Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia.
Cross-sectional and longitudinal studies suggest pharmacological treatment used in patients with glucokinase mutations does not alter glycaemia.
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DOI：
10.1007/s00125-013-3075-x
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发表时间：
2014-01
期刊：
影响因子：
8.2
通讯作者：
Hattersley, Andrew T.
中科院分区：
文献类型：
--
作者：
Stride, Amanda;Shields, Beverley;Gill-Carey, Olivia;Chakera, Ali J.;Colclough, Kevin;Ellard, Sian;Hattersley, Andrew T.
杂合子葡萄糖激酶（GCK）突变导致出生时轻度空腹高血糖症。尽管患者通常无症状，且血糖在目标范围内，但有些患者仍接受药物治疗。我们的目的是调查有多少患者正在接受药物治疗以及治疗对血糖控制的影响。确定了799例杂合GCK突变患者的治疗详情。在一项单独的纵向研究中，获得了16例在治疗期间接受胰岛素（n = 10）或口服降糖药（OHA）（n = 6）的连续患者的HbA 1c，这些患者在基因诊断为GCK-MODY后再次停止治疗。为了进行比较，在未接受药物治疗的对照组（n = 18）中研究了基因检测前后的HbA 1c。在转介进行基因检测时，168/799（21%）例患者接受药物治疗（13.5% OHA，7.5%胰岛素）。与未接受治疗的患者相比，这些患者的HbA 1c无差异（中位数[IQR]：分别为48 [43，51] vs 46 [43，50] mmol/mol; 6.5% [6.1%，6.8%] vs 6.4% [6.1%，6.7%]; p = 0.11）。16例患者在药物治疗中止后，HbA 1c未发生变化。HbA 1c的平均变化为−0.68 mmol/mol（95% CI：−2.97，1.61）（−0.06% [95% CI：−0.27，0.15]）。在基因诊断之前，21%的患者正在接受药物治疗。HbA 1c不高于未经治疗的患者，并且在停止治疗时没有变化，表明对高血糖没有影响。对药物治疗缺乏反应可能反映了这些患者由于葡萄糖感知缺陷而出现的调节性高血糖，这是药物遗传学的一个例子。本文的在线版本（doi：10.1007/s 00125 -013-3075-x）包含同行评审但未经编辑的补充材料，可供授权用户使用。
Heterozygous glucokinase (GCK) mutations cause mild, fasting hyperglycaemia from birth. Although patients are usually asymptomatic and have glycaemia within target ranges, some are put on pharmacological treatment. We aimed to investigate how many patients are on pharmacological treatment and the impact of treatment on glycaemic control. Treatment details were ascertained for 799 patients with heterozygous GCK mutations. In a separate, longitudinal study, HbA1c was obtained for 16 consecutive patients receiving insulin (n = 10) or oral hypoglycaemic agents (OHAs) (n = 6) whilst on treatment, and again having discontinued treatment following a genetic diagnosis of GCK-MODY. For comparison, HbA1c before and after genetic testing was studied in a control group (n = 18) not receiving pharmacological therapy. At referral for genetic testing, 168/799 (21%) of patients were on pharmacological treatment (13.5% OHAs, 7.5% insulin). There was no difference in the HbA1c of these patients compared with those receiving no treatment(median [IQR]: 48 [43, 51] vs 46 [43, 50] mmol/mol, respectively; 6.5% [6.1%, 6.8%] vs 6.4% [6.1%, 6.7%]; p = 0.11). Following discontinuation of pharmacological treatment in 16 patients, HbA1c did not change. The mean change in HbA1c was −0.68 mmol/mol (95% CI: −2.97, 1.61) (−0.06% [95% CI: −0.27, 0.15]). Prior to a genetic diagnosis, 21% of patients were on pharmacological treatment. HbA1c was no higher than in untreated patients and did not change when therapy was discontinued, suggesting no impact on glycaemia. The lack of response to pharmacological therapy is likely to reflect the regulated hyperglycaemia seen in these patients owing to their glucose sensing defect and is an example of pharmacogenetics. The online version of this article (doi:10.1007/s00125-013-3075-x) contains peer reviewed but unedited supplementary material, which is available to authorised users.
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