Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents
Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents
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DOI：
10.1007/s00431-006-0106-3
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Hansen, T.
中科院分区：
文献类型：
--
作者：
Feigerlova, E.;Pruhová, S.;Hansen, T.
简介：随机估计无症状个体的空腹高血糖可能代表胰腺 β 细胞功能障碍的第一个迹象。目的：我们的目的是明确一组儿童和青少年无症状高血糖的遗传病因。对象和方法：我们分析了 82 名年龄 0.2-18.5 岁（中位数：13.1）的非肥胖儿科受试者（38 名男性）的病因学诊断，这些受试者被转诊以阐明随机发现的血糖水平高于 5.5 mmol/l。除了空腹血糖和循环胰岛素和C肽水平外，受试者还接受口服葡萄糖耐量试验和静脉注射葡萄糖耐量试验，并筛选编码葡萄糖激酶(GCK)、HNF-1α(TCF1)、Kir6.2(KCNJ11)(如果年龄<2岁)和HNF-4α(HNF4A)(有糖尿病阳性家族史的人)的基因突变。结果和讨论：我们鉴定了 35 名导致 MODY2 的 GCK 突变携带者、两名导致 MODY3 的 TCF1 突变携带者、一名导致 MODY1 的 HNF4A 突变携带者和一名导致永久性新生儿糖尿病的 KCNJ11 突变携带者。其余患者中，11 名进展为 1 型糖尿病 (T1DM)，9 名患有糖耐量受损或原因不明的糖尿病。在 23 名受试者中，未证实血糖水平受损。我们得出的结论是，82 名随机发现空腹高血糖的儿科患者中，有 39 名 (48%) 患有单基因缺陷，其中 MODY2 最为常见。另外 11 名患者 (13%) 进展为明显的 T1DM。无症状高血糖儿童和青少年的病因学诊断是引入早期有效治疗的线索，或者在 MODY2 中，是防止未来进行任何广泛的重新调查的线索。
Introduction: Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic beta-cell dysfunction. Objective: We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents. Subjects and methods: We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1 alpha (TCF1), Kir6.2 (KCNJ11) (if aged < 2 years) and HNF-4 alpha (HNF4A) (those with a positive family history of diabetes). Results and discussion: We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.