[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

JP4516470B2 - Judgment method of abnormal glucose tolerance for collected blood - Google Patents

Judgment method of abnormal glucose tolerance for collected blood Download PDF

Info

Publication number
JP4516470B2
JP4516470B2 JP2005112648A JP2005112648A JP4516470B2 JP 4516470 B2 JP4516470 B2 JP 4516470B2 JP 2005112648 A JP2005112648 A JP 2005112648A JP 2005112648 A JP2005112648 A JP 2005112648A JP 4516470 B2 JP4516470 B2 JP 4516470B2
Authority
JP
Japan
Prior art keywords
blood
reference value
value
concentration
fasting
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2005112648A
Other languages
Japanese (ja)
Other versions
JP2006292521A (en
Inventor
金沢裕一
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nippon Kayaku Co Ltd
Original Assignee
Nippon Kayaku Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nippon Kayaku Co Ltd filed Critical Nippon Kayaku Co Ltd
Priority to JP2005112648A priority Critical patent/JP4516470B2/en
Publication of JP2006292521A publication Critical patent/JP2006292521A/en
Application granted granted Critical
Publication of JP4516470B2 publication Critical patent/JP4516470B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Description

本発明は、採取された血液中の空腹時血糖値ならびに血中1,5−アンヒドログルシトール濃度(血中1,5AG濃度)をそれぞれ測定し、その測定値と空腹時血糖値ならびに血中1,5AG濃度について設定される基準値との高低を確認して、採取された血液の耐糖能異常を判定する方法に関する。   The present invention measures the fasting blood glucose level and blood 1,5-anhydroglucitol concentration (blood 1,5AG concentration) in the collected blood, respectively, and the measured value, fasting blood glucose level and blood The present invention relates to a method for determining abnormal glucose tolerance of collected blood by confirming the level of a reference value set for medium 1,5AG concentration.

糖尿病は現代社会における代表的な生活習慣病であり、近年では、食生活の高栄養化や日常的な運動不足等から、その患者数は年々増加の一途をたどっている。日本における糖尿病の患者数は、2003年厚生労働省発表の「糖尿病実態調査」によると、糖尿病が強く疑われる人740万人(1998年の調査より+60万人)、可能性を否定できない人880万人(同、+190万人)で、総数1620万人(同、+250万人)に達する。   Diabetes mellitus is a typical lifestyle-related disease in modern society. In recent years, the number of patients has been increasing year by year due to high nutrition of diet and lack of daily exercise. According to the “Diabetes Survey” published by the Ministry of Health, Labor and Welfare in 2003, the number of diabetic patients in Japan is 7.4 million people who are strongly suspected of having diabetes (+600,000 people from the 1998 survey). People (+1.9 million), reaching a total of 16.2 million (+2.5 million).

糖尿病の治療は糖尿病診断時の新患教育が重要であるが、それと共に、糖尿病予備群ともいえる境界型と呼ばれる耐糖能異常を示す者あるいは境界型に準じたより軽度の血糖上昇を示す耐糖能異常(準境界型)を示す者を早期に発見(スクリーニング)し、これらに対して生活習慣を変える指導を行うことなどによって、糖尿病への進展を予防することも非常に重要である。境界型と呼ばれる耐糖能異常とは、糖尿病ではないが血糖状態が正常ではない軽度の耐糖能異常であって、空腹時血糖値と75g経口糖負荷試験(75gOGTT)2時間値の結果で判定される正常型あるいは糖尿病型のいずれにも属さず、それらの中間の状態にあるものと理解されている(非特許文献1)。また、75gOGTTの1時間値が180mg/dl以上であるものは、準境界型と呼ばれる耐糖能異常であり、これも糖尿病へと悪化する危険があると考えられている(非特許文献2)。ここで、耐糖能とは、血糖値を一定の幅の中にコントロールする、本来的にヒトに備わっている能力のことである。
これらの境界型あるいは準境界型耐糖能異常を発見、選別して、これを治療したり、あるいはそれ以上耐糖能の異常が進まないように処置したりするために、地域や職域において一般健診や糖尿病検診が実施されている。
For the treatment of diabetes, it is important to educate new patients at the time of diagnosis of diabetes, but at the same time, those who exhibit impaired glucose tolerance called borderline type, which can be said to be a pre-diabetes group, or glucose intolerance exhibiting milder blood glucose level according to the boundary type It is also very important to prevent the advancement of diabetes by discovering (screening) those who show (quasi-boundary type) at an early stage and providing guidance for changing their lifestyle. Glucose intolerance called borderline is mild glucose intolerance that is not diabetic but blood glucose is not normal, and is determined by the results of fasting blood glucose level and 2-hour value of 75 g oral glucose tolerance test (75 gOGTT). It is understood that it does not belong to any normal type or diabetic type, and is in an intermediate state between them (Non-patent Document 1). Moreover, the one-hour value of 75 gOGTT is 180 mg / dl or more is an abnormal glucose tolerance called a quasi-boundary type, which is also considered to have a risk of worsening to diabetes (Non-patent Document 2). Here, glucose tolerance is the ability inherently provided to humans to control blood glucose levels within a certain range.
In order to detect and select these boundary-type or quasi-boundary glucose tolerance abnormalities, treat them, or treat them so that abnormal glucose tolerance does not progress any further And diabetes screening.

従来これらの検診では、空腹時血糖値を指標とし、この値が一定の値、すなわち基準値を超えて高いか否かを確認することで耐糖能異常を判定する場合が多い。この基準値は、例えば日本糖尿病学会、米国National Diabetes Data Groupその他の機関によって、臨床学的に定められている、正常者と耐糖能異常者とを区別するための値であり、日本糖尿病学会の委員会報告「糖尿病の分類と診断基準に関する委員会報告」(1999年、糖尿病、第42巻、第5号、第385〜401頁)によれば、空腹時血糖値の基準値は110mg/dlとされている。
この空腹時血糖値の基準値を指標とした方法で耐糖能異常と判定される者は、被検診者全体に対して6〜8%といわれている。一方、40歳以上のヒト集団に対する詳細な検討及び各地で行われた75gOGTTを一次検査とする疫学調査から、糖尿病有病率は10%、境界型を含む軽度の耐糖能異常を加えると25%にのぼり(非特許文献2)、このことから検出された者の40%から半数近くは既に糖尿病と診断されるレベルにあるということになる。すなわち、空腹時血糖値とその基準値に基づく従来のスクリーニング方法では、保健指導すべき対象である軽度の耐糖能異常者が多く見逃されていることになる。
Conventionally, in these examinations, an abnormal glucose tolerance is often determined by using a fasting blood glucose level as an index and checking whether this value is higher than a certain value, that is, a reference value. This reference value is a value that is clinically determined by, for example, the Japan Diabetes Society, the National Diabetes Data Group, and other organizations to distinguish between normal and impaired glucose tolerance. According to the Committee Report “Committee Report on Diabetes Classification and Diagnosis Criteria” (1999, Diabetes, Vol. 42, No. 5, pp. 385-401), the fasting blood glucose reference value is 110 mg / dl. It is said that.
Those who are determined to have impaired glucose tolerance by the method using the fasting blood glucose level as an index are said to be 6 to 8% of the entire examinees. On the other hand, from a detailed study on the human population over 40 years old and an epidemiological study with 75gOGTT conducted as a primary test in various places, the prevalence of diabetes is 10%, and 25% when mild glucose intolerance including borderline is added. Nobori (Non-Patent Document 2), 40% to nearly half of those detected from this fact are already at the level of being diagnosed with diabetes. That is, in the conventional screening method based on fasting blood glucose level and its reference value, many people with mild glucose intolerance who are subjects for health guidance are overlooked.

また、慢性の高血糖状態を反映するために糖尿病の治療効果の指標として有用であるHbA1c濃度が、耐糖能異常のスクリーニングにおいても有効であろうと期待し、HbA1c値を耐糖能異常の検診における指標として使っている例もある。しかし、最近、その問題点の指摘がなされてきている(非特許文献3)。これは、HbA1c値の異常は耐糖能異常がある程度進んで糖尿病に至った状態でよく観察される、すなわち慢性の高血糖状態を反映する指標であるので、糖尿病治療における病態の変化を表す指標としてHbA1c値は非常に有用であるものの、75gOGTTにおいて軽度の耐糖能異常と判定される血液におけるHbA1cの平均値と正常な血液におけるその平均値との差はわずかであり、また、正常者と異常者の値の分布はかなりの部分でオーバーラップしており、検診における軽度の耐糖能異常を示す指標としては、HbA1c値は必ずしも十分ではないためである。事実、空腹時血糖値という指標にHbA1c値という指標を追加して検査を行っても、境界型や準境界型を含む軽度の耐糖能異常を検出する感度は、余り向上しない。このことは、75gOGTTの判定区分別にみたHbA1c値の分布において、正常型と境界型ではHbA1c値の差がほとんどないことからも判断される(非特許文献2)。   In addition, it is expected that the HbA1c concentration that is useful as an index of the therapeutic effect of diabetes in order to reflect a chronic hyperglycemia state will be effective in screening for impaired glucose tolerance, and the HbA1c value is an index for screening for impaired glucose tolerance. There is also an example that uses it. However, recently, the problem has been pointed out (Non-patent Document 3). This is because an abnormality in the HbA1c value is often observed in a state in which glucose tolerance abnormality has progressed to a certain degree and has led to diabetes, that is, an index reflecting a chronic hyperglycemia state. Although the HbA1c value is very useful, the difference between the average value of HbA1c in blood judged as mildly impaired glucose tolerance at 75 gOGTT and the average value in normal blood is slight, and normal and abnormal subjects This is because the HbA1c value is not necessarily sufficient as an index indicating a slight abnormality in glucose tolerance at the screening. In fact, even if the test is performed by adding an index called HbA1c value to the index called fasting blood glucose level, the sensitivity for detecting mild glucose intolerance including the boundary type and quasi-boundary type does not improve much. This is also judged from the fact that there is almost no difference in the HbA1c value between the normal type and the boundary type in the distribution of the HbA1c value according to the judgment category of 75 gOGTT (Non-patent Document 2).

日本糖尿病学会編、科学的根拠に基づく糖尿病診療ガイドライン、南江堂、2004年、6頁。Edited by Japan Diabetes Society, Guidelines for Diabetes Diagnosis Based on Scientific Basis, Nanedo, 2004, p. 6. 葛谷健、伊藤千賀子ら、糖尿病 42巻5号、1999年、385〜401頁。Ken Katsuraya, Chikako Ito et al., Diabetes 42, 5, 1999, 385-401. Medical Tribune, 2002年3月21日 p.35。Medical Tribune, March 21, 2002 p. 35.

上記したように、これまでの空腹時血糖値やHbA1c値の測定値とそれぞれの基準値との比較による判定では、耐糖能異常と判断された半数近くの患者が既に糖尿病と診断されるレベルにあり、血糖異常が一定以上進展した状態でないと耐糖能異常としてスクリーニングできないという問題がある。
その一方、軽度の耐糖能異常をより多くスクリーニングしようとして空腹時血糖値等の基準値を低くすれば、同時に正常者が異常と判定される偽陽性も増加してしまい、75gOGTTを行う必要のある者の数が増えて、被験者ならびに75gOGTTを実施する機関双方に対して負担を与える結果となりかねない。逆に、空腹時血糖等の基準値を徒に高くすれば、異常者が正常と判定される偽陰性が増えてしまい、血糖値検査本来の趣旨を没却することにもなる。
従って、境界型あるいは準境界型を含む軽度の耐糖能異常を示す血液を有する者を選択的に発見し、糖尿病や心血管合併症への進展を予防する措置を講じることができるようにするために、従来見逃されがちであった境界型や準境界型を含む軽度の耐糖能異常を示す血液を出来るだけ見逃しなく選別でき、かつ正常が耐糖能異常と判定されてしまう偽陽性を極力少なくできる、バランスのとれた検査方法が求められている。
As described above, in the determination by comparing the measured values of the fasting blood glucose level and the HbA1c value with the respective reference values, nearly half of the patients determined to have impaired glucose tolerance have already been diagnosed as having diabetes. In addition, there is a problem that screening for abnormal glucose tolerance is not possible unless the blood glucose abnormality has progressed beyond a certain level.
On the other hand, if the reference value such as fasting blood glucose level is lowered in order to screen more mild glucose intolerances, false positives at which normal persons are determined to be abnormal also increase, and 75 gOGTT needs to be performed. This could result in a burden on both the subject and the organization implementing the 75 g OGTT. On the other hand, if the reference value such as fasting blood glucose is increased, the number of false negatives in which the abnormal person is determined to be normal increases, and the original purpose of the blood glucose level test is lost.
Therefore, in order to be able to selectively find people with blood that shows mild glucose intolerance, including borderline or quasiboundary types, and to take measures to prevent progression to diabetes and cardiovascular complications In addition, blood that shows mild glucose intolerance, including boundary types and quasi-boundary types that have been often overlooked, can be selected as much as possible, and false positives in which normal is determined to be glucose intolerance can be minimized. A well-balanced inspection method is required.

本発明者は、前記したような問題点を解決すべく鋭意検討を重ねた結果、臨床検査において一般的に使用が認められている検査項目である空腹時血糖値ならびに血中1,5AG濃度に着目し、空腹時血糖値と血中1,5AG濃度の測定値が、それぞれの基準値とそれらに対して設定される一定の値との間にあるか否かを確認することにより、効率的かつ高感度に境界型ならびに準境界型を含む軽度の耐糖能異常を示す血液をスクリーニングすることができることを見出し、本発明を完成した。
即ち本発明は、採取された血液の空腹時血糖値ならびに血中1,5AG濃度を測定すること、空腹時血糖値ならびに血中1,5AG濃度の基準値を設定すること、空腹時血糖値の基準値の0.80〜0.90倍に相当する値として規定される低値基準値と血中1,5AG濃度の基準値の1.2〜1.5倍に相当する値として規定される高値基準値とをそれぞれ設定すること、及び測定された空腹時血糖値ならびに血中1,5AG濃度と、空腹時血糖値ならびに血中1,5AG濃度について設定した基準値、低値基準ならびに高値基準値との高低を確認することを含む、採取された血液の耐糖能異常を判定する方法に関する。
As a result of intensive studies to solve the above-mentioned problems, the present inventor has found that fasting blood glucose levels and blood 1,5AG concentrations, which are test items generally accepted in clinical tests, are used. Pay attention and check whether the fasting blood glucose level and the measured value of blood 1,5AG concentration are between the respective reference values and a fixed value set for them. In addition, the present inventors have found that blood showing mild glucose intolerance including boundary type and quasi-boundary type can be screened with high sensitivity, and the present invention has been completed.
That is, the present invention measures the fasting blood glucose level and blood 1,5AG concentration of the collected blood, sets the reference value of the fasting blood glucose level and blood 1,5AG concentration, It is defined as a low value reference value defined as a value corresponding to 0.80 to 0.90 times the reference value and a value corresponding to 1.2 to 1.5 times the reference value of 1,5AG concentration in blood. Setting high reference value respectively, and measured fasting blood glucose level and blood 1,5AG concentration, and reference value, low value reference and high value reference set for fasting blood glucose level and blood 1,5AG concentration The present invention relates to a method for determining abnormal glucose tolerance in collected blood, including confirming the level of the value.

本発明の方法は、耐糖能異常を示す血液の判定に関する偽陽性や偽陰性という誤判定を、従来の方法に比べて低くすることができる。また、境界型あるいは準境界型と呼ばれる耐糖能異常を含む軽度の耐糖能異常を示す血液を、従来の方法に比べ効率的に選別することが可能となる。この様にして発見された耐糖能異常を示す血液が採取された者に対して、運動療法や食事療法等による生活態度の改善やそれらを含めた治療を施すことにより、血糖の高値異常への進展、即ち糖尿病の罹患を防ぐことが可能となる。   The method of the present invention can reduce false positives such as false positives and false negatives relating to the determination of blood exhibiting abnormal glucose tolerance compared to conventional methods. In addition, it is possible to efficiently sort blood exhibiting mild glucose intolerance, including glucose intolerance called boundary type or quasi-boundary type, as compared with conventional methods. For those who have collected blood showing abnormal glucose tolerance discovered in this way, improvement of life attitudes by exercise therapy, diet therapy, etc. and treatment including them can be used to improve abnormal blood glucose levels. Progress, that is, prevention of diabetes can be prevented.

以下、本発明を詳細に説明する。   Hereinafter, the present invention will be described in detail.

本発明は、血中1,5AG(1,5-アンヒドログルシトール)濃度を、採取された血液の耐糖能異常、特に軽度の耐糖能異常の判定における指標のひとつとして利用する。1、5AGは、その化学構造がグルコースのそれに似たポリオールである。
ヒト体内における血液中の1、5AGは、腎尿細管の1,5AG/マンノース/フルクトース共輸送体により、そのほぼ99.9%が再吸収されている。そのため、血中1,5AG濃度の変化量はごくわずかで、正常な状態であれば検査時期に因らず血中1、5AG濃度はほとんど変化しないが、高血糖に伴う尿糖によって1,5AGの再吸収が競合阻害を受けることで1,5AGが尿中へ排出され、その結果、血中1,5AG濃度が低下することが知られている。
この様に、血中1,5AG濃度は、尿糖の影響を受けて増減すること、さらに血糖の近正常域(HbA1cで6〜8%のレベル)で大きな変動幅を有するために、他の血糖指標よりも正確で、検査時ないし検査直近の血糖状態とよい相関を有する客観的な血糖情報を提供する指標として、広く利用されている。
血中1,5AG濃度の測定それ自体は、広く知られた方法、例えば自動分析機用の市販試薬(例えばラナ1,5AGオートリキッド(商標))を用いて簡便に行うことができる。
In the present invention, the blood 1,5AG (1,5-anhydroglucitol) concentration is used as one of the indicators in the determination of abnormal glucose tolerance of the collected blood, particularly mild glucose tolerance. 1,5AG is a polyol whose chemical structure is similar to that of glucose.
Almost 99.9% of 1,5AG in blood in the human body is reabsorbed by the 1,5AG / mannose / fructose symporter of renal tubules. Therefore, the amount of change in the blood 1,5AG concentration is very small, and in the normal state, the blood 1,5AG concentration hardly changes regardless of the examination time, but urine sugar accompanying hyperglycemia causes 1,5AG to change. It is known that 1,5AG is excreted into the urine due to competitive inhibition of the reabsorption of blood, resulting in a decrease in the blood 1,5AG concentration.
In this way, the blood 1,5AG concentration increases or decreases under the influence of urine sugar, and has a large fluctuation range in the near normal range of blood glucose (6 to 8% level in HbA1c). It is widely used as an index that provides objective blood glucose information that is more accurate than the blood glucose index and has a good correlation with the blood glucose state at the time of or immediately after the test.
Measurement of the blood 1,5AG concentration itself can be easily performed using a widely known method, for example, a commercially available reagent for an automatic analyzer (for example, Rana 1,5AG Auto Liquid (trademark)).

本発明は、空腹時血糖値ならびに血中1,5AG濃度について、それぞれの基準値に加えて、各基準値に対する一定の値として設定される低値/高値基準値を利用して、耐糖能異常を判定する。
空腹時血糖値の基準値は、例えば日本糖尿病学会、米国National Diabetes Data Groupその他の機関によって臨床学的に定められている。日本糖尿病学会の委員会報告「糖尿病の分類と診断基準に関する委員会報告」(1999年、糖尿病、第42巻、第5号、第385〜401頁)によれば、空腹時血糖値の基準値は110mg/dlとされており、この基準値以上の空腹時血糖値を示す血液が耐糖能異常として判定されることとなっている。また、血中1,5AG濃度の現在の基準値は、男性、女性共通に14μg/mlとされており、この基準値未満の血中1,5AG濃度を示す血液が耐糖能異常とすることとなっている。
The present invention uses a low / high reference value set as a constant value for each reference value in addition to the respective reference values for fasting blood glucose level and blood 1,5AG concentration. Determine.
The reference value of fasting blood glucose level is clinically determined by, for example, the Japan Diabetes Society, the National Diabetes Data Group, and other institutions. According to the Committee Report of the Committee on Diabetes Classification and Diagnosis Criteria of the Diabetes Society of Japan (1999, Diabetes, Vol. 42, No. 5, pp. 385-401), reference values for fasting blood glucose levels Is 110 mg / dl, and blood that exhibits a fasting blood glucose level that is equal to or higher than this reference value is determined as abnormal glucose tolerance. In addition, the current standard value of blood 1,5AG concentration is 14 μg / ml for both men and women, and blood having a blood 1,5AG concentration lower than this standard value has abnormal glucose tolerance. It has become.

従来の方法は、耐糖能異常を示す血液の判定を、空腹時血糖値あるいは血中1,5AG値の測定値がそれぞれの基準値に対して高低(あるいは前後、上下、多少等)のいずれに位置するかで行なっていた。これに対して、本発明は、空腹時血糖値の基準値の0.80〜0.90倍の血糖値を低値基準値として、さらに血中1,5AG濃度の基準値の1.2〜1.5倍の濃度を高値基準値としてそれぞれ設定し、これらを耐糖能異常、特に軽度の耐糖能異常を示す血液の判定に利用するものである。
具体的には、空腹時血糖値ならびに血中1,5AG値の両測定値が、各基準値ならびにこれらに対して設定される低値/高値基準値に対して高低等のいずれに位置するかを確認することで、より詳しくは、測定された空腹時血糖値が低値基準値以上基準値未満でありかつ測定された血中1,5AG濃度が基準値以上高値基準値未満であることを確認することで、境界型や準境界型と呼ばれる軽度の耐糖能異常を示す血液を判定するものである。
According to the conventional method, blood that shows glucose intolerance is determined based on whether the fasting blood glucose level or the measured value of 1,5AG in the blood is high or low (or front / back, up / down, somewhat). It was done by positioning. On the other hand, the present invention sets the blood glucose level 0.80 to 0.90 times the reference value of fasting blood glucose level as a low level reference value, and further sets the blood 1,5AG concentration reference value 1.2 to The concentration of 1.5 times is set as the high reference value, and these are used for the determination of blood showing abnormal glucose tolerance, in particular, mild glucose tolerance.
Specifically, whether the measured values of fasting blood glucose level and blood 1,5AG level are higher or lower than each reference value and the low / high reference value set for them More specifically, it is confirmed that the measured fasting blood glucose level is not less than the low reference value and less than the reference value, and the measured blood 1,5AG concentration is not less than the reference value and less than the high value reference value. By checking, blood that shows mild glucose tolerance abnormality called boundary type or quasi-boundary type is determined.

以上の関係を、空腹時血糖値と血中1,5AG濃度の基準値、低値/高値基準値と耐糖能異常との関係においてグラフ化したものを、図1に示す。図1の縦軸は血中1,5AG濃度を、横軸は空腹時血糖値をそれぞれ示す。グラフのA1、A2は、それぞれ血中1,5AG濃度の基準値と高値基準値を示し、グラフのB1、B2は、それぞれ空腹時血糖値の基準値と低値基準値を示す。また曲線Cと曲線Dは、採取された血液中の血中1,5AG濃度と空腹時血糖値の個々の実際の測定値が概ねプロットされる領域の境を示す線である。   FIG. 1 is a graph showing the above relationship in terms of the relationship between the fasting blood glucose level and the reference value of blood 1,5AG concentration, and the relationship between the low / high reference value and abnormal glucose tolerance. The vertical axis in FIG. 1 indicates the blood 1,5AG concentration, and the horizontal axis indicates the fasting blood glucose level. A1 and A2 in the graph indicate a reference value and a high reference value for the blood 1,5AG concentration, respectively, and B1 and B2 in the graph indicate a reference value and a low reference value for the fasting blood glucose level, respectively. Curves C and D are lines indicating boundaries between regions in which individual actual measurement values of blood 1,5AG concentration and fasting blood glucose level in the collected blood are approximately plotted.

図中[I]を記した領域は、空腹時血糖と血中1,5AG濃度のいずれかまたは両方が異常値となっている領域であり、採取された血液の空腹時血糖値及び/又は血中1,5AG濃度の測定値がこの領域にプロットされるときは、その様な血液は耐糖能異常がある程度またはそれ以上進展した状態にある血液であると判定されることになる。この領域に属することとなる血液は、従来の方法、すなわち空腹時血糖値、血中1,5AG濃度のいずれか一方でもその基準値を超えたときに耐糖能異常と判定する方法でも、同様に耐糖能異常として判定される。   The region marked with [I] in the figure is a region where either or both of fasting blood glucose and blood 1,5AG concentration are abnormal values, and the fasting blood glucose level and / or blood of the collected blood When measured values of medium 1,5AG concentration are plotted in this region, it is determined that such blood is in a state where abnormal glucose tolerance has progressed to some extent or more. In the conventional method, that is, the method of determining that glucose tolerance is abnormal when any one of the fasting blood glucose level and the blood 1,5AG concentration exceeds the reference value, Determined as impaired glucose tolerance.

一方、図中の[II]の領域は、両指標がそれぞれ明らかな異常値であるとは言えないまでも、軽度の耐糖能異常の状態にある領域であり、採取された血液の空腹時血糖値及び血中1,5AG濃度の測定値がこの領域にプロットされるときは、その様な血液は少なくとも軽度の耐糖能異常を示す血液であると判定されることになる。   On the other hand, the region [II] in the figure is a region where mild glucose intolerance is present, although both indicators are not clearly abnormal values. When the value and the measured value of 1,5AG concentration in blood are plotted in this region, it is determined that such blood is blood exhibiting at least mild glucose intolerance.

本発明は、採取された血液の空腹時血糖値及び血中1,5AG濃度の測定値が図中[II]の領域にプロットされる血液を、耐糖能異常としてスクリーニング対象とする。このように本発明の方法では、空腹時血糖値と血中1,5AG濃度が両者ともに軽度異常値として図中[II]の領域にプロットされる血液を陽性(異常)と判定し、その結果、異常であるにもかかわらず正常と判定される偽陰性を減らして耐糖能異常を示す血液をスクリーニングする能力、即ちスクリーニング感度を上げることが出来る。
この様にして陽性と判定された血液を有する者については、さらに確認のため75gOGTT等の精密な検査を行ってもよく、必要に応じて生活指導や治療を行うことになる。
In the present invention, blood whose fasting blood glucose level and blood 1,5AG concentration measured in the collected blood are plotted in the region [II] in the figure is screened as an abnormal glucose tolerance. As described above, in the method of the present invention, the fasting blood glucose level and the blood 1,5AG concentration are both judged to be positive (abnormal) as the blood plotted in the region [II] in the figure as mildly abnormal values, and the result The ability to screen blood showing abnormal glucose tolerance by reducing false negatives that are judged to be normal despite being abnormal, that is, screening sensitivity can be increased.
For those who have blood determined to be positive in this way, a precise test such as 75 gOGTT may be performed for further confirmation, and life guidance and treatment will be performed as necessary.

なお、学術的な観点等から、先に述べた空腹時血糖値ならびに血中1,5AG濃度の各基準値は、その値の適否が見直される結果、それまでの値とは数値的に異なる新たな基準値に変更されることもあり得る。その場合には、かかる変更された新しい基準値に対して本発明で規定する割合に相当する血中濃度として、空腹時血糖値の低値基準値ならびに血中1,5AG濃度の高値基準値を設定すればよい。特に、空腹時血糖値の基準値が110mg/mlである場合、低値基準値として95mg/mlを設定することが好ましい。
また、空腹時血糖値ならびに血中1,5AG濃度の各基準値は、検体者の年齢や性別に応じて、それぞれ異なる値となることもあるが、この場合も、それぞれの特定の基準値に対して本発明で規定する割合に相当する血中濃度として、空腹時血糖値の低値基準値ならびに血中1,5AG濃度の高値基準値を設定すればよい。
特に本発明では、男性、女性共通に14μg/mlとして定められている血中1,5AG濃度の基準値に代わり、男性については14μg/ml、女性については10μg/mlをそれぞれ採用し、それぞれについて本発明で規定する割合に相当する高値基準値を、例えば男性については18μg/ml、女性については14μg/mlを設定して使用することが好ましい。この性別に応じた血中1,5AG濃度の基準値と高値基準値を利用することで、採取された血液の耐糖能異常の判定の精度を、より高めることができる。
From an academic point of view, the reference values for fasting blood glucose level and blood 1,5AG concentration described above are numerically different from the previous values as a result of reviewing the suitability of the values. The reference value may be changed. In that case, as the blood concentration corresponding to the ratio specified in the present invention with respect to the changed new reference value, the low reference value of the fasting blood glucose level and the high reference value of the blood 1,5AG concentration are used. You only have to set it. In particular, when the reference value of fasting blood glucose level is 110 mg / ml, it is preferable to set 95 mg / ml as the low value reference value.
In addition, each reference value for fasting blood glucose level and blood 1,5AG concentration may be different depending on the age and sex of the subject. On the other hand, as a blood concentration corresponding to the ratio defined in the present invention, a low reference value for fasting blood glucose level and a high reference value for blood 1,5AG concentration may be set.
In particular, the present invention adopts 14 μg / ml for men and 10 μg / ml for women instead of the standard value of blood 1,5AG concentration, which is determined as 14 μg / ml for both men and women. It is preferable to use a high reference value corresponding to the ratio defined in the present invention by setting, for example, 18 μg / ml for men and 14 μg / ml for women. By using the reference value and the high reference value of 1,5AG concentration in blood according to this gender, the accuracy of determination of abnormal glucose tolerance in the collected blood can be further increased.

以下に実施例により本発明を具体的に説明するが、本発明はこれに限定されるものではない。   EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto.

実施例1
12時間以上断食した被験者に対して通常の採血後処理を行った血液について、 空腹時血糖値ならびに血中1、5AG値を測定した。空腹時血糖値の基準値を110mg/dl、その低値基準値を95mg/dl(0.86倍)と設定し、また血中1,5AG濃度については、男性から採取された血液に対する基準値を14μg/ml、高値基準値を18μg/ml(1.29倍)、女性から採取された血液に対する基準値を10μg/ml、高値基準値を14μg/ml(1.4倍)とそれぞれ設定し、測定された値から耐糖能異常の有無を判定した。
その結果、空腹時血糖値が低値基準値以上基準値未満でありかつ血中1,5AG濃度が基準値以上高値基準値未満である血液、すなわち図1の[II]の領域にプロットされる血液14検体がスクリーニングされた。
このスクリーニングされた血液を採取した被験者に対して75gOGTTを実施して耐糖能異常を調べ、この試験による判定結果と本発明の方法による判定結果を比較したところ、本発明では軽度の耐糖能異常と判定されたが75gOGTT試験では正常型と判定された3例(×印のもの)を除き、本発明による方法と75gOGTTとで判定が一致したのは11例(糖尿病型と判定した検体を含む)であり、79%の一致率であった。以上の結果を表1に示す。
この結果は、本発明の方法による判定結果と75gOGTTの確定判定とが極めて高い確率で一致することを示すものである。また、本発明でスクリーニングされた検体は従来の基準値のみを用いた方法ではスクリーニングされないものであることから、本発明の方法は、耐糖能異常を補足するのに優れた方法である。
Example 1
About the blood which performed the normal blood-collecting process with respect to the test subject fasted for 12 hours or more, the fasting blood glucose level and the blood 1, 5AG value were measured. The fasting blood glucose level is set to 110 mg / dl, the low level is set to 95 mg / dl (0.86 times), and the blood 1,5AG concentration is the reference value for blood collected from men. Is 14 μg / ml, the high standard value is 18 μg / ml (1.29 times), the standard value for blood collected from women is 10 μg / ml, and the high standard value is 14 μg / ml (1.4 times). Then, the presence or absence of abnormal glucose tolerance was determined from the measured values.
As a result, blood whose fasting blood glucose level is not lower than the reference value and lower than the reference value and blood 1,5AG concentration is not lower than the reference value and lower than the reference value, that is, plotted in the region [II] in FIG. 14 blood samples were screened.
The subjects who collected the screened blood were subjected to 75 g OGTT to examine abnormal glucose tolerance, and the determination result by this test was compared with the determination result by the method of the present invention. Except for 3 cases (× marked) that were determined to be normal in the 75 gOGTT test, 11 cases (including specimens that were determined to be diabetic) matched with the method of the present invention and 75 gOGTT. The coincidence rate was 79%. The results are shown in Table 1.
This result shows that the determination result according to the method of the present invention and the final determination of 75 gOGTT agree with a very high probability. In addition, since the specimen screened by the present invention is not screened by the conventional method using only the reference value, the method of the present invention is an excellent method for supplementing abnormal glucose tolerance.

Figure 0004516470
Figure 0004516470

実施例2
本発明の判定方法を利用したマススクリーニングの例として、正常、軽度の耐糖能異常あるいは糖尿病と判定される検体を合わせたスクリーニング例を示す。12時間以上断食したある職域におけるボランティア(成人男性54名、成人女性41名の計95名、平均年齢34.7歳)から採取され、通常の採血後処理を行った血液について、空腹時血糖値ならびに血中1,5AG値を測定した。空腹時血糖値の基準値を110mg/dl、その低値基準値を95mg/dlと設定し、また血中1,5AG濃度については、男性の基準値を14μg/ml、高値基準値を18μg/ml、女性の基準値を10μg/ml、高値基準値を14μg/mlとそれぞれ設定した。測定された値から耐糖能異常の有無を判定し、軽度の耐糖能異常の検体と、空腹時血糖値が基準値以上または血中1,5AG濃度が基準値未満の検体とを合わせて選別した。耐糖能異常として選別された検体は15であった。
一方、同じボランティアに75gOGTTを実施して耐糖能異常を判定したところ、糖尿病を含む耐糖能異常は13名であり、正常は82名であった。
上記の空腹時血糖値と1,5AG濃度を用いる判定により選別された15検体のうち、75gOGTTで耐糖能異常と判定されたものの検体は11であった(耐糖能異常選出数)。また、上記の空腹時血糖値と1,5AG濃度を用いる判定により選別されずに正常と判定された検体は80であったが、このうち75gOGTTで正常と判定されたのは78であった(正常非選出数)。これらを感度(耐糖能異常選出数/13(75gOGTTによる耐糖能異常数)x100)、特異度(正常非選出数/82(75gOGTTによる正常数)x100)で表し、結果を表2−Aに示す。
Example 2
As an example of mass screening using the determination method of the present invention, a screening example in which specimens determined as normal, mild glucose intolerance or diabetes is shown. Fasting blood glucose levels of blood collected from volunteers in an occupational area that fasted for 12 hours or longer (54 adult men and 41 adult women for a total of 95 people, average age: 34.7 years old) In addition, blood 1,5AG values were measured. The fasting blood glucose level is set to 110 mg / dl, the low level is set to 95 mg / dl, and the blood 1,5AG concentration is set to 14 μg / ml for the male and 18 μg / ml for the high level. ml, the female reference value was set to 10 μg / ml, and the high value reference value was set to 14 μg / ml. Based on the measured value, the presence or absence of impaired glucose tolerance was determined, and a sample with mild glucose intolerance and a sample with a fasting blood glucose level above the reference value or a blood 1,5AG concentration below the reference value were selected. . Fifteen specimens were selected for abnormal glucose tolerance.
On the other hand, when 75 gOGTT was performed on the same volunteers to determine abnormal glucose tolerance, 13 abnormal glucose tolerance including diabetes and 82 normal.
Of the 15 specimens selected by the determination using the fasting blood glucose level and the 1,5AG concentration, 11 specimens were determined to have impaired glucose tolerance by 75 gOGTT (number of abnormally selected glucose tolerance). In addition, 80 specimens were determined to be normal without being selected by the determination using the fasting blood glucose level and the 1,5AG concentration, and of these, 78 were determined to be normal by 75 gOGTT (78 Normal unselected number). These are expressed by sensitivity (number of abnormal glucose tolerance selection / 13 (number of abnormal glucose tolerance by 75 gOGTT) × 100) and specificity (normal non-selection number / 82 (normal number by 75 gOGTT) × 100), and the results are shown in Table 2-A. .

さらに、同じ血液に対して空腹時血糖値のみを指標とし、その基準値を95μg/ml、100μg/ml、110μg/mlとそれぞれ定めた場合の判定結果を、表2−B−1〜3に示す。また、同じ血液に対して血中1,5AG濃度のみを指標とし、その基準値を18μg/ml、14μg/ml、10μg/mlとそれぞれ定めた場合の判定結果を、表2−C−1〜3に示す。さらに、男性から採取された血液に対する血中1,5AG濃度の基準値を18μg/mlとし、女性から採取された血液に対する血中1,5AG濃度の基準値を14μg/mlとそれぞれ設定して、血中1,5AG濃度のみを指標として判定した結果を表2−C−4に示す。また、本発明の方法において、男性から採取された血液に対する血中1,5AG濃度の基準値を14μg/mlとし、女性から採取された血液に対する血中1,5AG濃度の基準値を10μg/mlとそれぞれ設定して、血中1,5AG濃度のみを指標として判定した結果を、感度ならびに特異性と共に表2−C−5に示す。
また、同じ血液95例について、空腹時血糖と血中1,5AG濃度についてそれぞれ3種類の基準値を設定してこれらを互いに組み合わせ、空腹時血糖値が基準値以上かつ血中1、5AG濃度が基準値未満である血液、ならびに空腹時血糖値が基準値以上または血中1、5AG濃度が基準値未満である血液をいずれも耐糖能異常と判定した場合の結果を、感度ならびに特異性と共に表3−A−1〜表3−C−6に示す。
Furthermore, only the fasting blood glucose level for the same blood is used as an index, and the determination results when the reference values are set to 95 μg / ml, 100 μg / ml, and 110 μg / ml are shown in Tables 2-B-1 to 2-3. Show. In addition, the determination results when only the blood 1,5AG concentration is used as an index for the same blood and the reference values are set to 18 μg / ml, 14 μg / ml, and 10 μg / ml are shown in Table 2-C-1. 3 shows. Furthermore, the reference value of blood 1,5AG concentration for blood collected from men is set to 18 μg / ml, and the reference value of blood 1,5AG concentration for blood collected from women is set to 14 μg / ml, respectively. The results of determination using only blood 1,5AG concentration as an index are shown in Table 2-C-4. In the method of the present invention, the reference value of blood 1,5AG concentration for blood collected from men is set to 14 μg / ml, and the reference value of blood 1,5AG concentration for blood collected from women is set to 10 μg / ml. Table 2-C-5 shows the results of determination using only the blood 1,5AG concentration as an index together with sensitivity and specificity.
In addition, for 95 cases of the same blood, three kinds of reference values are set for fasting blood glucose and blood 1,5AG concentration, and these are combined with each other. The results of determining blood glucose levels below the reference value and blood whose fasting blood glucose level is higher than the reference value or blood whose blood 1 or 5AG concentration is lower than the reference value are abnormal glucose tolerance, together with sensitivity and specificity. It shows in 3-A-1 to Table 3-C-6.

表2−Aは、感度84.6%(耐糖能異常者13名中11名を選別)、特異度95.1%(正常者82名中78名選別)という結果を示しており、特異度を95%以上の高い値に保ちながら80%以上の感度を確保しており、両者がともに高いことが望ましいスクリーニング法であるが、空腹時血糖値や血中1,5AG濃度を単独の指標として判定した結果と比べて、良好なスクリーニング結果を与えた。
一方、血中1,5AG濃度の基準値を男性18μg/ml、女性14μg/mlとして、血中1,5AG濃度のみを指標としてスクリーニングした場合(表2−C−4)は、感度76.9%、特異度87.8%とバランスがとれた成績となってはいるが、本発明の方法による判定成績よりも、感度、特異度ともに7.3%低い結果となっている。また、その他の成績の中には、たとえば表2−B−2、表2−B−3、表2−C−3、表2−C−5のように、特異度において本発明による方法より高いものがあるが、感度においては最高でも表2−B−2、表2−C−5での61.5%と、本発明の方法での84.6%に比べ大幅に低くなっている。
Table 2-A shows the results of sensitivity 84.6% (selection of 11 out of 13 subjects with impaired glucose tolerance) and specificity of 95.1% (selection of 78 out of 82 normal subjects). Is a screening method that ensures a sensitivity of 80% or higher while maintaining a high value of 95% or higher, and it is desirable that both are high, but fasting blood glucose level and blood 1,5AG concentration as single indicators Compared with the judged result, a good screening result was given.
On the other hand, when the standard value of blood 1,5AG concentration is 18 μg / ml for men and 14 μg / ml for women, and screening is performed using only the blood 1,5AG concentration as an index (Table 2-C-4), the sensitivity is 76.9. % And specificity of 87.8%, but the sensitivity and specificity are 7.3% lower than the judgment result by the method of the present invention. In addition, among other results, for example, as shown in Table 2-B-2, Table 2-B-3, Table 2-C-3, Table 2-C-5, the method according to the present invention is more specific. Although there are high ones, the sensitivity is 61.5% in Table 2-B-2 and Table 2-C-5 at the maximum, which is much lower than 84.6% in the method of the present invention. .

空腹時血糖値が基準値以上かつ血中1、5AG濃度が基準値未満である血液、すなわち空腹時血糖値と血中1,5AG値の両者が同時に異常である血液をスクリーニング対象とするような組み合わせでは、全て特異度は高いが、感度が50%程度またはそれ以下の低い結果となっている。また空腹時血糖値又は血中1,5AG値のいずれかが異常である血液をスクリーニング対象とするような組み合わせの場合には、比較的バランスの取れた成績であるように見えるが、特異度が低く偽陰性を与えやすいという結果となった。これらの結果は、本発明の判定方法を利用したスクリーニングが優れていることを示している。   Blood whose fasting blood glucose level is higher than the reference value and blood 1,5AG concentration is lower than the reference value, that is, blood whose fasting blood glucose level and blood 1,5AG level are both abnormal simultaneously is targeted for screening In all combinations, the specificity is high, but the sensitivity is as low as about 50% or less. In addition, in the case of a combination in which blood whose fasting blood glucose level or blood 1,5AG level is abnormal is targeted for screening, it seems that the results are relatively balanced, but the specificity is The result was low and easy to give false negatives. These results indicate that screening using the determination method of the present invention is excellent.

Figure 0004516470

Figure 0004516470

Figure 0004516470


Figure 0004516470

Figure 0004516470

Figure 0004516470

Figure 0004516470

Figure 0004516470

Figure 0004516470


Figure 0004516470

Figure 0004516470

Figure 0004516470

図1は、空腹時血糖値の基準値とその低値基準値、血中1、5AG濃度の基準値とその高値基準値ならびにこれらと耐糖能異常との関係をグラフ化したものを示す。FIG. 1 is a graph showing a reference value of a fasting blood glucose level and a low reference value thereof, a reference value of a blood 1, 5AG concentration and a high reference value thereof, and a relationship between these and abnormal glucose tolerance.

Claims (3)

血中1,5−アンヒドログルシトール濃度の基準値及び空腹時血糖値の基準値を設定して、採取された血液の耐糖能異常を判定する方法において、採取された血液の空腹時血糖値ならびに血中1,5−アンヒドログルシトール濃度を測定すること、空腹時血糖値ならびに血中1,5−アンヒドログルシトール濃度の基準値を設定すること、更に、空腹時血糖値の基準値の0.80〜0.90倍に相当する値として規定される低値基準値と血中1,5−アンヒドログルシトール濃度の基準値の1.2〜1.5倍に相当する値として規定される高値基準値とをそれぞれ設定すること、そして、それぞれの測定値について、空腹時血糖値ならびに血中1,5−アンヒドログルシトール濃度についてそれぞれ設定した基準値との高低を確認すること、更に、測定された空腹時血糖値が低値基準値以上、基準値未満であり、かつ測定された血中1,5−アンヒドログルシトール濃度が基準値以上、高値基準値未満である場合に該当するかを確認し、該当する場合には、採取された血液を軽度の耐糖能異常と判定することを含む、採取された血液の耐糖能異常を判定する方法。 In a method of determining a glucose tolerance abnormality of a collected blood by setting a reference value of a blood 1,5-anhydroglucitol concentration and a reference value of a fasting blood glucose level, the fasting blood glucose of the collected blood Value and blood 1,5-anhydroglucitol concentration, setting fasting blood glucose level and reference value of blood 1,5-anhydroglucitol concentration , and fasting blood glucose level Low standard value defined as a value corresponding to 0.80 to 0.90 times the standard value of blood and 1.2 to 1.5 times the standard value of blood 1,5-anhydroglucitol concentration And setting a high reference value defined as a corresponding value, and for each measured value, a fasting blood glucose level and a reference value set for blood 1,5-anhydroglucitol concentration. Check the height, , The measured fasting glucose level is low the value reference value or more and less than the reference value, and the measured blood 1,5-anhydroglucitol concentration reference value or more, is less than high reference value A method for determining an abnormal glucose tolerance of collected blood, which includes determining whether the collected blood is mildly impaired glucose tolerance, if applicable . 男性から採取された血液ならびに女性から採取された血液それぞれに対して異なる血中1,5−アンヒドログルシトール濃度の基準値を使用する、請求項1に記載の方法。 2. The method of claim 1, wherein different blood 1,5-anhydroglucitol levels are used for blood collected from men and blood collected from women. 男性から採取された血液ならびに女性から採取された血液に対する血中1,5−アンヒドログルシトール濃度の基準値が、それぞれ14μg/mlならびに10μg/mlである、請求項に記載の方法。 The method according to claim 2 , wherein the reference values of blood 1,5-anhydroglucitol concentration for blood collected from men and blood collected from women are 14 μg / ml and 10 μg / ml, respectively.
JP2005112648A 2005-04-08 2005-04-08 Judgment method of abnormal glucose tolerance for collected blood Active JP4516470B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2005112648A JP4516470B2 (en) 2005-04-08 2005-04-08 Judgment method of abnormal glucose tolerance for collected blood

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2005112648A JP4516470B2 (en) 2005-04-08 2005-04-08 Judgment method of abnormal glucose tolerance for collected blood

Publications (2)

Publication Number Publication Date
JP2006292521A JP2006292521A (en) 2006-10-26
JP4516470B2 true JP4516470B2 (en) 2010-08-04

Family

ID=37413248

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2005112648A Active JP4516470B2 (en) 2005-04-08 2005-04-08 Judgment method of abnormal glucose tolerance for collected blood

Country Status (1)

Country Link
JP (1) JP4516470B2 (en)

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000135079A (en) * 1998-08-28 2000-05-16 Kdk Corp 1,5-anhydroglucitol dehydrogenase
JP2000300293A (en) * 1998-12-11 2000-10-31 Kyowa Medex Co Ltd Determination of 1,5-anhydroglucitol and deterioration reagent
JP2000316570A (en) * 1999-05-13 2000-11-21 Dai Ichi Pure Chem Co Ltd Gene encoding 1,5-anhydroglucitol dehydrogenase, recombinant vector containing the same gene, transformant containing the same recombinant vector, recombinant 1,5-anhydroglucitol dehydrogenase obtained from the same transformant
JP2002241298A (en) * 2001-02-15 2002-08-28 Nissei Marine Kogyo Kk Composition effective for reducing blood glucose

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000135079A (en) * 1998-08-28 2000-05-16 Kdk Corp 1,5-anhydroglucitol dehydrogenase
JP2000300293A (en) * 1998-12-11 2000-10-31 Kyowa Medex Co Ltd Determination of 1,5-anhydroglucitol and deterioration reagent
JP2000316570A (en) * 1999-05-13 2000-11-21 Dai Ichi Pure Chem Co Ltd Gene encoding 1,5-anhydroglucitol dehydrogenase, recombinant vector containing the same gene, transformant containing the same recombinant vector, recombinant 1,5-anhydroglucitol dehydrogenase obtained from the same transformant
JP2002241298A (en) * 2001-02-15 2002-08-28 Nissei Marine Kogyo Kk Composition effective for reducing blood glucose

Also Published As

Publication number Publication date
JP2006292521A (en) 2006-10-26

Similar Documents

Publication Publication Date Title
American Diabetes Association Screening for type 2 diabetes
Bates et al. A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis
Herman et al. Hemoglobin A
Ramachandran et al. Classification and diagnosis of diabetes
Jung et al. Visceral adiposity index and longitudinal risk of incident metabolic syndrome: Korean genome and epidemiology study (KoGES)
Klimkowicz-Mrowiec et al. Predictors of poststroke dementia: results of a hospital-based study in Poland
JP4516470B2 (en) Judgment method of abnormal glucose tolerance for collected blood
Herath et al. Use of HbA1c to diagnose type 2 diabetes mellitus among high risk Sri Lankan adults
Lapić et al. Haemoglobin A1c-based screening for prediabetes and diabetes mellitus: a multi-center study in Croatian adult population
Huang et al. Handgrip strength and cognitive performance in a multiethnic cohort in Singapore
US9470697B2 (en) Methods for detecting risk of fatal prostate cancer using serum calcium
Apollos et al. Performance evaluation of Veri-Q red haemoglobin meter for point-of-care haemoglobin and packed cell volume estimations
Çalışkan et al. The frequency of metabolic syndrome in women with polycystic ovaries at reproductive age and comparison of different diagnostic criteria for metabolic syndrome
Ejima et al. Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up
US20210293831A1 (en) Method of Performing Differential Diagnosis of Neurodegenerative Diseases in a Subject
Potisat et al. The relationship between microalbuminuria by using urine dipsticks and diabetic retinopathy in type 2 diabetes
Tyagi et al. Hemoglobin Levels Estimation using Aspen HB Meter
Somers et al. Screening for diabetes mellitus in learners residing in the Belhar, Delft and Mfuleni communities of Cape Town, Western Cape, South Africa
Al-Mahmood et al. The metabolic syndrome in normal weight Malay subjects
Lynn et al. Accuracy and the proper use of the point-of-care analysis in hemoglobin A1C measurement
US20220196682A1 (en) Catecholamine concentrations in a blood sample and arterial hypertension status in a subject for a differential diagnosis of neurodegenerative diseases including alzheimer's disease
Darraj et al. Comparison of Point of Care Hba1c Analytical Systems Against Laboratory Analysis Among Type 2 Diabetes Patients in Primary Health Centers in Riyadh
Steiner et al. The medical evaluation and risk estimation of end stage renal disease for living kidney donors
JP2024059214A (en) Screening method for borderline diabetic patient
Shaher et al. Prevalence of Hematuria among School Children in Shueub and Bani al-Harith in Sana'a city, Yemen

Legal Events

Date Code Title Description
A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20050517

A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20080215

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20100112

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20100209

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20100409

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20100511

A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20100514

R150 Certificate of patent or registration of utility model

Ref document number: 4516470

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

Free format text: JAPANESE INTERMEDIATE CODE: R150

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20130521

Year of fee payment: 3

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20160521

Year of fee payment: 6

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

S531 Written request for registration of change of domicile

Free format text: JAPANESE INTERMEDIATE CODE: R313531

R350 Written notification of registration of transfer

Free format text: JAPANESE INTERMEDIATE CODE: R350

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250