Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
ABSTRACT
1 MSc,Kerman University of Medical Objectives: Early diagnosis of diabetes is crucially important in
Science, Physiology Research Centre, reduction of the complications. Although HbA1c is an accurate
Jahad street, Kerman, Iran. marker for the prediction of complications, less information is
2 MD,PhD,Kerman University of
available about its accuracy in diagnosis of diabetes. In this study,
Medical Science, Faculty of Health,
the association between HbA1c and FBS was assessed through a
Haftbagh-Alavi Highway, Kerman,
Iran.
cross-sectional population-based study.
Methods: A random sample of population in Kerman city was
Correspondence to: selected. The total number was 604 people. Their HbA1c and fast-
Dr. Farzaneh Zolala, Faculty of Health, ing blood sugar (FBS) were tested. The association between
Kerman University of Medical Science, HbA1c and FBS and also their sensitivity, specificity and predic-
Haftbagh-Alavi Highway, Kerman, tive values in detection of abnormal values of each other were
Iran. Postal Code: 7616913555, Post Box:
determined.
76175-531.
Results: The association of HbA1c with FBS was relatively strong
Original Article
Email: farzanehzolala@yahoo.com
particularly in diabetic subjects. Generally, FBS was a more accurate
predictor for HbA1c compared with HbA1c as a predictor of FBS.
Although the optimum cutoff point of HbA1c was >6.15%, its pre-
cision was comparable with the conventional cutoff point of >6%.
Conclusions: In conclusion, FBS sounds more reliable to separate
diabetic from non-diabetic subjects than HbA1c. In case of being
interested in using HbA1c in screening, the conventional cutoff
points of 6% is an acceptable threshold for discrimination of dia-
Date of Submission: 3 Mar 2010 betics from non-diabetics.
Date of Acceptance: 3 May 2010 Keywords: HbA1c; Blood glucose; Diabetics.
Int J Prev Med 2010; 1(3): 187-194
or prevalence.2 Apart from the efficacy of for separation of diabetics and non-diabetics was
HbA1c in detection of diabetes, it is an impor- explored.
tant marker to assess the microvascular compli-
cations and plasma glucose.7 The relationship METHODS
between HbA1c and blood glucose is docu- This cross-sectional population based study
mented in the literature denoting a straight rela- was carried out in Kerman city, which is the
tionship.8-10 However, this relationship has not center of the largest province in south east of
been confirmed by others.11 There is a contro- Iran. Considering 80% as the minimum sensitiv-
versy about the performance of HbA1c in case ity and specificity of HbA1c in the prediction of
finding. It has been argued that due to problems FBS>126mg/dl, precision of 3% and significant
in standardization and variations in styles of level of 95%, sample size of 600 people were
HbA1c test, it is not recommended as a routine computed. A total number of 604 individuals
test for screening of diabetes.12 In addition, other were recruited. The city is divided into 30 postal
factors such as abnormal hemoglobin, anemia areas. Participants were recruited through a pro-
and some drugs may affect the results of HbA1c portional cluster sampling across the city. In
test.13 Also, demographic factors such as race each household, people between 18 and 75 years
and gender are other effective factors.14,15 Saudek were informed verbally about the study objec-
and his colleagues compared FBS and HbA1c as tives and were requested for their participation.
screening tests. They argued that HbA1c is pref- All participants who were invited to participate
erable because it is more time-flexible and in- in the study, agreed for collaboration. They were
formative in long-term conditions. Their criteri- given a written formal consent form. Since sub-
ons have been stabilized in recent years.16 How- jects were requested to attend in our reference
ever, in an epidemiological study, it has been laboratory for taking blood samples, those who
concluded that FBS is more accurate than could not attend or did not consent were ex-
HbA1c.17 The best cutoff point for defining high cluded. The data were collected through a struc-
HbA1c is another important issue. The Diabetes tural face to face interview and laboratory tests.
Control and Complications Trial suggested the Data collection form included two main sec-
value of 6% as HbA1c cut point.18 The United tions, the demographic characteristics and also
Kingdom Prospective Diabetes Study consid- some questions about history of diabetes and
ered 6.2 as the normal level,19 while many labo- taking medications. FBS was measured once
ratories consider 4-6 as a normal range.20 It using enzyme method and the cutoff point of
seems that in different settings such as screening, 126 mg/dl.2 was considered as diagnostic crite-
diagnosis and prediction of progression of diabe- rion for the diabetes. In order to measure
tes we need to define different cut off points. For HbA1c, we used Biosystem kit. The cutoff point
example, It is suggested the value of 6.5% or of 6%, based on the Diabetes Control and Com-
greater as a diabetes diagnostic criterion and 6% plications Trial,18 was considered as diagnostic
and 4.7 for screening test.16,21 Inoue and his col- criterion for diabetes at the beginning. Then, we
leagues used the value of 5.8% for the prediction checked the sensitivity and specificity of other
of progression of diabetes type 2,22 and the val- cutoff points using ROC curve to optimize the
ue <7 as a good predictive of satisfactory blood accuracy of HbA1c in detection of FBS>126
glucose control in type 1 diabetes.23 The main mg/dl. Afterwards, parameters including sensi-
aim of major primary studies carried out in dia- tivity, specificity, predictive values (positive and
betes in Iran was to recognize the range of negative), and the chance of detecting diabetes
HbA1c in the diabetics, tracing back the compli- and the chance of ruling out diabetes before and
cations of diabetes and diabetes control.10,24,25 A after test were calculated. Data were analyzed
few researches have been carried out to find out from descriptive and analytical point of view
the cutoff value of HbA1c in screening; how- using Stata software, version 10. The Pearson
ever, they mainly used a selective samples correlation coefficient between HbA1c and FBS
mainly focusing on high risk groups.26,27 Fur- was estimated in the whole sample, and in sub-
thermore, a study has determined the normal groups (diabetics versus non-diabetics). In order
range of HbA1c in a sample of non-diabetics.28 to explore the effects of possible confounder, in
Based on the above explanation and to fill the the univariate analysis, the association between
gaps, this study aimed to explore the relation- each variable and the FBS and also HbA1c was
ship of HbA1c and FBS in general population. checked. Variables with univariate p value <0.1
In addition, the optimum cutoff point of HbA1c were entered in multivariate analysis.
Table 1. Summary statistics of subjects classified in diabetic and non-diabetic subgroups based on FBS >126 mg/dl.
Categorical Variable Non-diabetics Diabetics Univariate P-value
Frequency (%) Frequency (%)
Sex Female 296 (56.3) 51 (64.6) 0.171
male 229 (43.7) 28 (35.4)
Marriage status Married 456 (86.9) 77 (97.47) .006
single 69 (13.1) 2 (2.53)
Table 2. Prediction of HbA1c based on FBS, and the prediction of FBS based on HbA1c.
FBS126 mg/dl FBS>126 mg/dl
Crude Adjusted* Crude Adjusted*
Beta P-value Beta P-value Beta P-value Beta P-value
Prediction of HbA1c based on FBS
0.13 <0.001 0.09 <0.001 0.18 <0.001 0.18 <0.001
Prediction of FBS based on HbA1c
*The adjusted values were computed in a multivariable regression model with sex, BMI and age as independent variables.
FBS>126 mg/dl were 86%, 78%, 36%, and 97%, tes by around 25% (from 13% to 38%), while
respectively. HbA1c>6 increased the chance of HbA1c6 increased the chance of non-diabetics
diabetics almost by 23% (pre-test=13% to post- by 10% (from 87% to 97%, Table 3). On the
test=36%), while HbA1c6 increased the chance other hand, the accuracy of FBS>126 mg/dl in
of non-diabetics by 10% (from 87% to 97%). Our the prediction of high HbA1c based on these
ROC curve showed that 6.15% is the best cutoff two cutoff points of 6% and 6.15% was compa-
point graph (Figures 1-4). Based on this opti- rable (54% versus 56%). Although the specificity
mum cutoff point, the sensitivity, specificity, of FBS for HbA1c>6 and HbA1c>6.15 was ex-
positive predictive value and negative predictive actly the same (97%), the sensitivity of the latter
value of HbA1c in the prediction of FBS>126 cut point was slightly greater (38% versus 36%,
mg/dl were 85%, 79%, 38%, and 97%, respec- Table 3).
tively. HbA1c>6 increased the chance of diabe-
1.00
0.75
Sensitivity
0.50
0.25
0.00
Figure 1. Roc plot for FBS>126 (reference variable) and HbA1c>6 (classification variable).
Table 3. Comparison of sensitivity and specificity achieved for the diagnosis of diabetes based on HbA1c, at various
levels of FBS at various levels of HbA1c.
HbA1c>6 and FBS>126 mg/dl HbA1c>6.15 and FBS>126 mg/dl
Variable Gold standard Gold standard Gold standard Gold standard
FBS>126 mg/dl HbA1c>6% FBS>126 mg/dl HbA1c>6.15%
Sensitivity (%) 86 36 85 38
Specificity (%) 77 97 79 97
Accuracy (%) 78 90 80 80
Positive predictive value (%) 36 86 38 85
Difference between the chance of dis- 23 54 25 56
ease after the test and the chance of
disease before the test (%)
Negative predictive value (%) 97 77 97 79
Figure 2. Roc plot for HbA1c>6 (reference variable) and FBS>126 (classification variable).
1.00
0.75
Sensitivity
0.50
0.25
0.00
Figure 3. Roc plot for FBS >126 (reference variable) and HbA1c>6.15 (classification variable).
1.00
0.75
Sensitivity
0.50
0.25
0.00
Figure 4. Roc plot for HbA1c>6.15 (reference variable) and FBS>126 (classification variable).
3. Haghdoost AA, Rezazadeh-Kermani M, Sadghirad screening and diagnosing diabetes mellitus. J Clin
B, Baradaran HR. Prevalence of type 2 diabetes in Endocrinol Metab 2008; 93(7): 2447-53.
the Islamic Republic of Iran: systematic review and 17. Gomyo M, Sakane N, Kamae I, Sato S, Suzuki K,
meta-analysis. East Mediterr Health J 2009; 15(3): Tominaga M, et al. Effects of sex, age and BMI on
591-9. screening tests for impaired glucose tolerance. Dia-
4. Deedwania PC, Fonseca VA. Diabetes, prediabetes, betes Res Clin Pract 2004; 64(2): 129-36.
and cardiovascular risk: shifting the paradigm. Am J 18. Anonymous. The diabetes control and complications
Med 2005; 118(9): 939-47. trial and follow-up study. U.S. Department of
5. American Diabetes Association. Standards of medi- Health and Human Services; 2008.
cal care in diabetes. diabetes care 2005 [cited 2010 19. American Diabetes Association. Implications of the
May 29]; Available from: URL: United Kingdom prospective Diabetes Study. Diabe-
http://care.diabetesjournals.org/content/28/suppl_1/s tes Care 2000; 23 Suppl 1: S27-S31.
4.full 20. Burtis A, Ashwood ER, Bruns D. TIETZ textbook of
6. Obuchowski NA, Graham RJ, Baker ME, Powell clinical chemistry and molecular Diagnostics. 2006.
KA. Ten criteria for effective screening: their appli- 21. Norberg M, Eriksson JW, Lindahl B, Andersson C,
cation to multi-slice CT screening for pulmonary Rolandsson O, Stenlund H, et al. A combination of
and colorectal cancers. AJR Am J Roentgenol 2001; HbA1c, fasting glucose and BMI is effective in
176(6): 1357-62. screening for individuals at risk of future type 2 dia-
7. Kilpatrick ES, Rigby AS, Atkin SL. Variability in betes: OGTT is not needed. J Intern Med 2006;
the relationship between mean plasma glucose and 260(3): 263-71.
HbA1c: implications for the assessment of glycemic 22. Inoue K, Matsumoto M, Kobayashi Y. The combi-
control. Clin Chem 2007; 53(5): 897-901. nation of fasting plasma glucose and glycosylated
8. Rohlfing CL, Wiedmeyer HM, Little RR, England hemoglobin predicts type 2 diabetes in Japanese
JD, Tennill A, Goldstein DE. Defining the relation- workers. Diabetes Res Clin Pract 2007; 77(3): 451-8.
ship between plasma glucose and HbA1c: analysis 23. Brennan AL, Gyi KM, Wood DM, Hodson ME,
of glucose profiles and HbA1c in the diabetes con- Geddes DM, Baker EH. Relationship between gly-
trol and complications trial. Diabetes Care 2002; cosylated hemoglobin and mean plasma glucose
25(2): 275-8. concentration in cystic fibrosis. J Cyst Fibros 2006
9. Nathan DM, Kuenen J, Borg R, Zheng H, Schoen- Jan; 5(1): 27-31.
feld D, Heine RJ. Translating the A1C assay into es- 24. Danaee N, Tamadon M, Monesan M. Investigation
timated average glucose values. Diabetes Care 2008; of diabetes control and related factors in outpatients
31(8): 1473-8. in Fatemieh Hospital in Semnan. The scientific
10. Mohammadi A, Esmaeili N. Diabetes control and its Journal of Semnan Medical university 2005; 6(1):
relationship with HbA1c and blodd sugar. The Jour- 31-6.
nal of Qazvin University of Med 2001; (16): 23-6. 25. Vaghari G, Azari G, Marjani A, Kordjazi M. inves-
11. Derakhshan a, Akhavan M, Karamifar H. Evaluation tigation of parameters related to diabetes mellitus in
of microalbuminuria 4 to 6 years following type 1 diabetics in Gorgan. Journal of Sabzevar Medical
diabetes in children. Iran J Pediatr 2007; 17(3). University 2005; (4): 40-4.
12. Tanaka Y, Atsumi Y, Matsuoka K, Mokubo A, Asa- 26. Farahani H, Naeemi A. A comparison between
hina T, Hosokawa K, et al. Usefulness of stable HbA1c and GTT in diagnostic of diabetes in people
HbA1c for supportive marker to diagnose diabetes with disturbed FBS test. The scientific Journal of
mellitus in Japanese subjects. Diabetes Res Clin Arak Medical university 2004; (4).
Pract 2001; 53(1): 41-5. 27. Amini M, Hoseinpoor M, Satari G, Sasan H. Inves-
13. Kilpatrick ES. Haemoglobin A1c in the diagnosis tigation of the measure of HbA1c in screening of di-
and monitoring of diabetes mellitus. J Clin Pathol abetes and GTT in Isfahan. The Journal of Diabetes
2008; 61(9): 977-82. and Lipid Iran 2001; 1(1): 67-72.
14. Ginde AA, Cagliero E, Nathan DM, Camargo CA, 28. Oset mellaty A, Sharifi F, Amir Aghdami H. Deter-
Jr. Value of risk stratification to increase the predic- mination of normal range for HbA1c in non diabet-
tive validity of HbA1c in screening for undiagnosed ics in Zanjan. The Scientific Journal of Zanjan Med-
diabetes in the US population. J Gen Intern Med ical University 1998; (22): 11-9.
2008; 23(9): 1346-53. 29. Tian H, Lian J, Zhang X. [Glycosylated hemoglobin
15. Anand SS, Razak F, Vuksan V, Gerstein HC, in the diagnosis of diabetes mellitus]. Hua Xi Yi Ke
Malmberg K, Yi Q, et al. Diagnostic strategies to de- Da Xue Xue Bao 1990; 21(2):197-200.
tect glucose intolerance in a multiethnic population. 30. Mirzazadeh A, Baradaran HR, Haghdoost AA, Sala-
Diabetes Care 2003; 26(2): 290-6. ri P. Related factors to disparity of diabetes care in
16. Saudek CD, Herman WH, Sacks DB, Bergenstal Iran. Med Sci Monit 2009; 15(5): H32-H36.
RM, Edelman D, Davidson MB. A new look at