ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this study of 699 youth 10 to < 18 years old with <2 years duration of type 2 diabetes (T2D) at 15 centers across the USA, baseline HbA1c level, and the change in HbA1c level in the first 6 months are predictors of rapid glycemic deterioration. In addition, subsequent loss of control can be predicted based on both baseline and ongoing clinical characteristics.

Comment: The population of individuals with youth-onset T2D is heterogeneous. Two large subsets are characterized as those at risk of losing glycemic control rapidly, and those who maintain glycemic control, defined as HbA1c <8%, for a more prolonged period.

The incidence of complications is high among children and teenagers with T2D. Currently good drug treatment options are available. On the other hand, 50% of youth can maintain good glycemic control without the use of medication. Therefore, early identification of the parameters that characterize high-risk individuals, before deterioration, is important. This can prompt initiation of early treatment and differentiate individuals who do not require medications.

These authors assessed baseline anthropometric and metabolic parameters from participants of the TODAY study, aged 10 to <18 years old at baseline with <2 years T2D duration. Their baseline data were assessed as predictors of glycemic deterioration at two time points: after 4 years and at the end of follow-up, at 6.8 years. The predicting parameters at 4 years were baseline HbA1c at study entry, the change in HbA1c after the first 6 months, measures of insulin secretion (C peptide and oral disposition index), measures of insulin processing (proinsulin to insulin ratio) and a maternal history of diabetes. One-third of those who had good glycemic control after 4 years subsequently lost it. Reduced baseline insulin secretion (C-peptide index) also predicted late glycemic deterioration. Additional parameters assessed at the 4^th year that predicted late deterioration were: an elevated HbA1c level, impaired insulin processing (proinsulin/insulin ratio) and a rise in proinsulin between baseline and 48 months. Of importance, the changes in HbA1c over the first 6 months of treatment were a significant predictor even after 9 years.

Based on these findings, the authors suggest that dysfunctional insulin processing (represented by elevated proinsulin) might be an initial step in the decline of beta-cell function. This dysfunction could be followed by a decrease in insulin secretory capacity, which subsequently contributes to worsening blood sugar control. In summary, clinicians can distinguish youth with T2DM who do not need additional drug therapy from those who are high-risk and need early and more aggressive intervention.