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 HbA1C levels and percentage of normoglycemia were efficient and sufficient to predict partial remission. These parameters were entered into a formula, called glycemic target-adjusted HbA1C (GTAA1C), that corresponded to HbA1C(%) − (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 GTAA1C, based on routine and objective markers of glycemic variability, as a valid alternative for definition of partial remission in type 1 diabetes.
Highlights
In type 1 diabetes (T1D), there is a longstanding autoimmune attack of pancreatic β-cells [1] recognizable by seroconversion of specific antibodies [2] that develops on genetic susceptibility grounds [3] and leads to symptomatic insulinopenia when β-cell mass is drastically reduced [4]
The Hvidoere study group on childhood diabetes proposed the identification of remitters using the insulin dose-adjusted hemoglobin A1C (IDAA1C) formula [13], which strongly correlated with residual β-cell function estimated by stimulated C-peptide levels during mixedmeal tolerance test, when being lower or equal to 9
In the 239 newly diagnosed patients with T1D, remission occurred in 71.1% (n = 170, all being partial) with similar rates of remission in girls (46.9%) and boys (53.1%), girls were significantly older than boys at diagnosis (Table 1)
Summary
In type 1 diabetes (T1D), there is a longstanding autoimmune attack of pancreatic β-cells [1] recognizable by seroconversion of specific antibodies [2] that develops on genetic susceptibility grounds [3] and leads to symptomatic insulinopenia when β-cell mass is drastically reduced [4]. Alleviation of hyperglycemia by administration of exogenous insulin is accompanied in about 60% of patients by a rapid reduction of daily insulin requirements (DIR) for maintenance of normal glycemia and HbA1C levels [5]. This defines a transitory state of partial remission (PR) (or “honeymoon period”) with residual β-cell function, improved insulin sensitivity [6], and reduced risk of severe hypoglycemia (SH) [7, 8]. The IDAA1C threshold (i.e., ≤9) was successfully used elsewhere to identify remitters [10, 16, 17] and level out other parameters, such as daily insulin dose per kilogram of body weight [12]
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