Intraoperative diagnosis of type 1 diabetes and diabetic ketoacidosis during scoliosis surgery.

Diabetic ketoacidosis is the leading cause of morbidity and mortality in children with type 1 diabetes. Management of diabetic ketoacidosis requires meticulous monitoring and treatment of severe dehydration and metabolic derangement. We present an adolescent patient who was diagnosed with diabetic ketoacidosis during spinal fusion for idiopathic scoliosis and discuss the management of this unexpected intraoperative emergency.

Bone Density in the Obese Child: Clinical Considerations and Diagnostic Challenges.

The prevalence of obesity in children has reached epidemic proportions. Concern about bone health in obese children, in part, derives from the potentially increased fracture risk associated with obesity. Additional risk factors that affect bone mineral accretion, may also contribute to obesity, such as low physical activity and nutritional factors. Consequences of obesity, such as inflammation, insulin resistance, and non-alcoholic fatty liver disease, may also affect bone mineral acquisition, especially during the adolescent years when rapid increases in bone contribute to attaining peak bone mass. Further, numerous pediatric health conditions are associated with excess adiposity, altered body composition, or endocrine disturbances that can affect bone accretion. Thus, there is a multitude of reasons for considering clinical assessment of bone health in an obese child. Multiple diagnostic challenges affect the measurement of bone density and its interpretation. These include greater precision error, difficulty in positioning, and the effects of increased lean and fat tissue on bone health outcomes. Future research is required to address these issues to improve bone health assessment in obese children.

Hypercalcemia Secondary to Elevated PTHrP in an Infant Followed by Progression to Nephrotic Syndrome.

In infants, hypercalcemia from elevated parathyroid hormone-related protein (PTHrP) is rare, often signaling neoplasm or renal or urinary anomalies. We report an infant who presented with failure to thrive and hypercalcemia at 10 months old, with initial evaluation showing elevated PTHrP of unclear etiology with imaging negative for neoplasm and no structural anomalies of the kidneys or ureters on ultrasound. Within 6 months of presentation, the patient developed nephrotic syndrome and by 2 years had progressed to end-stage kidney disease, necessitating kidney transplantation. Genetic testing was inconclusive but suggested congenital nephrotic syndrome. While reports of hypercalcemia secondary to elevated PTHrP exist in children with known structural renal anomalies, this is the first to demonstrate hypercalcemia and PTHrP elevation before detection of renal abnormalities. Experimental models have suggested a role for increased PTHrP expression in renal cells following acute kidney injury from nephrotic syndrome, and clinically detectable PTHrP levels may indicate progression of renal injury. We suggest monitoring of renal function for early detection of nephrotic syndrome in infants and children with elevated PTHrP who otherwise lack anatomical renal anomalies or detectable malignancies.

Long-term Continuous Glucose Monitor Use in Very Young Children With Type 1 Diabetes: One-Year Results From the SENCE Study.

OBJECTIVES: Achieving optimal glycemic outcomes in young children with type 1 diabetes (T1D) is challenging. This study examined the durability of continuous glucose monitoring (CGM) coupled with a family behavioral intervention (FBI) to improve glycemia. STUDY DESIGN: This one-year study included an initial 26-week randomized controlled trial of CGM with FBI (CGM+FBI) and CGM alone (Standard-CGM) compared with blood glucose monitoring (BGM), followed by a 26-week extension phase wherein the BGM Group received the CGM+FBI (BGM-Crossover) and both original CGM groups continued this technology. RESULTS: Time in range (70-180 mg/dL) did not improve with CGM use (CGM+FBI: baseline 37%, 52 weeks 41%; Standard-CGM: baseline 41%, 52 weeks 44%; BGM-Crossover: 26 weeks 38%, 52 weeks 40%). All three groups sustained decreases in hypoglycemia (<70 mg/dL) with CGM use (CGM+FBI: baseline 3.4%, 52 weeks 2.0%; Standard-CGM: baseline 4.1%, 52 weeks 2.1%; BGM-Crossover: 26 weeks 4.5%, 52 weeks 1.7%, P-values <.001). Hemoglobin A1c was unchanged with CGM use (CGM+FBI: baseline 8.3%, 52 weeks 8.2%; Standard-CGM: baseline 8.2%, 52 weeks 8.0%; BGM-Crossover: 26 weeks 8.1%, 52 weeks 8.3%). Sensor use remained high (52-week study visit: CGM+FBI 91%, Standard-CGM 92%, BGM-Crossover 88%). CONCLUSION: Over 12 months young children with T1D using newer CGM technology sustained reductions in hypoglycemia and, in contrast to prior studies, persistently wore CGM. However, pervasive hyperglycemia remained unmitigated. This indicates an urgent need for further advances in diabetes technology, behavioral support, and diabetes management educational approaches to optimize glycemia in young children.

Poor Glycemic Control Is Associated With Impaired Bone Accrual in the Year Following a Diagnosis of Type 1 Diabetes.

CONTEXT: Type 1 diabetes (T1D) is associated with an increased fracture risk across the life course. The effects on bone accrual early in the disease are unknown. OBJECTIVE: To characterize changes in bone density and structure over the year following diagnosis of T1D and to identify contributors to impaired bone accrual. DESIGN: Prospective cohort study. SETTING: Academic children's hospital. PARTICIPANTS: Thirty-six children, ages 7 to 17 years, enrolled at diagnosis of T1D. OUTCOMES: Whole body and regional dual-energy X-ray absorptiometry and tibia peripheral quantitative computed tomography obtained at baseline and 12 months. The primary outcome was bone accrual assessed by bone mineral content (BMC) and areal bone mineral density (aBMD) velocity z score. RESULTS: Participants had low total body less head (TBLH) BMC (z = -0.46 ± 0.76), femoral neck aBMD (z = -0.57 ± 0.99), and tibia cortical volumetric BMD (z = -0.44 ± 1.11) at diagnosis, compared with reference data, P < 0.05. TBLH BMC velocity in the year following diagnosis was lower in participants with poor (hemoglobin A1c ≥7.5%) vs good (hemoglobin A1c <7.5%) glycemic control at 12 months, z = -0.36 ± 0.84 vs 0.58 ± 0.71, P = 0.003. TBLH BMC velocity was correlated with gains in tibia cortical area (R = 0.71, P = 0.003) and periosteal circumference (R = 0.67, P = 0.007) z scores in participants with good, but not poor control. CONCLUSIONS: Our results suggest that the adverse effects of T1D on BMD develop early in the disease. Bone accrual following diagnosis was impaired in participants with poor glycemic control and appeared to be mediated by diminished bone formation on the periosteal surface.

Effects of a Randomized Weight Loss Intervention Trial in Obese Adolescents on Tibia and Radius Bone Geometry and Volumetric Density.

Obese adolescents have increased fracture risk, but effects of alterations in adiposity on bone accrual and strength in obese adolescents are not understood. We evaluated 12-month changes in trabecular and cortical volumetric bone mineral density (vBMD) and cortical geometry in obese adolescents undergoing a randomized weight management program, and investigated the effect of body composition changes on bone outcomes. Peripheral quantitative computed tomography (pQCT) of the radius and tibia, and whole-body dual-energy X-ray absorptiometry (DXA) scans were obtained at baseline, 6 months, and 12 months in 91 obese adolescents randomized to standard care versus behavioral intervention for weight loss. Longitudinal models assessed effects of body composition changes on bone outcomes, adjusted for age, bone length, and African-American ancestry, and stratified by sex. Secondary analyses included adjustment for physical activity, maturation, vitamin D, and inflammatory biomarkers. Baseline body mass index (BMI) was similar between intervention groups. Twelve-month change in BMI in the standard care group was 1.0 kg/m2 versus -0.4 kg/m2 in the behavioral intervention group (p < 0.01). Intervention groups were similar in bone outcomes, so they were combined for subsequent analyses. For the tibia, BMI change was not associated with change in vBMD or structure. Greater baseline lean body mass index (LBMI) associated with higher cortical vBMD in males, trabecular vBMD in females, and polar section modulus (pZ) and periosteal circumference (Peri-C) in both sexes. In females, change in LBMI positively associated with gains in pZ and Peri-C. Baseline visceral adipose tissue (VFAT) was inversely associated with pZ in males and cortical vBMD in females. Change in VFAT did not affect bone outcomes. For the radius, BMI and LBMI changes positively associated with pZ in males. Thus, in obese adolescents, weight loss intervention with modest changes in BMI was not detrimental to radius or tibia bone strength, and changes in lean, but not adiposity, measures were beneficial to bone development. © 2017 American Society for Bone and Mineral Research.

Increased Non-High-Density Lipoprotein Cholesterol in Children and Young Adults with Turner Syndrome Is Not Explained By BMI Alone.

BACKGROUND: Turner syndrome (TS) is associated with an increased risk of cardiovascular disease. Non-high-density lipoprotein cholesterol (non-HDL-C) is a convenient measure of atherogenicity (normal concentration <120 mg/dL) but has not been investigated in TS. We aim to evaluate non-HDL-C patterns in a cohort of pediatric and young adult females with TS. METHODS: A retrospective chart review was used to obtain demographics, body composition, genetic reports, and lipid profiles in females with TS. RESULTS: Lipid profiles were assessed in 158 females (mean age 13.6 years). Mean non-HDL-C was 118.9 mg/dL (±32.0); the prevalence of high non-HDL-C (≥144 mg/dL) was 17.7% (n = 28). In TS females aged 8-17 years (n = 46), the prevalence of high non-HDL-C was 23.9% (95% CI 11.1-36.7; n = 11) between 2011 and 2012, compared to 9.2% (95% CI 5.6-14.1) in females of the same age in the general population reported in the National Health and Nutrition Examination Survey (NHANES) dataset (p < 0.005). Body mass index (BMI) accounted for only 6% of variance in non-HDL-C values (ß coefficient = 1.31, p < 0.05). CONCLUSIONS: Children and adolescents aged 8-17 years with TS appear to have a greater prevalence of adverse non-HDL-C levels compared to the general adolescent population. The prevalence of high non-HDL-C was not fully explained by BMI.

A case of severe acquired hypertriglyceridemia in a 7-year-old girl.

We report a case of severe type I hyperlipoproteinemia caused by autoimmunity against lipoprotein lipase (LPL) in the context of presymptomatic Sjögren's syndrome. A 7-year-old mixed race (Caucasian/African American) girl was admitted to the intensive care unit at Vanderbilt Children's Hospital with acute pancreatitis and shock. She was previously healthy aside from asthma and history of Hashimoto's thyroiditis. Admission triglycerides (TGs) were 2191 mg/dL but returned to normal during the hospital stay and in the absence of food intake. At discharge, she was placed on a low-fat, low-sugar diet. She did not respond to fibrates, prescription fish oil, metformin, or orlistat, and during the following 2 years, she was hospitalized several times with recurrent pancreatitis. Except for a heterozygous mutation in the promoter region of LPL, predicted to have no clinical significance, she had no further mutations in genes known to affect TG metabolism and to cause inherited type I hyperlipoproteinemia, such as APOA5, APOC2, GPIHBP1, or LMF1. When her TG levels normalized after incidental use of prednisone, an autoimmune mechanism was suspected. Immunoblot analyses showed the presence of autoantibodies to LPL in the patient's plasma. Autoantibodies to LPL decreased by 37% while patient was on prednisone, and by 68% as she subsequently transitioned to hydroxychloroquine monotherapy. While on hydroxychloroquine, she underwent a supervised high-fat meal challenge and showed normal ability to metabolize TG. For the past 3 years and 6 months, she has had TG consistently <250 mg/dL, and no symptoms of, or readmissions for, pancreatitis.