Metabolic Disorders in Patients With Impaired Glucose Tolerance, With or Without Underlying Ischaemic Heart Disease

Milena Brkić; Danijel Đekić; Jelena Jovanić; Goran Topić; Aleksandra Grbić; Tatjana Šutilović

doi:10.5937/scriptamed53-36711

Milena Brkić Faculty of Medicine, University of Banja Luka
Danijel Đekić ¹ Faculty of Medicine, University of Banja Luka,Clinic of Internal medicine, Department of endocrinology, University Clinical Center of Republic of Srpska, Banja Luka,Faculty of Medicine, University of Banja Luka
Jelena Jovanić Faculty of Medicine, University of Banja Luka, Clinic of Cardiology, University Clinical Center of Republic of Srpska, Banja Luka, Faculty of Medicine, University of Banja Luka
Goran Topić Faculty of Medicine, University of Banja Luka, Clinic of Internal medicine, Department of nephrology, University Clinical Center of Republic of Srpska, Banja Luka,Faculty of Medicine, University of Banja Luka
Aleksandra Grbić Faculty of Medicine, University of Banja Luka, Clinic of Internal medicine, Department of endocrinology, University Clinical Center of Republic of Srpska, Banja Luka,Faculty of Medicine, University of Banja Luka
Tatjana Šutilović Faculty of Medicine, University of Banja Luka, Clinic for vascular surgery , University Clinical Center of Republic of Srpska, Banja Luka,Faculty of Medicine, University of Banja Luka

DOI: https://doi.org/10.5937/scriptamed53-36711

Keywords: Impaired glucose tolerance, Insulin resistance, Coronary heart disease, Chronic inflammation mediators

Abstract

Background/Aim: The evidence showed that in the development of diabetes mellitus type 2 (DMT2) and coronary heart disease (CHD) significant role is played by metabolic risk factors: insulin resistance (IR), dyslipidaemia and obesity. Beside metabolic factors, increase in inflammatory markers such as fibrinogen and hs-C reactive protein (hsCRP) plays a role in developing CHD. Metabolic disorders are thought to also be present in patients with impaired glucose tolerance (IGT) and could contribute to development of CHD in these individuals. Aim of this study was to investigate the behaviour of metabolic parameters and chronic inflammation markers in patients with IGT on glucose tolerance test and associated CHD.

Methods: The trial included 4 groups of 30 subjects: a) IGT with CHD, b) IGT without CHD, c) CHD without IGT and d) control group without CHD and with normal glucose tolerance (NGT). Within each group glucoregulation parameters were measured (fasting glucose and Hb1Ac). Oral glucose tolerance test (OGTT) with 75 g glucose load was performed and IR parameters calculated (using HOMA-IR, Matsuda index, Quicki index, HOMA1- %B), lipid profile was done, waist/hip ratio was measured, as well as fibrinogen and hsCRP. CHD diagnosis was determined by typical signs of previous myocardial infarction on ECG, echocardiogram and/or ergometry (Bruce protocol).

Results: Subjects with IGT, but no CHD and those with both IGT and CHD had statistically significantly higher triglyceride and cholesterol levels and manifest IR with decreased insulin sensitivity compared to subjects with CHD, but no IGT and control group. Group with both IGT and CHD was found to have significantly higher fibrinogen and hsCRP concentrations.

Conclusion: IR and hyperlipidaemia, together with chronic inflammation mediators, are potential predictors of the development of glucose tolerance disorders; hence interventional treatment during IGT period or during hyperinsulinaemia could give patients better opportunity to prevent or postpone onset or development of diabetes and its complications.

References

DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001 Feb 12;161(3):397-405.

Arnold SV, Lipska KJ, Li Y, McGuire DK, Goyal A, Spertus JA, et al. Prevalence of glucose abnormalities among patients presenting with an acute myocardial infarction. Am Heart J 2014 Oct;168(4):466-70.e1.

Katzmarzyk PT, Church TS, Janssen I, Ross R, Blair SN. Metabolic syndrome, obesity, and mortality: impact of cardiorespiratory fitness. Diabetes Care 2005 Feb;28(2):391-7.

Lorenzo C, Williams K, Hunt KJ, Haffner SM. Trend in the prevalence of the metabolic syndrome and its impact on cardiovascular disease incidence: the San Antonio Heart Study. Diabetes Care 2006 Mar;29(3):625-30.

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 Jun 22;359(9324):2140-4.

Bowden DW, Rudock M, Ziegler J, Lehtinen AB, Xu J, Wagenknecht LE, et al. Coincident linkage of type 2 diabetes, metabolic syndrome, and measures of cardiovascular disease in a genome scan of the diabetes heart study. Diabetes 2006 Jul;55(7):1985-94.

Zhang Y, Lee ET, Howard BV, Best LG, Umans JG, Yeh J, et al. Insulin resistance, incident cardiovascular diseases, and decreased kidney function among nondiabetic American Indians: the Strong Heart Study. Diabetes Care 2013 Oct;36(10):3195-200.

Meigs JB, Muller DC, Nathan DM, Blake DR, Andres R; Baltimore Longitudinal Study of Aging. The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging. Diabetes 2003 Jun;52(6):1475-84.

Weiss R, Dufour S, Taksali SE, Tamborlane WV, Petersen KF, Bonadonna RC, et al. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. Lancet 2003 Sep 20;362(9388):951-7.

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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) final report. Circulation 2002 Dec 17;106(25):3143-421.

Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Bonadonna RC, Muggeo M; Bruneck study. Carotid atherosclerosis and coronary heart disease in the metabolic syndrome: prospective data from the Bruneck study. Diabetes Care 2003 Apr;26(4):1251-7.

Ford ES, Giles WH. A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 2003 Mar;26(3):575-81.

Devaraj S, Xu DY, Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 2003 Jan 28;107(3):398-404.

Ryden L. GAMI: Glucose abnormalities in patients with myocardial infarction—prevalence, diagnosis and prognostic implications. The European Society of Cardiology Congress 2004, 29 August-1 September, Munich, Germany.

Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003 Jan 1;289(1):76-9.

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 Jun 22;359(9324):2140-4.

DeFronzo RA, Ferrannini E. Regulation of hepatic glucose metabolism in humans. Diabetes Metab Rev 1987 Apr;3(2):415-59.

Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999 Sep;22(9):1462-70.

Hills SA, Balkau B, Coppack SW, Dekker JM, Mari A, Natali A, et al; Report prepared on behalf of the EGIR-RISC Study Group. The EGIR-RISC STUDY (The European group for the study of insulin resistance: relationship between insulin sensitivity and cardiovascular disease risk): I. Methodology and objectives. Diabetologia 2004 Mar;47(3):566-70.

Kanauchi M. A new index of insulin sensitivity obtained from the oral glucose tolerance test applicable to advanced type 2 diabetes. Diabetes Care 2002 Oct;25(10):1891-2.

Adam JM, Tarigan NP. Comparison of The World Health Organization (WHO) two-step strategy and OGTT for diabetes mellitus screening. Acta Med Indones 2004 Jan-Mar;36(1):3-7.

The American Diabetes Association (ADA). Classification and diagnosis of diabetes: standards of medical care in diabetes—2020. Diabetes Care 2020 Dec;43(1):S14–S31.

Yang G, Li C, Gong Y, Fang F, Tian H, Li J, et al. Assessment of insulin resistance in subjects with normal glucose tolerance, hyperinsulinemia with normal blood glucose tolerance, impaired glucose tolerance, and newly diagnosed type 2 diabetes (Prediabetes Insulin Resistance Research). J Diabetes Res 2016;2016:9270768. doi: 10.1155/2016/9270768.

Pyörälä M, Miettinen H, Laakso M, Pyörälä K. Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality: the 22-year follow-up results of the Helsinki Policemen Study. Diabetes Care 2000 Aug;23(8):1097-102.

Srinivasan MP, Kamath PK, Manjrekar PA, Unnikrishnan B, Ullal A, Kotekar MF, et al. Correlation of severity of coronary artery disease with insulin resistance. N Am J Med Sci 2013 Oct;5(10):611-4.

Hirai FE, Moss SE, Klein BE, Klein R. Relationship of glycemic control, exogenous insulin, and C-peptide levels to ischemic heart disease mortality over a 16-year period in people with older-onset diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). Diabetes Care 2008 Mar;31(3):493-7.

de Rooij SR, Dekker JM, Kozakova M, Mitrakou A, Melander O, Gabriel R, et al; RISC Group Investigators. Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study. Eur J Endocrinol 2009 Aug;161(2):223-30.

Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002 Dec 4;288(21):2709-16.

Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary artery calcium score combined with Framingham score for risk prediction in asymptomatic individuals. JAMA 2004 Jan 14;291(2):210-5.

Lorenzo C, Williams K, Hunt KJ, Haffner SM. Trend in the prevalence of the metabolic syndrome and its impact on cardiovascular disease incidence: the San Antonio Heart Study. Diabetes Care 2006 Mar;29(3):625-30.

Kim HK, Kim CH, Kim EH, Bae SJ, Choe J, Park JY, et al. Impaired fasting glucose and risk of cardiovascular disease in Korean men and women: the Korean Heart Study. Diabetes Care 2013 Feb;36(2):328-35.

Genuth S, Alberti KG, Bennett P, Buse J, Defronzo R, Kahn R, et al; Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003 Nov;26(11):3160-7.

Abdul-Ghani MA, Jayyousi A, DeFronzo RA, Asaad N, Al-Suwaidi J. Insulin resistance the link between T2DM and CVD: basic mechanisms and clinical implications. Curr Vasc Pharmacol 2019;17(2):153-63.

Ferrannini E, Haffner SM, Mitchell BD, Stern MP. Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia 1991 Jun;34(6):416-22.

Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005 Apr 16-22;365(9468):1415-28.

Antuna-Puente B, Faraj M, Karelis AD, Garrel D, Prud'homme D, Rabasa-Lhoret R, et al. HOMA or QUICKI: is it useful to test the reproducibility of formulas? Diabetes Metab 2008 Jun;34(3):294-6.

Yokoyama H, Emoto M, Fujiwara S, Motoyama K, Morioka T, Komatsu M, et al. Quantitative insulin sensitivity check index and the reciprocal index of homeostasis model assessment are useful indexes of insulin resistance in type 2 diabetic patients with wide range of fasting plasma glucose. J Clin Endocrinol Metab 2004 Mar;89(3):1481-4.

Dalla Man C, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C. Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model. Am J Physiol Endocrinol Metab 2005 Nov;289(5):E909-14.

Rewers M, Zaccaro D, D'Agostino R, Haffner S, Saad MF, Selby JV, et al; Insulin Resistance Atherosclerosis Study Investigators. Insulin sensitivity, insulinemia, and coronary artery disease: the Insulin Resistance Atherosclerosis Study. Diabetes Care 2004 Mar;27(3):781-7.

Defronzo RA. Impaired glucose tolerance: do pharmacological therapies correct the underlying metabolic disturbance? Br J Diabetes Vasc Dis 2003 May;3(1):suppl. doi: 10.1177/1474651403003001S0601.

Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 2004 Jun;27(6):1496-504.

Farmer JA. Diabetic dyslipidemia and atherosclerosis: evidence from clinical trials. Curr Atheroscler Rep 2007 Aug;9(2):162–8.

Frostegård J. Immunity, atherosclerosis and cardiovascular disease. BMC Med 2013 May 1;11:117. doi: 10.1186/1741-7015-11-117.

Fonseca L, Paredes S, Ramos H, Oliveira JC, Palma I. Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol. Lipids Health Dis 2020 Jun 6;19(1):127. doi:10.1186/s12944-020-01292-w.

Lim Y, Yoo S, Lee SA, Chin SO, Heo D, Moon JC, et al. Apolipoprotein B is related to metabolic syndrome independently of low density lipoprotein cholesterol in patients with type 2 diabetes. Endocrinol Metab (Seoul) 2015 Jun;30(2):208-15.

Iraj B, Salami R, Feizi A, Amini M. The profile of hypertension and dyslipidemia in prediabetic subjects; results of the Isfahan Diabetes Prevention program: A large population-based study. Adv Biomed Res 2015 Jan 30;4:27. doi:10.4103/2277-9175.150415.

Tuttolomondo A, Di Raimondo D, Pecoraro R, Arnao V, Pinto A, Licata G. Atherosclerosis as an inflammatory disease. Current Pharmaceutical Design 2012;18(28):4266-88.

Hidalgo A, Tello L, Toro EF. Numerical and analytical study of an atherosclerosis inflammatory disease model. J Math Biol 2014 Jun;68(7):1785-814.

Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, et al. C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 2004 Apr 1;350(14):1387-97.

Williams TN, Zhang CX, Game BA, He L, Huang Y. C-reactive protein stimulates MMP-1 expression in U937 histiocytes through Fc[gamma]RII and extracellular signal-regulated kinase pathway:: an implication of CRP involvement in plaque destabilization. Arterioscler Thromb Vasc Biol 2004 Jan;24(1):61-6.

Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3rd, Criqui M, et al; Centers for Disease Control and Prevention; American Heart Association. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003 Jan 28;107(3):499-511.

Avilés-Rosas G, Dávila-Sosa D, Rubio-Guerra AF, Elizalde-Barrera CI, Huerta-Ramírez S. Relationship between impaired fasting glucose and fibrinogen levels. Medicina Interna de Mexico 2016 Jan;32(5):515-26.

Ghule A, Kamble TK, Talwar D, Kumar S, Acharya S, Wanjari A, et al. Association of serum high sensitivity C-reactive protein with pre-diabetes in rural population: a two-year cross-sectional study. Cureus 2021 Oct 28;13(10):e19088. doi: 10.7759/cureus.19088.

Stramba-Badiale M, Fox KM, Priori SG, Collins P, Daly C, Graham I, et al. Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology. Eur Heart J 2006 Apr;27(8):994-1005.

Yang XP, Reckelhoff JF. Estrogen, hormonal replacement therapy and cardiovascular disease. Curr Opin Nephrol Hypertens 2011Mar;20(2):133-8.

Mosca L, Barrett-Connor E, Wenger NK. Sex/gender differences in cardiovascular disease prevention: what a difference a decade makes. Circulation 2011 Nov 8;124(19):2145-54.

Ford ES, Capewell S. Coronary heart disease mortality among young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol 2007 Nov 27;50(22):2128-32.

Asia Pacific Cohort Studies Collaboration. The impact of cardiovascular risk factors on the age-related excess risk of coronary heart disease. Int J Epidemiol 2006 Aug;35(4):1025-33.

Hu FB, Stampfer MJ, Solomon CG, Liu S, Willett WC, Speizer FE, et al. The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up. Arch Intern Med 2001 Jul 23;161(14):1717-23.

Cook NR, Buring JE, Ridker PM. The effect of including C-reactive protein in cardiovascular risk prediction models for women. Ann Intern Med 2006 Jul 4;145(1):21-9.

Banks E, Joshy G, Korda RJ, Stavreski B, Soga K, Egger S, et al. Tobacco smoking and risk of 36 cardiovascular disease subtypes: fatal and non-fatal outcomes in a large prospective Australian study. BMC Med 2019 Jul 3;17(1):128. doi: 10.1186/s12916-019-1351-4.

Mons U, Müezzinler A, Gellert C, Schöttker B, Abnet CC, Bobak M, et al; CHANCES Consortium. Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium. BMJ 2015 Apr 20;350:h1551. doi: 10.1136/bmj.h1551.

Tolstrup JS, Hvidtfeldt UA, Flachs EM, Spiegelman D, Heitmann BL, Bälter K, et al. Smoking and risk of coronary heart disease in younger, middle-aged and older adults. Am J Public Health 2014 Jan;104(1):96-102.

Willett WC, Green A, Stampfer MJ, Speizer FE, Colditz GA, Rosner B, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med 1987 Nov 19;317(21):1303-9.

DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001 Feb 12;161(3):397-405.