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Clinical and Immunogenetic Characteristics of Fulminant Type 1 Diabetes Associated with Pregnancy

Department of Internal Medicine, Ehime Prefectural Imabari Hospital (I.S.), Imabari 794-0006, Japan; Department of Laboratory Medicine, Ehime University School of Medicine (H.M.), Toon 791-0295, Japan; Department of Internal Medicine and Molecular Science, Osaka University Graduate School of Medicine (A.I., H.I.), Suita 565-0871, Japan; Diabetes Center, Tokyo Women’s Medical University School of Medicine (Y.U.), Tokyo 162-8666, Japan; Diabetes Center, Chiba Central Medical Center (A.K.), Chiba 264-0017, Japan; Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital of Medicine and Dentistry (E.K.), Nagasaki 852-8501, Japan; Third Department of Internal Medicine, University of Yamanashi School of Medicine (T.K.), Tamaho 409-3898, Japan; Department of Internal Medicine, Keio University School of Medicine (A.S.), Tokyo 160-0016, Japan; Department of Internal Medicine, Saitama Social Insurance Hospital (T.M.), Saitama 330-0074, Japan; and First Department of Internal Medicine, Osaka Medical College (A.I., T.H.), Takatsuki 569-8686, Japan

Address all correspondence and requests for reprints to: Dr. Hideichi Makino, Department of Laboratory Medicine, Ehime University School of Medicine, Toon City, Ehime 791-0295, Japan. E-mail: hidemak{at}m.ehime-u.ac.jp.

Objective: The objective of this study was to characterize the clinical and immunogenetic features of Japanese pregnancy-associated fulminant type 1 diabetes (PF). A group of patients with PF was compared with a group of patients of child-bearing age with fulminant type 1 diabetes that was not associated with pregnancy (NPF) in a nationwide survey conducted from 2000–2004.

Patients: The clinical characteristics of the 22 patients in the PF group were compared with those of the 48 patients in the NPF group. Human leukocyte antigen (HLA) class II DR and DQ genotyping of 17 PF and 20 NPF patients was performed.

Results: Arterial pH was significantly lower (P = 0.0366), and amylase values tended to increase in PF patients compared with NPF patients (P = 0.0515). In 22 PF patients, 18 developed disease during pregnancy (26.3 wk; range, 7–38), whereas four cases occurred immediately after delivery (10.5 d; range, 7–14 d). Twelve cases that developed during pregnancy resulted in stillbirth (67%), and five of the six fetal cases that survived were delivered by cesarean section. The haplotype frequency of HLA DRB1*0901-DQB1*0303 in PF was significantly higher than those in NPF (P = 0.0244) and controls (P = 0.0001), whereas that of DRB1*0405-DQB1*0401 in NPF was significantly higher than those in PF (P = 0.0162) and controls (P < 0.0001).

Conclusions: The clinical symptoms of PF patients were more severe than those of NPF patients, and the prognosis of their fetuses was extremely poor. The type 1 diabetes-susceptible HLA class II haplotype is distinct in PF and NPF patients, suggesting that different HLA haplotypes underlie the presentation of PF or NPF.