临床表现
在任何年龄段人群中,均可诊断出 1 型糖尿病,在 10-14 岁左右儿童中,诊断率最高。[13]Norris JM, Johnson RK, Stene LC. Type 1 diabetes-early life origins and changing epidemiology. Lancet Diabetes Endocrinol. 2020 Mar;8(3):226-38.
https://www.clinicalkey.com/#!/content/playContent/1-s2.0-S2213858719304127
http://www.ncbi.nlm.nih.gov/pubmed/31999944?tool=bestpractice.com
在 18 岁以下儿童和年轻人中,1 型糖尿病的体征包括:[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
还可能出现其他症状,例如视物模糊。[35]Usher-Smith JA, Thompson MJ, Zhu H, et al. The pathway to diagnosis of type 1 diabetes in children: a questionnaire study. BMJ Open. 2015 Mar 17;5(3):e006470.
https://bmjopen.bmj.com/content/5/3/e006470.long
http://www.ncbi.nlm.nih.gov/pubmed/25783422?tool=bestpractice.com
患有 1 型糖尿病的成人通常会出现高血糖,并且通常(但不总是)有以下一种或多种情况:[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17
酮症
体重迅速下降
年龄< 50 岁
BMI <25 kg/m²
自身免疫性疾病个人和/或家族史。
1 型糖尿病成人患者很少通过常规血液检验得到诊断。在发生慢性并发症之前很久之前就已经诊断出该病。
许多患者出现糖尿病酮症酸中毒,这是 1 型糖尿病的一种急性并发症。[37]Cherubini V, Grimsmann JM, Åkesson K, et al. Temporal trends in diabetic ketoacidosis at diagnosis of paediatric type 1 diabetes between 2006 and 2016: results from 13 countries in three continents. Diabetologia. 2020 Aug;63(8):1530-41.
https://link.springer.com/article/10.1007%2Fs00125-020-05152-1
http://www.ncbi.nlm.nih.gov/pubmed/32382815?tool=bestpractice.com
[38]Usher-Smith JA, Thompson MJ, Sharp SJ, et al. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011 Jul 7;343:d4092.
https://www.doi.org/10.1136/bmj.d4092
http://www.ncbi.nlm.nih.gov/pubmed/21737470?tool=bestpractice.com
这些患者有脱水和酸中毒的症状,比如恶心呕吐、腹痛、呼吸急促、心动过速以及昏睡。请参阅“糖尿病酮症酸中毒”专题。
还有一种进展缓慢的自身免疫性糖尿病,称为成人隐匿性自身免疫糖尿病(latent autoimmune diabetes in adults, LADA)。[2]O'Neal KS, Johnson JL, Panak RL. Recognizing and appropriately treating latent autoimmune diabetes in adults. Diabetes Spectr. 2016 Nov;29(4):249-52.
http://spectrum.diabetesjournals.org/content/29/4/249
http://www.ncbi.nlm.nih.gov/pubmed/27899877?tool=bestpractice.com
LADA 患者可能在若干年内不需要胰岛素治疗,因此在早期可能被误诊为 2 型糖尿病。[2]O'Neal KS, Johnson JL, Panak RL. Recognizing and appropriately treating latent autoimmune diabetes in adults. Diabetes Spectr. 2016 Nov;29(4):249-52.
http://spectrum.diabetesjournals.org/content/29/4/249
http://www.ncbi.nlm.nih.gov/pubmed/27899877?tool=bestpractice.com
提示患者为 LADA 而不是 2 型糖尿病的特点包括以下 2 项或更多项:发病年龄小于 50 岁、急性症状、体重指数小于 25 kg/m²、有自身免疫性疾病个人史或者家族史。[4]Fourlanos S, Perry C, Stein MS, et al. A clinical screening tool identifies autoimmune diabetes in adults. Diabetes Care. 2006 May;29(5):970-5.
http://www.ncbi.nlm.nih.gov/pubmed/16644622?tool=bestpractice.com
流感患儿的诊断
根据世界卫生组织(World Health Organization, WHO)的标准,对于存在以下情况的 18 岁以下儿童和青少年,需怀疑糖尿病:[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
[1]World Health Organization. Classification of diabetes mellitus. Geneva: World Health Organization; 2019.
https://www.who.int/publications/i/item/classification-of-diabetes-mellitus
有症状的患者,随机血糖 ≥11.1 mmol/L(≥ 200 mg/dL)或
空腹血糖 ≥7.0 mmol/L(≥ 126 mg/dL)或
口服 75 g 葡萄糖后 2 小时,血糖 ≥11.1 mmol/L(≥200 mg/dL)或
糖化血红蛋白(HbA1c)≥6.5%(≥48 mmol/mol)。
请谨记,对于多数病例,需要重复确认性检查。
如果您怀疑儿童患有 1 型糖尿病,请立即(在同一天)将其转诊给多学科儿科糖尿病团队,他们可以确认诊断,并给予及时治疗。[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
对于儿童和青少年患者,除非具有明显的 2 型糖尿病、单基因或线粒体糖尿病指征,否则推定患有 1 型糖尿病。[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
请参阅儿童 2 型糖尿病专题。
对于具有以下情况的疑似糖尿病儿童或青少年,考虑 2 型糖尿病:[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
对于具有以下任何特征的疑似糖尿病儿童或青少年,考虑其他类型糖尿病(即非 1 型或 2 型糖尿病):[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
在儿童糖尿病病例中,单基因糖尿病病例所占比例高达 4%,胰岛素治疗不适合用于这类病例。[39]Chiang JL, Maahs DM, Garvey KC, et al. Type 1 diabetes in children and adolescents: a position statement by the American Diabetes Association. Diabetes Care. 2018 Aug 9;41(9):2026-44.
http://care.diabetesjournals.org/content/41/9/2026.long
http://www.ncbi.nlm.nih.gov/pubmed/30093549?tool=bestpractice.com
单基因糖尿病的两种主要类型为青少年发病的成人型糖尿病(maturity-onset diabetes of the young, MODY)和新生儿型糖尿病(neonatal diabetes mellitus, NDM)。就 NDM 而言,糖尿病在出生后最初 6 个月被诊断出来,可能为短暂性(在 12 月龄前消退)或永久性。超过 90% 的永久性新生儿型糖尿病病例由 KCNJ11 或 ABCC8 基因改变引起,该基因改变会影响血糖水平感知与胰腺 β 细胞释放胰岛素之间的联系。[40]Pearson ER et al Switching from insulin to oral sulphonylurea in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77
https://www.nejm.org/doi/full/10.1056/NEJMoa061759
http://www.ncbi.nlm.nih.gov/pubmed/16885550?tool=bestpractice.com
基因检测是确定性的检查方法,可以用来为患者和家庭成员提供咨询。
在首次就诊时,为了区分 1 型糖尿病与 2 型糖尿病,请勿常规测定 C 肽和/或糖尿病特异性自身抗体滴度。英国国家卫生与临床优化研究所(National Institute for Health and Care Excellence, NICE)的建议指出,仅在难以区分 1 型糖尿病与其他类型糖尿病的情况下,才考虑测定 C 肽。[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
如果需要进行 C 肽测定,应考虑到,在首次就诊后越晚进行测定,其鉴别价值越高。[34]National Institute for Health and Care Excellence. Diabetes (type 1 and type 2) in children and young people: diagnosis and management. Dec 2020 [internet publication].
https://www.nice.org.uk/guidance/ng18
在临床实践中,C 肽测定应仅在有配对血糖的情况下实施。在实际操作中,这可通过在患者进餐后取单份非空腹随机血液或尿液样本,然后对其使用 C 肽来实现。[41]National Institute for Health and Care Excellence. 2019 surveillance of Type 1 diabetes in adults: diagnosis and management (2015) NICE guideline NG17. 2019 [internet publication].
https://www.nice.org.uk/guidance/ng17/evidence/appendix-a1-summary-of-evidence-from-surveillance-ng17-pdf-6837997934
否则,C 肽可能会被抑制,从而更可能出现假阳性结果。如果患者已开始接受可引起低血糖的治疗(如胰岛素治疗),这是一个特别值得关注的问题。
有关 1 型糖尿病儿童初始筛查性检查和持续监测的信息,请参阅监测章节。
成人的诊断
如果成人患者出现高血糖,NICE 建议根据临床表现诊断 1 型糖尿病,应谨记上述临床表现中的典型特征。[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17
一旦确诊,就应立即将患者转诊至当地眼科筛查服务机构。[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17
必须进行筛查:[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17
尽快转诊,最晚不迟于初次转诊后 3 个月
此后每年一次。
有关 1 型糖尿病成人初始筛查性检查和持续监测的信息,请参阅监测章节。
为了确诊成人 1 型糖尿病,请勿常规测定 C 肽和/或糖尿病特异性自身抗体滴度。NICE 的建议指出,仅在以下情况下,考虑进行此类检测:[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17
您怀疑患者有 1 型糖尿病,但临床表现包括非典型特征(例如,年龄 >50 岁、BMI >25 kg/m²、高血糖进展缓慢或前驱症状时间较长)
已诊断为 1 型糖尿病且开始治疗,但在临床上怀疑此人可能患有单基因糖尿病,并且 C 肽和/或自身抗体检测可能能够指导基因检测的使用
分类尚不确定,并且确诊 1 型糖尿病会影响可用的治疗(例如连续皮下胰岛素输注 [CSII 或“胰岛素泵”] 治疗)。
当需要进行 C 肽和/或糖尿病特异性自身抗体滴度测定时,请谨记:[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17
自身抗体检测在诊断时假阴性率最低;此后假阴性率上升
在诊断后越晚进行检测,C 肽鉴别价值越高
在进行自身身抗体检测时,针对两种不同的糖尿病特异性自身抗体进行检测,至少其中一种为阳性,这样做可降低假阴性率
在临床实践中,C 肽测定应仅在有配对血糖的情况下实施。在实际操作中,这可通过在患者进餐后取单份非空腹随机血液或尿液样本,然后对其使用 C 肽来实现。[41]National Institute for Health and Care Excellence. 2019 surveillance of Type 1 diabetes in adults: diagnosis and management (2015) NICE guideline NG17. 2019 [internet publication].
https://www.nice.org.uk/guidance/ng17/evidence/appendix-a1-summary-of-evidence-from-surveillance-ng17-pdf-6837997934
否则,C 肽可能会被抑制,从而更可能出现假阳性结果。如果患者已开始接受可引起低血糖的治疗(如胰岛素治疗),这是一个特别值得关注的问题。
对 1 型糖尿病成人的建议,应由具有糖尿病诊疗技能的多学科团队合作给出。[36]National Institute for Health and Care Excellence. Type 1 diabetes in adults: diagnosis and management. Jul 2021 [internet publication].
https://www.nice.org.uk/guidance/ng17