Sandström C S, Ohlsson B, Melander O, Westin U, Mahadeva R, Janciauskiene S
Chronic and Degenerative Disease Research Unit, University Hospital Malmoe, Lund University, Malmo, Sweden.
Diabet Med. 2008 Nov;25(11):1370-3. doi: 10.1111/j.1464-5491.2008.02584.x.
Alpha(1)-Antitrypsin (AAT) is a serine protease inhibitor which recently has been shown to prevent Type 1 diabetes development, to prolong islet allograft survival and to inhibit pancreatic B-cell apoptosis in vivo. It has also been reported that Type 1 diabetic patients have significantly lower plasma concentrations of AAT, suggesting the potential role of AAT in the pathogenesis of Type 1 diabetes. We have investigated whether plasma AAT levels are altered in Type 2 diabetes.
The study included patients with Type 2 diabetes (n = 163) and non-diabetic control subjects matched for age, sex and smoking habits (n = 158) derived from the population-based Malmö Diet and Cancer study. Plasma samples were analysed for AAT concentration and phenotype and serum glucose, insulin, C-reactive protein and lipid levels were measured. Glycated haemoglobin was also measured.
In the diabetic group, the women had higher mean plasma AAT levels than men (P < 0.05). The mean plasma AAT levels did not differ between diabetic and control subjects. However, the number of individuals with low AAT levels (< 1.0 mg/ml) was 50% higher in the diabetic group (P < 0.05) and the frequency of AAT deficiency genotypes was 50% higher (NS) in diabetic compared with control subjects. In the group of diabetic patients with AAT < 1 mg/ml, AAT directly correlated with systolic blood pressure (P = 0.048) and inversely correlated with waist-hip ratio (P = 0.031).
Our results provide evidence that deficiency of AAT may be associated with an increased risk of developing Type 2 diabetes.
α1-抗胰蛋白酶(AAT)是一种丝氨酸蛋白酶抑制剂,最近研究表明它可预防1型糖尿病的发生、延长胰岛移植存活时间并在体内抑制胰腺β细胞凋亡。也有报道称1型糖尿病患者血浆中AAT浓度显著降低,提示AAT在1型糖尿病发病机制中可能发挥作用。我们研究了2型糖尿病患者血浆AAT水平是否发生改变。
该研究纳入了来自基于人群的马尔默饮食与癌症研究的2型糖尿病患者(n = 163)以及年龄、性别和吸烟习惯相匹配的非糖尿病对照受试者(n = 158)。分析血浆样本中的AAT浓度和表型,并测量血清葡萄糖、胰岛素、C反应蛋白和血脂水平。同时也测量糖化血红蛋白。
在糖尿病组中,女性的平均血浆AAT水平高于男性(P < 0.05)。糖尿病患者和对照受试者的平均血浆AAT水平无差异。然而,AAT水平低(< 1.0 mg/ml)的个体数量在糖尿病组中高出50%(P < 0.05),糖尿病患者中AAT缺乏基因型的频率比对照受试者高出50%(无统计学意义)。在AAT < 1 mg/ml的糖尿病患者组中,AAT与收缩压直接相关(P = 0.048),与腰臀比呈负相关(P = 0.031)。
我们的结果表明,AAT缺乏可能与2型糖尿病发病风险增加有关。