Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes.
OBJECTIVE
To determine if autologous nonmyeloablative hematopoietic stem cell transplantation (AHSCT) was beneficial for type 1 diabetic adolescents with diabetic ketoacidosis (DKA) at diagnosis.


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.
Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolism Diseases, Endocrine and Metabolic E-Institutes of Shanghai Universities and Key Laboratory for Endocrinology and Metabolism of Chinese Health Ministry, Shanghai, People's Republic of China.
Weiqiong
W
Gu
Jiong
J
Hu
Weiqing
W
Wang
Lirong
L
Li
Wei
W
Tang
Shouyue
S
Sun
Weijuan
W
Cui
Lei
L
Ye
Yifei
Y
Zhang
Jie
J
Hong
Dalong
D
Zhu
Guang
G
Ning
D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D016883:Diabetic Ketoacidosis / Q000628:therapy*; D005260:Female; D005951:Glucose Tolerance Test; D005968:Glutamate Decarboxylase / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D011446:Prospective Studies; D012074:Remission Induction; D014182:Transplantation, Autologous
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D005968:Glutamate Decarboxylase