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Modulation of coronary heart disease risk by insulin resistance in subjects with normal glucose tolerance or prediabetes

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Abstract

Aims

This study was based on the hypothesis that: (1) coronary heart disease (CHD) risk is accentuated in the insulin-resistant subset of persons with normal glucose tolerance (NGT) or prediabetes (PreDM); (2) the prevalence of insulin resistance, and associated abnormalities, is greater in subjects with PreDM; and (3) insulin resistance is the major contributor to increased CHD risk in these individuals.

Methods

A 75 g oral glucose challenge was used to classify volunteers as having NGT or PreDM. Steady-state plasma glucose (SSPG) concentrations during the insulin suppression test subdivided both groups into insulin sensitive (IS = SSPG < 8.4 mmol/L) or resistant (IR = SSPG ≥ 8.4 mmol/L). Measurements were made of demographic characteristics, blood pressure, and lipid and lipoprotein concentrations, and comparisons made between the subgroups.

Results

Subjects with PreDM (n = 127) were somewhat older, more likely to be non-Hispanic men, with increased adiposity than those with NGT (n = 315). In addition, they had higher FPG concentrations, were insulin resistant (SSPG concentration; 11.4 vs. 7.2 mmol/L), with higher blood pressures, and a significantly more adverse CHD risk lipid profile (p < 0.001). Twice as many subjects with PreDM were IR (72 vs. 35 %), and the CHD risk profile was significantly worse in the IR subgroups in those with either NGT or PreDM.

Conclusions

Coronary heart disease risk profile is significantly more adverse in subjects with PreDM as compared to individuals with NGT. However, glucose tolerance status is not the only determinant of CHD risk in nondiabetic individuals, and differences in degree of insulin resistance significantly modulate CHD risk in subjects with NGT or PreDM.

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References

  1. American Diabetes Association (2013) Standards of medical care in diabetes—2013. Diabetes Care 36(Suppl 1):S11–S66. doi:10.2337/dc13-S011

    Article  PubMed Central  Google Scholar 

  2. Helfand M, Buckley DI, Freeman M, Fu R, Rogers K, Fleming C, Humphrey LL (2009) Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force. Ann Intern Med 151(7):496–507

    Article  PubMed  Google Scholar 

  3. Sarwar N, Aspelund T, Eiriksdottir G, Gobin R, Seshasai SR, Forouhi NG, Sigurdsson G, Danesh J, Gudnason V (2010) Markers of dysglycaemia and risk of coronary heart disease in people without diabetes: reykjavik prospective study and systematic review. PLoS Med 7(5):e1000278. doi:10.1371/journal.pmed.1000278

    Article  PubMed Central  PubMed  Google Scholar 

  4. Emerging Risk Factors Collaboration, Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733):2215–2222. doi:10.1016/S0140-6736(10)60484-9

    Article  CAS  PubMed  Google Scholar 

  5. Onat A, Can G, Cicek G, Ayhan E, Dogan Y, Kaya H (2013) Fasting, non-fasting glucose and HDL dysfunction in risk of pre-diabetes, diabetes, and coronary disease in non-diabetic adults. Acta Diabetol 50(4):519–528. doi:10.1007/s00592-011-0313-x

    Article  CAS  PubMed  Google Scholar 

  6. Kim SH, Reaven GM (2008) Isolated impaired fasting glucose and peripheral insulin sensitivity: not a simple relationship. Diabetes Care 31(2):347–352. doi:10.2337/dc07-1574

    Article  CAS  PubMed  Google Scholar 

  7. American Diabetes Association (2005) Diagnosis and classification of diabetes mellitus. Diabetes Care 28(Suppl 1):S37–S42

    Article  Google Scholar 

  8. Pei D, Jones CN, Bhargava R, Chen YD, Reaven GM (1994) Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test. Diabetologia 37(8):843–845

    Article  CAS  PubMed  Google Scholar 

  9. Greenfield MS, Doberne L, Kraemer F, Tobey T, Reaven G (1981) Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp. Diabetes 30(5):387–392

    Article  CAS  PubMed  Google Scholar 

  10. Knowles JW, Assimes TL, Tsao PS, Natali A, Mari A, Quertermous T, Reaven GM, Abbasi F (2013) Measurement of insulin-mediated glucose uptake: direct comparison of the modified insulin suppression test and the euglycemic, hyperinsulinemic clamp. Metabolism 62(4):548–553. doi:10.1016/j.metabol.2012.10.002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Shen SW, Reaven GM, Farquhar JW (1970) Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest 49(12):2151–2160. doi:10.1172/JCI106433

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Facchini FS, Hua N, Abbasi F, Reaven GM (2001) Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab 86(8):3574–3578. doi:10.1210/jcem.86.8.7763

    Article  CAS  PubMed  Google Scholar 

  13. Yip J, Facchini FS, Reaven GM (1998) Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab 83(8):2773–2776. doi:10.1210/jcem.83.8.5005

    Article  CAS  PubMed  Google Scholar 

  14. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419

    Article  CAS  PubMed  Google Scholar 

  15. Abbasi F, Okeke Q, Reaven GM (2014) Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR). Acta Diabetol 51(2):193–197. doi:10.1007/s00592-013-0461-2

    Article  CAS  PubMed  Google Scholar 

  16. Evaluation EPoD, Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). J Am Med Assoc 285(19):2486–2497

    Article  Google Scholar 

  17. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16):1640–1645. doi:10.1161/CIRCULATIONAHA.109.192644

    Article  CAS  PubMed  Google Scholar 

  18. Ceriello A (2010) Point: postprandial glucose levels are a clinically important treatment target. Diabetes Care 33(8):1905–1907. doi:10.2337/dc10-0634

    Article  PubMed Central  PubMed  Google Scholar 

  19. Holman RR, Haffner SM, McMurray JJ, Bethel MA, Holzhauer B, Hua TA, Belenkov Y, Boolell M, Buse JB, Buckley BM, Chacra AR, Chiang FT, Charbonnel B, Chow CC, Davies MJ, Deedwania P, Diem P, Einhorn D, Fonseca V, Fulcher GR, Gaciong Z, Gaztambide S, Giles T, Horton E, Ilkova H, Jenssen T, Kahn SE, Krum H, Laakso M, Leiter LA, Levitt NS, Mareev V, Martinez F, Masson C, Mazzone T, Meaney E, Nesto R, Pan C, Prager R, Raptis SA, Rutten GE, Sandstroem H, Schaper F, Scheen A, Schmitz O, Sinay I, Soska V, Stender S, Tamas G, Tognoni G, Tuomilehto J, Villamil AS, Vozar J, Califf RM (2010) Effect of nateglinide on the incidence of diabetes and cardiovascular events. N Engl J Med 362(16):1463–1476. doi:10.1056/NEJMoa1001122

    Article  CAS  PubMed  Google Scholar 

  20. Reaven GM (2003) The insulin resistance syndrome. Curr Atheroscler Rep 5(5):364–371

    Article  PubMed  Google Scholar 

  21. World Health Organization (1999) Definition, diagnosis and classification of diabetes mellitus and its complications: report of a WHO consultation. Part 1: Diagnosis and classification of diabetes mellitus. Department of Noncommunicable Disease Surveillance, Geneva, Switzerland

  22. Ortega FJ, Mercader JM, Moreno-Navarrete JM, Rovira O, Guerra E, Esteve E, Xifra G, Martinez C, Ricart W, Rieusset J, Rome S, Karczewska-Kupczewska M, Straczkowski M, Fernandez-Real JM (2014) Profiling of circulating microRNAs reveals common microRNAs linked to type 2 diabetes that change with insulin sensitization. Diabetes Care 37(5):1375–1383. doi:10.2337/dc13-1847

    Article  CAS  PubMed  Google Scholar 

  23. Yang Z, Chen H, Si H, Li X, Ding X, Sheng Q, Chen P, Zhang H (2014) Serum miR-23a, a potential biomarker for diagnosis of pre-diabetes and type 2 diabetes. Acta Diabetol 51(5):823–831. doi:10.1007/s00592-014-0617-8

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was conduced with support from a KL2 Mentored Career Development Award of the Stanford Clinical and Translational Science Award to Spectrum (NIH KL2 TR 001083) and an American Diabetes Association Mentor-Based Postdoctoral Fellowship Award.

Conflict of interest

Danit Ariel and Gerald Reaven declare that they have no conflict of interest.

Human and Animal Rights disclosure

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.

Informed consent disclosure

Informed consent was obtained from all patients before being included in the study.

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Authors and Affiliations

  1. Department of Medicine, Stanford University School of Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room S025, Stanford, CA, 94305-5103, USA

    Danit Ariel & Gerald Reaven

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  1. Danit Ariel
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  2. Gerald Reaven
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Correspondence to Danit Ariel.

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Ariel, D., Reaven, G. Modulation of coronary heart disease risk by insulin resistance in subjects with normal glucose tolerance or prediabetes. Acta Diabetol 51, 1033–1039 (2014). https://doi.org/10.1007/s00592-014-0667-y

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  • DOI: https://doi.org/10.1007/s00592-014-0667-y

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