Integration of Routine Parameters of Glycemic Variability in a Simple Screening Method for Partial Remission in Children with Type 1 Diabetes

Abstract

Although different criteria were used to define partial remission in type 1 diabetes, the IDAA1C formula has prevailed as it correlates with stimulated C-peptide levels. Our retrospective study evaluated clinical variables associated with the occurrence of IDAA1C-defined partial remission in a series of 239 pediatric patients. Diabetic ketoacidosis and age at diagnosis, but no other clinical feature, influenced the occurrence of remission. We then evaluated whether parameters of glycemic variability used in clinical routine may reliably define partial remission, as these would alleviate confounding factors related to insulin treatment. Using multiple linear regression, we observed that HbA_1C levels and percentage of normoglycemia were efficient and sufficient to predict partial remission. These parameters were entered into a formula, called glycemic target-adjusted HbA_1C (GTAA_1C), that corresponded to HbA_1C(%) - (3 × % of normoglycemic values_{(70-180 mg/dL)}). With a threshold of 4.5, this alternative formula predicted partial remission with a sensitivity and a specificity of 72.3% and 92%, respectively, and yielded strong correlation with IDAA1C levels and BETA-2 score, which is a correlate of β-cell function after islet transplantation. We propose GTAA_1C, based on routine and objective markers of glycemic variability, as a valid alternative for definition of partial remission in type 1 diabetes.

Figure 1

Evolution of HbA_1C and C-peptide values at diagnosis and during follow-up. Graphs represent mean HbA_1C levels (in %) in PR (a) and no PR (b) groups, mean C-peptide values (in pmol/mL) in PR (c) and no PR (d) groups at diagnosis, and one and two years postdiagnosis. Mean HbA_1C levels were at 10.6 ± 2.6% in PR and 11.2 ± 3% in no PR group (P = 0.33). Those levels were, respectively, at 6.9% (6.2–7.5) and 7.7% (6.9–8.6) at one year (P < 0.001) and at 7.5% (6.7–8.1) and 7.7% (6.9–8.5) at two years (P = 0.023), in patients with PR and without PR. For the remitter group, median C-peptide levels were, respectively, at 0.21 pmol/mL (0.11–0.35), 0.22 pmol/mL (0.1–0.41), and 0.11 pmol/mL (0–0.28) at diagnosis, one year and two years postdiagnosis. For the nonremitter group, median C-peptide levels were, respectively, at 0.15 pmol/mL (0.1–0.23), 0.05 pmol/mL (0–0.17), and 0 pmol/mL (0–0.09) at diagnosis, one year and two years postdiagnosis. ^∗Compared HbA_1C levels at diagnosis among age subgroups (i.e., 9.7 ± 1.9%, 10.4 ± 2.2%, and 11.4 ± 3.1% for the <5 years, 5–10 years, and ≥10 years, resp.; P = 0.0017).

Figure 2

Correlation of BETA-2 score with IDAA1C and GTAA_1C definitions of PR. Graphs show correlation between BETA-2 score and IDAA1C-based ((a) P < 0.001) or GTAA_1C-based ((b) P < 0.001) criteria for PR in a subgroup of 90 patients from our cohort. These correlations (BETA-2 and IDAA1C versus BETA-2 and GTAA_1C) were not statistically different in multivariate analysis. Related r ² were noted in the corresponding graphs.