-
摘要:
目的 探讨1型糖尿病的一种特殊亚型——暴发性1型糖尿病(fulminant type 1 diabetes mellitus, FT1DM)患者的临床特征。 方法 收集2010–2019年在四川大学华西医院住院、以糖尿病酮症酸中毒(diabetic ketoacidosis, DKA)起病的1型糖尿病(type 1 diabetes mellitus, T1DM)和FT1DM患者的临床资料,并对FT1DM患者进行随访。 结果 以DKA起病的住院T1DM患者共70例,其中FT1DM17例(24.3%),非FT1DM患者53例。两组患者(FT1DM组和非FT1DM组)平均年龄分别为(33.2±12.8)岁和(27.5±11.2)岁,平均体质量指数分别为(22.6±2.9) kg/m2和(19.2±2.9) kg/m2。14例FT1DM患者起病前有上呼吸道感染或急性胃肠炎症状,4例与妊娠相关,FT1DM组患者起病到初诊DKA时间〔中位数(P25~ P75):2(1~4) d〕, P<0.001)短于T1DM组患者〔30(17~78) d〕。FT1DM组患者初诊时平均最高血糖〔(39.9±11.4) mmol/L〕高于非FT1DM患者〔(28.9±9.2) mmol/L,P<0.001〕,但糖化血红蛋白 (6.6%±0.6%,P<0.001)和糖化血清白蛋白(21.4%±3.0%,P=0.001)低于非FT1DM组患者(糖化血红蛋白:12.8%±2.7%;糖化血清白蛋白:44.8%±15.0%)。FT1DM组患者血清淀粉酶高于非FT1DM组患者〔101(54~336) IU/L vs. 54(42~166) IU/L,P=0.045〕,血清脂肪酶有高于T1DM组患者的趋势〔81(57~154) IU/L vs. 46(28~195) IU/L,P=0.051〕。8.7%的非FT1DM患者GAD-Ab阳性,而FT1DM患者均阴性。出院时FT1DM患者日均胰岛素剂量(0.67±0.22) IU/kg,与非FT1DM组患者〔(0.74±0.29) IU/kg〕相比差异无统计学意义(P=0.349)。对FT1DM组患者随访约6.5年后,其日均胰岛素剂量为(0.73±0.19) IU/kg,与出院时差异无统计学意义(P=0.409) 。 结论 相比DKA起病的非FT1DM患者,FT1DM患者“三多一少”症状更少,空腹C-肽水平更低,血淀粉酶水平更高,呕吐等胃肠道感染症状发生率增加,在临床上更容易误诊。因此,临床医生早期识别FT1DM患者并予早期且长期胰岛素替代治疗至关重要。 Abstract:Objective To explore the clinical characteristics of adult patients with fulminant type 1 diabetes mellitus (FT1DM), a specific subtype of type 1 diabetes mellitus (T1DM). Methods We collected the clinical data of patients who were admitted to West China Hospital, Sichuan University in 2010-2019 for FT1DM and type 1 diabetes mellitus (T1DM) presenting with diabetic ketoacidosis (DKA) at the onset. In addition, all the FT1DM patients were followed up. Results A total of 70 patients presenting with DKA at the onset of T1DM were admitted to and received treatment at West China Hospital in 2010–2019. Among them, 17 (24.3%) had FT1DM and 53 did not. The mean ages of the FT1DM patients and the non-FT1DM patients were (33.2±12.8) years and (27.5±11.2) years, and the mean body mass indices were (22.6±2.9) kg/m2 and (19.2±2.9) kg/m2, respectively. A total of 14 FT1DM cases had symptoms of upper respiratory tract infection or acute gastroenteritis before the onset of the disease and 4 cases were related to pregnancy. The median time from the onset of the disease to the first diagnosis of DKA of the FT1DM group (median [P25-P75]: 2 [1-4] days, P<0.001) was significantly shorter than that of the non-FT1DM group (median [P25-P75]: 30 [17-78] days). The mean maximum blood glucose levels at the time of the first visit to the doctor of the FT1DM patients ([39.9±11.4] mmol/L, P<0.001) were significantly higher than that of the non-FT1DM patients ([28.9±9.2] mmol/L), but the HbA1c (6.6%±0.6%, P<0.001) and glycosylated serum albumin (GA) (21.4%±3.0%, P=0.001) levels of the FT1DM patients were significantly lower than those of the non-FT1DM group (HbA1c: 12.8%±2.7%; GA: 44.8%±15.0%). The median serum amylase in the FT1DM group was significantly higher than that in the non-FT1DM group (101 [54-336] IU/L vs. 54 [42-166] IU/L, P=0.045) and the median serum lipase in the FT1DM group showed a trend of being higher than that in the T1DM group (81 [57-154] IU/L vs. 46 [28-195] IU/L, P=0.051). 8.7% of the non-FT1DM patients tested positive for anti-glutamic acid decarboxylase antibody (GAD-Ab), while the FT1DM patients all tested negative. At the time of discharge, the mean daily insulin dose of the FT1DM patients was (0.67±0.22) IU/kg, which was not significantly different from that of the non-FT1DM group ([0.74±0.29] IU/kg, P=0.349). After about 6.5 years of follow-up, the mean daily insulin dose of the FT1DM patients was (0.73±0.19) IU/kg, which was similar to the insulin dosage on discharge (P=0.409). Conclusion Compared with the non-FT1DM patients presenting with DKA at the onset, FT1DM patients have fewer typical diabetic symptoms, lower fasting C-peptide levels, higher serum amylase levels, and increased incidence of vomiting or other symptoms of gastrointestinal infections, and are more likely to be misdiagnosed. Therefore, it is very important for clinicians to correctly identify FT1DM as early as possible and administer early and long-term insulin replacement therapy. -
Key words:
- Fulminant type 1 diabetes mellitus /
- Type 1 diabetes mellitus /
- Ketoacidosis /
- Antibodies /
- Pregnancy
-
表 1 FT1DM组与以非FT1DM的T1DM组患者临床特征比较
Table 1. Comparison of the clinical characteristics between the FT1DM group and the non-FT1DM T1DM group
Clinical feature FT1DM group (n=17) T1DM group (n=53) P (Male∶female)/case 6∶11 27∶26 0.261 Age/yr., $\bar x\pm s $ 33.2±12.8 27.5±11.2 0.057 BMI/(kg/m2), $\bar x\pm s $ 22.6±2.9 19.2±2.9 0.001 Duration/d*, median (P25-P75) 2 (1-4) 30 (17-78) <0.001 Family history of diabetes/case (%) 1 (5.9) 2 (3.8) 1.000& Diabetes symptoms/case (%) # 13 (76.5) 51 (96.2) 0.042 Flu-like symptoms/case (%) 6 (35.3) 13 (24.5) 0.579 Gastrointestinal symptoms/case (%) 13 (76.5) 25 (47.2) 0.035 Consciousness disorder/case (%) 6 (35.3) 8 (15.1) 0.143 * Duration is the period of time between onset to occurrence of DKA; # including polyuria, thirst, body mass loss, and hyperphagia; & Fisher's exact test. 表 2 FT1DM组与以非FT1DM的T1DM组患者实验室检查结果比较
Table 2. Comparison of laboratory test results between the FT1DM group and the non-FT1DM T1DM group
Item FT1DM group (n=17) T1DM group (n=53) P Glucose/(mmol/L)*, $\bar x\pm s $ 39.9±11.4 28.9±9.2 <0.001 HbA1c/%, $\bar x\pm s $ 6.6±0.6 12.7±2.7 <0.001 GA/%, $\bar x\pm s $ 21.4±3.0 44.8±15.0 0.001 Fasting C-peptide/(nmol/L), median (P25-P75) 0.036 (0.011-0.046) 0.154 (0.067-0.274) <0.001 Amylase/(IU/L), median (P25-P75) 101 (54-336) 54 (42-166) 0.045 Lipase/(IU/L), median (P25-P75) 81 (57-154) 46 (28-195) 0.051 β-HBA/(mmol/L), median (P25-P75) 2.58 (1.15-9.18)# 7.89 (5.20-10.18) 0.147# TPOAb positive/case (%)# 0 13 (48.1) 1.000& TgAb positive/case (%)# 0 7 (25.9) 1.000& GAD-Ab positive/case (%)# 0 4 (8.7) 0.529 ICA positive/case (%)# 1 (6.3) 5 (10.4) 1.000 IAA positive/case (%)# 2 (12.5) 7 (14.6) 1.000 HbA1c: glycated hemoglobin; GA: glycosylated serum albumin; β-HBA: β-hydroxybutyric acid; TPOAb: thyroid peroxidase antibody; TgAb: thyroglobulin antibody; GAD-Ab: anti-glutamic acid decarboxylase antibody; ICA: islet cell antibody; IAA: insulin autoantibody. * The highest glucose on admission; # there was missing value; & Fisher's exact test. -
[1] SHIMIZU I, MAKINO H, IMAGAWA A, et al. Clinical and immunogenetic characteristics of fulminant type 1 diabetes associated with pregnancy. J Clin Endocrinol Metab,2006,91(2): 471–476. doi: 10.1210/jc.2005-1943 [2] IMAGAWA A, HANAFUSA T, MIYAGAWA J, et al. A novel subtype of type 1 diabetes mellitus characterized by a rapid onset and an absence of diabetes-related antibodies. Osaka IDDM Study Group. N Engl J Med,2000,342(5): 301–307. doi: 10.1056/NEJM200002033420501 [3] MOREAU C, DRUI D, ARNAULT-OUARY G, et al. Fulminant type 1 diabetes in Caucasians: a report of three cases. Diabetes Metab,2008,34(5): 529–532. doi: 10.1016/j.diabet.2008.05.003 [4] MCCAULEY R A, WANG X. Fulminant type 1 diabetes mellitus-like presentation in a Hispanic woman in the United States. Diabetes Metab,2011,37(4): 356–358. doi: 10.1016/j.diabet.2011.04.005 [5] HANAFUSA T, IMAGAWA A. Fulminant type 1 diabetes: a novel clinical entity requiring special attention by all medical practitioners. Nat Clin Pract Endocrinol Metab,2007,3(1): 36–45. doi: 10.1038/ncpendmet0351 [6] CHO Y M, KIM J T, KO K S, et al. Fulminant type 1 diabetes in Korea: high prevalence among patients with adult-onset type 1 diabetes. Diabetologia,2007,50(11): 2276–2279. doi: 10.1007/s00125-007-0812-z [7] LUO S, ZHANG Z, LI X, et al. Fulminant type 1 diabetes: a collaborative clinical cases investigation in China. Acta Diabetol,2013,50(1): 53–59. doi: 10.1007/s00592-011-0362-1 [8] 王雅静, 赵思童, 贾晓蒙, 等. 暴发性1型糖尿病临床特点的比较分析. 解放军医学杂志,2019,44(11): 936–941. [9] 吴晗, 方兴宇, 于淼, 等. 单中心22例暴发性1型糖尿病临床特征分析. 中华糖尿病杂志,2018,10(9): 590–595. doi: 10.3760/cma.j.issn.1674-5809.2018.09.005 [10] 郑超, 林健, 杨琳, 等. 暴发性1型糖尿病的患病状况及其特征. 中华内分泌代谢杂志,2010,26(3): 188–191. doi: 10.3760/cma.j.issn.1000-6699.2010.03.004 [11] 李照青, 张金苹. 暴发性1型糖尿病患者的患病情况及临床特征. 中华内科杂志,2016,55(11): 849–853. doi: 10.3760/cma.j.issn.0578-1426.2016.11.007 [12] 林乐韦华, 全会标, 陈道雄, 等. 16例暴发性1型糖尿病患者临床特点分析. 中国全科医学,2016,19(21): 2567–2571. doi: 10.3969/j.issn.1007-9572.2016.21.015 [13] 王晓晶, 王彤, 于淼, 等. 12例暴发性1型糖尿病临床特征分析. 中国糖尿病杂志,2018,26(1): 69–73. [14] 冼晶, 梁杏欢, 李励, 等. 暴发性1型糖尿病23例临床分析. 广西医科大学学报,2017,34(6): 924–926. doi: 10.16190/j.cnki.45-1211/r.2017.06.039 [15] WORLD HEALTH ORGANIZATION. Classification of diabetes mellitus. Geneva: World Health Organization, 2019. (2019-04-21)[2020-11-12]. https://apps.who.int/iris/handle/10665/325182 [16] LAPOLLA A, AMARO F, BRUTTOMESSO D, et al. Diabetic ketoacidosis: a consensus statement of the Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology and Pediatric Diabetoloy (SIEDP). Nutr Metab Cardiovasc Dis,2020,30(10): 1633–1644. doi: 10.1016/j.numecd.2020.06.006 [17] IMAGAWA A, HANAFUSA T, AWATA T, et al. Report of the Committee of the Japan Diabetes Society on the research of fulminant and acute-onset type 1 diabetes mellitus: new diagnostic criteria of fulminant type 1 diabetes mellitus (2012). J Diabetes Investig,2012,3(6): 536–539. doi: 10.1111/jdi.12024 [18] GU Y, WANG Y, LI P, et al. Fulminant type 1 diabetes in children: a multicenter study in China. Diabetes Res,2017,2017: 1–6. doi: 10.1155/2017/6924637 [19] YANG D, ZHOU Y, LUO S, et al. Clinical characteristics of fulminant type 1 diabetes compared with typical type 1 diabetes: one-year follow-up study from the Guangdong T1DM translational medicine study. J Diabetes Res,2020,2020: 1–7. doi: 10.1155/2020/8726268 [20] SHIBASAKI S, IMAGAWA A, HANAFUSA T. Fulminant type 1 diabetes mellitus: a new class of type 1 diabetes. Adv Exp Med Biol,2012,771: 20–30. doi: 10.1007/978-1-4614-5441-0_3 [21] YING L, MA X, LU J, et al. Fulminant type 1 diabetes: the clinical and continuous glucose monitoring characteristics in Chinese patients. Clin Exp Pharmacol Physiol,2019,46(9): 806–812. doi: 10.1111/1440-1681.13099 [22] HOSOKAWA Y, HANAFUSA T, IMAGAWA A. Pathogenesis of fulminant type 1 diabetes: genes, viruses and the immune mechanism, and usefulness of patient-derived induced pluripotent stem cells for future research. J Diabetes Investig,2019,10(5): 1158–1164. doi: 10.1111/jdi.13091 [23] IMAGAWA A, HANAFUSA T. Pathogenesis of fulminant type 1 diabetes. Rev Diabet Stud,2006,3(4): 169–177. doi: 10.1900/RDS.2006.3.169 [24] IMAGAWA A, HANAFUSA T, UCHIGATA Y, et al. Different contribution of class Ⅱ HLA in fulminant and typical autoimmune type 1 diabetes mellitus. Diabetologia,2005,48(2): 294–300. doi: 10.1007/s00125-004-1626-x [25] IMAGAWA A, HANAFUSA T. Fulminant type 1 diabetes mellitus. Rinsho Byori,2010,58(3): 216–224. doi: 4 [26] 应令雯, 马晓静, 周健. 暴发性1型糖尿病病因及发病机制的研究进展. 中华糖尿病杂志,2017,9(2): 139–142. doi: 10.3760/cma.j.issn.1674-5809.2017.02.012 [27] CHIOU C C, CHUNG W H, HUNG S I, et al. Fulminant type 1 diabetes mellitus caused by drug hypersensitivity syndrome with human herpesvirus 6 infection. J Am Acad Dermatol,2006,54(Suppl 2): 14–17. doi: 10.1016/j.jaad.2005.03.057 [28] MINEGAKI Y, HIGASHIDA Y, OGAWA M, et al. Drug-induced hypersensitivity syndrome complicated with concurrent fulminant type 1 diabetes mellitus and Hashimoto's thyroiditis. Int J Dermatol,2013,52(3): 355–357. doi: 10.1111/j.1365-4632.2011.05213.x [29] WANG Z, ZHENG Y, TU Y, et al. Immunological aspects of fulminant type 1 diabetes in Chinese. J Immunol Res,2016,2016: 1–6. doi: 10.1155/2016/1858202 [30] LIU L, MAO J, LU Z, et al. Clinical characteristics of fulminant type 1 diabetes associated with pregnancy in China. Endocrine,2011,40(3): 408–412. doi: 10.1007/s12020-011-9496-8 [31] LIU L, JIA W, LIU R, et al. Clinical study of pregnancy-associated fulminant type 1 diabetes. Endocrine,2018,60(2): 301–307. doi: 10.1007/s12020-018-1556-x -

计量
- 文章访问数: 15
- HTML全文浏览量: 3
- PDF下载量: 1
- 被引次数: 0