Prenatal phthalate exposure impairs testicular function and shortens anogenital distance (AGD) in male rodents. We present data from the first study to examine AGD and other genital measurements in relation to prenatal phthalate exposure in humans. A standardized measure of AGD was obtained in 134 boys 2–36 months of age. AGD was significantly correlated with penile volume ( R = 0.27, p = 0.001) and the proportion of boys with incomplete testicular descent ( R = 0.20, p = 0.02). We defined the anogenital index (AGI) as AGD divided by weight at examination [AGI = AGD/weight (mm/kg)] and calculated the age-adjusted AGI by regression analysis. We examined nine phthalate monoester metabolites, measured in prenatal urine samples, as predictors of age-adjusted AGI in regression and categorical analyses that included all participants with prenatal urine samples ( n = 85). Urinary concentrations of four phthalate metabolites [monoethyl phthalate (MEP), mono- n -butyl phthalate (MBP), monobenzyl phthalate (MBzP), and monoisobutyl phthalate (MiBP)] were inversely related to AGI. After adjusting for age at examination, p -values for regression coefficients ranged from 0.007 to 0.097. Comparing boys with prenatal MBP concentration in the highest quartile with those in the lowest quartile, the odds ratio for a shorter than expected AGI was 10.2 (95% confidence interval, 2.5 to 42.2). The corresponding odds ratios for MEP, MBzP, and MiBP were 4.7, 3.8, and 9.1, respectively (all p -values < 0.05). We defined a summary phthalate score to quantify joint exposure to these four phthalate metabolites. The age-adjusted AGI decreased significantly with increasing phthalate score ( p -value for slope = 0.009). The associations between male genital development and phthalate exposure seen here are consistent with the phthalate-related syndrome of incomplete virilization that has been reported in prenatally exposed rodents. The median concentrations of phthalate metabolites that are associated with short AGI and incomplete testicular descent are below those found in one-quarter of the female population of the United States, based on a nationwide sample. These data support the hypothesis that prenatal phthalate exposure at environmental levels can adversely affect male reproductive development in humans.

OBJECTIVE -The safety and efficacy of insulin aspart continuous subcutaneous insulin infusion (CSII) was compared with that of insulin lispro CSII in children and adolescents with type 1 diabetes.RESEARCH DESIGN AND METHODS -Children and adolescents aged 4 -18 years with diagnosed type 1 diabetes Ն1 year previously and treated with insulin analog in a CSII Ն3 months were randomly assigned 2:1 to 16 weeks of insulin aspart CSII (n ϭ 198) or insulin lispro CSII (n ϭ 100) in this open-label, parallel-group, multicenter study. Standard diabetes safety and efficacy parameters were assessed.RESULTS -Baseline demographics, subject characteristics, and diabetes history were similar between treatment groups. After 16 weeks of treatment, insulin aspart CSII was noninferior to insulin lispro CSII as measured by change in A1C from baseline (aspart, Ϫ0.15 Ϯ 0.05%; lispro, Ϫ0.05 Ϯ 0.07% [95% CI of the treatment difference Ϫ0.27 to 0.07]; P ϭ 0.241). No significant differences between treatment groups were observed in fasting plasma glucose, hyperglycemia, and rates of hypoglycemic episodes. At week 16, 59.7% of subjects in the aspart group and 43.8% of subjects in the lispro groups achieved age-specific American Diabetes Association A1C goals (Ͻ8.5% for subjects aged Ͻ6 years; Ͻ8% for subjects aged 6 -18 years) (P ϭ 0.040, corrected for baseline). Daily insulin dose (units per kilogram) was significantly lower at week 16 for subjects treated with aspart compared with those treated with lispro (0.86 Ϯ 0.237 vs. 0.94 Ϯ 0.233, P ϭ 0.018).CONCLUSIONS -Insulin aspart was as safe and effective as insulin lispro for use in a CSII in children and adolescents with type 1 diabetes. Diabetes Care 31:210-215, 2008

Insulin glargine substantially improved glycemic control in children and adolescents with poorly controlled type 1 diabetes. This response was most remarkable in those with a baseline hemoglobin A1c level > 12.0%, and may have been related to increased supervision of injections.

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