NIHR Exeter Clinical Research Facility, University of Exeter, Exeter, Devon, United Kingdom.
PLoS One. 2013 Jun 14;8(6):e65326. doi: 10.1371/journal.pone.0065326. Print 2013.
HaemoglobinA1c (HbA1c) is recommended for diabetes diagnosis but fasting plasma glucose (FPG) has been useful for identifying patients with glucokinase (GCK) mutations which cause lifelong persistent fasting hyperglycaemia. We aimed to derive age-related HbA1c reference ranges for these patients to determine how well HbA1c can discriminate patients with a GCK mutation from unaffected family members and young-onset type 1 (T1D) and type 2 diabetes (T2D) and to investigate the proportion of GCK mutation carriers diagnosed with diabetes using HbA1c and/or FPG diagnostic criteria.
Individuals with inactivating GCK mutations (n = 129), familial controls (n = 100), T1D (n = 278) and T2D (n = 319) aged ≥18years were recruited. Receiver Operating Characteristic (ROC) analysis determined effectiveness of HbA1c and FPG to discriminate between groups.
HbA1c reference ranges in subjects with GCK mutations were: 38-56 mmol/mol (5.6-7.3%) if aged ≤40years; 41-60 mmol/mol (5.9-7.6%) if >40years. All patients (123/123) with a GCK mutation were above the lower limit of the HbA1c age-appropriate reference ranges. 69% (31/99) of controls were below these lower limits. HbA1c was also effective in discriminating those with a GCK mutation from those with T1D/T2D. Using the upper limit of the age-appropriate reference ranges to discriminate those with a mutation from those with T1D/T2D correctly identified 97% of subjects with a mutation. The majority (438/597 (73%)) with other types of young-onset diabetes had an HbA1c above the upper limit of the age-appropriate GCK reference range. HbA1c ≥48 mmol/mol classified more people with GCK mutations as having diabetes than FPG ≥7 mmol/l (68% vs. 48%, p = 0.0009).
Current HbA1c diagnostic criteria increase diabetes diagnosis in patients with a GCK mutation. We have derived age-related HbA1c reference ranges that can be used for discriminating hyperglycaemia likely to be caused by a GCK mutation and aid identification of probands and family members for genetic testing.
血红蛋白 A1c（HbA1c）推荐用于糖尿病诊断，但空腹血浆葡萄糖（FPG）有助于识别因葡萄糖激酶（GCK）突变引起的终生持续性空腹高血糖的患者。我们旨在为这些患者推导出与年龄相关的 HbA1c 参考范围，以确定 HbA1c 如何区分 GCK 突变患者与未受影响的家族成员以及年轻起病的 1 型糖尿病（T1D）和 2 型糖尿病（T2D），并调查使用 HbA1c 和/或 FPG 诊断标准诊断的 GCK 突变携带者的比例。
招募了患有失活 GCK 突变的个体（n=129）、家族对照（n=100）、T1D（n=278）和 T2D（n=319），年龄≥18 岁。接收者操作特征（ROC）分析确定了 HbA1c 和 FPG 区分各组的有效性。
GCK 突变患者的 HbA1c 参考范围为：≤40 岁时为 38-56 mmol/mol（5.6-7.3%）；>40 岁时为 41-60 mmol/mol（5.9-7.6%）。所有 GCK 突变患者（123/123）均高于 HbA1c 年龄相关参考范围的下限。99%的对照者（31/99）低于这些下限。HbA1c 也可有效区分 GCK 突变患者与 T1D/T2D 患者。使用年龄相关参考范围的上限来区分突变患者与 T1D/T2D 患者，正确识别了 97%的突变患者。大多数（438/597（73%））具有其他类型的年轻起病糖尿病的患者的 HbA1c 高于年龄适宜的 GCK 参考范围上限。HbA1c≥48mmol/mol 将更多的 GCK 突变患者归类为患有糖尿病，而 FPG≥7mmol/L 则为 48%（p=0.0009）。
目前的 HbA1c 诊断标准增加了 GCK 突变患者的糖尿病诊断。我们已经推导出与年龄相关的 HbA1c 参考范围，可用于区分可能由 GCK 突变引起的高血糖，并有助于识别高血糖的先证者和家族成员进行基因检测。
