PECULIARITIES OF CARBOHYDRATE METABOLISM IN PATIENTS WITH COMORBID COURSE OF TYPE 2 DIABETES MELLITUS: RELATIONSHIP WITH IRS1 GENE POLYMORPHISM

Authors

  • U. P. Hevko I. Horbachevsky Ternopil National Medical University
  • M. I. Marushchak I. Horbachevsky Ternopil National Medical University
  • R. O. Bobyk I. Horbachevsky Ternopil National Medical University
  • A. M. Shumeliak I. Horbachevsky Ternopil National Medical University

DOI:

https://doi.org/10.11603/bmbr.2706-6290.2021.1.12102

Keywords:

цукровий діабет 2 типу, ожиріння, хронічний панкреатит, коморбідність, ген IRS1, алель, генотип

Abstract

Summary. Despite significant advances in genetic predisposition to type 2 diabetes mellitus (T2DM), which have been confirmed by large-scale genomic and clinical studies, most of the genetic factors that cause the development of T2DM remain unclear.

The aim of the study – to determine the association of IRS1 gene polymorphism (rs2943640) with carbohydrate metabolism in patients with type 2 diabetes mellitus in combination with obesity and chronic pancreatitis.

Materials and Methods. The study included 33 patients with T2DM (patients with T2DM, T2DM + obesity, T2DM + obesity + chronic pancreatitis) and 10 healthy individuals. The level of glycated hemoglobin (HbA1c) was determined using an automatic biochemical analyzer COBAS 6000 (Roche Hitachi, Germany). The level of insulin in the blood was determined on an enzyme-linked immunosorbent assay from Thermo Scientific Multiskan FC, and the glucose concentration was determined using standard kits on an automatic biochemical analyzer from COBAS INTEGRA® 400 (Roche Diagnostics). Polymorphism of the IRS1 gene (rs2943640) C> A was genotyped by real-time PCR TaqMan method (Applied Biosystems, Foster City, CA, USA).

Results. Carriers of the C allele of the IRS1 gene (rs2943640), patients with combined type 2 diabetes, obesity and chronic pancreatitis have the highest levels of insulin and HOMA-IR, which are probably higher than in patients with type 2 diabetes (329.75 %, respectively) and 65.13 %) and in patients with combined type 2 diabetes and obesity (314.53 % and 69.23 %, respectively). Patients with type 2 diabetes mellitus, regardless of the presence/absence of comorbid obesity and chronic pancreatitis, carriers of the C/C genotype of the IRS1 gene (rs2943640) have the highest carbohydrate metabolism, relative to the data of carriers of the C/A genotype.

Conclusions. In patients with combined course of type 2 diabetes, obesity and chronic pancreatitis, the nature of carbohydrate metabolism disorders is influenced by polymorphism of the IRS1 gene (rs2943640).

References

Zheng Y, Ley SH, Frank BH. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat. Rev. Endocrinol. 2018;14(2): 88-98.

Kaiser A, Zhang N, Der Pluijm WV. Global prevalence of type 2 diabetes over the next ten years (2018–2028). Diabetes. 2018;67(1): 202-LB.

International Diabetes Federation. IDF Diabetes Atlas 9th edition 2019. International Diabetes Federation [Internet]. [cited 2020 Aug 21]. Available from: https://www.idf.org/aboutdiabetes/what-is-diabetes/facts-figures.html.

Blüher M, Stumvoll M. Diabetes and Obesity. In: Bonora E., De Fronzo R. (eds) Diabetes Complications, Comorbidities and Related Disorders. Endocrinology. Springer, Cham. 2018.

Melikhova SP, Shevcova VI, Zujkova AA, Kotova JuA. [Studying of comorbid pathology at the 2 type s diabetes as the complication of the metabolic syndrome]. The Russian Archives of Internal Medicine. 2018;8(5): 366-71. Russian.

Hosseini S, Alipour M, Zakerkish M, Cheraghian B, Ghandil P. Effects of epigallocatechin gallate on total antioxidant capacity, biomarkers of systemic low-grade inflammation and metabolic risk factors in patients with type 2 diabetes mellitus: the role of FTO-rs9939609 polymorphism. Archives of Medical Science. 2020.

Saboor Aftab SA, Reddy N, Smith E, Barber TM. Obesity and Type 2 Diabetes Mellitus. Intern Med. 2014;S6: 002. DOI:10.4172/2165-8048.S6-002.

Lin YK, Johnston PC, Arce K, Hatipoglu BA. Chronic pancreatitis and diabetes mellitus. Current Treatment Options in Gastroenterology. 2015;13(3): 319-31.

Hardt PD, Hauenschild A, Nalop J, Marzeion AM, Jaeger C, Teichmann J, et al. High prevalence of exocrine pancreatic insufficiency in diabetes mellitus. A multicenter study screening fecal elastase 1 concentrations in 1,021 diabetic patients. Pancreatology. 2003;3(5): 395-402. Available from: https://doi.org/10.1159/000073655.

Zhuravleva LV, Shekhovtsova YuA. Comorbidity of chronic pancreatitis and diabetes type 2: possible options of pharmacoteraphy. Practical likar. 2016;5(3): 21-5.

Flannick J, Florez JC. Type 2 diabetes: genetic data sharing to advance complex disease research. Nature Reviews Genetics. 2016;17(9): 535.

Fuchsberger C, Flannick J, Teslovich TM , Mahajan A, Agarwala V, Gaulton KJ et al. The genetic architecture of type 2 diabetes. Nature. 2016; 536(7614): 41.

Plengvidhya N, Chanprasert C, Chongjaroen N, Yenchitsomanus Pt, Homsanit M, Tangjittipokin W. Impact of KCNQ1, CDKN2A/2B, CDKAL1, HHEX, MTNR1B, SLC30A8, TCF7L2, and UBE2E2 on risk of developing type 2 diabetes in Thai population. BMC Med Genet. 2018;19: 93.

Musiienko VA, Marushchak MI. [Type 2 diabetes and thyroid disease: Finding common mechanisms]. Visn med i biol dosl. 2020;1: 74-82. Ukrainian.

Yiannakourisa N, Cooper JA, Shah S, Drenos F, Ireland HA, W. Stephens JW et al. IRS1 gene variants, dysglycaemic metabolic changes and type-2 diabetes risk. Nutr Metab Cardiovasc Dis. 2012;22(12): 1024-30.

Yousef AA, Behiry EG, Allah WMA, Hussien AM, Abdelmoneam AA, Imam MH, et al. IRS-1 genetic polymorphism (r.2963G>A) in type 2 diabetes mellitus patients associated with insulin resistance. Appl Clin Genet. 2018;11: 99-106.

American Diabetes Association. Standards of Medical Care in Diabetes – 2019 abridged for primary care providers. Clin Diabetes. 2019;37(1): 11-34.

Conwell DL, Lee LS, Yadav D, Longnecker DS, Miller FH, Mortele KJ et al. American Pancreatic Association Practice Guidelines in Chronic Pancreatitis: evidence-based report on diagnostic guidelines. Pancreas. 2014; 43(8): 1143-62. Available from: https://doi.org/10.1016/j.numecd.2011.05.009

Roy S, Sherman A, Monari-Sparks MJ, Schweiker O, Jain N, Sims E et al. Association of Comorbid and Metabolic Factors with Optimal Control of Type 2 Diabetes Mellitus. N Am J Med Sci. 2016;8(1): 31-9. DOI: 10.4103/1947-2714.175197. PMID: 27011945; PMCID: PMC4784181.

Nowakowska M, Zghebi SS, Ashcroft DM The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort. BMC Med.2019; 17:145. Available from: https://doi.org/10.1186/s12916-019-1373-y.

Tirkes T, Jeon CY, Li L, Joon AY, Seltman TA, Meghana Sankar M et al. Association of pancreatic steatosis with chronic pancreatitis, obesity, and type 2 diabetes. Pancreas. 2019;48(3): 420-6. 10.1097/MPA.0000000000001252

Iribarren C, Karter AJ, Go AS, Ferrara A, Liu JY, Sidney S et al. Glycemic control and heart failure among adult patients with diabetes. Circulation. 2001;103(22): 2668-73. Available from: https://doi.org/10.1161/01.CIR.103.22.2668

Jabir M, Lang C. Glycaemic control & heart failure development in the diabetic patient. SUMJ. 2012;1: 63-75.

Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care. 2001;24(9): 1614-9.

Yang Q, Graham TE, Mody N, Preitner F. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. 2005;436(7049): 356. DOI: 10.1038/nature03711. [PubMed] [CrossRef] [Google Scholar]

Muoio DM, Newgard CB. Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol. 2008;9(3): 193-205. DOI: 10.1038/nrm2327. [PubMed] [CrossRef] [Google Scholar]

Jakobsen SN, Hardie DG, Morrice N, Tornqvist HE. 5′-AMP-activated protein kinase phosphorylates IRS-1 on Ser-789 in mouse C2C12 myotubes in response to 5-aminoimidazole-4-carboxamide riboside. J Biol Chem. 2001;276(50): 46912-6. DOI: 10.1074/jbc.C100483200.

Kilpelainen TO, Zillikens MC, Stancakova A, Finucane FM, Ried JS, Langenberg C et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet. 2011;43(8): 753-60.

Shu XO, Long J, Cai Q, Qi L, Xiang YB, Cho YS et al. Identification of new genetic risk variants for type 2 diabetes. PLoS Genet. 2010;6(9):e1001127. Available from: https://doi.org/10.1371/journal.pgen.1001127.

Shalimova AS. Association of IRS>1 gene polymorphism with violations of blood lipid spectrum in patients with essential hypertension and concomitant type 2 diabetes. FAMILY MEDICINE. 2015;3(59): 102-4.

Minchenko DO, Davydov VV, Budreiko OA, Moliavko OS, Kulieshova DK, Tiazhka OV et al. The expression of CСN2, IQSEC, RSPO1, DNAJC15, RIPK2, IL13RA2, IRS1, and IRS2 genes in blood of obese boys with insulin resistance. Physiology Journal. 2015;1(61): 10-8.

Vassy JL, Hivert MF, Porneala B, Dauriz M, Jose C. Florez JC et al. Polygenic type 2 diabetes prediction at the limit of common variant detection. Diabetes. 2014;63: 2172-82 . DOI: 10.2337/db13-1663.

Qi Q, Bray GA, Smith SR, HuFB, Sacks FM, Qi L. Insulin receptor substrate 1 gene variation modifies insulin resistance response toweight-loss diets in a 2year randomized trial: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Circulation. 2011;124(5): 563-71.

Samuel VT, Petersen KF, Shulman GI. Lipid-induced insulin resistance: unravelling the mechanism. Lancet. 2010;375: 2267-77.

Published

2021-05-22

How to Cite

Hevko, U. P., Marushchak, M. I., Bobyk, R. O., & Shumeliak, A. M. (2021). PECULIARITIES OF CARBOHYDRATE METABOLISM IN PATIENTS WITH COMORBID COURSE OF TYPE 2 DIABETES MELLITUS: RELATIONSHIP WITH IRS1 GENE POLYMORPHISM. Bulletin of Medical and Biological Research, (1), 37–45. https://doi.org/10.11603/bmbr.2706-6290.2021.1.12102