Factors contributing to partial remission in type 1 diabetes: analysis based on the insulin dose-adjusted HbA1c in 3657 children and adolescents from Germany and Austria

Abstract

This research on a large cohort provides insight into epidemiologic characteristics of PREM in T1D defined by IDAA1c. As IDAA1c does not discriminate between insulin sensitivity and secretion, available data cannot resolve whether the sex-difference in PREM reflects innate higher insulin resistance in girls, or better beta-cell recovery in boys. Further research is needed to clarify the usefulness and performance of IDAA1c in clinical practice.

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

“…It may be defined as an insulin requirement of <0.5 units/kg of body weight per day and HbA1c <7%, but a new formula combining both values has recently been proposed: “insulin dose-adjusted HbA1c” (IDDAA1c) defined as HbA1c (%) + 4 × (insulin dose in units/kg/24 h), which suggests that a value of <9 would indicate partial remission. This definition correlates well with a stimulated C-peptide >300 pmol/l and has been validated in large cohort studies [14-16]. We firmly believe that for several reasons IDDAA1c criteria should be the standard for defining the T1D remission phase: (1) it takes into account insulin doses and metabolic control; (2) it displays a good correlation with C-peptide levels; (3) it has been validated in large cohorts of T1D children and adolescents [16]; (4) it has been recommended by the International Society for Pediatric and Adolescent Diabetes (ISPAD) [17].…”

“…This definition correlates well with a stimulated C-peptide >300 pmol/l and has been validated in large cohort studies [14-16]. We firmly believe that for several reasons IDDAA1c criteria should be the standard for defining the T1D remission phase: (1) it takes into account insulin doses and metabolic control; (2) it displays a good correlation with C-peptide levels; (3) it has been validated in large cohorts of T1D children and adolescents [16]; (4) it has been recommended by the International Society for Pediatric and Adolescent Diabetes (ISPAD) [17]. According to this new definition, the T1D remission phase can be predicted to occur in 61% at 3 months, in 44% at 6 months, and in 18% after 12 months.…”

“…A sustained honeymoon phase (i.e., lasting some years) and even a total remission of T1D have been reported as uncommon phenomena, especially in children [16, 48]. Although immunological changes during remission are poorly characterized [49], an extension of this stage may benefit T1D patients, since residual β-cell function has been associated with a reduction in long-term and acute complications [50].…”

Temporal dynamics of serum let‐7g expression mirror the decline of residual beta‐cell function in longitudinal observation of children with type 1 diabetes

“…Although the underlying mechanism responsible for islet destruction is not completely understood, T1DM is known to be characterized by insulitis (inflammation of the islets of Langerhans) and the presence of pancreatic autoantibodies. Clinical onset of T1DM and introduction of insulin therapy are often followed by a remission phase, characterized by improved metabolic control and a temporary recovery of residual beta‐cell function …”

Type 1 Diabetes: Disease Stratification

“…Residual C-peptide can be detected in some individuals years to decades after diagnosis but more commonly with adultonset versus childhood-onset T1D [122,123] . Several biomarkers and genes have been identified and modeled that predict a lack or presence of a honeymoon/remission in stage 3 T1D [124][125][126][127] . With the clinical presentation of frank insulin dependence, all forms of T1D are treated with combinations of rapid-acting (bolus) and long-acting (basal) insulins to compensate for the loss of endogenous insulin production.…”