New definition for the partial remission period in children and adolescents with type 1 diabetes

Abstract

OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual beta-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A 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 beta-cell function. RESULTS By 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 x insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C < or =9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C < or =9 had a significantly higher agreement (P < 0.001) with residual beta-cell function than use of a definition of A1C < or =7.5%. Between 6 and 12 months after diagnosis, for IDAA1C < or =9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C < or =7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose < or =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. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual beta-cell function and has better stability compared with the conventional definitions.

Figure 1

A: The thresholds for partial remission based on IDAA1C ≤9 (solid green line) and A1C ≤7.5% and insulin doses ≤0.5 units · kg⁻¹ · 24 h⁻¹ (rectangular dashed box). Each diagonal red line corresponds to one IDAA1C value. The numbers in boxes are the predicted values for stimulated C-peptide concentrations for a 10-year-old boy at the relevant IDAA1C value and, as illustrated, other threshold values for IDAA1C correspond to different predicted C-peptide values. The + signs give the distribution of 257 patients with type 1 diabetes after 6 months' duration. B: Age at onset influences the rate of partial remission as assessed by IDAA1C in children with type 1 diabetes. The proportion of partial remission is lowest in the youngest age-group (0–;4.9 years). Because of lower insulin sensitivity, the proportions of partial remission in the old age-group (≥10 years) and the school-age children (5–;9.9 years) seem to be similar despite higher residual β-cell function. C: The proportion of children in partial remission according to the different definitions. From 3 to 12 months, the curves for IDAA1C (curve 1), C-peptide (curve 2), and insulin dose (curve 4) show close agreement. Using the new definition, partial remission occurred in 61% at 3 months, in 44% at 6 months, and in 18% after 12 months. D: Agreement between definitions of those in partial remission, A1C ≤7.5% (left panel, dashed vertical line), IDAA1C ≤9 (right panel, dashed vertical line), and stimulated C-peptide >300 pmol/l (dashed horizontal line) at 12 months. The arrows point to the areas showing that A1C ≤7.5% disagrees significantly more than IDAA1C ≤9 with C-peptide >300 pmol/l, probably because the children receive more exogenous insulin, which is accounted for in the insulin dose–;adjusted model. E: The relationship of IDAA1C ≤9 (dashed vertical line) and stimulated C-peptide >300 pmol/l (dashed horizontal line) at 6 and 12 months. Individual observations are shown by age-groups. The regression lines for 6 (——) and 12 (– – –) months show the linear correlation of IDAA1C and C-peptide over a continuum of stimulated C-peptide values.

Figure 1

A: The thresholds for partial remission based on IDAA1C ≤9 (solid green line) and A1C ≤7.5% and insulin doses ≤0.5 units · kg⁻¹ · 24 h⁻¹ (rectangular dashed box). Each diagonal red line corresponds to one IDAA1C value. The numbers in boxes are the predicted values for stimulated C-peptide concentrations for a 10-year-old boy at the relevant IDAA1C value and, as illustrated, other threshold values for IDAA1C correspond to different predicted C-peptide values. The + signs give the distribution of 257 patients with type 1 diabetes after 6 months' duration. B: Age at onset influences the rate of partial remission as assessed by IDAA1C in children with type 1 diabetes. The proportion of partial remission is lowest in the youngest age-group (0–;4.9 years). Because of lower insulin sensitivity, the proportions of partial remission in the old age-group (≥10 years) and the school-age children (5–;9.9 years) seem to be similar despite higher residual β-cell function. C: The proportion of children in partial remission according to the different definitions. From 3 to 12 months, the curves for IDAA1C (curve 1), C-peptide (curve 2), and insulin dose (curve 4) show close agreement. Using the new definition, partial remission occurred in 61% at 3 months, in 44% at 6 months, and in 18% after 12 months. D: Agreement between definitions of those in partial remission, A1C ≤7.5% (left panel, dashed vertical line), IDAA1C ≤9 (right panel, dashed vertical line), and stimulated C-peptide >300 pmol/l (dashed horizontal line) at 12 months. The arrows point to the areas showing that A1C ≤7.5% disagrees significantly more than IDAA1C ≤9 with C-peptide >300 pmol/l, probably because the children receive more exogenous insulin, which is accounted for in the insulin dose–;adjusted model. E: The relationship of IDAA1C ≤9 (dashed vertical line) and stimulated C-peptide >300 pmol/l (dashed horizontal line) at 6 and 12 months. Individual observations are shown by age-groups. The regression lines for 6 (——) and 12 (– – –) months show the linear correlation of IDAA1C and C-peptide over a continuum of stimulated C-peptide values.