Silva A Arslanian

University of Pittsburgh, Pittsburgh, Pennsylvania, United States

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Publications (189)901.75 Total impact

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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; · 2.13 Impact Factor
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    ABSTRACT: 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.
    Diabetes Care 09/2014; 37(9):2632-9. · 8.57 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; · 3.61 Impact Factor
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    ABSTRACT: 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; · 2.29 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; · 7.90 Impact Factor
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    Anales de Pediatría 05/2014; · 0.72 Impact Factor
  • Anales de Pediatría. 01/2014;
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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.
    The Journal of pediatrics 11/2013; · 4.02 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; · 7.74 Impact Factor
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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; · 6.31 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; · 4.51 Impact Factor
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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; · 4.30 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:A22. · 0.66 Impact Factor
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    ABSTRACT: Prepubertal African American (AA) youth compared with their Caucasian (C) peers have higher insulin secretion which correlates positively with free fatty acid (FFA) concentration. In our continued efforts to explain the racial disparity in insulinemia, and because FFAs modulate insulin secretion, we hypothesized that AA youth would have a greater response to FFA-induced β-cell insulin secretion than C youth. We compared the short-term effects of FFA elevation on fasting and glucose-stimulated C-peptide-modeled insulin secretion in prepubertal normal-weight AA versus C peers during a 2-hour hyperglycemic clamp (12.5mmol/L) on two occasions: a) infusion of normal saline (NS) and b) infusion of 20% intralipid (IL). During IL infusion, insulin sensitivity (IS) declined comparably in AA and C youth. Glucose sensitivity of 1(st) and 2(nd) phase insulin secretion showed a significant condition x race interaction being higher in AA youth. Disposition index, β-cell function relative to IS, declined with IL infusion in both AA and C youth with a significantly greater decrease in Cs compared with AAs. In conclusion, both AA and C prepubertal youth demonstrated a decline in β-cell function relative to IS during IL infusion, indicative of acute lipotoxicity. The greater decline in C youth compared with AAs may suggest that either C youth are more susceptible to β-cell lipotoxicity than AA youth, or alternatively, AA youth are hypersensitive to FFA stimulation of β-cell insulin secretion consistent with our theory.
    Diabetes 04/2013; · 7.90 Impact Factor
  • Tamara S Hannon, Dana L Rofey, Sojung Lee, Silva A Arslanian
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    ABSTRACT: OBJECTIVE: Although higher rates of depression are found among individuals with type 2 diabetes, it remains unknown if the presence of depressive symptoms is associated with heightened metabolic risk for the development of type 2 diabetes among youth. The objective of this study was to evaluate whether depressive symptoms in obese adolescents are associated with impaired β-cell function relative to insulin sensitivity [oral disposition index (oDI)] and/or dysglycemia or prediabetes, predictors of type 2 diabetes development. RESEARCH DESIGN AND METHODS: Fasting and oral glucose tolerance test (OGTT)-derived indices of glucose tolerance, insulin sensitivity, secretion, and oDI were evaluated in obese youth (n = 56, age 15.0 ± 1.6 yr, 68% female). The Children's Depression Inventory was utilized to determine depressive symptomatology. RESULTS: Despite no association between depressive symptoms and measures of adiposity, youth with higher depressive symptoms had (i) significantly higher fasting and stimulated glucose levels (13% higher glucose area under the OGTT curve), (ii) ∼50% lower oDI, and (iii) a 50% frequency of prediabetes. CONCLUSIONS: These data point to an important relationship between depressive symptoms and a heightened metabolic risk for type 2 diabetes in obese adolescents, including prediabetes and impairment in β-cell function relative to insulin sensitivity. While the directionality of these relationships is unknown, it should be determined if treating one disorder improves the other or vice versa.
    Pediatric Diabetes 03/2013; · 2.13 Impact Factor
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    ABSTRACT: Objective:Overweight/obese (OW/OB) African American (AA) adolescents have a more diabetogenic insulin secretion/sensitivity pattern compared with their American white (AW) peers. The present study investigated β-cell lipotoxicity to test whether increased free fatty acid (FFA) levels result in greater β-cell dysfunction in AA vs AW OW/OB adolescents.Research Design and Methods:Glucose-stimulated insulin secretion was modeled, from glucose and C-peptide concentrations during a 2-hour hyperglycemic (225 mg/dL) clamp in 22 AA and 24 AW OW/OB adolescents, on 2 occasions after a 12-hour overnight infusion of either normal saline or intralipid (IL) in a random sequence. β-Cell function relative to insulin sensitivity, the disposition index (DI), was examined during normal saline and IL conditions. Substrate oxidation was evaluated with indirect calorimetry and body composition and abdominal adiposity with dual-energy X-ray absorptiometry and magnetic resonance imaging at L4-L5, respectively.Results:Age, sex, body mass index, total and sc adiposity were similar between racial groups, but visceral adiposity was significantly lower in AAs. During IL infusion, FFAs and fat oxidation increased and insulin sensitivity decreased similarly in AAs and AWs. β-Cell glucose sensitivity of first- and second-phase insulin secretion did not change significantly during IL infusion in either group, but DI in each phase decreased significantly and similarly in AAs and AWs.Conclusions:Overweight/obese AA and AW adolescents respond to an overnight fat infusion with significant declines in insulin sensitivity, DI, and β-cell function relative to insulin sensitivity, suggestive of β-cell lipotoxicity. However, contrary to our hypothesis, there does not seem to be a race differential in β-cell lipotoxicity. Longer durations of FFA elevation may unravel such race-related contrasts.
    The Journal of Clinical Endocrinology and Metabolism 03/2013; · 6.31 Impact Factor
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    S Lee, S F Burns, D White, J L Kuk, S Arslanian
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    ABSTRACT: Objective:We examined the effects of acute exercise on postprandial triglyceride (TG) metabolism following a high-fat meal in overweight black vs white adolescents.Design and subjects:Twenty-one black and 17 white adolescents (12-18 yrs, body mass index 85th percentile) were evaluated twice, during control versus exercise trials, 1-4 weeks apart, in a counterbalanced randomized design. In the control trial, participants performed no exercise on day 1. In the exercise trial, participants performed a single bout of 60-min exercise (50% VO2 peak) on a cycle ergometer on day 1. On day 2 of both trials, participants consumed a high-fat breakfast (70% calories from fat) and blood was sampled for TG concentration in the fasted state and for 6 h postprandially.Results:There was a significant main effect of condition on postprandial peak TG concentration (P=0.01) and TG area under the curve (AUC) (P=0.003), suggesting that independent of race, peak TG and TG-AUC was lower in the exercise trial vs control trial. Including Tanner stage, gender, total fat (kg) and visceral adipose tissue (VAT) as independent variables, stepwise multiple regression analyses revealed that in whites, VAT was the strongest (P<0.05) predictor of postprandial TG-AUC, explaining 56 and 25% of the variances in TG-AUC in the control and exercise trials, respectively. In blacks, VAT was not associated with postprandial TG-AUC, independent of trial.Conclusion:A single bout of aerobic exercise preceding a high-fat meal is beneficial to reduce postprandial TG concentrations in overweight white adolescents to a greater extent than black adolescents, particularly those with increased visceral adiposity.International Journal of Obesity advance online publication, 19 March 2013; doi:10.1038/ijo.2013.29.
    International journal of obesity (2005) 03/2013; · 5.22 Impact Factor
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    ABSTRACT: OBJECTIVE To 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes, and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and β-cell function in this cohort.RESEARCH DESIGN AND METHODS Plasma 25(OH)D concentrations were examined in banked specimens in 9- to 20-year-old obese youth (n = 175; male 42.3%, black 46.3%) (NGT, n = 105; impaired glucose tolerance [IGT], n = 43; type 2 diabetes, n = 27) who had in vivo insulin sensitivity and secretion measured by hyperinsulinemic-euglycemic and hyperglycemic clamp techniques and had an assessment of total body composition and abdominal adiposity.RESULTSThe mean age and BMI of the subjects were 14.3 ± 2.1 years and 35.7 ± 5.6 kg/m(2), respectively. BMI, plasma 25(OH)D, and the proportion of vitamin D-deficient and -insufficient children did not differ across the three groups. Furthermore, there was no association between 25(OH)D and in vivo insulin sensitivity or β-cell function relative to insulin sensitivity (disposition index) in all groups combined or in each group separately.CONCLUSIONS Our data in obese youth show 1) no differences in plasma 25(OH)D concentrations across the glucose tolerance groups, and 2) no relationship between 25(OH)D and in vivo insulin sensitivity and β-cell function relative to insulin sensitivity in any of the groups. It remains uncertain if enhancement of the vitamin D status could improve pathophysiological mechanisms of prediabetes and type 2 diabetes in obese youth.
    Diabetes care 01/2013; · 7.74 Impact Factor
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    ABSTRACT: OBJECTIVE: To compare indices of insulin secretion, insulin sensitivity (IS), and oral disposition index (oDI) during the liquid mixed-meal test in obese youth with clinically diagnosed type 2 diabetes mellitus (T2DM) and negative autoantibodies (Ab(-)) versus those with T2DM and positive autoantibodies (Ab(+)) to examine whether differences in β-cell function can be detected between the 2 groups. STUDY DESIGN: Twenty-seven youth with Ab(-) and 15 youth with Ab(+) clinically diagnosed T2DM underwent a mixed-meal test (Boost; 55% carbohydrate, 25% protein, and 20% fat). Fasting and mixed-meal-derived insulin and C-peptide indices of IS, secretion (30-minute insulinogenic [ΔI(30)/ΔG(30)] and C-peptide [ΔC(30)/ΔG(30)]), and oDI were calculated. RESULTS: Indices of insulin secretion were ∼40%-50% lower in patients with Ab(+) T2DM compared with those with Ab(-) T2DM. After controlling for body mass index, ΔI(30)/ΔG(30), ΔC(30)/ΔG(30), C-peptide area under the curve (AUC)/glucose AUC, and insulin AUC/glucose AUC were significantly (P < .05) lower in the Ab(+) group compared with the Ab(-) group. Sensitivity indices were significantly higher in the Ab(+) group. The oDI, 1/fasting insulin × ΔI(30)/ΔG(30) (0.04 ± 0.02 vs 0.12 ± 0.02 mg/dL(-1); P = .005), and 1/fasting C-peptide × ΔC(30)/ΔG(30) (0.02 ± 0.009 vs 0.05 ± 0.006 mg/dL(-1); P = .018) were lower in the Ab(+) group. Receiver operating characteristic curve analyses revealed that fasting C-peptide <3.2 ng/mL had 87% sensitivity and 74% specificity and ΔC(30)/ΔG(30) <0.075 ng/mL per mg/dL had 93% sensitivity and 80% specificity for identifying youth with Ab(+) T2DM. CONCLUSION: During a liquid mixed-meal test, indices of β-cell function were lower and IS was higher in patients with Ab(+) T2DM versus those with Ab(-) T2DM, with high sensitivity and specificity for fasting and stimulated C-peptide as markers of Ab(+) status. Indices of insulin secretion during this standardized mixed-meal test could be used to assess β-cell function in therapeutic trials of β-cell restoration in youth with T2DM.
    The Journal of pediatrics 01/2013; · 4.02 Impact Factor

Publication Stats

6k Citations
901.75 Total Impact Points

Institutions

  • 1990–2014
    • University of Pittsburgh
      • • Division of Pediatric Pathology at Children's Hospital of Pittsburgh of UPMC
      • • Department of Pediatrics
      • • Department of Human Genetics
      • • Center for Research on Health Care
      • • School of Medicine
      Pittsburgh, Pennsylvania, United States
  • 2012–2013
    • Baylor College of Medicine
      Houston, Texas, United States
    • Nanyang Technological University
      Tumasik, Singapore
    • Virginia Commonwealth University
      • Department of Internal Medicine
      Richmond, VA, United States
  • 2011–2013
    • Indiana University-Purdue University Indianapolis
      • Department of Pediatrics
      Indianapolis, IN, United States
    • Hospital Universitario Cruces
      Bilbo, Basque Country, Spain
  • 1990–2013
    • Childrens Hospital of Pittsburgh
      • • Weight Management and Wellness Center
      • • Division of Pediatric Endocrinology, Diabetes and Metabolism
      • • Department of Pediatrics
      Pittsburgh, Pennsylvania, United States
  • 2005
    • Bloomsburg University
      • Department of Exercise Science
      Bloomsburg, Pennsylvania, United States
  • 2000
    • The Ohio State University
      • School of Physical Activity and Educational Services
      Columbus, OH, United States
  • 1999
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States
  • 1994
    • Children's National Medical Center
      Washington, Washington, D.C., United States