葡萄糖激酶基因突变导致的青少年起病的成人型糖尿病家系三年随访观察及文献复习

A three-year follow-up observation of a pedigree of maturity onset diabetes of the young caused by a novel mutation of glucokinase and literature review

目的:探索葡萄糖激酶(GCK)基因突变导致的青少年起病的成人型糖尿病(MODY)家系的临床特点。方法:对北京协和医院内分泌科诊断的1例GCK基因突变导致的MODY(GCK-MODY)患者及其家系进行临床特点分析,采用全外显子测序及Sanger测序验证对先证者及相关家系成员行GCK基因的检测,对先证者及其父亲进行为期3年的随访,并对GCK-MODY治疗随访相关文献进行检索和复习。结果:先证者及其父亲均检测到GCK基因10号外显子突变c.1348G>T(p.Ala450Thr)。对先证者采用饮食及运动控制,2019年随访,空腹血糖(FPG,6.8 mmol/L)、餐后2 h血糖(2hPG,7.4 mmol/L)及糖化血红蛋白(HbA1c,6.3%)均在目标范围之内,稳态模型法评估的胰岛素抵抗指数(HOMA-IR)较基线(4.09)有所改下降(2.32),葡萄糖处置指数(DI)较基线(16.22)有所改善(20.05)。对先证者父亲治疗则从胰岛素+阿卡波糖调整为磺脲类单药治疗,空腹及餐后血糖控制尚可,HbA1c较基线下降0.5%~0.7%,HOMA-IR及胰岛β细胞功能稳定。结论:及时对临床表现符合GCK-MODY的患者进行基因检测,并对家系相关成员进行筛查,可减少GCK-MODY的漏诊、误诊。制定合理、个性化的治疗策略,可减少不必要的过度医疗及药物不良反应,并获得良好的HbA1c达标率,延缓胰岛β细胞功能恶化。

Objective To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young(MODY)induced by a novel mutation of glucokinase(GCK).Methods The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed.Genomic DNA was extracted,and Sanger sequencing was performed to detect the gene mutation of the family members.The proband and her father were followed up for 3 years.Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD.Results Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T(p.Ala450Thr).The proband was treated with diet and exercise control only.At the end of the follow-up,her fasting plasma glucose(FPG,6.8 mmol/L),2 h postprandial plasma glucose(2hPG,7.4 mmol/L),and glycated hemoglobin(HbA1c,6.3%)were all within the control targets.Additionally,the levels homeostasis model assessment of insulin resistance(HOMA-IR)tended to improved comparing to that at baseline(4.09 to 2.32),and glucose disposition index(DI)was improved compared with baseline(16.22 to 20.05).As to the proband′s father,the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy.His FPG and 2hPG mostly were within the target range,and the levels of HbA1c were significantly reduced by 0.5%-0.7%when compared to that at baseline.The HOMA-IR or islet beta cell function was comparable to those at baseline.Conclusions Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY,so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.