Insulin sensitivity and partial clinical remission in childhood type 1 diabetes; a longitudinal study

Background and aim. Insulin sensitivity (IS) is an important factor in pediatric type 1 diabetes. Adolescents with type 1 diabetes are less insulin sensitive than healthy peers with same body mass index, and there seems to be a relation with factors such as sex, glyceamic control, total body fat, waist and age. The remission phase represents a time of decreased need for external insulin. A low IS is associated with a lower chance of experiencing remission phase; but the association between IS and the length of the remission phase remains unclear. Previous studies have shown that insulin production by pancreatic beta-cells is not the only factor affecting the remission phase and it has been speculated if insulin sensitivity could be a factor to address. Material and methods. 78 children and adolescents (68% boys) were included within 3 months from diagnosis. They were tested with a mixed meal tolerance test three times with 6 months apart. They had a DXA-scan at the first and last visit. Variables included biometric data, a surrogate marker for insulin sensitivity, a surrogate marker for partial remission (IDAA1c) and stimulated c-peptide as representation of endogenous insulin production. Results. The mean age was 11.4 yrs at visit 1. 75, 71 and 60 participants completed visit 1, 2 and 3 respectively. There were significantly more participants with a stimulated c-peptide above 300 pmol/L than participants in remission defined by IDAA1c ≤9 at visit 1 (p=0.02) and visit 3 (p=0.02). At visit 2 this was equal. The participants not in remission at visit 3 despite stimulated c peptide >300 p mol/L had a lower IS-score defined by the surrogate marker at both visit 1 (p=0.01), visit 2 (p=0.05) and visit 3 (p=0.006) compared to the rest. BMI Z-score and total body fat z-score was elevated in this group, but this was not significant. The surrogate marker of IS did not show any changes in insulin sensitivity throughout the study, neither on group nor individual level. Conclusion and perspective. The participants who were not in remission at visit 3 despite sufficient stimulated c-peptide production had a significant lower IS score less than 3 months from diagnosis. Identifying children and adolescents with low IS early after diagnosis opens a window for intervention in this specific group to improve insulin sensitivity by lifestyle and/or pharmaceutical interventions to extend the length of the remission phase and to improve glycemic control and minimize long term complications.