第49届欧洲糖尿病研究协会年会(EASD2013)于9月23-27日在西班牙巴塞罗那召开。当地时间9月24日上午，在“生物标志物与风险评分(Biomarkers and risk scores)”专场上，波兰Jagiellonian大学Natalia Nowak博士报告的一项研究提示，血清生长素可能临床上鉴别诊断肝细胞核因子1A(HNF1A)基因突变的年轻成人发病型糖尿病(HNF1A-MODY)和
生长素(Ghrelin)是一种非糖基化激素，由28个
研究纳入47例HNF1A基因突变携带者、55例2型糖尿病(T2DM)患者、42例1型糖尿病(T1DM)患者及31例伴有糖尿病的
结果显示，HNF1A-MODY患者的平均生长素浓度为0.77±0.33 ng/ml，分别是T2DM组及T1DM组的2倍和1.5倍，与GCK-MODY组相比无显着差异(0.7±0.2ng/ml，P=0.32)。在多因素模型中，校正相关混杂因素后，HNF1A-MODY与T1DM之间仍存在显着差异（P<0.001）；HNF1A突变携带状态是与生长素水平相关的唯一独立变量。采用血清生长素对T1DM及HNF1A-MODY进行鉴别诊断的精度(以曲线下面积AUC表示)为0.74（95%CI：0.63~0.84，P<0.001），敏感性及特异性分别为74%和66.7%。校正年龄及BMI后，HNF1A-MODY与T2DM之间的生长素水平无显着差异(P=0.18)。
研究表明，与两种常见的多基因糖尿病相比，HNF1A-MODY患者的血清生长素水平更低。尽管因精度较低血清生长素无法作为HNF1A-MODY的独立筛查因素，但血清生长素可能是临床上鉴别诊断HNF1A-MODY和T1DM有价值的补充标志物。对T2MD患者而言，可能是由于T2MD和HNF1A-MODY的临床特征不同，导致研究中观察到的两组患者间生长素水平存在差异。
研究摘要：
| Assessment of serum ghrelin as a biomarker of HNF1A-MODY（血清生长素是HNF1A-MODY的生物标志物） |
| Background and aims: Ghrelin is a non-glycosylated hormone composed of 28 amino acids. It is present in the serum in two major molecular forms - desacyl and acylated ones. Ghrelin expression by the digestive tract epithelium is regulated by the hepatocyte nuclear factor 1A (HNF1A), a transcription factor whose mutations cause one of the forms of maturity onset diabetes of the young (MODY). As shown in an animal model, ghrelin expression is increased by approximately five-fold in homozygous HNF1A knock-out mice (Hnf-/-) as compared to a wild type. Furthermore, this is followed by its five-fold higher concentration in serum with a subsequent reduction in insulin secretion. The relationship between ghrelin and HNF1A gene mutations in humans has not yet been evaluated. In this study, we assessed ghrelin level in various forms of diabetes and evaluated it as a potential biomarker for HNF1A MODY. Materials and methods: We examined 47 diabetic HNF1A gene mutation carriers, 55 type 2 diabetes (T2DM) subjects, 42 type 1 diabetes (T1DM) patients and 31 glucokinase (GCK) gene mutation carriers with diabetes. Blood specimens for the ghrelin measurement were taken in the fasting state. Ghrelin was measured using a commercially available EIA kit with polyclonal antibodies against the C-terminal fragment of its both forms (total ghrelin). Samples were diluted prior the analysis. Comparisons of ghrelin concentrations were performed with the t-test and linear regression. Ghrelin concentration was used as a dependent variable and group, BMI, HbA1c, age at examination were covariates in the multiple analysis. To control the extent of degradation of the analyte, we also included length of storage, defined as the time between blood collection and assay determination, as a covariate. Results: Mean ghrelin concentration in HNF1A-MODY subjects was 0.77 ng/ml (SD=0.33 ng/ml). It was twofold higher than in T2DM group (0.39±1.6 ng/ml; p<0.001) and by 50% higher than in the T1DM group (0.49±0.19 ng/ml; p<0.001). No significant differences were found between HNF1A and GCK MODY (0.7±0.2 ng/ml; p=0.32). The difference between HNF1A-MODY and T1DM remained significant (p<0.001) after adjusting for the relevant confounders and HNF1A mutation carrier status was the only independent variable associated with ghrelin in the multivariate model. The discriminative accuracy as expressed by the area under the curve (AUC) of serum ghrelin between T1DM and HNF1A-MODY was 0.74 (95%CI: 0.63; 0.84; p<0.001) with the corresponding sensitivity and specificity of 74% and 66.7%. The difference between HNF1A-MODY and T2DM was not significant (p=0.18) after adjusting for age and BMI. Conclusion: Serum ghrelin level is lower in HNF1A-MODY than in both common polygenic forms of diabetes. It may be a valuable complementary marker for clinical differential diagnosis between HNF1A-MODY subjects and T1DM patients although, its discriminative accuracy is too low to allow use as a sole screening test. For T2DM, it appears that differences in clinical characteristics contributed to the observed difference against HNF1A-MODY in ghrelin levels. |
点击进入>>EASD2013年会专题
我要投稿
