Screening of glucokinase gene in pregnancy women with abnormal glucose metabolism

doi:10.3969/j.issn.1006-7795.2020.01.009

Abstract

Abstract: Objective To estimate the prevalence of maturity onset diabetes of the young 2 (MODY2) caused by glucokinase (GCK) gene mutation and to establish a clinical strategy for identifying GCK gene mutation in pregnancy woman. Methods A retrospective study was conducted on pregnant women undergoing pregnant examination at Luhe Hospital, Capital Medical University on January 1, 2016 and December 31, 2018.The GCK gene was sequenced in patients meeting the following criteria:fasting blood glucose(FBG) ≥ 5.5 mmol/L (at least 3 times) and triglyceride (TG) ≤ 1.43 mmol/L (at least once). The 2-hour increment of 75 g glucose tolerance test was less than 4.6 mmol/L in 24-28 weeks of gestation. Results A total of 2 454 subjects were screened of which 12 patients met the screening criteria. DNA samples of 5 patients were sequenced, with 1 patient with GCK mutation identified. Conclusion Our screening method based on FBG ≥ 5.5 mmol/L (at least 3 times), triglyceride ≤ 1.43 mmol/L(at least once) and oral glucose tolerance test(OGTT)2 h glucose increment < 4.6 mmol/L is feasible for screening GCK gene mutation in pregnant women. GCK mutation is not the main cause of abnormal gestational blood glucose in China.

Key words: abnormal blood glucose during pregnancy, maturity onset diabetes of the young 2, glucokinase-maturity onset diabetes the young

CLC Number:

R587

Yuan Shasha, Ma Yan, Wu Nannan, Xu Yuechao, Yang Longyan, Ke Jing, Zhao Dong. Screening of glucokinase gene in pregnancy women with abnormal glucose metabolism[J]. Journal of Capital Medical University, 2020, 41(1): 45-49.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2020.01.009

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2020/V41/I1/45

References

[1] Froguel P, Vaxillaire M, Sun F, et al. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus[J]. Nature,1992, 356(6365):162-164.
[2] Byrne M M, Sturis J, Clement K, et al. Insulin secretory abnormalities in subjects with hyperglycemia due to glucokinase mutations[J].J Clin Invest,1994, 93(3):1120-1130.
[3] Stride A, Vaxillaire M, Tuomi T, et a1. The genetic abnormality in the beta cell determines the response to an oral glucose load[J].Diabetologia,2002,45(3):427-435.
[4] Ellard S, Bellanne-Chantelot C, Hattersley A T. Best practice guidelines for the molecular genetic diagnosis of maturity-onset diabetes of the young[J]. Diabetologia,2008, 51(4):546-553.
[5] Ma Y, Han X, Zhou X, et al. A new clinical screening strategy and prevalence estimation for glucokinase variant-induced diabetes in an adult Chinese population[J]. Genet Med,2019, 21(4):939-947.
[6] Stoffel M, Froguel P, Takeda J, et al. Human glucokinase gene:isolation, characterization, and identification of two missense mutations linked to early-onset non-insulin-dependent (type 2) diabetes mellitus[J]. Proc Nat Acad Sci USA,1992, 89(16):7698-7702.
[7] Ping Xiao Y, Hua Xu X, Lan Fang Y, et al. GCK mutations in Chinese MODY2 patients:a family pedigree report and review of Chinese literature[J]. J Pediatr Endocrinol Metab, 2016, 29(8):959-964.
[8] 王志新,平凡,张茜,等.中国妊娠期血糖异常人群葡萄糖激酶基因突变初步筛查[J].中华糖尿病杂志,2014,6(6):397-401.
[9] Liu L,Liu Y,Ge X, et al. Insights into pathogenesis of five novel GCK mutations identified in Chinese MODY patients[J]. Metabolism, 2018 Dec, 89:8-17.
[10] Craig M E, Jefferies C, Dabelea D, et al. ISPAD clinical practice consensus guidelines 2014. Definition, epidemiology, and classification of diabetes in children and adolescents[J]. Pediatr Diabetes, 2014,15(S20):4-17.
[11] Chakera A J, Spyer G, Vincent N, et al. The 0.1% of the population with glucokinase monogenic diabetes can be recognized by clinical characteristics in pregnancy:the Atlantic Diabetes in Pregnancy cohort[J]. Diabetes Care,2014, 37(5):1230-1236.
[12] Lachance C H, Baillargeon M. Should the clinical criteria for suspecting glucokinase mutation-related hyperglycemia (MODY-2) be revisited during pregnancy?[J]. Can J Diabetes,2018, 42(3):226-228.
[13] Chakera A J, Steele A M, Gloyn A L, et al. Recognition and management of individuals with hyperglycemia because of a heterozygous glucokinase mutation[J]. Diabetes care,2015, 38(7):1383-1392.
[14] Stride A, Shields B,Gill-Carey O, et al. Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia[J]. Diabetologia, 2014,57(1):54-56.
[15] Gloyn A L, van de Bunt M, Stratton I M, et al. Prevalence of GCK mutations in individuals screened for fasting hyperglycaemia[J]. Diabetologia, 2009, 52(1):172-174.
[16] Chakera A J, Steele A M, Gloyn A L, et al. Recognition and management of individuals with hyperglycemia because of a heterozygous glucokinase mutation[J]. Diabetes Care,2015, 38(7):1383-1392.
[17] Wang Z, Ping F, Zhang Q, et al. Preliminary screening of mutations in the glucokinase gene of Chinese patients with gestational diabetes. J Diabetes Investig, 2018,9(1):199-203.