45Th And Penn, 3Rd Floor Children's Hospital Drive
Pittsburgh PA 15201
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License #: MD436563
Taxonomy Codes:208000000X 2080P0205X
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Early Biomarkers of Subclinical Atherosclerosis in Obese Adolescent Girls with Polycystic Ovary Syndrome. - The Journal of pediatrics
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.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.PWV was higher in OB-PCOS (664Â Â±Â 24Â cm/s) and OB-non-PCOS (624Â Â±Â 37Â cm/s) compared with NW-non-PCOS (468Â Â±Â 13Â cm/s, PÂ <Â .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 (rsÂ =Â .46), insulin sensitivity index (homeostatic model assessment-insulin resistance rsÂ =Â .31), systolic blood pressure (rsÂ =Â .24; PÂ â‰¤Â .003 for all), and free testosterone (rsÂ =Â .24; PÂ =Â .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)Â =Â 0.068, PÂ =Â .003).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.Copyright Â© 2015 Elsevier Inc. All rights reserved.
Triglyceride glucose index as a surrogate measure of insulin sensitivity in obese adolescents with normoglycemia, prediabetes, and type 2 diabetes mellitus: comparison with the hyperinsulinemic-euglycemic clamp. - Pediatric diabetes
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)â€‰Ã—â€‰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 (8.3â€‰Â±â€‰0.5, 8.6â€‰Â±â€‰0.5, 8.9â€‰Â±â€‰0.6, pâ€‰<â€‰0.0001). The correlation of TyG index to Rd was -0.419 (pâ€‰<â€‰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, pâ€‰<â€‰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.Â© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
The Diagnosis of Polycystic Ovary Syndrome during Adolescence. - Hormone research in paediatrics
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. Â© 2015 S. Karger AG, Basel.
Relationship of adiponectin and leptin with autoimmunity in children with new-onset type 1 diabetes: a pilot study. - Pediatric diabetes
To explore racial differences in adiponectin, and leptin and their relationship with islet autoimmunity in children with new-onset type 1 diabetes (T1D).Medical records were reviewed from a cohort of new-onset clinically diagnosed T1D subjects matched by race, age, gender, and year of diagnosis. Sera were available for 156 subjects (77 African American (AA), 79 Caucasian (C), 48% male, age of 11.1â€‰Â±â€‰3.8â€‰yr) and assayed for adiponectin and leptin prior to (D0), 3, 5â€‰d, and 2-4â€‰months (M3) after insulin therapy and islet autoantibodies to GAD, IA2, insulin, and ICA were measured at onset.Adiponectin levels increased significantly following insulin therapy by day 5 (D5) (D0: 13.7â€‰Â±â€‰7.2 vs. D5: 21.3â€‰Â±â€‰9.9â€‰Âµg/mL, pâ€‰<â€‰0.0001), but no further significant increase from D5 to M3. At DO, AA had lower adiponectin levels (10.5 vs. 15.7â€‰Âµg/mL, pâ€‰=â€‰0.01), were more often overweight than C (55 vs. 18%, BMIâ€‰â‰¥â€‰85thâ€°) and fewer had positive autoantibodies (72 vs. 87%, pâ€‰=â€‰0.05). Racial differences in adipocytokines disappeared after adjustment for BMI. At M3, subjects with more number of positive autoantibodies had higher adiponectin levels (pâ€‰=â€‰0.043) and adiponectin/leptin ratio (ALR) (pâ€‰=â€‰0.01), and lower leptin levels (pâ€‰=â€‰0.016).Adiponectin levels increased acutely with insulin therapy. Significantly lower adiponectin levels in AA were related to greater adiposity and not race. These pilot data showing those with the fewest autoantibodies had the lowest adiponectin levels, supporting the concept that insulin-resistant subjects may present with clinical T1D at earlier stages of Î²-cell damage.Â© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Liver disease and other comorbidities in Wolcott-Rallison syndrome: different phenotype and variable associations in a large cohort. - Hormone research in pÃ¦diatrics
Wolcott-Rallison syndrome (WRS) is caused by recessive EIF2AK3 mutations and characterized by early-onset diabetes and skeletal dysplasia. Hepatic dysfunction has been reported in 60% of patients.To describe a cohort of WRS patients and discuss the pattern and management of their liver disease.Detailed phenotyping and direct sequencing of EIF2AK3 gene were conducted in all patients.Twenty-eight genetically confirmed patients (67% male; mean age 4.6 years) were identified. 17 different EIF2AK3 mutations were detected, of which 2 were novel. The p.S991N mutation was associated with prolonged survival and p.I650T with delayed onset. All patients presented before 25 months with diabetes with variation in the frequency and severity of 10 other features. Liver disease, first manifested as non-autoimmune hepatitis, was the commonest extra-pancreatic feature identified in 85.7% (24/28). 22/24 had at least one episode of acute hepatic failure which was the cause of death in all deceased patients (13/28). One child was treated by liver transplantation and had no liver disease and better diabetes control for the following 6 years.Liver disease in WRS is more frequent than previously described and carries high mortality. The first experience with liver transplantation in WRS is encouraging.Â© 2015 S. Karger AG, Basel.
Pre-diabetes in overweight youth and early atherogenic risk. - Metabolism: clinical and experimental
To compare atherogenic lipoprotein particles and vascular smooth muscle biomarkers in overweight youth with pre-diabetes (PD) vs. normal glucose tolerance (NGT).144 adolescents (60 black, 84 white; 102 female; PD=45, NGT=99) aged 10-19 years underwent a fasting blood draw and 2-h 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.Compared with NGT, PD adolescents had smaller LDL (meanÂ±SE: 20.5Â±0.1 vs. 21.0Â±0.1 nm; P=0.002) and HDL (8.62Â±0.05 vs. 8.85Â±0.04 nm; P=0.013) size and elevated medium small (159.2Â±10.3 vs. 123.8Â±6.4 nmol/L; P=0.037) and very small (626.3Â±45.4 vs. 458.5Â±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.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.Copyright Â© 2014 Elsevier Inc. All rights reserved.
Coronary artery calcification in obese youth: what are the phenotypic and metabolic determinants? - Diabetes care
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.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).A total of 50% had CACs (CAC+: Agatston CAC score â‰¥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.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.Â© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Î²-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes. - Diabetes
Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Î²-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Î²-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Î²-Cell function parameters were derived from established mathematical models yielding Î²-cell glucose sensitivity (Î²CGS), 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-Î²CGS to the 2-h hyperglycemic clamp-Î²CGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, Î²CGS 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.Â© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Dubowitz syndrome: common findings and peculiar urine odor. - The application of clinical genetics
Dubowitz syndrome is a rare, autosomal recessive disorder characterized by intrauterine and postnatal growth retardation, severe microcephaly, psychomotor retardation, hyperactivity, eczema, and characteristic dysmorphic facial features. Although many cases have been reported, the cause of this disease is still unknown.We present here the case of a Lebanese girl with Dubowitz syndrome in whom an unpleasant urine odor was persistently reported since birth.Although Dubowitz syndrome has been largely described in the medical literature, this is the first time that a peculiar urine odor was reported. This case report adds a new and unusual feature to the numerous findings related to this rare polymorphous syndrome.
Polycystic ovary syndrome and nonalcoholic fatty liver in obese adolescents: association with metabolic risk profile. - Fertility and sterility
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 â‰¥ -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.Copyright Â© 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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