI, fasting and 2-hour postload plasma glucose, fasting and 2-hour insulin, triglycerides, systolic blood pressure, diastolic blood pressure, and decreased HDL cholesterol at ages 5-16 years relative to normal weight (WHZ ≤1). For example, at ages 5-9 years, 2-hour glucose was 10.4 mg/dL higher (95% CI: 5.6-15.3 mg/dL) and fasting insulin was 4.29 µU/mL higher (95% CI: 2.96-5.71 µU/mL) in those with overweight/obesity in early childhood. Associations were attenuated and no longer significant when adjusted for concurrent BMI. A low height-for-age (HAZ < -2) at ages 1-59 months was associated with 5.37 mg/dL lower HDL (95% CI: 2.57-8.17 mg/dL) and 27.5 µU/mL higher 2-hour insulin (95% CI: 3.41-57.6 µU/mL) at ages 10-16 years relative to an HAZ ≥0. CONCLUSIONS: In this American Indian population, findings suggest a strong contribution of overweight/obesity in early childhood to cardiometabolic risks in later childhood and adolescence, mediated through persistent overweight/obesity into later ages. Findings also suggest potential adverse effects of low height-for-age, which require confirmation.

Increase in the Number of Pediatric New-Onset Diabetes and Diabetic Ketoacidosis Cases During the COVID-19 Pandemic.

OBJECTIVE: Infection with SARS-CoV-2 induces a proinflammatory state that causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA) in patients with known or new-onset diabetes. We examined the trends in new-onset diabetes and DKA prior to and following the onset of the COVID-19 pandemic. METHODS: This single-center retrospective observational study included pediatric patients (aged 0 to <18 years) hospitalized with new-onset type 1 diabetes or type 2 diabetes (T2D) before (March 1, 2018, to February 29, 2020) and after (March 1, 2020 to December 31, 2020) the pandemic onset. Demographic, anthropometrics, laboratory and clinical data, and outcomes were obtained. RESULTS: Among 615 children admitted with new-onset diabetes during the entire study period, 401 were admitted before the pandemic onset, and 214 were admitted after the pandemic onset. Children admitted with new-onset diabetes in the postpandemic period were significantly more likely to present with DKA (odds ratio, 1.76; 95% confidence interval, 1.24-2.52) than in the prepandemic phase. Children with DKA after the pandemic onset had higher lengths of hospitalization and were significantly more likely to experience severe DKA (odds ratio, 2.17; 95% confidence interval, 1.34-3.52). A higher proportion of children with DKA admitted to the pediatric intensive care unit required oxygen support after the pandemic onset than before the pandemic onset (8.85% vs 1.92%). Most cases of T2D with DKA occurred following the onset of the pandemic (62.5%). CONCLUSION: A significant increase in T2D cases occurred following the onset of the COVID-19 pandemic with a greater risk of DKA and severe ketoacidosis. Racial disparity was evident with a higher proportion of Black and American Indian children presenting with ketoacidosis following the pandemic onset.

Pediatric Cervical Spine Clearance and Immobilization Practice Among Prehospital Emergency Medical Providers: A Statewide Survey.

OBJECTIVES: Pediatric cervical spine injuries are rare but potentially life threatening. Although published guidelines for assessment of such injuries exist, there is less uniformity in its implementation in out-of-hospital settings. Our purpose was to assess the knowledge and practice patterns for pediatric cervical spine immobilization among prehospital emergency medical services (EMS) providers in Arizona. METHODS: A cross-sectional web-based survey was conducted (October-December 2018), using an electronic mailing list of certified EMS providers (ground and air) in Arizona. A 20-question structured web-based survey was developed and deployed. RESULTS: One hundred eight EMS stations were contacted with the survey. Sixty-eight providers responded; majority were emergency medical paramedics (73.1%). Most of the stations surveyed did not have a pediatric trauma center (66.2%). When treating children younger than 3 years, half of the respondents stated they did not know of a specific cervical spine clearance criterion; 59.3% felt that cervical spine immobilization was required "sometimes," and 40.0% were unaware of the state's EMS pediatric cervical spine clearance algorithm; 93.9% of EMS providers felt that an age-based algorithm for cervical spine clearance in children would be useful. CONCLUSIONS: In this statewide survey involving prehospital EMS providers, we found that pediatric cervical spine clearance and immobilization practices, even within a specific geographic location, remain inconsistent.

Role of Salivary Biomarkers in Predicting Significant Traumatic Brain Injury: An Exploratory Study.

OBJECTIVES: The highest rates of traumatic brain injury (TBI)-related morbidity and mortality occur in young children and adolescents. The objective of this study was to describe the levels of 3 biomarkers (S100B, glial fibrillary acidic protein, neuron-specific enolase) in saliva of children with TBI requiring inpatient admission at a pediatric trauma center and compare these levels in children without TBI. METHODS: A convenience sample of 24 children aged 0 to 18 years, presenting with acute isolated TBI, was enrolled prospectively. The non-TBI comparison groups consisted of patients with medical complaints and musculoskeletal injuries only. Salivary specimens were collected, and biomarkers were measured using quantitative enzyme-linked immunosorbent assay method. Demographic, clinical data, and brain imaging findings were obtained. RESULTS: Seventy-four children were enrolled. Twenty-four had TBI (mean age, 5.07 years; SD, 4.8 years); 14 subjects (58.3%) with TBI were found to have significant traumatic brain injury (SBI) on computed tomography scan. S100B levels were significantly higher in TBI group compared with those with musculoskeletal injury only (median, 113.2 pg/mL vs 18 pg/mL; P = 0.021). Area under the receiver operating characteristic curve for S100B in predicting SBI was 0.675; the optimum threshold for S100B to achieve the optimum sensitivity and specificity of SBI was at 86.9 pg/mL for SBI versus no injury group. CONCLUSIONS: S100B levels in saliva were higher in children with TBI and may be predictive of SBI identified by presence of computed tomography abnormalities. Larger studies are needed to replicate our findings in using a noninvasive diagnostic measure for children with TBI and SBI.

Assessment of the potential role of natural selection in type 2 diabetes and related traits across human continental ancestry groups: comparison of phenotypic with genotypic divergence.

AIMS/HYPOTHESIS: Prevalence of type 2 diabetes differs among human ancestry groups, and many hypotheses invoke differential natural selection to account for these differences. We sought to assess the potential role of differential natural selection across major continental ancestry groups for diabetes and related traits, by comparison of genetic and phenotypic differences. METHODS: This was a cross-sectional comparison among 734 individuals from an urban sample (none of whom was more closely related to another than third-degree relatives), including 83 African Americans, 523 American Indians and 128 European Americans. Participants were not recruited based on diabetes status or other traits. BMI was calculated, and diabetes was diagnosed by a 75 g oral glucose tolerance test. In those with normal glucose tolerance (n = 434), fasting insulin and 30 min post-load insulin, adjusted for 30 min glucose, were taken as measures of insulin resistance and secretion, respectively. Whole exome sequencing was performed, resulting in 97,388 common (minor allele frequency ≥ 5%) variants; the coancestry coefficient (FST) was calculated across all markers as a measure of genetic divergence among ancestry groups. The phenotypic divergence index (PST) was also calculated from the phenotypic differences and heritability (which was estimated from genetic relatedness calculated empirically across all markers in 761 American Indian participants prior to the exclusion of close relatives). Under evolutionary neutrality, the expectation is PST = FST, while for traits under differential selection PST is expected to be significantly greater than FST. A bootstrap procedure was used to test the hypothesis PST = FST. RESULTS: With adjustment for age and sex, prevalence of type 2 diabetes was 34.0% in American Indians, 12.4% in African Americans and 10.4% in European Americans (p = 2.9 × 10-10 for difference among groups). Mean BMI was 36.3, 33.4 and 33.0 kg/m2, respectively (p = 1.9 × 10-7). Mean fasting insulin was 63.8, 48.4 and 45.2 pmol/l (p = 9.2 × 10-5), while mean 30 min insulin was 559.8, 553.5 and 358.8 pmol/l, respectively (p = 5.7 × 10-8). FST across all markers was 0.130, while PST for liability to diabetes, adjusted for age and sex, was 0.149 (p = 0.35 for difference with FST). PST was 0.094 for BMI (p = 0.54), 0.095 for fasting insulin (p = 0.54) and 0.216 (p = 0.18) for 30 min insulin. For type 2 diabetes and BMI, the maximum divergence between populations was observed between American Indians and European Americans (PST-MAX = 0.22, p = 0.37, and PST-MAX = 0.14, p = 0.61), which suggests that a relatively modest 22% or 14% of the genetic variance, respectively, can potentially be explained by differential selection (assuming the absence of neutral drift). CONCLUSIONS/INTERPRETATION: These analyses suggest that while type 2 diabetes and related traits differ significantly among continental ancestry groups, the differences are consistent with neutral expectations based on heritability and genetic distances. While these analyses do not exclude a modest role for natural selection, they do not support the hypothesis that differential natural selection is necessary to explain the phenotypic differences among these ancestry groups. Graphical abstract.

Age-Based Characteristics of Pediatric Burn Injuries From Outdoor Recreational Fires.

Accidental burns from outdoor recreational activities, such as campfires, bonfires, ceremonial fires, and firepits, are not uncommon; however, few studies describe the nature of such injuries in children. The objective of this study was to examine the age-based pattern of pediatric burn injuries from outdoor fires. Children and adolescents 0 to 18 years, admitted to the Burn Center between 2008 and 2018 with acute burn injuries from outdoor fires, were included in the current study. Demographic and clinical data were obtained from the burn injury database. Patients were categorized into three age groups: 0 to 5 years, 5 to 10 years, and 10 to 18 years. One hundred and sixty-seven children were included in the data analysis, the mean age of the cohort was 6.4 (SD ± 4.9) years, and the majority (66.5%) were males. More than half (52.1%) were less than 5 years of age, they commonly sustained hand burns and frequently required inpatient burn management. Burn severity varied between age groups, and the mean total burn surface area (TBSA) was significantly higher in adolescents (10.9%). Almost half the injuries (49.7%) resulted from a fall onto a campfire, bonfire, or a firepit. In this study, we found age-specific variation in the mechanism and pattern of burn injuries. Children at least 5 years and adolescents were least common victims of burns due to outdoor fires but suffered from more serious injuries with significantly higher TBSA involvement, longer intensive care unit, and ventilator days. Raising awareness among parents, caregivers, and children about outdoor fire safety is important for the prevention of such injuries.

Weight tracking in childhood and adolescence and type 2 diabetes risk.

AIMS/HYPOTHESIS: The aim of this work was to examine the associations of average weight and weight velocity in three growth periods from birth through adolescence with type 2 diabetes incidence. METHODS: Child participants were selected from a 43 year longitudinal study of American Indians to represent three growth periods: pre-adolescence (birth to ~8 years); early adolescence (~8 to ~13 years); and late adolescence (~13 to ~18 years). Age-, sex- and height-standardised weight z score mean and weight z score velocity (change/year) were computed for each period. Participants were followed for up to 25 years from the end of each growth period until they developed diabetes. Associations of weight z score mean or weight z score velocity with diabetes incidence were determined with sex-, birth date- and maternal diabetes-adjusted Poisson regression models. RESULTS: Among 2100 participants representing the pre-adolescence growth period, 1558 representing the early adolescence period and 1418 representing the late adolescence period, there were 290, 315 and 380 incident diabetes cases, respectively. During the first 10 years of follow-up, the diabetes incidence rate ratio (95% CI) was 1.72 (1.40, 2.11)/SD of log10 weight z score mean in pre-adolescence, 2.09 (1.68, 2.60)/SD of log10 weight z score mean in early adolescence and 1.85 (1.58, 2.17)/SD of log10 weight z score mean in late adolescence. The diabetes incidence rate ratio (95% CI) was 1.79 (1.49, 2.17)/SD of log10 weight z score velocity in pre-adolescence, 1.13 (0.91, 1.41)/SD of log10 weight z score velocity in early adolescence and 1.29 (1.09, 1.51)/SD of log10 weight z score velocity in late adolescence. There were strong correlations in the weight z score means and weak correlations in the weight z score velocities between successive periods. CONCLUSIONS/INTERPRETATION: Higher weight and accelerated weight gain in all growth periods associate with increased type 2 diabetes risk. Importantly, higher weight and greater weight velocity during pre-adolescence jointly associate with the highest type 2 diabetes risk. Graphical abstract.

Provider Preference for Growth Charts in Tracking Children with Obesity.

A web-based survey of pediatric care providers revealed differences in their preference for clinical charts that monitor growth in children with obesity. These findings are attributed to pediatric specialty training. Very few providers believe the currently available Centers for Disease Control and Prevention 2000 body mass index-for-age charts adequately track growth in children with obesity.

Birthweight and early-onset type 2 diabetes in American Indians: differential effects in adolescents and young adults and additive effects of genotype, BMI and maternal diabetes.

AIMS/HYPOTHESIS: The aim of this work was to estimate the impact of birthweight on early-onset (age <40 years) type 2 diabetes. METHODS: A longitudinal study of American Indians, aged ≥5 years, was conducted from 1965 to 2007. Participants who had a recorded birthweight were followed until they developed diabetes or their last examination before the age of 40 years, whichever came first. Age- and sex-adjusted diabetes incidence rates were computed and Poisson regression was used to model the effect of birthweight on diabetes incidence, adjusted for sex, BMI, a type 2 diabetes susceptibility genetic risk score (GRS) and maternal covariates. RESULTS: Among 3039 participants, there were 652 incident diabetes cases over a median follow-up of 14.3 years. Diabetes incidence increased with age and was greater in the lowest and highest quintiles of birthweight. Adjusted for covariates, the effect of birthweight on diabetes varied over time, with a non-linear effect at 10-19 years (p < 0.001) and a negative linear effect at older age intervals (20-29 years, p < 0.001; 30-39 years, p = 0.003). Higher GRS, greater BMI and maternal diabetes had additive but not interactive effects on the association between birthweight and diabetes incidence. CONCLUSIONS/INTERPRETATION: In this high-risk population, both low and high birthweights were associated with increased type 2 diabetes risk in adolescence (age 10-19 years) but only low birthweight was associated with increased risk in young adulthood (20-39 years). Higher type 2 diabetes GRS, greater BMI and maternal diabetes added to the risk of early-onset diabetes.

Use of graded Semmes Weinstein monofilament testing for ascertaining peripheral neuropathy in people with and without diabetes.

AIMS: To assess peripheral neuropathy (PN) using graded Semmes Weinstein monofilaments (SWMs) and determine factors associated with PN among adult volunteers with and without diabetes. METHODS: Adult volunteers were assessed for distal sensory PN using three graded SWMs. Four PN levels were defined: 0 (no PN; felt all three filaments), 1 (subclinical PN; insensate to 1-g filament), 2 (insensate to 10-g), or 3 (insensate to 75-g). Levels 2-3 were considered clinical PN. Associations with PN were determined using ordinal logistic regression. RESULTS: In 1564 subjects (median age 41.9 years, 50.1% women), PN was subclinical or worse in 68.9% and clinical in 11.2%. Age-sex-race-adjusted prevalence of clinical PN was greater in people with diabetes (15.3%) than without (6.1%; P < 0.001). Associated factors included older age, male sex, greater BMI, greater heart rate, lower mean arterial pressure, and family history of diabetes or cardiovascular diseases. Higher PN levels associated with worse albuminuria and retinopathy. Only older age and male sex associated with PN both in people with and without diabetes. CONCLUSIONS: PN is common in our sample, notably in those without diabetes, although diabetes greatly increases its risk. Using graded SWMs may have a prognostic value as it permits the identification of subclinical PN.

Comparing clinical outcomes between two scorpion antivenom dosing strategies in children.

Background and Objectives: The clinical course from scorpion envenomation can range from mild to life threatening, particularly in younger children. The F(ab')2 antivenom currently available in the United States is extremely effective for countering the neurotoxic effects but extremely expensive. This dose comparison study assesses clinical outcomes between two antivenom dosing strategies. Methods: This was a retrospective review of medical records of pediatric patients treated in the pediatric emergency department (PED) with grade 3 or 4 envenomation requiring antivenom. Treatments rendered at two time-periods were assessed: 3-vial first dose (May 2007-August 2011) and single-vial-serial dose (September 2011-June 2016). Primary outcome was the proportion of patients who achieved complete symptom resolution within 4 h post antivenom dose. Results: One hundred and forty-one children met entry criteria, 76 in 3-vial first dose and 65 in single-vial-serial dose. Median age was 4 years (Q1:2-Q3:7), 56.2% males. There were no demographic and differences in clinical severity at presentation between the two dosing groups. All children, irrespective of group assignment, achieved the primary end-point of symptom resolution within 4 h. Median time to complete resolution of symptoms was longer for the single-vial-serial-dosing group vs. the 3-vial-first dose group [90 min (Q1:63-Q3:124) vs. 62 min (Q1:40-Q3:90), p = 0.002]. There were no statistically significant differences between the two groups regarding clinical outcomes including PED discharge, intubation, hospitalization, or death. Conclusion: In this retrospective analysis, children in both single-vial-serial dosing group, and 3-vial-full dosing group, achieved symptom resolution within 4 h of initiating therapy with no additional complications or adverse clinical outcomes.

Effect of severe obesity in childhood and adolescence on risk of type 2 diabetes in youth and early adulthood in an American Indian population.

OBJECTIVES: The risk of early-onset type 2 diabetes associated with the severity of obesity in youth is not well understood. This study aims to determine metabolic alterations and type 2 diabetes risk among American Indian children who are obese or severely obese. METHODS: Incidence rates of diabetes before 20 years (youth-onset) and 45 years were computed in 2728 children who were from 5 to <10 years and 4317 adolescents who were from 10 to <18 years without diabetes examined between 1965 and 2007. Obesity was defined as age-sex-adjusted body mass index (BMI) ≥95th percentile, and its severity was quantified as the percentage of the 95th percentile (%BMIp95 ). RESULTS: In the younger cohort, 0.9% of those non-obese and 2.9% of those with 100% to <120%BMIp95 had impaired glucose tolerance (IGT) compared to 8.6% of those with ≥140%BMIp95 . In the older cohort, 2.9% of those non-obese and 9.8% of those with 100% to <120%BMIp95 had IGT compared to 13.3% of those with ≥160%BMIp95 . The incidence of youth-onset diabetes was 3.8 and 4.9/1000 person-years in the child and adolescent cohorts, respectively, and before the age of 45 was 12.3 and 16.8/1000 person-years, respectively. Incidence rates of youth-onset diabetes in those with the most severe obesity (≥140%BMIp95 ) were 2.3 to 5.1 times as high as in those with the least severe obesity (100 to <120%BMIp95 ), and for onset of diabetes before the age of 45 were 1.6 to 2.2 times as high. CONCLUSIONS: Severe obesity in an American Indian population is a major driver of type 2 diabetes developing in adolescents and young adults.

Growth Tracking in Severely Obese or Underweight Children.

OBJECTIVES: To illustrate the difficulties in optimal growth monitoring of children with severe obesity or underweight by using the Centers for Disease Control and Prevention (CDC) 2000 age- and sex-specific BMI percentile growth charts. We also aimed to examine the utility of a new modified CDC BMI z score chart to monitor growth in children with normal and extreme BMI percentiles by using real-life clinical scenarios. METHODS: Modified BMI z score charts were created by using the 2000 CDC algorithm. Three cases of children with extreme BMI values and abnormal growth patterns were plotted by using the standard CDC 2000 clinical growth chart, the modified BMI z score chart, and the CDC BMI percentile chart, modified to include the percentage of the 95th percentile (%BMIp95) curves. RESULTS: Children with severe obesity could not be plotted on the standard CDC BMI percentile chart because their BMI points lay above the chart cutoff. Children with a low BMI (<3%) were also difficult to track on the standard BMI percentile chart. The addition of the %BMIp95 scale to the standard BMI percentile chart allowed tracking of severely obese children; however, it did not address severely underweight children and required a change of units within the chart when transitioning from normal to obese BMIs. The modified BMI z score chart allowed uniform tracking. CONCLUSIONS: The modified CDC z score chart is suitable for growth tracking of children with normal and extreme growth patterns; the measures correlate well with the %BMIp95, and the chart can be incorporated easily into existing electronic health record systems for clinical use.

HbA1c and the Prediction of Type 2 Diabetes in Children and Adults.

OBJECTIVE: Long-term data validating glycated hemoglobin (HbA1c) in assessing the risk of type 2 diabetes in children are limited. HbA1c, fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population. RESEARCH DESIGN AND METHODS: Incident diabetes (FPG ≥126 mg/dL [7.0 mmol/L], 2hPG ≥200 mg/dL [11.1 mmol/L], HbA1c ≥6.5% [8 mmol/mol], or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA1c, FPG, and 2hPG in predicting diabetes within 10 years were compared. RESULTS: During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA1c ≥5.7% as in those with HbA1c ≤5.3%-greater rate ratios than experienced by adults in the same HbA1c categories. Analyses of ROCs revealed no significant differences between HbA1c, FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes. CONCLUSIONS: HbA1c is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG.

Cost Minimization Analysis of Different Strategies of Management of Clinically Significant Scorpion Envenomation Among Pediatric Patients.

OBJECTIVE: Scorpion antivenom was recently approved for use in patients with clinically significant scorpion envenomation in the United States; no formal economic analysis on its impact on cost of management has been performed. METHODS: Three different strategies of management of scorpion envenomation with systemic neurotoxic symptoms in children were compared for cost minimization from a societal perspective. In strategy I, patients were managed with supportive care only without antivenom. In strategy II, an aggressive strategy of full-dose antivenom (initial dose of 3 vials with the use of additional vials administered 1 vial at a time) was considered. In strategy III, a single-vial serial antivenom dosing strategy titrated to clinical response was considered. Clinical probabilities for the different strategies were obtained from retrospective review of medical records of patients with scorpion envenomation over a 10-year period at our institution. Baseline cost values were obtained from patient reimbursement data from our institution. RESULTS: In baseline analysis, strategy I of supportive care only with no antivenom was least costly at US $3466.50/patient. Strategy III of single-vial serial dosing was intermediate but less expensive than strategy II of full-dose antivenom, with an incremental cost of US $3171.08 per patient. In a 1-way sensitivity analysis, at a threshold antivenom cost of US $1577.87, strategy III of single-vial serial dosing became the least costly strategy. CONCLUSIONS: For children with scorpion envenomation, use of a management strategy based on serial dosing of antivenom titrated to clinical response is less costly than a strategy of initial use of full-dose antivenom.

Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children.

CONTEXT: Data are lacking on how metabolic risk factors during childhood affect the long-term risk of type 2 diabetes. OBJECTIVES: Assess four metabolic risk factors as predictors of type 2 diabetes and determine whether the risk differs between younger and older children. DESIGN: In a prospective cohort study conducted between 1965 and 2007, participants were followed for development of diabetes. Baseline measurements included body mass index (BMI), blood pressure, serum cholesterol, and 2-hour plasma glucose after an oral glucose tolerance test. Additional analyses divided subjects into two groups according to baseline age, 5­11 and 12­19 years. SETTING: Gila River Indian Community in Arizona. PARTICIPANTS: A total of 5532 nondiabetic Pima Indian children 5­19 years old. RESULTS: A total of 1281 children developed diabetes (median follow-up, 12.4 years). Diabetes incidence was higher in overweight children (BMI ≥ 85th percentile) than in nonoverweight children. Nonoverweight children had the lowest risk of diabetes (20-year cumulative incidence, 9.5%), whereas overweight children with impaired glucose tolerance (2-hour glucose ≥ 140 mg/dL) had the highest (79.0%). The relative risk for children with metabolic abnormalities compared with their healthy counterparts was higher in younger children than in older children early in follow-up. BMI and 2-hour glucose were related to incident diabetes in multivariable models (predicted 15-year cumulative incidence for the highest vs lowest quartile was 3.9 and 1.8 times as high for BMI and 2-hour glucose, respectively; P < .001), whereas blood pressure and cholesterol were not. CONCLUSIONS: BMI and impaired glucose tolerance in children are strong predictors of type 2 diabetes. Other components of the "metabolic syndrome" are not.