Silva A Arslanian

UPMC, Pittsburgh, Pennsylvania, United States

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Publications (217)1048.57 Total impact

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    ABSTRACT: Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated β-cell function and insulin hypersecretion, in response to intravenous (iv) glucose, compared with Whites. To investigate if the same holds true during an oral glucose challenge and because of the important role of glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in augmenting insulin secretion, we examined β-cell function and incretin hormones in 85 Black and 78 White obese adolescents, with normal glucose tolerance (NGT), during a 2-h oral glucose tolerance test (OGTT) with mathematical modeling of plasma glucose and C-peptide concentrations to assess β-cell glucose sensitivity (βCGS), rate sensitivity, potentiation factor, and insulin sensitivity. Incretin, pancreatic polypeptide, and glucagon concentrations were measured during the OGTT. Black obese youth had a heightened early insulin secretion together with significantly greater βCGS, rate sensitivity, and potentiation factor compared with Whites, with no differences in incretin and glucagon concentrations. Basal and stimulated insulin clearance was lower (p = 0.001) in Black vs. White youth. In conclusion, during an OGTT Black obese youth with NGT demonstrate a pronounced early insulin secretion jointly with heightened β-cell glucose sensitivity, rate sensitivity, and potentiation factor. These racial disparities in β-cell function and the pathophysiological components of T2D are unlikely to be attributed to incretin hormones and remain to be investigated further to explain the metabolic basis for the enhanced risk of T2D in back youth.
    No preview · Article · Jan 2016 · Pediatric Diabetes
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    ABSTRACT: Objective: Children whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and β-cell function in children recently diagnosed with type 2 diabetes. Research design and methods: The sample included 632 youth (aged 10-17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff. Results: Youth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA1c increased by 0.3% [3.4 mmol/mol]), and had reduced β-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092).The effect of maternal diabetes on β-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal. Conclusions: Maternal diabetes prior to or during pregnancy was associated with poorer glycemic control and β-cell function overall but particularly in non-Hispanic Black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.
    No preview · Article · Nov 2015 · Diabetes care
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    ABSTRACT: Objectives: Because in obese youth, pulse wave velocity (PWV), an early cardiovascular disease marker, is elevated, we tested if obese girls with polycystic ovary syndrome (OB-PCOS) have higher PWV and carotid intima-media thickness (cIMT) compared with obese girls without PCOS (OB-non-PCOS) and normal-weight girls without PCOS (NW-non-PCOS) and whether PWV and cIMT correlate with inflammatory and circulating endothelial function biomarkers. Study design: Cross-sectional study of PWV and cIMT in 91 OB-PCOS, 30 obese controls (OB-non-PCOS), and 19 normal-weight controls (NW-non-PCOS). Body composition, blood pressure, fasting glucose, insulin, lipid concentrations, and endothelial function biomarkers were measured. OB-non-PCOS and OB-PCOS underwent 2-hour oral glucose tolerance testing. Results: PWV was higher in OB-PCOS (664 ± 24 cm/s) and OB-non-PCOS (624 ± 37 cm/s) compared with NW-non-PCOS (468 ± 13 cm/s, P < .001), with no differences in cIMT. Systolic blood pressure, low-density lipoprotein, and non-high-density lipoprotein cholesterol were higher, and high-density lipoprotein cholesterol and indices of insulin sensitivity were lower in OB-PCOS and OB-non-PCOS compared with NW-non-PCOS. Vascular cell adhesion molecule-1 and high-sensitivity C-reactive protein were higher in OB-PCOS compared with NW-non-PCOS. PWV correlated with adiposity (rs = .46), insulin sensitivity index (homeostatic model assessment-insulin resistance rs = .31), systolic blood pressure (rs = .24; P ≤ .003 for all), and free testosterone (rs = .24; P = .03). In multiple regression analysis with PWV as the dependent variable and age, race, body mass index, PCOS, and dysglycemia as independent variables, only body mass index was an independent contributor to the model (r(2) = 0.068, P = .003). Conclusions: In adolescent girls, obesity and not PCOS appears to be associated with heightened cardiovascular disease risk. Increased PWV, vascular cell adhesion molecule-1, and high-sensitivity C-reactive protein may be the earliest subclinical atherosclerosis biomarkers in OB-PCOS.
    No preview · Article · Nov 2015 · The Journal of pediatrics
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    Tamara S Hannon · Silva A Arslanian
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    ABSTRACT: The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high-risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in β cell function and relative insulin deficiency in the absence of diabetes-related immune markers. In contrast to adult T2D, the decline in β cell function in youth T2D is three- to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes-related morbidity and mortality at younger ages.
    Preview · Article · Oct 2015 · Annals of the New York Academy of Sciences
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    ABSTRACT: There is a need for simple surrogate estimates of insulin sensitivity in epidemiological studies of obese youth because the hyperinsulinemic-euglycemic clamp is not feasible on a large scale. (i) To examine the triglyceride glucose (TyG) index (Ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) and its relationship to in vivo insulin sensitivity in obese adolescents (OB) along the spectrum of glucose tolerance and (ii) to compare TyG index with triglyceride/high-density lipoprotein TG/HDL and 1/fasting insulin (1/IF ), other surrogates of insulin sensitivity. Cross-sectional data in 225 OB with normal glucose tolerance (NGT), prediabetes (preDM), and type 2 diabetes (T2DM) who had a 3-h hyperinsulinemic-euglycemic clamp and fasting lipid measurement. Insulin-stimulated glucose disposal (Rd) declined significantly across the glycemic groups from OB-NGT to OB-preDM to OB-T2DM with a corresponding increase in TyG index (8.3 ± 0.5, 8.6 ± 0.5, 8.9 ± 0.6, p < 0.0001). The correlation of TyG index to Rd was -0.419 (p < 0.0001). The optimal TyG index for diagnosis of insulin resistance was 8.52 [receiver operating characteristic-area under the ROC curves (ROC-AUC) 0.750, p < 0.0001]. The ROC-AUC for 1/IF was 0.836. In multiple regression analysis, 64.8% of the variance in Rd was explained by TyG index, 1/IF , body mass index (BMI) z-score, glycemic group, and sex. The TyG index affords an easily and widely available simple laboratory method as a surrogate estimate of insulin sensitivity that could be used repeatedly in large-scale observational and/or interventional cohorts of OB. Although not superior to 1/IF , TyG index offers the advantage of having a standardized method of measuring triglyceride and glucose, which is not the case for insulin assays. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
    No preview · Article · Aug 2015 · Pediatric Diabetes
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    ABSTRACT: Type 2 Diabetes Mellitus (T2DM) and obesity are linked to specific patterns of subcortical brain atrophy and decreased microstructural integrity of white matter. Fifteen adolescents (12-21-years-old, 80% Caucasian, 15% African American, mean BMI=32)-five with T2DM confirmed by oral glucose tolerance test, five matched obese adolescent controls without diabetes (OBCN), and five matched (race, sex) normal-weight controls (NWCN)-underwent Magnetic Resonance Imaging (MRI) for the collection of gray matter volume and white matter integrity. Analyses of Variance (ANOVAs) of the neuroimaging data revealed significant differences in caudate nucleus volume [F(2,12)=7.79, p<0.05] such that the normal-weight group had significantly greater volume than the obese and T2DM groups (NWCN>OBCN, p=0.020; OBCN>T2DM, p=0.042; and NWCN>T2DM; p=0.003) after controlling for participant Body Mass Index (BMI). Similarly, there was a main effect for the volume of the thalamus [F(2,12)=4.39, p<0.05] with greater volume for both the NWC and the OBC groups in comparison to the T2DM group (NWC>T2DM, p=0.020; OBC>T2DM; p=0.040). Finally, an examination of white matter integrity among the three groups illustrated a pattern of white matter integrity reduction between normal-weight participants and both obese controls and T2DM participants, with T2DM demonstrating the greatest deficit in functional anisotropy (FA) volume, but these results were not significant after further controlling for BMI. Results from the current pilot study illuminate a host of brain morphology differences between youth with T2DM, obese youth, and normal-weight controls; future research with a larger sample size is critical. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jul 2015 · International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience
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    ABSTRACT: Excessive gestational weight gain (GWG) increases the risk of childhood obesity, but little is known about its association with infant growth patterns. The aim of this study was to examine the association between GWG and infant growth patterns. Pregnant women (n = 743) self-reported GWG at delivery, which we classified as inadequate, adequate or excessive based on the current guidelines. Offspring weight-for-age z-score (WAZ), length-for-age z-score (LAZ (with height-for-age (HAZ) in place of length at 36 months)) and body mass index z-score (BMIZ) were calculated at birth, 8, 18 and 36 months using the 2006 World Health Organization growth standards. Linear mixed models estimated the change in z-score from birth to 36 months by GWG. The mean (SD) WAZ was -0.22 (1.20) at birth. Overall, WAZ and BMIZ increased from birth to, approximately, 24 months and decreased from 24 to 36 months, while LAZ/HAZ decreased from birth through 36 months. Excessive GWG was associated with higher offspring WAZ and BMIZ at birth, 8 and 36 months, and higher HAZ at 36 months, compared with adequate GWG. Compared with the same referent, inadequate GWG was associated with smaller WAZ and BMIZ at birth and 8 months. Excessive GWG may predispose infants to obesogenic growth patterns, while inadequate GWG may not have a lasting impact on infant growth. © 2015 S. Karger AG, Basel.
    No preview · Article · Jul 2015 · Annals of Nutrition and Metabolism
  • JC Diesel · CL Eckhardt · NL Day · MM Brooks · SA Arslanian · LM Bodnar
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    ABSTRACT: Objective To study the association between gestational weight gain (GWG) and offspring obesity risk at ages chosen to approximate prepuberty (10 years) and postpuberty (16 years).DesignProspective pregnancy cohort.SettingPittsburgh, PA, USA.SampleLow-income pregnant women (n = 514) receiving prenatal care at an obstetric residency clinic and their singleton offspring.Methods Gestational weight gain was classified based on maternal GWG-for-gestational-age Z-score charts and was modelled using flexible spline terms in modified multivariable Poisson regression models.Main outcome measuresObesity at 10 or 16 years, defined as body mass index (BMI) Z-scores ≥95th centile of the 2000 CDC references, based on measured height and weight.ResultsThe prevalence of offspring obesity was 20% at 10 years and 22% at 16 years. In the overall sample, the risk of offspring obesity at 10 and 16 years increased when GWG exceeded a GWG Z-score of 0 SD (equivalent to 30 kg at 40 weeks); but for gains below a Z-score of 0 SD there was no relationship with child obesity risk. The association between GWG and offspring obesity varied by prepregnancy BMI. Among mothers with a pregravid BMI <25 kg/m2, the risk of offspring obesity increased when GWG Z-score exceeded 0 SD, yet among overweight women (BMI ≥25 kg/m2), there was no association between GWG Z-scores and offspring obesity risk.Conclusions Among lean women, higher GWG may have lasting effects on offspring obesity risk.Tweetable abstractMaternal weight gain is associated with offspring obesity at 10 and 16 years in a prospective study.
    No preview · Article · May 2015 · BJOG An International Journal of Obstetrics & Gynaecology
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    ABSTRACT: The diagnostic criteria for polycystic ovary syndrome (PCOS) in adolescence are controversial, primarily because the diagnostic pathological features used in adult women may be normal pubertal physiological events. Hence, international pediatric and adolescent specialty societies have defined criteria that have sufficient evidence to be used for the diagnosis of PCOS in adolescents. The literature has been reviewed and evidence graded to address a series of questions regarding the diagnosis of PCOS during adolescence including the following: clinical and biochemical evidence of hyperandrogenism, criteria for oligo-anovulation and polycystic ovary morphology, diagnostic criteria to exclude other causes of hyperandrogenism and amenorrhea, role of insulin resistance, and intervention. Features of PCOS overlap normal pubertal development. Hence, caution should be taken before diagnosing PCOS without longitudinal evaluation. However, treatment may be indicated even in the absence of a definitive diagnosis. While obesity, insulin resistance, and hyperinsulinemia are common findings in adolescents with hyperandrogenism, these features should not be used to diagnose PCOS among adolescent girls. © 2015 S. Karger AG, Basel.
    No preview · Article · Apr 2015 · Hormone Research in Paediatrics
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    ABSTRACT: Objective Obese youth clinically diagnosed with type 2 diabetes mellitus (T2DM) frequently have evidence of islet cell autoimmunity. We investigated the clinical and biochemical differences, and therapeutic modalities among autoantibody positive (Ab+) vs. autoantibody negative (Ab−) youth at the time of diagnosis and over time in a multi-provider clinical setting.Study designChart review of 145 obese youth diagnosed with T2DM from January 2003 to July 2012. Of these, 70 patients were Ab+ and 75 Ab−. The two groups were compared with respect to clinical presentation, physical characteristics, laboratory data, and therapeutic modalities at diagnosis and during follow up to assess the changes in these parameters associated with disease progression.ResultsAt presentation, Ab+ youth with a clinical diagnosis of T2DM were younger, had higher rates of ketosis, higher hemoglobin A1c (HbA1c) and glucose levels, and lower insulin and c-peptide concentrations compared with the Ab− group. The Ab− group had a higher body mass index (BMI) z-score and cardiometabolic risk factors at diagnosis and such difference remained over time. Univariate analysis revealed that treatment modality had no effect on BMI in either group. Generalized estimating equations for longitudinal data analysis revealed that (i) BMI z-score and diastolic blood pressure (DBP) were significantly affected by duration of diabetes; (ii) systolic blood pressure (SBP) and ALT were affected by changes in BMI z-score; and (iii) changes in HbA1c had an effect on lipid profile and cardiometabolic risk factors regardless of antibody status.Conclusions Irrespective of antibody status and treatment modality, youth who present with obesity and diabetes, show no improvement in obesity status over time, with the deterioration in BMI z-score affecting blood pressure (BP) and ALT, but the lipid profile being mostly impacted by HbA1c and glycemic control. Effective control of BMI and glycemia are needed to lessen the future macrovascular complications irrespective of antibody status.
    No preview · Article · Dec 2014 · Pediatric Diabetes
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    ABSTRACT: Objective We examined the association between gestational weight gain (GWG) and offspring obesity at age 36 months.Methods Mother–infant dyads (n = 609) were followed from a first study visit (mean [standard deviation]: 18.8 [2.7] weeks gestation) to 36 months postpartum. Total GWG over the entire pregnancy was defined as excessive or non-excessive according to the 2009 Institute of Medicine guidelines. Four mutually exclusive categories of excessive or non-excessive GWG across early (conception to first study visit) and late (first study visit to delivery) pregnancy defined GWG pattern. Body mass index (BMI) z-scores ≥95th percentile of the 2000 Centers for Disease Control (CDC) references defined offspring obesity at 36 months. Multivariable log-binomial models adjusted for pre-pregnancy BMI and breastfeeding were used to estimate the association between GWG and childhood obesity risk.ResultsNearly half of the women had total excessive GWG. Of these, 46% gained excessively during both early and late pregnancy while 22% gained excessively early and non-excessively late, and the remaining 32% gained non-excess weight early and excessively later. Thirteen per cent of all children were obese at 36 months. Excessive total GWG was associated with more than twice the risk of child obesity (adjusted risk ratio [95% confidence interval]: 2.20 [1.35, 3.61]) compared with overall non-excessive GWG. Compared with a pattern of non-excessive GWG in both early and late pregnancy, excessive GWG in both periods was associated with an increased risk of obesity (2.39 [1.13, 5.08]).Conclusions Excessive GWG is a potentially modifiable factor that may influence obesity development in early childhood.
    No preview · Article · Oct 2014 · Pediatric Obesity
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    ABSTRACT: Objective: Obesity in adolescence has been associated with increased risk for coronary heart disease in adulthood. This study evaluated subclinical atherosclerosis in obese youth and the underlying risk factors. Research design and methods: Ninety obese adolescents (37 normal glucose tolerant, 27 prediabetes, and 26 type 2 diabetes) underwent evaluation of coronary artery calcifications (CACs) by electron beam computed tomography, aortic pulse wave velocity (PWV), carotid intima-media thickness (IMT), lipids, leptin, inflammatory markers, and body composition (DEXA). A total of 68 underwent evaluation of insulin sensitivity (IS) (hyperinsulinemic-euglycemic clamp) and abdominal adiposity (computed tomography). Results: A total of 50% had CACs (CAC+: Agatston CAC score ≥1). CAC+ youth had higher BMI, fat mass, and abdominal fat, with no difference in sex, race, IS per fat-free mass (ISFFM), glucose tolerance, PWV, or IMT compared with the CAC- group. PWV was inversely related to IS. In multiple regression analyses with age, race, sex, HbA1c, BMI (or waist circumference), ISFFM, diastolic blood pressure, non-HDL cholesterol, and leptin as independent variables, BMI (or waist) (R(2) = 0.41; P = 0.001) was the significant determinant of CAC; leptin (R(2) = 0.37; P = 0.034) for PWV; and HbA1c, race, and age (R(2) = 0.34; P = 0.02) for IMT. Conclusions: Early in the course of obesity, there is evidence of CAC independent of glycemia. The different biomarkers of subclinical atherosclerosis appear to be differentially modulated, adiposity being the major determinant of CAC, hyperglycemia, age, and race for IMT, and leptin and IS for arterial stiffness. These findings highlight the increased cardiovascular disease risk in obese youth and the need for early interventions to reverse obesity and atherosclerosis.
    Preview · Article · Sep 2014 · Diabetes Care
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    ABSTRACT: Purpose To compare atherogenic lipoprotein particles and vascular smooth muscle biomarkers in overweight youth with pre-diabetes (PD) vs. normal glucose tolerance (NGT). Methods 144 adolescents (60 black, 84 white; 102 female; PD = 45, NGT = 99) aged 10-19 years underwent a fasting blood draw and 2-hr OGTT. Lipoprotein particle size and subclass concentration and vascular smooth muscle biomarkers (ICAM-1, VCAM-1 and E-selectin) were compared between youth with PD and NGT. Results Compared with NGT, PD adolescents had smaller LDL (mean ± SE: 20.5 ± 0.1 vs. 21.0 ± 0.1 nm; P = 0.002) and HDL (8.62 ± 0.05 vs. 8.85 ± 0.04 nm; P = 0.013) size and elevated medium small (159.2 ± 10.3 vs. 123.8 ± 6.4 nmol/L; P = 0.037) and very small (626.3 ± 45.4 vs. 458.5 ± 26.4 nmol/L; P = 0.032) LDL particle concentrations, after adjustment for race and BMI. Further adjusting for fasting insulin or visceral adiposity obviated these differences between the groups except for LDL size. ICAM-1 and E-selectin did not differ in youth with PD but correlated with LDL and HDL size, and small LDL particle concentrations. Conclusions Overweight adolescents with PD have an atherogenic lipoprotein profile of small LDL and HDL size and increased concentrations of small LDL, moderated by insulin resistance and visceral adiposity, but independently driven by dysglycemia for LDL size. Associations between smooth muscle biomarkers and lipoproteins could be an early signal heralding the atherogenic process. It remains to be determined if correction of dysglycemia and associated lipoprotein abnormalities in obese youth could prove effective in halting this process.
    No preview · Article · Aug 2014 · Metabolism
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    ABSTRACT: Background: The prevalence of type 2 diabetes (T2D) in youth is increasing. Treatment options beyond metformin and insulin are needed. The safety, tolerability, pharmacokinetics, and pharmacodynamics of liraglutide once daily in youth (10-17 years old) with T2D were investigated in a randomized, double-blind, placebo-controlled trial. Subjects and methods: Youth treated with diet/exercise alone or with metformin and having a hemoglobin A1c (HbA1c) level of 6.5-11% were randomized to liraglutide (n=14) or placebo (n=7). Starting at 0.3 mg/day, doses were escalated weekly to 0.6, 0.9, 1.2, and 1.8 mg/day (or placebo equivalent) for 5 weeks. Results: Nineteen participants completed the trial. Baseline characteristics were similar between groups, with mean (SD) values for age of 14.8 (2.2) years, weight of 113.2 (35.6) kg (range, 57-214 kg), diabetes duration of 1.7 (1.4) years, and HbA1c level of 8.1% (1.2%). No serious adverse events (AEs), including severe hypoglycemia, occurred. Transient gastrointestinal AEs were most common at lower liraglutide doses during dose escalation. No significant changes in safety and tolerability parameters occurred. There was no evidence of pancreatitis or lipase elevations above three times the upper normal limit; calcitonin levels remained within the normal range. For liraglutide 1.8 mg, mean half-life was 12 h, and clearance was 1.7 L/h. After 5 weeks, the decline in HbA1c level was greater with liraglutide versus placebo (-0.86 vs. 0.04%, P=0.0007), whereas mean body weight remained stable (-0.50 vs. -0.54 kg, P=0.9703). Conclusions: Liraglutide was well tolerated in youth with T2D, with safety, tolerability, and pharmacokinetic profiles similar to profiles in adults.
    Full-text · Article · Jul 2014 · Diabetes Technology & Therapeutics
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    ABSTRACT: Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT βCGS to the 2-h hyperglycemic clamp βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia.
    Full-text · Article · Jun 2014 · Diabetes

  • No preview · Article · Jun 2014 · Diabetes
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    Full-text · Article · May 2014 · Anales de Pediatría

  • No preview · Article · Jan 2014
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    ABSTRACT: To examine relationships among blood pressure (BP), adiposity, and sleep quality with the use of overnight polysomnography in obese adolescents. Overnight polysomnogram and morning BP measurements were performed in obese (body mass index [BMI] >95th percentile) nondiabetic adolescents (eligible age range 12-18 years, n = 49). Subjects were stratified into 2 groups, one with normal BP, and one with elevated BP, and demographic and clinical characteristics were compared between the groups. Multiple linear regression analysis was used to assess the effects of sleep quality on BP. Participants (n = 27) had a normal morning BP, and 22 (44.9%) had elevated morning BP. There were no differences in age (P = .53), sex (P = .44), race (P = .58), or BMI (P = .56) between the 2 BP groups. The group with elevated BP spent shorter percentages of time in rapid eye movement (REM; P = .006) and slow-wave sleep (SWS; P = .024). Multiple linear regression analysis showed that a lower percentage of both REM and SWS was associated with increased morning BP after we adjusted for pubertal stage, sex, race, and BMI. Lack of deeper stages of sleep, REM sleep, and SWS is associated with greater morning BP in obese adolescents, independent of BMI. Poor sleep quality should be considered in the work-up of obese youth with hypertension. Intervention studies are needed to evaluate whether improving the quality of sleep will decrease BP elevation.
    No preview · Article · Nov 2013 · The Journal of pediatrics
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    ABSTRACT: Objective The Restoring Insulin Secretion (RISE) Consortium is testing interventions designed to preserve or improve islet-cell function in prediabetes or early type 2 diabetes.Research Design and Methodsß-cell function is measured using hyperglycemic clamps and oral glucose tolerance tests (OGTT). The adult medication protocol randomizes participants to 12 months of placebo, metformin alone, liraglutide plus metformin or insulin (3 months) followed by metformin (9 months). The pediatric medication protocol randomizes participants to metformin or insulin followed by metformin. The adult surgical protocol randomizes participants to gastric banding or metformin (24 months). Adult medication protocol inclusion criteria include fasting plasma glucose (FPG) 95-125 mg/dl (5.3-6.9 mmol/l), OGTT 2-hour glucose (2hG) ≥140 mg/dl (≥7.8 mmol/l), HbA1c 5.8-7.0% (40-53 mmol/mol), and BMI 25-40 kg/m(2). Adult surgical protocol criteria are similar, except FPG ≥90 mg/dl (≥5.0 mmol/l), BMI 30-40 kg/m(2), HbA1c <7.0% (<53 mmol/mol) and diabetes <12 months. Pediatric inclusion criteria include FPG ≥90 mg/dl (≥5.0 mmol/l), 2hG ≥140 mg/dl (≥7.8 mmol/l), HbA1c ≤8.0% (≤64 mmol/mol), BMI >85%ile and ≤50 kg/m(2), age 10-19 years, and diabetes <6 months.ResultsPrimary outcomes are clamp-derived glucose-stimulated C-peptide secretion and maximal C-peptide response to arginine during hyperglycemia. Measurements are made at baseline, after 12 months on-treatment and 3 months after treatment withdrawal (medication protocols) or 24 months post-intervention (surgery protocol). OGTT-derived measures are also obtained at these time points.ConclusionsRISE is determining whether medication or surgical intervention strategies can mitigate progressive ß-cell dysfunction in adults and youth with prediabetes or early type 2 diabetes.
    Preview · Article · Nov 2013 · Diabetes care

Publication Stats

9k Citations
1,048.57 Total Impact Points


  • 2011-2015
    • UPMC
      Pittsburgh, Pennsylvania, United States
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 1993-2015
    • Childrens Hospital of Pittsburgh
      • • Weight Management and Wellness Center
      • • Division of Pediatric Endocrinology, Diabetes and Metabolism
      Pittsburgh, Pennsylvania, United States
  • 1991-2015
    • University of Pittsburgh
      • • Division of Pediatric Pathology at Children's Hospital of Pittsburgh of UPMC
      • • Department of Pediatrics
      • • Division of Pediatric Endocrinology
      • • Center for ALS Research
      Pittsburgh, Pennsylvania, United States
  • 2012
    • Pittsburg State University
      Питсбург, Kansas, United States
    • George Washington University
      • Biostatistics Center
      Washington, Washington, D.C., United States
  • 2007
    • Mahidol University
      Krung Thep, Bangkok, Thailand
    • Children's Hospital of Richmond
      Ричмонд, Virginia, United States
  • 2000
    • The Ohio State University
      • School of Physical Activity and Educational Services
      Columbus, Ohio, United States
  • 1994
    • Children's National Medical Center
      Washington, Washington, D.C., United States
  • 1990
    • Allegheny General Hospital
      • Department of Pediatrics
      Pittsburgh, Pennsylvania, United States