Relationship between plasma adipokines, inflammation, insulin resistance and subclinical atherosclerosis in newly diagnosed type 2 diabetes
Razvan Vasilescu, Silvi Ifrim, Constantin Ionescu-Tirgoviste
DOI: 10.4236/jdm.2011.12004   PDF    HTML     3,965 Downloads   8,792 Views   Citations


Background: The aim of this study was to investigate the occurrence of subclinical atherosclerosis, evaluated by carotid artery intima-media thickness (CIMT) in subjects with newly diagnosed type 2 diabetes. Methods: A total of 167 subjects, 50 newly diagnosed type 2 diabetic subjects and 117 non-diabetic subjects were included in the study. Obese and overweight newly diagnosed type 2 diabetic patients were matched for age and BMI with obese and overweight non-diabetic subjects. Only postmenopausal women were selected. The following biomarkers were analyzed: fasting glucose, HbA1c, fasting insulin, fasting proinsulin, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, adiponectin, leptin, hs-CRP, urine albumin/creatinine ratio. 75 g oral glucose tolerance test was performed in all subjects. Ultrasound imaging was used to evaluate IMT of the common carotid artery. Results: CIMT was greater in newly diagnosed type 2 patients compared to non-diabetic subjects. When analyzed by BMI, the difference regarding CIMT between diabetic and non-diabetic subjects was significant only in overweight subjects, in both sexes. In univariate analysis in men with newly diagnosed type 2 diabetes, CIMT was positively correlated with age, SBP, triglycerides, leptin and negatively correlated with HDL-cholesterol and in women CIMT was positively correlated with SBP and leptin. Independent determinants of CIMT in patients with newly diagnosed type 2 diabetes were in men age (β = 0.556, p = 0.0028) and log leptin (β = 0.393, p = 0.049) and in women systolic blood pressure (β = 0.48, p = 0.026). Conclusions: Subclinical atherosclerosis is present in newly diagnosed type 2 diabetic subjects. Body fat accumulation in men and hypertension in postmenopausal women have a primary role in increase carotid intima-media thickness.

Share and Cite:

Vasilescu, R. , Ifrim, S. and Ionescu-Tirgoviste, C. (2011) Relationship between plasma adipokines, inflammation, insulin resistance and subclinical atherosclerosis in newly diagnosed type 2 diabetes. Journal of Diabetes Mellitus, 1, 17-25. doi: 10.4236/jdm.2011.12004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Kannel, W.B., McGee, D.L. (1979) Diabetes and cardiovascular disease: The framingham study. JAMA, 241, 2035-2038. doi:10.1001/jama.241.19.2035
[2] Pignoli, P., Tremoli, E., Poli, A., Oreste, P. and Paoletti R. (1986) Intimal plus medial thickness of the arterial wall: A direct measurement with ultrasound imaging. Circulation, 74, 1399-1406.
[3] Poli, A., Tremoli, E., Colombo, A., Sirtori, M., Pignoli, P. and Paoletti, R. (1988) Ultrasonographic measurement of the common carotid artery wall thickness in hypercholestero-lemic patients. A nnew model for the quantitation and follow-up of preclinical atheroslcerosis in living human subjects. Atherosclerosis, 70, 235-261. doi:10.1016/0021-9150(88)90176-1
[4] de Groot, E., Hovingh, K., Wiegman, A., Duriez, P., Smit, A.J., Fruchart, J.C., Kastelein, J.J.P. (2004) Measurement of arterial wall thickness as a surrogate marker for atherosclerosis. Circulation, 109 (suppl III): 33-38. doi:10.1161/
[5] Cupini LM, Pasqualetti P, Diomedi M, Vernieri F, Silvestrini M, Rizzato B, Ferrante F, Bernardi G: Carotid artery intima-media thickness and lacunar versus nonla- cunar infarcts. Stroke, 33, 689-694. doi:10.1161/hs0302.103661
[6] O’Leary, D.H., Bots, M.L. (2010) Imaging of atherosclerosis: Carotid intima-media thickness. Euro- pean Heart Journal, 31, 1682-1689. doi:10.1093/eurheartj/ehq185
[7] O’Leary, D.H., Polak, J.F., Kronmal, R.A., Kittner, S.J., Bond, M.G., Wolfson, S.K., Bommer, W., Price, T.R., Gardin, J.M. and Savage, P.J., for the CHS Collaborative Group (1992) Distribution and correlates of sonogra- phically detected carotid artery disease in the Cardiovascular Health Study. Stroke, 23, 1752-1760.
[8] Salonen, R., Salonen, J.T. (1991) Determinants of carotid intimamedia thickness: A population based ultrasono- graphy study in eastern Finnish men. Journal of Internal Medicine, 229, 225-231. doi:10.1111/j.1365-2796.1991.tb00336.x
[9] Bots, M.L., Hoes, A.W., Koudstaal, P.J., Hofman, A., Grobbee, D.E. (1997) Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation, 96, 1432-1437.
[10] Chambless, L.E., Heiss, G., Folsom, A.R., Rosamond, W., Szklo, M., Sharrett, A.R., Clegg, L.X. (1997) Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993. American Journal of Epidemiol, 146, 483-494.
[11] Kawamori, R., Yamasaki, Y., Matsushima, H., Nishizawa, H., Nao, K., Hougaku, H., Maeda, H., Handa, N., Matsumoto, M., Kamada, K. (1992) Prevalence of carotid atherosclerosis in diabetic patients. Diabetes Care, 15, 1290-1294. doi:10.2337/diacare.15.10.1290
[12] Wagenknecht, L.E., D’Agostino, R. Jr., Savage, P.J., O’Leary, D.H., Saad, M.F. and Haffner, S.M.(1997) Duration of diabetes and carotid wall thickness: the Insulin Resistance Athero-sclerosis Study (IRAS). Stroke, 28, 999-1005.
[13] Pujia, A., Gnasso, A., Irace, C., Colona, A., Mattioli, P.L. (1994) Common carotid arterial wall thickness in NIDDM subjects. Diabetes Care, 17, 1330-1336. doi:10.2337/diacare.17.11.1330
[14] Ifrim, S. and Vasilescu, R. (2004) Early detection of atherosclerosis in type 2 diabetic patients by endothelial dysfunction and intima-media thickness. Romanian Journal of Internal Medicine, 42, 343-354.
[15] Dullaart, R.P.F., de Vries, R., van Tol, A., Sluiter, W.J. (2007) Lower plasma adiponectin is a marker of increased intima- media thickness associated with type 2 diabetes mellitus and with male gender. European Journal of Endocrinol, 156, 387-394. doi:10.1530/EJE-06-0681
[16] Niskanen, L., Rauramaa, R., Miettinen, H., Haffner, S.M., Mercuri, M. and Uusitupa, M.(1996) Carotid artery intima-media thickness in elderly people with NIDDM and in non-diabetic subjects. Stroke, 27, 1986-1992.
[17] Bonora, E., Tessari, R., Micciolo, R., Zenere, M., Targher, G., Padovani, R., Falezza, G., Muggeo, M. (1997) Intimal-medial thickness of the carotid artery in nondiabetic and NIDDM patients. Relationship with insulin resistance. Diabetes Care, 20, 627-631. doi:10.2337/diacare.20.4.627
[18] Goff, D.C., D’Agostino, R.B., Haffner, S.M., Saad, N.F., Wagenknecht, L.E. (2000) Lipoprotein concentrations and carotid atherosclerosis by diabetes status: results from the Insulin Resistance Atherosclerosis Study. Diabetes Care, 23, 1006-1011. doi:10.2337/diacare.23.7.1006
[19] Hegazi, R.A.F., Sutton-Tyrrell, K., Evans, R.W., Kuller, L.H., Belle, S., Yamamoto, M., Edmundowicz, D., Kelley, D.E.: Relationship of adiposity to subclinical atherosclerosis in obese patients with type 2 diabetes. Obesity Research; 11, 1597-1605. doi:10.1038/oby.2003.212
[20] Kang, E.S., Kim, H.J., Kim, Y.M., Lee, S., Cha, B.S., Lim, S.K., Kim, H.J. and Lee, H.C. (2004) Serum high sensitivity C-reactive protein is associated with carotid intima-media thickness in type 2 diabetes. Diabetes Res Clin Pract, 66 (Suppl 1), S115-120. doi:10.1016/j.diabres.2004.05.009
[21] Tajiri, Y., Mimura, K. and Umeda, F. (2005) High- sensitivity C-reactive protein in Japanese patients with type 2 diabetes. Obesity Research, 13, 1810-1816. doi:10.1038/oby.2005.220
[22] Temelkova-Kurktschiev, T.S., Koehler, C., Leonhardt, W., Schaper, F., Henkel, E., Siegert, G., Hanefeld, M. (1999) Increased intimal-medial thickness in newly detected type 2 diabetes. Diabetes Care, 22, 333-338. doi:10.2337/diacare.22.2.333
[23] Sigurdardottir, V., Fagerberg, B. and Hulthe, J. (2004) Preclinical atherosclerosis and inflammation in 61-year-old men with newly diagnosed diabetes and established diabetes. Diabetes Care, 27, 880-884. doi:10.2337/diacare.27.4.880
[24] Gong, W., Lu, B., Yang, Z., Ye, W., Du, Y., Wang, M., Li, Q., Zhang, W., Pan, Y., Feng, X., Zhou, W., Zhang, Y., Yang, Z., Yang, Y., Zhu, X. and Hu, R. (2009) Early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus and impaired glucose tolerance. Diabetes Metab, 35, 458-462. doi:10.1016/j.diabet.2009.05.005
[25] Ahmed, J., Hammed, B., Das, G., Siddiqui, M.A., Ahmed, I. (2005) Postprandial hypertriglyceridemia and carotid intima-media thickness in north Indian type 2 diabetic subjects. Diabetes Research and Clinical Practice, 69, 142-150. doi:10.1016/j.diabres.2004.11.012
[26] Beltowski, J. (2006) Leptin and atherosclerosis. Atherosclerosis, 189,47-60. doi:10.1016/j.atherosclerosis.2006.03.003
[27] Correia, M.L., Rahmouni, K. (2006) Role of leptin in the cardio- vascular and endocrine complications of metabolic syndrome. Diabetes, Obesity and Metabolism, 8, 603-610. doi:10.1111/j.1463-1326.2005.00562.x
[28] Werner, N. and Nickenig, G. (2004) From fat fighter to risk factor: The zigzag trek of leptin. Arterioscler Thromb Vasc Biol, 24, 7-9. doi:10.1161/
[29] Chiba, T., Shinozaki, S., Nakazawa, T., Kawakami, A., Ai, M., Kaneko, E., Kitagawa, M., Kondo, K., Chait, A., Shimokado, K. (2008) Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice. Atherosclerosis, 196, 68-75. doi:10.1016/j.atherosclerosis.2007.01.040
[30] Sundell, J., Huupponen, R., Raitakari, O.T., Nuutila, P., Knuuti, J. (2003) High serum leptin is associated with attenuated coronary vasoreactivity. Obesity Research, 11, 776-782. doi:10.1038/oby.2003.108
[31] Li, L., Mamputu, J.C., Wiernsperger, N., Renier, G. (2005) Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metallo- proteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes. 54, 2227-2234. doi:10.2337/diabetes.54.7.2227
[32] Xu, F.P., Chen, M.S., Wang, Y.Z., Yi, Q., Lin, S.B., Chen, A.F. and Luo, J.D. (2004) Leptin induces hypertrophy via endothelin-1-reacttive oxygen species pathway in cultured nenonatal rat cardiomyocytes, 110, 1269-1275.
[33] Loffreda, S., Yang, S.Q., Lin, H.Z, Karp, C.L., Brengman, M.L., Wang, D.J., Klein, A.S., Bulkley, G.B., Bao, C, Noble, P.W., Lane, M.D. and Diehl, A.M. (1998) Leptin regulates proinflammatory immune responses. The FASEB Journal, 12, 57-65.
[34] Bodary, P.E., Westrick, R.J., Wickenheiser K.J., Shen, Y., Eitzman, D.T. (2002) Effect of leptin on arterial thrombosis following vascular injury in mice. Journal of the American Medical Association, 287, 1706-1709.
[35] Hall, J.E., Hildebrandt, D.A. and Kuo, J. (2001) Obesity hypertension: role of leptin and sympathetic nervous system. American Journal of Hypertens, 14, 103S-115S. doi:10.1016/S0895-7061(01)02077-5
[36] Mark, A.L., Correia, M.L.G., Rahmouni, K. and Haynes, W.G. (2004) Loss of leptin actions in obesity: two concepts with cardiovascular implications. Clinical and experimental hypertension, 26, 629-636. doi:10.1081/CEH-200031948
[37] Clement, K., Lahlou, N., Ruiz, J., Hager, I., Bougneres, P., Basdevant, A., Guy-Grand, B., Froguel, P. (1997) Association of poorly controlled diabetes with low serum leptin in morbid obesity. International Journal of Obesity, 21, 556-561. doi:10.1016/S1056-8727(02)00167-8
[38] Sandoval, D.A., Davis, S.N. (2003) Leptin: metabolic control and regulation. Journal of Diabetes and its Complications, 17, 108-113. doi:10.1016/S1056-8727(02)00167-8
[39] Knudson, J.D., Payne, G.A., Borbouse, L. and Tune, J.D. (2008) Laptin and mechanisms of endothelial dusfunction and cardiovascular disease. Current Hypertens Reports, 10, 434-439. doi:10.1007/s11906-008-0082-2
[40] Gary, S. (2010) Cardiovascular effects of leptin. Nature Reviews Cardiology, 7, 22-29. doi:10.1038/nrcardio.2009.224
[41] Koh, K.K., Park, S.M. and Quon, M.J. (2008) Leptin and cardiovascular disease. Response to therapeutic interventions. Ciculation, 117, 3238-3249. doi:10.1161/CIRCULATIONAHA.107.741645
[42] Wallace, A.M., McMahon, A.D., Packard, C.J., Kelly, A., Shepherd, J., Gaw, A., and Sattar, N. on behalf of the Woscops executive committee, (2001) Plasma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention study (WOSCOPS). Circulation, 104, 3052-3056. doi:10.1161/hc5001.101061
[43] Reilly, M.P., Iqbal, N, Schutta, M., Wolfe, M.L., Scally, W.M., Localio, A.R., Rader, D.J. and Kimmel, S.E. (2004) Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes. The Journal of Clinical Endocrinology & Metabolism, 89, 3872-3878. doi:10.1210/jc.2003-031676
[44] Qasim, A., Mehta, N.M., Tadesse, M.G., Wolfe, M.L., Rhodes, T., Girman, C. and Reilly, M.P. (2008) Adipokines, insulin resistance and coronary artery calcification. Journal of the American College of Cardiology, 52, 231-236. doi:10.1016/j.jacc.2008.04.016
[45] Ciccone, M., Vettor, R., Pannacciulli, N., Minenna, A., Bellacicco, M., Rizzon, P., Giorgino, R. and De Pergola, G. (2001) Plasma leptin is independently associated with the intima- media thickness of the common carotid artery. International Journal of Obesity, 25, 805-810. doi:10.1038/sj.ijo.0801623
[46] van den Beld, A.W., Bots, M.L., Janssen, J.A., Pols, H.A., Lamberts, S.W. and Grobbee, D.E. Endogenous hormones and carotid atherosclerosis in elderly men. American Journal of Epidemiol, 157, 25-31. doi:10.1093/aje/kwf160
[47] Bountouris, J., Paraskevas, K.I., Koutousis, M., Tzavara, V., Nikolaou, N., Nomikos, A., Barbatis, C., Andrikopoulos, V., Mikhailidis, D.P., Andrikopoulou, M., Kyriakide, Z.S., Geogopoulos, S., Michail, P.O. and BAstounis, E. (2009) Serum leptin levels in patients undergoing carotid endarectomy: A pilot study. Angiology, 60, 698-704. doi:10.1177/0003319709350133
[48] Stork, S., Bots, M.L., Angerer, P., von Schacky, C., Grobbee, D.E., Angermann, C.E., Seufert, J. (2007) Low levels of adiponectin predict worsening of arterial morphology and function. Atherosclerosis, 194, e147- e153. doi:10.1016/j.atherosclerosis.2006.11.044
[49] Ionescu-Tirgoviste, C., Ioacara, S., Guja, C., Sabau, S. et al. (2006) A pathophysiological approach to metabolic syndrome using factor analysis in an adult Romanian population. Archives of Physiology and Biochemistry 112(3), 182-188. doi:10.1080/13813450600976374
[50] Hansen, D., Dendale, P., Beelen, M., Jonkers, R.A.M., Mullens, A., Corluy, L., Meeusen, R., van Loon, L.J.C. (2010) Plasma adipokine and inflammatory marker concentrations are altered in obese, as opposed to non-obese, type 2 diabetes patients. European Journal of Applied Physiology, 109, 397-404. doi:10.1007/s00421-010-1362-5

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.