Skip to main content
SpringerLink
Log in

Elevated A1C is associated with impaired early-phase insulin secretion rather than insulin resistance in Koreans at high risk for developing diabetes

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

An Erratum to this article was published on 07 July 2012

Abstract

The purpose of this study is to examine the association of A1C with beta-cell dysfunction, insulin resistance, and cardiovascular risk factors in Koreans with the relatively high risk for the future development of diabetes. This cross-sectional study recruited subjects from the pre-diabetic cohort of the Korea National Diabetes Program. Among study subjects (n = 616) aged 21–77 years with a history of hyperglycemia (fasting plasma glucose (FPG) ≥5.5 mmol/mL), analyses were conducted on 504 participants (296 women, 208 men) except for subjects with FPG ≥ 7.0 mmol/L or 120-min post-challenge plasma glucose ≥11.1 mmol/L or A1C ≥ 6.5 %. For insulin sensitivity and β-cell function classified by the categories of A1C levels, ∆Ins30-0/∆Glu30-0 was lower in the highest quartile group than other groups. Although there was no significant difference in HOMA-IR according to the A1C categories, even lowest A1C group (≤5.3 %) already included many subjects with abnormal glucose tolerance. A1C showed a significant association with hsCRP, number of metabolic syndrome (MetS) components and ∆Ins30-0/∆Glu30-0 after adjusting for age, gender, BMI, and medications whereas HOMA-IR was insignificantly associated with A1C. Stepwise regression analysis for A1C showed that A1C is independently and negatively associated with ∆Ins30-0/∆Glu30-0, and positively associated with hsCRP. Our study showed that higher A1C was associated with impaired early-phase insulin secretion, MetS, and low grade inflammation in Koreans with the relatively high risk for the future development of diabetes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. J.C. Chan, V. Malik, W. Jia, T. Kadowaki, C.S. Yajnik, K.H. Yoon, F.B. Hu, Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 301, 2129–2140 (2009)

    Article  PubMed  CAS  Google Scholar 

  2. K.G. Alberti, P.Z. Zimmet, Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet. Med. 15, 539–553 (1998)

    Article  PubMed  CAS  Google Scholar 

  3. R.G. Barr, D.M. Nathan, J.B. Meigs, D.E. Singer, Tests of glycemia for the diagnosis of type 2 diabetes mellitus. Ann. Intern. Med. 137, 263–272 (2002)

    PubMed  Google Scholar 

  4. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20, 1183–1197 (1997)

  5. International expert committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 32, 1327–1334 (2009)

  6. Y. Tahara, K. Shima, Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level. Diabetes Care 18, 440–447 (1995)

    Article  PubMed  CAS  Google Scholar 

  7. K.H. Tseng, Standards of medical care in diabetes—2006: response to the American Diabetes Association. Diabetes Care 29, 2563–2564 (2006). author reply 2564–2565

    Article  PubMed  Google Scholar 

  8. C. Meyer, W. Pimenta, H.J. Woerle, T. Van Haeften, E. Szoke, A. Mitrakou, J. Gerich, Different mechanisms for impaired fasting glucose and impaired postprandial glucose tolerance in humans. Diabetes Care 29, 1909–1914 (2006)

    Article  PubMed  CAS  Google Scholar 

  9. K. Faerch, A. Vaag, J.J. Holst, T. Hansen, T. Jorgensen, K. Borch-Johnsen, Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care 32, 439–444 (2009)

    Article  PubMed  CAS  Google Scholar 

  10. M.A. Abdul-Ghani, C.P. Jenkinson, D.K. Richardson, D. Tripathy, R.A. DeFronzo, Insulin secretion and action in subjects with impaired fasting glucose and impaired glucose tolerance: results from the Veterans Administration Genetic Epidemiology Study. Diabetes 55, 1430–1435 (2006)

    Article  PubMed  CAS  Google Scholar 

  11. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. National Diabetes Data Group. Diabetes 28, 1039–1057 (1979)

  12. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26 Suppl 1, S5–20 (2003)

    Google Scholar 

  13. W.T. Friedewald, R.I. Levy, D.S. Fredrickson, Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem. 18, 499–502 (1972)

    PubMed  CAS  Google Scholar 

  14. A. Caumo, G. Perseghin, A. Brunani, L. Luzi, New insights on the simultaneous assessment of insulin sensitivity and beta-cell function with the HOMA2 method. Diabetes Care 29, 2733–2734 (2006)

    Article  PubMed  CAS  Google Scholar 

  15. T.M. Wallace, J.C. Levy, D.R. Matthews, Use and abuse of HOMA modeling. Diabetes Care 27, 1487–1495 (2004)

    Article  PubMed  Google Scholar 

  16. M. Matsuda, R.A. DeFronzo, Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22, 1462–1470 (1999)

    Article  PubMed  CAS  Google Scholar 

  17. C.C. Jensen, M. Cnop, R.L. Hull, W.Y. Fujimoto, S.E. Kahn, Beta-cell function is a major contributor to oral glucose tolerance in high-risk relatives of four ethnic groups in the US. Diabetes 51, 2170–2178 (2002)

    Article  PubMed  CAS  Google Scholar 

  18. S.M. Grundy, J.I. Cleeman, S.R. Daniels, K.A. Donato, R.H. Eckel, B.A. Franklin, D.J. Gordon, R.M. Krauss, P.J. Savage, S.C. Smith Jr, J.A. Spertus, F. Costa, Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Executive summary. Cardiol. Rev. 13, 322–327 (2005)

    PubMed  Google Scholar 

  19. U.K. prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes 44, 1249–1258 (1995)

    Google Scholar 

  20. V.A. Fonseca, Identification and treatment of prediabetes to prevent progression to type 2 diabetes. Clin. Cornerstone 9, 51–59 (2008). discussion 60-51

    Article  PubMed  Google Scholar 

  21. D. Edelman, M.K. Olsen, T.K. Dudley, A.C. Harris, E.Z. Oddone, Utility of hemoglobin A1c in predicting diabetes risk. J. Gen. Intern. Med. 19, 1175–1180 (2004)

    Article  PubMed  Google Scholar 

  22. C. Droumaguet, B. Balkau, D. Simon, E. Caces, J. Tichet, M.A. Charles, E. Eschwege, Use of HbA1c in predicting progression to diabetes in French men and women: data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR). Diabetes Care 29, 1619–1625 (2006)

    Article  PubMed  CAS  Google Scholar 

  23. A.D. Pradhan, N. Rifai, J.E. Buring, P.M. Ridker, Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women. Am. J. Med. 120, 720–727 (2007)

    Article  PubMed  CAS  Google Scholar 

  24. K.K. Sato, T. Hayashi, N. Harita, T. Yoneda, Y. Nakamura, G. Endo, H. Kambe, Combined measurement of fasting plasma glucose and A1C is effective for the prediction of type 2 diabetes: the Kansai Healthcare Study. Diabetes Care 32, 644–646 (2009)

    Article  PubMed  CAS  Google Scholar 

  25. T. Shimazaki, T. Kadowaki, Y. Ohyama, K. Ohe, K. Kubota, Hemoglobin A1c (HbA1c) predicts future drug treatment for diabetes mellitus: a follow-up study using routine clinical data in a Japanese university hospital. Transl. Res. 149, 196–204 (2007)

    Article  PubMed  CAS  Google Scholar 

  26. L.S. Geiss, L. Pan, B. Cadwell, E.W. Gregg, S.M. Benjamin, M.M. Engelgau, Changes in incidence of diabetes in US adults, 1997–2003. Am. J. Prev. Med. 30, 371–377 (2006)

    Article  PubMed  Google Scholar 

  27. S.E. Kahn, R.L. Prigeon, D.K. McCulloch, E.J. Boyko, R.N. Bergman, M.W. Schwartz, J.L. Neifing, W.K. Ward, J.C. Beard, J.P. Palmer et al., Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42, 1663–1672 (1993)

    Article  PubMed  CAS  Google Scholar 

  28. R.N. Bergman. Orchestration of homeostasis of glucose metabolism. Journ Annu Diabetol Hotel Dieu, 127–138 (2007)

  29. K.M. Utzschneider, R.L. Prigeon, D.B. Carr, R.L. Hull, J. Tong, J.B. Shofer, B.M. Retzlaff, R.H. Knopp, S.E. Kahn, Impact of differences in fasting glucose and glucose tolerance on the hyperbolic relationship between insulin sensitivity and insulin responses. Diabetes Care 29, 356–362 (2006)

    Article  PubMed  Google Scholar 

  30. J. Hong, W.Q. Gu, Y.F. Zhang, Y.S. Yang, C.F. Shen, M. Xu, X.Y. Li, W.Q. Wang, G. Ning, The interplay of insulin resistance and beta-cell dysfunction involves the development of type 2 diabetes in Chinese obeses. Endocrine 31, 93–99 (2007)

    Article  PubMed  CAS  Google Scholar 

  31. C.A. Slentz, C.J. Tanner, L.A. Bateman, M.T. Durheim, K.M. Huffman, J.A. Houmard, W.E. Kraus, Effects of exercise training intensity on pancreatic beta-cell function. Diabetes Care 32, 1807–1811 (2009)

    Article  PubMed  CAS  Google Scholar 

  32. C.S. Shin, H.K. Lee, C.S. Koh, Y.I. Kim, Y.S. Shin, K.Y. Yoo, H.Y. Paik, Y.S. Park, B.G. Yang, Risk factors for the development of NIDDM in Yonchon County, Korea. Diabetes Care 20, 1842–1846 (1997)

    Article  PubMed  CAS  Google Scholar 

  33. A. Dehghan, I. Kardys, M.P. de Maat, A.G. Uitterlinden, E.J. Sijbrands, A.H. Bootsma, T. Stijnen, A. Hofman, M.T. Schram, J.C. Witteman, Genetic variation, C-reactive protein levels, and incidence of diabetes. Diabetes 56, 872–878 (2007)

    Article  PubMed  CAS  Google Scholar 

  34. T.S. Han, N. Sattar, K. Williams, C. Gonzalez-Villalpando, M.E. Lean, S.M. Haffner, Prospective study of C-reactive protein in relation to the development of diabetes and metabolic syndrome in the Mexico City Diabetes Study. Diabetes Care 25, 2016–2021 (2002)

    Article  PubMed  CAS  Google Scholar 

  35. F.B. Hu, J.B. Meigs, T.Y. Li, N. Rifai, J.E. Manson, Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes 53, 693–700 (2004)

    Article  PubMed  CAS  Google Scholar 

  36. S. Nakanishi, K. Yamane, N. Kamei, M. Okubo, N. Kohno, Elevated C-reactive protein is a risk factor for the development of type 2 diabetes in Japanese Americans. Diabetes Care 26, 2754–2757 (2003)

    Article  PubMed  CAS  Google Scholar 

  37. A.D. Pradhan, J.E. Manson, N. Rifai, J.E. Buring, P.M. Ridker, C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286, 327–334 (2001)

    Article  PubMed  CAS  Google Scholar 

  38. R.H. Eckel, S.M. Grundy, P.Z. Zimmet, The metabolic syndrome. Lancet 365, 1415–1428 (2005)

    Article  PubMed  CAS  Google Scholar 

  39. S.M. Grundy, H.B. Brewer Jr, J.I. Cleeman, S.C. Smith Jr, C. Lenfant, Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arter. Thromb. Vasc. Biol. 24, e13–e18 (2004)

    Article  CAS  Google Scholar 

  40. D.E. Laaksonen, H.M. Lakka, L.K. Niskanen, G.A. Kaplan, J.T. Salonen, T.A. Lakka, Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study. Am. J. Epidemiol. 156, 1070–1077 (2002)

    Article  PubMed  Google Scholar 

  41. R.L. Hanson, G. Imperatore, P.H. Bennett, W.C. Knowler, Components of the “metabolic syndrome” and incidence of type 2 diabetes. Diabetes 51, 3120–3127 (2002)

    Article  PubMed  CAS  Google Scholar 

  42. E.S. Ford, C. Li, N. Sattar, Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care 31, 1898–1904 (2008)

    Article  PubMed  Google Scholar 

  43. E.S. Kang, Y.S. Yun, S.W. Park, H.J. Kim, C.W. Ahn, Y.D. Song, B.S. Cha, S.K. Lim, K.R. Kim, H.C. Lee, Limitation of the validity of the homeostasis model assessment as an index of insulin resistance in Korea. Metabolism 54, 206–211 (2005)

    Article  PubMed  CAS  Google Scholar 

  44. J.M. Mooy, P.A. Grootenhuis, H. de Vries, P.J. Kostense, C. Popp-Snijders, L.M. Bouter, R.J. Heine, Intra-individual variation of glucose, specific insulin and proinsulin concentrations measured by two oral glucose tolerance tests in a general Caucasian population: the Hoorn Study. Diabetologia 39, 298–305 (1996)

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by a Korean Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant No. A102065).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 152-050, Korea

    Tae Nyun Kim, Sae Jeong Yang & Sei Hyun Baik

  2. Department of Internal Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Korea

    Tae Nyun Kim

  3. Department of Statistics, College of Natural Sciences, Sungshin Women’s University, Seoul, Korea

    Man Sik Park & Seong Keon Lee

  4. Department of Internal Medicine, Ajou University College of Medicine, Suwon, Korea

    Kwan Woo Lee

  5. Department of Internal Medicine, Inha University College of Medicine, Incheon, Korea

    Moon Suk Nam

  6. Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea

    Yong Soo Park

  7. Department of Internal Medicine, Kyung Hee University College of Medicine, Seoul, Korea

    Jeong Taek Woo & Young Seol Kim

Authors
  1. Tae Nyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Man Sik Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seong Keon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sae Jeong Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kwan Woo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Moon Suk Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yong Soo Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jeong Taek Woo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Young Seol Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sei Hyun Baik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sei Hyun Baik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, T.N., Park, M.S., Lee, S.K. et al. Elevated A1C is associated with impaired early-phase insulin secretion rather than insulin resistance in Koreans at high risk for developing diabetes. Endocrine 42, 584–591 (2012). https://doi.org/10.1007/s12020-012-9666-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9666-3

Keywords

Search

Navigation