Fulminant type 1 diabetes in China: a case report and review of the literature

Fulminant type 1 diabetes in China: a case report and review of the literature 1 first-author 2 1 1 1 1 corresp ‡Corresponding Author ‡Corresponding Author †E-mail:jgshen@medmail.com.cn †E-mail:jgshen@medmail.com.cn jgshen@medmail.com.cn Department of Endocrinology and Metabolism, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China Department of Endocrinology and Metabolism, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China Department of Emergency, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China Department of Emergency, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China Fulminant type 1 diabetes is a recently discovered subtype of idiopathic type 1 diabetes, defined as diabetes with an extremely rapid process of β-cell destruction and progression to hyperglycemia and ketoacidosis. In this report, we present a case of fulminant type 1 diabetes in a 45-year-old Chinese woman, along with a review of the literature. The patient presented with sudden onset of polydipsia and polyuria after flu-like symptoms. Findings on admission included a high blood glucose level and ketoacidosis, but normal HbA1c level. The C-peptide stimulation test showed severe impairment of insulin secretion. Autoantibodies to glutamic acid decarboxylase (GAD) were negative. These results are compatible with the diagnosis of fulminant type 1 diabetes. Human leukocyte antigen-DR7 (HLA-DR7) was available in this case. It is concluded that this rapidly progressing type of diabetes exists, and we propose that HLA-DR7 might be predisposed to fulminant type 1 diabetes in Chinese patients. Fulminant type 1 diabetes Diabetic ketoacidosis Flu-like symptoms Introduction 1 Fulminant type 1 diabetes is a recently discovered subtype of type 1 diabetes. It was first introduced by Imagawa et al. ( 2000 2000 ), and defined as diabetes in which the process of β-cell destruction and the progression of hyperglycemia and ketoacidosis are extremely rapid. Fulminant type 1 diabetes is characterized by a rapid onset of diabetic ketoacidosis within a short period, normal or near-normal HbA1c level at onset, and complete β-cell destruction. Although evidence has suggested that viral infection and genetics are associated with the development of fulminant type 1 diabetes, the pathogenesis of this type of diabetes remains unknown. According to the data from a nationwide survey in Japan (Imagawa et al., 2003 2003 ), fulminant diabetes accounted for 15%–20% of Japanese type 1 diabetes with ketosis or ketoacidosis at onset. In Korea, the prevalence of fulminant type 1 diabetes was 7.1% among all patients newly diagnosed with type 1 diabetes, and 30.4% among patients with adult-onset diabetes (Cho et al., 2007 2007 ). Only a few related cases have been reported in China, but without genotypic analysis (Zhou et al., 2007 2007 ; Zhang and Wen, 2008 2008 ). Here we report one case of fulminant type 1 diabetes with human leukocyte antigen-DR7 (HLA-DR7) from the First Affiliated Hospital, School of Medicine, Zhejiang University, China, along with a review of the literature. Case report 1 A 45-year-old Han Chinese woman presented to a local hospital with fever and chills over 8 d and the highest temperature up to 40 °C. She had been diagnosed as having an infectious fever and was given levofloxacin. However, 2 d later she developed obvious polydipsia and polyuria with normal temperature, and her plasma glucose was 50.6 mmol/L. Thus she was transferred to our hospital immediately. Physical data on admission showed a height of 160 cm and a weight of 55 kg, with a body mass index of 21.5 kg/m 2 . Laboratory data showed that urinary and blood ketone were strongly positive, arterial pH was 7.31 (normal range 7.35–7.45), serum level of bicarbonate was 25.8 mmol/L (normal range 35–45 mmol/L), and standard base excess (SBE) was −12.4 mmol/L (normal range −3.0–3.0 mmol/L). Her plasma glucose was 14.21 mmol/L, whereas HbA1c was 5.7% (normal range 3.8%–5.8%). Complete blood count was as follows: white blood cell count (WBC), 17.0×10 9 L −1 ; nitrogen (N), 81.5%; haematocrit (Hct), 29.2%; haemoglobin (Hb) level, 102 g/L. Serum level of amylase was 256 U/L (normal range 17–220 U/L). Blood chemistry showed potassium 3.3 mmol/L (normal range 3.5–5.5 mmol/L), and all of aspartate aminotransferase (AST), alanine transaminase (ALT), albumin, sodium, urea nitrogen, total cholesterol, and triglyceride were normal. Abdominal ultrasound showed no remarkable findings in the pancreas on admission. Chest X-ray, electrocardiogram, urine examinations, and serum troponin I (TNI), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), and lactate dehydrogenase (LDH) measurements were negative. According to above data, we considered the patient to have type 1 diabetes and diabetic ketoacidosis. The patient was treated by intravenous infusion of saline and insulin and eventually switched to intensive insulin therapy four times a day. After initial treatment, her condition was stabilized gradually. Further examination showed that the autoantibodies to GAD were negative. C-peptide stimulation tests on admission and 18 d later showed that the serum C-peptide was < 0.5 ng/ml at different time points after oral administration of 83.5 g glucose. The results showed severe impairment of insulin secretion. Two weeks later, serological tests of virus antibody titers showed that immunoglobulin G (IgG) antibody titers for cytomegalovirus and Epstein-Barr virus (EBV) were 8.2 and 1.7, respectively, while all of immunoglobulin M (IgM) antibody titers for cytomegalovirus, EBV, coxsackie virus, and enterovirus RNA test were negative. Genotypic analysis revealed that the patient was heterozygous for HLA-DR7-DQ2 and HLA-DR9-DQ9. The case demonstrated a rapid progression of hyperglycemia and ketoacidosis, C-peptide at all points < 0.5 ng/ml, and hyperglycemia on admission with normal HbA1c. According to criteria set by fulminant type 1 diabetes research of Hanafusa and Imagawa ( 2007 2007 ), the patient was diagnosed with fulminant type 1 diabetes. We have no competing interests to declare. Discussion 1 Fulminant type 1 diabetes is a subtype of type 1 diabetes, and the pathogenesis of this disease involves both genetic background and viral infection (Imagawa and Hanafusa, 2006 2006 ; Kawasaki and Eguchi, 2006 2006 ; Nagata et al., 2007 2007 ; Goto et al., 2008 2008 ; Sano et al., 2008 2008 ; Akatsuka et al., 2009 2009 ). Accumulated evidence has shown that class II HLA is associated with this disease (Imagawa et al., 2005 2005 ; Kawabata et al., 2009 2009 ). In Japanese people, it is reported that the percentage of HLA-DR4-DQ4 in fulminant type 1 diabetes is 41.8%, higher than that in classic type 1 diabetes (22.8%). The Japanese study suggests that the CTLA4 gene increases the risk of fulminant type 1 diabetes (Kawasaki et al., 2008 2008 ). Recently, another study strongly suggested the presence of a circuit of enterovirus infection, CXC chemokine ligand 10 (CXCL10), and CXC receptor 3 (CXCR3) for the destruction of β-cells in fulminant type 1 diabetes (Tanaka et al., 2009 2009 ). However, HLA-DR7 is rare in the Japanese population, and patients with fulminant type 1 diabetes and HLA-DR7 have not been reported thus far (Imagawa et al., 2005 2005 ). A case was reported in France (Moreau et al., 2008 2008 ). In this case, HLA-DR7 was available too. No genotypic analysis in Chinese fulminant type 1 diabetes has been reported to date. Here we propose that HLA-DR7 might be predisposed to fulminant type 1 diabetes in Chinese patients, but further study is required. In this case, the patient presented a sudden onset of hyperglycemic and flu-like symptoms, with laboratory features typical of fulminant type 1 diabetes. Fulminant type 1 diabetes should be considered in Chinese diabetics, because without prompt and correct diagnosis and treatment, it may be fatal. References H Akatsuka , Y Yano , EC Gabazza , J Morser , R Sasaki , T Suzuki , R Fujiwara , A Katsuki , Y Takei , Y Sumida . A case of fulminant type 1 diabetes with coxsackie B4 virus infection diagnosed by elevated serum levels of neutralizing antibody . Diabetes Res Clin Pract , 2009 . 84 ( 3 ): e50 - e52 . 19362384 DOI: 10.1016/j.diabres.2009.03.009 http://doi.org/10.1016/j.diabres.2009.03.009 . A case of fulminant type 1 diabetes with coxsackie B4 virus infection diagnosed by elevated serum levels of neutralizing antibody YM Cho , JT Kim , KS Ko , BK Koo , SW Yang , MH Park . Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes . Diabetologia , 2007 . 50 ( 11 ): 2276 - 2279 . 17724575 DOI: 10.1007/s00125-007-0812-z http://doi.org/10.1007/s00125-007-0812-z . Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes A Goto , Y Takahashi , M Kishimoto , Y Nakajima , K Nakanishi , H Kajio , M Noda . A case of fulminant type 1 diabetes associated with significant elevation of mumps titers . Endocr J , 2008 . 55 ( 3 ): 561 - 564 . 18520103 DOI: 10.1507/endocrj.K07E-126 http://doi.org/10.1507/endocrj.K07E-126 . A case of fulminant type 1 diabetes associated with significant elevation of mumps titers T Hanafusa , A Imagawa . Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nature clinical practice . Endocrinol Metabol , 2007 . 3 ( 1 ): 36 - 45 . . Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nature clinical practice A Imagawa , T Hanafusa . Pathogenesis of fulminant type1 diabetes . Rev Diabet Stud , 2006 . 3 ( 4 ): 169 - 177 . 17487341 DOI: 10.1900/RDS.2006.3.169 http://doi.org/10.1900/RDS.2006.3.169 . Pathogenesis of fulminant type1 diabetes A Imagawa , T Hanafusa , J Miyagawa , Y Matsuzawa . Osaka IDDM Study Group A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies . N Engl J Med , 2000 . 342 ( 5 ): 301 - 307 . 10655528 DOI: 10.1056/NEJM200002033420501 http://doi.org/10.1056/NEJM200002033420501 . A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies A Imagawa , T Hanafusa , Y Uchigata , A Kanatsuka , E Kawasaki , T Kobayashi , A Shimada . Fulminant type 1 diabetes: a nationwide survey in Japan . Diabetes Care , 2003 . 26 ( 8 ): 2345 - 2352 . 12882860 DOI: 10.2337/diacare.26.8.2345 http://doi.org/10.2337/diacare.26.8.2345 . Fulminant type 1 diabetes: a nationwide survey in Japan A Imagawa , T Hanafusa , Y Uchigata , A Kanatsuka , E Kawasaki , T Kobayashi , A Shimada , I Shimizu , T Maruyama , H Makino . Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus . Diabetologia , 2005 . 48 ( 2 ): 294 - 300 . 15688210 DOI: 10.1007/s00125-004-1626-x http://doi.org/10.1007/s00125-004-1626-x . Different contribution of class II HLA in fulminant and typical autoimmune type 1 diabetes mellitus Y Kawabata , H Ikegami , T Awata , A Imagawa , T Maruyama , E Kawasaki , S Tanaka , A Shimada , H Osawa , T Kobayashi , 等 . Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset . Diabetologia , 2009 . 52 ( 12 ): 2513 - 2521 . 19812988 DOI: 10.1007/s00125-009-1539-9 http://doi.org/10.1007/s00125-009-1539-9 . Differential association of HLA with three subtypes of type 1 diabetes: fulminant, slowly progressive and acute-onset E Kawasaki , K Eguchi . Genetics of fulminant type 1 diabetes . Ann N Y Acad Sci , 2006 . 1079 ( 1 ): 24 - 30 . 17130528 DOI: 10.1196/annals.1375.004 http://doi.org/10.1196/annals.1375.004 . Genetics of fulminant type 1 diabetes E Kawasaki , A Imagawa , H Makino , M Uga , N Abiru , T Hanafusa , Y Uchigata , K Eguchi . Differences in the contribution of the CTLA4 gene to susceptibility to fulminant and type 1A diabetes in Japanese patients . Diabetes Care , 2008 . 31 ( 8 ): 1608 - 1610 . 18443194 DOI: 10.2337/dc08-0280 http://doi.org/10.2337/dc08-0280 . Differences in the contribution of the CTLA4 gene to susceptibility to fulminant and type 1A diabetes in Japanese patients C Moreau , D Drui , G Arnault-Ouary , B Charbonnel , L Chaillous , B Cariou . Fulminant type 1 diabetes in Caucasians: a report of three cases . Diabetes Metab , 2008 . 34 ( 5 ): 529 - 532 . 18829363 DOI: 10.1016/j.diabet.2008.05.003 http://doi.org/10.1016/j.diabet.2008.05.003 . Fulminant type 1 diabetes in Caucasians: a report of three cases M Nagata , H Moriyama , R Kotani , H Yasuda , M Kishi , M Kurohara , K Hara , K Yokono . Immunological aspects of ‘fulminant type 1 diabetes’ . Diabetes Res Clin Pract , 2007 . 77 ( 3 ): S99 - S103 . 17478003 DOI: 10.1016/j.diabres.2007.01.041 http://doi.org/10.1016/j.diabres.2007.01.041 . Immunological aspects of ‘fulminant type 1 diabetes’ H Sano , J Terasaki , C Tsutsumi , A Imagawa , T Hanafusa . A case of fulminant type 1 diabetes mellitus after influenza B infection . Diabetes Res Clin Pract , 2008 . 79 ( 3 ): e8 - e9 . 18177974 DOI: 10.1016/j.diabres.2007.10.030 http://doi.org/10.1016/j.diabres.2007.10.030 . A case of fulminant type 1 diabetes mellitus after influenza B infection S Tanaka , Y Nishida , K Aida , T Maruyama , A Shimada , M Suzuki , H Shimura , S Takizawa , M Takahashi , D Akiyama , 等 . Enterovirus infection, CXC chemokine ligand 10 (CXCL10), and CXCR3 circuit: a mechanism of accelerated beta-cell failure in fulminant type 1 diabetes . Diabetes , 2009 . 58 ( 10 ): 2285 - 2291 . 19641142 DOI: 10.2337/db09-0091 http://doi.org/10.2337/db09-0091 . Enterovirus infection, CXC chemokine ligand 10 (CXCL10), and CXCR3 circuit: a mechanism of accelerated beta-cell failure in fulminant type 1 diabetes YJ Zhang , D Wen . Treatment of five cases of fulminant type 1 diabetes . Chin J Gen Pract , 2008 . 6 ( 9 ): 950 (in Chinese) . Treatment of five cases of fulminant type 1 diabetes J Zhou , WP Jia , YQ Bao , W Lu , JQ Lu , Q Li , F Liu , SH Wu , KS Xiang . A case of fulminant type 1 diabetes with rhabdomyolysis . Chin J Intern Med , 2007 . 46 ( 11 ): 944 - 945 . (in Chinese) . A case of fulminant type 1 diabetes with rhabdomyolysis 10.1631/jzus.B1000080 2010-03-08 2010-10-19 2010-09-01 2022-01-05 Copyright © Zhejiang University and Springer-Verlag Berlin Heidelberg 2010 2010 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 11 11