Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial.

BACKGROUND: The incidence of type 2 diabetes in young people is increasing, but treatments remain limited. We aimed to assess the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycaemic control in young people with type 2 diabetes. METHODS: In this double-blind, placebo-controlled trial done in 108 centres in 15 countries, participants with type 2 diabetes (aged 10-17 years; HbA1c 6·5-10·5% [48-91 mmol/mol]) who had been previously treated with metformin or insulin were randomly assigned (1:1:1) to oral empagliflozin 10 mg, oral linagliptin 5 mg, or placebo. Participants in the empagliflozin group who did not have HbA1c below 7·0% (<53 mmol/mol) by week 12 underwent a second double-blinded randomisation (1:1) at week 14, either remaining on 10 mg or increasing to 25 mg. Participants in the placebo group were randomly reassigned (1:1:1) in a double-blinded manner at week 26 to linagliptin 5 mg or one of the empagliflozin doses (10 mg or 25 mg). Investigators were masked throughout the trial and received assignments of blinded medication kits through interactive response technology for all participants at the initial randomisation and for the re-randomisations at weeks 14 and 26. The primary outcome was change from baseline in HbA1c at 26 weeks. For empagliflozin, results were based on a pooled analysis for all participants on empagliflozin. Safety was assessed until week 52. This trial is registered with ClinicalTrials.gov, NCT03429543. FINDINGS: Between April 26, 2018, and May 26, 2022, of 262 screened participants, 158 (60%) were randomly assigned to treatment (53 [34%] to placebo, 52 [33%] to empagliflozin 10 mg, and 53 [34%] to linagliptin). For the primary outcome, the adjusted mean HbA1c change from baseline at week 26 was -0·84% [-9·2 mmol/mol] in the empagliflozin pooled group versus placebo (95% CI -1·50 to -0·19 [-16·4 to -2·1]; p=0·012); the corresponding change from baseline for linagliptin versus placebo was -0·34% [-3·8 mmol/mol; 95% CI -0·99 to 0·30 [-10·8 to 3·3]; p=0·29). Adverse events occurred in 34 (64%) participants in the placebo group, 40 (77%) in the empagliflozin pooled group, and 37 (71%) in the linagliptin group, up to week 26. Of these, severe adverse events were reported in two (4%) participants in the placebo group, one (2%) in the empagliflozin pooled group, and one (2%) in the linagliptin group. Hypoglycaemia was the most frequently reported adverse event with higher rates for those on active drug treatment compared with placebo. No severe hypoglycaemia cases were reported. INTERPRETATION: Empagliflozin provided clinically relevant placebo-corrected reductions in HbA1c, whereas linagliptin did not, and might offer a new treatment option for young people with type 2 diabetes. FUNDING: The Boehringer Ingelheim and Eli Lilly and Company Alliance.

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.

Racial and Ethnic Disparities in Comorbidities in Youth With Type 2 Diabetes in the Pediatric Diabetes Consortium (PDC).

BACKGROUND: Type 2 diabetes in the U.S. is more prevalent in youth of minority racial-ethnic background, but disparities in health outcomes have not been examined in this population. RESEARCH DESIGN AND METHODS: We examined racial-ethnic differences in the initial presentation and subsequent comorbidities in 1,217 youth with type 2 diabetes (63% girls) enrolled in the Pediatric Diabetes Consortium (PDC) Registry from February 2012 to June 2018. Demographic and clinical data were collected from medical records and participant self-report. RESULTS: Overall, the mean age at presentation was 13.4 ± 2.4 years, and BMI was 35.0 ± 9.4 kg/m2. HbA1c was higher and C-peptide was lower in non-Hispanic Black (NHB) and Hispanic (H) youth compared with non-Hispanic White (NHW) youth. NHB were three times as likely to present in diabetic ketoacidosis (19%) versus NHW (6.3%) and H (7.5%), and NHB and H both had a worse HbA1c trajectory compared with NHW peers. Microalbuminuria was documented in 11%, hypertension in 34%, and dyslipidemia in 42% of Registry participants, with no significant difference among racial-ethnic groups. Nonalcoholic fatty liver disease (NAFLD) was diagnosed in 9% and 11% of H and NHW, respectively, versus 2% in NHB. CONCLUSIONS: NHB and H youth with type 2 diabetes presented with worse metabolic control and had persistently worse HbA1c trajectories compared with NHW. Comorbidities exist in a large percentage of these youth independent of race-ethnicity, except for NAFLD being less prevalent in NHB. Greater efforts are needed to mitigate racial-ethnic disparities at diagnosis and in the management of youth with type 2 diabetes.

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.

Home Telemedicine (CoYoT1 Clinic): A Novel Approach to Improve Psychosocial Outcomes in Young Adults With Diabetes.

PURPOSE: To assess the impact of a home telemedicine clinic model (CoYoT1 Clinic) on psychosocial and behavioral outcomes designed for young adults (YAs) with type 1 diabetes (T1D). METHODS: YAs self-selected to participate in the CoYoT1 Clinic or serve as a usual care control. CoYoT1 Clinic visits consisted of an individual appointment with a provider and a group appointment with other YAs with T1D using home telemedicine. Psychosocial and behavioral functioning was assessed by 4 measures: Diabetes Distress Scale, Self-Efficacy for Diabetes Scale, Self-Management of Type 1 Diabetes in Adolescence Scale, and Center for Epidemiologic Studies Depression Scale. RESULTS: Forty-two patients participated in the CoYoT1 Clinic and 39 patients served as controls. CoYoT1 participants reported lower levels of distress (P = .03), increased diabetes self-efficacy (P = .01), and improved ability to communicate with others about diabetes (P = .04) over the study period compared to controls. YA males in the control group reported increases in depressive symptoms (P = .03) during the study period, but CoYoT1 participants showed no changes. CONCLUSION: Group home telemedicine for YAs with T1D positively affects diabetes distress, self-efficacy, and diabetes-specific communication. These positive findings have the potential to also affect the YAs' long-term diabetes outcomes. Further investigation of the model is needed.

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.

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.

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.

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.

CoYoT1 Clinic: Home Telemedicine Increases Young Adult Engagement in Diabetes Care.

BACKGROUND: Young adults with type 1 diabetes (T1D) experience poor glycemic control, disengagement in care, and are often lost to the medical system well into their adult years. Diabetes providers need a new approach to working with the population. The goal of this study was to determine whether an innovative shared telemedicine appointment care model (CoYoT1 Clinic [pronounced as "coyote"; Colorado Young Adults with T1D]) for young adults with T1D improves care engagement, satisfaction, and adherence to American Diabetes Association (ADA) guidelines regarding appointment frequency. SUBJECTS AND METHODS: CoYoT1 Clinic was designed to meet the diabetes care needs of young adults (18-25 years of age) with T1D through home telemedicine. Visits occurred every 3 months over the 1-year study (three times by home telemedicine and one time in-person). Outcomes were compared to patients receiving treatment as usual (control). RESULTS: Compared with controls, CoYoT1 patients attended significantly more clinic visits (P < 0.0001) and increased their number of clinic visits from the year before the intervention. Seventy-four percent of CoYoT1 patients were seen four times over the 12-month study period, meeting ADA guidelines, but none in the control group met the ADA recommendation. CoYoT1 patients used diabetes technologies more frequently and reported greater satisfaction with care compared with controls. CONCLUSIONS: Delivering diabetes care by home telemedicine increases young adults' adherence to ADA guidelines and usage of diabetes technologies, and improves retention in care when compared to controls. Home telemedicine may keep young adults engaged in their diabetes care during this challenging transition period.

Racial/Ethnic Minority Youth With Recent-Onset Type 1 Diabetes Have Poor Prognostic Factors.

OBJECTIVE: To compare races/ethnicities for characteristics, at type 1 diabetes diagnosis and during the first 3 years postdiagnosis, known to influence long-term health outcomes. RESEARCH DESIGN AND METHODS: We analyzed 927 Pediatric Diabetes Consortium (PDC) participants <19 years old (631 non-Hispanic white [NHW], 216 Hispanic, and 80 African American [AA]) diagnosed with type 1 diabetes and followed for a median of 3.0 years (interquartile range 2.2-3.6). Demographic and clinical data were collected from medical records and patient/parent interviews. Partial remission period or "honeymoon" was defined as insulin dose-adjusted hemoglobin A1c (IDAA1c) ≤9.0%. We used logistic, linear, and multinomial regression models, as well as repeated-measures logistic and linear regression models. Models were adjusted for known confounders. RESULTS: AA subjects, compared with NHW, at diagnosis, were in a higher age- and sex-adjusted BMI percentile (BMI%), had more advanced pubertal development, and had higher frequency of presentation in diabetic ketoacidosis, largely explained by socioeconomic factors. During the first 3 years, AA subjects were more likely to have hypertension and severe hypoglycemia events; had trajectories with higher hemoglobin A1c, BMI%, insulin doses, and IDAA1c; and were less likely to enter the partial remission period. Hispanics, compared with NHWs, had higher BMI% at diagnosis and over the three subsequent years. During the 3 years postdiagnosis, Hispanics had higher prevalence of dyslipidemia and maintained trajectories of higher insulin doses and IDAA1c. CONCLUSIONS: Youth of minority race/ethnicity have increased markers of poor prognosis of type 1 diabetes at diagnosis and 3 years postdiagnosis, possibly contributing to higher risk of long-term diabetes complications compared with NHWs.

Initial Presentation of Type 2 Diabetes in Adolescents Predicts Durability of Successful Treatment with Metformin Monotherapy: Insights from the Pediatric Diabetes Consortium T2D Registry.

BACKGROUND/AIMS: Many adolescents with type 2 diabetes (T2D) have rapid deterioration of glycemic control on metformin monotherapy within 2 years of diagnosis. METHODS: Enrollment data from the Pediatric Diabetes Consortium T2D Registry were used to categorize 276 youth with a T2D duration ≥2 years into two groups: (1) participants with HbA1c <7.5% on metformin monotherapy (group 1, n = 75) and (2) participants treated with insulin ± metformin (group 2, n = 201). The characteristics of the groups were compared. RESULTS: At enrollment, groups 1 and 2 did not differ in age (16.2 vs. 16.8 years) or BMI percentile (99 vs. 98%); group 2 had higher HbA1c (9.9% [85 mmol/mol] vs. 5.9% [41 mmol/mol], p < 0.001). Lower HbA1c and metformin monotherapy at diagnosis were associated with a greater likelihood of adequate control with metformin alone (p < 0.001). In multivariable analysis, HbA1c at diagnosis (p = 0.001) and diabetes duration (p = 0.009) were associated with adequate control on metformin. The HbA1c trajectory after diagnosis was worse in group 2. CONCLUSION: Durable metabolic control of T2D with metformin monotherapy is most likely in youth presenting with lower HbA1c and with shorter diabetes duration, independent of age, race-ethnicity, and BMI. Elevated HbA1c levels in those on insulin therapy highlight the importance of early diagnosis and a better understanding of glycemic control barriers.

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.

Predictors of Loss to Follow-Up among Children with Type 2 Diabetes.

BACKGROUND/AIMS: Youth with type 2 diabetes (T2D) have poor compliance with medical care. This study aimed to determine which demographic and clinical factors differ between youth with T2D who receive care in a pediatric diabetes center versus youth lost to follow-up for >18 months. METHODS: Data were analyzed from 496 subjects in the Pe-diatric Diabetes Consortium registry. Enrollment variables were selected a priori and analyzed with univariable and multivariable logistic regression models. RESULTS: After a median of 1.3 years from enrollment, 55% of patients were lost to follow-up. The final model included age, race/ethnicity, parent education, and estimated distance to study site. The odds ratio (99% confidence interval) of loss to follow-up was 2.87 (1.34, 6.16) for those aged 15 to <18 years versus those aged 10 to <13 years and 6.57 (2.67, 16.15) for those aged ≥18 years versus those aged 10 to <13 years. Among patients living more than 50 miles from the clinic, the odds ra tio of loss to follow-up was 3.11 (1.14, 8.49) versus those living within 5 miles of the site. CONCLUSION: Older adolescents with T2D are more likely to be lost to follow-up, but other socioeconomic factors were not significant predictors of clinic follow-up.

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.

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.