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Relation of adipose tissue insulin resistance to prediabetes

Abstract

Purpose

The degree of adipose tissue insulin resistance increases in obesity, prediabetes and type 2 diabetes, but whether it associates with prediabetes is unclear.

Methods

This is a cross-sectional study of 426 participants. The degree of adipose tissue insulin resistance was assessed using the index of adipose tissue insulin resistance (Adipo-IRI), calculated as the product of fasting insulin and free fatty acids. The association of adipose tissue insulin resistance and prediabetes was assessed by multivariate logistic regression. Area under curves (AUCs) of receiver operating characteristic cure analyses were calculated to assess their diagnostic value in distinguishing prediabetes of the following: insulin resistance in the adipose tissue and peripheral tissue, general and abdominal obesity, and elevated triglycerides.

Results

The median age of the participants was 59 years with males accounting for 47.7%. After adjustment for potential confounding factors, Adipo-IRI was associated with prediabetes and its phenotypes in both genders. The diagnostic value of adipose tissue insulin resistance (AUC, male: 0.71 (95% CI, 0.65–0.77) and female: 0.74 (95% CI, 0.68–0.95)) for prediabetes were superior or similar to peripheral tissue insulin resistance, body mass index, waist circumference and triglycerides.

Conclusions

Adipose tissue insulin resistance is associated with prediabetes and should be considered for use in population studies.

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References

  1. 1.

    L. Wang, P. Gao, M. Zhang, Z. Huang, D. Zhang, Q. Deng, Y. Li, Z. Zhao, X. Qin, D. Jin, M. Zhou, X. Tang, Y. Hu, L. Wang, Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013. JAMA 317(24), 2515–2523 (2017). https://doi.org/10.1001/jama.2017.7596

  2. 2.

    A.G. Tabak, C. Herder, W. Rathmann, E.J. Brunner, M. Kivimaki, Prediabetes: a high-risk state for diabetes development. Lancet 379(9833), 2279–2290 (2012). https://doi.org/10.1016/s0140-6736(12)60283-9

  3. 3.

    R.J. Tapp, G. Tikellis, T.Y. Wong, C.A. Harper, P.Z. Zimmet, J.E. Shaw, Longitudinal association of glucose metabolism with retinopathy: results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study. Diabetes Care 31(7), 1349–1354 (2008). https://doi.org/10.2337/dc07-1707

  4. 4.

    L.C. Plantinga, D.C. Crews, J. Coresh, E.R. Miller 3rd, R. Saran, J. Yee, E. Hedgeman, M. Pavkov, M.S. Eberhardt, D.E. Williams, N.R. Powe, Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin. J. Am. Soc. Nephrol. 5(4), 673–682 (2010). https://doi.org/10.2215/cjn.07891109

  5. 5.

    N. Sarwar, P. Gao, S.R. Seshasai, R. Gobin, S. Kaptoge, E. Di Angelantonio, E. Ingelsson, D.A. Lawlor, E. Selvin, M. Stampfer, C.D. Stehouwer, S. Lewington, L. Pennells, A. Thompson, N. Sattar, I.R. White, K.K. Ray, J. Danesh, Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733), 2215–2222 (2010). https://doi.org/10.1016/s0140-6736(10)60484-9

  6. 6.

    E. Ferrannini, E.J. Barrett, S. Bevilacqua, R.A. DeFronzo, Effect of fatty acids on glucose production and utilization in man. J. Clin. Investig. 72(5), 1737–1747 (1983). https://doi.org/10.1172/jci111133

  7. 7.

    C. Rattarasarn, Dysregulated lipid storage and its relationship with insulin resistance and cardiovascular risk factors in non-obese Asian patients with type 2 diabetes. Adipocyte 7(2), 71–80 (2018). https://doi.org/10.1080/21623945.2018.1429784

  8. 8.

    D.J. Cuthbertson, T. Steele, J.P. Wilding, J.C. Halford, J.A. Harrold, M. Hamer, F. Karpe, What have human experimental overfeeding studies taught us about adipose tissue expansion and susceptibility to obesity and metabolic complications? Int. J. Obes. 41(6), 853–865 (2017). https://doi.org/10.1038/ijo.2017.4

  9. 9.

    G.I. Shulman, Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N. Engl. J. Med. 371(12), 1131–1141 (2014). https://doi.org/10.1056/NEJMra1011035

  10. 10.

    M.D. Jensen, Role of body fat distribution and the metabolic complications of obesity. J. Clin. Endocrinol. Metab. 93(11 Suppl 1), S57–S63 (2008). https://doi.org/10.1210/jc.2008-1585

  11. 11.

    D. Sugimoto, Y. Tamura, K. Takeno, H. Kaga, Y. Someya, S. Kakehi, T. Funayama, Y. Furukawa, R. Suzuki, S. Kadowaki, M. Nishitani-Yokoyama, K. Shimada, H. Daida, S. Aoki, A. Kanazawa, R. Kawamori, H. Watada, Clinical features of non-obese, apparently healthy Japanese men with reduced adipose tissue insulin sensitivity. J. Clin. Endocrinol. Metab. (2019). https://doi.org/10.1210/jc.2018-02190

  12. 12.

    M.J. Armstrong, J.M. Hazlehurst, D. Hull, K. Guo, S. Borrows, J. Yu, S.C. Gough, P.N. Newsome, J.W. Tomlinson, Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis. Diabetes Obes. Metab. 16(7), 651–660 (2014). https://doi.org/10.1111/dom.12272

  13. 13.

    R. Lomonaco, C. Ortiz-Lopez, B. Orsak, A. Webb, J. Hardies, C. Darland, J. Finch, A. Gastaldelli, S. Harrison, F. Tio, K. Cusi, Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. Hepatology 55(5), 1389–1397 (2012). https://doi.org/10.1002/hep.25539

  14. 14.

    C. Ortiz-Lopez, R. Lomonaco, B. Orsak, J. Finch, Z. Chang, V.G. Kochunov, J. Hardies, K. Cusi, Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care 35(4), 873–878 (2012). https://doi.org/10.2337/dc11-1849

  15. 15.

    P. Portillo-Sanchez, F. Bril, M. Maximos, R. Lomonaco, D. Biernacki, B. Orsak, S. Subbarayan, A. Webb, J. Hecht, K. Cusi, High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels. J. Clin. Endocrinol. Metab. 100(6), 2231–2238 (2015). https://doi.org/10.1210/jc.2015-1966

  16. 16.

    R. Lomonaco, F. Bril, P. Portillo-Sanchez, C. Ortiz-Lopez, B. Orsak, D. Biernacki, M. Lo, A. Suman, M.H. Weber, K. Cusi, Metabolic impact of nonalcoholic steatohepatitis in obese patients with type 2 diabetes. Diabetes Care 39(4), 632–638 (2016). https://doi.org/10.2337/dc15-1876

  17. 17.

    E. Sondergaard, A.E. Espinosa De Ycaza, M. Morgan-Bathke, M.D. Jensen, How to measure adipose tissue insulin sensitivity. J. Clin. Endocrinol. Metab. 102(4), 1193–1199 (2017). https://doi.org/10.1210/jc.2017-00047

  18. 18.

    K. Hershkop, O. Besor, N. Santoro, B. Pierpont, S. Caprio, R. Weiss, Adipose insulin resistance in obese adolescents across the spectrum of glucose tolerance. J. Clin. Endocrinol. Metab. 101(6), 2423–2431 (2016). https://doi.org/10.1210/jc.2016-1376

  19. 19.

    A. Gastaldelli, M. Gaggini, R.A. DeFronzo, Role of adipose tissue insulin resistance in the natural history of type 2 diabetes: results from the san antonio metabolism study. Diabetes 66(4), 815–822 (2017). https://doi.org/10.2337/db16-1167

  20. 20.

    J.Y. Kim, F. Bacha, H. Tfayli, S.F. Michaliszyn, S. Yousuf, S. Arslanian, Adipose tissue insulin resistance in youth on the spectrum from normal weight to obese and from normal glucose tolerance to impaired glucose tolerance to type 2 diabetes. Diabetes Care 42(2), 265–272 (2019). https://doi.org/10.2337/dc18-1178

  21. 21.

    L. Mu, R. Li, Y. Lai, Y. Zhao, J. Qiao, Adipose insulin resistance is associated with cardiovascular risk factors in polycystic ovary syndrome. J. Endocrinol. Investig. (2018). https://doi.org/10.1007/s40618-018-0949-2

  22. 22.

    W. Yang, J. Lu, J. Weng, W. Jia, L. Ji, J. Xiao, Z. Shan, J. Liu, H. Tian, Q. Ji, D. Zhu, J. Ge, L. Lin, L. Chen, X. Guo, Z. Zhao, Q. Li, Z. Zhou, G. Shan, J. He, Prevalence of diabetes among men and women in China. N. Engl. J. Med. 362(12), 1090–1101 (2010). https://doi.org/10.1056/NEJMoa0908292

  23. 23.

    G. Chen, L. Shi, L. Cai, W. Lin, H. Huang, J. Liang, L. Li, L. Lin, K. Tang, L. Chen, J. Lu, Y. Bi, W. Wang, G. Ning, J. Wen, Comparison of insulin resistance and beta-cell dysfunction between the Young and the elderly in normal glucose tolerance and prediabetes population: a prospective study. Horm. Metab. Res. 49(2), 135–141 (2017). https://doi.org/10.1055/s-0042-111325

  24. 24.

    X. Cai, L. Xia, Y. Pan, D. He, H. Zhu, T. Wei, Y. He Differential role of insulin resistance and beta-cell function in the development of prediabetes and diabetes in middle-aged and elderly Chinese population. Diabetol. Metab. Syndr. 11, 24 (2019). https://doi.org/10.1186/s13098-019-0418-x

  25. 25.

    T. Siddiquee, B. Bhowmik, R.K. Karmaker, A. Chowdhury, H. Mahtab, A.K. Azad Khan, A. Hussain, Association of general and central obesity with diabetes and prediabetes in rural Bangladeshi population. Diabetes Metab. Syndr. 9(4), 247–251 (2015). https://doi.org/10.1016/j.dsx.2015.02.002

  26. 26.

    F. Haghighatdoost, M. Amini, A. Aminorroaya, M. Abyar, A. Feizi, Different metabolic/obesity phenotypes are differentially associated with development of prediabetes in adults: results from a 14-year cohort study. World J. Diabetes 10(6), 350–361 (2019). https://doi.org/10.4239/wjd.v10.i6.350

  27. 27.

    L.E. Simental-Mendia, M. Rodriguez-Moran, F. Guerrero-Romero, The hypertriglyceridemia is associated with isolated impaired glucose tolerance in subjects without insulin resistance. Endocr. Res. 40(2), 70–73 (2015). https://doi.org/10.3109/07435800.2014.934963

  28. 28.

    S.X. Lin, I. Berlin, R. Younge, Z. Jin, C.T. Sibley, P. Schreiner, M. Szklo, A.G. Bertoni, Does elevated plasma triglyceride level independently predict impaired fasting glucose?: the Multi-Ethnic Study of Atherosclerosis (MESA). Diabetes Care 36(2), 342–347 (2013). https://doi.org/10.2337/dc12-0355

  29. 29.

    A. Beshara, E. Cohen, E. Goldberg, P. Lilos, M. Garty, I. Krause, Triglyceride levels and risk of type 2 diabetes mellitus: a longitudinal large study. J. Investig. Med. 64(2), 383–387 (2016). https://doi.org/10.1136/jim-2015-000025

  30. 30.

    E. Sondergaard, M.D. Jensen, Quantification of adipose tissue insulin sensitivity. J. Investig. Med. 64(5), 989–991 (2016). https://doi.org/10.1136/jim-2016-000098

  31. 31.

    K.W. Ter Horst, K.A. van Galen, P.W. Gilijamse, A.V. Hartstra, P.F. de Groot, F.M. van der Valk, M.T. Ackermans, M. Nieuwdorp, J.A. Romijn, M.J. Serlie, Methods for quantifying adipose tissue insulin resistance in overweight/obese humans. Int. J. Obes. 41(8), 1288–1294 (2017). https://doi.org/10.1038/ijo.2017.110

  32. 32.

    Classification and Diagnosis of Diabetes Standards of medical care in diabetes-2019. Diabetes Care 42(Suppl 1), S13–S28 (2019). https://doi.org/10.2337/dc19-S002

  33. 33.

    C. Chen, F.C. Lu, The guidelines for prevention and control of overweight and obesity in Chinese adults. Biomed. Environ. Sci. 17(Suppl 1), 1–36 (2004).

  34. 34.

    K.G. Alberti, P. Zimmet, J. Shaw, The metabolic syndrome-a new worldwide definition. Lancet 366(9491), 1059–1062 (2005). https://doi.org/10.1016/s0140-6736(05)67402-8

  35. 35.

    J. Chalmers, S. MacMahon, G. Mancia, J. Whitworth, L. Beilin, L. Hansson, B. Neal, A. Rodgers, C. Ni Mhurchu, T. Clark, World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization. Clinical and experimental hypertension (New York, N.Y.: 1993) 21(5–6), 1009–1060 (1999). https://doi.org/10.3109/10641969909061028

  36. 36.

    Joint Committee for Developing Chinese guidelines on Prevention and Treatment of lipidemia in Adults Chinese guidelines on prevention and treatment of dyslipidemia in adults, 2016 revised edition [in Chinese]. Chin. Circ J. 31, 937–953 (2016)

  37. 37.

    E. Jorge-Galarza, A. Medina-Urrutia, R. Posadas-Sanchez, C. Posadas-Romero, G. Cardoso-Saldana, G. Vargas-Alarcon, N. Caracas-Portilla, C. Gonzalez-Salazar, M. Torres-Tamayo, J.G. Juarez-Rojas, Adipose tissue dysfunction increases fatty liver association with pre diabetes and newly diagnosed type 2 diabetes mellitus. Diabetol. Metab. Syndr. 8, 73 (2016). https://doi.org/10.1186/s13098-016-0189-6

  38. 38.

    V.K.R. Nayak, K. Raghurama Nayak, S. Vidyasagar, A: Kamath, Body composition analysis, anthropometric indices and lipid profile markers as predictors for prediabetes. PloS ONE 13 (8), e0200775 (2018). https://doi.org/10.1371/journal.pone.0200775

  39. 39.

    Classification and Diagnosis of Diabetes Standards of medical care in diabetes-2018. Diabetes Care 4(Suppl 1), S13–S27 (2018). https://doi.org/10.2337/dc18-S002

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Acknowledgements

All authors appreciate the efforts of all participants who contributed to sample measurements and data collection.

Funding

This study was funded by the National Natural Science Foundation of China (31672375, 81971091), Beijing Municipal Administration of Hospitals (QML20190501), and the Ministry of Science and Technology of the People’s Republic of China (2017YFC1310902, 2018YFC1311700, and 2018YFC1311706).

Author contributions

Each author has been involved in and contributed to this paper. JW and XC carried out the statistical analyses and drafted the paper. They contributed equally to this study and share first authorship. JJ, GL and MW participated in the data analysis. JZ and WL participated in the literature search. XC and YP participated in the data collection, study management and study coordination. HYG and YP contributed to editing the paper to correct English. YH and YP contributed to the study design and review of this paper. All authors read and approved the final paper.

Author information

Correspondence to Yuesong Pan or Yan He.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was reviewed and approved by the Committee on Human Research of Lishui Central Hospital, and all procedures were performed in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

The study methods and potential risks were fully explained to all participants, and each participant provided a written informed consent prior to enrollment.

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Cite this article

Wen, J., Cai, X., Zhang, J. et al. Relation of adipose tissue insulin resistance to prediabetes. Endocrine (2020) doi:10.1007/s12020-020-02186-8

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Keywords

  • Adipose tissue insulin resistance
  • Prediabetes
  • Association
  • Diagnostic value
  • Indicator