Youth with type 2 diabetes have a high rate of treatment failure after discontinuation of insulin: A Pediatric Diabetes Consortium study.

Insulin is commonly used to reverse gluco-toxicity in youth with newly diagnosed type 2 diabetes (T2D), but many are subsequently weaned off insulin. We analyzed Pediatric Diabetes Consortium (PDC) data to determine how long glycemic control is maintained after termination of initial insulin treatment. Youth with T2D who had previously been on insulin but were on either an intensive lifestyle intervention alone or metformin alone upon enrollment in the PDC T2D Registry were studied (N = 183). The primary outcome was time to treatment failure, defined by need to restart insulin or metformin or another diabetes medication. Data were analyzed using logistic regression to assess risk factors for treatment failure. Of the 183 participants studied (mean age 15 years, diabetes duration 1.7 years), 54% experienced treatment failure (median follow-up time 1.7 years). In the subgroup on metformin monotherapy (N = 140), 45% subsequently required restart of insulin. Moreover, of participants in the subgroup treated with an intensive lifestyle intervention alone (N = 43), 81% restarted insulin or were treated with metformin or other diabetes medication. In both groups, median time to treatment failure was 1.2 years. Higher HbA1c at enrollment was significantly associated with treatment failure (p < 0.001). Youth with T2D who are initially treated with insulin have a high rate of treatment failure when switched to intensive lifestyle alone or metformin alone. Our data highlight the severe and progressive nature of youth onset T2D, hence patients should be monitored closely for deteriorating glycemic control after being weaned off insulin.

Psychosocial outcomes in young adolescents with type 1 diabetes participating in shared medical appointments.

For youth with type 1 diabetes (T1D), the early adolescent period is associated with worsening diabetes management and high rates of negative psychosocial issues, including depressive symptoms and family conflict. Alternative clinical models may help improve both diabetes and psychosocial outcomes. Our study aims to investigate whether Team Clinic, a shared medical appointment model developed specifically for adolescents with T1D, will improve psychosocial outcomes for middle school-aged youth. Youth with T1D, 11-13 years of age, and their caregivers, participated in a randomized controlled trial comparing Team Clinic to traditional clinic visits (control group). Diabetes characteristics were obtained at every visit. Participants and caregivers completed depression screening and family conflict questionnaires at baseline and end of study. Changes in mean scores on clinical and psychosocial outcomes from baseline to end of study were compared between groups using linear mixed-effects models. Eighty-six youth (51% female; 74% White; 10% Hispanic) completed at least one visit during the 12-month study period. At the end of the study, control group participants reported increases in Emotional Problems compared to Team Clinic participants, including higher levels of Negative Mood/Physical Symptoms (p = 0.02). Team Clinic participants reported reduced family conflict surrounding diabetes at study end, compared to control group participants (p = 0.03). Caregivers did not report change in depressive symptoms or family conflict during the study. Hemoglobin A1C levels did not change over time in either group. Participation in Team Clinic was associated with improved psychosocial outcomes in middle school-aged participants with T1D.

Receipt of recommended complications and comorbidities screening in youth and young adults with type 1 diabetes: Associations with metabolic status and satisfaction with care.

OBJECTIVES: This study sought to: (a) assess the prevalence of diabetes complications and comorbidities screening as recommended by the American Diabetes Association (ADA) for youth and young adults (YYAs) with type 1 diabetes (T1D), (b) examine the association of previously measured metabolic status related to diabetes complications with receipt of recommended clinical screening, and (c) examine the association of satisfaction with diabetes care with receipt of recommended clinical screening. METHODS: The study included 2172 SEARCH for Diabetes in Youth participants with T1D (>10 years old, diabetes duration >5 years). Mean participant age was 17.7 ± 4.3 years with a diabetes duration of 8.1 ± 1.9 years. Linear and multinomial regression models were used to evaluate associations. RESULTS: Sixty percent of participants reported having three or more hemoglobin A1c (HbA1c) measurements in the past year. In terms of diabetes complications screening, 93% reported having blood pressure measured, 81% having an eye examination, 71% having lipid levels checked, 64% having a foot exam, and 63% completing albuminuria screening in accordance with ADA recommendations. Youth known to have worse glycemic control in the past had higher odds of not meeting HbA1c screening criteria (OR 1.11, 95% CI = 1.05, 1.17); however, after adjusting for race/ethnicity, this was no longer statistically significant. Greater satisfaction with diabetes care was associated with increased odds of meeting screening criteria for most of the ADA-recommended measures. CONCLUSIONS: Efforts should be made to improve diabetes complications screening efforts for YYAs with T1D, particularly for those at higher risk for diabetes complications.

Novel, culturally sensitive, shared medical appointment model for Hispanic pediatric type 1 diabetes patients.

BACKGROUND/OBJECTIVE: Latino patients with type 1 diabetes (T1D) face cultural and language barriers leading to poor outcomes. Shared medical appointments (SMAs) are recognized as effective models of care. Our aim is to develop a culturally sensitive, cost effective SMA program for Latino T1D. SUBJECTS: Spanish speaking Latinos 1 to 20 years with T1D (n = 88) and their families. METHODS: Routine care alternating with SMAs that included group education was provided. Teens, ages >11 received the SMA separate from parents. Younger children were seen together. Hemoglobin A1c (HbA1c), behavioral questionnaires, and use of diabetes technology were measured at baseline and every 3 to 6 months. RESULTS: 57.7% of children and 77.27% of teens completed the 2 years of the Program. There was a significant association between age and change in HbA1c from baseline to year 1 (P = .001) and baseline to year 2 (P = <.0001). For participants <12 years, there was a significant improvement in HbA1c from baseline to year 1 (P = .0146) and from year 1 to year 2 (P = .0069). Participants ≥12 years, had an increase in HbA1c from year 1 to year 2 (P = .0082). Technology use increased significantly from baseline to year 2 for participants <12 years of age (19%-60%, P = .0455) and for participants who were ≥12 years of age (10%-23%, P = .0027). Participants reported a 98% satisfaction rate. CONCLUSIONS: The culturally sensitive SMA proved to be an appreciated, feasible, and effective alternative to care for Latinos with T1D.

The rate of hyperglycemia and ketosis with insulin degludec-based treatment compared with insulin detemir in pediatric patients with type 1 diabetes: An analysis of data from two randomized trials.

BACKGROUND: Historically, data on the rate of hyperglycemia and ketosis have not been collected in clinical trials. However, it is clinically important to assess the rate of these events in children with type 1 diabetes (T1D). This question was addressed in two pediatric trials using insulin degludec (degludec). OBJECTIVE: To assess the rate of hyperglycemia and ketosis in two-phase 3b trials investigating degludec (Study 1) and degludec with insulin aspart (IDegAsp [Study 2]) vs insulin detemir (IDet). SUBJECTS: Patients (aged 1-17 years inclusive) with T1D treated with insulin for ≥3 months. METHODS: Study 1: patients were randomized to degludec once daily (OD) or IDet OD/twice daily (BID) for 26 weeks, followed by a 26-week extension phase. Study 2: patients were randomized to IDegAsp OD or IDet OD/BID for 16 weeks. Bolus mealtime IAsp was included in both studies. In Study 1, hyperglycemia was recorded if plasma glucose (PG) was >11.1 mmol/L, with ketone measurement required with significant hyperglycemia (>14.0 mmol/L). In Study 2, hyperglycemia was recorded with PG >14.0 mmol/L where the subject looked/felt ill, with ketone measurement also required in these hyperglycemic patients. In this post hoc analysis, the hyperglycemia threshold was 14.0 mmol/L for uniformity. RESULTS: Despite similar rates of hyperglycemia with degludec/IDegAsp compared with IDet, the rates of ketosis were lower with degludec/IDegAsp. CONCLUSIONS: These trials, the first to systematically collect data on ketosis in pediatric patients with T1D, demonstrate the potential of degludec/IDegAsp to reduce rates of metabolic decompensation, compared with IDet.

Healthcare and associated costs related to type 2 diabetes in youth and adolescence: the TODAY clinical trial experience.

The economic issues related to medical treatments in youth with type 2 diabetes (T2D) are rarely reported and thus not fully understood. The Treatment Options for type 2 Diabetes in Adolescents and Youth clinical trial of youth recently diagnosed with T2D collected healthcare and related cost information from the largest cohort studied to date. Costs related to medical treatments and expenses faced by caregivers were identified over a 2-year period from 496 participants. Data were collected by surveys and diaries to document frequency of use of diabetes care (excluding study laboratory tests), non-diabetes care services and treatments, caregiver time, and expenses related to exercise and dietary activities recommended for patients. Economic costs were derived by applying national cost values to the reported utilization frequency data. Annual medical costs in the first year varied by the treatment group, averaging $1798 in those assigned to metformin alone (M), $2971 to combination drug therapy with metformin + rosiglitazone (M + R), and $2092 to metformin + an intensive lifestyle and behavior change program (M + L). Differences were primarily due to costs related to combination drug therapy. Adult caregiver support costs were higher for participants in the lifestyle program, which was delivered in weekly sessions in the first 6 months. Expenses for purchases to enhance diet and exercise change did not vary by treatment assignment. In year 2, medication costs increased in M and M + L due to the initiation of insulin in subjects who failed to maintain glycemic control on the assigned treatment. Data are reported for use by researchers and those providing healthcare to this vulnerable patient population.

Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: A randomized trial.

BACKGROUND: Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. OBJECTIVE: To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). SUBJECTS: Children and adolescents (aged 1 to <18 years) with T1D. METHODS: A 16-week, phase 3b, treat-to-target, parallel-group, open-label, non-inferiority trial was conducted at 63 sites in 14 countries from October 2013 to November 2014. Patients were randomized 1:1 (age stratified: 1-<6 years; 6-<12 years; 12-<18 years) to IDegAsp once daily (OD) plus insulin aspart (IAsp) for remaining meals (IDegAsp + IAsp), or IDet OD or twice daily plus mealtime IAsp (IDet + IAsp). The primary end-point was HbA1c change from baseline at week 16. RESULTS: A total of 362 participants were randomized to IDegAsp + IAsp (n = 182) or IDet + IAsp (n = 180). HbA1c decreased from baseline to week 16 by 0.3% in both groups (estimated treatment difference: -0.04%-points [-0.23; 0.15]95%CI (-0.45 mmol/mol [-2.51; 1.60]95%CI ), confirming non-inferiority. There were no significant differences between treatment groups in fasting or self-measured plasma glucose. Confirmed hypoglycemia rates did not significantly differ between groups. There was a significant reduction in basal and total insulin dose with IDegAsp + IAsp vs IDet + IAsp (post hoc analysis). Mean number of injections/day was 3.6 and 4.9 with IDegAsp + IAsp and IDet + IAsp, respectively (post hoc analysis). A non-significant higher rate of severe hypoglycemia was observed with IDegAsp + IAsp vs IDet + IAsp. The most frequent adverse events in both groups were hypoglycemia, headache, and nasopharyngitis. CONCLUSIONS: IDegAsp + IAsp was non-inferior to IDet + IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.

Adolescent type 2 diabetes: Comparing the Pediatric Diabetes Consortium and Germany/Austria/Luxemburg Pediatric Diabetes Prospective registries.

OBJECTIVE: To examine and compare the clinical characteristics and treatment of youth with type 2 diabetes (T2D) in two registries: one in Europe and one in the United States. METHODS: Youth with onset of T2D at 10 to 18 years of age with current age <20 years and an office visit after diabetes duration >1 year were identified in the European (Prospective Diabetes Follow-up, DPV) and the United States (Pediatric Diabetes Consortium, PDC) databases. Demographic, physical and clinical characteristics and treatment at diagnosis as well as physical characteristics, treatment, laboratory data, and diabetes adverse events at most recent visit were analyzed from both registries. RESULTS: At diagnosis, the majority were female and obese; 70% of DPV vs 34% of PDC youth were diagnosed by targeted diabetes testing. PDC youth were younger, 12 vs 13 years (P < 0.001), had a greater body mass index-SDS, 3.07 vs 2.74 (P < 0.001), a higher hemoglobin A1c (HbA1c), 9.9% vs 7.1% (P < 0.001), were more likely to present in DKA, 7.5% vs 1.3% (P < 0.001) and more likely to be treated with insulin, 62% vs 32% (P < 0.001); insulin treatment difference was not significant when adjusted for HbA1c. At follow-up, DPV youth had shorter diabetes duration, 2.1 vs 3.2 years (P < 0.001), lower HbA1c, 6.5% vs 7.8% (P < 0.001), were less likely to be treated with insulin, 36% vs 56%, (P < 0.001), and were more likely to have dyslipidemia and hypertension than PDC youth. PDC youth had a higher rate of microalbuminuria. CONCLUSIONS: Both DPV and PDC youth have multiple risks for diabetes complications. Understanding reasons for persistently higher HbA1c in PDC youth requires further study.

Eligibility for clinical trials is limited for youth with type 2 diabetes: Insights from the Pediatric Diabetes Consortium T2D Clinic Registry.

BACKGROUND/OBJECTIVE: Restrictive eligibility criteria have hampered enrollment into trials for new drugs for youth with type 2 diabetes (T2D). We utilized Pediatric Diabetes Consortium (PDC) T2D Registry enrollment data to estimate the percentage of patients who would be excluded from current T2D trials based on out-of-range HbA1c levels. We also examined whether well-controlled patients could be included because baseline HbA1c would rise during a 6 to 12-month study if assigned to control group. METHODS: Clinical characteristics and HbA1c levels were collected from 956 T2D patients aged 10 to <18 years upon Registry enrollment. HbA1c levels were also analyzed in 6-month intervals during the first 30 months of T2D duration. RESULTS: There was an approximately 2:1 ratio of females to males; the majority were obese and from economically disadvantaged minority families. On enrollment in the Registry, 53% of patients would be excluded from current trials because HbA1c levels were either <6.5% (<48 mmol/mol) (37%) or >10.5% (>91 mmol/mol) (16%). Furthermore, in patients with HbA1c levels <6.5% (<48 mmol/mol) and T2D duration between 6 and 30 months, mean HbA1c levels increased by 0.6% (6 mmol/mol) and 0.9% (10 mmol/mol) over the subsequent 6 and 12 months, respectively. CONCLUSIONS: Eligibility criteria for current clinical trials still exclude a large proportion of pediatric T2D patients because of HbA1c levels. Including patients with HbA1c <6.5% (<48 mmol/mol) would enhance recruitment and allow comparisons of the investigational treatment with placebo-assigned subjects in whom HbA1c levels would on average increase during the 6 to 12 months of the trial.

Barriers to participation in industry-sponsored clinical trials in pediatric type 2 diabetes.

BACKGROUND: The rapid emergence of type 2 diabetes (T2D) in the pediatric population has left pediatric endocrinologists with limited artillery in terms of management. While multiple medications are available for adults, Food and Drug Administration (FDA)-approved medications in children are limited to only metformin and insulin. Additional treatment options require randomized controlled trials, yet heretofore several barriers at the participant and institutional level have impeded these studies from proceeding in children and adolescents. Identification of the most challenging obstacles that pediatric endocrinologists experience in participating in industry-sponsored T2D trials may facilitate development of feasible platforms for future studies. MATERIALS AND METHODS: We conducted an anonymous online survey consisting of 31 questions that assessed potential barriers to industry-sponsored clinical trials in pediatric patients with T2D. The survey was sent to members of the Pediatric Endocrine Society (PES), and members conducted the survey between October and November of 2014. As part of the survey, respondents rated the significance of several possible barriers to participation in industry-sponsored T2D studies. RESULTS: We received a total of 207 responses from members of PES. Baseline demographics showed that 50% of represented institutions care for 50 or fewer T2D patients age 18 years and younger; 70% of institutions diagnose 20 or fewer new T2D cases per year; and 3 racial groups predominated: African American, Hispanic, and Caucasian. A total of 70% of responders have a research infrastructure to participate in clinical trials, but only half have dedicated research nurses. Protocol restrictions on participant recruitment due to current glycemic control or medication use as well as frequent visit schedules were reported to be major obstacles. In addition, the financial support provided to centers to carry out the studies is insufficient. CONCLUSIONS: Efforts must be made to ease the burden of research participation on both pediatric T2D patients as well as pediatric endocrinologists.

A survey of youth with new onset type 1 diabetes: Opportunities to reduce diabetic ketoacidosis.

OBJECTIVE: Pediatric patients in Colorado with new onset type 1 diabetes (T1D) presenting with diabetic ketoacidosis (DKA) increased from 29.9% to 46.2% from 1998 to 2012. The purpose of this study was to compare differences between patients with newly diagnosed T1D who presented in DKA with those who did not across three domains: sociodemographic factors, access to medical care, and medical provider factors, aiming to identify potential targets for intervention. METHODS: Sixty-one patients <17 years of age with T1D duration <6 months completed the questionnaire. Groups were compared using Fisher's exact test or the Kruskal-Wallis test. RESULTS: Parents of 28% of patients researched their child's symptoms on the Internet prior to diagnosis. At the first healthcare visit for symptoms of T1D, 23% were not diagnosed. There were no significant differences between groups (DKA vs non-DKA) in demographics, first healthcare setting for T1D symptoms, provider type at first visit or at diagnosis, insurance status, or specific barriers to care. DKA patients had a longer interval between previous well visit to diagnosis (median 172 vs 263 days, P = 0.01). Non-DKA patients were more likely to have blood glucose measured at P = 0.02, and had fewer symptoms prior to (P = 0.01) the first visit for diabetes symptoms. Parents of non-DKA patients were more likely to be familiar with symptoms of diabetes (P < 0.001) and to suspect diabetes (P = 0.01). CONCLUSION: Targets for campaigns to prevent DKA include increasing provider glucose and ketone testing, increasing public knowledge about diabetes, and understanding how socio-demographic factors may delay T1D diagnosis.

Clinical outcomes in youth beyond the first year of type 1 diabetes: Results of the Pediatric Diabetes Consortium (PDC) type 1 diabetes new onset (NeOn) study.

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<7.5% (58 mmol/mol). The percentage of participants in partial remission estimated by insulin dose adjusted HbA1c [HbA1c % + (4×insulin dose unit/kg/24 h)] ≤9 sharply declined from 23% at 12 months to 7% at 36 months. The percentage of participants developing diabetic ketoacidosis (DKA) was 1% in the first year after diagnosis, increasing to 6% in years 2 and 3. CONCLUSIONS: These results demonstrate the gradual decline in glycemic control due to waning residual endogenous insulin secretion with increasing duration of T1D in children and adolescents. These data indicate the need to translate recent advances in automated insulin delivery, new insulin analogs, and adjunctive pharmacologic agents into novel treatment strategies to maintain optimal glycemic control even early in the course of T1D.

A cross-sectional view of the current state of treatment of youth with type 2 diabetes in the USA: enrollment data from the Pediatric Diabetes Consortium Type 2 Diabetes Registry.

OBJECTIVE: To describe the clinical characteristics, treatment approaches, clinical outcomes, and co-morbidities of youth with type 2 diabetes (T2D) enrolled in the Pediatric Diabetes Consortium (PDC) T2D Registry. METHODS: PDC enrolled 598 youth <21 yr of age with T2D from February 2012 to July 2015 at eight centers. Data were collected from medical records and interviews with participants and/or parents and included glycated hemoglobin (HbA1c), diabetes treatments, prevalence of diabetes comorbidities (hypertension (HTN), dyslipidemia (DL), microalbuminuria (MA), and nonalcoholic fatty liver disease (NAFLD). RESULTS: Insulin use was observed in 45% of those with T2D duration <1 yr, 44% for 1-<2 yr, 55% for 2-3 yr and 60% for ≥4 yr. Median HbA1c was 6.7% (50 mmol/mol), 8.5% (69 mmol/mol), 9.6% (81 mmol/mol), and 9.7% (82 mmol/mol) in those with disease duration <1, 1-<2, 2-3 and ≥4 yr, respectively. Only 33 and 11% of those with HTN and DL respectively, were being treated. MA and NAFLD were observed in 5-6% of the participants. Prevalence of HTN was associated with higher BMI (p < 0.001), DL with higher HbA1c (p < 0.001), and MA with longer diabetes duration (p = 0.001). CONCLUSIONS: Frequency of insulin therapy in youth with T2D was associated with increased disease duration and those with longer duration rarely achieve target HbA1c level. This highlights the aggressive course of T2D in youth and adolescents. Additionally, co-morbidities are not being adequately treated. Follow up data from the PDC will provide additional important information about the natural history of T2D and patterns of gaps in treatment.

Team Clinic: An Innovative Group Care Model for Youth with Type 1 Diabetes-Engaging Patients and Meeting Educational Needs.

The purpose of this pilot was to implement an innovative group care model, "Team Clinic", for adolescents with type 1 diabetes and assess patient and provider perspectives. Ninety-one intervention patients and 87 controls were enrolled. Ninety-six percent of intervention adolescents endorsed increased support and perceived connecting with peers as important. The medical providers and staff also provided positive feedback stating Team Clinic allowed more creativity in education and higher quality of care. Team Clinic may be a promising model to engage adolescents and incorporate education and support into clinic visits in a format valued by patients and providers.

Reduced Bone Mineral Density Is Associated with Celiac Disease Autoimmunity in Children with Type 1 Diabetes.

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 (ß = -1.25 ± 0.85, P = .0016) and tTGA (ß = -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.

Characteristics of maturity onset diabetes of the young in a large diabetes center.

Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes caused by a mutation in a single gene, often not requiring insulin. The aim of this study was to estimate the frequency and clinical characteristics of MODY at the Barbara Davis Center. A total of 97 subjects with diabetes onset before age 25, a random C-peptide ≥0.1 ng/mL, and negative for all diabetes autoantibodies (GADA, IA-2, ZnT8, and IAA) were enrolled, after excluding 21 subjects with secondary diabetes or refusal to participate. Genetic testing for MODY 1-5 was performed through Athena Diagnostics, and all variants of unknown significance were further analyzed at Exeter, UK. A total of 22 subjects [20 (21%) when excluding two siblings] were found to have a mutation in hepatocyte nuclear factor 4A (n = 4), glucokinase (n = 8), or hepatocyte nuclear factor 1A (n = 10). Of these 22 subjects, 13 had mutations known to be pathogenic and 9 (41%) had novel mutations, predicted to be pathogenic. Only 1 of the 22 subjects had been given the appropriate MODY diagnosis prior to testing. Compared with MODY-negative subjects, the MODY-positive subjects had lower hemoglobin A1c level and no diabetic ketoacidosis at onset; however, these characteristics are not specific for MODY. In summary, this study found a high frequency of MODY mutations with the majority of subjects clinically misdiagnosed. Clinicians should have a high index of suspicion for MODY in youth with antibody-negative diabetes.

C-peptide levels in pediatric type 2 diabetes in the Pediatric Diabetes Consortium T2D Clinic Registry.

OBJECTIVE: To describe C-peptide levels in a large cohort of children with type 2 diabetes T2D and examine associations with demographic and clinical factors. METHODS: 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). RESULTS: 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 (p < 0.001), lower body mass index (p < 0.001), hemoglobin A1c (HbA1c) ≥9% (p < 0.001), 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. CONCLUSIONS: 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.

Presentation of youth with type 2 diabetes in the Pediatric Diabetes Consortium.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Vitamin D status in youth with type 1 and type 2 diabetes enrolled in the Pediatric Diabetes Consortium (PDC) is not worse than in youth without diabetes.

OBJECTIVE: To describe vitamin D levels and prevalence of vitamin D sufficiency, insufficiency and deficiency in a large, ethnically/racially diverse population of youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) in comparison to national data and examine the associations between clinical/demographic factors and vitamin D levels. METHODS: 25-hydroxy vitamin D (25OHD) levels were measured in 215 youth with T1D and 326 youth with T2D enrolled in the Pediatric Diabetes Consortium (PDC). These levels were compared with those of youth of the same age without diabetes from the 2005-2006 NHANES Survey. RESULTS: Vitamin D deficiency (<21 ng/mL) was present in 36% of PDC participants, and insufficiency (21-29 ng/mL) was present in an additional 34%. About 36% of age-matched youth in the NHANES Survey were vitamin D deficient and an additional 41% were insufficient. Deficiency or insufficiency varied by race/ethnicity, being highest in African-Americans (86%), intermediate in Hispanics (77%), and lowest in non-Hispanic whites (47%). Lower 25OHD levels were observed in African-American and Hispanic youth, during fall and winter, and at sites in the northern United States (all p-values < 0.001). Youth with T2D had significantly lower 25OHD levels than youth with T1D (p < 0.001), but this difference was largely eliminated after adjusting for race/ethnicity and socio-economic status. CONCLUSIONS: Vitamin D deficiency/insufficiency is present in a substantial proportion of youth with diabetes, particularly minorities, but the prevalence appears similar to that in youth without diabetes. Further studies are needed to examine whether youth with diabetes would benefit from vitamin D supplementation.

Body mass index changes in youth in the first year after type 1 diabetes diagnosis.

OBJECTIVES: To describe changes in weight and body mass index (BMI) during the first year following diagnosis of type 1 diabetes (T1D) and associations with demographic and clinical characteristics. STUDY DESIGN: The Pediatric Diabetes Consortium includes 7 US centers with prospective longitudinal data from initial T1D diagnosis. This analysis includes 530 youth with diabetes duration of ≥1 year and measures of BMI at 3 and 12 months after diagnosis. BMI trajectory of participants and relationships between the change in BMI z-score from baseline (3 months) to 12 months with demographic characteristics, hemoglobin A1c at baseline, and insulin delivery mode at baseline were evaluated. RESULTS: As a group, BMI z-scores increased sharply from diagnosis for 1-3 months but remained relatively stable from +0.51 at 3 months to +0.48 at 12 months. Children aged 2-<5 years experienced a significant positive change in BMI z-score between 3 and 12 months, and there was a similar trend among girls that did not reach statistical significance. No significant differences were found for race, socioeconomic status, or insulin delivery mode. CONCLUSIONS: These data suggest that increased BMI during the first year of treatment of most youth with T1D reflects regain of weight lost before diagnosis. There is, however, a propensity toward additional weight gain in younger children and girls.