The association between the skeletal muscle state, lipid metabolism disorders and the development of insulin resistance in children with type 1 diabetes mellitus

Authors

DOI:

https://doi.org/10.14739/2310-1210.2022.6.261182

Keywords:

children, diabetes mellitus, diabetic myopathy, dyslipidemia, insulin resistance

Abstract

The aim of the study. To establish a possible association between the skeletal muscles state, changes in lipid metabolism and the development of insulin resistance in children with type I diabetes mellitus.

Materials and methods. 98 children with type 1 diabetes, aged from 11 to 17 years, were examined. Children were divided into 3 groups depending on the state of skeletal muscles: the first group – 22 children without disorders of the muscular system; the second group – 42 children with dynapenia; the third group – 34 patients with diabetic myopathy. The control group – 30 conditionally healthy children. The groups were representative by age, sex, and body mass index.

Children were subjected to examinations of skeletal muscle mass and fat mass, followed by calculation of the skeletal muscle index and body fat percentage, sonomyography of the anterior group of thigh muscles with their thickness determination, measurements of the degree and coefficient of muscle hypotrophy, fasting blood glucose level, serum cholesterol, triglycerides and triglyceride-glucose (TyG) index. Insulin resistance was diagnosed when the TyG index was higher than 4.33 c. u.

Results. It was found that the development of diabetic myopathy, in addition to a decrease in muscle mass, was characterized by a redistribution of the body component composition due an increase in the fat mass proportion. These changes were accompanied by a disturbance of lipid metabolism in the form of increase in serum cholesterol level, triglycerides and TyG index, which was 4.33 c. u. higher in 32.4 % of children with diabetic myopathy, and in 9.5 % of children with dynapenia, while among patients with normal state of the muscular system, the TyG index exceeded the threshold value in no case. Comparison of clinical and laboratory indicators depending on the TyG index level found an increase in the fat mass proportion, a violation of glycemic control, an increase in the daily dose of insulin, appearance of combined hyperlipidemia and the dawn phenomenon in children with an indicator that was higher than 4.33 c. u. All these were indicative of the insulin resistance development.

Conclusions. Skeletal muscle dysfunction in children with type 1 diabetes is a causal risk factor for the development of insulin resistance, a sensitive marker of which is the TyG index. The simplicity of calculating this indicator allows it to be used in daily clinical practice.

Author Biographies

H. O. Lezhenko, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Head of the Department of Hospital Pediatrics

O. Ye. Pashkova, Zaporizhzhia State Medical University, Ukraine

MD, PhD, DSc, Professor of the Department of Hospital Pediatrics

N. I. Chudova, Zaporizhzhia State Medical University, Ukraine

Assistant of the Department of Hospital Pediatrics

References

  1. Bjornstad, P., & Eckel, R. H. (2018). Pathogenesis of Lipid Disorders in Insulin Resistance: a Brief Review. Current diabetes reports, 18(12), 127. https://doi.org/10.1007/s11892-018-1101-6
  2. Tagi, V. M., Giannini, C., & Chiarelli, F. (2019). Insulin resistance in children. Frontiers in endocrinology, 10, 342. https://doi.org/10.3389/fendo.2019.00342
  3. Amin, S. N., Hussein, U. K., Yassa, H. D., Hassan, S. S., & Rashed, L. A. (2018). Synergistic actions of vitamin D and metformin on skeletal muscles and insulin resistance of type 2 diabetic rats. Journal of Cellular Physiology, 233(8), 5768-5779. https://doi.org/10.1002/jcp.26300
  4. Gancheva, S., Ouni, M., Jelenik, T., Koliaki, C., Szendroedi, J., Toledo, F. G., & Roden, M. (2019). Dynamic changes of muscle insulin sensitivity after metabolic surgery. Nature communications, 10(1), 1-13. https://doi.org/10.1038/s41467-019-12081-0
  5. Bergman, B. C., Howard, D., Schauer, I. E., Maahs, D. M., Snell-Bergeon, J. K., Eckel, R. H., & Rewers, M. (2012). Features of hepatic and skeletal muscle insulin resistance unique to type 1 diabetes. The Journal of Clinical Endocrinology, 97(5), 1663-1672. https://doi.org/10.1210/jc.2011-3172
  6. Kaul, K., Apostolopoulou, M., & Roden, M. (2015). Insulin resistance in type 1 diabetes mellitus. Metabolism, 64(12), 1629-1639 https://doi.org/10.1016/j.metabol.2015.09.002
  7. Garneau, L., & Aguer, C. (2019). Role of myokines in the development of skeletal muscle insulin resistance and related metabolic defects in type 2 diabetes. Diabetes & metabolism, 45(6), 505-516. https://doi.org/10.1016/j.diabet.2019.02.006
  8. Spartano, N. L., Stevenson, M. D., Xanthakis, V., Larson, M. G., Andersson, C., Murabito, J. M., & Vasan, R. S. (2017). Associations of objective physical activity with insulin sensitivity and circulating adipokine profile: the Framingham Heart Study. Clinical obesity, 7(2), 59-69. https://doi.org/10.1111/cob.12177
  9. Haddad, D., Al Madhoun, A., Nizam, R., & Al-Mulla, F. (2020). Role of Caveolin-1 in Diabetes and Its Complications. Oxidative medicine and cellular longevity, 2020, 9761539. https://doi.org/10.1155/2020/9761539
  10. Sushko, O. O., Iskra, R. J., & Ponkalo, L. I. (2019). Influence of chromium citrate on oxidative stress in the tissues of muscle and kidney of rats with experimentally induced diabetes. Regulatory Mechanisms in Biosystems, 10(2), 209-214. https://doi.org/10.15421/0219231
  11. Guy, J., Ogden, L., Wadwa, R. P., Hamman, R. F., Mayer-Davis, E. J., Liese, A. D., & Dabelea, D. (2009). Lipid and lipoprotein profiles in youth with and without type 1 diabetes: the SEARCH for Diabetes in Youth case-control study. Diabetes care, 32(3), 416-420. https://doi.org/10.2337/dc08-1775
  12. DuBose, S. N., Hermann, J. M., Tamborlane, W. V., Beck, R. W., Dost, A., DiMeglio, L. A., & Criego, A. (2015). Obesity in youth with type 1 diabetes in Germany, Austria, and the United States. The Journal of pediatrics, 167(3), 627-632. https://doi.org/10.1016/j.jpeds.2015.05.046
  13. Petersen, M. C., & Shulman, G. I. (2018). Mechanisms of insulin action and insulin resistance. Physiological reviews, 98(4), 2133-2223. https://doi.org/10.1152/physrev.00063.2017
  14. Ormazabal, V., Nair, S., Elfeky, O., Aguayo, C., Salomon, C., & Zuñiga, F. A. (2018). Association between insulin resistance and the development of cardiovascular disease. Cardiovascular Diabetology, 17(1), 122. https://doi.org/10.1186/s12933-018-0762-4
  15. García, A. G., Treviño, M. V. U., Sánchez, D. C. V., & Aguilar, C. A. (2019). Diagnostic accuracy of triglyceride/glucose and triglyceride/HDL index as predictors for insulin resistance in children with and without obesity. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13(4), 2329-2334. https://doi.org/10.1016/j.dsx.2019.05.020
  16. Peters, A. M., Snelling, H. L. R., Glass, D. M., & Bird, N. J. (2012). Estimation of Lean Body Mass in Children. Survey of Anesthesiology, 56(1), 26-27. https://doi.org/10.1097/01.SA.0000410700.55371.0f
  17. Boer, P. (1984). Estimated lean body mass as an index for normalization of body fluid volumes in humans. American Journal of Physiology-Renal Physiology, 247(4), F632-F636. https://doi.org/10.1152/ajprenal.1984.247.4.F632
  18. Janssen, I., Heymsfield, S. B., & Ross, R. (2002). Low relative skeletal muscle mass (sarcopenia) in older persons is associated with functional impairment and physical disability. Journal of the American Geriatrics Society, 50(5), 889-896. https://doi.org/10.1046/j.1532-5415.2002.50216.x
  19. Deurenberg, P., Weststrate, J. A., & Seidell, J. C. (1991). Body mass index as a measure of body fatness: age-and sex-specific prediction formulas. British journal of nutrition, 65(2), 105-114. https://doi.org/10.1079/bjn19910073
  20. Akay, A. F., Gedik, A., Tutus, A., Şahin, H., & Bircan, M. K. (2007). Body mass index, body fat percentage, and the effect of body fat mass on SWL success. International urology and nephrology, 39(3), 727-730. https://doi.org/10.1007/s11255-006-9133-2
  21. Chudova, N. I. (2021). Rannia diahnostyka, prohnozuvannia vynyknennia ta obgruntuvannia pidkhodiv do profilaktyky porushen miazovoi systemy u ditei, khvorykh na tsukrovyi diabet [Early diagnosis, prediction and objectives of approaches to the prevention of muscular system disorders in children suffering from diabetes mellitus (PhD Thesis)]. Zaporizhzhia State Medical University of the Ministry of Health of Ukraine, Zaporizhzhia. https://zsmu.edu.ua/upload/updisert/dfpediatr/12022022_dis_chudova.pdf
  22. Sokol, V. K. (2019) Otsinka strukturno-funktsionalnoho stanu miaziv u razi naslidkiv perelomiv kistok homilky za danymy ultrazvukovoho doslidzhennia [Evaluation of the muscles structural and functional state during the оutcome of fracture of the shin bones according to ultrasound data]. Сlinical and experimental pathology, 18(2). 148-152. [in Ukrainian]. https://doi.org/10.24061/1727-4338.XVIII.2.68.2019.28
  23. Dikaiakou, E., Vlachopapadopoulou, E. A., Paschou, S. A., Athanasouli, F., Panagiotopoulos, Ι., Kafetzi, M., & Michalacos, S. (2020). Τriglycerides-glucose (TyG) index is a sensitive marker of insulin resistance in Greek children and adolescents. Endocrine, 70(1), 58-64. https://doi.org/10.1007/s12020-020-02374-6
  24. Sánchez-Escudero, V., García Lacalle, C., González Vergaz, A., Mateo, L. R., & Marqués Cabrero, A. (2021). The triglyceride/glucose index as an insulin resistance marker in the pediatric population and its relation to eating habits and physical activity. Endocrinologia, diabetes y nutricion, 68(5), 296-303. https://doi.org/10.1016/j.endien.2020.08.015
  25. Sachs, S., Zarini, S., Kahn, D. E., Harrison, K. A., Perreault, L., Phang, T., Newsom, S. A., Strauss, A., Kerege, A., Schoen, J. A., Bessesen, D. H., Schwarzmayr, T., Graf, E., Lutter, D., Krumsiek, J., Hofmann, S. M., & Bergman, B. C. (2019). Intermuscular adipose tissue directly modulates skeletal muscle insulin sensitivity in humans. American journal of physiology. Endocrinology and metabolism, 316(5), E866-E879. https://doi.org/10.1152/ajpendo.00243.2018
  26. Pashkova, O. Ye., Chudova, N. I., & Litvinenko, O. S. (2021) Rol miokiniv u rozvytku insulinorezystentnosti u ditei, khvorykh na tsukrovyi diabet 1 typu [The role of myokines in the development of insulin resistance in children, with type 1 diabetes mellitus]. Ukrainskyi zhurnal dytiachoi endokrynolohii, (2), 19-26. [in Ukrainian]. https://doi.org/10.30978/UJPE2021-2-19
  27. Kim, K., & Park, S. M. (2018). Association of muscle mass and fat mass with insulin resistance and the prevalence of metabolic syndrome in Korean adults: a cross-sectional study. Scientific reports, 8(1), 1-8. https://doi.org/10.1038/s41598-018-21168-5
  28. Shou, J., Chen, P. J., & Xiao, W. H. (2020). Mechanism of increased risk of insulin resistance in aging skeletal muscle. Diabetology & Metabolic Syndrome, 12(1), 1-10. https://doi.org/10.1186/s13098-020-0523-x
  29. Ferrannini, E., Iozzo, P., Virtanen, K. A., Honka, M. J., Bucci, M., & Nuutila, P. (2018). Adipose tissue and skeletal muscle insulin-mediated glucose uptake in insulin resistance: role of blood flow and diabetes. The American journal of clinical nutrition, 108(4), 749-758. https://doi.org/10.1093/ajcn/nqy162
  30. Wolosowicz, M., Lukaszuk, B., & Chabowski, A. (2020). The causes of insulin resistance in type 1 diabetes mellitus: is there a place for quaternary prevention?. International Journal of Environmental Research and Public Health, 17(22), 8651. https://doi.org/10.3390/ijerph17228651
  31. Unger, G., Benozzi, S. F., Perruzza, F., & Pennacchiotti, G. L. (2014). Índice triglicéridos y glucosa: un indicador útil de insulinorresistencia. Endocrinología y Nutrición, 61(10), 533-540. https://doi.org/10.1016/j.endoen.2014.11.006
  32. Guerrero-Romero, F., Simental-Mendía, L. E., González-Ortiz, M., Martínez-Abundis, E., Ramos-Zavala, M. G., Hernández-González, S. O., & Rodríguez-Morán, M. (2010). The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp. The Journal of Clinical Endocrinology & Metabolism, 95(7), 3347-3351. https://doi.org/10.1210/jc.2010-0288
  33. Simental-Mendía, L. E., Rodríguez-Morán, M., & Guerrero-Romero, F. (2008). The product of fasting glucose and triglycerides as surrogate for identifying insulin resistance in apparently healthy subjects. Metabolic syndrome and related disorders, 6(4), 299-304. https://doi.org/10.1089/met.2008.0034
  34. Liu, X. C., He, G. D., Lo, K., Huang, Y. Q., & Feng, Y. Q. (2021). The triglyceride-glucose index, an insulin resistance marker, was non-linear associated with all-cause and cardiovascular mortality in the general population. Frontiers in Cardiovascular Medicine, 7, 628109. https://doi.org/10.3389/fcvm.2020.628109
  35. Paing, A. C., McMillan, K. A., Kirk, A. F., Collier, A., Hewitt, A., & Chastin, S. F. M. (2019). Dose–response between frequency of interruption of sedentary time and fasting glucose, the dawn phenomenon and night‐time glucose in Type 2 diabetes. Diabetic Medicine, 36(3), 376-382. https://doi.org/10.1111/dme.13829
  36. Du, S., Shi, M. J., Sun, Z. Z., & Li, W. (2018). Clinical diagnosis for dusk phenomenon of diabetes. Medicine, 97(34), e11873-e11873. https://doi.org/10.1097/MD.0000000000011873
  37. Ormazabal, V., Nair, S., Elfeky, O., Aguayo, C., Salomon, C., & Zuñiga, F. A. (2018). Association between insulin resistance and the development of cardiovascular disease. Cardiovascular diabetology, 17(1), 122. https://doi.org/10.1186/s12933-018-0762-4
  38. Giha, H. A., Alamin, O. A., Sater, M. S. (2022). Diabetic sarcopenia: metabolic and molecular appraisal. Acta Diabetologica, 59, 989-1000. https://doi.org/10.1007/s00592-022-01883-2
  39. Guimarães, J. P. T., Filgueiras, L. R., Martins, J. O., & Jancar, S. (2019). Leukotriene Involvement in the Insulin Receptor Pathway and Macrophage Profiles in Muscles from Type 1 Diabetic Mice. Mediators of inflammation, 2019, 4596127. https://doi.org/10.1155/2019/4596127
  40. Gregory, J. M., Cherrington, A. D., & Moore, D. J. (2020). The peripheral peril: injected insulin induces insulin insensitivity in type 1 diabetes. Diabetes, 69(5), 837-847. https://doi.org/10.2337/dbi19-0026
  41. Shannon, C., Merovci, A., Xiong, J., Tripathy, D., Lorenzo, F., McClain, D., DeFronzo, R. A. (2018). Effect of chronic hyperglycemia on glucose metabolism in subjects with normal glucose tolerance. Diabetes, 67(12), 2507-2517. https://doi.org/10.2337/db18-0439

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Published

2022-12-20

How to Cite

1.
Lezhenko HO, Pashkova OY, Chudova NI. The association between the skeletal muscle state, lipid metabolism disorders and the development of insulin resistance in children with type 1 diabetes mellitus. Zaporozhye Medical Journal [Internet]. 2022Dec.20 [cited 2026May31];24(6):687-94. Available from: https://zmj.zsmu.edu.ua/article/view/261182

Issue

Vol. 24 No. 6 (2022)

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Original research

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