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.

Aims/hypothesis Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. Methods Age/sex-standardised incidence rates for the 0-to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. Results Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0-to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5-to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10-to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. Conclusions/interpretation Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals. An 18-year-old woman presented with primary amenorrhea and an absence of müllerian-derived structures, unilateral renal agenesis, and clinical signs of androgen excess--a phenotype resembling the Mayer-Rokitansky-Küster-Hauser syndrome and remarkably similar to that of female Wnt4-knockout mice. A genetic evaluation revealed a loss-of-function mutation in the WNT4 gene. WNT4 appears to be important in the development and maintenance of the female phenotype in women, by means of the regulation of müllerian-duct formation and control of ovarian steroidogenesis.