Silva A Arslanian

Childrens Hospital of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (209)1005.66 Total impact

  • 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.
    Annals of the New York Academy of Sciences 10/2015; DOI:10.1111/nyas.12939 · 4.38 Impact Factor
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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.
    Pediatric Diabetes 08/2015; DOI:10.1111/pedi.12303 · 2.57 Impact Factor
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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.
    International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 07/2015; 46. DOI:10.1016/j.ijdevneu.2015.07.003 · 2.58 Impact Factor
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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.
    Hormone Research in Paediatrics 04/2015; 83(6). DOI:10.1159/000375530 · 1.57 Impact Factor
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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.
    Pediatric Diabetes 12/2014; 16(5). DOI:10.1111/pedi.12249 · 2.57 Impact Factor
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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.
    Diabetes Care 09/2014; 37(9):2632-9. DOI:10.2337/dc14-0193 · 8.42 Impact Factor
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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.
    Metabolism 08/2014; 63(12). DOI:10.1016/j.metabol.2014.08.008 · 3.89 Impact Factor
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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.
    Diabetes Technology &amp Therapeutics 07/2014; 16(10). DOI:10.1089/dia.2013.0366 · 2.11 Impact Factor
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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.
    Diabetes 06/2014; 63(11). DOI:10.2337/db13-1951 · 8.10 Impact Factor
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    Anales de Pediatría 05/2014; 82(2). DOI:10.1016/j.anpedi.2014.04.005 · 0.83 Impact Factor
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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.
    The Journal of pediatrics 11/2013; 164(2). DOI:10.1016/j.jpeds.2013.10.011 · 3.79 Impact Factor
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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.
    Diabetes care 11/2013; DOI:10.2337/dc13-1879 · 8.42 Impact Factor
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    ABSTRACT: Purpose: To adapt a hospital-based pediatric weight management program for use in primary care (PC) and train and support PC providers to deliver the program. Methods: Using the Chronic Care Model as a framework, a children's hospital-based multidisciplinary team of obesity specialists partnered with a large network of pediatric PC practices to (1) establish a standardized clinical pathway to provide patients with appropriate and preferred levels and types of weight management services; (2) develop and pilot a modified version of the hospital-based specialty program to be administered in PC by providers and nurses trained as lifestyle coaches (LCs); (3) train PC providers and LCs to utilize a motivational interviewing style of communication and cognitive behavioral techniques to administer the weight management program in compliance with evidence-based guidelines, and effectively promote healthy lifestyles and incremental behavior change; (4) devise a system for providing PC with ongoing support, resources, and continuing education on obesity-related counseling; (5) build prompts, assessment tools, and counseling strategies into the PC electronic health record (EHR) system to facilitate proven approaches to discussing and addressing weight issues; (6) utilize EHR systems to enhance informational exchange and support shared treatment plans between among providers; and (7) establish metrics and an automated reporting system to enable continuous monitoring of programmatic and clinical performance goals. As a first step in measuring program impact, program adoption, reach, and utilization were tracked. Results: Since forming the partnership, 26 pediatric practices implemented the weight management program and 28 nurses were trained as LCs. During the first 6 months following program initiation, 16,575 well-child visits were completed; 3,715 patients were identified as overweight or obese. For patients with elevated weight, 537 caregivers expressed concern with their child's weight status and 498 patients/families attended at least one weight management visit with a LC. Average reimbursement for LC visits was $30 per 30 minute visit increment. In addition, LCs' satisfaction with and confidence in delivering the weight management program were assessed 6 months after program initiation: 78% were very satisfied in their LC role; 89% rated the quality of the program as very good or excellent; 72% were more or much more confident in delivering pediatric weight management services; and 100% were satisfied to very satisfied with program-related EHR features. Conclusions: Our findings indicate that given the proper infrastructure to assess and treat pediatric obesity, community-based PC practices can be an appropriate setting for offering pediatric weight management services, and PC providers can develop efficacy in treating overweight and obese children. Continued efforts to demonstrate scalability of effective clinical pediatric weight management programs that can be offered in the PC setting are imperative given the need for population-based approaches to address the obesity epidemic.
    2013 American Academy of Pediatrics National Conference and Exhibition; 10/2013
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    ABSTRACT: Objective:The aim was to formulate practice guidelines for the diagnosis and treatment of polycystic ovary syndrome (PCOS).Participants:An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer developed the guideline.Evidence:This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence.Consensus Process:One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of The Endocrine Society and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize supporting evidence.Conclusions:We suggest using the Rotterdam criteria for diagnosing PCOS (presence of two of the following criteria: androgen excess, ovulatory dysfunction, or polycystic ovaries). Establishing a diagnosis of PCOS is problematic in adolescents and menopausal women. Hyperandrogenism is central to the presentation in adolescents, whereas there is no consistent phenotype in postmenopausal women. Evaluation of women with PCOS should exclude alternate androgen-excess disorders and risk factors for endometrial cancer, mood disorders, obstructive sleep apnea, diabetes, and cardiovascular disease. Hormonal contraceptives are the first-line management for menstrual abnormalities and hirsutism/acne in PCOS. Clomiphene is currently the first-line therapy for infertility; metformin is beneficial for metabolic/glycemic abnormalities and for improving menstrual irregularities, but it has limited or no benefit in treating hirsutism, acne, or infertility. Hormonal contraceptives and metformin are the treatment options in adolescents with PCOS. The role of weight loss in improving PCOS status per se is uncertain, but lifestyle intervention is beneficial in overweight/obese patients for other health benefits. Thiazolidinediones have an unfavorable risk-benefit ratio overall, and statins require further study.
    The Journal of Clinical Endocrinology and Metabolism 10/2013; 98(12). DOI:10.1210/jc.2013-2350 · 6.21 Impact Factor
  • Lama Farchoukh · Sara Michaliszyn · Silva Arslanian
    49th EASD Annual Meeting; 09/2013
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    ABSTRACT: It is unclear whether regular exercise alone (without calorie restriction) is a useful strategy to reduce adiposity and obesity-related metabolic risk factors in obese girls. We examined the effects of aerobic (AE) versus resistance exercise (RE) alone on visceral adipose tissue (VAT), intrahepatic lipid and insulin sensitivity in obese girls. Forty-four obese adolescent girls (BMI >95(th), 12-18 yrs) were randomized to 3-months of 180 min/week AE (n=16) or RE (n=16) or a non-exercising control group (n=12). Total fat and VAT were assessed by MRI and intrahepatic lipid by proton magnetic resonance spectroscopy. Intermuscular AT (IMAT) was measured by CT. Insulin sensitivity was evaluated by a 3-hour hyperinsulinemic (80 mU/m(2)/min)-euglycemic clamp. Compared with controls (0.13 ± 1.10 kg), Body weight did not change (P>0.1) in the AE (-1.31 ± 1.43 kg) and RE (-0.31 ± 1.38 kg) groups. Despite the absence of weight loss, total body fat (%) and IMAT decreased (P<0.05) in both exercise groups compared with control. Compared with control, significant (P<0.05) reductions in VAT (Δ -15.68 ± 7.64 cm(2)) and intrahepatic lipid (Δ -1.70 ± 0.74%), and improvement in insulin sensitivity (Δ 0.92 ± 0.27 mg/kg/min per µU/ml) were observed in the AE group, but not the RE group. Improvements in insulin sensitivity in the AE group were associated with the reductions in total AT mass (r = -0.65, P=0.02). In obese adolescent girls, aerobic exercise, but not resistance exercise is effective in reducing liver fat, visceral adiposity and improving insulin sensitivity independent of weight loss or calorie restriction.
    AJP Endocrinology and Metabolism 09/2013; 305(10). DOI:10.1152/ajpendo.00285.2013 · 3.79 Impact Factor
  • Sara F Michaliszyn · Sojung Lee · Hala Tfayli · Silva Arslanian
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    ABSTRACT: To investigate the relationship between liver fat and in vivo insulin sensitivity, body composition, abdominal adiposity, and lipid metabolism in obese adolescent girls with polycystic ovary syndrome (PCOS). Cross-sectional case-control study. Research center. Thirty Tanner stage V obese girls with PCOS. None. Liver fat, abdominal adiposity, in vivo insulin-stimulated glucose disposal, whole-body lipolysis, fat oxidation, lipoprotein particle size and concentration, and liver enzymes (alanine aminotransferase and aspartate aminotransferase). Fatty liver index <1 is indicative of fatty liver. Fatty liver was present in 6.7% of the individuals (6.7%). Levels of alanine aminotransferase and aspartate aminotransferase were not different between those with fatty liver vs. without. Fatty liver index was associated with age (r = -0.53), body mass index (r = -0.41), total (r = -0.43) and subcutaneous (r = -0.41) abdominal adiposity, insulin-stimulated glucose disposal (r = 0.36), and small, medium small, and very small low-density lipoprotein concentrations (r ≥ -0.43). In a multiple regression analysis, age, total T, race, and insulin-stimulated glucose disposal explained 43% of the variance (R(2) = 0.43) in fatty liver index, with age (R(2) = 0.28) and total T (R(2) = 0.11) being independent contributors. Liver fat is associated with increasing age, even in the narrow adolescent age range, increasing abdominal adiposity, worsening insulin sensitivity, and dyslipoproteinemia in obese adolescent girls with PCOS. Targeting these abnormalities early in the course of PCOS may halt future nonalcoholic fatty liver disease in adulthood.
    Fertility and sterility 09/2013; 100(6). DOI:10.1016/j.fertnstert.2013.08.015 · 4.59 Impact Factor
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    ABSTRACT: Introduction L’augmentation de la prévalence du diabète de type-2 (DT2) chez les adolescents nécessite de proposer plusieurs options thérapeutiques. Matériels et méthodes Essai randomisé, en double-aveugle, contrôlé versus placebo, évaluant la sécurité, la tolérance et les paramètres pharmacocinétiques/pharmacodynamiques du liraglutide chez des adolescents (10–17 ans) ayant un DT2 traité par un régime approprié associé à une activité physique ou par la metformine. Augmentation progressive de la dose du liraglutide (0,3 ; 0,6 ; 0,9 ; 1,2 ; 1,8 mg/jour) chaque semaine sur 5 semaines. Résultats 21 patients ont été randomisés (ratio 2 : 1) : 14 traités par le liraglutide et 17 par le placebo ; 19 patients ont complété l’étude. À l’inclusion, les caractéristiques des patients étaient comparables dans les deux groupes : moyenne d’âge 14,8 (± 2,2) ans, poids 113,2 (± 35,6) kg, ancienneté du diabète 1,7 (± 1,4) ans, taux d’HbA1c 8,1 % (± 1,2 %). Aucun événement indésirable (EIs) grave n’a été rapporté. Les EIs les plus fréquents étaient les EIs gastro-intestinaux, qui étaient transitoires, indépendamment de la dose du liraglutide et du poids. Les profils de sécurité et de tolérance étaient similaires entre les deux groupes. Aucune pancréatite n’a été rapportée. La calcitoninémie était dans les normes. Après l’administration du liraglitude (1,8 mg/jour), la demivie (t1/2) était de 12h en moyenne et la clairance était de 1,7 L/h ; ces paramètres étaient comparables à ceux de l’adulte (t1/2 13h, CL 1,2 L/h). Après 5 semaines, la réduction de l’HbA1c était significativement plus importante dans le groupe liraglutide comparé au placebo (−0,86 vs 0,04 %, p = 0,0007). Le poids moyen restait stable (−0,50 vs −0,54 kg, p = 0,9703). Conclusion Le liraglutide était bien toléré chez les adolescents ayant un DT2. Les profils de sécurité, de tolérance et les paramètres pharmacocinétiques/pharmacodynamiques étaient comparables à ceux de l’adulte.
    Annales d Endocrinologie 09/2013; 39(4):A22. DOI:10.1016/S1262-3636(13)71702-6 · 0.87 Impact Factor
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    ABSTRACT: OBJECTIVE-The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and metformin plus lifestyle was intermediate. Herein we describe the temporal changes in measures of beta-cell function and insulin sensitivity over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS TODAY-participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/I-F]), insulinogenic index (Delta I-30/Delta G(30)) or C-peptide index (Delta C-30/Delta G(30)), and beta-cell function relative to insulin sensitivity (oral disposition index to [oDI]). RESULTS-During the first 6 months, metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower beta-cell function (similar to 50%), higher fasting glucose concentration, and higher HbA(1c) at randomization compared with those who did not fail. CONCLUSIONS-The beneficial change in insulin sensitivity and the resultant lower burden on beta-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial beta-cell reserve and HbA(1c) at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve beta-cell function before significant loss occurs and to reduce HbA(1c) may be beneficial in the treatment of youth with type 2 diabetes.
    Diabetes Care 06/2013; 36(6):1749-1757. DOI:10.2337/dc12-2393 · 8.42 Impact Factor

Publication Stats

8k Citations
1,005.66 Total Impact Points


  • 2000–2015
    • Childrens Hospital of Pittsburgh
      • • Department of Pediatrics
      • • Division of Pediatric Endocrinology, Diabetes and Metabolism
      • • Weight Management and Wellness Center
      Pittsburgh, Pennsylvania, United States
    • The Ohio State University
      • School of Physical Activity and Educational Services
      Columbus, OH, United States
  • 2013–2014
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 1991–2014
    • 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
  • 2011
    • University of Massachusetts Boston
      Boston, Massachusetts, United States
  • 2007
    • Mahidol University
      Krung Thep, Bangkok, Thailand
    • Children's Hospital of Richmond
      Ричмонд, Virginia, 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