Insulin Resistance and Contrainsular Response in Type 2 Diabetes Mellitus Patients with Acute Coronary Syndrome
DOI:
https://doi.org/10.3889/oamjms.2020.4674Keywords:
Insulin resistance, Glucagon/Glucagon-like peptide-1, Type 2 diabetes mellitus, Acute coronary syndromeAbstract
BACKGROUND: The number of patients with diabetes mellitus (DM) is progressively increasing all over the world. Over the past three decades, the global burden of diabetes has increased from 30 million in 1985 to 382 million in 2015, and current trends indicate that the prevalence of diabetes grows progressively. The phenomenon of insulin resistance established in the majority of type 2 DM (T2DM) patients. T2DM is associated with β-cell deficiency, α-cell resistance to insulin, and reduced effects of incretin. However, the role of insulin and glucagon in the process of cardiovascular complications in diabetic patients is a matter of debate.
AIM: Our study aims to estimate insulin resistance and the contrainsular response in patients with T2DM and acute coronary syndrome (ACS).
METHODS: The 104 T2DM patients aged 18–70 years participated in the observational study carried out in the Karaganda regional cardiosurgery hospital and ambulatory. The first group included 37 patients hospitalized for ACS in the first 24 h of admission. The second group included 67 patients without ACS. Determination of insulin resistance and contrainsular response was provided using a multiplex immunological assay with XMap technology on Bioplex 3D.
RESULTS: During the research, we have discovered a decreased level of glucagon and increased homeostasis model assessment of insulin resistance (HOMA-IR) in patients with T2DM diabetes and ACS. Evaluation of traditional correlation interactions of HOMA-IR and indicators of carbohydrate metabolism showed a positive correlation with fasting plasma glucose in both study groups (Group 1: R = 0.47, p = 0.003; Group 2: R = 0.41, p = 0.024). Glucagon-like peptide (GLP)-1 has a weak positive correlation with HOMA-IR only in the first group (R = 0.32, p = 0.006). Increased insulin resistance was associated with high GLP-1 levels and low glucagon. The logistic regression model established that an increased HOMA-IR index rises the chance of ACS by 10.6% (OR = 1.106 [95% CI 1.105–1.206], p = 0,021). The logistic regression model, reflecting the relation between glucagon and ACS, shows that increased glucagon reduces the ACS odds (OR = 0.989 [95% CI 0.979–0.999], p = 0.026). The adjusted regression model showed no significant influence of early presented factors on the probability of ACS.
CONCLUSION: There is a trend toward elevated HOMA-IR insulin resistance index and decreased level of glucagon in diabetic patients with ACS.
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Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in Type 2 diabetes: A systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17(1):83. https://doi.org/10.1186/s12933-018-0728-6 PMid:29884191
Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care. 1993;16(2):434-44. https://doi.org/10.2337/diacare.16.2.434 PMid:8432214
Mazurek M, Kowalczyk J, Lenarczyk R, Zielinska T, Sedkowska A, Pruszkowska-Skrzep P, et al. The prognostic value of different glucose abnormalities in patients with acute myocardial infarction treated invasively. Cardiovasc Diabetol. 2012;11:78. https://doi.org/10.1186/1475-2840-11-78 PMid:22741568
Nishimura M, Tokoro T, Nishida M, Hashimoto T, Kobayashi H, Yamazaki S, et al. Association of insulin resistance with de novo coronary stenosis after percutaneous coronary artery intervention in hemodialysis patients. Nephron Clin Pract. 2008;109(1):c9-17. https://doi.org/10.1159/000132391 PMid:18483462
Uetani T, Amano T, Harada K, Kitagawa K, Kunimura A, Shimbo Y, et al. Impact of insulin resistance on post-procedural myocardial injury and clinical outcomes in patients who underwent elective coronary interventions with drug-eluting stents. JACC Cardiovasc Interv. 2012;5(11):1159-67. https://doi.org/10.1016/j.jcin.2012.07.008 PMid:23174640
Tenenbaum A, Adler Y, Boyko V, Tenenbaum H, Fisman EZ, Tanne D, et al. Insulin resistance is associated with increased risk of major cardiovascular events in patients with preexisting coronary artery disease. Am Heart J. 2007;153(4):559-65. https://doi.org/10.1016/j.ahj.2007.01.008 PMid:17383294
Yanase M, Takatsu F, Tagawa T, Kato T, Arai K, Koyasu M, et al. Insulin resistance and fasting hyperinsulinemia are risk factors for new cardiovascular events in patients with prior coronary artery disease and normal glucose tolerance. Circ J. 2004;68(1):47-52. https://doi.org/10.1253/circj.68.47 PMid:14695465
Hedblad B, Nilsson P, Engström G, Berglund G, Janzon L. Insulin resistance in non-diabetic subjects is associated with increased incidence of myocardial infarction and death. Diabet Med. 2002;19(6):470-5. https://doi. org/10.1046/j.1464-5491.2002.00719.x PMid:12060058
Iguchi T, Hasegawa T, Otsuka K, Matsumoto K, Yamazaki T, Nishimura S, et al. Insulin resistance is associated with coronary plaque vulnerability: Insight from optical coherence tomography analysis. Eur Heart J Cardiovasc Imaging. 2014;15(3):284-91. https://doi.org/10.1093/ehjci/jet158 PMid:24022065
An X, Yu D, Zhang R, Zhu J, Du R, Shi Y, et al. Insulin resistance predicts progression of de novo atherosclerotic plaques in patients with coronary heart disease: A one-year follow-up study. Cardiovasc Diabetol. 2012;11:71. https://doi.org/10.1186/1475-2840-11-71 PMid:22709409
Okita K, Iwahashi H, Kozawa J, Okauchi Y, Funahashi T, Imagawa A, et al. Homeostasis model assessment of insulin resistance for evaluating insulin sensitivity in patients with Type 2 diabetes on insulin therapy. Endocr J. 2013;60(3):283-90. https://doi.org/10.1507/endocrj.ej12-0320 PMid:23149658
Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani F, Zenere MB, et al. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: Studies in subjects with various degrees of glucose tolerance and insulin sensitivity. Diabetes Care. 2000;23(1):57- 63. https://doi.org/10.2337/diacare.23.1.57 PMid:10857969
Gruden G, Landi A, Bruno G. Natriuretic peptides, heart, and adipose tissue: New findings and future developments for diabetes research. Diabetes Care. 2014;37(11):2899-908. https://doi.org/10.2337/dc14-0669 PMid:25342830
Asztalos BF, Collins D, Cupples LA, Demissie S, Horvath KV, Bloomfield HE, et al. Value of high-density lipoprotein (HDL) subpopulations in predicting recurrent cardiovascular events in the veterans affairs HDL intervention trial. Arterioscler Thromb Vasc Biol. 2005;25(10):2185-91. https://doi.org/10.1161/01.atv.0000183727.90611.4f PMid:16123324
Stähli BE, Nozza A, Schrieks IC, Buse JB, Malmberg K, Mellbin L, et al. Homeostasis model assessment of insulin resistance and survival in patients with diabetes and acute coronary syndrome. J Clin Endocrinol Metab. 2018;103(7):2522-33. https://doi.org/10.1210/jc.2017-02772 PMid:29659887
Hippisley-Cox J, Coupland C. Development and validation of risk prediction equations to estimate future risk of heart failure in patients with diabetes: A prospective cohort study. BMJ Open. 2015;5(9):e008503. https://doi.org/10.1136/ bmjopen-2015-008503 PMid:26353872
Bonora E, Formentini G, Calcaterra F, Lombardi S, Marini F, Zenari L, et al. HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in Type 2 diabetic subjects: Prospective data from the Verona diabetes complications study. Diabetes Care. 2002;25(7):1135-41. https://doi.org/10.2337/diacare.25.7.1135 PMid:12087010
Adler AI, Levy JC, Matthews DR, Stratton IM, Hines G, Holman RR. Insulin sensitivity at diagnosis of Type 2 diabetes is not associated with subsequent cardiovascular disease (UKPDS 67). Diabet Med. 2005;22(3):306-11. https://doi.org/10.1111/j.1464-5491.2004.01418.x PMid:15717879
Ahrén B. Glucagon--early breakthroughs and recent discoveries. Peptides. 2015;67:74-81. https://doi.org/10.1016/j.peptides.2015.03.011 PMid:25814364
Jones BJ, Tan T, Bloom SR. Minireview: Glucagon in stress and energy homeostasis. Endocrinology. 2012;153(3):1049-54. https://doi.org/10.1210/en.2011-1979 PMid:22294753
Cartañà J, Arola L. Nickel-induced hyperglycaemia: The role of insulin and glucagon. Toxicology. 1992;71(1-2):181-92. https://doi.org/10.1016/0300-483x(92)90065-m PMid:1729765
Ceriello A. Oxidative stress and diabetes-associated complications. Endocr Pract. 2006;12 Suppl 1:60-2 PMid:16627383
Klimontov VV, Myakina NE. Glycaemic variability in diabetes: A tool for assessing the quality of glycaemic control and the risk of complications. J Diabetes Mellit. 2014;17(2):76-82. https://doi.org/10.14341/dm2014276-82
Summary of the 2007 European Society of Hypertension (ESH) and European Society of Cardiology (ESC) guidelines for the management of arterial hypertension. Vasc Health Risk Manag. 2007;3(6):783-95. https://doi.org/10.1080/08037050701461084 PMid:18200799
Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003;26 Suppl 1:S5-20. https://doi.org/10.2337/diacare.21.1.s5 PMid:12502614
Yamagishi S, Fukami K, Matsui T. Crosstalk between advanced glycation end products (AGEs)-receptor RAGE axis and dipeptidyl peptidase-4-incretin system in diabetic vascular complications. Cardiovasc Diabetol. 2015;14:2. https://doi.org/10.1186/s12933-015-0176-5 PMid:25582643
Ali S, Drucker DJ. Benefits and limitations of reducing glucagon action for the treatment of Type 2 diabetes. Am J Physiol Endocrinol Metab. 2009;296(3):E415-21. PMid:19116373
Godoy-Matos AF. The role of glucagon on Type 2 diabetes at a glance. Diabetol Metab Syndr. 2014;6(1):91. https://doi.org/10.1186/1758-5996-6-91 PMid:25177371
Winnick JJ, Kraft G, Gregory JM, Edgerton DS, Williams P, Hajizadeh IA, et al. Hepatic glycogen can regulate hypoglycemic counterregulation via a liver-brain axis. J Clin Invest. 2016;126(6):2236-48. https://doi.org/10.1172/jci79895 PMid:27140398
Unger RH, Cherrington AD. Glucagonocentric restructuring of diabetes: A pathophysiologic and therapeutic makeover. J Clin Invest. 2012;122(1):4-12. https://doi.org/10.1172/jci60016 PMid:22214853
Norhammar A, Tenerz A, Nilsson G, Hamsten A, Efendíc S, Rydén L, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: A prospective study. Lancet. 2002;359(9324):2140-4. https://doi.org/10.1016/s0140-6736(02)09089-x PMid:12090978
Hayward RA, Reaven PD, Wiitala WL, Bahn GD, Reda DJ, Ge L, et al. Follow-up of glycemic control and cardiovascular outcomes in Type 2 diabetes. N Engl J Med. 2015;372(23):2197- 206. https://doi.org/10.1056/nejmoa1414266 PMid:26039600
Nichols GA, Joshua-Gotlib S, Parasuraman S. Glycemic control and risk of cardiovascular disease hospitalization and all-cause mortality. J Am Coll Cardiol. 2013;62(2):121-7. https://doi.org/10.1016/j.jacc.2013.04.031 PMid:23665365
Muggeo M, Zoppini G, Bonora E, Brun E, Bonadonna RC, Moghetti P, et al. Fasting plasma glucose variability predicts 10-year survival of Type 2 diabetic patients: The Verona diabetes study. Diabetes Care. 2000;23(1):45-50. https://doi.org/10.2337/diacare.23.1.45 PMid:10857967
Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, et al. Association of glycaemia with macrovascular and microvascular complications of Type 2 diabetes (UKPDS 35): Prospective observational study. BMJ. 2000;321(7258):405-12. https://doi.org/10.1136/bmj.321.7258.405 PMid:10938048
Khan HA, Alhomida AS, Sobki SH. Lipid profile of patients with acute myocardial infarction and its correlation with systemic inflammation. Biomark Insights. 2013;8:1-7. https://doi.org/10.4137/bmi.s11015 PMid:23400110
Chinwong D, Patumanond J, Chinwong S, Siriwattana K, Gunaparn S, Hall JJ, et al. Statin therapy in patients with acute coronary syndrome: Low-density lipoprotein cholesterol goal attainment and effect of statin potency. Ther Clin Risk Manag. 2015;11:127-36. https://doi.org/10.2147/tcrm.s75608 PMid:25670902
Ozaki Y, Tanaka A, Nishiguchi T, Komukai K, Taruya A, Satogami K, et al. High-density lipoprotein cholesterol as a therapeutic target for residual risk in patients with acute coronary syndrome. PLoS One. 2018;13(7):e0200383. https://doi.org/10.1371/journal.pone.0200383 PMid:29995934
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Copyright (c) 2020 Dinara Sheryazdanova, Yelena M. Laryushina, Larissa Muravlyova, Lyudmila G. Turgunova, Assel R. Alina, Natalya V. Vassilyeva, Anar A. Turmukhambetova (Author)
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