Fasting Serum IGFBP-1 as a Marker of Insulin Resistance in Diverse School Age Groups.

Introduction: The known markers of insulin resistance in obese children are well studied. However, they require serial measurements and complicated calculations. The objective is to study IGFBP-1 and its relation with other known risk measures. Materials and Methods: The study included 98 New York City school students of diverse ethnic/racial backgrounds (57 males and 41 females), 11-15 years of age. Subjects were enrolled in a cross-sectional study, and anthropometric measures were collected. They underwent fasting intravenous glucose tolerance tests (IVGTT), and glucose, insulin, lipids, IGFBP-1, adiponectin and inflammatory markers were collected. Results: The subjects were stratified into 3 groups based upon the BMI Z-score. Out of all the subjects, 65.3% were in the group with a BMI Z-score <1 SDS, 16.3% subjects were in the group with a BMI Z-score of 1 to 2 SDS, and 18.4% of the subjects were in the group with a BMI Z-score of more than 2 SDS. The group with a BMI Z-score of more than 2 SDS had increased waist circumference (WC), body fat, increased fasting insulin, and triglycerides (TG). This group had decreased levels of adiponectin and HDL and low IGFBP-1 as compared to the group with BMI <1 SDS. The group with a BMI Z-score of 1 to 2 SDS had a decreased level of IGFBP-1 as compared to the group with a BMI Z-score less than 1 SDS. IGFBP-1 inversely correlated with age, WC, BMI, body fat, TG, and insulin levels. IGFBP-1 positively correlated with adiponectin and HDL levels. Conclusion: IGFBP-1 in children can identify the presence of insulin resistance in the group with BMI 1 to 2 SDS, even before the known markers of insulin resistance such as elevated triglycerides and even before decreased HDL and adiponectin levels are identified.

Retinol binding protein 4 is associated with adiposity-related co-morbidity risk factors in children.

OBJECTIVE: In adults, elevated levels of retinol binding protein 4 (RBP4) have been associated with biochemical markers of adiposity-related co-morbidities including insulin resistance, dyslipidemia, hypertension, and abdominal obesity. This study examined the relationship between RBP4 and risk factors for co-morbidities of adiposity in a population of ethnically diverse children in early- to mid-adolescence in the public school system of New York City. MATERIALS/METHODS: We analyzed anthropometric (body mass index, % body fat, waist circumference), metabolic (lipids, glucose), and inflammatory (TNF-alpha, interleukin-6, C-reactive protein, adiponectin) markers for adiposity-related co-morbidities and serum alanine aminotransferase (ALT) in 106 school children (65 males, 41 females) 11-15 years of age (mean +/- SD = 13.0 +/- 0.1 years) who were enrolled in the Reduce Obesity and Diabetes (ROAD) project. Insulin sensitivity was assessed by quantitative insulin sensitivity check index. Insulin secretory capacity was measured as acute insulin response and glucose disposal index. RESULTS: Serum RBP4 was significantly correlated directly with ALT, triglycerides, and triglyceride z-score, and inversely correlated with adiponectin. Correlations with ALT and adiponectin remained significant when corrected for % body fat, age, and gender. There were significant ethnic differences in the relationship of RBP4 to ALT, glucose disposal index and adiponectin. CONCLUSIONS: In early- to mid-adolescents, circulating concentrations of RBP4 are correlated with multiple risk factors for adiposity-related co-morbidities. The observation that many associations persisted when corrected for % body fat, suggests that RBP4 can be viewed as an independent marker of adiposity-related co-morbidity risk in children.

Poor glycemic control is associated with abnormal changes in 24-hour ambulatory blood pressure in children and adolescents with type 1 diabetes mellitus.

INTRODUCTION: Twenty-four hour ambulatory blood pressure (ABPM) is emerging as a valuable tool to assess blood pressure (BP) changes in children with type 1 diabetes mellitus (DM1). Hypertension (HTN) is an important risk factor for, and may be an important indicator of diabetic nephropathy. Early accurate identification of HTN in DM1 may improve outcomes. AIM: To evaluate BP in adolescents with DM1 using 24-hour ABPM, and to identify risk factors associated with abnormal blood pressure. METHOD: The ABPM of 105 children with DM1 was reviewed. Mean systolic BP (sBP) percentile was determined from the National High Blood Pressure Education Program (NHBPEP) tables. The patients with abnormal sBP were compared to those with normal sBP with respect to age, race, sex, body mass index (BMI) percentile, duration of DM1, average hemoglobin A1c (HbA1c) over the preceding year, and family history of hypertension. RESULTS: Mean sBP was normal in 71%, whereas 23% had pre-hypertension, and 6% had stage 1 hypertension. Those who had abnormal sBP (pre-hypertension and stage 1 hypertension) had higher HbA1c (p = 0.023) and were more likely to be male (p = 0.03) than those with normal sBP. CONCLUSION: Stage 1 hypertension is present in 6%, and pre-hypertension in 23% of adolescents with DM1. Poor diabetes control and male gender appear to be risk factors for abnormal sBP as measured by 24-hour ambulatory blood pressure monitoring.

Vitamin D in Health and Disease in Adolescents: When to Screen, Whom to Treat, and How to Treat.

The existing guidelines on screening and treatment are confusing because different guidelines target different populations. The IOM and AAP guidelines target generally healthy populations, whereas the Endocrine Society and other subspecialty guidelines target individuals with specific medical conditions associated with increased bone fragility. These distinctions have not always been well articulated. For healthy adolescents, the AAP does not recommend universal screening or screening of obese or dark-skinned individuals. Increased dietary intake of vitamin D is recommended, and vitamin D supplementation can be considered if the RDA cannot be met. For adolescents with chronic medical illnesses associated with increased fracture risk, screening for vitamin D deficiency should be performed by obtaining a serum 25-OHD level. Those found to be deficient (25-OHD level < 20 ng/mL) should be treated with doses of vitamin D2 or vitamin D3 higher than the daily requirement (as discussed in the section on vitamin D and chronic disease), followed by a maintenance dose. A repeat 25-OHD level should be obtained after the therapeutic course is completed. Some experts advocate for achievement of 25-OHD levels greater than 30 ng/mL in conditions associated with increased bone fragility, and several pediatric subspecialty organizations have made recommendations specific to the diseases they treat. In such instances, the recommendations of the pediatric subspecialty organizations should take precedence over the AAP recommendations for adolescents with chronic illnesses associated with increased bone fragility because the AAP recommendations were primarily targeted at a healthy population.

Bone Health in Adolescence.

Osteoporosis occurs during childhood and adolescence as a heritable condition such as OI, with acquired disease (eg, IBD), or iatrogenically as a result of high-dose glucocorticoid therapy. However, the number of children affected by osteoporosis during youth is small compared to the numbers who will develop osteoporosis in adulthood. Prevention of adult osteoporosis requires that an optimal environment for the achievement of peak bone mass be established during the growing years. Detection of low BMD can be achieved using modalities such as DXA and pQCT. Standard radiologic studies, especially vertebral radiography, may also be helpful in children and adolescents at high risk for osteoporosis. It is critical to the development of healthy bones that adolescents have proper nutrition with adequate calcium and vitamin D intake and that they participate in regular physical activity (especially weight-bearing exercise). In the recent past, the dual goals of proper nutrition and exercise were not being achieved by many, if not most, adolescents. Those caring for adolescents should strive to educate teens and their families on the importance of dietary calcium and vitamin D as well as advocate for supportive environments in schools and communities that foster the development of healthy habits with regard to diet and exercise. In order to help identify the population at risk for osteoporosis, a bone health screen with assessment of calcium intake and determination of family history of adult osteoporosis (hip fracture, kyphosis) should be a routine part of adolescent health care. Universal screening of healthy adolescents with serum 25OHD levels is not recommended. Adolescents with conditions associated with reduced bone mass should undergo bone densitometry or other studies as a baseline, and BMD should be monitored at intervals no more frequently than yearly. Although controversy remains regarding the optimum dose of vitamin D for treatment of osteoporosis, all would agree that vitamin D should be provided, and in doses somewhat higher than previously recommended. Excessive vitamin D should be avoided. The use of bisphosphonates is recommended for the treatment of OI, as well as for treatment of select children with severe osteoporosis associated with chronic conditions that lead to frequent or painful fragility fractures. In such situations, bisphosphonates should be prescribed only in the context of a comprehensive clinical program with specialists knowledgeable in the management of osteoporosis in children.

Identifying risk factors for the development of diabetic ketoacidosis in new onset type 1 diabetes mellitus.

To identify risk factors associated with the development of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes mellitus, a retrospective chart review of 139 new onset type 1 diabetes patients from 1995 to 1998 was conducted. Categorical data were examined with contingency table analysis. Age range was 0.5 to 18 years. Overall, 38% of the patients presented in DKA. Sixty-two percent of the patients with either Medicaid or no insurance presented in DKA compared to 34% of the patients with private insurance, odds ratio 3.17 (92% CI 1.2-8.3) p = 0.03. Sixty-eight percent of patients in whom the diagnosis was missed (n = 25) presented in DKA (mean age, 5.4 +/- 4.4 years) compared to 32% in whom the diagnosis was not missed (mean age, 8.8 +/- 4.0 years) odds ratio 4.6 (95% CI 1.9-11.7), p = 0.0012; age p = 0.00019. Lack of private insurance, although a risk factor for the development of DKA, did not increase the likelihood of a missed diagnosis. Lack of private insurance (a proxy for socioeconomic status) and young age are apparent risk factors for the development of ketoacidosis. Misdiagnosis by the physician at initial patient encounter is especially prevalent in the young child but not related to insurance. Both increased public awareness and greater medical alertness are necessary to reduce the high rates of DKA in new-onset type 1 diabetic children.

Effects of parental origins and length of residency on adiposity measures and nutrition in urban middle school students: a cross-sectional study.

BACKGROUND: The prevalence of obesity in U.S. has been rising at an alarming rate, particularly among Hispanic, African, and Asian minority groups. This trend is due in part to excessive calorie consumption and sedentary lifestyle. We sought to investigate whether parental origins influence eating behaviors in healthy urban middle school students. METHODS: A multiethnic/racial population of students (N = 182) enrolled in the ROAD (Reduce Obesity and Diabetes) Study, a school-based trial to assess clinical, behavioral, and biochemical risk factors for adiposity and its co-morbidities completed questionnaires regarding parental origins, length of US residency, and food behaviors and preferences. The primary behavioral questionnaire outcome variables were nutrition knowledge, attitude, intention and behavior, which were then related to anthropometric measures of waist circumference, BMI z-scores, and percent body fat. Two-way analysis of variance was used to evaluate the joint effects of number of parents born in the U.S. and ethnicity on food preference and knowledge score. The Tukey-Kramer method was used to compute pairwise comparisons to determine where differences lie. Analysis of covariance (ANCOVA) was used to analyze the joint effects of number of parents born in the US and student ethnicity, along with the interaction term, on each adiposity measure outcome. Pearson correlation coefficients were used to examine the relationships between maternal and paternal length of residency in the US with measures of adiposity, food preference and food knowledge. RESULTS: African Americans had significantly higher BMI, waist circumference and body fat percentage compared to other racial and ethnic groups. Neither ethnicity/race nor parental origins had an impact on nutrition behavior. Mothers' length of US residency positively correlated with students' nutrition knowledge, but not food attitude, intention or behavior. CONCLUSIONS: Adiposity measures in children differ according to ethnicity and race. In contrast, food behaviors in this middle school sample were not influenced by parental origins. Longer maternal US residency benefited offspring in terms of nutrition knowledge only. We suggest that interventions to prevent obesity begin in early childhood.

Racial/ethnic differences in clinical and biochemical type 2 diabetes mellitus risk factors in children.

OBJECTIVE: To examine whether periadolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults. DESIGN AND METHODS: Family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) were examined in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other). RESULTS: Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance. CONCLUSIONS: Children show some of the same racial/ethnic differences in risk factors for adiposity-related comorbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related comorbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history.

Vitamin D, osteocalcin, and risk for adiposity as comorbidities in middle school children.

Nonclassic actions of vitamin D include potential regulation of immune function and glucose homeostasis. The bone-metabolism loop has recently been expanded to include osteocalcin, which appears to play a more direct role in pancreatic beta cell function and energy metabolism. We hypothesized that both vitamin D and osteocalcin would correlate negatively with indices of adiposity-related comorbidity risk in periadolescents, varying by ethnic group. We analyzed anthropometric, metabolic, and inflammatory markers from a multiethnic population of 106 school children 11 to 14 years of age studied as part of the Reduce Obesity and Diabetes (ROAD) consortium. As expected, 25-hydroxyvitamin D (25-OH vitamin D) was inversely correlated with intact parathyroid hormone (iPTH); total osteocalcin (OCN) and uncarboxylated osteocalcin (uOCN) were directly correlated with each other. OCN and uOCN concentrations correlated inversely with age. Vitamin D deficiency was most prevalent among East Asians (EA) and African Americans (AA). The highest lipid risk scores and homeostatic model for assessment of insulin resistance (HOMA-IR) values were seen in the South Asian (SA) group. Overall, adiposity measures were inversely correlated with OCN and iPTH, whereas such relationships were not observed for vitamin D. Acute insulin response to glucose challenge correlated negatively with uOCN in all subjects; however, lipid risk score correlated negatively with uOCN only in whites. The relationships between markers of calcium metabolism and body composition, glucose homeostasis, lipids, and inflammation all showed racial and ethnic differences. No consistent relationship was found between vitamin D and adiposity or vitamin D and glucose metabolism; instead vitamin D levels varied by race and ethnicity in this school-based group. These findings are consistent with the hypothesis that markers of calcium and bone metabolism may reflect risk for adiposity-related comorbidities in children.

Twenty-four hour ambulatory blood pressure monitoring in adolescents with type 1 diabetes: getting started.

Twenty-four hour ambulatory blood pressure monitoring (ABPM) is a valuable tool in the pediatric and adolescent population with type 1 diabetes. It provides useful information not readily available from sporadic clinic blood pressure (BP) measurements and a more reliable estimation of the subject's BP over an extended period of time. Ambulatory blood pressure monitoring is gaining popularity with clinicians and investigators alike. The American Heart Association has recently issued recommendations for the use of ABPM in children and adolescents. We have incorporated ABPM into our adolescent diabetes practice and present useful information for clinicians planning to initiate 24 h ABPM in their clinical practice.