Prevalence of Vascular Complications Among Patients With Glucokinase Mutations and Prolonged, Mild Hyperglycemia
Prevalence of Vascular Complications Among Patients With Glucokinase Mutations and Prolonged, Mild Hyperglycemia
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DOI：
10.1001/jama.2013.283980
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发表时间：
2014-01-15
影响因子：
120.7
通讯作者：
Hattersley, Andrew T.
中科院分区：
文献类型：
--
作者：
Steele, Anna M.;Shields, Beverley M.;Hattersley, Andrew T.
糖尿病中的Glycoprotein靶点已经被开发出来，以最大限度地降低并发症风险。具有杂合失活葡萄糖激酶（GCK）突变的患者从出生起就有轻度空腹高血糖，导致糖化血红蛋白（HbA（1c））水平升高，模拟1型和2型糖尿病的推荐水平。和参与者2008年8月至2010年12月期间在英国进行的横断面研究。对99名GCK突变携带者进行了35岁或以上参与者的微血管和大血管并发症评估（中位年龄48.6岁），91例非糖尿病家族性非突变携带者（对照）（中位年龄，52.2岁），83例确诊为45岁或以下的初发2型糖尿病（YT 2D）患者主要结果和测量肾病、视网膜病变、周围神经病变、周围血管疾病和心血管疾病的患病率和严重程度。结果GCK突变患者的中位HbA 1c为6.9%，对照组为5.8%，YT 2D患者为7.8%。GCK患者具有临床意义的微血管并发症的发生率较低（1% [95%CI，0%-5%]），与对照组（2% [95%CI，0.3%-8%]，P= 0.52）无显著差异，且低于YT 2D患者（36% [95%CI，25%-47%]，P = 0.005）。
IMPORTANCE Glycemic targets in diabetes have been developed to minimize complication risk. Patients with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA(1c)) level that mimics recommended levels for type 1 and type 2 diabetes.OBJECTIVE To assess the association between chronic, mild hyperglycemia and complication prevalence and severity in patients with GCK mutations.DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study in the United Kingdom between August 2008 and December 2010. Assessment of microvascular and macrovascular complications in participants 35 years or older was conducted in 99 GCK mutation carriers (median age, 48.6 years), 91 nondiabetic, familial, nonmutation carriers (control) (median age, 52.2 years), and 83 individuals with young-onset type 2 diabetes (YT2D), diagnosed at age 45 years or younger (median age, 54.7 years).MAIN OUTCOMES AND MEASURES Prevalence and severity of nephropathy, retinopathy, peripheral neuropathy, peripheral vascular disease, and cardiovascular disease.RESULTS Median HbA1c was 6.9% in patients with the GCK mutation, 5.8% in controls, and 7.8% in patients with YT2D. Patients with GCK had a low prevalence of clinically significant microvascular complications (1% [95% CI, 0%-5%]) that was not significantly different from controls (2% [95% CI, 0.3%-8%], P=.52) and lower than in patients with YT2D (36% [95% CI, 25%-47%], P