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Hemoglobin A1c Diagnostic Cutoff Differences Between Black and White Persons

Yusuke Tsugawa, MD, MPH; Kenneth J. Mukamal, MD, MPH; and Christina C. Wee, MD, MPH
[+] Article and Author Information

From Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2083.


Ann Intern Med. 2013;158(1):73-74. doi:10.7326/0003-4819-158-1-201301010-00018
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January 1, 2013
Samuel Dagogo-Jack, MD, MBBS
AIM. 2013;158(1):73  doi:10.7326/0003-4819-158-1-201301010-00017



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Multiple Factors Modulating of blood HbA1C level and Diabetic retinopathy demands different cut of values in different racial groups .
Posted on February 7, 2013
Kanjaksha Ghosh, Kinjalka Ghosh*
Director , National Institute of Immunohaematology , Mumbai , India. * Resident Department of Biochemistry, Indira Gandhi Government Medical College, Nagpur, India
Conflict of Interest: None Declared

Comments of Dagogo Jack (1) on a paper published by Tsugawa et al (2) deserves detailed discussion. Retinopathy is one of the important complication of diabetics, however the prevalence of this complication is not only dependent on degree of control of hypertension, viscosity of blood, ischaemic pathology in the retinal vasculature and over all other hormonal milieu like growth hormone levels. Ateliotic dwarfs with diabetes do not develop diabetic retinopathy (3) and unilateral constriction of carotid artery also prevents development of diabetic retinopathy in that eye supplied by stenotic vessel (4). Patient’s with Down syndrome almost never develops diabetic retinopathy (5). Moreover certain unrelated conditions like Hb S-C disease, sickle cell anemia, hyperviscosity syndrome due to paraproteins, post retinal venous occlusion produce some of the retinal pathology like diabetic retinopathy even though none of the above mentioned condition are associated with diabetes. Moreover as discussed in the letter 3% of healthy NHANES III population showed lesion resembling diabetic retinopathy.

The salutary effect of photocoagulation shows that retinal ischaemia is a predominant cause of retinal vascular change in diabetics mellitus.HbA1C level in the blood on the other hand depends on levels of hyperglycaemia and period through which hyperglycaemia tests. This level is also dependent upon mean red cell life span, so that HbA1C levels are reduced in haemolytic states. Moreover structural haemoglobinopathy like Hb S, Hb C etc are glycosylated but on HPLC based techniques for measurement of HbA1C level may not quantitate variant hemoglobins which is glycosylated. Variant Hb like Hb S may not be glycosylated at the same rate as adult Hb levels. Hb S also alters the oxygen dissociation curve of Hb and shifts the curve to right as a result more oxygen is available to retina and this property is likely to have opposite effect on retinopathy. Black population has higher prevalence of hemoglobinopathies, essential hypertension and probably also has less tight glycaemic control (6).Hence there are multiple reasons why Caucasian and black race may have different values of blood HbA1C levels above which retinopathy risk increases.

In this discussion we have not discussed the differences in the biology of endothelial cell health markers and angiogenic gene and HIF and related gene polymorphism which may predispose to differential tendency of developing diabetic retinopathy at similar levels of hyperglycaemic compared to Caucasian population. VEGF also has many polymorphisms and association of diabetic retinopathy with levels of circulating VEGF is now firmly established. Anti VEGF monoclonal antibody Bevacijumab is also success fully used to treat diabetic retinopathy. Moreover many of these VEGF polymorphisms which determines amount of VEGF produced has differential distribution in different populations. All these suggests that there are many other variables which determines development of retinopathy in diabetes and these variables are variably distributed in different races making racial comparison of HbA1c levels for diabetic retinopathy on a single cut off value of HbA1c unrealistic. Preanalytic and analytic variables (7) (Techniques measuring more labile Aldimine linked HbA1C along with more stable keto-amine linked HbA1C or only stable Ketoamine product) in measurement of HbA1C may also be important but that is likely to be similar for both Caucasian and black population in US.

Hence we have to understand that plasma (serum) Hb A1C level is only a surrogate marker of degree of glycaemic control and diabetic retinopathy in two different population may be modulated by many different factors hence between two populations HbA1C may not strictly be comparable with relation to some of the diabetic complication like retinopathy.

References :

1. Dagogo –Jack S. Haemoglobin A1c Diagnostic cut off differences between black and while persons. Ann. Intern. Med 2013; 158:73.

2. Tsugawa Y, Mukamalk J, Davis RB, Taylor WC, Wec CC: Should the hemoglobin A (1c) diagnostic cut off differ between blacks and whites ? a cross sectional study. Ann. Intern. Med 2012; 157:153-9.

3. Merimee TJ, Fineburg SE, Mckusick VA, Hall J. Diabetes mellitus and sexual ateliotic dwarfism: a comparative study. J Clin. Invest. 1970; 49:1096-1102.

4. Patel V, Rassam S, Newsom R, Wiek J, Kohner E. Retinal Blood flow in diabetic retinopathy. Br.Med.J. 1992, 305:678-83.

5. Ryeom D, Folkman J. Role of endogenous angiogenesis inhibitors in Down syndrome. J. Craniofac. Surg. 2009; 20(S1): 595-96.

6. Karter AJ, Ferrara A, Liu Ly, Noffel A, Ackerson LM, Selby JV, Ethnic disparities in diabetic complications in an insured population. JAMA 2002, 287:2519-27.7. Goldstein DE, Peth SB, England JD, Hess RL, Da-Costa J. Effects of acute changes in Blood glucose on HbA1C. Diabetes 1980, 29:623-627.

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