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Context Autoantibodies to 21-hydroxylase (21OH-AA) precede onset of autoimmune Addison's disease (AD). Progression to AD can take months to years, and early detection of metabolic decompensation may prevent morbidity and mortality.

Background:The Afinion HbA1c (Axis-Shield) is a newer point-of-care device for measurement of hemoglobin A1c (A1C) using a boronate affinity method unlike the more commonly used DCA immunoassay method (Siemens Medical Solutions Diagnostics). The Afinion's accuracy and precision, when compared with high-performance liquid chromatography (HPLC) and DCA methods, have not been established in pediatric practice settings.Methods:Capillary blood was collected from 700 subjects with diabetes mellitus at seven Pediatric Diabetes Consortium sites. Each subject's A1C was measured locally using Afinion and DCA devices, and by a central laboratory (University of Minnesota) using a Tosoh HPLC method. In addition, repeated measurements on six whole blood samples provided by the National Glycohemoglobin Standardization Program (NGSP) were taken at three clinical centers using the Afinion and DCA methods and centrally using the Tosoh HPLC method to assess the precision of each device.Results:The coefficient of variation f...

The purpose of this study was to assess the performance and acceptability of a blood glucose meter coupled with a gaming system for children, adolescents, and young adults with type 1 diabetes. During an in-clinic visit, duplicate blood samples were tested by subjects (N = 147; aged 5-24 yr) and health care providers (HCPs) to evaluate the accuracy and precision of the Didget® system. Subjects' meter results were compared against Yellow Springs Instruments (YSI) reference results and HCP results using least squares regression and error grid analyses. Precision was measured by average within-subject and within-HCP coefficient of variation (CV). During the home-use component of this study, subjects (n = 58) tested their blood glucose at least two to three times daily for 3-5 d to evaluate routine use of the system. Subjects' meter results showed significant correlations with both YSI (r(2) = 0.94; p < 0.001 for regression slope) and HCP results (r(2) = 0.96; p < 0.001). Average within-subject and within-HCP CVs were 5.9 and 7.2%, respectively. Overall satisfaction was assessed by subjects, their parents or guardians, and HCP surveys. Subject satisfaction with the Didget® system was good to excellent; most subjects found the system easy to use, motivating, and helpful for building good blood glucose monitoring habits. Most HCPs agreed that the system fulfilled a need in diabetes management. In conclusion, the Didget® system was precise and clinically accurate in the hands of children, adolescents, and young adults with type 1 diabetes.

OBJECTIVE To describe an etiologic approach to classification of diabetes types in youth based on the 1997 American Diabetes Association (ADA) framework, using data from the SEARCH for Diabetes in Youth Study. RESEARCH DESIGN AND METHODS SEARCH conducted a comprehensive assessment of 2,291 subjects aged RESULTS Most subjects fell into either the autoimmune plus IS (54.5%) or nonautoimmune plus IR categories (15.9%) and had characteristics that align with traditional descriptions of type 1 or type 2 diabetes. The group classified as autoimmune plus IR (19.5%) had similar prevalence and titers of diabetes autoantibodies and similar distribution of HLA risk genotypes to those in the autoimmune plus IS group, suggesting that it includes individuals with type 1 diabetes who are obese. The group classified as nonautoimmune plus IS (10.1%) likely includes individuals with undetected autoimmunity but may also include those with monogenic diabetes and thus requires further testing. CONCLUSIONS The SEARCH study offers researchers and clinicians a practical application for the etiologic classification of diabetes type and at the same time identifies a group of youths who would benefit from further testing.

Background: Measurement of anti-islet autoantibodies at the time of disease onset contributes greatly to the differentiation of Type 1A diabetes with HLA Class II subtyping also contributing. Methods: Blood samples were obtained from 900 patients with age from 1 month to 25 years (median age 11.1 years) within 2 weeks of diabetes onset to test anti-islet autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), insulinoma antigen (IA-2AA), the zinc transporter-8 (ZnT8AA), and islet-cell antibodies (ICA). Polymorphisms of the HLA Class II gene were typed in 547 randomly selected patients. Results: Of the 900 subjects analyzed, 145 (16.1%) were negative for all five anti-islet autoantibodies, and autoantibody negativity significantly increased with age: 10.2% (38/372) among children 14 years of age (P

ObjectiveTo explore demographic, socioeconomic, diabetes-related, and behavioral correlates of dietary intake of dairy, fruit, vegetables, sweetened soda, fiber, calcium, and saturated fat in youth with diabetes.MethodsCross-sectional study of youth 10-22 years old with type 1 (T1DM, n=2,176) and type 2 diabetes (T2DM, n=365). Association of dietary intake, demographics, socioeconomic status, behavioral, and diabetes-related measures was explored with quantile regression.ResultsT1DM males had lower consumption of vegetables, fruit, and fiber, and higher consumption of soda and saturated fat than females (P < .01). African Americans had lower dairy and higher soda intake than non-Hispanic T1DM whites (P < .01). Soda consumption was higher in older T2DM youth than in younger participants (P < .01). Lifestyle and physical activity patterns were also significantly associated with dietary intake.Conclusions and ImplicationsIdentified demographic and behavioral correlates may help dietitians to focus on groups of youth with diabetes who have lower adherence to a healthful diet. Diet counseling groups may be tailored according to these major determinants.

OBJECTIVE We explore continuous glucose monitoring (CGM) as a new approach to defining early hyperglycemia and diagnosing type 1 diabetes in children with positive islet autoantibodies (Ab+). RESEARCH DESIGN AND METHODS Fourteen Ab+ children, free of signs or symptoms of diabetes, and nine antibody-negative (Ab−) subjects, followed by the Diabetes Autoimmunity Study in the Young, were asked to wear a Dexcom SEVEN CGM. RESULTS The Ab+ subjects showed more hyperglycemia, with 18% time spent above 140 mg/dL, compared with 9% in Ab− subjects (P = 0.04). Their average maximum daytime glucose value was higher, and they had increased glycemic variability. The mean HbA1c in the Ab+ subjects was 5.5% (37 mmol/mol). Among Ab+ subjects, ≥18–20% CGM time spent above 140 mg/dL seems to predict progression to diabetes. CONCLUSIONS CGM can detect early hyperglycemia in Ab+ children who are at high risk for progression to diabetes. Proposed CGM predictors of progression to diabetes require further validation.

OBJECTIVE To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical type 1 diabetes in the sample interval following detection of enteroviral RNA in serum (three diabetes cases diagnosed among 17 intervals) was significantly increased compared with that in intervals following a negative serum enteroviral RNA test (33 cases diagnosed among 1,064 intervals; hazard ratio 7.02 [95% CI 1.95–25.3] after adjusting for number of autoantibodies). Results remained significant after adjustment for ZnT8-autoantibodies and after restriction to various subgroups. Enteroviral RNA in rectal swabs was not predictive of progression to type 1 diabetes. No evidence for viral persistence was found. CONCLUSIONS This novel observation suggests that progression from islet autoimmunity to type 1 diabetes may increase after an enterovirus infection characterized by the presence of viral RNA in blood.

OBJECTIVE To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings. RESEARCH DESIGN AND METHODS Children (10–17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations. RESULTS Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects. CONCLUSIONS Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes.

Objective Studies have suggested that the age at diagnosis of Type 1 diabetes (T1D) is decreasing over time. The overload hypothesis postulates that risk factors, such as accelerated growth, may be responsible for this decrease. We assessed changes in age, body mass index (BMI), weight and height at diagnosis with T1D in non-Hispanic white (NHW) and Hispanic (HISP) young people from Colorado, using data from the IDDM Registry and SEARCH Study. Methods In three time periods, 656 (1978–1983), 562 (1984–1988) and 712 (2002–2004) young people aged 2–17 years were newly diagnosed with T1D. Age, weight, height and presence of diabetic ketoacidosis (DKA) at diagnosis with T1D were obtained from medical records. Trends over the three time periods were assessed with regression analyses. Results Age at diagnosis decreased by 9.6 months over time (P = 0.0002). Mean BMI standard deviation score (SDS), weight SDS and height SDS increased over time (P

Catherine Pihokera, Gun Forsanderb, Bereket Fantahunc, Anju Virmanid, Xiaoping Luoe, Marie Hallmanb, Joseph Wolfsdorff and David M Maahsg aDepartment of Pediatrics, University of Washington, Seattle, WA, USA ; bDivision of Diabetes, The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden; cDepartment of Pediatrics, Addis Ababa University, Addis Ababa, Ethiopia; dDepartment of Pediatrics, Apollo, Max, Pentamed and SL Jain Hospitals, Delhi, India; eDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; fDivision of Endocrinology, Boston Children’s Hospital, Harvard University, Boston, MA, USAand gBarbara Davis Center for Childhood Diabetes, Aurora, CO, USA

This article reports pilot study results evaluating the accuracy of carbohydrate counting among adolescents with type 1 diabetes. This cross-sectional observational study included 48 adolescents ages 12–18 years (mean 15.2 ± 1.8 years) with type 1 diabetes of > 1 year in duration (mean A1C 8.0 ± 1.0%) who used insulin:carbohydrate (I:C)ratios for at least one meal per day. The adolescents were asked to assess the amount of carbohydrate in 32 foods commonly consumed by youths. Foods were presented either as food models or as actual food, with some items presented as standard serving sizes and some self-served by study participants. T-tests were used to assess the significance of over- or underestimation of carbohydrate content. For each meal, accuracy was categorized as accurate (within 10 grams), overestimated (by > 10 grams),or underestimated (by > 10 grams) based on the commonly used I:C ratio of 1 unit of insulin per 10 grams of carbohydrate. Only 23% of adolescents estimated daily carbohydrate within 10 grams of the true amount despite selection of common meals. For dinner meals, individuals with accurate estimation of carbohydrate grams had the lowest A1C values (7.69± 0.82%, P = 0.04). The pilot study provides preliminary evidence that adolescents with type 1 diabetes do not accurately count carbohydrates. Further data are needed on carbohydrate counting accuracy and other factors that affect glycemic control.

OBJECTIVE—To estimate the prevalence and incidence of diabetes, clinical characteristics, and risk factors for chronic complications among Navajo youth, using data collected by the SEARCH for Diabetes in Youth Study (SEARCH study). RESEARCH DESIGN AND METHODS—The SEARCH study identified all prevalent cases of diabetes in 2001 and all incident cases in 2002–2005 among Navajo youth. We estimated denominators with the user population for eligible health care facilities. Youth with diabetes also attended a research visit that included questionnaires, physical examination, blood and urine collection, and extended medical record abstraction. RESULTS—Diabetes is infrequent among Navajo youth aged CONCLUSIONS—Our data provide evidence that diabetes is an important health problem for Navajo youth. Targeted efforts aimed at primary prevention of diabetes in Navajo youth and efforts to prevent or delay the development of chronic complications among those with diabetes are warranted.

Since a 'type 2 phenotype' has become increasingly common in patients with type 1 diabetes, the etiology of diabetes can no longer be established exclusively on the basis of phenotypic presentation. This Case Study illustrates the difficulty of diagnosis in an obese adolescent with new onset diabetes, and discusses management and follow-up strategies. Background A 14-year-old, obese, African American boy presented to his pediatrician with polyuria, polydipsia, and a significant unintentional weight loss. He was dehydrated, with high levels of blood sugar and urinary ketones. He had no history of previous illnesses and was not taking any medications. He had a family history of type 2 diabetes mellitus. Investigations Physical examination included assessing stigmata of insulin resistance, and measuring blood pressure, pulse, and BMI. Blood samples were obtained for measurement of venous blood pH, bicarbonate, serum glucose, electrolytes, HbA1C, aminotransferases and lipids. Urine was sampled for measurement of ketones. Subsequently, measurements of fasting C-peptide and immunoassays for insulin autoantibodies (IAA), islet-cell autoantibodies (ICA-512) and glutamic acid decarboxylase autoantibodies (GAD-65) were performed. Diagnosis New-onset diabetes mellitus with diabetic ketoacidosis, initially diagnosed as type 2 diabetes mellitus, but later determined as type 1 diabetes mellitus. Management After treatment of diabetic ketoacidosis with hydration and insulin infusion, the patient was discharged on subcutaneous insulin. He was diagnosed with type 2 diabetes mellitus and was transferred to oral insulin-sensitizing agents. He re-presented 18 months later with an insulin requirement during an asthma exacerbation treated with steroids. Due to the worsening of his diabetic symptoms, the patient was tested for islet autoantibodies and was found to be positive for GAD-65 and IAA, that is, diagnostic of type 1 diabetes mellitus. He has continued to require subcutaneous insulin.

OBJECTIVE—Type 1 diabetes is associated with a wide spectrum of susceptibility and protective genotypes within the HLA class II system. It has been reported that adults diagnosed with youth-onset type 1 diabetes more recently have been found to have fewer classical high-risk HLA class II genotypes than those diagnosed several decades ago. We hypothesized that such temporal trends in the distribution of HLA-DR, DQ genotypes would be evident, and perhaps even stronger, among 5- to 17-year-old Hispanic and non-Hispanic white (NHW) youth diagnosed with type 1 diabetes in Colorado between 1978 and 2004. RESEARCH DESIGN AND METHODS—HLA-DR, DQ was typed using PCR and sequence-specific oligonucleotide hybridization in 100 youth diagnosed during the period of 1978–1988 and 264 diagnosed during 2002–2004. Logistic regression was used to adjust for confounders and assess temporal trends. RESULTS—The frequency of the highest-risk genotype (DRB1*03-DQB1*02/DRB1*04-DQB1*03) was higher (39%) in children diagnosed during the period 1978–1988 than in those diagnosed during 2002–2004 (28%). A similar pattern was observed in NHWs and Hispanics. CONCLUSIONS—We found that high-risk HLA genotypes are becoming less frequent over time in youth with type 1 diabetes of NHW and Hispanic origin. This temporal trend may suggest that increasing environmental exposure is now able to trigger type 1 diabetes in subjects who are less genetically susceptible.

Objective Current data are limited on the course of type 1 diabetes (T1D) in children and adolescents through the first few years of diabetes. The Pediatric Diabetes Consortium T1D new onset (NeOn) Study was undertaken to prospectively assess natural history and clinical outcomes in children treated at 7 US diabetes centers from the time of diagnosis. This paper describes clinical outcomes in the T1D NeOn cohort during the first 3 years postdiagnosis. Results A total of 1048 participants (mean age 9.2 years, 49% female, 65% non-Hispanic White) were enrolled between July 2009 and April 2011. Mean glycated hemoglobin (HbA1c) (±SD) was 7.2% (55 mmol/mol) at 3 months, followed by a progressive rise to 8.4% (68 mmol/mol) at 36 months postdiagnosis, with only 30% of participants achieving target HbA1c

Marian J Rewersa, Kuben Pillayb, Carine de Beaufortc, Maria E Craigd, Ragnar Hanase, Carlo L Acerinif and David M Maahsa aBarbara Davis Center, University of Colorado Denver, Aurora, CO, USA; bWestville Hospital, Durban, South Africa; cDECCP, Clinique Pediatrique/CHL, Luxembourg, Luxembourg; dInstitute of Endocrinology and Diabetes, Westmead, Australia; eDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden and fDepartment of Pediatrics, University of Cambridge, Cambridge, UK

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.

Children with positive islet autoantibodies monitored prospectively avoid metabolic decompensation at type 1 diabetes (T1D) diagnosis. However, the effects of early diagnosis and treatment on preservation of insulin secretion and long-term metabolic control are unknown. We compared characteristics of children detected through research screening (Diabetes Autoimmunity Study in the Young [DAISY]) versus community controls at baseline and, in a subset, 6- and 12-month metabolic outcomes.This was a case-control study comparing DAISY children with T1D to children diagnosed in the general community. All participants underwent mixed-meal tolerance testing; a subset wore a continuous glucose monitoring (CGM) device. Fasting and stimulated C-peptide levels, insulin dose-adjusted hemoglobin A1c (IDAA1c), and CGM variables were compared.Children (21 DAISY, 21 community) were enrolled and matched by age, time of diagnosis, and diabetes duration; 18 were enrolled within 2 months and 24 within 2.5 years on average from diagnosis. In the overall group and the subgroup of participants enrolled 2.5 years from diagnosis, there were no IDAA1c or C-peptide differences between DAISY versus community children. The subgroup of DAISY versus community children enrolled near diagnosis, however, had lower baseline hemoglobin A1c (6.5±1.4% vs. 9.2±2.9%; P=0.0007) and IDAA1c (7.4±2.1% vs. 11.2±3.5%; P=0.04) and higher stimulated C-peptide (2.5±0.5 vs. 1.6±0.2 ng/mL; P=0.02). In this subgroup, IDAA1c differences persisted at 6 months but not at 1 year. CGM analyses revealed lower minimum overnight glycemia in community children (72 vs. 119 mg/dL; P=0.01).Favorable patterns of IDAA1c and C-peptide seen in research-screened versus community-diagnosed children with T1D within 2 months of diagnosis are no longer apparent 1 year from diagnosis.

OBJECTIVE To evaluate the frequency of depressive symptoms and the diagnosis and management of depression in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium T1D and T2D registries. RESEARCH DESIGN AND METHODS The Children’s Depression Inventory (CDI) 2 Self-Report (Short) version was completed by 261 T1D and 339 T2D youth aged 10–17 years. RESULTS Symptoms of depression were identified in 13% of T1D and 22% of T2D (P = 0.007) participants; of these, only 4% of T1D and 9% of T2D youth were treated by a therapist within the prior 12 months. Depressive symptoms were associated with lower family income (P = 0.006) and obesity (P = 0.002) in T1D but not T2D youth. CONCLUSIONS Depressive symptoms are more frequent than diagnosed depression in youth with T1D or T2D. These results underscore the need for regular depression screening and appropriate referral for youth with diabetes.

OBJECTIVE—The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH DESIGN AND METHODS—This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA1c (A1C) values ≥8.0%. Twenty-four subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus alarms (experimental group), while the other 24 subjects continued use of their current insulin pumps (control group) without meal bolus alarms. RESULTS—After 3 months of study, the number of missed meal boluses per week was significantly lower in the experimental group (from 4.9 ± 3.7 to 2.5 ± 2.5; P = 0.0005) but not significantly lower in the control group (from 4.3 ± 2.7 to 4.2 ± 3.9; P = 0.7610). Also after 3 months, the mean A1C value of the experimental group declined significantly (from 9.32 ± 1.12 to 8.86 ± 1.10; P = 0.0430). No significant decline in A1C was present for the control group (from 8.93 ± 1.04 to 8.67 ± 1.17; P = 0.1940). After 6 months of study, the significant decline in A1C from baseline in the experimental group was no longer present. Pooling of all available data from the control and experimental groups showed that at baseline and 3 and 6 months, the number of missed meal boluses per week was significantly correlated with A1C values. CONCLUSIONS—While meal bolus alarms may have the potential to improve suboptimal glycemic control in youth using CSII, our results demonstrated that these alarms had only a transient, modest effect in doing so.

Objective: To illustrate that rapid diagnosis and aggressive treatment of rhinocerebral mucormycosis with internal carotid artery occlusion in a pediatric patient can prevent mortality and significant morbidity. Research Designs and Methods: Rhinocerebral mucormycosis infrequently occurs in the pediatric population, and when it involves thrombosis of an internal carotid artery, it has been almost uniformly fatal. We present an 8-yr-old girl with type 1 diabetes mellitus who has survived such an infection for 2 yr, and who has minimal residual morbidity. We believe she is the youngest patient to survive rhinocerebral mucormycosis complicated by internal carotid artery and cavernous sinus thromboses. She has survived with an intensive regimen including aggressive surgical debridement, amphotericin B, rigorous glucose control, hyperbaric oxygen therapy, interferon-γ, posaconazole (an experimental antifungal), and granulocyte-macrophage colony-stimulating factor. Conclusions: This article illustrates the importance of prompt recognition and aggressive treatment of fungal infection in patients with diabetes. Additionally, it emphasizes that such treatment can have an excellent outcome, and mortality and significant morbidity can be avoided. Finally, we provide a review of the literature regarding mucormycosis infections and treatment options.

Nonalcoholic fatty liver disease, a cause of chronic liver disease in obese adults also occurs in obese children. In susceptible populations, fatty liver progresses to nonalcoholic steatohepatitis and eventually to fibrosis and cirrhosis. Nonalcoholic steatohepatitis is associated with elevation of alanine aminotransferase, although the aminotransferases can also be normal. The prevalence of nonalcoholic fatty liver disease in type 2 diabetes is unclear in adults and unknown in children.The aim of this study was to estimate the prevalence of elevated serum aminotransferases as a marker of nonalcoholic fatty liver disease in pediatric type 2 diabetes and to identify correlates of aminotransferase elevation.A chart review was completed on 115 children with type 2 diabetes at a pediatric diabetes clinic. The prevalence of elevated alanine aminotransferase was calculated from the 42% of patients with available aminotransferase measurements and correlations with fasting lipids, hemoglobin A-1c, body mass index, age and diabetes therapy were sought.The prevalence of elevated alanine aminotransferase was 48%. There was no association between elevations and other variables. Among subjects with elevated alanine aminotransferase, 39% were one to two times above normal, 26% were two to three times normal and 35% were greater than three times above normal. Several patients experienced improvement in aminotransferase elevations after using insulin-sensitizing medications.There is a high prevalence of elevated serum aminotransferases among children with type 2 diabetes unrelated to age, body mass index, glycemic control, blood lipids or diabetic therapy. The significance of this abnormality and its relationship to nonalcoholic fatty liver disease requires further evaluation.

Objectives: (a) To determine the incidence and severity of diabetic ketoacidosis (DKA) and (b) to stratify according to insurance status at the initial diagnosis of type 1 diabetes (T1DM). Research Design and Methods: Subjects included children

During recent years, the American Diabetes Association (ADA) has published detailed guidelines and recommendations for the management of diabetes in the form of technical reviews, position statements, and consensus statements. Recommendations regarding children and adolescents have generally been included as only a minor portion of these documents. For example, the most recent ADA position statement on “Standards of Medical Care for Patients With Diabetes Mellitus” (last revised October 2003) included “special considerations” for children and adolescents (1). Other position statements included age-specific recommendations for screening for nephropathy (2) and retinopathy (3) in children with diabetes. In addition, the ADA has published guidelines pertaining to certain aspects of diabetes that apply exclusively to children and adolescents, including care of children with diabetes at school (4) and camp (5) and a consensus statement on type 2 diabetes in children and adolescents (6). The purpose of this document is to provide a single resource on current standards of care pertaining specifically to children and adolescents with type 1 diabetes. It is not meant to be an exhaustive compendium on all aspects of the management of pediatric diabetes. However, relevant references are provided and current works in progress are indicated as such. The information provided is based on evidence from published studies whenever possible and, when not, supported by expert opinion or consensus (7). Several excellent detailed guidelines and chapters on type 1 diabetes in pediatric endocrinology texts exist, including those by the International Society of Pediatric and Adolescent Diabetes (ISPAD) (8), by the Australian Pediatric Endocrine Group (www.chw.edu/au/prof/services/endocrinology/apeg), in Lifshitz’s Pediatric Endocrinology (9–11), and by Plotnick and colleagues (12,13). Children have characteristics and needs that dictate different standards of care. The management of diabetes in children must take the major differences between children of various ages and …

OBJECTIVE—The objective of this study was to determine whether earlier diagnosis of diabetes in prospectively followed autoantibody-positive children lowered onset morbidity and improved the clinical course after diagnosis. RESEARCH DESIGN AND METHODS—The Diabetes Autoimmunity Study in the Young (DAISY) follows genetically at-risk children for the development of diabetes. Increased genetic risk is identified by family history of type 1 diabetes or expression of diabetes-associated HLA genotypes. Of the 2,140 prospectively followed children, 112 have developed islet autoantibodies and 30 have progressed to diabetes. Diabetes onset characteristics and early clinical course of these 30 children followed to diabetes were compared with those of 101 age- and sex-matched children concurrently diagnosed with diabetes in the community. RESULTS—Pre-diabetic children followed to diabetes were less often hospitalized than the community cases (3.3 vs. 44%; P < 0.0001). They had a lower mean HbA1c at onset (7.2 vs. 10.9%; P < 0.0001) and 1 month after diagnosis (6.9 vs. 8.6%; P < 0.0001) but not after 6 months of diabetes. The mean insulin dose was lower in the DAISY group at 1 (0.30 vs. 0.51 U · kg−1 · day−1; P = 0.003), 6 (0.37 vs. 0.58; P = 0.001), and 12 months (0.57 vs. 0.72; P = 0.03). There was no difference in growth parameters between the two groups. Comparisons limited to children with a family history of type 1 diabetes in both groups showed a similar pattern. CONCLUSIONS—Childhood type 1 diabetes diagnosed through a screening and follow-up program has a less severe onset and a milder clinical course in the first year after diagnosis.

Purpose: To redefine the clinical remission period for different aged children receiving the current standard of diabetes care. Methods: An electronic patient records system was used to identify 552 children newly diagnosed with type 1 diabetes (T1D) from 1997 to 2001 who had an initial hemoglobin A1c (HbA1c) value at the time of diagnosis and at least one other value measured in the ensuing year. The insulin dosage previously used to define the remission period [0.5 U/kg/d by 9 months after diagnosis. The mean HbA1c values were above 8% by 6 months after diagnosis for the 6–9 and the 10–12 yr age groups and by 9 months after diagnosis for the ≥13 yr age group. The percentage of children ≤5 yr of age who continued to receive

OBJECTIVE—The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age ≤15 months. Information on indicators of infection was collected by structured interviews soon after birth and at ages 3–15 months. Clinic visits were scheduled at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity for one or more islet autoantibodies (to GAD65, insulin, or IA-2/ICA512) at two or more consecutive visits. During a mean follow-up of 4.2 years, 52 children developed islet autoimmunity. RESULTS—Children whose mother reported at least one symptom of infection during pregnancy (mostly respiratory or gastrointestinal) had a significantly lower risk of islet autoimmunity compared with other children (hazard ratio 0.48; 95% CI 0.27–0.83). After stratification, the association appeared among girls (0.21; 0.09–0.48) but not among boys (1.09; 0.47–2.51) with a P value for interaction of 0.005. Symptoms of neonatal infections, early daycare attendance, exposure to cats or dogs, and household crowding were not related to islet autoimmunity. CONCLUSIONS—Symptoms of maternal infections in pregnancy predicted a significantly lower risk of islet autoimmunity in young girls, suggesting a protective effect of such infections.

The transition of pediatric patients into the adult world is a major medical issue and a high-risk time period (1–4). In patients with type 1 diabetes, glycemic control is at its worst during adolescence and emerging adulthood (5,6). The goal of this study was to investigate the feasibility and acceptability of a novel clinical care approach to the type 1 diabetes transition population that would require no additional resources or staff, would be applicable in all clinical settings, could be sustainable outside of a grant setting, and would not require additional time or appointments for patients and families. Alternative medical care approaches, specifically shared medical appointments (SMAs), have successfully increased patient and provider satisfaction, maximized billing, and improved outcomes in other challenging patient populations. The SMA model has been used in adults with chronic medical conditions (including diabetes), women receiving prenatal care, patients requiring urgent care visits, and patients needing routine health care maintenance (7–10). Although not reflected strongly in the literature, the SMA model has also been successful in the pediatric population. In the literature, SMA models have resulted in improved patient outcomes, increased satisfaction of providers and patients, and improved billing and efficiency. Group scheduling has allowed for more comprehensive visits, with increased screening rates and more frequent educational interventions (e.g., from dietitians, nursing staff, and mental health providers). The SMA model has also been found to be more efficient for medical providers, allowing them to see more patients in the same time period (10). Based on the success of SMAs in other chronic medical conditions, the Team Clinic SMA clinic was developed for adolescent patients receiving care at a large pediatric diabetes center. A multidisciplinary team of providers caring for patients in the diabetes center, including social workers, dietitians, certified …

We thank Brancato and Provenzano (1) for their comments on our article (2). They pointed out their previously published study (3) of continuous glucose monitoring (CGM) in 31 islet autoantibody–negative children with incidental hyperglycemia, followed for 6–48 months for development of diabetes. Incidental hyperglycemia was defined as fasting or random, blood glucose ≥126 or ≥200 mg/dL, respectively, without symptoms of diabetes and not …

BACKGROUND AND OBJECTIVES:Previous research has documented racial/ethnic disparities in diabetes treatments and outcomes. It remains controversial whether these disparities result from differences in socioeconomic status (SES) or other factors. We examined racial/ethnic disparities in therapeutic modalities and diabetes outcomes among the large number of pediatric participants in the T1D Exchange Clinic Registry.METHODS:The cohort included 10 704 participants aged RESULTS:Insulin pump use was higher in white participants than in black or Hispanic participants (61% vs 26% and 39%, respectively) after adjusting for gender, age, diabetes duration, and SES (P < .001). Mean hemoglobin A1c was higher (adjusted P < .001) in black participants than in white or Hispanic participants (9.6%, 8.4%, and 8.7%). More black participants experienced diabetic ketoacidosis and severe hypoglycemic events in the previous year than white or Hispanic participants (both, P < .001). There were no significant differences in hemoglobin A1c, diabetic ketoacidosis, or severe hypoglycemia between white and Hispanic participants after adjustment for SES.CONCLUSIONS:Even after SES adjustment, marked disparities in insulin treatment method and treatment outcomes existed between black versus Hispanic and white children within this large pediatric cohort. Barriers to insulin pump use and optimal glycemic control beyond SES should be explored in all ethnic groups.

To describe C-peptide levels in a large cohort of children with type 2 diabetes T2D and examine associations with demographic and clinical factors.The Pediatric Diabetes Consortium (PDC) T2D Registry has collected clinical and biologic data from youth with T2D cared for at eight US Pediatric Diabetes Centers. In this study, we assessed C-peptide levels in 331 youth with T2D (mean age, 16.1 ± 2.5 yr; median T2D duration, 2.4 yr).Median (interquartile range) for 90 fasted C-peptide measurements was 3.5 ng/mL (2.3-4.8 ng/mL) [1.2 nmol/L (0.8-1.6 nmol/L)] and for 241 random non-fasted C-peptide measurements were 4.2 ng/mL (2.6-7.0 ng/mL) [1.4 nmol/L (0.9-2.3 nmol/L)]. C-peptide levels were lower with insulin therapy (p0.001), lower body mass index (p0.001), hemoglobin A1c (HbA1c) ≥9% (p0.001), and T2D duration ≥ 6 yr (p = 0.04). Among those with duration ≥6 yr being treated with insulin and with a HbA1c level ≥9.0% (75 mmol/L), 75% of the fasted and 80% of the non-fasted C-peptide values were above 0.2 nmol/L.In youth with T2D, a decline in C-peptide is associated with deterioration of metabolic control and the need for insulin treatment. C-peptide levels decrease over time. However, even insulin-treated patients with 6 or more years of T2D and elevated HbA1c levels retain substantial endogenous insulin secretion.

A total of 21,000 general population newborns (NECs) and 693 young siblings-offspring of patients with type 1A diabetes (SOCs) were class II genotyped and 293 NECs and 72 SOCs with the high-risk genotype, DR3/4, DQB1*0302 have been prospectively evaluated. Seventeen individuals who converted to persistent autoantibody positivity and two autoantibody-negative control groups (35 SOCs and 24 NECs) were typed for HLA-A class I alleles. The A1, A2 genotype was significantly increased among the autoantibody-positive subjects (47%) compared to autoantibody-negative SOCs (14%, P = 0.01) and NECs (13%, P = 0.02). Life-table analysis of DR3/4, DQB1*0302 siblings revealed a risk of 75% for development of islet autoantibodies by the age of 2 years for those with A1, A2. The HLA-A2 phenotype frequency was increased among an independent DR3/4, DQB1*0302 young diabetes cohort (64% versus 33% for autoantibody-negative NECs). These results suggest that a high incidence and early appearance of islet autoantibodies for siblings of patients with type 1A diabetes are associated with DR3/4, DQB1*0302 and potentially increased with HLA-A genotype A1, A2.

OBJECTIVE We sought to define the prevalence of nonislet, organ-specific autoantibodies at diagnosis of type 1 diabetes and to determine the prevalence of comorbid autoimmune diseases. RESEARCH DESIGN AND METHODS Children (n = 491) diagnosed with type 1 diabetes at the Barbara Davis Center for Childhood Diabetes were screened for autoimmune thyroid disease (thyroid peroxidase autoantibodies [TPOAb]), celiac disease (tissue transglutaminase autoantibodies [TTGAb]), and Addison disease (21-hydroxylase autoantibodies [21OHAb]). RESULTS Of the 491 children, 161 had at least one nonislet autoantibody, and of these, 122 (24.8%) were positive for TPOAb, and 15 of the 122 (12.3%) had autoimmune thyroid disease. There were 57 (11.6%) who were positive for TTGAb, of whom 14 (24.6%) had celiac disease. Five (1.0%) were positive for 21OHAb, of whom one had Addison disease. CONCLUSIONS Many autoantibody-positive subjects present with additional autoimmune disorders. Detection of these autoantibodies at type 1 diabetes onset may prevent complications associated with delayed diagnosis of these disorders.

Insulin degludec (IDeg) once-daily was compared with insulin detemir (IDet) once- or twice-daily, with prandial insulin aspart in a treat-to-target, randomized controlled trial in children 1-17 yr with type 1 diabetes, for 26 wk (n = 350), followed by a 26-wk extension (n = 280). Participants were randomized to receive either IDeg once daily at the same time each day or IDet given once or twice daily according to local labeling. Aspart was titrated according to a sliding scale or in accordance with an insulin:carbohydrate ratio and a plasma glucose correction factor. Randomization was age-stratified: 85 subjects 1-5 yr. (IDeg: 43), 138 6-11 yr (IDeg: 70) and 127 12-17 yr (IDeg: 61) were included. Baseline characteristics were generally similar between groups overall and within each stratification. Non-inferiority of IDeg vs. IDet was confirmed for HbA1c at 26 wk; estimated treatment difference (ETD) 0.15% [-0.03; 0.32]95% CI . At 52 wk, HbA1c was 7.9% (IDeg) vs. 7.8% (IDet), NS; change in mean FPG was -1.29 mmol/L (IDeg) vs. +1.10 mmol/L (IDet) (ETD -1.62 mmol/L [-2.84; -0.41]95% CI , p = 0.0090) and mean basal insulin dose was 0.38 U/kg (IDeg) vs. 0.55 U/kg (IDet). The majority of IDet treated patients (64%) required twice-daily administration to achieve glycemic targets. Hypoglycemia rates did not differ significantly between IDeg and IDet, but confirmed and severe hypoglycemia rates were numerically higher with IDeg (57.7 vs. 54.1 patient-years of exposure (PYE) [NS] and 0.51 vs. 0.33, PYE [NS], respectively) although nocturnal hypoglycemia rates were numerically lower (6.0 vs. 7.6 PYE, NS). Rates of hyperglycemia with ketosis were significantly lower for IDeg vs. IDet [0.7 vs. 1.1 PYE, treatment ratio 0.41 (0.22; 0.78)95% CI , p = 0.0066]. Both treatments were well tolerated with comparable rates of adverse events. IDeg achieved equivalent long-term glycemic control, as measured by HbA1c with a significant FPG reduction at a 30% lower basal insulin dose when compared with IDet. Rates of hypoglycemia did not differ significantly between the two treatment groups; however, hyperglycemia with ketosis was significantly reduced in those treated with IDeg.

Type 2 diabetes (T2D) in youth is recognized as a pediatric disease, but few reports describe the characteristics during diagnosis. We describe the clinical presentation of 503 youth with T2D.The Pediatric Diabetes Consortium (PDC) T2D Clinic Registry enrolled T2D participants from eight pediatric diabetes centers in the USA. Clinical and laboratory characteristics at the time of diagnosis were analyzed.In total 67% presented with symptoms of diabetes and confirming laboratory data, but 33% were identified by testing at risk children, 11% presented with diabetic ketoacidosis (DKA), and 2% with hyperglycemic hyperosmolar state (HHS). The mean age was 13.1 ± 2.3 yr (range, 4.6-19.8 yr) with 38 (8%) less than 10 yr of age at diagnosis. The majority was female (65%), Hispanic (54%) and had a family history of T2D (92%). The median body mass index (BMI) z-score was 2.3 (interquartile range 2.0-2.6). Fewer than half (46%) lived with both parents, only 30% had parents with education beyond high school, and 43% lived in a household with an income of$25 000 per year. In the initial month after diagnosis, almost all (92%) were treated with insulin (30%), metformin (31%), or a combination of insulin and metformin (32%); 7% were treated with lifestyle modification alone.The demographics of T2D in youth indicate significant social vulnerability which may affect outcomes. Metformin and insulin were the initial treatment in most youth. Importantly, T2D may occur at younger ages than previously thought and should be considered in all high-risk children presenting with diabetes.

To describe parent perceptions of children's diabetes care at school including: availability of licensed health professionals; staff training; logistics of provision of care; and occurrence and treatment of hypo- and hyperglycemia; and to examine parents' perceptions of their children's safety and satisfaction in the school environment.A survey was completed by parents of children with type 1 diabetes from permissive (trained, non-medical school personnel permitted to provide diabetes care; N = 237) and non-permissive (only licensed health care professionals permitted to provide diabetes care; N = 198) states.Most parents reported that schools had nurses available for the school day; teachers and coaches should be trained; nurses, children, and parents frequently provided diabetes care; and hypo- and hyperglycemia occurred often. Parents in permissive states perceived children to be as safe and were as satisfied with care as parents in non-permissive states.Training non-medical staff will probably maximize safety of children with diabetes when a school nurse is not available.

Objective: The purpose of this study was twofold (i): to evaluate metabolic control in patients receiving CSII therapy in a routine pediatric diabetes clinic by describing reasons for initiating therapy and daily management issues, including needle fear; and (ii) to assess the change in parental involvement and anxiety once their child initiated CSII therapy. Research design and methods: The study included 52 subjects (aged 7.6–23.6 yr) from a general pediatric diabetes clinic. Management issues were defined as diet, exercise, home blood glucose monitoring (HBGM) frequency, and self/staff assessment of needle fear. Characteristics were analyzed both according to a 0.5% change in HbA1c status (decreased vs. stable vs. increased) compared with pre-CSII therapy, and final HbA1c achieved (≤ 8.1 vs. > 8.1%). Results: The primary recommendation source for CSII use was most often the physician/diabetes team (48.1%), followed by a combination of the former with a personal referral source (32.7%). The most common reason (71.2%) for CSII initiation was a combination of wanting to achieve better metabolic control, dislike of insulin injections, and/or increased flexibility in daily living. Over one-quarter (26.9%) of subjects were identified as being needle-fearful, and this characteristic was predictive of final metabolic control (3/25 subjects ≤ 8.1% vs. 11/27 subjects > 8.1%, p = 0.03). On CSII therapy, dietary carbohydrate consistency was highly variable, and most subjects (65.3%) exclusively used an insulin to carbohydrate ratio for insulin bolus dosage calculation. The most common adjustment strategy (63.5%) for exercise was a combination of decreasing the insulin basal rate, disconnecting the pump, and/or eating extra carbohydrates. For the total cohort, the frequency of HBGM significantly increased on CSII therapy (4.31–4.85 tests/day, p = 0.02). Females did not have a significant change in HBGM frequency, while the youngest subjects had the highest HBGM frequency. Parental involvement and anxiety primarily stayed the same or decreased, regardless of the child's age (≤ 18 vs. > 18 yr) or metabolic control. Conclusions: Analyses of the various characteristics identified only needle fearfulness as being predictive of poor metabolic control. Interestingly, poor control with CSII therapy did not result in a significant increase in parental involvement and/or anxiety.

OBJECTIVE We sought to examine whether age at menarche has changed over the past 4 decades by comparing age at menarche by year of diagnosis with type 1 diabetes. RESEARCH DESIGN AND METHODS This work consisted of a cross-sectional study of age at menarche in two cohorts: adolescents (ages 11–24 years, n = 228) and adults (ages 19–55 years, n = 290, enrolled in the Coronary Artery Calcification in Type 1 Diabetes study). RESULTS The adolescent cohort reported a younger age of menarche than the adult women with type 1 diabetes (12.69 ± 0.08 vs. 13.22 ± 0.12 years, mean ± SE, P < 0.001). Age at menarche was later in both adolescent girls and adult women with type 1 diabetes diagnosed before menarche (12.82 ± 1.16 and 13.7 ± 2.23 years) than for individuals diagnosed after menarche (12.12 ± 1.25 and 12.65 ± 1.38 years, P < 0.001 for both). Age at menarche was then examined by decade of type 1 diabetes diagnosis (1970–1979, 1980–1989, 1990–1999, and 2000–2009). Age at menarche significantly declined over the 4 decades (P = 0.0002). However, the delay in menarche among girls diagnosed with type 1 diabetes before menarche compared with those diagnosed after menarche was also significant across all decades (P < 0.0001) and did not change significantly over time (P = 0.41 for interaction of cohort and diagnosis premenarche). CONCLUSIONS Age at menarche has declined over the past 4 decades among girls with type 1 diabetes, but a delay in age at menarche remains among individuals diagnosed before menarche compared with individuals diagnosed after menarche.

Our objective was to investigate whether notification of high-risk status for type 1 diabetes in newborn infants results in an increased maternal-parenting stress level when compared with notification of low-risk status for type 1 diabetes. Maternal parenting stress level was assessed at 5–7 weeks postpartum (baseline) and was reassessed 4–5 months after parents were informed of their newborn infants' genetic screening results (follow-up). Parenting stress level was measured using the total stress score (TSS) of the Parenting Stress Index/Short Form. The outcome variable, change in TSS, was calculated by subtracting the baseline TSS from the follow-up TSS. Demographic variables such as maternal race, maternal age, maternal education level, maternal marital status, child's birth order, and total family income were assessed through a structured phone interview at the time of baseline assessment. The risk factor of interest was the child's human leukocyte antigen (HLA) status for type 1 diabetes, i.e., whether child was at a high or moderate (combined into “high”) genetic risk or at a low genetic risk for type 1 diabetes. A sample of 88 mothers (23 with a high-risk child and 65 with a low-risk child) was evaluated. Baseline median TSSs were 65 and 74 for mothers of low-risk infants and mothers of high-risk infants, respectively. Both groups' median TSS decreased between baseline and follow-up. No significant differences were found between change in TSS and maternal age, race, education level, marital status, total family income, or child's birth order. Although the median decrease in TSS was smaller in mothers with a high-risk child when compared with mothers of a low-risk child, this difference was not statistically significant. We did not find an association between newborn's HLA status and change in maternal TSS. The results of this study suggest that notification of high-risk status for type 1 diabetes in newborn infants may not result in an increased level of parenting stress among mothers. Am. J. Med. Genet. 86:219–226, 1999. © 1999 Wiley-Liss, Inc.

Diagnosis of diabetes in youth is increasing in the U.S. (1,2). It is not known how much of this change is due to an increase in diabetes and how much is due to improved case detection, especially for type 2 diabetes. Some researchers have hypothesized that part of the explanation for the increase in diabetes diagnosis in youth is increased screening, resulting in a higher percentage of cases being identified. The objective of this study was to assess whether the change in diabetes could be explained by changes in case identification by examining trends from 2002 to 2010 in self-reported case presentation of diabetes. Briefly, there were 9,054 youth aged