Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes

Weiqiong Gu, Jiong Hu, Weiqing Wang, Lirong Li, Wei Tang, Shouyue Sun, Weijuan Cui, Lei Ye, Yifei Zhang, Jie Hong, Dalong Zhu, Guang Ning, Weiqiong Gu, Jiong Hu, Weiqing Wang, Lirong Li, Wei Tang, Shouyue Sun, Weijuan Cui, Lei Ye, Yifei Zhang, Jie Hong, Dalong Zhu, Guang Ning

Abstract

Objective: To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis.

Research design and methods: We enrolled 28 patients with type 1 diabetes, aged 14-30 years, in a prospective AHSCT phase II clinical trial. HSCs were harvested from the peripheral blood after pretreatment consisting of a combination of cyclophosphamide and antithymocyte globulin. Changes in the exogenous insulin requirement were observed and serum levels of HbA(1c), C-peptide, and anti-glutamic acid decarboxylase antibody were measured before and after the AHSCT.

Results: After transplantation, complete remission (CR), defined as insulin independence, was observed in 15 of 28 patients (53.6%) over a mean period of 19.3 months during a follow-up ranging from 4 to 42 months. The non-DKA patients achieved a greater CR rate than the DKA patients (70.6% in non-DKA vs. 27.3% in DKA, P = 0.051). In the non-DKA group, the levels of fasting C-peptide, peak value during oral glucose tolerance test (C(max)), and area under C-peptide release curve during oral glucose tolerance test were enhanced significantly 1 month after transplantation and remained high during the 24-month follow-up (all P < 0.05). In the DKA group, significant elevation of fasting C-peptide levels and C(max) levels was observed only at 18 and 6 months, respectively. There was no mortality.

Conclusions: We have performed AHSCT in 28 patients with type 1 diabetes. The data show AHSCT to be an effective long-term treatment for insulin dependence that achieved a greater efficacy in patients without DKA at diagnosis.

Trial registration: ClinicalTrials.gov NCT00807651.

Figures

Figure 1
Figure 1
Insulin dose (IU/kg/day) in type 1 diabetic patients after treatment of AHSCT. *P < 0.001 compared with month 0 (pretransplantation). d, day; mo, month.
Figure 2
Figure 2
Time course of HbA1c, insulin dose, fasting C-peptide, Cmax, AUCC, and LnGAD level (because of the uneven data distribution) in the non-DKA group and DKA group, respectively. Solid line, non-DKA group; dotted line, DKA group. mo, month.

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