Endocrinol Metab.  2020 Dec;35(4):873-881. 10.3803/EnM.2020.798.

Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity

• Yoo S
• Jung J
• Kim H
• Kim KY
• Kim SK
• Jung J
• Hahm JR
• Baek JH

• KMID: 2511014
• DOI: http://doi.org/10.3803/EnM.2020.798

Abstract

Background
To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity.
Methods
In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index.
Results
During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable.
Conclusion
Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Keyword

Glycated hemoglobin A; Glucose tolerance test; Diabetes mellitus; type 2; Obesity; abdominal

Figure

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  Fig. 1 The correlation between 2-hour postprandial glucose (2hPG; translated into mmol/L) and glycated hemoglobin (HbA1c; %) stratified by the presence of central obesity. (A) Non-obese population. (B) Obese population. Central obesity, ≥90 cm (men) ≥85 cm (women).

Reference

1. Ford ES, Zhao G, Li C. Pre-diabetes and the risk for cardiovascular disease: a systematic review of the evidence. J Am Coll Cardiol. 2010; 55:1310–7.

2. Huang Y, Cai X, Mai W, Li M, Hu Y. Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis. BMJ. 2016; 355:i5953.

3. Dauriz M, Targher G, Temporelli PL, Lucci D, Gonzini L, Nicolosi GL, et al. Prognostic impact of diabetes and prediabetes on survival outcomes in patients with chronic heart failure: a post-hoc analysis of the GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca-Heart Failure) Trial. J Am Heart Assoc. 2017; 6:e005156.

4. Kiviniemi AM, Lepojarvi ES, Tulppo MP, Piira OP, Kentta TV, Perkiomaki JS, et al. Prediabetes and risk for cardiac death among patients with coronary artery disease: the ARTEMIS study. Diabetes Care. 2019; 42:1319–25.

5. International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. 2009; 32:1327–34.

6. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2013; 36(Suppl 1):S67–74.

7. Qiao Q, Jousilahti P, Eriksson J, Tuomilehto J. Predictive properties of impaired glucose tolerance for cardiovascular risk are not explained by the development of overt diabetes during follow-up. Diabetes Care. 2003; 26:2910–4.

8. Warren B, Pankow JS, Matsushita K, Punjabi NM, Daya NR, Grams M, et al. Comparative prognostic performance of definitions of prediabetes: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study. Lancet Diabetes Endocrinol. 2017; 5:34–42.

9. Rosella LC, Lebenbaum M, Fitzpatrick T, Zuk A, Booth GL. Prevalence of prediabetes and undiagnosed diabetes in Canada (2007–2011) according to fasting plasma glucose and HbA1c screening criteria. Diabetes Care. 2015; 38:1299–305.

10. Kim CH, Kim HK, Kim EH, Bae SJ, Choe J, Park JY. Risk of progression to diabetes from prediabetes defined by HbA1c or fasting plasma glucose criteria in Koreans. Diabetes Res Clin Pract. 2016; 118:105–11.

11. Hu Y, Liu W, Chen Y, Zhang M, Wang L, Zhou H, et al. Combined use of fasting plasma glucose and glycated hemoglobin A1c in the screening of diabetes and impaired glucose tolerance. Acta Diabetol. 2010; 47:231–6.

12. Fajans SS, Herman WH, Oral EA. Insufficient sensitivity of hemoglobin A(₁C) determination in diagnosis or screening of early diabetic states. Metabolism. 2011; 60:86–91.

13. Engelgau MM, Thompson TJ, Herman WH, Boyle JP, Aubert RE, Kenny SJ, et al. Comparison of fasting and 2-hour glucose and HbA1c levels for diagnosing diabetes: diagnostic criteria and performance revisited. Diabetes Care. 1997; 20:785–91.

14. Kramer CK, Araneta MR, Barrett-Connor E. A1C and diabetes diagnosis: the Rancho Bernardo Study. Diabetes Care. 2010; 33:101–3.

15. Meijnikman AS, De Block CE, Dirinck E, Verrijken A, Mertens I, Corthouts B, et al. Not performing an OGTT results in significant underdiagnosis of (pre)diabetes in a high risk adult Caucasian population. Int J Obes (Lond). 2017; 41:1615–20.

16. Hu X, Zhang Q, Zeng TS, Zhang JY, Min J, Tian SH, et al. Not performing an OGTT results in underdiagnosis, inadequate risk assessment and probable cost increases of (pre)diabetes in Han Chinese over 40 years: a population-based prospective cohort study. Endocr Connect. 2018; 7:1507–17.

17. Sacks DB. A1C versus glucose testing: a comparison. Diabetes Care. 2011; 34:518–23.

18. Thewjitcharoen Y, Jones Elizabeth A, Butadej S, Nakasatien S, Chotwanvirat P, Wanothayaroj E, et al. Performance of HbA1c versus oral glucose tolerance test (OGTT) as a screening tool to diagnose dysglycemic status in high-risk Thai patients. BMC Endocr Disord. 2019; 19:23.

19. Vajravelu ME, Lee JM. Identifying prediabetes and type 2 diabetes in asymptomatic youth: should HbA1c be used as a diagnostic approach? Curr Diab Rep. 2018; 18:43.

20. Yu EY, Wong CK, Ho SY, Wong SY, Lam CL. Can HbA1c replace OGTT for the diagnosis of diabetes mellitus among Chinese patients with impaired fasting glucose? Fam Pract. 2015; 32:631–8.

21. Unwin N, Howitt C, Rose AM, Samuels TA, Hennis AJ, Hambleton IR. Prevalence and phenotype of diabetes and prediabetes using fasting glucose vs HbA1c in a Caribbean population. J Glob Health. 2017; 7:020407.

22. Iskandar S, Migahid A, Kamal D, Megahed O, DeFronzo RA, Zirie M, et al. Glycated hemoglobin versus oral glucose tolerance test in the identification of subjects with prediabetes in Qatari population. BMC Endocr Disord. 2019; 19:87.

23. Drzewoski J, Czupryniak L. Concordance between fasting and 2-h post-glucose challenge criteria for the diagnosis of diabetes mellitus and glucose intolerance in high risk individuals. Diabet Med. 2001; 18:29–31.

24. Li J, Ma H, Na L, Jiang S, Lv L, Li G, et al. Increased hemoglobin A1c threshold for prediabetes remarkably improving the agreement between A1c and oral glucose tolerance test criteria in obese population. J Clin Endocrinol Metab. 2015; 100:1997–2005.

25. He X, Mo Y, Ma X, Ying L, Zhu W, Wang Y, et al. Associations of body mass index with glycated albumin and glycated albumin/glycated hemoglobin A1c ratio in Chinese diabetic and non-diabetic populations. Clin Chim Acta. 2018; 484:117–121.

26. Kim Y, Han BG; KoGES group. Cohort profile: the Korean Genome and Epidemiology Study (KoGES) Consortium. Int J Epidemiol. 2017; 46:e20.

27. Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000; 23:57–63.

28. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009; 150:604–12.

29. Yoon YS, Oh SW. Optimal waist circumference cutoff values for the diagnosis of abdominal obesity in Korean adults. Endocrinol Metab (Seoul). 2014; 29:418–26.

30. Marseglia L, Manti S, D’Angelo G, Nicotera A, Parisi E, Di Rosa G, et al. Oxidative stress in obesity: a critical component in human diseases. Int J Mol Sci. 2014; 16:378–400.

31. Sathiyapriya V, Selvaraj N, Nandeesha H, Bobby Z, Agrawal A, Sridhar MG, et al. Increased glycation of hemoglobin and plasma proteins in normotensive, non-diabetic obese Indian subjects: putative role of lipid peroxides. Clin Chem Lab Med. 2007; 45:996–9.

32. Lorenzo C, Wagenknecht LE, Hanley AJ, Rewers MJ, Karter AJ, Haffner SM. A1C between 5.7 and 6.4% as a marker for identifying pre-diabetes, insulin sensitivity and secretion, and cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care. 2010; 33:2104–9.

33. Rodriguez-Segade S, Rodriguez J, Camina F, Sanmartin-Portas L, Gerpe-Jamardo J, Pazos-Couselo M, et al. Prediabetes defined by HbA1c and by fasting glucose: differences in risk factors and prevalence. Acta Diabetol. 2019; 56:1023–30.

34. NCD Risk Factor Collaboration (NCD-RisC). Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331,288 participants. Lancet Diabetes Endocrinol. 2015; 3:624–37.