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Objective: Children with type 1 diabetes (T1DM) are at increased risk for celiac disease (CD); however, the benefits of screening for IgA tissue transglutaminase autoantibodies (TG), a marker for CD, are unclear. Study design: We compared 71 screening-identified TG+ with 63 matched TG– children with TIDM. Growth, bone density, and diabetes control measures were obtained. Results: The group was 10 ± 3 years of age, 46% male, with TIDM for 4 ± 3 years. Z scores for weight (0.3 ± 1 vs 0.7 ± 0.8, P = .024), body mass index (BMI) (0.3 ± 0.9 vs 0.8 ± –0.8, P = .005), and midarm circumference (0.3 ± 1.1 vs 0.6 ± 0.9, P = .031) were lower in the TG+ group. Bone mineral density and diabetes control measures were similar. When limiting the analysis to the 35 TG+ subjects with biopsy changes of CD, the BMI Z score was lower than the control group (0.4 ± 0.9 vs 0.7 ± 0.7, P = .05). Conclusions: In children with TIDM, screening-identified evidence of CD is associated with altered body composition, but not bone mineral density or diabetes control. Further study is needed to determine the benefit of early diagnosis and treatment of CD in TIDM children. [Copyright &y& Elsevier]

Objective: Because cardiovascular disease (CVD) is the leading cause of death in patients with type 1 diabetes (T1D) and dyslipidemia is an important CVD risk factor, we investigated dyslipidemia and its treatment in children with T1D. Study design: Subjects had T1D (n = 360), repeated lipid measurements (n = 1095; mean, 3.04 ± 0.94; range, 2 to 11), and were seen between 1994 and 2004. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and non-HDL cholesterol (non-HDL) were categorized on the basis of published guidelines. Age, diabetes duration, sex, body mass index, HbA1c, and lipid-lowering medication use were recorded. Predictors of TC, HDL, and non-HDL were determined. Results: Sustained abnormalities existed for TC ≥200 mg/dL (16.9%); HDL <35 mg/dL (3.3%); and non-HDL ≥130 mg/dL (27.8%), ≥160 mg/dL (10.6%), and ≥190 mg/dL (3.3%). Lipid-lowering medications were started on 23 patients. In mixed model longitudinal data analyses, HbA1c was significantly related to TC and non-HDL. Body mass index z-score was inversely related to HDL. Conclusions: In this retrospective, longitudinal study of pediatric patients with T1D with repeated lipid measurements, sustained abnormal levels for TC, HDL, and non-HDL were present. Prospective longitudinal data for dyslipidemia in youth with T1D are needed. [Copyright &y& Elsevier]

Objective: To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and to identify an optimal testing strategy for detecting preclinical diabetes. Study design: Diabetes Prevention Trial—Type 1 Diabetes (DPT-1) randomized subjects to oral (n = 372) and parenteral (n = 339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. Results: Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of first phase insulin response (FPIR) at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline body mass index (BMI), FPIR, and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal FPIR and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs 73%). Conclusions: Most (97%) subjects had abnormal IVGTTs and/or OGTTs before the development of diabetes. The highest sensitivity is achieved using both tests. [Copyright &y& Elsevier]

Objective: To determine whether mixing insulin glargine (IG) with a rapid-acting insulin (RAI) analogue in the same syringe had any deleterious effects on glycemic control in children with type 1 diabetes mellitus. Study design: Data from 55 children mixing the IG with a RAI analogue was collected for 6 months before and 6 months after the insulin mixing began. Data from a control group of 55 children not mixing the insulins was collected at similar intervals. Parameters evaluated included hemoglobin A1c (HbA1c) values, number of non-severe and severe hypoglycemic events, number of diabetic ketoacidosis (DKA) events, and blood glucose distribution patterns. Results: After 6 months of study, HbA1c values were equivalent for the control and test groups (8.54 ± 1.14 vs 8.61 ± 1.14, respectively; P = 1.0000). Percentages of blood glucose values in, above, and below the target range did not vary significantly in the groups. There were no significant differences in the groups in the occurrence of non-severe or severe hypoglycemic events or of DKA events. Conclusion: There were no significant differences in glycemic control between children who mixed IG in the same syringe with a RAI analogue compared with children who took separate injections. [Copyright &y& Elsevier]

This study reports serum lipid levels in 682 children with type 1 diabetes mellitus. We found that 3.5% of the subjects had a high-density lipoprotein (HDL) cholesterol level < 35 mg/dL, 15.4% had a total cholesterol (TC) level>200 mg/dL, and 18.6% were abnormal for either HDL or TC, compared with prevalences of 5.7%, 11.2%, and 16.3%, respectively, reported in the National Health and Nutrition Examination Survey 2001-02. Hemoglobin A1c value was significantly related to TC and non-HDL cholesterol levels. [Copyright &y& Elsevier]

Objective: To evaluate the association between bone mineral density (BMD), glycemic control (hemoglobin A1c [HbA1c]), and celiac autoimmunity in children with type 1 diabetes mellitus (T1D) and in an appropriate control population.Study Design: BMD was assessed cross-sectionally in 252 children with T1D (123 positive for anti-tissue transglutaminase antibody [tTGA] and 129 matched children who were negative for tTGA). In addition, BMD was assessed in 141 children without diabetes who carried T1D-associated HLD-DR, DQ genotypes (71 positive for tTGA and 70 negative).Results: Children with T1D who were positive for tTGA had significantly worse BMD L1-L4 z-score compared with children with T1D who were negative for tTGA (-0.45 ± 1.22 vs 0.09 ± 1.10, P = .0003). No differences in growth measures, urine N-telopeptides, 25-hydroxyvitamin D, ferritin, thyroid stimulating hormone, or HbA1c were found. However, both higher HbA1c (β = -1.25 ± 0.85, P = .0016) and tTGA (β = -0.13 ± 0.05, P = .0056) were significant and independent predictors of lower BMD in multivariate analyses. No differences in BMD or other variables measured were found between children without diabetes who were positive vs negative for tTGA.Conclusions: The results suggest a synergistic effect of hyperglycemia and celiac autoimmunity on low BMD. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of a second newborn screen for congenital adrenal hyperplasia (CAH) in the state of Colorado and report characteristics associated with cases identified on the first versus second screen. Study design: Colorado implemented newborn screening for CAH with 17-hydroxyprogesterone beginning August 2000. The first screening is performed within 72 hours of life and the second between 8 and 14 days of life. We compared infants diagnosed on the basis of the first versus second newborn screen. Results: The first screen identified 29 cases of which 28 represented classical CAH. The incidence of classical CAH on the first screen was 1:24 766. The second screen identified 17 additional cases, of which 11 represented classical CAH. Combined, the incidence of classical CAH was 1:17 789. The sensitivity of the first screen was 71.79%. The false negative rate of the first screen was 28.2%. In the absence of a second screen, 1:47 824 infants would have been missed. Infants diagnosed on the first screen had higher 17-hydroxyprogesterone values compared with those diagnosed on the second screen (P = .0008). Conclusions: The use of a single newborn screen for CAH missed nearly 30% of classical CAH cases in Colorado. Addition of a second screen, therefore, can improve the operating characteristics of the newborn screening program. [Copyright &y& Elsevier]

Objective: To identify trends in the recent onset of type 1 diabetes (T1D) in Colorado youth seen at the Barbara Davis Center (BDC) and compare these changes over time. Study design: A retrospective chart review was performed of patients ages 0-20 years at diagnosis of T1D and type 2 diabetes who were seen at the BDC, were living within Colorado at diagnosis, and were seen within 1 month of diagnosis between 1996 and 2010. The review included age of onset, sex, month and season of onset, islet autoantibodies, diabetes type, hemoglobin A1c level, and body mass index. Results: Newly diagnosed youth with diabetes (n = 2841) were seen at the BDC between 1996 and 2010. Of these, 2686 (94.4%) had T1D. The number of newly diagnosed youth increased over the 15 years by 5.71% per year when adjusted for population (P < .0001). When analyzed in 5-year periods, the average number of new onset T1D cases, age-adjusted to the population, increased by 9.46% per year from 1996-2000 to 2001-2005. The increase was only 4.86% per year from 2001-2005 to 2006-2010. Islet autoimmune markers appeared to correlate with changes in T1D new onset cases. Conclusion: T1D in youth increased significantly from the late 1990s-2005 and has increased at a lesser rate more recently. Data suggests that even though T1D has increased in all age groups, the greatest increase was in the 5-9 year age category. [ABSTRACT FROM AUTHOR]

Objective: To determine the benefits of screening for celiac autoimmunity via immunoglobulin A transglutaminase autoantibodies (TG) in children with type 1 diabetes (T1D). Study design: We followed up 79 screening-identified TG+ and 56 matched TG- children with T1D for 2 years to evaluate growth, bone mineral density, nutritional status, and diabetes control. TG+ subjects self-selected to gluten-free or gluten-containing diet. Results: Of the initial cohort, 80% were available for reexamination after 2 years. TG+ subjects had consistently lower weight z-scores and higher urine N-telopeptides than TG− subjects, but similar measures of bone density and diabetes outcomes. TG+ children who remained on a gluten-containing diet had lower insulin-like growth factor binding protein 3 z-scores compared with TG+ subjects who reported following a gluten-free diet. Children who continued with high TG index throughout the study had lower bone mineral density z-scores, ferritin, and vitamin D 25OH levels, compared with the TG- group. Conclusions: No significant adverse outcomes were identified in children with T1D with screening-identified TG+ who delay therapy with a gluten-free diet for 2 years. Children with persistently high levels of TG may be at greater risk. The optimal timing of screening and treatment for celiac disease in children with T1D requires further investigation. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects of reducing overnight basal insulin or a bedtime dose of terbutaline on nocturnal blood glucose (BG) nadir and hypoglycemia after exercise in children with type 1 diabetes mellitus. Study design: Sixteen youth (mean age 13.3 years) on insulin pumps were studied overnight on 3 occasions after a 60-minute exercise session with BG measurements every 30 minutes. Admissions were randomized to bedtime treatment with oral terbutaline 2.5 mg, 20% basal rate insulin reduction for 6 hours, or no treatment. Results: Mean overnight nadir BG was 188 mg/dL after terbutaline and 172 mg/dL with basal rate reduction compared with 127 mg/dL on the control night (P = .002 and .042, respectively). Terbutaline eliminated nocturnal hypoglycemia but resulted in significantly more hyperglycemia (≥250 mg/dL) when compared with the control visit (P < .0001). The basal rate reduction resulted in fewer BG readings <80 and <70 mg/dL but more readings ≥250 mg/dL when compared with the control visit. Conclusions: A basal insulin rate reduction was safe and effective in raising post-exercise nocturnal BG nadir and in reducing hypoglycemia in children with type 1 diabetes mellitus. Although effective at preventing hypoglycemia, a 2.5-mg dose of terbutaline was associated with hyperglycemia. [ABSTRACT FROM AUTHOR]