In the participating centers with a multidisciplinary team, only one third of the patients had an HbA1c level of < 8%.

OBJECTIVETo find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment.RESEARCH DESIGN AND METHODSA total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function.RESULTSBy multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient −0.21, P < 0.001) and insulin dose (−0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose–adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg−1 · 24 h−1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months.CONCLUSIONSA new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions.

OBJECTIVE -It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families.RESEARCH DESIGN AND METHODS -The study involved 2,101 adolescents, aged 10 -18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA 1c was analyzed centrally (normal range 4.4 -6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires.RESULTS -Mean HbA 1c was 8.7% (range 4.8 -17.4). Lower HbA 1c was associated with lower impact (P Ͻ 0.0001), fewer worries (P Ͻ 0.05), greater satisfaction (P Ͻ 0.0001), and better health perception (P Ͻ 0.0001) for adolescents. Girls showed increased worries (P Ͻ 0.01), less satisfaction, and poorer health perception (P Ͻ 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P Ͻ 0.0001).Patients from ethnic minorities had poorer scores for impact (P Ͻ 0.0001), worries (P Ͻ 0.05), and health perception (P Ͻ 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores.CONCLUSIONS -In a multiple regression model, lower HbA 1c was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

OBJECTIVE -To reevaluate the persistence and stability of previously observed differences between pediatric diabetes centers and to investigate the influence of demography, language communication problems, and changes in insulin regimens on metabolic outcome, hypoglycemia, and ketoacidosis. RESULTS -Mean A1C was 8.2 Ϯ 1.4%, with substantial variation between centers (mean A1C range 7.4 -9.2%; P Ͻ 0.001). There were no significant differences between centers in rates of severe hypoglycemia or diabetic ketoacidosis. Language difficulties had a significant negative impact on metabolic outcome (A1C 8.5 Ϯ 2.0% vs. 8.2 Ϯ 1.4% for those with language difficulties vs. those without, respectively; P Ͻ 0.05). After adjustement for significant confounders of age, sex, duration of diabetes, insulin regimen, insulin dose, BMI, and language difficulties, the center differences persisted, and the effect size for center was not reduced. Relative center ranking since 1998 has remained stable, with no significant change in A1C. RESEARCH DESIGN AND METHODSCONCLUSIONS -Despite many changes in diabetes management, major differences in metabolic outcome between 21 international pediatric diabetes centers persist. Different application between centers in the implementation of insulin treatment appears to be of more importance and needs further exploration.

This study aims to identify key miRNAs in circulation, which predict ongoing beta-cell destruction and regeneration in children with newly diagnosed Type 1 Diabetes (T1D). We compared expression level of sera miRNAs from new onset T1D children and age-matched healthy controls and related the miRNAs expression levels to beta-cell function and glycaemic control. Global miRNA sequencing analyses were performed on sera pools from two T1D cohorts (n = 275 and 129, resp.) and one control group (n = 151). We identified twelve upregulated human miRNAs in T1D patients (miR-152, miR-30a-5p, miR-181a, miR-24, miR-148a, miR-210, miR-27a, miR-29a, miR-26a, miR-27b, miR-25, miR-200a); several of these miRNAs were linked to apoptosis and beta-cell networks. Furthermore, we identified miR-25 as negatively associated with residual beta-cell function (est.: −0.12, P = 0.0037), and positively associated with glycaemic control (HbA1c) (est.: 0.11, P = 0.0035) 3 months after onset. In conclusion this study demonstrates that miR-25 might be a “tissue-specific” miRNA for glycaemic control 3 months after diagnosis in new onset T1D children and therefore supports the role of circulating miRNAs as predictive biomarkers for tissue physiopathology and potential intervention targets.