Jørgensen Lone G M, Brandslund Ivan, Hyltoft Petersen Per, Stahl Marta, de Fine Olivarius Niels
Department of Clinical Biochemistry, Vejle County Hospital, Vejle, Denmark.
Clin Chem Lab Med. 2004;42(7):817-23. doi: 10.1515/CCLM.2004.135.
Reference intervals are recommended for naturally occurring quantities and required in the evaluation of new components in order to provide clinically useful information. The aim of the present study is to present a method for selecting reference individuals for the determination of fasting venous plasma glucose (f-vPG) reference intervals and ways to determine if disease groups can share reference intervals with an ideal reference population. Reference subjects were randomly selected, eligibility was judged according to predetermined inclusion and exclusion criteria. Using the literature we selected risk indicators for diabetes mellitus (DM) and used these indicators to rule out high-risk individuals in order to obtain a reference distribution of f-vPG determined using individuals with low risk of DM. The distribution of f-vPG in the high-risk individuals was compared with that determined for the low-risk group. We then estimated the ability of the high-risk individuals to share the reference interval of the low-risk individuals, and calculated the fraction that was outside this interval. Distributions were also investigated for linearity in the cumulated frequency rankit distribution of In-values. The allowable difference between two reference limits could not exceed 0.375 times the population biological variation. Most risk indicators were powerful predictors of high f-vPG values. Subgroups with these risk indicators should not be included in the homogeneous In-normally distributed reference distribution. Distributions of f-vPG concentrations in individuals with risk factors were not homogeneous and varying percentages of individuals were outside the reference distribution, having f-vPG greater than 7.0 mmol/l. We conclude that randomisation is only useful to recruit candidate reference subjects. To rule out subjects according to clinical risk factors for diabetes, it is necessary to identify a reference population with low risk of exhibiting increased f-vPG concentrations. This method may be used to validate a reference interval for a particular analyte with respect to an investigated disease, and to stratify risk factors of importance.
对于自然存在的量，推荐使用参考区间，在评估新成分时则需要参考区间，以便提供临床有用信息。本研究的目的是提出一种选择参考个体的方法，用于确定空腹静脉血浆葡萄糖（f-vPG）参考区间，以及确定疾病组是否可以与理想参考人群共享参考区间的方法。参考对象是随机选择的，根据预先确定的纳入和排除标准判断其是否符合条件。我们利用文献选择了糖尿病（DM）的风险指标，并使用这些指标排除高危个体，以便获得使用DM低风险个体确定的f-vPG参考分布。将高危个体的f-vPG分布与低风险组确定的分布进行比较。然后，我们估计了高危个体共享低风险个体参考区间的能力，并计算了超出该区间的比例。还研究了In值累积频率概率分布的线性。两个参考限之间的允许差异不得超过总体生物学变异的0.375倍。大多数风险指标是高f-vPG值的有力预测指标。具有这些风险指标的亚组不应纳入均匀的In正态分布参考分布中。有风险因素个体的f-vPG浓度分布不均匀，不同百分比的个体超出参考分布，f-vPG大于7.0 mmol/l。我们得出结论，随机化仅有助于招募候选参考对象。为了根据糖尿病的临床风险因素排除对象，有必要确定f-vPG浓度升高风险较低的参考人群。该方法可用于验证特定分析物相对于所研究疾病的参考区间，并对重要的风险因素进行分层。
