Partial Remission Definition: Validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish Children with New-Onset Type 1 Diabetes

Andersen, Marie Louise C Max; Hougaard, Philip; Pörksen, Sven; Nielsen, L.B.; Fredheim, Siri; Svensson, Jannet; Thomsen, Jane Frølund; Vikre-Jørgensen, Jennifer; Hertel, Thomas; Petersen, J.; Hansen, Lars; Mortensen, Henrik B.

doi:10.1111/pedi.12208

Cited by 57 publications

(68 citation statements)

References 23 publications

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“…Missing data were taken into consideration in the statistical analysis using the linear mixed model. DKA was defined by a pH of <7.35, blood glucose of >200 mg/dL, and serum bicarbonate of <15 ng/mL [5]; while PCR was defined by insulin-dose adjusted hemoglobin A1c (IDAA1C), which is a new two-dimensional definition that correlates insulin dose and measured HbA1c with residual β-cell function[23]. IDAA1C has the best correlation with stimulated C-peptide of >300 pmol/L when compared to previous definitions [24].…”

Section: Methodsmentioning

confidence: 99%

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A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes

et al. 2017

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Importance>50% of patients with new-onset type 1 diabetes (T1D) do not enter partial clinical remission (PCR); early identification of these patients may improve initial glycemic control and reduce long-term complications.AimTo determine whether routinely obtainable clinical parameters predict non-remission in children and adolescents with new-onset T1D.Subjects and methodsData on remission were collected for the first 36 months of disease in 204 subjects of ages 2–14 years with new-onset type 1 diabetes. There were 86 remitters (age 9.1±3.0y; male 57%), and 118 non-remitters (age 7.0±3.1y; male 40.7%). PCR was defined as insulin-dose adjusted hemoglobin A1c of ≤9.ResultsNon-remission occurred in 57.8% of subjects. Univariable analysis showed that the risk for non-remission was increased 9-fold in patients with 4 diabetes-associated auto-antibodies (OR = 9.90, p = 0.010); 5-fold in patients <5 years old (odds ratio = 5.38, p = 0.032), 3-fold in those with bicarbonate of <15 mg/dL at diagnosis (OR = 3.71, p = 0.008). Combined estimates of risk potential for HC03 and the number of autoantibodies by multivariable analysis, adjusted for BMI standard deviation score, showed HC03 <15 mg/dL with a clinically significant 10-fold risk (OR = 10.1, p = 0.074); and the number of autoantibodies with a 2-fold risk for non-remission (OR = 1.9, p = 0.105). Male sex and older age were associated with decreased risk for non-remission. A receiver-operating characteristic curve model depicting sensitivity by 1-specificity for non-remission as predicted by bicarbonate <15 mg/dL, age <5y, female sex, and >3 diabetes-associated autoantibodies had an area under the curve of 0.73.ConclusionsMore than 50% of children and adolescents with new-onset T1D do not undergo partial clinical remission and are thus at an increased risk for long-term complications of diabetes mellitus. A predictive model comprising of bicarbonate <15 mg/dL, age <5y, female sex, and >3 diabetes-associated autoantibodies has 73% power for correctly predicting non-remission in children and adolescents with new-onset T1D. Early identification of these non-remitters may guide the institution of targeted therapy to limit dysglycemia and reduce the prevalence of long-term deleterious complications.

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Section: Methodsmentioning

confidence: 99%

“…The formula for IDAA1C is HbA1c (%) + [4 X total daily dose of insulin (units/kg/24h)]. PCR is defined as IDAA1C of ≤9[23]. Vitamin D deficiency was defined as 25(OH)D of <50 nmol/L[25].…”

Section: Methodsmentioning

confidence: 99%

A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes

et al. 2017

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“…We have demonstrated that metabolic control has improved7 and severe hypoglycemic events have decreased 8,9. Furthermore, diabetic ketoacidosis at disease onset is associated with worse metabolic control and higher daily insulin requirement for equal HbA1c values (ie, higher insulin dose-adjusted [IDA]A1c)10 several years after diagnosis 11…”

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confidence: 99%

Danish Registry of Childhood and Adolescent Diabetes

Svensson¹,

Cerqueira²,

Kjærsgaard³

et al. 2016

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AimThe aims of the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) are to monitor and improve the quality of care for children and adolescents with diabetes in Denmark and to follow the incidence and prevalence of diabetes.Study populationThe study population consists of all children diagnosed with diabetes before the age of 15 years since 1996. Since 2015, every child followed up at a pediatric center (<18 years of age) will be included.Main variablesThe variables in the registry are the quality indicators, demographic variables, associated conditions, diabetes classification, family history of diabetes, growth parameters, self-care, and treatment variables. The quality indicators are selected based on international consensus of measures of good clinical practice. The indicators are metabolic control as assessed by HbA1c, blood pressure, albuminuria, retinopathy, neuropathy, number of severe hypoglycemic events, and hospitalization with ketoacidosis.Descriptive dataThe number of children diagnosed with diabetes is increasing with ∼3% per year mainly for type 1 diabetes (ie, 296 new patients <15 years of age were diagnosed in 2014). The disease management has changed dramatically with more children treated intensively with multiple daily injections, insulin pumps, and increased number of self-monitored blood glucose values per day. These initiatives have resulted in a significant improvement in HbA1c over the years and a decrease in the number of children experiencing severe hypoglycemia, diabetic nephropathy, and retinopathy.ConclusionThe systematic collection of data in DanDiabKids documents improved quality of care over the last 12 years, despite a substantial increase in the number of patients cared for by pediatric departments in Denmark, fulfilling the purpose of the registry.

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“…HbA 1c measurement HbA 1c was analysed centrally using a high-pressure liquid chromatographic method (normal range 4.3-5.8% [23-40 mmol/mol]); Tosoh Bioscience, South San Francisco, CA, USA) as described previously [19].…”

Section: Methodsmentioning

confidence: 99%

The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes

et al. 2014

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Aims/hypothesis The influence of glucagon on glycaemic control in type 1 diabetes is debated. We investigated the relationship between postprandial glucagon levels and HbA 1c during a period up to 60 months after diagnosis of childhood type 1 diabetes. Methods The Danish remission phase cohort comprised 129 children (66 boys) with type 1 diabetes whose mean (SD) age at onset was 10.0 (3.9) years. Liquid mixed-meal tests were performed prospectively at 1, 3, 6 and 12 months and a subset of 40 patients completed follow-up at 60 months. Postprandial (90 min) plasma levels of glucagon, glucose (PG), C-peptide, total glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and HbA 1c were analysed. Multivariate regression (repeated measurements with all five visits included) was applied and results expressed as relative change (95% CI). Results Postprandial glucagon levels increased 160% from 1 to 60 months after diagnosis (p<0.0001). A doubling in postprandial PG corresponded to a 21% increase in postprandial glucagon levels (p=0.0079), whereas a doubling in total GLP-1 levels corresponded to a 33% increase in glucagon levels (p<0.0001). Postprandial glucagon associated negatively with postprandial C-peptide (p=0.017). A doubling in postprandial glucagon corresponded to a 3% relative increase in HbA 1c levels (p=0.0045). Conclusions/interpretation Postprandial glucagon levels were associated with deterioration of glycaemic control and declining beta cell function in the first 5 years after diagnosis of type 1 diabetes. The positive association of glucagon with total GLP-1 and PG suggests that physiological regulation of alpha cell secretion in type 1 diabetes is seriously disturbed.

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Partial Remission Definition: Validation based on the insulin dose-adjusted HbA1c (IDAA1C) in 129 Danish Children with New-Onset Type 1 Diabetes

Abstract: The diagnostic and prognostic power of the IDAA1c measure is kept but due to the higher Boost stimulation in the Danish cohort, the specificity of the formula is lower with the chosen limits for SCP (300 pmol/L) and IDAA1c ≤9, respectively.

Cited by 57 publications

References 23 publications

A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes

A predictive model for lack of partial clinical remission in new-onset pediatric type 1 diabetes

Danish Registry of Childhood and Adolescent Diabetes

The influence of glucagon on postprandial hyperglycaemia in children 5 years after onset of type 1 diabetes

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