Comparison of islet cell transplantation with medical therapy for management of severe hypoglycemia in T1DM — ASN Events

Comparison of islet cell transplantation with medical therapy for management of severe hypoglycemia in T1DM (#3)

Jane Holmes-Walker 1
  1. Westmead Hospital, Westmead, NSW, Australia

Islet cell transplantation (ICT) is currently indicated for treatment of recurrent asymptomatic and severe hypoglycemia in type I diabetes subjects and is approved in Australia for therapeutic use in 6 patients pa. The majority referred have long duration of diabetes (mean duration of diabetes 36 years). In the Westmead cohort we have compared outcomes of best medical therapy using CSII prior to islet cell transplant and have more recently begun a study of CSII with real time continuous glucose monitoring (CGM) prior to ICT.

T1DM subjects on MDI and/or CSII at baseline were assessed with HbA1c, Edmonton HYPOscore,  CGM with analysis using continuous overlapping net glycemic action (CONGA; measure of glycemic variability) at baseline, 6 and 12 months post ICT.

Difference in HYPOscore between MDI and CSII showed a significant fall of 982 (p < 0.001) in 9 paired studies but in 13/19 on CSII pre transplant HYPOscore remained  >90th centile. HbA1c, and mean glucose did not fall between MDI and CSII treated but sd glucose fell by 1.1 mmol/L and CGM % time in hypoglycemia fell from 11 to 1% (p<0.01) and reduced by 4% in paired analysis of MDI versus CSII. CONGA reduced significantly in CSII treated cf MDI (P<0.05).

Following ICT (n=21) all were C-peptide positive. At one year  8/21 were insulin independent, mean insulin use 0.2 units per kg cf 0.5 units/kg pre-ICT. At 6 months and 1 year post transplant there was a significant reduction in all parameters: HbA1c, mean glucose, sd glucose, HYPOscore , CGM % time in hypoglycemia and CONGA cf optimal medical therapy prior to ICT

While severe hypoglycemia is reduced with use of CSII cf MDI in subjects referred for ICT, restoration of endogenous beta cell function with ICT, as compared with CSII treatment, improved all outcome measures regardless of insulin independence.