Long-term outcome of islet transplantation on insulin-dependent diabetes mellitus: An observational cohort study

Abstract

Aims/introduction: To investigate the long-term efficacy and safety of islet transplantation (ITx) compared with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII).

Materials and methods: Among 619 patients diagnosed as insulin-dependent diabetes mellitus or type 1 diabetes at Kyoto University, Kyoto, Japan, seven patients were selected as the ITx group and 26 age-matched patients with no endogenous insulin secretion were selected as the MDI/CSII group. Hemoglobin A1c, aspartate aminotransferase/alanine aminotransferase (AST/ALT) and creatinine were assessed retrospectively at 1, 2, 5 and 10 years for both groups; serum C-peptide immunoreactivity was assessed for the ITx group. Major clinical events were also assessed.

Results: Hemoglobin A1c improvement in ITx was significant at 1 year (8.4% [7.8-9.9%] at baseline to 7.1% [6.3-7.4%] in ITx vs 8.2% [7.4-9.8%] at baseline to 8.1% [7.3-9.5%] in MDI/CSII, P < 0.01 between groups), and was maintained at 2 years (7.4% [6.3-8.2%] vs 8.4% [7.4-9.6%], P = 0.11). The increase of stimulated C-peptide immunoreactivity was significant at 1 year (0.57 ng/mL [0.26-0.99 ng/mL], P < 0.05 from baseline) and 2 years (0.43 ng/mL [0.19-0.67 ng/mL], P < 0.05), although it became insignificant thereafter. There was no significant difference in AST/ALT or creatinine at 10 years, although a transient AST/ALT elevation was observed in ITx. In regard to clinical events, the occurrence of severe hypoglycemia was 14% vs 31% (relative risk 0.46, P = 0.64), that of infectious disease was 43% vs 12% (relative risk 3.71, P = 0.09) and digestive symptoms was 43% vs 7.7% (relative risk 5.57, P = 0.05) in ITx vs MDI/CSII, respectively. No patient died in either group.

Conclusions: The present findings showed that ITx was considered to contribute to the reduction of hypoglycemia and better glycemic control with tolerable, but attention-requiring, risks over a period of 10 years compared with MDI/CSII.

Keywords: Insulin-dependent diabetes mellitus; Islet transplantation; Long-term outcome.

Figure 1

Graft function and glycemic control after islet transplantation. Changes of (a) stimulated serum C‐peptide immunoreactivity (sCPR), (b) ad libitum (Ad‐lib) serum C‐peptide reactivity and (c) hemoglobin A1c (HbA1c; %) in the islet transplantation group. Data are shown as box and whisker plots and a supplemental line graph of mean values that are presented as cross marks. *P < 0.05 from baseline. Pre, pre‐first transplantation.

Figure 2

Glycemic control of islet transplantation (ITx) group and multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) group. Comparison of (a) changes of hemoglobin A1c (HbA1c; %) and (b) box and whisker plots of ΔHbA1c (the difference between 10 years and baseline; %) in the ITx group and the MDI/CSII group. *P < 0.05 from baseline, ^†† P < 0.01 from MDI/CSII. Pre, pre‐first transplantation.

Figure 3

Liver and kidney function after islet transplantation. Changes of (a) aspartate aminotransferase (AST), (b) alanine aminotransferase (ALT) and (c) creatinine in the islet transplantation group. *P < 0.05 from baseline. Pre, pre‐first transplantation.

Figure 4

Liver and kidney function of islet transplantation (ITx) group and multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) group. Comparison of changes of (a) aspartate aminotransferase (AST), (c) alanine aminotransferase (ALT) and (e) creatinine, and box and whisker plots of (b) ΔAST (the difference between 10 years and baseline), (d) ΔALT and (f) Δcreatinine in the ITx group and the MDI/CSII group.^†† P < 0.01 from MDI/CSII, * P < 0.05 from baseline, NS, not significant; Pre, pre‐first transplantation.