- Email: [email protected]
Biological diagnosis of diabetes mellitus
G Model
PATBIO-3204; No. of Pages 4 Pathologie Biologie xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Review
Biological diagnosis of diabetes mellitus Diagnostic biologique du diabe`te sucre´ M. Zendjabil Laboratoire de biochimie, E´tablissement Hospitalier Universitaire d’Oran 1er Novembre 1954, BP No. 4166, Ibn Rochd, Oran, Algeria
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 July 2015 Accepted 7 October 2015 Available online xxx
Diabetes mellitus is a common disease whose complications are severe. For decades, the diagnosis of diabetes and prediabetes was using only fasting glucose or glucose two hours during an oral glucose tolerance test. Recently, it is possible to use HbA1c. Each of these tests has advantages and limitations that must be well known by clinicians for better care for patients. So they could use one, two or three of this tests to reach to a proper diagnosis. The aim of this article is about the strong and weak points of these tests. ß 2015 Elsevier Masson SAS. All rights reserved.
Keywords: Diabetes mellitus Diagnosis OGTT HbA1c
R E´ S U M E´
Mots cle´s : Diabe`te sucre´ Diagnostic HGPO HbA1c
Le diabe`te sucre´ est une maladie fre´quente dont les complications sont graves. Pendant des de´cennies, le diagnostic du diabe`te et du pre´diabe`te faisait uniquement appel a` la glyce´mie a` jeun ou la glyce´mie deux heures apre`s une e´preuve de glyce´mie provoque´e par voie orale. Depuis peu, il est possible d’utiliser l’HbA1c. Chacun de ces tests a des avantages et des limites qui doivent eˆtre bien connus par les cliniciens pour une meilleure prise en charge des patients. Donc, ils pourraient utiliser un, deux ou trois de ces tests pour arriver a` un bon diagnostic. Le but de cet article est de traiter les points forts et les inconve´nients de ces tests. ß 2015 Elsevier Masson SAS. Tous droits re´serve´s.
1. Introduction Diabetes mellitus is a very common disease with deadly complications. The number of diabetics patients in 2013 was 382 million and it is expected to increase to reach 592 million in 2035 [1]. Diabetes mellitus often goes unnoticed and the average lag between onset and diagnosis is 7 years [2]. In the United States of America, approximately 30% of diabetics or 6,2 million people are underdiagnosed [3]. The definition of diabetes is mainly biological view and has changed throughout the years, especially with the recent introduction of HbA1c. The aim of this article is about the strong and weak points of the tests used to diagnose this disease.
2. Fasting plasma glucose (FPG) Diabetes mellitus is defined according to American Diabetes Association (ADA) and World Health Organization (WHO) by a E-mail address: [email protected]
concentration of FPG higher than 126 mg/dl twice or a blood glucose above 200 mg/dl at any time of day [4,5]. The threshold of 126 mg/dl was chosen because it is from this level that the risk of microvascular complications, including diabetic retinopathy, becomes important. Three epidemiological studies have contributed to establish this threshold. However, these studies had a strong bias: research retinopathy was made in an incomplete and imprecise manner. New research has shown that the threshold value of 126 mg/dl had a sensitivity of less than 40% and a specificity of between 81 and 96% for the detection of diabetic retinopathy. So there appears to be no threshold value for evaluating the presence of this complication [6]. Glucose can be measured in serum, plasma or blood. Plasma values are 11–13% higher than the measured blood glucose in the case of a normal hematocrit, this is due to the difference of the amount of water between erythrocytes and plasma [7]. The glucose assay must be done in laboratory. Point of care tests (POCT) glucometers are very useful for monitoring diabetes mellitus, but should not be used for the diagnosis due to both insufficient precision and accuracy and the inherent, sample-dependent flaw
http://dx.doi.org/10.1016/j.patbio.2015.10.002 0369-8114/ß 2015 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Zendjabil M. Biological diagnosis of diabetes mellitus. Pathol Biol (Paris) (2015), http://dx.doi.org/ 10.1016/j.patbio.2015.10.002
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of results [8]. However, some authors suggest otherwise, arguing that POCT instruments have sufficient accuracy to be used as diagnostic tools for diabetes [9].
3. Oral glucose tolerance test (OGTT) This is the most known dynamic test in diabetology, which has been widely used. This test is to administer in less than 5 mins, 250 ml of water with a glucose load of 75 g for adults and 1.75 g/kg body weight for children. Then, blood glucose dosage is carried out at different times. Standardization was established for reducing the importance of variation coefficients for different glucose concentrations determined during the test. Thus, we should take into consideration only the FPG and blood glucose 2 h after an OGTT (2-h PG) [10] and it is no longer necessary to extend this test to 3 or 5 h. If positive, it is necessary to repeat the test to confirm the result; this is not always respected in practice because of various constraints imposed by the test. Depending on the value of 2-h PG after the load, patients are classified into normal subjects for levels below 140 mg/dl, subjects with impaired glucose tolerance (IGT) when values are between 140–199 mg/dl and diabetics when blood glucose exceeds 200 mg/dl. This test was first described in 1922 and was designed to assess the ability to tolerate a glucose load. It was only in 1979 that the National Diabetes Data Group has recommended its use for the diagnosis of diabetes mellitus, followed by the WHO a few years later. In 1997, a group of experts recommend not to use this test primarily for the diagnosis of diabetes [11]. The ADA had probably the wish that this test becomes obsolete because it has a low reproducibility; it is expensive, long and mobilizes the staff for significant period. By issuing these recommendations, the ADA hoped to attract more patients to be screened, diagnosed and treated with simple measurement of FPG. The OGTT is indicated when the FPG value is between 110– 126 mg/dl without a metabolic syndrome, if the FPG is normal in presence of glycosuria or when FPG is normal while the PPG is between 140–200 mg/dl. However, OGTT should not be used in certain situations: when FPG and lipid levels are normal, if the patient’s age is above 70 years because the result does not influence the therapeutic management. It was also demonstrated that the OGTT was not of interest when FPG level is greater than 126 mg/dl, because this value is equivalent to 2-h PG higher than 200 mg/dl, in the risk of development of diabetic retinopathy [12]. Although the OGTT is decried in favor of FPG, it has been widely used in clinical and epidemiological research studies and it is still considered as ‘‘the gold standard’’. It also keeps an important place in clinical practice, in particular for the early detection of IGT for which it has better sensitivity than FPG. Determining parameters other than glucose such as insulin and C-peptide during the test allows for calculation of indices reflecting insulin secretion and insulin resistance are used in the field of research [13]. In a study including 406 subjects with prediabetes, many indices were studied and it was found that high levels of glucose and a low concentration of C-peptide at 30 mins after OGTT may be a good predicator for diabetes conversion [14]. The OGTT is particularly useful in the diagnosis of gestational diabetes (GD) that may be accompanied by some perinatal complications. Thus, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study which included over 25,000 women showed a continuum between blood glucose levels in pregnant women and the risk of perinatal complications such as fetal hyperinsulinemia, macrosomia, neonatal hypoglycemia and cesarean [15]. The use of OGTT to search for GD was the subject of many controversies including the best time to conduct the test, the glucose load to administer 75 or 100 g, and the thresholds to be
considered as pathological. Due to an international consensus of International Association of Diabetes in Pregnancy Study Group (IADPSG) [16], responses have been made to these questions. Thus, the OGTT should be performed between 24 and 28 weeks of gestation with a glucose load of 75 g. The thresholds of blood glucose values are 92 mg/dl for the FPG, 180 mg/dl after 1 h and 153 mg/dl after 2 h [17,18]. These recommendations tend to increase GD’s prevalence [19] (from 5–10% to 15–20%). In two randomized controlled trials, 80 to 90% of women with mild GD diagnosed by this strategy could be managed with life-style therapy only. Other well-designed clinical studies are required to determine the best way to detect and treat women with GD, diagnosed according to the IADPSG recommendations [20]. The determination of postprandial blood glucose (PPG) involves measuring blood glucose 1 h or 2 h after a meal. Normal values of PPG are less than 140 mg/dl. The value of PPG depends on many factors such as the nature of the meal, various gastrointestinal and pancreatic hormones, or the rate at which gastric emptying is carried out. PPG appears to be an independent minor cardiovascular risk factor, but when it is combined with other risk factors such as high cholesterol, high blood pressure or smoking; the risk is significantly increased; which could explain the high prevalence of cardiovascular morbidity and mortality in diabetic patients, particularly in type 2 diabetes [21]. The multicenter European study DECODE showed that the risk of cardiovascular morbidity and mortality is more correlated with postprandial hyperglycemia during an OGTT than FPG [22]. The PPG has been recognized as an independent cardiovascular risk factor in several other metaanalyzes [23,24], but the relationship between GPP and microvascular risk remains to our knowledge little studied. Further studies report a reduction in cardiovascular events in patients treated with drugs reducing PPG like acarbose [25,26]. Postprandial hyperglycemia is therefore an interesting therapeutic target, particularly when the HbA1c is close to the aim.
4. Glycohemoglobin HbA1c HbA1c is defined by the slow and irreversible binding of glucose to the N-terminal valine of one or both of the beta chains of hemoglobin. It reflects glycemic control of two or three months [27]. HbA1c was discovered in the 1960s. The first demonstration of this marker increase in diabetes was made by Trivelli et al. in 1971 [28]. In 1986, the NGSP (National Glycohemoglobin Standardization Program) has established a reference method using HPLC (High Performance Liquid Chromatography) based on the DCCT (Diabetes Control and Complications Trial) and UKPDS (United Kingdom Prospective Diabetes Study) studies that showed a significant correlation between HbA1c and the risk of occurrence of complications in diabetic patients [29]. The IFCC has proposed in 2002 a reference technique using HPLC coupled with capillary electrophoresis (HPLC-CE) or mass spectrometry (HPLC-MS) and has defined the N-terminal hexapeptide of the standard to use [30]. Several consensuses have been established in the late of 2000s that is allowed to standardize the A1 C test [31,32]. It was also decided that the results provided by the laboratories must now be expressed in two units: mmol/mol (IFCC) and % (NGSP), with a master equation linking the two expression systems. For decades, the diagnosis of diabetes was based only on FPG or 2-h PG after an OGTT. The use of HbA1c as a diagnostic tool was suggested in the 1970s and early 1980s but with an adaptation of the values for pregnant women and elderly [33]. Eventually in 2009, a committee of experts supported by the ADA and EASD (European Association for the Study of Diabetes) proposed HbA1c as a diagnostic marker [34]. This decision was followed by the WHO in 2011 [35]. The chosen criteria are: HbA1c 48 mmol/mol
Please cite this article in press as: Zendjabil M. Biological diagnosis of diabetes mellitus. Pathol Biol (Paris) (2015), http://dx.doi.org/ 10.1016/j.patbio.2015.10.002
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( 6, 5%) twice or HbA1c 48 mmol/mol one time with FPG higher than or equal to 200 mg/dl. Like for FPG, the threshold of 48 mmol/ mol was selected based on the risk of developing diabetic retinopathy and like FPG, there seems to be no threshold value for evaluating the presence of this complication. An HbA1c between 38 and 46 mmol/mol (5, 7 and 6, 4%) is used to diagnose impaired fasting glucose (IFG). In clinical practice, HbA1c remained mostly used as a reference biologic parameter in monitoring diabetic patients but is rarely used in the diagnosis of diabetes mellitus. In the laboratory of biochemistry at the University Hospital Establishment of Oran in Algeria, 172 prescriptions has been analyzed during the period from 01/01/2014 to 30/06/2014, only 8, 14% of these exams were for diagnostic purposes (personal data). The HbA1c has a number of advantages compared to glucose’s determination. The advantage of HbA1c is to integrate both fasting blood glucose and to use PPG on them [36]. In addition, fasting is not required for HbA1c’s determination. Significant errors can occur in the determination of glucose levels in blood due to preanalytical factors. Blood glucose may be underestimated if the assay is not performed quickly after collection. Indeed, there is a glycolysis in vitro which can be reduced by using antiglycolytics such as sodium fluoride or monoiodoacetate. In absence of antiglycolytics, the average drop in blood glucose is around 7.26 mg/dl/h [37]. HbA1c has limitations that make it lose its interest in some cases. Indeed, any qualitative or quantitative anomaly concerning the hemoglobin as a transfusion, anemia or a hemoglobinopathy can be a source of interference [27]. A study that compares the impact of the most frequent hemoglobinopathies on three field methods to the HPLC-MS reference method, showed no influence on the interpretation of results [38]. However, we must always interpret HbA1c’s results with caution in presence of hemoglobin variants. Chronic kidney failure can skew the results in two ways: it causes anemia by reducing lifespan of red blood cells and by formation of carbamylated hemoglobin, favored by hyperuremia [39]. In fact, HbA1c and mean glucose concentration were strongly correlated in non haemodialysed type 2 diabetic (HD T2) patients but weakly correlated in HD T2 patients, suggesting a poor value of HbA1c in HD diabetic patients [40]. Drugs such as antiretroviral and aspirin also interfere. Moreover, it is currently not recommended to use this test as a diagnostic tool in the diagnosis of GD, it is possible that this situation will change in the coming years, because it was found that several points of HbA1c in combination with OGTT may be a useful diagnostic tool for GD [41]. Studies that have led to the use of HbA1c as a diagnostic marker were performed in adults, making uncertain its use in children [42]. In recent studies conducted in patients with coronary artery disease, a large discrepancy in classification of patients was observed between FPG, HbA1c and OGTT. FPG and HbA1c diagnosed a lower number of diabetic patients compared to the OGTT [43,44]. The combination of HbA1c and FPG seems to be a good approach, to limit the defects of the two tests. A study on a Chinese population of 141 type 2 diabetics showed that the combination of these two parameters provides a sensitivity of 83.7% and a specificity of 89.3% [45].
5. Diagnosis of prediabetes The term ‘‘prediabetes’’ encompasses the entities of IGT and/or IFG. Most studies suggest that 5 to 10% of prediabetics develop a diabetes mellitus each year [46]. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030 [47]. Moreover, microvascular complications, including retinopathy, chronic kidney disease, and neuropathy, and cardiovascular risk have been
3
associated with prediabetes [48]. Therefore, early detection of prediabetes is important. IFG is diagnosed when FPG is of 110–125 mg/dl according to WHO criteria and 100–125 mg/dl according to ADA criteria [49]. Whereas, IGT is diagnosed when 2-h PG values after an OGTT are between 140 and 200 mg/dl. It has been shown that IGT and IFG are not equivalent, the viewpoint of pathophysiological, prognosis or clinical significance. A study conducted between 1999 and 2000 which included 10,428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), suggests that diabetes mellitus and IFG are independent predictors of cardiovascular disease mortality, but IGT was not [50]. Otherwise, the Funagata Study showed a higher cardiovascular mortality rate in persons with IGT compared with individuals with IFG [51]. 6. Conclusion In addition to FPG, 2-h PG and HbA1c can be used to diagnose diabetes and prediabetes. So clinicians could use one, two or the three tests to reach to a proper diagnosis. The point is the setting of them and how to use every measure in a certain situation. Thus, elements such as age, pregnancy or ethnicity should be considered when interpreting the results. Disclosure of interest The authors declare that they have no competing interest. References [1] Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103(2):137–49. [2] Harris MI, Undiagnosed NIDDM:. clinical and public health issues. Diabetes Care 1993;16:642–52. [3] Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D, Davidson MB. A new look at screening and diagnosing diabetes mellitus. J Clin Endocrinol Metab 2008;93:2447–53. [4] World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation, Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; 1999. [5] American Diabetes, Association. Standards of medical care in diabetes. Diabetes Care 2005;28(1):S4–36. [6] Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008;371:736–43. [7] Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48(3):436–72. [8] Vucˇic´ Lovrencˇic´ M, Radisˇic´ Biljak V, Bozˇicˇevic´ S, Pape-Medvidovic´ E, Ljubic´ S. Validation of Point-of-Care glucose testing for diagnosis of type 2 diabetes. Intern J Endocrinol 2013;2013. http://dx.doi.org/10.1155/2013/206309 [Article ID: 206309, 6 pages]. [9] Delatour V, Lalere B, Saint-Albin K, Peignaux M, Hattchouel JM, Dumont G, et al. Continuous improvement of medical test reliability using reference methods and matrix-corrected target values in proficiency testing schemes: Application to glucose assay. Clin Chim Acta 2012;413(23):1872–8. [10] Bartoli E, Fra GP, Schianca GC. The oral glucose tolerance test (OGTT) revisited. Europ J Internal Med 2011;22(1):8–12. [11] Gavin JR, Alberti K, Davidson MB, DeFronzo RA. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes care 1997;20(7):1183. [12] Vassault A. Glucose hyperglyce´mie provoque´e. EMC (Elsevier Masson SAS, Paris), Biologie clinique, 90-10-0485; 2007. [13] Scheen AJ, Luyckx FH. L’hyperglyce´mie provoque´e par voie orale (HGPO) revisite´e: 2e partie: Indices d’insulinose´cre´tion, d’insulinosensibilite´ et de disposition orale. Med Mal Metabol 2010;4(6):684–90. [14] Kima YA, Ku EJ, Khang AR, Hong ES, Kim AM, Moon JH, et al. Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes. Diabetes Res Clin Pract 2014;106(2):351–9. [15] HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002. ˜ oz E, Parra A, Castillo-Mora A, Ortega-Gonza´lez C. Effect of the [16] Reyes-Mun diagnostic criteria of the International Association of Diabetes and Pregnancy
Please cite this article in press as: Zendjabil M. Biological diagnosis of diabetes mellitus. Pathol Biol (Paris) (2015), http://dx.doi.org/ 10.1016/j.patbio.2015.10.002
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PATBIO-3204; No. of Pages 4 M. Zendjabil / Pathologie Biologie xxx (2015) xxx–xxx
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[17] [18]
[19]
[20] [21]
[22]
[23]
[24]
[25]
[26]
[27] [28] [29]
[30]
[31]
[32]
[33] [34]
Study Groups on the prevalence of gestational diabetes mellitus in urban Mexican women: a cross-sectional study. Endocr Pract 2011;18(2):146–51. Shang M, Lin L. IADPSG criteria for diagnosing gestational diabetes mellitus and predicting adverse pregnancy outcomes. J Perinatol 2014;34(2):100–4. World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy; 2013, http://apps.who.int/iris/ bitstream/10665/85975/1/WHO_NMH_MN13.2_eng.pdf. Mayo K, Melamed N, Vandenberghe H, Berger H. The impact of adoption of the International Association of Diabetes in Pregnancy Study Group criteria for the screening and diagnosis of gestational diabetes. Am J Obstet Gynecol 2015;212(2):224-e1. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2015;38(S1):S8–16. Raccah D. Importance of blood glucose management in the multifactorial approach of absolute cardiovascular risk in type 2 diabetes: the lessons from the Steno 2 study. Diabetes Metab 2006;32:2S48-2S51. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis of diagnostic criteria in Europe. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999;354:617–21. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999;22:233–40. World Health Organization. Cardiovascular risk profile assessment in glucoseintolerant Asian individuals. An evaluation of the World Health Organization two-step strategy: the DECODA Study (Diabetes epidemiology: collaborative analysis of diagnostic criteria in Asia). Diabet Med 2002;19:549–57. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. The Lancet 2002;359(9323):2072–7. Kusunoki Y, Katsuno T, Myojin M, Miyakoshi K, Ikawa T, Matsuo T, et al. Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin. Endocrine J 2013;60(4):431–9. Zendjabil M. L’he´moglobine glyque´e : indication, interpre´tation et limites. Ann Pharm Fr 2015;73(5):336–9. Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;7:353–7. Little RR. Glycated hemoglobin standardization-National Glycohemoglobin Standardization Program (NGSP) perspective. Clin Chem Lab Med 2003;41(9):1191–8. Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, et al. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med 2002;40(1):78–89. American Diabetes Association, European Association for the Study of Diabetes. Consensus statement on the worldwide standardisation of the HbA1c measurement. Diabetologia 2007;50(10):2042. Hanas R, John G. International HbA1(c) Consensus Committee. 2010 consensus statement on the worldwide standardization of the hemoglobin A(1c) measurement. Diabetes Res Clin Pract 2010;90(2):228–30. Gillery P. A history of HbA1c through clinical chemistry and laboratory medicine. Clin Chem Lab Med 2013;51(1):65–74. The International Expert Committee: International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 2009;32(7):1327–34.
[35] World health Organization Department of Noncommunicable Disease Surveillance, Geneva. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Abbreviated report of a WHO consultation; 2011, http:// www.who.int/cardiovascular_diseases/report-hba1c_2011_edited.pdf. [36] Monnier L, Colette C, Boniface H. Contribution of postprandial glucose to chronic hyperglycaemia: from the ‘‘glucose triad’’ to the trilogy of ‘‘sevens’’. Diabetes Metab 2006;32:2S11-2S16. [37] Diallo F, Fall M, Ndiaye A, Doupa D, Diatta A, Cisse´ F, et al. Influence de l’utilisation d’un antiglycolytique et de la tempe´rature de conservation sur la stabilite´ du dosage de la glyce´mie avant centrifugation. Open Sci Reposit Biol 2014;e45011803. [38] Jaisson S, Leroy N, Desroches C, Tonye-Libyh M, Guillard E, Gillery P. Interference of the most frequent haemoglobin variants on quantification of HbA 1c: comparison between the LC-MS (IFCC reference method) and three routinely used methods. Diabet Metab 2013;39(4):363–9. [39] Jaisson S, Pietrement C, Gillery P. Carbamylation derived products (CDPs): bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis. Clin Chem 2011;57:1499–505. [40] Riveline JP, Teynie J, Belmouaz S, Franc S, Dardari D, Bauwens M, et al. Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a continuous glucose monitoring system. Nephrol Dial Transplant 2009;24(9):2866–71. [41] Renz PB, Cavagnolli G, Weinert LS, Silveiro SP, Camargo JL. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus. PloS One 2015;10(8): e0135989. [42] Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care 2011;34:1306–11. [43] Farhan S, Jarai R, Tentzeris I, Kautzky-Willer A, Samaha E, Smetana P, et al. Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease. Clin Res Card 2012;101(8):625–30. [44] Hage C, Lundman P, Ryde´n L, Mellbin L. Fasting glucose, HbA1c, or oral glucose tolerance testing for the detection of glucose abnormalities in patients with acute coronary syndromes. Eur J Prev Cardio 2013;20(4):549–54. [45] Mo M, Zhong W, Zhao G, Ruan Y, Zhang H, Shi L, et al. Combining glycosylated hemoglobin A1c and fasting plasma glucose for diagnosis of type 2 diabetes in Chinese adults. BMC Endocr Disord 2013;13(1):44. [46] Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract 2007;78(3):305–12. [47] Taba´k AG, Herder C, Rathmann W, Brunner EJ, Kivima¨ki M. Prediabetes: a highrisk state for diabetes development. The Lancet 2012;379(9833):2279–90. [48] Buysschaert M, Bergman M. Definition of prediabetes. Med Clin North Am 2011;95(2):289–97. [49] Zhang X, Gregg EW, Williamson DF, Barker LE, Thomas W, Bullard KW, et al. A1c level and future risk of diabetes: a systematic review. Diabetes Care 2010;33:1665–73. [50] Barr ELM, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose and impaired glucose tolerance: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Circulation 2007;116(2):151–7. [51] Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose: the Funagata Diabetes Study. Diabetes Care 1999;22(6):920–4.
Please cite this article in press as: Zendjabil M. Biological diagnosis of diabetes mellitus. Pathol Biol (Paris) (2015), http://dx.doi.org/ 10.1016/j.patbio.2015.10.002
PATBIO-3204; No. of Pages 4 Pathologie Biologie xxx (2015) xxx–xxx
Available online at
ScienceDirect www.sciencedirect.com
Review
Biological diagnosis of diabetes mellitus Diagnostic biologique du diabe`te sucre´ M. Zendjabil Laboratoire de biochimie, E´tablissement Hospitalier Universitaire d’Oran 1er Novembre 1954, BP No. 4166, Ibn Rochd, Oran, Algeria
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 July 2015 Accepted 7 October 2015 Available online xxx
Diabetes mellitus is a common disease whose complications are severe. For decades, the diagnosis of diabetes and prediabetes was using only fasting glucose or glucose two hours during an oral glucose tolerance test. Recently, it is possible to use HbA1c. Each of these tests has advantages and limitations that must be well known by clinicians for better care for patients. So they could use one, two or three of this tests to reach to a proper diagnosis. The aim of this article is about the strong and weak points of these tests. ß 2015 Elsevier Masson SAS. All rights reserved.
Keywords: Diabetes mellitus Diagnosis OGTT HbA1c
R E´ S U M E´
Mots cle´s : Diabe`te sucre´ Diagnostic HGPO HbA1c
Le diabe`te sucre´ est une maladie fre´quente dont les complications sont graves. Pendant des de´cennies, le diagnostic du diabe`te et du pre´diabe`te faisait uniquement appel a` la glyce´mie a` jeun ou la glyce´mie deux heures apre`s une e´preuve de glyce´mie provoque´e par voie orale. Depuis peu, il est possible d’utiliser l’HbA1c. Chacun de ces tests a des avantages et des limites qui doivent eˆtre bien connus par les cliniciens pour une meilleure prise en charge des patients. Donc, ils pourraient utiliser un, deux ou trois de ces tests pour arriver a` un bon diagnostic. Le but de cet article est de traiter les points forts et les inconve´nients de ces tests. ß 2015 Elsevier Masson SAS. Tous droits re´serve´s.
1. Introduction Diabetes mellitus is a very common disease with deadly complications. The number of diabetics patients in 2013 was 382 million and it is expected to increase to reach 592 million in 2035 [1]. Diabetes mellitus often goes unnoticed and the average lag between onset and diagnosis is 7 years [2]. In the United States of America, approximately 30% of diabetics or 6,2 million people are underdiagnosed [3]. The definition of diabetes is mainly biological view and has changed throughout the years, especially with the recent introduction of HbA1c. The aim of this article is about the strong and weak points of the tests used to diagnose this disease.
2. Fasting plasma glucose (FPG) Diabetes mellitus is defined according to American Diabetes Association (ADA) and World Health Organization (WHO) by a E-mail address: [email protected]
concentration of FPG higher than 126 mg/dl twice or a blood glucose above 200 mg/dl at any time of day [4,5]. The threshold of 126 mg/dl was chosen because it is from this level that the risk of microvascular complications, including diabetic retinopathy, becomes important. Three epidemiological studies have contributed to establish this threshold. However, these studies had a strong bias: research retinopathy was made in an incomplete and imprecise manner. New research has shown that the threshold value of 126 mg/dl had a sensitivity of less than 40% and a specificity of between 81 and 96% for the detection of diabetic retinopathy. So there appears to be no threshold value for evaluating the presence of this complication [6]. Glucose can be measured in serum, plasma or blood. Plasma values are 11–13% higher than the measured blood glucose in the case of a normal hematocrit, this is due to the difference of the amount of water between erythrocytes and plasma [7]. The glucose assay must be done in laboratory. Point of care tests (POCT) glucometers are very useful for monitoring diabetes mellitus, but should not be used for the diagnosis due to both insufficient precision and accuracy and the inherent, sample-dependent flaw
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of results [8]. However, some authors suggest otherwise, arguing that POCT instruments have sufficient accuracy to be used as diagnostic tools for diabetes [9].
3. Oral glucose tolerance test (OGTT) This is the most known dynamic test in diabetology, which has been widely used. This test is to administer in less than 5 mins, 250 ml of water with a glucose load of 75 g for adults and 1.75 g/kg body weight for children. Then, blood glucose dosage is carried out at different times. Standardization was established for reducing the importance of variation coefficients for different glucose concentrations determined during the test. Thus, we should take into consideration only the FPG and blood glucose 2 h after an OGTT (2-h PG) [10] and it is no longer necessary to extend this test to 3 or 5 h. If positive, it is necessary to repeat the test to confirm the result; this is not always respected in practice because of various constraints imposed by the test. Depending on the value of 2-h PG after the load, patients are classified into normal subjects for levels below 140 mg/dl, subjects with impaired glucose tolerance (IGT) when values are between 140–199 mg/dl and diabetics when blood glucose exceeds 200 mg/dl. This test was first described in 1922 and was designed to assess the ability to tolerate a glucose load. It was only in 1979 that the National Diabetes Data Group has recommended its use for the diagnosis of diabetes mellitus, followed by the WHO a few years later. In 1997, a group of experts recommend not to use this test primarily for the diagnosis of diabetes [11]. The ADA had probably the wish that this test becomes obsolete because it has a low reproducibility; it is expensive, long and mobilizes the staff for significant period. By issuing these recommendations, the ADA hoped to attract more patients to be screened, diagnosed and treated with simple measurement of FPG. The OGTT is indicated when the FPG value is between 110– 126 mg/dl without a metabolic syndrome, if the FPG is normal in presence of glycosuria or when FPG is normal while the PPG is between 140–200 mg/dl. However, OGTT should not be used in certain situations: when FPG and lipid levels are normal, if the patient’s age is above 70 years because the result does not influence the therapeutic management. It was also demonstrated that the OGTT was not of interest when FPG level is greater than 126 mg/dl, because this value is equivalent to 2-h PG higher than 200 mg/dl, in the risk of development of diabetic retinopathy [12]. Although the OGTT is decried in favor of FPG, it has been widely used in clinical and epidemiological research studies and it is still considered as ‘‘the gold standard’’. It also keeps an important place in clinical practice, in particular for the early detection of IGT for which it has better sensitivity than FPG. Determining parameters other than glucose such as insulin and C-peptide during the test allows for calculation of indices reflecting insulin secretion and insulin resistance are used in the field of research [13]. In a study including 406 subjects with prediabetes, many indices were studied and it was found that high levels of glucose and a low concentration of C-peptide at 30 mins after OGTT may be a good predicator for diabetes conversion [14]. The OGTT is particularly useful in the diagnosis of gestational diabetes (GD) that may be accompanied by some perinatal complications. Thus, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study which included over 25,000 women showed a continuum between blood glucose levels in pregnant women and the risk of perinatal complications such as fetal hyperinsulinemia, macrosomia, neonatal hypoglycemia and cesarean [15]. The use of OGTT to search for GD was the subject of many controversies including the best time to conduct the test, the glucose load to administer 75 or 100 g, and the thresholds to be
considered as pathological. Due to an international consensus of International Association of Diabetes in Pregnancy Study Group (IADPSG) [16], responses have been made to these questions. Thus, the OGTT should be performed between 24 and 28 weeks of gestation with a glucose load of 75 g. The thresholds of blood glucose values are 92 mg/dl for the FPG, 180 mg/dl after 1 h and 153 mg/dl after 2 h [17,18]. These recommendations tend to increase GD’s prevalence [19] (from 5–10% to 15–20%). In two randomized controlled trials, 80 to 90% of women with mild GD diagnosed by this strategy could be managed with life-style therapy only. Other well-designed clinical studies are required to determine the best way to detect and treat women with GD, diagnosed according to the IADPSG recommendations [20]. The determination of postprandial blood glucose (PPG) involves measuring blood glucose 1 h or 2 h after a meal. Normal values of PPG are less than 140 mg/dl. The value of PPG depends on many factors such as the nature of the meal, various gastrointestinal and pancreatic hormones, or the rate at which gastric emptying is carried out. PPG appears to be an independent minor cardiovascular risk factor, but when it is combined with other risk factors such as high cholesterol, high blood pressure or smoking; the risk is significantly increased; which could explain the high prevalence of cardiovascular morbidity and mortality in diabetic patients, particularly in type 2 diabetes [21]. The multicenter European study DECODE showed that the risk of cardiovascular morbidity and mortality is more correlated with postprandial hyperglycemia during an OGTT than FPG [22]. The PPG has been recognized as an independent cardiovascular risk factor in several other metaanalyzes [23,24], but the relationship between GPP and microvascular risk remains to our knowledge little studied. Further studies report a reduction in cardiovascular events in patients treated with drugs reducing PPG like acarbose [25,26]. Postprandial hyperglycemia is therefore an interesting therapeutic target, particularly when the HbA1c is close to the aim.
4. Glycohemoglobin HbA1c HbA1c is defined by the slow and irreversible binding of glucose to the N-terminal valine of one or both of the beta chains of hemoglobin. It reflects glycemic control of two or three months [27]. HbA1c was discovered in the 1960s. The first demonstration of this marker increase in diabetes was made by Trivelli et al. in 1971 [28]. In 1986, the NGSP (National Glycohemoglobin Standardization Program) has established a reference method using HPLC (High Performance Liquid Chromatography) based on the DCCT (Diabetes Control and Complications Trial) and UKPDS (United Kingdom Prospective Diabetes Study) studies that showed a significant correlation between HbA1c and the risk of occurrence of complications in diabetic patients [29]. The IFCC has proposed in 2002 a reference technique using HPLC coupled with capillary electrophoresis (HPLC-CE) or mass spectrometry (HPLC-MS) and has defined the N-terminal hexapeptide of the standard to use [30]. Several consensuses have been established in the late of 2000s that is allowed to standardize the A1 C test [31,32]. It was also decided that the results provided by the laboratories must now be expressed in two units: mmol/mol (IFCC) and % (NGSP), with a master equation linking the two expression systems. For decades, the diagnosis of diabetes was based only on FPG or 2-h PG after an OGTT. The use of HbA1c as a diagnostic tool was suggested in the 1970s and early 1980s but with an adaptation of the values for pregnant women and elderly [33]. Eventually in 2009, a committee of experts supported by the ADA and EASD (European Association for the Study of Diabetes) proposed HbA1c as a diagnostic marker [34]. This decision was followed by the WHO in 2011 [35]. The chosen criteria are: HbA1c 48 mmol/mol
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( 6, 5%) twice or HbA1c 48 mmol/mol one time with FPG higher than or equal to 200 mg/dl. Like for FPG, the threshold of 48 mmol/ mol was selected based on the risk of developing diabetic retinopathy and like FPG, there seems to be no threshold value for evaluating the presence of this complication. An HbA1c between 38 and 46 mmol/mol (5, 7 and 6, 4%) is used to diagnose impaired fasting glucose (IFG). In clinical practice, HbA1c remained mostly used as a reference biologic parameter in monitoring diabetic patients but is rarely used in the diagnosis of diabetes mellitus. In the laboratory of biochemistry at the University Hospital Establishment of Oran in Algeria, 172 prescriptions has been analyzed during the period from 01/01/2014 to 30/06/2014, only 8, 14% of these exams were for diagnostic purposes (personal data). The HbA1c has a number of advantages compared to glucose’s determination. The advantage of HbA1c is to integrate both fasting blood glucose and to use PPG on them [36]. In addition, fasting is not required for HbA1c’s determination. Significant errors can occur in the determination of glucose levels in blood due to preanalytical factors. Blood glucose may be underestimated if the assay is not performed quickly after collection. Indeed, there is a glycolysis in vitro which can be reduced by using antiglycolytics such as sodium fluoride or monoiodoacetate. In absence of antiglycolytics, the average drop in blood glucose is around 7.26 mg/dl/h [37]. HbA1c has limitations that make it lose its interest in some cases. Indeed, any qualitative or quantitative anomaly concerning the hemoglobin as a transfusion, anemia or a hemoglobinopathy can be a source of interference [27]. A study that compares the impact of the most frequent hemoglobinopathies on three field methods to the HPLC-MS reference method, showed no influence on the interpretation of results [38]. However, we must always interpret HbA1c’s results with caution in presence of hemoglobin variants. Chronic kidney failure can skew the results in two ways: it causes anemia by reducing lifespan of red blood cells and by formation of carbamylated hemoglobin, favored by hyperuremia [39]. In fact, HbA1c and mean glucose concentration were strongly correlated in non haemodialysed type 2 diabetic (HD T2) patients but weakly correlated in HD T2 patients, suggesting a poor value of HbA1c in HD diabetic patients [40]. Drugs such as antiretroviral and aspirin also interfere. Moreover, it is currently not recommended to use this test as a diagnostic tool in the diagnosis of GD, it is possible that this situation will change in the coming years, because it was found that several points of HbA1c in combination with OGTT may be a useful diagnostic tool for GD [41]. Studies that have led to the use of HbA1c as a diagnostic marker were performed in adults, making uncertain its use in children [42]. In recent studies conducted in patients with coronary artery disease, a large discrepancy in classification of patients was observed between FPG, HbA1c and OGTT. FPG and HbA1c diagnosed a lower number of diabetic patients compared to the OGTT [43,44]. The combination of HbA1c and FPG seems to be a good approach, to limit the defects of the two tests. A study on a Chinese population of 141 type 2 diabetics showed that the combination of these two parameters provides a sensitivity of 83.7% and a specificity of 89.3% [45].
5. Diagnosis of prediabetes The term ‘‘prediabetes’’ encompasses the entities of IGT and/or IFG. Most studies suggest that 5 to 10% of prediabetics develop a diabetes mellitus each year [46]. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030 [47]. Moreover, microvascular complications, including retinopathy, chronic kidney disease, and neuropathy, and cardiovascular risk have been
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associated with prediabetes [48]. Therefore, early detection of prediabetes is important. IFG is diagnosed when FPG is of 110–125 mg/dl according to WHO criteria and 100–125 mg/dl according to ADA criteria [49]. Whereas, IGT is diagnosed when 2-h PG values after an OGTT are between 140 and 200 mg/dl. It has been shown that IGT and IFG are not equivalent, the viewpoint of pathophysiological, prognosis or clinical significance. A study conducted between 1999 and 2000 which included 10,428 participants of the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), suggests that diabetes mellitus and IFG are independent predictors of cardiovascular disease mortality, but IGT was not [50]. Otherwise, the Funagata Study showed a higher cardiovascular mortality rate in persons with IGT compared with individuals with IFG [51]. 6. Conclusion In addition to FPG, 2-h PG and HbA1c can be used to diagnose diabetes and prediabetes. So clinicians could use one, two or the three tests to reach to a proper diagnosis. The point is the setting of them and how to use every measure in a certain situation. Thus, elements such as age, pregnancy or ethnicity should be considered when interpreting the results. Disclosure of interest The authors declare that they have no competing interest. References [1] Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014;103(2):137–49. [2] Harris MI, Undiagnosed NIDDM:. clinical and public health issues. Diabetes Care 1993;16:642–52. [3] Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D, Davidson MB. A new look at screening and diagnosing diabetes mellitus. J Clin Endocrinol Metab 2008;93:2447–53. [4] World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation, Part 1: diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; 1999. [5] American Diabetes, Association. Standards of medical care in diabetes. Diabetes Care 2005;28(1):S4–36. [6] Wong TY, Liew G, Tapp RJ, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008;371:736–43. [7] Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem 2002;48(3):436–72. [8] Vucˇic´ Lovrencˇic´ M, Radisˇic´ Biljak V, Bozˇicˇevic´ S, Pape-Medvidovic´ E, Ljubic´ S. Validation of Point-of-Care glucose testing for diagnosis of type 2 diabetes. Intern J Endocrinol 2013;2013. http://dx.doi.org/10.1155/2013/206309 [Article ID: 206309, 6 pages]. [9] Delatour V, Lalere B, Saint-Albin K, Peignaux M, Hattchouel JM, Dumont G, et al. Continuous improvement of medical test reliability using reference methods and matrix-corrected target values in proficiency testing schemes: Application to glucose assay. Clin Chim Acta 2012;413(23):1872–8. [10] Bartoli E, Fra GP, Schianca GC. The oral glucose tolerance test (OGTT) revisited. Europ J Internal Med 2011;22(1):8–12. [11] Gavin JR, Alberti K, Davidson MB, DeFronzo RA. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes care 1997;20(7):1183. [12] Vassault A. Glucose hyperglyce´mie provoque´e. EMC (Elsevier Masson SAS, Paris), Biologie clinique, 90-10-0485; 2007. [13] Scheen AJ, Luyckx FH. L’hyperglyce´mie provoque´e par voie orale (HGPO) revisite´e: 2e partie: Indices d’insulinose´cre´tion, d’insulinosensibilite´ et de disposition orale. Med Mal Metabol 2010;4(6):684–90. [14] Kima YA, Ku EJ, Khang AR, Hong ES, Kim AM, Moon JH, et al. Role of various indices derived from an oral glucose tolerance test in the prediction of conversion from prediabetes to type 2 diabetes. Diabetes Res Clin Pract 2014;106(2):351–9. [15] HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008;358:1991–2002. ˜ oz E, Parra A, Castillo-Mora A, Ortega-Gonza´lez C. Effect of the [16] Reyes-Mun diagnostic criteria of the International Association of Diabetes and Pregnancy
Please cite this article in press as: Zendjabil M. Biological diagnosis of diabetes mellitus. Pathol Biol (Paris) (2015), http://dx.doi.org/ 10.1016/j.patbio.2015.10.002
G Model
PATBIO-3204; No. of Pages 4 M. Zendjabil / Pathologie Biologie xxx (2015) xxx–xxx
4
[17] [18]
[19]
[20] [21]
[22]
[23]
[24]
[25]
[26]
[27] [28] [29]
[30]
[31]
[32]
[33] [34]
Study Groups on the prevalence of gestational diabetes mellitus in urban Mexican women: a cross-sectional study. Endocr Pract 2011;18(2):146–51. Shang M, Lin L. IADPSG criteria for diagnosing gestational diabetes mellitus and predicting adverse pregnancy outcomes. J Perinatol 2014;34(2):100–4. World Health Organization. Diagnostic criteria and classification of hyperglycaemia first detected in pregnancy; 2013, http://apps.who.int/iris/ bitstream/10665/85975/1/WHO_NMH_MN13.2_eng.pdf. Mayo K, Melamed N, Vandenberghe H, Berger H. The impact of adoption of the International Association of Diabetes in Pregnancy Study Group criteria for the screening and diagnosis of gestational diabetes. Am J Obstet Gynecol 2015;212(2):224-e1. American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care 2015;38(S1):S8–16. Raccah D. Importance of blood glucose management in the multifactorial approach of absolute cardiovascular risk in type 2 diabetes: the lessons from the Steno 2 study. Diabetes Metab 2006;32:2S48-2S51. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis of diagnostic criteria in Europe. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999;354:617–21. Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999;22:233–40. World Health Organization. Cardiovascular risk profile assessment in glucoseintolerant Asian individuals. An evaluation of the World Health Organization two-step strategy: the DECODA Study (Diabetes epidemiology: collaborative analysis of diagnostic criteria in Asia). Diabet Med 2002;19:549–57. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. The Lancet 2002;359(9323):2072–7. Kusunoki Y, Katsuno T, Myojin M, Miyakoshi K, Ikawa T, Matsuo T, et al. Effect of additional administration of acarbose on blood glucose fluctuations and postprandial hyperglycemia in patients with type 2 diabetes mellitus under treatment with alogliptin. Endocrine J 2013;60(4):431–9. Zendjabil M. L’he´moglobine glyque´e : indication, interpre´tation et limites. Ann Pharm Fr 2015;73(5):336–9. Trivelli LA, Ranney HM, Lai HT. Hemoglobin components in patients with diabetes mellitus. N Engl J Med 1971;7:353–7. Little RR. Glycated hemoglobin standardization-National Glycohemoglobin Standardization Program (NGSP) perspective. Clin Chem Lab Med 2003;41(9):1191–8. Jeppsson JO, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, et al. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med 2002;40(1):78–89. American Diabetes Association, European Association for the Study of Diabetes. Consensus statement on the worldwide standardisation of the HbA1c measurement. Diabetologia 2007;50(10):2042. Hanas R, John G. International HbA1(c) Consensus Committee. 2010 consensus statement on the worldwide standardization of the hemoglobin A(1c) measurement. Diabetes Res Clin Pract 2010;90(2):228–30. Gillery P. A history of HbA1c through clinical chemistry and laboratory medicine. Clin Chem Lab Med 2013;51(1):65–74. The International Expert Committee: International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes. Diabetes Care 2009;32(7):1327–34.
[35] World health Organization Department of Noncommunicable Disease Surveillance, Geneva. Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus. Abbreviated report of a WHO consultation; 2011, http:// www.who.int/cardiovascular_diseases/report-hba1c_2011_edited.pdf. [36] Monnier L, Colette C, Boniface H. Contribution of postprandial glucose to chronic hyperglycaemia: from the ‘‘glucose triad’’ to the trilogy of ‘‘sevens’’. Diabetes Metab 2006;32:2S11-2S16. [37] Diallo F, Fall M, Ndiaye A, Doupa D, Diatta A, Cisse´ F, et al. Influence de l’utilisation d’un antiglycolytique et de la tempe´rature de conservation sur la stabilite´ du dosage de la glyce´mie avant centrifugation. Open Sci Reposit Biol 2014;e45011803. [38] Jaisson S, Leroy N, Desroches C, Tonye-Libyh M, Guillard E, Gillery P. Interference of the most frequent haemoglobin variants on quantification of HbA 1c: comparison between the LC-MS (IFCC reference method) and three routinely used methods. Diabet Metab 2013;39(4):363–9. [39] Jaisson S, Pietrement C, Gillery P. Carbamylation derived products (CDPs): bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis. Clin Chem 2011;57:1499–505. [40] Riveline JP, Teynie J, Belmouaz S, Franc S, Dardari D, Bauwens M, et al. Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a continuous glucose monitoring system. Nephrol Dial Transplant 2009;24(9):2866–71. [41] Renz PB, Cavagnolli G, Weinert LS, Silveiro SP, Camargo JL. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus. PloS One 2015;10(8): e0135989. [42] Nowicka P, Santoro N, Liu H, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care 2011;34:1306–11. [43] Farhan S, Jarai R, Tentzeris I, Kautzky-Willer A, Samaha E, Smetana P, et al. Comparison of HbA1c and oral glucose tolerance test for diagnosis of diabetes in patients with coronary artery disease. Clin Res Card 2012;101(8):625–30. [44] Hage C, Lundman P, Ryde´n L, Mellbin L. Fasting glucose, HbA1c, or oral glucose tolerance testing for the detection of glucose abnormalities in patients with acute coronary syndromes. Eur J Prev Cardio 2013;20(4):549–54. [45] Mo M, Zhong W, Zhao G, Ruan Y, Zhang H, Shi L, et al. Combining glycosylated hemoglobin A1c and fasting plasma glucose for diagnosis of type 2 diabetes in Chinese adults. BMC Endocr Disord 2013;13(1):44. [46] Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, et al. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract 2007;78(3):305–12. [47] Taba´k AG, Herder C, Rathmann W, Brunner EJ, Kivima¨ki M. Prediabetes: a highrisk state for diabetes development. The Lancet 2012;379(9833):2279–90. [48] Buysschaert M, Bergman M. Definition of prediabetes. Med Clin North Am 2011;95(2):289–97. [49] Zhang X, Gregg EW, Williamson DF, Barker LE, Thomas W, Bullard KW, et al. A1c level and future risk of diabetes: a systematic review. Diabetes Care 2010;33:1665–73. [50] Barr ELM, Zimmet PZ, Welborn TA, Jolley D, Magliano DJ, Dunstan DW, et al. Risk of cardiovascular and all-cause mortality in individuals with diabetes mellitus, impaired fasting glucose and impaired glucose tolerance: the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Circulation 2007;116(2):151–7. [51] Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose: the Funagata Diabetes Study. Diabetes Care 1999;22(6):920–4.
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