Three-Variate Longitudinal Patterns of Metabolic Control, Body Mass Index, and Insulin Dose during Puberty in a Type 1 Diabetes Cohort: A Group-Based Multitrajectory Analysis.

To analyze the interrelationship of metabolic control, age- and sex-adjusted body mass index, and daily insulin dose and to identify heterogeneous multivariate developmental curves from childhood to young adulthood in a large cohort of children with type 1 diabetes (T1D) STUDY DESIGN: Data were extracted from the diabetes follow-up registry DPV. Longitudinal data from 9239 participants with T1D age 8-18 years with diabetes duration ≥2 years and ≥5 years of follow-up were analyzed. We applied group-based multitrajectory modeling to identify latent groups of subjects following similar developmental curves across outcomes (hemoglobin A1c [HbA1c], age/sex-standardized body mass index [BMI-SDS], daily insulin dose per kg). Group number was based on Bayes information criterion and group size (≥5%). The group-based multitrajectory approach revealed 5 heterogeneous 3-variate trajectories during puberty. Individuals with stable good metabolic control, high-normal increasing BMI-SDS, and rising insulin dose patterns were classified as group 1 (33%). Group 2 (20%) comprised youths with intermediate-increasing HbA1c, low BMI-SDS, and steeply increasing insulin dose trajectories. Group 3 (11%) followed intermediate-rising HbA1c and high-normal increasing BMI-SDS developmental curves, while insulin dose increased steeply. In group 4 (14%), both high-increasing HbA1c and insulin dose trajectories were observed, while BMI-SDS was stable-normal. Group 5 (22%) included subjects with intermediate-rising HbA1c patterns, high-increasing BMI-SDS, and increasing insulin dose patterns. This study identified 5 distinct 3-variate curves of HbA1c, BMI-SDS, and insulin dose during puberty among youths with T1D. This approach demonstrates a considerable heterogeneity highlighting the importance of personalized medical care.

Schwandt A ，Kuss O ，Dunstheimer D ，Karges B ，Kapellen T ，Meissner T ，Witsch M ，Flury M ，Straubinger S ，Holl RW ，Diabetes-Patienten-Verlaufsdokumentation (DPV) Initiative ... -  《-》

Three-variate trajectories of metabolic control, body mass index, and insulin dose: Heterogeneous response to initiation of pump therapy in youth with type 1 diabetes.

Continuous subcutaneous insulin infusion (CSII) in youths with type 1 diabetes (T1D) is often associated with lower HbA1c, lower total daily insulin dose (TDD), and lower body mass index (BMI) compared with multiple daily injections (MDI). Individual responses to CSII are diverse. The aim was to identify unique three-variate patterns of HbA1c, BMI standard deviation score (SDS), and TDD after switching to CSII. Five thousand one hundred and thirty-three youths (≤20 years; 48% boys; median age at pump start 12.5 years) with T1D duration ≥3 years at CSII initiation were selected from the multicenter DPV registry. We applied group-based multitrajectory modeling to identify groups of individuals following similar trajectories. Measurements were aggregated quarterly during a 3-year follow-up period. Trajectory variables were changes of HbA1c, BMI-SDS, and TDD from baseline (delta = quarterly aggregated values at each time point [i] minus the respective baseline value). Four groups of diverging Delta-HbA1c, Delta-BMI-SDS, and Delta-TDD patterns were identified. All showed improvements in HbA1c during the first 3 months. Group 1 (12%) was characterized by modest HbA1c increase thereafter, TDD reduction, and stable BMI-SDS. In Group 2 (39%), increasing HbA1c, decreasing BMI-SDS, and stable TDD were found. By contrast, sustainably improved HbA1c, increasing BMI-SDS, and stable TDD were observed in Group 3 (32%). Group 4 (17%) was characterized by increasing levels for HbA1c, BMI-SDS, and TDD. Between-group differences in baseline HbA1c, BMI-SDS, TDD as well as in sex ratio, age at diabetes onset and at pump start were observed. Definite trajectories of glycemic control, BMI, and TDD over 3 years after CSII initiation were identified in youths with T1D allowing a more personalized treatment recommendation.

Tauschmann M ，Schwandt A ，Prinz N ，Becker M ，Biester T ，Hess M ，Holder M ，Karges B ，Näke A ，Kuss O ，von Sengbusch S ，Holl RW ，DPV Initiative ... -  《-》

Proportion of Basal to Total Insulin Dose Is Associated with Metabolic Control, Body Mass Index, and Treatment Modality in Children with Type 1 Diabetes-A Cross-Sectional Study with Data from the International SWEET Registry.

To investigate in a large population the proportion of daily basal insulin dose (BD) to daily total insulin dose (TD) (BD/TD) and its association with glycated hemoglobin A1c (HbA1c), body mass index (BMI)- SDS, and treatment modality in children with type 1 diabetes. Cross-sectional study in subjects with type 1 diabetes, age ≤18 years, and ≥2 years of diabetes duration, registered in the international multicenter Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference registry in March 2018. Variables included region, sex, age, diabetes duration, treatment modality (multiple daily injections [MDI] or continuous subcutaneous insulin infusion [CSII]), self-monitoring blood glucose, HbA1c, BD/TD, and BMI-SDS. BMI was converted to BMI-SDS using World Health Organization charts as reference. Hierarchic linear regression models were applied with adjustment for age, sex, and diabetes duration. A total of 19 687 children with type 1 diabetes (49% female, 49% CSII users) with median age 14.8 (11.5; 17.2) years and diabetes duration 6.0 (3.9; 9.0) years were included. HbA1c was 63 (55; 74) mmol/mol (7.9 [7.2; 8.9]%), and BMI-SDS 0.55 (-0.13; 1.21). Unadjusted, a lower BD/TD was associated with lower HbA1c, male sex, younger age, shorter diabetes duration, lower BMI-SDS, higher numbers of self-monitoring blood glucose and CSII (all P < .01). After adjustment for confounders, lower BD/TD was associated with lower HbA1c (P < .01) and lower BMI-SDS (P < .01) in children on CSII, but not on MDI. Lower BD/TD is positively associated with lower HbA1c and lower BMI-SDS in children with type 1 diabetes on CSII. It remains to be investigated in a prospective study whether reducing BD/TD insulin will improve metabolic control and normalize body weight in children with type 1 diabetes.

Rasmussen VF ，Vestergaard ET ，Schwandt A ，Beltrand J ，Rami-Merhar B ，O'Riordan SMP ，Jarosz-Chobot P ，Castro-Correia C ，Gevers EF ，Birkebæk NH ... -  《-》

Trajectories of Body Mass Index from Childhood to Young Adulthood among Patients with Type 1 Diabetes-A Longitudinal Group-Based Modeling Approach Based on the DPV Registry.

To identify distinct longitudinal patterns of body mass index (BMI) z score in type 1 diabetes from childhood to young adulthood and secondly to determine sex differences as well as associated clinical covariates. A total of 5665 patients with type 1 diabetes (51% male) with follow-up from 8 to 20 years of age from the multicenter diabetes prospective registry DPV were studied (baseline diabetes duration ≥1 years, BMI z score aggregated per year of life). Latent class growth modeling (SAS: PROC TRAJ) was applied to analyze BMI z score over time. Six distinct BMI z score trajectories were identified (group 1: 7% of patients, group 2: 22%, group 3: 20%, group 4: 16%, group 5: 25%, and group 6: 10%). Group 1, 2, 5, and 6 had an almost stable BMI z score, either in the low, near-normal, high stable, or chronic overweight range. Group 3 (60% girls) increased their BMI during puberty, whereas group 4 (65% boys) had a BMI decrease. Similar patterns were observed for girls only, whereas boys followed nearly stable trajectories without fluctuation over time. Between the near-normal and the other groups, significant differences (P < .05) in sex ratio, migration background, mental health, height z score, glycated hemoglobin A1c, diabetes treatment, dyslipidemia, hypertension, and smoking were observed. In youth with type 1 diabetes, a great heterogeneity of BMI z score trajectories exists that highlight the importance of personalized sex-specific intervention programs for subjects at risk for unfavorable BMI development.

Prinz N ，Schwandt A ，Becker M ，Denzer C ，Flury M ，Fritsch M ，Galler A ，Lemmer A ，Papsch M ，Reinehr T ，Rosenbauer J ，Holl RW ... -  《-》

Longitudinal Trajectories of Metabolic Control From Childhood to Young Adulthood in Type 1 Diabetes From a Large German/Austrian Registry: A Group-Based Modeling Approach.

Worsening of glycemic control in type 1 diabetes during puberty is a common observation. However, HbA1c remains stable or even improves for some youths. The aim is to identify distinct patterns of glycemic control in type 1 diabetes from childhood to young adulthood. A total of 6,433 patients with type 1 diabetes were selected from the prospective, multicenter diabetes patient registry Diabetes-Patienten-Verlaufsdokumentation (DPV) (follow-up from age 8 to 19 years, baseline diabetes duration ≥2 years, HbA1c aggregated per year of life). We used latent class growth modeling as the trajectory approach to determine distinct subgroups following a similar trajectory for HbA1c over time. Five distinct longitudinal trajectories of HbA1c were determined, comprising group 1 = 40%, group 2 = 27%, group 3 = 15%, group 4 = 13%, and group 5 = 5% of patients. Groups 1-3 indicated stable glycemic control at different HbA1c levels. At baseline, similar HbA1c was observed in group 1 and group 4, but HbA1c deteriorated in group 4 from age 8 to 19 years. Similar patterns were present in group 3 and group 5. We observed differences in self-monitoring of blood glucose, insulin therapy, daily insulin dose, physical activity, BMI SD score, body-height SD score, and migration background across all HbA1c trajectories (all P ≤ 0.001). No sex differences were present. Comparing groups with similar initial HbA1c but different patterns, groups with higher HbA1c increase were characterized by lower frequency of self-monitoring of blood glucose and physical activity and reduced height (all P < 0.01). Using a trajectory approach, we determined five distinct longitudinal patterns of glycemic control from childhood to early adulthood. Diabetes self-care, treatment differences, and demographics were related to different HbA1c courses.

Schwandt A ，Hermann JM ，Rosenbauer J ，Boettcher C ，Dunstheimer D ，Grulich-Henn J ，Kuss O ，Rami-Merhar B ，Vogel C ，Holl RW ，DPV Initiative ... -  《-》