Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Diabetes Research Division, Department of Medicine, Gentofte Hospital, University of Copenhagen, Hellerup, DenmarkDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkNNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
Diabetes Care. 2014 Jul;37(7):1797-805. doi: 10.2337/dc13-3007.
The most common form of maturity-onset diabetes of the young (MODY), hepatocyte nuclear factor 1α (HNF1A diabetes: MODY3) is often treated with sulfonylureas that confer a high risk of hypoglycemia. We evaluated treatment with GLP-1 receptor agonists (GLP-1RAs) in patients with HNF1A diabetes.
Sixteen patients with HNF1A diabetes (8 women; mean age 39 years [range 23-67 years]; BMI 24.9 ± 0.5 kg/m(2) [mean ± SEM]; fasting plasma glucose [FPG] 9.9 ± 0.9 mmol/L; HbA1c 6.4 ± 0.2% [47 ± 3 mmol/mol]) received 6 weeks of treatment with a GLP-1RA (liraglutide) and placebo (tablets), as well as a sulfonylurea (glimepiride) and placebo (injections), in randomized order, in a double-blind, crossover trial. Glimepiride was up-titrated once weekly in a treat-to-target manner; liraglutide was up-titrated once weekly to 1.8 mg once daily. At baseline and at the end of each treatment period a standardized liquid meal test was performed, including a 30-min light bicycle test.
FPG decreased during the treatment periods (-1.6 ± 0.5 mmol/L liraglutide [P = 0.012] and -2.8 ± 0.7 mmol/L glimepiride [P = 0.003]), with no difference between treatments (P = 0.624). Postprandial plasma glucose (PG) responses (total area under the curve) were lower with both glimepiride (2,136 ± 292 min × mmol/L) and liraglutide (2,624 ± 340 min × mmol/L) compared with baseline (3,127 ± 291 min × mmol/L; P < 0.001, glimepiride; P = 0.017, liraglutide), with no difference between treatments (P = 0.121). Eighteen episodes of hypoglycemia (PG ≤3.9 mmol/L) occurred during glimepiride treatment and one during liraglutide treatment.
Six weeks of treatment with glimepiride or liraglutide lowered FPG and postprandial glucose excursions in patients with HNF1A diabetes. The glucose-lowering effect was greater with glimepiride at the expense of a higher risk of exclusively mild hypoglycemia.
最常见的青少年发病型成年糖尿病（MODY）形式，即肝细胞核因子 1α（HNF1A）糖尿病：MODY3，通常使用磺酰脲类药物治疗，但会带来严重低血糖的风险。我们评估了 GLP-1 受体激动剂（GLP-1RA）在 HNF1A 糖尿病患者中的治疗效果。
16 例 HNF1A 糖尿病患者（8 名女性；平均年龄 39 岁[范围 23-67 岁]；BMI 24.9±0.5kg/m2[平均值±SEM]；空腹血糖[FPG]9.9±0.9mmol/L；糖化血红蛋白[HbA1c]6.4±0.2%[47±3mmol/mol]）接受 6 周的 GLP-1RA（利拉鲁肽）和安慰剂（片剂）以及磺酰脲类药物（格列美脲）和安慰剂（注射剂）治疗，两种治疗方案均采用随机、双盲、交叉试验。格列美脲每周递增一次，以达到目标剂量；利拉鲁肽每周递增一次，至 1.8mg/日 1 次。在基线和每个治疗期结束时，进行标准化液体餐测试，包括 30 分钟的轻骑自行车测试。
FPG 在治疗期间下降（利拉鲁肽治疗时下降了-1.6±0.5mmol/L[P=0.012]，格列美脲治疗时下降了-2.8±0.7mmol/L[P=0.003]），两种治疗方案之间无差异（P=0.624）。与基线相比（3,127±291min×mmol/L），两种药物（格列美脲：2,136±292min×mmol/L；利拉鲁肽：2,624±340min×mmol/L）的餐后血糖（PG）反应（总曲线下面积）均降低（P＜0.001，格列美脲；P=0.017，利拉鲁肽），且两种治疗方案之间无差异（P=0.121）。格列美脲治疗期间发生了 18 次低血糖（PG≤3.9mmol/L），利拉鲁肽治疗期间发生了 1 次低血糖。
6 周的格列美脲或利拉鲁肽治疗可降低 HNF1A 糖尿病患者的 FPG 和餐后血糖波动。格列美脲的降糖效果更强，但会带来更高的轻度低血糖风险。
