肢端肥大症合并糖代谢异常的临床特征及其影响因素

Clinical characteristics and risk factors of impaired glucose tolerance and diabetes mellitus in acromegaly

目的了解肢端肥大症患者糖代谢异常的发生情况,评估生化指标与胰岛素抵抗及胰岛细胞功能之间的相关性,明确肢端肥大症患者发生糖尿病的危险因素。方法回顾性分析88例肢端肥大症临床资料。按口服葡萄糖耐量试验或既往史糖代谢状态分为正常糖代谢组(NGT组)、糖调节受损组(IGR组)及糖尿病组(DM组),比较临床及生化指标,使用稳态模型评估的胰岛素抵抗指数(HOMA-IR)及胰岛β细胞功能指数(HOMA-β)。以logistic回归分析肢端肥大症患者发生糖尿病的独立危险因素。结果88例肢端肥大症患者中糖调节受损者25例(28.4%),糖尿病患者37例(42.0%)。与NGT及IGR组相比,DM组患者糖尿病家族史比例更高(P<0.05)。与NGT组相比,IGR及DM组基础及口服葡萄糖耐量试验各时间点血清生长激素(growth hormone, GH)水平较高,基础GH水平在DM组存在显著性差异(P<0.05)。血清胰岛素样生长因子1(insulin-like growth factor 1, IGF-1)水平在IGR组显著高于NGT组(P<0.01),DM组IGF-1水平则低于IGR组(P<0.01)。HOMA-β在IGR组高于NGT组,但差异无统计学意义。DM组HOMA-β显著低于NGT及IGR组(P<0.01)。HOMA-IR在IGR及DM组高于NGT组,但3组间差异无统计学意义(P>0.05)。多元回归分析显示血清GH水平(OR=1.075,95%CI 1.007~1.147, P=0.030)、年龄(OR=1.106,95%CI 1.018~1.202, P=0.017)及糖尿病家族史(OR=12.710,95%CI 1.176~137.30, P=0.036)是肢端肥大症患者发生糖尿病的独立危险因素。结论与普通人群相比,肢端肥大症患者糖代谢异常的发生风险显著增加。随着糖代谢异常加重,血清GH水平更高,IGF-1水平仅在糖尿病前期高于正常糖代谢肢端肥大症患者。年龄越大,GH水平越高以及阳性糖尿病家族史的肢端肥大症患者糖尿病发生风险增加。

Objective To investigate the frequencies of the impaired glucose tolerance and diabetes mellitus in a large cohort of active acromegaly and to identify risk factors associated with the presence of diabetes at diagnosis in these patients. Methods This study included 88 patients with newly diagnosed acromegaly. Patients were further divided into normal glucose tolerance(NGT), impaired glucose regulation(IGR), and diabetes(DM) groups according to oral glucose tolerance test or previous history. Insulin sensitivity and β cell function were also evaluated by homeostasis model assessment(HOMA). Logistic regression analysis was used to explore the independent risk factors for diabetes in patients with acromegaly. Results Impaired glucose regulation was found in 25(28.4%), and DM in 37(42.0%) acromegaly patients. Compared to NGT and IGR patients, higher proportion of DM patients had family history of diabetes(P<0.05). Compared to NGT group, higher post-OGTT growth hormone(GH) levels were detected in IGR and DM groups. Insulin-like growth factor 1(IGF-1) levels were higher in IGR group while lower in DM group(P<0.01). Homeostasis model assessment for β cell function(HOMA-β) was slightly higher in IGR group, but significantly lower in DM group(P<0.01). Homeostasis model assessment for insulin resistance(HOMA-IR) was slightly higher in IGR and DM groups but without significant difference among 3 groups. In multivariate analyses, family history of diabetes(OR=12.710, 95%CI 1.176-137.30, P=0.036), age(OR=1.106, 95%CI 1.018-1.202, P=0.017), and GH levels(OR=1.075, 95%CI 1.007-1.147, P=0.030) were independent risk factors of diabetes in acromegaly patients. Conclusion Impaired glucose metabolism is present in nearly 70% of patients at diagnosis of acromegaly, and is associated with age, family history of diabetes, and higher GH levels, but not with IGF-1 levels.