Wybranska Iwona, Malczewska-Malec Malgorzata, Partyka Lukasz, Kiec-Wilk Beata, Kosno Katarzyna, Leszczynska-Golabek Iwona, Zdzienicka Anna, Gruca Anna, Kwasniak Malgorzata, Dembinska-Kiec Aldona
Department of Clinical Biochemistry, The Jagiellonian University, Medical College, Krakow, Poland.
Clin Chem Lab Med. 2007;45(9):1124-32. doi: 10.1515/CCLM.2007.142.
New tools to identify genotype-phenotype interactions need to be described and implemented. The aim of this study was to identify correlation between the risk originating from gene variation and diet-dependent development of insulin resistance.
Insulin output in terms of area under the curve after an oral glucose tolerance test (AUC Ins OGTT) and lipid tolerance tests (AUC Ins OLTT) were measured in 167 overweight/obese patients. Estimation of the 18 common gene polymorphisms for obesity risk and standard phenotyping were performed.
Insulin output (AUC Ins OGTT) correlated strongly between both insulin treatments across the whole group. However, within the genotype sub-groups, correlation was lower or did not exist. Using a nutrient-induced insulin output ratio (NIOR), calculated as AUC Ins OLTT/AUC Ins OGTT, values ranged from 0.42 to 5.83 and correlated significantly with body mass index (BMI) and leptin, but not with age, gender, waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) or plasma adiponectin. High NIOR was found in a subgroup of carriers of rare allelic variants of genes characteristic for poorer tolerance to lipids in the diet. Low NIOR values were found within a sub-group with rare genetic variants regulating carbohydrate metabolism. Thus, the new insulin index NIOR may distinguish gene variant carriers into groups of glucose- or lipid-sensitive phenotypes.
We suggest that the OLTT/OGTT insulin output ratio (NIOR) may be predictive for identifying individuals who are phenotypically susceptible to insulin resistance in response to high fat or carbohydrate in their habitual diet.
需要描述并应用新工具来识别基因型与表型的相互作用。本研究旨在确定基因变异产生的风险与饮食依赖型胰岛素抵抗发展之间的相关性。
对167名超重/肥胖患者进行口服葡萄糖耐量试验（AUC Ins OGTT）和脂质耐量试验（AUC Ins OLTT）后，测量曲线下面积表示的胰岛素分泌量。对18种常见的肥胖风险基因多态性进行评估并进行标准表型分析。
在整个研究组中，两种胰岛素治疗方式下的胰岛素分泌量（AUC Ins OGTT）相关性很强。然而，在基因型亚组中，相关性较低或不存在。使用营养诱导胰岛素分泌比值（NIOR），即AUC Ins OLTT/AUC Ins OGTT计算得出，其值范围为0.42至5.83，与体重指数（BMI）和瘦素显著相关，但与年龄、性别、腰臀比（WHR）、胰岛素抵抗稳态模型评估（HOMA-IR）或血浆脂联素无关。在饮食中对脂质耐受性较差的特征性基因罕见等位基因变体携带者亚组中发现了高NIOR值。在具有调节碳水化合物代谢的罕见基因变体的亚组中发现了低NIOR值。因此，新的胰岛素指数NIOR可能将基因变体携带者区分为对葡萄糖或脂质敏感的表型组。
我们认为，OLTT/OGTT胰岛素分泌比值（NIOR）可能有助于预测那些在日常饮食中对高脂肪或高碳水化合物有表型易感性的胰岛素抵抗个体。
