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Objective Reduced testosterone, a recognized comorbidity of reduced insulin sensitivity ( IS) and type 2 diabetes ( T2D), has also been reported in adult males with type 1 diabetes ( T1D). However, there are limited data on how early reduced testosterone occurs, and whether it is related to the reduced IS in T1D. Leptin, a modulator of the HPG-axis, may also influence testosterone in T1D. We hypothesized that IS and leptin would be associated with total testosterone ( TT), and free androgen index ( FAI) in adolescent males with T1D. Methods T1D (n = 35), T2D (n = 13), lean (n = 13) and obese (n = 9) adolescent males had IS measured by hyperinsulinemic-euglycemic clamps (glucose infusion rate [ GIR]), in addition to leptin, sex hormone binding globulin ( SHBG), TT, and FAI. The cohort was stratified into those with T1D (n = 35) and those without (n = 35). Results TT and SHBG were lower in T2D boys vs. lean controls, and GIR and leptin correlated with FAI and TT in non- T1D participants. However, despite being insulin resistant, adolescent males with T1D had normal TT and FAI, unrelated to GIR. In T1D, leptin was inversely associated with TT (p = 0.005) and FAI (p = 0.01), independent of puberty, hemoglobin A1c ( HbA1c), diabetes duration, body mass index ( BMI) z-score and GIR. Conclusion Leptin accounted for a significant proportion of the variability of testosterone in T1D. However, despite reduced IS, there was no association between IS and testosterone in T1D adolescents. These observations suggest that the mechanisms affecting testosterone may differ between adolescent males with and without T1D. [ABSTRACT FROM AUTHOR]

Objectives: The goal of this study was to verify the association between type 1 diabetes (T1D) and the protein tyrosine phosphatase, non-receptor type 22 ( PTPN22) gene in non-Hispanic whites (NHWs) and Hispanics from Colorado. Subjects and methods: The C1858T single-nucleotide polymorphism within the PTPN22 gene was genotyped in 753 patients with T1D ascertained from the diabetes clinic at the Barbara Davis Center in Denver and 662 control population. Results: Both the PTPN22 CT genotype [odds ratio (OR) = 1.96; p < 0.0001] and TT genotype (OR = 4.41; p = 0.02) were significantly associated with T1D in the NHW population. While the association was stronger in subjects with non-HLA-DR3/4 genotypes than in those with the HLA-DR3/4 genotype, regression analyses did not reveal significant interaction between PTPN22 genotypes and HLA-DR3/4. The strength of the association was similar in males and females, patients diagnosed before and after age 10 yr, and in Hispanics and NHWs. Conclusion: In this study, we confirm that PTPN22 is associated with T1D in the Colorado population. [ABSTRACT FROM AUTHOR]

Background Insulin resistance increases during adolescence in those with type 1 diabetes mellitus ( T1DM), complicating glycemic control and potentially increasing cardiovascular disease ( CVD) risk. Metformin, typically used in type 2 diabetes mellitus ( T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. Objective We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. Design, setting, and participants This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages: 13-20 yr) with T1DM. Participants were randomized to receive either metformin or placebo for 6 months. Glycated hemoglobin ( HbA1c), insulin dose, waist circumference, body mass index ( BMI), and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. Results Total daily insulin dose, BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In the placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. Conclusions Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the effectiveness of directly integrating self-monitoring blood glucose (BG) information with insulin pump therapy on overall glycemic control. Methods: In this randomized trial, 34 youth with type 1 diabetes using insulin pump therapy were trained on the use of the Deltec Cozmo® Insulin Pump. Seventeen were randomized to use the CoZmonitor® Blood Glucose Module, a device that attaches to the back of the pump using FreeStyle® technology to perform BG tests which read directly on the pump screen. The remaining 17 (control group) used a FreeStyle Flash meter, a stand-alone BG meter, for their BG testing. At baseline, 3 and 6 months, the subjects filled out a questionnaire, had a hemoglobin A1c (HbA1c) test, and had pumps and meters downloaded. Results: After 3 months of study, there were no changes in mean HbA1c (± SD) values for the experimental (8.7 ± 1.1 to 8.6 ± 1.1) or the control groups (9.1 ± 1.4 to 9.2 ± 1.5). There were also no significant differences in HbA1c values after 6 months. The average number of BG tests per day did not change significantly in either group during the study. After 3 and 6 months, the experimental group rated satisfaction with the use of the CoZmonitor at 4.4 and 3.8 (respectively) on a five-point Likert scale, with 5 being the most satisfied. Conclusions: Although significant changes in HbA1c values or the number of BG tests were not found, use of the BG module had a positive level of satisfaction. [ABSTRACT FROM AUTHOR]