Published: 2016-12-27

Interleukin-6 in obese type II diabetes with hypertension

Victoria Laishram, Chanchal Lamabam, Shaini Laikangbam, Abhishek Dubey, Chubalemla Longkumer, Soumadip Sharma, Suman Debnath, Rupak Das


Background: Type II diabetes mellitus (T2DM) and obesity are found to be associated with increased incidence of hypertension, although the mechanisms facilitating hypertension in T2DM or nondiabetic individuals are not clear.

Methods: We compared the levels of fasting plasma glucose, HbA1c, lipid subfractions and inflammatory cytokine interleukin 6 (IL-6), being risk factors previously found to be associated with hypertension, in T2DM patients showing increased body weight (obese and overweight with body mass index, BMI ≥25 kg/m2) with hypertension (group A, n=30), or without hypertension (group B, n=30), and in non-obese (BMI <25 kg/m2), normotensive controls (group C, n=40).

Results: BMI, HbA1c, fasting plasma glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol were found to be significantly higher in group A, B Vs C (p <0.05). Also, IL-6 levels were significantly higher both in group A and B compared to group C. The highest level of IL-6 was found in group A, being significantly higher than in group B (A: 14.34 ± 4.98 pg/ml; B: 10.66 ± 1.16 pg/ml; C: 7.41 ± 0.54 pg/ml, A vs. B p<0.001; A, B vs. C p<0.001).

Conclusions: Our results have shown that appearance of hypertension in T2DM patients with increased body weight was dependent on rise in inflammatory marker IL-6 cytokine.  



Type II diabetes mellitus, Hypertension, Obesity, Interleukin-6

Full Text:



Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia. 1998;41:1241-8.

Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab. 1997;82:1313-6.

Pickup JC, Chusney GD, Mattock MB. The innate immune response and type 2 diabetes: evidence that leptin is associated with a stress-related (acute-phase) reaction. Clin Endocrinol (Oxf). 2000;52:107-12.

Bastard JP, Jardel C, Bruckert E, Blondy P, Capeau J, Laville M et al. Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab. 2000;85:3338-42.

Loppnow H, Libby P. Adult human vascular endothelial cells express the IL 6 gene differentially in response to LPS or IL1. Cell Immunol. 1989;122:493-503.

Loppnow H, Libby P. Comparative analysis of cytokine induction in human vascular endothelial and smooth muscle cells. Lymphokine Res. 1989;8:293-9.

Szekanecz Z, Shah MR, Pearce WH, Koch AE. Human atherosclerotic abdominal aortic aneurysms produce interleukin (IL)-6 and interferon-gamma but not IL-2 and IL-4: the possible role for IL-6 and interferon-gamma in vascular inflammation. Agents Actions. 1994;42:159-62.

Seino Y, Ikeda U, Ikeda M, Yamamoto K, Misawa Y, Hasegawa T, Kano S, Shimada K. Interleukin-6 gene transcripts are expressed in human atherosclerotic lesions. Cytokine. 1994;6:87-91.

Rus HG, Vlaicu R, Niculescu F. Interleukin-6 and interluekin-8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis. 1996;127:263-71.

Mestries JC, Kruithof EKO, Gascon MP, Herodin F, Agay D, Ythier A. In vivo modulation of coagulation and fibrinolysis by recombinant glycosylated human interleukin-6 in baboons. Eur Cytokine Netw. 1994;5:275-81.

Van der Poll T, Levi M, Hack CE, Ten Cate U, van Deventer SJH, Erenberg AJM, et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees. J Exp Med. 1994;179:1253-9.

Stouthard JML, Levi M, Hack CE, Beenhof CHN, Romijn HA, Sauerwein HP, et al. Interleukin-6 stimulates coagulation, not fibrinolysis, in humans. Thromb Haemost. 1996;76:738-42.

Savoia C, Schiffrin E. Vascular inflammation in hypertension and diabetes: molecular mechanisms and therapeutic interventions. Clin Sci. 2007;112:375-84.

Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M et al. Markers of inflammation and cardiovascular disease application to clinical and public health practice: a statement for healthcare professionals from the centres for disease control and prevention and the American heart association. Circulation. 2003;107:499-511.

Hotamisligil GS. The role of TNF alpha and TNF receptors in obesity and insulin resistance. J Intern Med. 1999;245:621-25.

Febbraio MA, Pedersen BK. Muscle derived interleukin-6: mechanisms for activation and possible biological roles. Faseb J. 2002;16:1335-47.

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793-801.

Chobanian, AV, Bakris GR, Black HF, Cushman WC, Green LA, Izzo JL. National heart, lung and blood institute joint national committee on prevention, detection, evaluation and treatment of high blood pressure; national high blood pressure education program coordinating committee: seventh report of joint national committee on prevention, detection, evaluation and treatment of high blood pressure; the JNC 7 report. J Amer Med Assoc. 2003;289:2560-72.

Weisberg SP, McCann M, Desai M, Rosenbaum R, Leibel L, Ferrante AW. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Investig. 2003;112:1796-808.

Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumour necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280:745-51.

Stephens JW, Hurel SJ, Cooper JA, Acharya J, Miller GJ, Humphries SE. A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus. Mol Genet Metab. 2004;82:180-6.

Popko E, Gorska A, Stelmaszczyk-Emmel A, Plywaczewski R, Stoklosa A, Gorecka D, et al. Proinflammatory cytokines IL-6 and TNF-α and the development of inflammation in obese subjects. Eur J Med Res. 2010;15:120-2.

Hu FB, Meigs JB, Li TY, Manson JE. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004; 53:693-700.

Schmidt MI, Duncan BB, Sharrett AR. Markers of inflammation and prediction of diabetes mellitus in adults (atherosclerosis risk in communities study): a cohort study. The Lancet. 1999;353:1649-52.

Pérez PA, Ybarra MJ, Blay CV, De Pablos VP. Obesity and cardiovascular disease. Public Health Nutr. 2007;10:1156-63.

De Jager J, Dekker JM, Kooy A, Kostense PJ, Nijpels G, Heine RJ et al. Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes The Hoorn Study. Arterioscler Thromb Vasc Boil. 2006;26:1086-93.

Ganne S, Arora SK, Dotsenko O, McFarlane SI, Whaley-Connell A. Hypertension in people with diabetes and the metabolic syndrome: Pathophysiologic insights and therapeutic update. Curr Diabetes Rep. 2007;7:208-17.

Reaven GM, Lithell H, Lansberg L. Hypertension and associated metabolic abnormalities-the role of insulin resistance and the sympathoadrenal system. N Engl J Med. 1996;334:374-81.

Pirro M, Schillaci G, Savarese G, Gemelli F, Mannarino MR, Siepi D et al. Attenuation of inflammation with short-term dietary intervention is associated with a reduction of arterial stiffness in subjects with hypercholesterolaemia. Eur J Cardiovasc Prev Rehabil. 2004;11:497-502.

Olson TP, Dengel DR, Leon AS, Schmitz KH. Changes in inflammatory biomarkers following one-year of moderate resistance training in overweight women. Int J Obes. 2007;31:996-1003.

Badawi A, Klip A, Haddad P, Cole DEC, Bailo BG, El-Sohemy A et al. Type 2 diabetes mellitus and inflammation: prospects for biomarkers of risk and nutritional intervention. Diabetes Metab Syndr Obes. 2010;26:173-86.

Christiansen T, Paulsen SK, Bruun JM, Pedersen SB, Richelsen B. Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study. Am J Physiol Endocrinol Metab. 2010; 298:824–31.

Rosenzweig JL, Ferrannini E, Grundy SM, Haffner SM, Heine RJ, Horton ES. Primary prevention of cardiovascular disease and type 2 diabetes in patients at metabolic risk: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2008;93:3671-89.

Lalic NM, Zamaklar M, Pudar G. Early detection and prevention of type 2 diabetes: national program Serbia. In diabetes prevention in practice, ISBN 978-3-00-030765-2; Schwarz P, Reddy P, Greaves C, Dunbar J, Schwarz J, Eds. Dresden, Germany: TUMAINI institute for prevention management; 2010:117-24.