Clemens Kamrath1, Sascha R Tittel2, Thomas M Kapellen3, Thekla von dem Berge4, Bettina Heidtmann5, Katrin Nagl6, Ulrike Menzel7, Simone Pötzsch8, Katja Konrad9, Reinhard W Holl2. 1. Division of Pediatric Endocrinology and Diabetology, Center of Child and Adolescent Medicine, Justus Liebig University, Giessen, Germany. Electronic address: clemens.kamrath@paediat.med.uni-giessen.de. 2. ZIBMT, Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany; German Center for Diabetes Research, Munich, Germany. 3. Department of Women and Child Health, Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany. 4. Diabetes Center for Children and Adolescents, Children's Hospital Auf der Bult, Hannover, Germany. 5. Department of Pediatric Endocrinology and Diabetology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany. 6. Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria. 7. Department of Paediatric Endocrinology, AKK Altonaer Kinderkrankenhaus, Hamburg, Germany. 8. Department for Children and Adolescent Medicine, Helios Vogtland Clinic Plauen, Plauen, Germany. 9. Department of Pediatric and Adolescent Medicine, Elisabeth-Hospital Essen, Essen, Germany.
Abstract
BACKGROUND: Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes. METHODS: We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]). The DPV registry comprises 501 diabetes centres from Germany, Austria, Switzerland, and Luxembourg. We included patients diagnosed with type 1 diabetes between 2004 and 2014, who were aged between 6 months and 15 years at the time of diagnosis, who had started insulin pump therapy either within the first 6 months (ie, the early treatment group) or in the second to third year (ie, the delayed treatment group) after diabetes diagnosis, and who were treated with insulin pump therapy for at least 1 year. The outcome parameters included the glycated haemoglobin (HbA1c) values, the cardiovascular risk profile, and rates of acute complications and diabetes-associated hospital admissions (ie, hospitalisation) during the most recent documented treatment year with insulin pump therapy. Statistical models were adjusted for age at diabetes diagnosis, year of diagnosis, sex, immigrant background, use of continuous glucose monitoring, centre size, and the German Index of Socioeconomic Deprivation 2012 terciles. FINDINGS: Our study sample comprised 8332 patients from 311 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The early treatment group consisted of 4004 (48·1%) of 8332 patients, and the delayed treatment group consisted of 4328 (51·9%). The median diabetes duration during follow-up was 6·7 years (IQR 5·1-8·7 in the early group; 5·0-8·7 in the delayed group) in both groups. Patients with early initiation of insulin pump therapy compared with those with delayed initiation of insulin pump therapy had significantly lower estimated mean HbA1c values (7·9% [95% CI 7·8-7·9] and 62·6 mmol/mol [95% CI 62·1-63·2] vs 8·0% [8·0-8·1] and 64·1 mmol/mol [63·6-64·6]; p=0·0006), and lower rates of hypoglycaemic coma (incidence risk ratio 0·44 [95% CI 0·24-0·79]; p=0·0064) and hospitalisation (0·86 [95% CI 0·78-0·94]; p=0·0016). A better cardiovascular risk profile was observed in patients with early initiation of insulin pump therapy than in those with delayed initiation: an estimated mean systolic blood pressure of 117·6 mm Hg (95% CI 117·2-117·9) versus 118·5 mm Hg (118·2-118·9), p=0·0007; and HDL cholesterol of 62·8 mg/dL (95% CI 62·2-63·5) versus 60·6 mg/dL (60·0-61·2), p<0·0001; however, diastolic blood pressure; concentrations of LDL cholesterol, non-HDL cholesterol, and triglycerides; and estimated body-mass index standard deviation scores during follow-up did not differ significantly between both groups. INTERPRETATION: Our findings provide evidence for improved clinical outcomes associated with the early initiation of insulin pump therapy in children with type 1 diabetes. FUNDING: The German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung), German Robert Koch Institute, German Diabetes Association, and Diabetes Agenda 2010.
BACKGROUND: Although continuous subcutaneous insulin infusion therapy (ie, insulin pump therapy) is associated with improved metabolic control compared with multiple daily insulin injections in children with type 1 diabetes, it is unclear when it is best to start it after diagnosis. In this study, we aimed to compare the outcomes between early and delayed start of insulin pump therapy in young patients with type 1 diabetes. METHODS: We based the current study on data from the multicentre, prospective diabetes follow-up registry (ie, Diabetes-Patienten-Verlaufsdokumentation [DPV]). The DPV registry comprises 501 diabetes centres from Germany, Austria, Switzerland, and Luxembourg. We included patients diagnosed with type 1 diabetes between 2004 and 2014, who were aged between 6 months and 15 years at the time of diagnosis, who had started insulin pump therapy either within the first 6 months (ie, the early treatment group) or in the second to third year (ie, the delayed treatment group) after diabetes diagnosis, and who were treated with insulin pump therapy for at least 1 year. The outcome parameters included the glycated haemoglobin (HbA1c) values, the cardiovascular risk profile, and rates of acute complications and diabetes-associated hospital admissions (ie, hospitalisation) during the most recent documented treatment year with insulin pump therapy. Statistical models were adjusted for age at diabetes diagnosis, year of diagnosis, sex, immigrant background, use of continuous glucose monitoring, centre size, and the German Index of Socioeconomic Deprivation 2012 terciles. FINDINGS: Our study sample comprised 8332 patients from 311 diabetes centres in Germany, Austria, Switzerland, and Luxembourg. The early treatment group consisted of 4004 (48·1%) of 8332 patients, and the delayed treatment group consisted of 4328 (51·9%). The median diabetes duration during follow-up was 6·7 years (IQR 5·1-8·7 in the early group; 5·0-8·7 in the delayed group) in both groups. Patients with early initiation of insulin pump therapy compared with those with delayed initiation of insulin pump therapy had significantly lower estimated mean HbA1c values (7·9% [95% CI 7·8-7·9] and 62·6 mmol/mol [95% CI 62·1-63·2] vs 8·0% [8·0-8·1] and 64·1 mmol/mol [63·6-64·6]; p=0·0006), and lower rates of hypoglycaemic coma (incidence risk ratio 0·44 [95% CI 0·24-0·79]; p=0·0064) and hospitalisation (0·86 [95% CI 0·78-0·94]; p=0·0016). A better cardiovascular risk profile was observed in patients with early initiation of insulin pump therapy than in those with delayed initiation: an estimated mean systolic blood pressure of 117·6 mm Hg (95% CI 117·2-117·9) versus 118·5 mm Hg (118·2-118·9), p=0·0007; and HDL cholesterol of 62·8 mg/dL (95% CI 62·2-63·5) versus 60·6 mg/dL (60·0-61·2), p<0·0001; however, diastolic blood pressure; concentrations of LDL cholesterol, non-HDL cholesterol, and triglycerides; and estimated body-mass index standard deviation scores during follow-up did not differ significantly between both groups. INTERPRETATION: Our findings provide evidence for improved clinical outcomes associated with the early initiation of insulin pump therapy in children with type 1 diabetes. FUNDING: The German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung), German Robert Koch Institute, German Diabetes Association, and Diabetes Agenda 2010.