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African-American (AA) children are hyperinsulinemic and insulin resistant compared with American White (AW) children. This study investigated 1) whether AA/AW differences in insulinemia are associated with differences in insulin clearance; 2) whether dietary patterns, mainly carbohydrate and fat intake, play a role; and 3) whether the quantitative relationship between insulin sensitivity and secretion is similar between AA and AW children. Forty-four prepubertal children (22 AA and 22 AW) with comparable body composition and visceral adiposity were studied. All underwent a 3-h hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp to calculate insulin sensitivity and insulin clearance and a 2-h hyperglycemic clamp (12.5 mmol/l) to assess first- and second-phase insulin responses. Twenty-four-hour food recalls were analyzed for macronutrient intake. Insulin clearance (19.5 +/- 0.7 vs. 22.9 +/- 1.1 ml x min(-1) x kg(-1) fat-free mass [FFM]; P = 0.011) and insulin sensitivity were lower in AA versus AW children (14.8 +/- 1.0 vs. 18.9 +/- 1.4 micro mol x min(-1) x kg(-1) FFM; P = 0.021). Both insulin clearance and insulin sensitivity correlated inversely with dietary fat/carbohydrate ratio, which was higher in AA than in white children. Fasting C-peptide and insulin were higher in AA children with no difference in proinsulin levels. First- and second-phase insulin concentrations and glucose disposition index (insulin sensitivity x first-phase insulin) were higher in AA than in white children (12.8 +/- 2.1 vs. 7.2 +/- 0.6 micro mol. min(-1) x kg(-1) FFM; P = 0.019). In conclusion, the hyperinsulinemia observed in AA children is due to both lower insulin clearance and higher insulin secretion compared with their white peers. The quantitative relationship between insulin secretion and sensitivity is upregulated in AA children. This suggests that increased insulin secretion in AA children is not merely a compensatory response to lower insulin sensitivity. Dietary factors may have a role. Additional studies are needed to determine whether metabolic/nutritional factors, possibly mediated through free fatty acids, may play a role in the hyperinsulinism observed in AA children. [ABSTRACT FROM AUTHOR]

Context: Cross-sectional observations show an inverse relationship between pubertal increase in GH and insulin sensitivity, suggesting that pubertal insulin resistance may be mediated by GH., Objective: Our objective was to assess longitudinally the effects of short-term GH supplementation in adolescent males with non-GH-deficient idiopathic short stature (ISS) on body composition, substrate metabolism, and insulin sensitivity. Children with ISS were studied to simulate the pubertal increase in GH secretion., Participants and Setting: Eight males with ISS (10.8-16.5 yr) were recruited from pediatric endocrinology clinics at an academic medical center., Study Design: Participants were evaluated in the General Clinical Research Center before and after 4 months of GH supplementation (0.3 mg/kg.wk). Body composition was assessed with dual-energy x-ray absorptiometry. Whole-body glucose, protein, and fat turnover were measured using stable isotopes. In vivo insulin action was assessed during a 3-h hyperinsulinemic (40 mU/m(2).min) euglycemic clamp., Results: GH supplementation led to 1) increase in hepatic glucose production and fasting insulin levels, 2) increase in lean body mass and decrease in fat mass, and 3) improvement in cardiovascular lipid risk profile. Plasma IGF-I levels correlated positively with insulin levels., Conclusions: Four months of GH supplementation in adolescent males with ISS is associated with significant body composition changes and hepatic insulin resistance.

Background: A range of allometric coefficients have been proposed in describing the maximal oxygen uptake (VO2max): body mass relation in children using weight-bearing ergometry. However, a wide deviation in the allometric coefficients for VO2max may be apparent when selected pediatric cohorts are studied in conjunction with clinical intervention for growth abnormalities., Aim: The purpose of this study was to determine the allometric coefficients for VO2max after short-term pharmacologically induced growth in pre- and early pubescent children., Subjects and Methods: The treatment group consisted of nine subjects with non-growth hormone (GH)-deficient short stature and one with GH-deficient short stature (mean age: 13.7+/-1.7 years). Ten pre- and early pubescent children matched for age, height, weight, VO2max and body mass index (BMI) were controls. The treatment group were evaluated before (Pre-GH) and after (Post-GH) 4 months of subcutaneous GH therapy (0.05 mgkg(-1)day(-1) x 6 days week(-1))., Results: The mean ontogenetic coefficient for the treatment group was 1.50+/-0.20 and for the control group was 0.77+/-0.34. The mean allometric coefficient for body mass relative to VO2max was significantly higher in the treatment group compared with the control group (p<0.05). Height, weight, fat free mass (FFM), VO2max indexed to body mass (mLkg(-1)min(-1)) and FFM (mLkgFFM(-1)min(-1)) increased (p<0.05) with GH therapy. GH therapy also increased insulin-like growth factor-I (IGF-I) and served as a biochemical marker of GH therapy (p<0.05). The control group had no significant differences in all the variables tested (p<0.05)., Conclusion: The scaling for oxygen uptake (VO2) for body mass varies with GH treatment and the increase in VO2max that commonly occurs in conjunction with physical growth in the pre-and early pubescent individual may be linked to an increase in FFM and linear size.

Functional adrenal hyperandrogenism occurs in women with polycystic ovary syndrome (PCOS). Insulin, similar to its ovarian effect, may impact the regulation of adrenal steroidogenesis by modulating the activity of P450c17alpha, the rate-limiting enzyme in androgen biosynthesis. We previously demonstrated that obese adolescents with PCOS are severely insulin resistant and are at heightened risk for impaired glucose tolerance and type 2 diabetes. In the present study we tested the hypothesis that metformin therapy in obese adolescents with PCOS will attenuate the adrenal steroidogenic response to ACTH, with reduction of insulin resistance/insulinemia. Fifteen adolescents with PCOS and impaired glucose tolerance received 3 months of metformin (850 mg, twice daily) therapy. Pre- and posttherapy they had oral glucose tolerance testing, ACTH stimulation test, a 3-h hyperinsulinemic (80 mU/m(2).min)-euglycemic clamp to assess insulin sensitivity and a hyperglycemic clamp to assess insulin secretion. After 3 months of metformin treatment, glucose intolerance improved, with eight subjects having normal glucose tolerance. Total and free T decreased [1.5 +/- 0.2 vs. 1.0 +/- 0.1 nmol/liter (P = 0.022) and 41.3 +/- 8.3 vs. 22.2 +/- 2.1 pmol/liter (P = 0.028), respectively]. Insulin-stimulated glucose disposal increased (21.5 +/- 2.2 vs. 25.0 +/- 2.2 micromol/kg.min; P = 0.041). Fasting insulin and oral glucose tolerance test insulin and glucose area under the curve decreased significantly. ACTH-stimulated increases in androstenedione, 17-hydroxyprogesterone, and 17-hydroxypregnenelone were lower after metformin treatment [2.8 +/- 0.4 vs. 1.7 +/- 0.3 nmol/liter (P = 0.014), 7.0 +/- 0.6 vs. 5.3 +/- 0.5 nmol/liter (P = 0.011), and 30.4 +/- 3.7 vs. 25.7 +/- 4.2 nmol/liter (P = 0.054)]. Fasting insulin correlated with the 17-hydroxypregnenelone response to ACTH stimulation (r = 0.52; P = 0.008). In summary, metformin treatment of obese adolescents with PCOS and impaired glucose tolerance is beneficial in improving glucose tolerance and insulin sensitivity, in lowering insulinemia, and in reducing elevated androgen levels. Moreover, metformin therapy is associated with attenuation of the adrenal steroidogenic response to ACTH. Metformin therapy was well tolerated. In conclusion, double blind, placebo-controlled studies will determine whether insulin-sensitizing therapy corrects not only ovarian hyperandrogenism but also functional adrenal hyperandrogenism in adolescents with PCOS.

Type 2 diabetes has been increasing in children, mostly affecting minority populations at around the age of puberty. Despite a multitude of studies demonstrating pubertal insulin resistance/hyperinsulinemia in white children, data are almost non-existent in African-American children. The aim of the present study was to investigate the impact of puberty on glucose metabolism, insulin sensitivity and secretion in African-American children. Twenty prepubertal and 16 pubertal African-American subjects participated. All underwent a 3-h hyperinsulinemic (40 mU/m(2)/min) euglycemic clamp to determine insulin-stimulated glucose disposal, and a 2-h hyperglycemic (12.5 mmol/L) clamp to assess first- and second-phase insulin secretion. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and visceral and subcutaneous abdominal adiposity with computed tomography (CT) scan at L4-L5. Total glucose disposal, glucose oxidation and non-oxidative glucose disposal were significantly lower in the pubertal group compared with the prepubertal one (53.8 +/- 3.9 vs. 72.2 +/- 5.0 micromol/kg/min, p = 0.009; 23.3 +/- 1.1 vs. 31.6 +/- 1.7 micromol/kg/min, p = 0.001; and 30.0 +/- 3.3 vs. 40.5 +/- 3.9 micromol/kg/min, p = 0.049, respectively). Insulin sensitivity was approximately 30% lower in the adolescents compared with the prepubertal children. However, first- and second-phase insulin secretions were not different between the two groups (971.4 +/- 180.6 vs. 1044.0 +/- 191.4 pmol/L and 999.6 +/- 159.6 vs. 955.8 +/- 142.2 pmol/L, respectively). In conclusion, despite approximately 30% lower insulin sensitivity in African-American adolescents compared with prepubertal children, insulin secretion is not higher. This is in contrast to published findings in white children in whom insulin secretion is higher during puberty. These racial differences in physiologic adaptation to puberty could play a role in the higher prevalence of type 2 diabetes in African-American children at the time of puberty.

Puberty is characterized by temporary insulin resistance, which subsides with the completion of pubertal development. This insulin resistance is manifested by lower rates of insulin-stimulated glucose metabolism and compensatory hyperinsulinemia in pubertal compared with prepubertal children. Whether or not pubertal insulin resistance is the result of sex steroids or GH or a combination of both has been investigated in our laboratory. Previously, we demonstrated that T treatment in adolescents with delayed puberty was not associated with the deterioration of insulin action. The present investigation evaluated the effects of 4 months of dihydrotestosterone administration (50 mg im every 2 wk) on body composition, glucose, fat, and protein metabolism, and insulin sensitivity. Ten adolescents with delayed puberty were evaluated before and after 4 months of DHT administration. Body composition was assessed by dual energy x-ray absorptiometry. Insulin-stimulated glucose metabolism was measured during a 3-h hyperinsulinemic (40 mU/m(2).min)-euglycemic clamp procedure. Lipolysis and proteolysis were evaluated by stable isotopes of [(2)H(5)]glycerol and [1-(13)C]leucine. After 4 months of dihydrotestosterone treatment, height, weight, and fat free mass increased and percentage of body fat decreased. IGF-I and nocturnal GH levels did not change. There was no significant change in insulin-stimulated glucose metabolism (57.2 +/- 3.9 vs. 58.3 +/- 3.9 micromol/kg.min). Total body proteolysis and lipolysis did not change. In summary, based on the present and past studies, we conclude that during puberty insulin resistance/hyperinsulinemia is not attributable to gonadal sex steroids in boys.

Objective: To investigate insulin sensitivity and secretion in young adolescent girls with childhood onset polycystic ovarian syndrome (PCOS) and to identify the early metabolic derangement(s)., Study Design: Twelve obese girls with PCOS (age 12.0+/-0.7 years) were compared with 10 obese nonhyperandrogenic girls (control group). The groups were matched for age, percent body fat, and abdominal fat. All subjects underwent a 3-hour hyperinsulinemic (80 mu/m(2)/min)-euglycemic clamp to determine in vivo insulin sensitivity and a 2-hour hyperglycemic clamp (225 mg/dL) to determine insulin secretion. Fasting hepatic glucose production was determined with the use of [6,6-(2)H(2)]glucose., Results: Fasting glucose and hepatic glucose production were comparable between the 2 groups, but fasting insulin was 2-fold higher in the PCOS group. The fasting glucose to insulin ratio was lower in the PCOS group versus the control group (1.9+/- 0.3 vs 3.1+/-0.3, P =.02). During the hyperinsulinemic-euglycemic clamp, insulin sensitivity was lower in the PCOS group (1.4+/-0.2 vs 2.7+/-0.3 mg/kg/min per microu/mL, P =.002). During the hyperglycemic clamp, insulin secretion was significantly higher in the PCOS group. Insulin sensitivity correlated negatively with fasting insulin (r = -0.71, P =.0002) and positively with the fasting glucose to insulin ratio (r = 0.79, P<.0001)., Conclusion: Adolescent girls with PCOS have profound metabolic derangements detected early in the course of the syndrome, including (1) approximately 50% reduction in peripheral tissue insulin sensitivity, (2) evidence of hepatic insulin resistance, and (3) compensatory hyperinsulinemia. These observations may predict an increased risk of type 2 diabetes mellitus in adolescents with PCOS.

The roles of insulin resistance and insulin secretion in the pathogenesis of glucose intolerance in polycystic ovary syndrome (PCOS) were evaluated in 11 adolescents with impaired glucose tolerance (IGT) and 10 with normal glucose tolerance (NGT). Hepatic glucose production and insulin-stimulated glucose disposal were measured using [6,6-(2)H(2)]glucose and a 3-h hyperinsulinemic (80 mu/m(2).min)-euglycemic clamp. First and second phase insulin secretions were evaluated during a hyperglycemic clamp. Automated blood pressure measurements were made to assess the nocturnal change in blood pressure. Hepatic glucose production was significantly higher in IGT vs. NGT. Insulin-stimulated glucose disposal was not different between the two groups. The first phase insulin level was lower in IGT (207.9 +/- 21.0 vs. 357.0 +/- 62.9 muu/mL; P = 0.025; 1247 +/- 126 vs. 2142 +/- 377 pmol/L) without a difference in second phase insulin. The glucose disposition index (product of insulin sensitivity x first phase insulin) was lower in IGT vs. NGT (278 +/- 40 vs. 567 +/- 119 mg/kg.min; P = 0.023; 1546 +/- 223 vs. 3249 +/- 663 micromol/kg.min). The glucose disposition index correlated inversely with OGTT glucose concentrations at 30, 60, and 120 min. Adolescents with PCOS-IGT lacked the normal nocturnal decline in blood pressure. We conclude that in obese adolescents with PCOS, glucose intolerance is associated with 1) decreased first phase insulin secretion, 2) decreased glucose disposition index, and 3) increased hepatic glucose production. These metabolic abnormalities are precursors of type 2 diabetes and are present early in the course of PCOS. Furthermore, the absence of nocturnal dipping in blood pressure may herald the early expression of cardiovascular disease risk in these adolescents.

Historically, type 2 diabetes has been considered rare in the pediatric population. However, over the last decade, there has been a disturbing upswing in the rate of non-type 1 diabetes in the pediatric age group, particularly adolescents, with a greater proportion of Black children being affected. In this review, the following questions will be addressed: (1) what are the clinical characteristics of youth-onset atypical diabetes, (2) how common is it, (3) what are the risk factors, and (4) how should it be treated?

Objective: To compare the cases of child abuse (CA) with other admissions in a pediatric intensive care unit (PICU) for differences in patient-specific health care costs, severity of illness (SI) and mortality, and describe their outcome., Method: A retrospective cohort study of all patients admitted to the PICU between January 1991 and August 1994. Discharge diagnosis, age, SI, mortality rate, length of stay, hospitalization charges ($Hosp), and mortality were retrieved., Results: There were 937 admissions; 13 were secondary to CA. Cases of CA represented 1.4% of admissions and 17% of deaths. CA patients had the highest SI (61%), $Hosp ($30,684), daily charges ($5,294) and mortality rates (53%) than any other group. In our patients, SI is a factor that affects charges. Even when compared to a cohort group with SI, child abuse patients had higher daily hospitalization charges (p < .05). The medical bills for the acute care of a CA patient averaged $35,641 per case. Even with these expenditures, 70% died and 60% of the survivors had severe residual morbidity., Conclusion: These results confirm that interventional medical care in response to severe CA is very costly and the ultimate outcome is significantly worse than other diseases. Therefore, we believe it is imperative to allocate resources to prevention.