ESPE Abstracts (2014) 82 FC3.3

Improved Hepatic Insulin Sensitivity in Children Randomized to CSII Treatment from Onset of Type 1 Diabetes

Klas Ekströma, Lars Skogsbergb, Hans Forsc, Christine Carlsson-Skwiruta & Peter Bangd

aPediatric Endocrinology Unit, Department of Women’s and Children’s Health, Karolinska Institute and University Hospital, Stockholm, Sweden; bDepartment of Pediatrics, Gävle Hospital, Gävle, Sweden; cDepartment of Pediatrics, Northern Älvsborgs Hospital, Trollhättan, Sweden; dDivision of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Background: Our first report of this randomized controlled trial (RCT) demonstrated improved treatment satisfaction but no difference in HbA1c between the CSII and MDI treated groups, and added to the controversy as to whether CSII improves HbA1c or not. Therefore, we thought it would be valuable to assess if CSII had other potential advantages and if our finding of lower insulin dose requirements could be explained.

Objective and Hypotheses: To study how different insulin regimens affect IGF1 and IGF-binding protein-1 (IGFBP1) in relation to fasting C-peptide and insulin doses in children with type 1 diabetes mellitus (T1DM).

Method: In an open, parallel, multicenter study, children (7–17 years of age) with newly diagnosed T1DM were randomized to receive multiple daily insulin (MDI) injections (n=38) or continuous s.c. insulin infusion (CSII) (n=34). At inclusion and after 6, 12, and 24 months IGF1, IGFBP1 and C-peptide concentrations were determined.

Results: The CSII group had significantly lower IGFBP1 levels at 12 and 24 months (P=0.007 and P<0.001 respectively). The mealtime and basal insulin doses in the CSII group were significantly lower at these time points. IGF1 or C-peptide did not differ between the treatment groups. The ln(C-peptide) correlated significantly with IGF1 and IGFBP1 at 6 and 12 months in both groups, and at 6 months the decrease in IGF1 and the increase in IGFBP1 for a given decrease in C-peptide were more marked in the MDI group.

Conclusion: Lower IGFBP1 in the CSII group is a marker of improved hepatic insulin sensitivity and, in accord therewith insulin dose requirements were lower. CSII treatment failed to normalize IGF1 deficiency and did not improve endogenous insulin secretion. One potential effect of the improved hepatic insulin sensitivity on CSII is that both generation of IGF1 and the inhibition of IGFBP1 are less dependent on endogenous insulin secretion.

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