Insulin Sensitivity and ß-Cell Function Improve after Gastric Bypass in Severely Obese Adolescents.

OBJECTIVE: To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). STUDY DESIGN: A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5-20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose ), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. RESULTS: In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m(2) (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved ß-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). CONCLUSIONS: RYGB reduced body mass index and improved both insulin sensitivity and ß-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00360373.

Smoking and arterial stiffness in youth with type 1 diabetes: the SEARCH Cardiovascular Disease Study.

OBJECTIVE: To evaluate the effects of smoking on early markers of cardiovascular disease (arterial stiffness) in adolescents with and without type 1 diabetes (T1D) in the SEARCH Cardiovascular Disease Study. STUDY DESIGN: Participants included 606 youth (18.9 ± 3.3 years, 83% non-Hispanic white; 50% male). Six groups were defined: (1) smokers with T1D (n = 80); (2) former smokers with T1D (n = 88); (3) nonsmokers with T1D (n = 232); (4) smokers without T1D (n = 40); (5) former smokers without T1D former (n = 51); and (6) nonsmokers without T1D (n = 115). Arterial stiffness measurements included pulse wave velocity (PWV), augmentation index, and brachial distensibility. Multivariate linear regression was used to assess the independent and joint effects of T1D and smoking on arterial stiffness. RESULTS: Nearly 20% of both youth with and without T1D and T1D were smokers. In youth without T1D, smokers had higher trunk and arm PWV. After adjustment for potential confounders, T1D, but not smoking, was an independent predictor of PWV (P < .05). Moreover, smoking status did not modify the association between T1D and increased arterial stiffness. CONCLUSIONS: We found a high prevalence of smoking among youth with and without T1D; however, smoking status was not independently associated with increased arterial stiffness in youth with T1D.

Prevalence of and disparities in barriers to care experienced by youth with type 1 diabetes.

OBJECTIVE: To describe the prevalence of access and process barriers to health care and to examine their relationship to sociodemographic and disease factors in a large and diverse cohort of US youth with type 1 diabetes. STUDY DESIGN: A cross-sectional analysis of 780 youth who participated in the SEARCH for Diabetes in Youth Study and were diagnosed with type 1 diabetes in 2002-2005. Experience of barriers to care was collected from parent report on questionnaires. Analyses included multivariate regression models to predict the presence of specific barriers to care. RESULTS: Overall, 81.7% of participants reported at least one barrier; the 3 most common were costs (47.5%), communication (43.0%), and getting needed information (48.4%). Problems with access to care, not having a regular provider, and receiving contextual care (care that takes into account personal and family context) were associated with poorer glycated hemoglobin levels. Adjusted multivariate models indicated that barriers related to access (regular provider, cost) were most likely for youth with low family income and those without public health insurance. Barriers associated with the processes of quality care (contextual care, communication) were more likely for Hispanic youth and those whose parents had less education. CONCLUSIONS: This study indicates that a large proportion of youth with type 1 diabetes experience substantial barriers to care. Barriers to access and those associated with processes of quality care differed by sociodemographic characteristics. Future investigators should expand knowledge of the systemic processes that lead to disparate outcomes for some youth with diabetes and assess potential solutions.

Glucose control predicts 2-year change in lipid profile in youth with type 1 diabetes.

OBJECTIVE: To test the hypothesis that a change in glycated hemoglobin (A1c) over a follow-up interval of approximately 2 years would be associated with concomitant changes in fasting lipids in individuals with type 1 diabetes (T1D). STUDY DESIGN: All subjects with T1D diagnosed in 2002-2005 in the SEARCH for Diabetes in Youth study with at least 2 study visits ∼12 and ∼24 months after an initial visit were included (age at initial visit, 10.6 ± 4.1 years; 48% female; diabetes duration, 10 ± 7 months; 76% non-Hispanic white; A1c = 7.7% ± 1.4%). Longitudinal mixed models were fit to examine the relationship between change in A1c and change in lipid levels (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], log triglycerides [TG], and non-HDL-c) with adjustment for possible confounders. RESULTS: Change in A1c over time was significantly associated with changes in TC, HDL-c, LDL-c, TG, and non-HDL-c over the range of A1c values. For example, for a person with an A1c of 10% and then a 2% decrease in A1c 2 years later (to 8%), the model predicted concomitant changes in TC (-0.29 mmol/L, -11.4 mg/dL), HDL-c (0.03 mmol/L, 1.3 mg/dL), LDL-c (-0.23 mmol/L, -9.0 mg/dL), and non-HDL-c (-0.32 mmol/L, -12.4 mg/dL) and an 8.5% decrease in TG (mmol/L). CONCLUSIONS: Improved glucose control over a 2-year follow-up was associated with a more favorable lipid profile but may be insufficient to normalize lipids in dyslipidemic T1D youth needing to decrease lipids to goal.

Relationship between elevated arterial stiffness and increased left ventricular mass in adolescents and young adults.

OBJECTIVE: To determine whether arterial stiffness relates to left ventricular mass (LVM) in adolescents and young adults. STUDY DESIGN: Demographic, anthropometric, laboratory, echo, carotid ultrasound and arterial stiffness data were obtained in 670 subjects 10 to 24 years of age (35% male, 62% non-Caucasian). Global stiffness index (GSI) was calculated from five measures of carotid artery stiffness, augmentation index, brachial distensibility, and pulse wave velocity (1 point if ≥95th% for subjects with body mass index <85th%). Stiff arteries (S = 73) were defined as GSI ≥95th%. Differences between flexible (F = 597) and S groups were evaluated by t tests. Models were constructed to determine whether GSI was an independent determinant of LVM index or relative wall thickness (RWT). RESULTS: The S group had more adverse cardiovascular risk factors, higher LVM index and RWT (P ≤ .05) with a trend for abnormal cardiac geometry. Independent determinants of LVM index were higher GSI, age, body mass index, systolic blood pressure, heart rate, glycated hemoglobin A1c, male sex, and sex-by-heart rate interaction (r(2) = 0.52; P ≤ .05). GSI was also an independent determinant of RWT. CONCLUSIONS: Increased arterial stiffness in adolescents and young adults is associated with LVM index independently of traditional cardiovascular risk factors. Screening for arterial stiffness may be useful to identify high risk adolescents and young adults.

Hostility and adiposity mediate disparities in insulin resistance among adolescents and young adults.

OBJECTIVE: This study explores whether the relationship between lower socioeconomic status and insulin resistance in adolescents is mediated by both physiological and psychological factors associated with increased cardiometabolic risk. STUDY DESIGN: School-based longitudinal cohort study of 1222 healthy, non-Hispanic black and white teens. Parent education (PE), youth-specific Cook-Medley hostility scale, waist circumference, height, weight, pubertal status, and fasting plasma insulin (FPI) were measured and FPI reassessed 1 year later. Regression analyses utilizing bootstrapping (n=2000) were used to estimate the direct and indirect effects of PE on FPI and assess the role of hostility and adiposity while adjusting for covariates. RESULTS: Lower PE predicted higher FPI (B=-1.52, P=.003), as did hostility (B=.19, P=.002) and adiposity (waist circumference B=.44, P<.001, BMI B=.98, P<.001). The effect of PE on FPI was mediated by both hostility and adiposity. When adiposity and hostility were accounted for, the effect of PE on FPI decreased by 32% (B=-1.04, P=.04); the total indirect estimate was -.485 (95% CI, -.652, -.041). Hostility accounted for 36% of the meditational effect. CONCLUSIONS: Lower PE influences insulin resistance through adiposity and hostility. Thus, interventions to reduce health disparities associated with insulin resistance should consider both physiological and psychological approaches.

Prevalence of increased arterial stiffness in children with type 1 diabetes mellitus differs by measurement site and sex: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: To discuss vascular stiffness commonly encountered in children with type 1 diabetes mellitus (T1DM). STUDY DESIGN: We examined 535 subjects with T1DM (14.6 years; 53% male, 88% non-Hispanic white) and 241 healthy control subjects (17.8 years; 42% male, 39% non-Hispanic white). Abnormalities in brachial distensibility (BrachD), pulse wave velocity, and augmentation index corrected to a HR of 75 (AIx-75) were examined. RESULTS: Subjects with T1DM had higher body mass index, LDL-cholesterol, fasting glucose, and blood pressure than control subjects. Diabetic subjects had lower BrachD and higher AIx-75 indicating increased stiffness. Age-adjusted pulse wave velocity-trunk (aorto-femoral) was higher in cases (all P

The association between adiponectin/leptin ratio and diabetes type: the SEARCH for Diabetes in Youth Study.

We tested the association of adiponectin/leptin ratio with diabetes type after adjusting for multiple factors in 1156 youths with newly diagnosed diabetes in the SEARCH study. Although adiponectin/leptin ratio is associated with diabetes type in youth, it is due to differences in adiponectin, but not leptin levels.

The relationship of retinol binding protein 4 to changes in insulin resistance and cardiometabolic risk in overweight black adolescents.

OBJECTIVE: To assess, among overweight non-hispanic black adolescents the relationship of changes in plasma retinol binding protein 4 (RBP4) over 3 years to changes in insulin resistance (IR) and 4 associated cardiometabolic risks. STUDY DESIGN: Nested, retrospective study of 51 overweight, post-pubertal non-Hispanic black participants in the Princeton School District Study. Participants were in the top (worsening IR) or bottom (improved IR) quartile for 3-year change in IR. RBP4 was measured by quantitative Western blot with frozen plasma. Regression analyses adjusted for age, sex, and adiposity (baseline and change). Three measures of adiposity were assessed (waist circumference, body mass index, and weight) in separate regression models. RESULTS: RBP4 increased in one third (n = 17). In logistic regression analyses, increased RBP4 was associated with significantly higher odds of worsening as opposed to improved IR independent of age, sex, or adiposity. Odds ratios were 5.6 (weight, P = .024), 6.0 (BMI, P = .025) and 7.4 (waist circumference, P = .015). Initial RBP4 (beta = 0.81, P = .005) and change in RBP4 (beta = 0.56, P = .046) also predicted change in triglycerides, but not change in high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, or fibrinogen. CONCLUSION: This retrospective cohort study provides evidence that RBP4 may be a mechanism through which obesity influences insulin resistance and hypertriglyceridemia in overweight postpubertal black youth and suggests utility of RBP4 as a biomarker of risk.

Glucose tolerance, insulin secretion, and insulin sensitivity in children and adolescents with cystic fibrosis and no prior history of diabetes.

OBJECTIVE: To determine the prevalence of abnormalities of glucose metabolism in pediatric outpatients with cystic fibrosis (CF). STUDY DESIGN: Children and adolescents (n = 73, mean age 15.0 +/- 3.7 years) with CF not previously diagnosed with diabetes underwent 3-hour oral glucose tolerance testing. All subjects with CF were clinically stable and were not being treated for active infection. A reference group of young lean adults was used for comparison. Subjects were classified as having normal glucose tolerance (NGT) or abnormal glucose metabolism (AGM), including impaired glucose tolerance (IGT), impaired fasting glucose (IFG), or diabetes, by standard criteria. The insulinogenic index was calculated as a measure of beta-cell function, and insulin resistance was estimated with the homeostatic model assessment. RESULTS: The reference group was significantly older than the patients with CF, but in the control subjects, the AGM and NGT were comparable in body mass index z-scores (-0.8 +/- 1.3, -0.6 +/- 1.1, -0.21 +/- 0.9 kg/m2). Thirty-eight percent of subjects with CF had AGM: 43% IGT, 29% IFG, 14% IGT/IFG, and 14% diabetes. In spite of distinct differences in glycemic response, the subjects with NGT and AGM had marked abnormalities of insulin secretion relative to the control subjects (Insulinogenic index 5.8 +/- 1.0, 5.3 +/- 0.8, and 53.5 +/- 10.0 uU/mL/mmol/L, respectively; P < .0001). Insulin sensitivity did not differ among the 3 groups, although there was a trend toward greater insulin resistance in the subjects with AGM (homeostatic model assessment: CF-NGT 1.5 +/- 0.2, CF-AGM 1.9 +/- 0.3, REF 1.3 +/- 0.1, P = NS). CONCLUSION: Abnormalities in glucose metabolism are frequent in young patients with CF without a prior diagnosis of diabetes and are associated with marked defects in insulin secretion. Given the poor beta-cell function in patients with CF, even small reductions in insulin sensitivity may be an important determinant of AGM.

Stability of adolescent body mass index during three years of follow-up.

OBJECTIVE: A 4-year longitudinal study was conducted to determine the prevalence of overweight, detect shifts in body mass index (BMI) distribution, and determine which adolescents were at risk for pathologic weight gain. STUDY DESIGN: BMI was analyzed in 1746 adolescents in years 1 (2001-2002) through 4 (2004-2005) of a school-based study. Changes in BMI-Z according to baseline BMI category were examined with general linear modeling. RESULTS: In year 1, the prevalence of at risk for overweight (BMI = 85th-95th percentile) and overweight (BMI > or = 95th percentile) was 19.1% and 18.1%, respectively. Between years 1 and 4, the cohort exhibited no increase in the prevalence of at risk for overweight (19.1% versus 17.2%) or overweight (18.2% versus 18.8%; P > .5). The mean BMI Z-score (BMI-Z) for the cohort was identical in years 1 and 4 (0.66 +/- 1.0 Z-score units). Although the overall cohort exhibited stability in BMI-Z, individuals at the lowest categories of BMI-Z (year 1 BMI Z-score < 0) exhibited significant increases in BMI Z-score by year 4 (P < .01), with lean girls gaining more than lean boys (P for difference < .007). CONCLUSION: The study cohort exhibited stability in adiposity during 3 years of follow-up. However, lean adolescents, particularly girls, experienced significant increases in BMI-Z, beyond that expected for age- and sex-related growth.

Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Study.

OBJECTIVE: Assessment of the prevalence of serum lipid abnormalities in US youth with type 1 or type 2 diabetes. STUDY DESIGN: The SEARCH for Diabetes in Youth Study was a cross-sectional, population-based study, conducted in six centers. Subjects were 2448 youth with diabetes who had a study examination. Outcome measures were fasting measures of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and non-HDL-C. Analysis was descriptive. RESULTS: The overall prevalence of high TC concentration (>240 mg/dL) was 5%; the overall prevalence of high LDL-C (>160 mg/dL) was 3%, and the overall prevalence of high triglyceride (>400 mg/dL) was 2%. About half of the participants (48%) had an LDL-C concentration above the optimal level of 100 mg/dL. Among youth ages 10+, the prevalence of abnormal lipids was higher in type 2 (n = 283) than in type 1 diabetes (n = 1963): 33% versus 19% had TC concentration >200 mg/dL; 24% versus 15% had LDL-C concentration >130 mg/dL; 29% versus 10% had triglyceride concentration >150 mg/dL; 44% versus 12% had HDL-C concentration <40 mg/dL. Only 1% of youth were receiving pharmacologic therapy for dyslipidemia. CONCLUSIONS: A substantial proportion of young patients with diabetes have abnormal serum lipids.

Adiponectin is present in human milk and is associated with maternal factors.

BACKGROUND: Previous studies have shown that human milk has a role in the gastrointestinal, neural, and immune development of neonates. If present in milk, adiponectin would be a promising candidate for influencing infant development, given its metabolic functions. OBJECTIVES: Our objectives were to determine whether adiponectin is present in human milk and to characterize maternal factors associated with potential variation in milk adiponectin concentrations. DESIGN: We quantified adiponectin concentrations in human milk samples from donors to the Cincinnati Children's Research Human Milk Bank and randomly selected participants in a cohort study in Mexico City funded by the National Institutes of Health. Using cross-sectional and longitudinal data, we examined milk adiponectin concentrations in relation to lactation duration, maternal body mass index (BMI; in kg/m(2)), and ethnicity. RESULTS: Adiponectin was detected in human skim milk (range: 4.2-87.9 ng/mL). In cross-sectional and longitudinal analyses, duration of lactation was negatively associated with milk adiponectin concentrations (beta = -0.059 +/- 0.024 and -0.059 +/- 0.007, respectively; P < 0.02 for both). Maternal postpregnancy BMI was positively associated with milk adiponectin concentrations (beta = 0.08 +/- 0.02, P < 0.0001; longitudinal analysis). Mexican mothers had lower median milk adiponectin concentrations at 1 mo than did the non-Hispanic white subjects from Cincinnati (11.5 and 19.8 ng/mL; P = 0.003). CONCLUSIONS: Adiponectin is present in human milk and its concentrations are associated with duration of lactation, maternal adiposity, and ethnicity. Given the importance of adiponectin in inflammation, insulin sensitivity, and fatty acid metabolism, future studies should examine milk adiponectin's role in infant metabolic development.

Frequency of abnormal carbohydrate metabolism and diabetes in a population-based screening of adolescents.

OBJECTIVE: To document the frequency of glucose intolerance in adolescents in a population-based study of primarily African-American/Non-Hispanic whites in an urban-suburban school district. STUDY DESIGN: Measurement of fasting and 2-hour post-glucose load plasma glucose concentrations. RESULTS: Carbohydrate intolerance (either impaired fasting glucose, impaired glucose tolerance, or both) was identified in 8.0%, near-diabetes (1 fasting glucose > or = 126 mg/dL [7.0 mmol/L] and/or 2-hour glucose > or = 200 mg/dL [11.1 mmol/L]) in 0.3%, and diabetes in 0.36% (type 1A = 0.24%; type 2 = 0.08%; undiagnosed type 2 = 0.04%). A model for abnormal carbohydrate metabolism was constructed with regression analysis in the Carbohydrate Intolerance (CI)/near-diabetes group and with logistic regression in the entire study population. Risk factors for the development of CI/near-diabetes included having a 1 unit increase in body mass index (BMI) z-score and either being non-Hispanic white or in the pubertal group. Increased fasting glucose correlated with having puberty and decreased BMI z-score, whereas 2-hour glucose correlated with increased BMI z-score. By using National Health and Nutrition Survey (NHANES) III (1988-1994) definitions, impaired fasting glucose was present in 2.0% in this study versus 1.7% (NHANES III). CONCLUSION: The prevalence of CI/near-diabetes was 8.3%. Undiagnosed diabetes mellitus was rare. One third of adolescents with diabetes mellitus could be classified as having type 2 diabetes mellitus. The adult model of the progression of insulin resistance to type 2 diabetes mellitus in adolescents may be valid. Despite the increase in the overweight population since NHANES III, abnormalities in glucose metabolism have not changed significantly.

Contrasting prevalence of and demographic disparities in the World Health Organization and National Cholesterol Education Program Adult Treatment Panel III definitions of metabolic syndrome among adolescents.

OBJECTIVE: To determine prevalence of metabolic syndrome (MS) among adolescents by using definitions from the National Cholesterol Education Program Adult Treatment Panel III (NCEP) and World Health Organization (WHO) guidelines and to compare the populations identified by these definitions. STUDY DESIGN: School-based, cross-sectional study of 1513 black, white, and Hispanic teens who had a fasting morning blood sample drawn and a physical examination. RESULTS: Overall, the prevalence of NCEP-defined MS was 4.2% and of WHO-defined MS was 8.4%. MS was found almost exclusively among obese teens, for whom prevalence of NCEP-defined MS was 19.5% and prevalence of WHO-defined MS was 38.9%. Agreement between definitions was poor (kappa statistic=0.41). No race or sex differences were present for NCEP-defined MS. However, nonwhite teens were more likely to have MS by WHO criteria (RR, 1.40; 95% CI, 1.04, 1.87), and MS was more common among girls if the WHO-based definition was used (RR, 1.26; 95% CI, 1.08, 1.88). CONCLUSIONS: Among adolescents, obesity is a powerful risk for MS. Important demographic and clinical differences exist in the typology of MS, depending on the definition. Such discrepancies suggest that the concept of a common pathologic syndrome or etiologic mechanism underlying MS as defined by these guidelines may be flawed.