These findings demonstrate that diabetic adolescents have significant insulin resistance, even compared with subjects of similar obesity and body fatness, and impaired insulin secretion relative to their degree of insulin resistance. However, the adolescent diabetic subjects retained a first-phase insulin response to glucose that was comparable to lean controls and did not have hyperproinsulinemia or hyperglucagonemia.

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Objective To test the hypothesis that insulin secretion and insulin sensitivity would be improved in adolescents after Roux-en-Y gastric bypass (RYGB). Study design A longitudinal study of 22 adolescents and young adults without diabetes undergoing laparoscopic RYGB (mean age 17.1 ± 1.42 years; range 14.5–20.1; male/female 8/14; Non-Hispanic White/African American 17/5) was conducted. Intravenous glucose tolerance tests were done to obtain insulin sensitivity (insulin sensitivity index), insulin secretion (acute insulin response to glucose), and the disposition index as primary outcome variables. These variables were compared over the 1 year of observation using linear mixed modeling. Results In the 1-year following surgery, body mass index fell by 38% from a mean of 61 ± 12.3 to 39 ± 8.0 kg/m2 (P < .01). Over the year following surgery, fasting glucose and insulin values declined by 54% and 63%, respectively. Insulin sensitivity index increased 300% (P < .01), acute insulin response to glucose decreased 56% (P < .01), leading to a nearly 2-fold increase in the disposition index (P < .01). Consistent with improved β-cell function, the proinsulin to C-peptide ratio decreased by 21% (P < .01). Conclusions RYGB reduced body mass index and improved both insulin sensitivity and β-cell function in severely obese teens and young adults. These findings demonstrate that RYGB is associated with marked metabolic improvements in obese young people even as significant obesity persists. Trial registration ClinicalTrials.gov: NCT00360373.

Abnormalities in glucose metabolism are frequent in young FA patients without prior diagnosis of diabetes, and are associated with marked defects in insulin secretion.

Background/ObjectiveYouth with obesity have an altered HDL subspecies profile characterized by depletion of large apoE rich HDL particles and an enrichment of small HDL particles. The goal of this study was to test the hypothesis that this atherogenic HDL profile would be reversed and that HDL function would improve with metabolic surgery.MethodsSerum samples from adolescent males with severe obesity mean ± SD age of 17.4 ± 1.6 years were studied at baseline and 1 year following vertical sleeve gastrectomy (VSG). HDL subspecies and HDL function were evaluated pre and post VSG using paired t-tests. A lean group of adolescents was included as a reference group.ResultsAfter VSG, BMI decreased by 32% and insulin resistance as estimated by HOMA-IR decreased by 75% (both p<0.01). Large apoE rich HDL subspecies increased following VSG (p<0.01) and approached that of lean adolescents despite participants with considerable residual obesity. Additionally, HDL function improved compared to baseline (cholesterol efflux capacity increased by 12%, HDL lipid peroxidation potential decreased by 30%, and HDL anti-oxidative capacity improved by 25%, all p<0.01).ConclusionsMetabolic surgery results in a significant improvement in the quantity of large HDL subspecies and HDL function. Our data suggest metabolic surgery may improve cardiovascular risk in adolescents and young adults.

ABSTRACT. Virilization, including penile enlargement and growth of pubic hair and facial acne, developed in a 2-year-old boy over a period of months. This sexual development was induced by incidental and unintentional dermal exposure to a testosterone cream that was applied to his father's arm and back as a part of body building regimen. Except for penile size, the other signs of virilization diminished several months after the exposure was discontinued. Pediatrics 1999;104(2). URL: http://www.pediatrics.org/cgi/content/full/104/2/e23; testosterone, sexual development, childhood, topical exposure.ABBREVIATIONS. T, testosterone; BA, bone age; DHT, dihydrotestosterone.V irilization in boys before puberty caused by exposure to exogenous androgens is rarely reported. We have evaluated a 2-year-old boy who developed androgenization, including progressive penile enlargement and development of pubic hair and facial acne, over a period of months. We discovered dermal exposure to exogenous androgens and ruled out the other causes of androgenization. Here, we discuss the differential diagnosis, laboratory testing, and outcome of this patient. Given the widespread availability of androgens in our society, we suspect that this is not an isolated event. CASE PRESENTATIONA 2.7-year-old boy presented to our pediatric endocrine clinic for evaluation of his sexual development. Over the past 4 to 5 months, he developed progressive enlargement of his penis. Over 1 to 2 months before this visit, he also developed facial acne and pubic hair. The patient was otherwise healthy and active. No change in behavior was noticed. There was no history of accidental ingestion of any medications. However, during approximately the past year, his father had been applying a topical cream containing 50 g of testosterone (T) per ounce to his arms and back (4 oz/day) as a part of a body building regimen. Although the cream was not applied directly to the boy, he had close contact with his father, as well as with his father's body building equipment and mats, which were smeared with the T cream.The patient was born at 31 weeks' gestation and subsequently was diagnosed with congenital hypothyroidism. He had been receiving thyroid replacement therapy successfully since 1 month of age. He had demonstrated a remarkable catch-up growth since birth, and his height crossed the 5th percentile at 21 months of age. He was seen in our pediatric endocrine clinic at 2 years of age. At that time, he was clinically and biochemically euthyroid and had no abnormalities of sexual development.The family history is unremarkable. His father measures 5 feet 7 inches, and his mother measures 5 feet 5 inches. There is no known family history of any causes of abnormal sexual development such as precocious puberty, intracranial tumor, or adrenal abnormalities.Physical examination revealed a very active, playful, and healthy boy. Vital signs were normal for his age. His standing height was 90.6 cm (15th percentile), and his weight was 12.2 kg (15th percentile). His height growt...

The incretin effect reflects the actions of enteral stimuli to promote prandial insulin secretion. Impairment of this measure has been proposed as an early marker of β-cell dysfunction and described in T2D, IGT, and even obesity without IGT. We sought to determine the effects of obesity and diabetes on the incretin effect in young subjects with short exposures to metabolic abnormalities and a few other confounding medical conditions. Subjects with T2D (n = 10; 18.0 ± 0.4 yr) or NGT, either obese (n = 11; 17.7 ± 0.4 yr) or lean (n = 8; 26.5 ± 2.3 yr), had OGTT and iso-iv. The incretin effect was calculated as the difference in insulin secretion during these tests and was decreased ∼50% in both the NGT-Ob and T2D subjects relative to the NGT-Ln group. The T2D group had impaired glucose tolerance and insulin secretion during the OGTT, whereas the lean and obese NGT subjects had comparable glucose excursions and β-cell function. During the iso-iv test, the NGT-Ob subjects had significantly greater insulin secretion than the NGT-Ln and T2D groups. These findings demonstrate that in young subjects with early, well-controlled T2D the incretin effect is reduced, similar to what has been described in diabetic adults. The lower incretin effect calculated for the obese subjects with NGT is driven by a disproportionately greater insulin response to iv glucose and does not affect postprandial glucose regulation. These findings confirm that the incretin effect is an early marker of impaired insulin secretion in persons with abnormal glucose tolerance but suggest that in obese subjects with NGT the incretin effect calculation can be confounded by exaggerated insulin secretion to iv glucose.

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