Gestational weight gain and the risk of offspring obesity at 10 and 16 years: a prospective cohort study in low-income women.

OBJECTIVE: To study the association between gestational weight gain (GWG) and offspring obesity risk at ages chosen to approximate prepuberty (10 years) and postpuberty (16 years). DESIGN: Prospective pregnancy cohort. SETTING: Pittsburgh, PA, USA. SAMPLE: Low-income pregnant women (n = 514) receiving prenatal care at an obstetric residency clinic and their singleton offspring. METHODS: Gestational weight gain was classified based on maternal GWG-for-gestational-age Z-score charts and was modelled using flexible spline terms in modified multivariable Poisson regression models. MAIN OUTCOME MEASURES: Obesity at 10 or 16 years, defined as body mass index (BMI) Z-scores ≥95th centile of the 2000 CDC references, based on measured height and weight. RESULTS: The prevalence of offspring obesity was 20% at 10 years and 22% at 16 years. In the overall sample, the risk of offspring obesity at 10 and 16 years increased when GWG exceeded a GWG Z-score of 0 SD (equivalent to 30 kg at 40 weeks); but for gains below a Z-score of 0 SD there was no relationship with child obesity risk. The association between GWG and offspring obesity varied by prepregnancy BMI. Among mothers with a pregravid BMI <25 kg/m(2) , the risk of offspring obesity increased when GWG Z-score exceeded 0 SD, yet among overweight women (BMI ≥25 kg/m(2) ), there was no association between GWG Z-scores and offspring obesity risk. CONCLUSIONS: Among lean women, higher GWG may have lasting effects on offspring obesity risk.

Is gestational weight gain associated with offspring obesity at 36 months?

OBJECTIVE: We examined the association between gestational weight gain (GWG) and offspring obesity at age 36 months. METHODS: Mother-infant dyads (n = 609) were followed from a first study visit (mean [standard deviation]: 18.8 [2.7] weeks gestation) to 36 months postpartum. Total GWG over the entire pregnancy was defined as excessive or non-excessive according to the 2009 Institute of Medicine guidelines. Four mutually exclusive categories of excessive or non-excessive GWG across early (conception to first study visit) and late (first study visit to delivery) pregnancy defined GWG pattern. Body mass index (BMI) z-scores ≥95th percentile of the 2000 Centers for Disease Control (CDC) references defined offspring obesity at 36 months. Multivariable log-binomial models adjusted for pre-pregnancy BMI and breastfeeding were used to estimate the association between GWG and childhood obesity risk. RESULTS: Nearly half of the women had total excessive GWG. Of these, 46% gained excessively during both early and late pregnancy while 22% gained excessively early and non-excessively late, and the remaining 32% gained non-excess weight early and excessively later. Thirteen per cent of all children were obese at 36 months. Excessive total GWG was associated with more than twice the risk of child obesity (adjusted risk ratio [95% confidence interval]: 2.20 [1.35, 3.61]) compared with overall non-excessive GWG. Compared with a pattern of non-excessive GWG in both early and late pregnancy, excessive GWG in both periods was associated with an increased risk of obesity (2.39 [1.13, 5.08]). CONCLUSIONS: Excessive GWG is a potentially modifiable factor that may influence obesity development in early childhood.

Effects of acute exercise on postprandial triglyceride response after a high-fat meal in overweight black and white adolescents.

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.

Relationships between insulin sensitivity, skeletal muscle mass and muscle quality in obese adolescent boys.

We examined the relationships between insulin sensitivity (IS), skeletal muscle (SM) mass and SM quality in youth. Forty obese adolescent boys (body mass index ≥ 95 th percentile, 12-18 years) participated in this study. IS and glucose tolerance was measured by a 3 h hyperinsulinemic-euglycemic clamp and a 2 h oral glucose tolerance test (OGTT), total SM mass and intermusular adipose tissue (IMAT) by whole-body magnetic resonance imaging, and muscular strength by one-repetition maximum leg and bench press. IMAT was associated (P<0.05) with IS (r=-0.53) and OGTT-insulin area under the curve (AUC; r=0.31). Similarly, muscular strength was associated (P<0.05) with both IS (r=0.39) and OGTT-insulin AUC (r=-0.32). By contrast, total SM mass was not associated with IS or any OGTT parameters (P>0.1). After accounting for race and tanner stage, IMAT and muscular strength remained significantly associated with IS, together explaining a total of 41% of the variance in IS. Our findings suggest that SM quality, but not SM mass, is associated with IS in obese adolescent boys.

Age variation and sexual dimorphism in the sixteen diagnostic clusters of risk factors for the metabolic syndrome.

OBJECTIVE: To document age- and sex-related differences in the 16 phenotypes of risk factors for the metabolic syndrome (MS) among adults in the Fels Longitudinal Study (FLS). METHODS: Data on risk factors for the MS were analyzed in 471 white men and 503 white women in the FLS. We used the Cochran-Armitage test to compare age- and sex-related differences in the prevalence of the 16 diagnostic clusters of positive risk factors. RESULTS: Of the 974 subjects, 238 were found to meet diagnostic criteria for 15 of a possible 16 phenotypes of the MS. The prevalence of the MS was four times greater in subjects older than 40 years than in subjects 20-40 years old. Older subjects had more risk factors exceeding criterion values than younger subjects. Among those who met three-to-five criteria for the MS, younger subjects were more likely to have dyslipidemia, less likely to have high blood pressure (HBP), and two times less likely to have impaired fasting plasma glucose (IFG) than subjects 40+ years old. Older men were more likely than older women to have HBP and IFG. . We found that if one of the five risk factors reaches a criterion value, the values for the other four risk factors move closer to their own diagnostic criterion values in apparent synchrony. CONCLUSIONS: Subjects 40+ years old are four times likelier to have the MS than younger subjects, and older men are at higher risk than older women. The mean values for each of the five risk factors get progressively worse as the number of risk factors meeting diagnostic criteria increases. Therefore, when one factor is found to meet its diagnostic criterion, levels of the other four risk factors should be measured. The different phenotypic patterns that comprise the MS should prompt clinicians to target specific risk factors for prevention or treatment. Certain phenotypes were found more commonly in women and certain others more commonly in men. Similarly, certain phenotypes were found more commonly in older than in younger age groups. These age- and sex-specific phenotypes should help clinicians to identify subjects at highest risk for certain risk factors and to initiate specifically tailored preventive and therapeutic interventions. Our observations should also stimulate clinical investigators and epidemiologists to ascertain what factors determine the sex and age specificity of certain phenotypes of the MS.

ß-cell autoimmunity in overweight non-diabetic youth: any implications?

BACKGROUND AND OBJECTIVE: The presence of ß-cell antibodies is associated with a high risk of type 1 diabetes. With increasing rates of obesity, the distinction between obese T1DM and T2DM has become difficult. Moreover, increasing body mass index (BMI) in at-risk children has been proposed not only as a possible contributor to T1DM by increasing insulin resistance, but also as exerting an effect via the immunomodulatory properties of certain adipokines. This study aimed to determine prevalence of ß-cell autoantibodies (AA) in overweight non-diabetic children and assess insulin sensitivity and secretion derived from an oral glucose tolerance test (OGTT) in those with vs. without ß-cell AA. RESEARCH DESIGN AND METHODS: A total of 357 overweight (BMI > 85%) youths underwent OGTTs, dual energy X-ray absorptiometry (DEXA) and measurement of GAD65 and IA-2 AA according to the NIDDK harmonization assay. Using the same methodology, AA were measured in 90 normal weight, non-diabetic individuals. RESULTS: About 1.9% of overweight and 4.4% of control normal weight children had evidence of ß-cell autoimmunity, with GAD65 AA detected in all subjects but none with IA-2. Youth with positive vs. those with negative AA had higher leptin/adiponectin ratio, glucose at 60 min and C-peptide at 90 min. CONCLUSIONS: These findings suggest that the prevalence of ß-cell AA in overweight youth may be similar to that in non-overweight children. Further studies using standardized methods are required.

Reproducibility of the oral glucose tolerance test in overweight children.

OBJECTIVE: We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results. DESIGN: Sixty overweight youth (8-17 yr old) completed two OGTTs (interval between tests 1-25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI). RESULTS: Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7+/-1.4 vs. 4.1+/-1.8, P=0.006, whole-body insulin sensitivity index of 1.3+/-0.6 vs. 2.2+/-1.1, P=0.003, and homeostasis model assessment of insulin resistance 10.6+/-8.1 vs. 5.7+/-2.8, P=0.001), had a lower GDI (0.45+/-0.58 vs. 1.02+/-1.0, P=0.03), and had higher low-density lipoprotein cholesterol (117.7+/-36.6 vs. 89.9+/-20.1, P=0.0005) without differences in physical characteristics. CONCLUSIONS: Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.

Cardiorespiratory fitness and abdominal adiposity in youth.

The purpose of this study was to determine whether cardiorespiratory fitness (CRF) is associated with lower abdominal adiposity in youth. Subjects included healthy 61 African-American and 52 white children and adolescents (age: 8-17 years). Body composition was measured by dual-energy X-ray absorptiometry and computed tomography. CRF (VO(2max)) was assessed using a graded maximal treadmill test. CRF was inversely related (P<0.05) to total adiposity, waist circumference, and visceral and abdominal subcutaneous adipose tissue (AT) independent of race. These findings remained significant (P<0.05) after adjusting for age, gender and pubertal status. Multiple regression analyses revealed that CRF is an independent contributor (P<0.05) of waist circumference, and visceral and abdominal subcutaneous AT after accounting for age, pubertal status, gender and body mass index percentile. Our observation suggest that in youth, CRF is associated with lower visceral and abdominal subcutaneous AT, and reinforces the notion that youth should engage in regular physical activity to improve aerobic fitness and reduce abdominal adiposity.

Dihydrotestosterone treatment in adolescents with delayed puberty: does it explain insulin resistance 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.

Lipolysis in African-American children: is it a metabolic risk factor predisposing to obesity?

Rates of obesity and type 2 diabetes are higher in African-American (AA), compared with American white (AW), adults and children. It is not known whether biologic and/or environmental differences are responsible for this racial disparity. We and others have demonstrated that AA children are hyperinsulinemic, compared with their AW peers. This investigation tested the hypothesis that hyperinsulinemia in AA children is associated with lower rates of lipolysis, which could be a risk factor for future obesity. Forty prepubertal children (20 AA and 20 AW) with comparable body composition (assessed by dual-energy x-ray absorptiometry) and visceral adiposity (evaluated with computed tomography scan) were studied. Total body lipolysis was measured with [(2)H(5)]glycerol after overnight fasting. Basal lipolysis was approximately 40% lower in AA vs. AW children, whether the data were expressed for total body (85.7 +/- 8.9 vs. 130.3 +/- 14.1 micromol/min, P = 0.011) or per-kilogram BW (2.4 +/- 0.2 vs. 3.8 +/- 0.4 micromol/min.kg, P = 0.002) or per kilogram fat free mass (FFM) (3.3 +/- 0.3 vs. 5.2 +/- 0.5 micromol/min.kg FFM, P = 0.004), or per kg fat mass (FM) (13.7 +/- 1.6 vs. 21.3 +/- 3.3 micromol/min.kg FM, P = 0.046). Fasting insulin levels were higher in AA children (99.6 +/- 7.8 vs. 77.4 +/- 5.9 pmol/L, P = 0.032). Lipolysis correlated positively with fat mass, percent body fat, and abdominal fat mass. However, in multiple-regression analysis models after controlling for insulin and body composition, race remained a significant contributor to the variance in lipolysis. In summary, the present study demonstrates that rates of lipolysis are significantly lower in AA children, compared with their white peers. This may constitute an early metabolic phenotype that may mediate fat trapping and susceptibility to obesity in a specific environmental context of energy excess conducive to fat accretion.

Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease.

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.

Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome.

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.

Peak oxygen consumption and skeletal muscle bioenergetics in African-American and Caucasian men.

OBJECTIVE: To compare peak oxygen consumption (VO2peak) and skeletal muscle oxidative metabolism between nine African-American and nine Caucasian men. METHODS: Subjects performed arm ergometry to exhaustion. On a separate occasion 31phosphorous-nuclear magnetic resonance spectroscopy (31P-NMRS) was used to determine the concentrations of phosphorous (Pi), phosphocreatine (PCr), and the intracellular pH of the flexor carpi radialis before and during 4 min of steady-state, wrist flexion exercise performed at 28% (15 W) of each subject's peak voluntary contraction. RESULTS: The Pi/PCr ratio was used as an indirect measure of skeletal muscle oxidative metabolism. VO2peak was lower in the African-Americans compared with the Caucasians (means +/- SD, 19.4 +/- 3.4 vs 23.3 +/- 4.0 mL x kg(-1) x min(-1)) (P < 0.05). No significant between group difference was noted in the Pi/PCr ratio at rest (0.10 +/- 0.02 both groups). However, resting pH was lower in the African-Americans (6.99 +/- 0.04 vs 7.03 +/- 0.05) (P < 0.05). Exercise caused an increase in the Pi/PCr ratio in the African-Americans (1.06 +/- 0.11), which was higher than the increase observed in the Caucasians (0.50 +/- 0.14) (P < 0.05). pH levels decreased to a lower level during exercise in the African-Americans (6.89 +/- 0.04) than in the Caucasians (6.98 +/- 0.05) (P < 0.05). CONCLUSIONS: This select group of African-American men achieved a lower VO2peak than the Caucasian men. Variations in skeletal muscle oxidative metabolic components may explain this difference.

Heart-type fatty acid binding protein as a marker of reperfusion after thrombolytic therapy.

Accurate, rapid, and simple noninvasive measures of infarct-related artery (IRA) patency are needed to identify patients with failed coronary reperfusion for rescue percutaneous coronary intervention (PCI). Heart-type Fatty Acid Binding Protein (H-FABP) is a small, cytosolic protein found in high concentrations in the myocardium. We evaluated the efficacy of H-FABP as a marker for successful reperfusion after thrombolysis. Fifty-eight subjects from the TIMI 14 trial had H-FABP and myoglobin concentrations measured at baseline (immediately prior to thrombolysis) and 60, 90, and 180 min after thrombolysis. All patients underwent coronary angiography at 90 min. By 60 min after thrombolysis, median concentrations of H-FABP and myoglobin were significantly higher in patients with a patent IRA than in those with an occluded IRA (P<0.01 for each). Similarly, the 60 and 90 min/baseline H-FABP and myoglobin ratios were significantly higher among patients with a patent IRA (P<0.01 for each). There were no significant differences in marker concentrations or ratios between patients with TIMI grade 2 and TIMI grade 3 flow. The area under the ROC curve tended to be greater for the 60 and 90 min/baseline myoglobin ratios than for similar ratios of H-FABP (0.71 and 0.73 vs. 0.64 and 0.62; P=ns). In conclusion, successful reperfusion can be detected within the first 60 min after thrombolysis with either H-FABP or myoglobin. Despite a favorable kinetic profile, however, H-FABP does not appear to represent a significant advance over myoglobin in the noninvasive detection of reperfusion after thrombolysis.

Can clinical factors estimate insulin resistance in type 1 diabetes?

An insulin resistance syndrome (IRS) score was developed based on clinical risk factors in adults with childhood-onset type 1 diabetes in the Epidemiology of Diabetes Complications (EDC) Study and was validated using euglycemic-hyperinsulinemic clamp studies. Hypertension, waist-to-hip ratio (WHR), triglyceride and HDL cholesterol levels, family history of type 2 diabetes, and glycemic control were risk factors used to define the score. A score of 1 (lowest likelihood IRS) to 3 (highest likelihood IRS) was assigned for each risk factor. Eligible subjects (n = 24) were recruited from the EDC cohort based on tertile of IRS score. Subjects received an overnight insulin infusion to normalize glucose levels, then underwent a 3-h euglycemic-hyperinsulinemic (60 mU x m(-2) x min(-1)) clamp. Glucose disposal rate (GDR) was determined during the last 30 min of the clamp. The GDR differed significantly by IRS group (9.65 +/- 2.99, 8.02 +/- 1.39, and 5.68 +/- 2.16 mg x kg(-1) x min(-1), P < 0.01). The GDR was inversely correlated with the IRS score (r = -0.64, P < 0.01). Using linear regression, the combination of risk factors that yielded the highest adjusted r2 value (0.57, P < 0.001) were WHR, hypertension, and HbA1. This study found that clinical risk factors can be used to identify subjects with type 1 diabetes who are insulin resistant, and it provides validation of a score based on clinical factors to determine the extent of insulin resistance in type 1 diabetes. This score will be applied to the entire EDC population in future studies to determine the effect of insulin resistance on complications.

No association between body mass index and beta(3)-adrenergic receptor variant (W64R) in children with premature pubarche and adolescent girls with hyperandrogenism.

OBJECTIVE: To determine if the Trp(64)Arg (W64R) variant of the beta(3)-adrenergic receptor (ADRB3) could be used as a genetic marker to define risk for polycystic ovary syndrom (PCOS) and/or obesity in children and adolescents. DESIGN: Association study. SETTING: Academic research environment. PATIENT(S): Children referred for evaluation of premature pubic hair (n = 63), adolescent girls referred for evaluation of hirsutism and/or oligomenorrhea (n = 33), and healthy adult controls (n = 67). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relationship of body mass index (BMI) to presence or absence of W64R variant and frequency of W64R variant in our patient population. RESULT(S): Body mass index (kg/m(2)) was determined for 63 children (55 girls and 8 boys) and 33 adolescent girls. Presence or absence of the W64R variant was assayed by polymerase chain reaction (PCR) amplification followed by allele-specific restriction fragment digest. Twelve subjects and 11 healthy controls were found to be heterozygous for the W64R variant. One subject was found to be homozygous for the W64R variant. Allele frequency for the W64R variant was comparable between patients and controls. Among the patients, mean BMI values were not different between carriers and noncarriers. CONCLUSION(S): Although other studies suggest that the W64R variant is associated with the development of obesity and insulin resistance, we cannot demonstrate that it has a major effect on BMI in children with premature pubarche or in adolescent girls with hyperandrogenism. Serial observations are necessary to determine if this variant predicts the development of obesity and/or PCOS in adulthood.

Type 2 diabetes mellitus in children: pathophysiology and risk factors.

Type 2 diabetes mellitus (DM) has been considered rare in the pediatric population. However, over the last decade, there has been a disturbing upswing in the rate of diagnosis of type 2 DM in the pediatric age group, mirroring the increasing rates of obesity in childhood. The pathophysiology of type 2 DM discussed in this article focuses on the delicate balance between insulin sensitivity and insulin secretion. The risk factors for youth-onset type 2 DM are presented, with careful evaluation of their impact on insulin sensitivity versus insulin secretion.

Type 2 diabetes mellitus in minority children and adolescents. An emerging problem.

Type 2 diabetes mellitus is a disease of adults and has been considered rare in the pediatric population. Over the last decade, however, there has been a disturbing trend of increasing cases of type 2 diabetes in children, particularly adolescents, and with a greater proportion of minority children being affected. This article reviews the clinical characteristics of youth with type 2 diabetes, presents the risk factors associated with insulin resistance and type 2 diabetes, discusses treatment options, and projects future directions in research. The ultimate goal is to raise awareness of this challenging entity among healthcare professionals.

Leptin concentrations in precocious puberty or untimely puberty with and without GnRH analogue therapy.

Nutritional status and body composition influence the development and maintenance of reproductive competence in mammals. It has been suggested that leptin concentrations communicate nutritional status to the neuroendocrine reproductive axis. To determine the interrelationship between circulating gonadotropin and leptin concentrations, leptin concentrations were measured in 39 children treated for GnRH dependent precocious or untimely puberty. Leptin concentrations were obtained during pubertal suppression with GnRH analogue therapy and during spontaneous pubertal gonadotropin secretion. The status of gonadotropin secretion (suppressed vs not suppressed) was verified by simultaneous GnRH stimulation tests and sex steroid concentrations. Leptin concentrations were similar at both time-points and correlated only with body mass index. Thus, no relationship was apparent between circulating concentrations of gonadotropins, sex steroids, and leptin.