Faculty Bibliography
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Interpretation of androgen and anti-Mullerian hormone profiles in a Hispanic cohort of 5- to 8-year-old girls with premature adrenarche
PURPOSE/OBJECTIVE:Premature adrenarche (PA) often leads to polycystic ovary syndrome (PCOS). Higher anti-mullerian hormone (AMH) levels are reported in PCOS. We studied the androgen profile and AMH profiles in Hispanic girls with PA (aged 5-8 years) and age and body mass index (BMI) matched controls. METHODS:Retrospective review of electronic medical records of girls who met the inclusion criteria for premature adrenarche were done. RESULTS:PA girls (n=76) were matched to control girls (n=12) for age (mean±standard deviation) (6.7±1 years vs. 6.2±1.3 years) and BMI (20±10 kg/m2 vs. 17.8±2.7 kg/m2). Dehydroepiandrostenedione sulfate (63.3±51.3 μg/dL vs. 29.8±17.3 μg/dL, P<0.001) and testosterone levels (11.4±4.8 ng/dL vs. 8.2±2.9 ng/dL, P=0.001) were significantly higher in the PA group than controls. AMH values (<14 years: reference range, 0.49-3.15 ng/mL) were 3.2±2.2 ng/mL vs. 4.6± 3.2 ng/mL respectively in the PA and control groups and were not different (P=0.4). AMH did not show a correlation with bone age (P=0.1), and testosterone (P=0.9) in the PA group. 17-hydroxyprogesterone levels (17-OHP ng/dL) were 39.5±30.5 ng/dL vs. 36.8±19.8 ng/dL in PA versus control girls. The concentration of 17-OHP was not statistically different between the control and PA groups. CONCLUSION/CONCLUSIONS:Higher AMH was not observed in PA girls and no correlation with BA and androgen levels was observed.
PMID: 30599482
ISSN: 2287-1012
CID: 3562792
Effect of one time high dose "stoss therapy" of vitamin D on glucose homeostasis in high risk obese adolescents
OBJECTIVE:To study the effect of using a one time high dose "stoss therapy" of vitamin D2 (ergocalciferol: VD2) on indices of insulin sensitivity {whole body sensitivity index: WBISI} and secretion {insulinogenic index: IGI} measured during an oral glucose tolerance test (OGTT) in obese adolescents with VDD (25 OHD; serum metabolite of vit D: < 30 ng/dL). SUBJECTS AND METHODS/METHODS:In a randomized placebo controlled cross over design 20 obese adolescents with vitamin D deficiency (VDD) had baseline OGTT. Arm A received one time high dose 300,000 IU of ergocalciferol and Arm B received placebo. After 6 weeks the adolescents were reassigned to Arm A if they were in Arm B and vice versa. 25OHD, calcium, parathyroid hormone, comprehensive metabolic panel, urine calcium creatinine ratio were measured at each study visit. OGTTs to assess indices of sensitivity and secretion were done at baseline, 6 weeks and 12 weeks respectively. RESULTS:Adolescents were obese and insulin resistant (mean ± SD: mean age = 15.1 ± 1.9 years; BMI: 32.7 ± 9.8; homeostatic model of insulin resistance: HOMA-IR: 4.2 ± 2.8). Stoss therapy with VD2 increased 25OHD from baseline (16.7 ± 2.9 to 19.5 ± 4.5; p = 0.0029) when compared to the placebo. WBISI (2.8 ± 1.9) showed a trend towards improvement in Rx group (p = 0.0577) after adjustment for covariates. IGI (3 ± 2.2) showed an improvement in both Rx and placebo groups. CONCLUSIONS:Our study demonstrated that using a high dose of VD2 (300,000 IU) did not have any beneficial effect on insulin sensitivity (whole body sensitivity index {WBISI}) and secretory indices (insulinogenic index {IGI}) in obese adolescents. High dose "stoss therapy" of VD2 did not appear to have any beneficial effect on glucose homeostasis on obese adolescents.
PMID: 29641737
ISSN: 2359-4292
CID: 3037362
Birth weight, early life weight gain and age at menarche: a systematic review of longitudinal studies
BACKGROUND AND OBJECTIVE/OBJECTIVE:Adiposity in pre- and postnatal life may influence menarcheal age. Existing evidence is primarily cross-sectional, failing to address temporality, for which the role of adiposity in early life remains unclear. The current study sought to systematically review longitudinal studies evaluating the associations between birth weight and infant/childhood weight status/weight gain in relation to menarcheal age. METHODS:PubMed, EMBASE, Web of Science, Global Health (Ovid) and CINAHL were systematically searched. Selected studies were limited to English-language articles presenting multi-variable analyses. Seventeen studies reporting risk estimates for birth weight (n = 3), infant/childhood weight gain/weight status (n = 4) or both (n = 10), in relation to menarcheal age were included. RESULTS:Lower vs. higher birth weight was associated with earlier menarche in nine studies and later menarche in one study, while three studies reported a null association. Greater BMI or weight gain over time and greater childhood weight were significantly associated with earlier menarche in nine of nine and six of seven studies, respectively. CONCLUSIONS:Studies suggested that lower birth weight and higher body weight and weight gain in infancy and childhood may increase the risk of early menarche. The pre- and postnatal period may thus be an opportune time for weight control interventions to prevent early menarche, and its subsequent consequences.
PMID: 28872224
ISSN: 1467-789x
CID: 2909212
Presentation of hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA) in adolescent diabetes [Meeting Abstract]
Introduction: Hyperosmolar hyperglycemic state (HHS) seen in uncontrolled Type 2 diabetes (T2DM) is characterized by severe hyperglycemia (>600 mg/dl), hyperosmolality (> 330 mOsm/kg), and mild/no ketosis(l). As compared to diabetic ketoacidosis (DKA), in HHS insulin action may be inadequate to facilitate glucose utilization by insulin sensitive tissues but sufficient for the prevention of lipolysis and ketogenesis. A mixed picture (HHS+ DKA) is usually characterized by glucose > 600 mg/dL, pH < 7.3, bicarbonate < 15 mEq/L and serum osmolality > 320 mOsm/kg(2). Actual incidence of this mixed picture (HHS+ DKA) in pediatric diabetes is not well known. Objective: a. Description of the clinical presentation and therapeutic challenges encountered in adolescents who presented with a mixed picture (HHS+ DKA); b. Define the metabolic aberrations encountered during their hospitalizations. Case Series: Patients # 1 & 2 had new onset T2DM and # 3 had T1 DM for two years. Patient ages were (mean +/- SD) 15+/-3.5 years and weight 84 +/-35 kg. Patient # 1 and 2 were African American while patient # 3 was Hispanic. They presented in severe dehydration (15-20%) and altered mental status. Initial labs: glucose 1552 +/-309 mg/dL, serum osmolality 439 +/-112 mOsm/kg, pH 7.1 +/-0.1; bicarbonate 10.3 +/-2.9 mEq/L; alanine aminotransferase (ALT) 43+/- 28 U/L, aspartate aminotransferase (AST) 44 +/-23 U/L; amylase 122 +/-87 U/L, serum creatinine 2 +/-1.2 mg/dL. Management: * Patients' fluid requirements in first 48 hrs: total 17.6 +/-8.3 L (maintenance and deficit correction 5.5 +/-1.3 & 12 +/-7 L respectively). Low dose insulin drip (0.05-0.08 U/kg/hr) was used to correct hyperglycemia and acidosis after initial resuscitation. *Severe hypernatremia (corrected sodium 168 +/-17 mEq/L) and hyperchloremia (130 +/-20 mEq/L) with maximum corrected sodium of 184 mEq/L (Patient # 1) was seen which required use of hypotonic fluids (%
EMBASE:617151358
ISSN: 0163-769x
CID: 2632112
Turner syndrome with 45, X mosaicism and Y/autosome translocation [Meeting Abstract]
Background:Y chromosome material is detected in 6% of Turner syndrome patients by karyotype (1). Y/autosome translocation in Turner syndrome is associated with a) female genitalia or signs of virilization; b) gonadal dysgenesis and a 7-30% future risk of gonadoblastoma (2). We present an atypical phenotype of a Turner syndrome female with 45,X/45,X,dic(Y;5)(p11.3; p15.3). Clinical case: A 9-year and 10-month-old girl presented with short stature (height: 121 cm, -3.2 SD; weight: 37.6 kg, 75%) and Turner syndrome habitus: wide short neck, broad chest, with no signs of virilization, no cardiac defects, no hepatosplenomegaly and with mild learning disability. Lab evaluation: LH 1.14 (<=2.91 U/L); FSH 50.9 (0.72-5.33 U/L); estradiol <2 (
EMBASE:617153110
ISSN: 0163-769x
CID: 2631962
A clinical pilot to assess improvement in health related quality of life (QOL), treatment satisfaction, and glycemic control in adolescents with type 2 diabetes (T2DM) using continuous subcutaneous insulin injection therapy (CSII) [Meeting Abstract]
Background: Treatment options for adolescents with Type 2 diabetes (T2DM) are limited to metformin and/or insulin (in adults there are >100 Rx options). Most adolescents with T2DM are in poor glycemic control 1. If this worrisome trend continues these adolescents, mostly of minority racial/ethnic groups, will have retinopathy, neuropathy and nephropathy in their twenties when compared to adults who are diagnosed with T2DM in their forties 2. Objectives: Pilot study to investigate whether insulin pump therapy is a feasible treatment modality, improves quality of life (QOL) in adolescents with T2DM over a 3-month period. Pumps are considered appropriate, safe and efficacious by the American Diabetes Association in children with T1 DM 3, though studies demonstrating their efficacy in adolescents with T2DM are lacking. Method: In an open-label pilot (clinicaltrials.gov#02748122) adolescents with T2DM in poor control (HbA1c > 8%) on insulin (0.5-1.5 U/kg/day or more) and/or oral hypoglycemic agents were recruited. Adolescents were placed on a continuous glucose monitoring system (CGMS) before the pump start. At 1, 2 and 3 months pumps were downloaded and settings were titrated accordingly. Validated QOL questionnaires: the Pediatric Quality of Life Inventory (PedsQL: generic and diabetes modules), diabetes empowerment and treatment satisfaction scales were administered at the start and end of the pilot. Insulin pump MMT 723 and i-Pro2 professional, both made by Medtronic Inc., were used. Results: Five female adolescents (mean +/- SD: age: 16.3+/- 1.9 years; duration of diabetes: 5.4+/- 3 years; BMI: 30+/- 3) have completed the pilot. The total daily dose (TDD) of Lantus at the start of the study was 53+/-3 units. At the end of the pilot pump settings were as follows: basal rate: 1.4+/-0.4 U/hr; insulin carbohydrate ratio: 7+/-1 and insulin sensitivity factor: 23+/-7. The average blood sugars at the start and end of the pilot were: 205+/-91 and 161+/-70 mg/dl, respectively. The Hba1c at the start and end of the pilot were 11.7+/-1.4% and 10.3+/-1.8%, respectively. The acceptance was 40% with two adolescents opting to continue with insulin pumps for their ongoing diabetes management. Insulin requirements went down by 30% and the QOL parameters showed a trend to improvement. Conclusions: At the end of the pilot HbA1 c decreased by 1.3% which was significant. This result validates that insulin pumps when used by motivated adolescents improve glycemic control even over a short-term period. Teaching pump therapy to these technologically savvy adolescents was easy and adherence was fair (two subjects wore the pump 50% of the time of the study duration). Until more Rx options get approval insulin pumps may be an option to consider as more adolescents fail metformin and insulin injections and face enormous physical and psychological challenges of their poorly controlled T2DM
EMBASE:617153112
ISSN: 0163-769x
CID: 2631952
The relationship between insulin resistance and endothelial dysfunction in obese adolescents
BACKGROUND: Insulin resistance and endothelial dysfunction share a reciprocal relationship that links the metabolic and cardiovascular sequelae of obesity. We characterized the brachial artery reactivity testing (BART) and carotid artery-intima media thickness (CIMT) in adolescents categorized as obese insulin resistant (OIR) and obese not insulin resistant (ONIR). Lipoprotein particle (p) analysis and inflammatory cytokines in OIR and ONIR groups were also analyzed. METHODS: Obese adolescents (n=40; mean body mass index [BMI] 35.6) were categorized as ONIR and OIR based on their homeostatic model assessment of insulin resistance (HOMA-IR) calculation ( than 3.4). Ultrasound measured conduit arterial function BART, microvascular function (post-ischemic hyperemia) and conduit artery structure CIMT. RESULTS: BART did not differ according to IR status (mean+/-SD: 7.0+/-4.3% vs. 5.9+/-3.4% in ONIR and OIR, respectively, p=0.3, but post-ischemic hyperemia was significantly greater in the ONIR group (4.5+/-2.2 vs. 3.5+/-3, p=0.04). Atherogenic lipoprotein particles; large VLDL particles and small LDL particles were higher in the OIR compared to ONIR group. CONCLUSIONS: OIR adolescents demonstrate an inflamed atherogenic milieu compared to the ONIR adolescents. Microvascular function, but not conduit vessel structure or function, was impaired in association with IR.
PMID: 28525354
ISSN: 2191-0251
CID: 2618642
Birth weight, early life weight gain and age at menarche: a systematic review of longitudinal studies [Meeting Abstract]
ISI:000405986500387
ISSN: 1530-6860
CID: 2706872
Prediabetes in Obese Adolescents: An Emerging Clinical Priority
PMID: 27941083
ISSN: 1938-2707
CID: 2363272
ANALYSIS OF INSULIN SECRETORY DYNAMICS DURING ORAL GLUCOSE TOLERANCE TEST (OGTT) IN OBESE PREDIABETIC CHILDREN AND ADOLESCENTS. [Meeting Abstract]
ISI:000412595405423
ISSN: 1663-2826
CID: 2746102
