研究顯示:血糖短期波動迅速影響糖化血紅蛋白A1c水平

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1980年的研究揭示,糖化血紅蛋白A1c的濃度在血糖短期變化下迅速變化。無論是體外還是體內,血糖濃度的快速變化都會引起A1c濃度的顯著增減。這一發現對於糖尿病患者日常生活中的血糖控制與監測具有重要意義,強調了低血糖環境下血液樣本處理的重要性。

Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentration

短期血糖濃度變化引起的色譜法測定糖化血紅蛋白 A1c 的快速變化

Svendsen PA, Christiansen JS, Søegaard U, Welinder BS, Nerup J. Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentration. Diabetologia. 1980;19(2):130-136. doi:10.1007/BF00421859

https://pubmed.ncbi.nlm.nih.gov/7418966/

Abstract

Chromatographically determined haemoglobin A1c concentration was measured during short-term (1–24 h) changes in glucose concentration in vitro and in vivo. In vitro at 37 °C the HbA1c concentration increased with glucose concentration and time both in normal and diabetic erythrocytes. In normal erythrocytes incubated in 20–100 mmol/l glucose, the increases in the HbA1c concentration were maximal after 4–6 h and then stable for the next 18–20 h. During the first hour, increases in the HbA1c concentration were linear with time and on average 0.034% HbA1c × h−1 × mmol/l glucose−1. In erythrocytes, after a rapidly produced increase (2h), HbA1c decreased to preincubation concentrations during a further incubation of the erythrocytes in a glucose-free medium at 37 °C for 4–6 h. The mean rate of linear decrease was 0.017% × h−1 × mmol/l glucose−1. After incubation of erythrocytes in 100 mmol/l glucose for 24 h, 1.3% HbA1c remained stable for 6 h in saline. The rapid increase in HbA1c concentration, as determined by chromatography, was not due to stable HbA1c (ketoamine linked glucose) as no increase was found in the HbA1c concentrations determined by the thiobarbiturate method. In juvenile diabetics controlled by an artificial beta-cell, rapid changes of blood glucose concentration (up to 20 mmol/l) resulted in increases in HbA1c concentration of as much as 1.9% within 12 h (mean 1.1%). Rapid in vivo increases in HbA1c concentration were reversible by normalization of the blood glucose concentration. That rapid changes in HbA1c may occur in daily diabetic life was evidenced by differences in HbA1c concentration between blood samples from out-patient diabetics incubated in saline for 16 hours at 4 °C and 37 °C (range of differences 0.2–1.4% HbA1c). The differences correlated to the blood glucose concentration at the time of sampling blood for HbA1c determination. Thus, incubation of blood at a low glucose concentration prior to determination of the glycosylated haemoglobin concentration may overcome interference from rapidly produced HbA1c.

摘要

透過色譜法測定的糖化血紅蛋白 A1c 濃度在體內外短期(1-24 小時)血糖濃度變化期間進行測量。體外在 37°C 下,HbA1c 濃度隨著血糖濃度和時間的增加而增加,無論是在正常還是糖尿病紅血球中。在 20-100 mmol/l 葡萄糖中孵育的正常紅血球中,HbA1c 濃度的增加在 4-6 小時後達到最大值,然後在接下來的 18-20 小時內保持穩定。在第一小時內,HbA1c 濃度隨時間呈線性增加,平均為 0.034% HbA1c × 小時−1 × mmol/l 葡萄糖−1。在紅血球中,經過快速增加(2 小時)後,HbA1c 在將紅血球在無葡萄糖介質中於 37°C 再孵育 4-6 小時期間,降至預孵育濃度。線性減少的平均速率為 0.017% × 小時−1 × mmol/l 葡萄糖−1。在 100 mmol/l 葡萄糖中孵育紅血球 24 小時後,1.3% HbA1c 在鹽水中穩定 6 小時。色譜法測定的 HbA1c 濃度的快速增加不是由於穩定的 HbA1c(酮胺鏈接的葡萄糖),因為使用硫代巴比妥酸方法測定的 HbA1c 濃度未發現增加。在由人工胰腺控制的青少年糖尿病患者中,血糖濃度的快速變化(達 20 mmol/l)在 12 小時內導致 HbA1c 濃度增加高達 1.9%(平均 1.1%)。HbA1c 濃度的快速體內增加可通過血糖濃度的正常化逆轉。日常糖尿病生活中 HbA1c 的快速變化證據來自於門診糖尿病患者在 4°C 和 37°C 下鹽水中孵育 16 小時的血樣中 HbA1c 濃度的差異(HbA1c 差異範圍 0.2-1.4%)。這些差異與抽血進行 HbA1c 測定時的血糖濃度相關。因此,在測定糖化血紅蛋白濃度之前將血液在低葡萄糖濃度下孵育,可能克服快速產生的 HbA1c 的干擾。

參考文獻

  1. Bunn HF, Haney DN, Kamin S, Gabbay KH, Gallop PM (1976) The biosynthesis of human hemoglobin A1c. J Clin Invest 57: 1652–1659

    Google Scholar 

  2. Stevens VJ, Vlassara H, Abati A, Cerami A (1977) Nonenzymatic glycosylation of hemoglobin. J Biol Chem 252 2998–3002

    Google Scholar 

  3. Bunn HF, Shapiro R, McManus M, Garrick L, McDonald MJ, Gallop PM, Gabbay KH (1979) Structural heterogeneity of human hemoglobin A due to nonenzymatic glycosylation. J Biol Chem 254: 3892–3898

    Google Scholar 

  4. Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976) Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus. N Engl J Med 295: 417–420

    Google Scholar 

  5. Gonen B, Rochman H, Rubenstein AH, Tanega SP, Horwitz DL (1977) Haemoglobin Al: an indicator of the metabolic control of diabetic patients. Lancet II: 734–736

    Google Scholar 

  6. Gabbay KH, Hasty K, Breslow JL, Ellison RC, Bunn HF, Gallop PM (1977) Glycosylated hemoglobins and long-term blood glucose control in diabetes mellitus. J Clin Endocrinol Metab 44: 859–864

    Google Scholar 

  7. Svendsen PAa, Christiansen JS, Welinder B, Nerup J (1979) Fast glycosylation of haemoglobin. Letter to the editor. Lancet I: 603

    Google Scholar 

  8. Svendsen PAa, Christiansen JS, Andersen AR, Welinder B, Nerup J (1979) Fast glycosylation of haemoglobin. Letter to the editor. Lancet I: 1142–1143

    Google Scholar 

  9. Trivelli LA, Ranney HM, Lai H-T (1971) Hemoglobin components in patients with diabetes mellitus. N Engl J Med 284: 353–357

    Google Scholar 

  10. McDonald MJ, Shapiro R, Bleichman M, Solway J, Bunn HF (1978) Glycosylated minor components of human adult hemoglobin. J Biol Chem 253: 2327–2332

    Google Scholar 

  11. Trinder P (1969) Determination of glucose in blood using glucose with an alternative oxygen receptor. Ann Clin Biochem 6: 24–27

    Google Scholar 

  12. Gabbay KH, Sosenko JA, Banuchi GA, Mininsohn MJ, Flückinger R (1979) Glycosylated hemoglobins: Increased glycosylation of hemoglobin A in diabetic patients. Diabetes 28: 337–340

    Google Scholar 

  13. Natvig H (1956) Nye høide-vekttabeller for norske kvinner og menn. Landsforeningen for Kosthold og Helse, Oslo

    Google Scholar 

  14. Christiansen JS, Svendsen PAa, Winther K, Mathiesen E, Deckert T (in press) Optimization of constants used in the algorithms of an artificial betacell (Biostator(R)). Acta Diabetol Lat

  15. Dolhofer R, Städele A, Wieland OH (1977) Clinical and biochemical studies on the significance and formation of hemoglobins A1c and A1a+b in diabetes mellitus. Klin Wochenschr 55: 945–954

    Google Scholar 

  16. Cole RA, Soeldner JS, Dunn PJ, Bunn HF (1978) A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography. Metabolism 27: 289–301

    Google Scholar 

  17. Graf RJ, Halter JB, Porte D (1978) Glycosylated hemoglobin in normal subjects and subjects with maturity-onset diabetes. Diabetes 27: 834–839

    Google Scholar 

  18. Davis JE, McDonald JM, Jarett L (1978) A high-performance liquid chromatography method for hemoglobin A1c. Diabetes 27: 102–106

    Google Scholar 

  19. Dunn PJ, Soeldner JS, Wacks M (1978) Measurement of glycosylated haemoglobins. Letter to the editor. Lancet II: 838

    Google Scholar 

  20. Bunn HF, Haney DN, Gabbay KH, Gallop PM (1975) Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun 67: 103–109

    Google Scholar 

  21. Koenig RJ, Blobstein SH, Cerami A (1977) Structure of carbohydrate of hemoglobin A1c. J Biol Chem 252: 2992–2997

    Google Scholar 

  22. Spicer KM, Allen RC, Hallett D, Buse MG (1979) Synthesis of hemoglobin A1c and related minor hemoglobins by erythrocytes. J Clin Invest 64: 40–48

    Google Scholar 

  23. Flückiger R, Winterhalter KH (1976) In vitro synthesis of hemoglobin A1c. FEBS Lett 71: 356–360

    Google Scholar 

  24. Bunn HF, Shapiro R, McDonald M, Haney DN (1977) The interaction of glucose with hemoglobin. In: Les Colloques de l’Institut National de la Santé et de la Recherche Médicale: Interactions moléculaires de l’hémoglobine. INSERM 70: 299–308

    Google Scholar 

  25. Karamanos B, Cristacopoulos P, Zachariou N, Korkolis S (1977) Rapid changes of the haemoglobin A1c fraction following alterations of diabetic control (abstr). Diabetologia 13: 406

    Google Scholar 

  26. Bolli G, Cartechini MG, Compagnucci P, Santeusanio F, Massi-Benedetti M, Calabrese G, Puxeddu A, Brunetti P (1980) Modification of glycosylated haemoglobin concentration during artificial endocrine pancreas treatment of diabetics. Diabetologia 18: 125–130

    Google Scholar 

  27. Leslie RDG, Pyke DA, John PN, White JM (1979) Fast glycosylation of haemoglobin. Letter to the editor. Lancet I: 773–774

    Google Scholar