Insulin resistance and adipokines serum levels in a caucasian cohort of hiv-positive patients undergoing antiretroviral therapy: a cross sectional study

BMC Endocrine Disorders

Stefan Sorin Arama¹  Adriana Hristea²  Daniela Munteanu²  Raluca Mihailescu²  Daniela Ion¹  Adrian Streinu-Cercel²  Catalin Tiliscan²  Victoria Arama² 

[1] Carol Davila University of Medicine and Pharmacy, Bucharest, Romania;Prof. Dr. Matei Bals National Institute of Infectious Diseases, Bucharest, Romania

关键词: HIV;    Insulin resistance;    Antiretroviral therapy;    Leptin;    Adiponectin;    Adipokines;   

Others  :  1086003
DOI  :  10.1186/1472-6823-13-4

 received in 2012-06-27, accepted in 2013-01-23,  发布年份 2013

【 摘 要 】

Background

Insulin resistance is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy. Cytokines secreted by adipose tissue (adipokines) are linked to insulin sensitivity. The present study is aimed to assess the prevalence of insulin resistance (IR) and its association with several adipokines, in a non-diabetic Romanian cohort of men and women with HIV-1 infection, undergoing combination antiretroviral therapy (cART).

Methods

A cross-sectional study was conducted in an unselected sample of 89 HIV-1-positive, non-diabetic patients undergoing stable cART for at least 6 months. Metabolic parameters were measured, including fasting plasma insulin, and circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Insulin resistance was estimated by measuring the Quantitative Insulin Sensitivity Check Index (QUICKI), using a cut-off value of 0.33. A linear regression model was fitted to QUICKI to test the association of IR and adipokines levels.

Results

A total of 89 patients (aged 18–65, median: 28 years) including 51 men (57.3%) and 38 women (42.7%) were included in the study. Fifty nine patients (66.3%) were diagnosed with IR based on QUICKI values lower than the cut-off point. IR prevalence was 72.5% in men and 57.6% in women. The presence of the IR was not influenced by either the time of the HIV diagnosis or by the duration of cART. Decreased adiponectin and increased serum triglycerides were associated with increased IR in men (R=0.43, p=0.007). Hyperleptinemia in women was demonstrated to be associated with the presence of IR (R=0.33, p=0.03).

Conclusions

Given the significant prevalence of the IR in our young non-diabetic cohort with HIV infection undergoing antiretroviral therapy reported in our study and the consecutive risk of diabetes and cardiovascular events, we suggest that the IR management should be a central component of HIV-infection therapeutic strategy. As adipokines play major roles in regulating glucose homeostasis with levels varying according to the sex, we suggest that further studies investigating adipokines should base their analyses on gender differences.

【 授权许可】

   
2013 Arama et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 7.

【 参考文献 】

• [1]Falutz J: Management of Fat Accumulation in Patients with HIV Infection. Curr HIV/AIDS Rep 2011 Sep, 8(3):200-208.
• [2]Giralt M, Domingo P, Villarroya F: Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol Metab 2011 Jun, 25(3):487-499.
• [3]Feeney ER, Mallon PW: Insulin resistance in treated HIV infection. Best Pract Res Clin Endocrinol Metab 2011 Jun, 25(3):443-458.
• [4]Giannarelli C, Klein RS, Badimon JJ: Cardiovascular implications of HIV-induced dyslipidemia. Atherosclerosis 2011 Dec, 219(2):384-389.
• [5]Koster JC, Remedi MS, Qiu H, Nichols CG, Hruz PW: HIV protease inhibitors acutely impair glucose-stimulated insulin release. Diabetes 2003 Jul, 52(7):1695-1700.
• [6]Hui DY: Effects of HIV protease inhibitor therapy on lipid metabolism. Prog Lipid Res 2003 Mar, 42(2):81-92.
• [7]Chaparro J, Reeds DN, Wen W, Xueping E, Klein S, Semenkovich CF, Bae KT, Quirk EK, Powderly WG, Yarasheski KE, Li E: Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy. Metabolism 2005 May, 54(5):561-567.
• [8]Rabe K, Lehrke M, Parhofer KG, Broedl UC: Adipokines and insulin resistance. Mol Med 2008, 14(11–12):51-741.
• [9]Vigouroux C, Maachi M, Nguyên TH, Coussieu C, Gharakhanian S, Funahashi T, Matsuzawa Y, Shimomura I, Rozenbaum W, Capeau J, Bastard JP: Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under antiretroviral therapy. AIDS 2003, 17:1503-1511.
• [10]Jones SP, Qazi N, Morelese J, Lebrecht D, Sutinen J, Yki-Jărvinen H, Back DJ, Pirmohamed M, Gazzard BG, Walker UA, Moyle GJ: Assessment of adipokine expression and mitochondrial toxicity in HIV patients with lipoatrophy on stavudine- and zidovudine-containing regimens. J Acquir Immune Defic Syndr 2005 Dec 15, 40(5):565-572.
• [11]World Health Organization: Obesity: Preventing and Managing the Global Epidemic. Geneva: Technical Report Series No. 894. WHO; 2000.
• [12]Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ: Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab 2000 Jul, 85(7):2402-2410.
• [13]Castaneda-Sceppa C, Bermudez OI, Wanke C, Forrester JE: Predictors of insulin resistance among Hispanic adults infected with or at risk of infection with the human immunodeficiency virus and hepatitis C virus. J Viral Hepat 2008 Dec, 15(12):878-887.
• [14]Jones CY, Wilson IB, Greenberg AS, Shevitz A, Knox TA, Gorbach SL, Spiegelman D, Jacobson DL, Wanke C: Insulin resistance in HIV-infected men and women in the nutrition for healthy living cohort. J Acquir Immune Defic Syndr 2005 Oct 1, 40(2):202-211.
• [15]Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R: Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care 2003 Dec, 26(12):3320-3325.
• [16]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985 Jul, 28(7):412-419.
• [17]Matti A, Nasta P, Borghi F, Cologni G, Ricci A, Gatti F, Puoti M, Carosi G: Predictors of insulin resistance (IR) in HIV/HCV co-infected patients treated with pegylated interferon alpha 2-a (Peg/IFN) and ribavirin (RBV). Treatment and Prevention: 4th IAS Conference on HIV Pathogenesis; 2007:22-25.
• [18]Lebovitz HE: Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes 2001, 109(Suppl. 2):S135-S148.
• [19]DeFronzo RA, Ferrannini E: Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991, 14:173-194.
• [20]Ford ES, Giles WH, Dietz WH: Prevalence of the metabolic syndrome among US adults: findings from the third national health and nutrition examination survey. JAMA 2002, 287:356-359.
• [21]Marques-Vidal P, Mazoyer E, Bongard V, Gourdy P, Ruidavets JB, Drouet L, Ferrières J: Prevalence of insulin resistance syndrome in southwestern France and its relationship with inflammatory and hemostatic markers. Diabetes Care 2002, 25:1371-1377.
• [22]Pyörälä M, Miettinen H, Halonen P, Laakso M, Pyörälä K: Insulin resistance syndrome predicts the risk of coronary heart disease and stroke in healthy middle-aged men: the 22-year follow-up results of the Helsinki policemen study. Arterioscler Thromb Vasc Biol 2000, 20:538-544.
• [23]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, 19:470-475.
• [24]Hommes MJ, Romijn JA, Endert E, Eeftinck Schattenkerk JK, Sauerwein HP: Insulin sensitivity and insulin clearance in human immunodeficiency virus-infected men. Metabolism 1991 Jun, 40(6):651-656.
• [25]Walli R, Herfort O, Michl GM, Demant T, Jäger H, Dieterle C, Bogner JR, Landgraf R, Goebel FD: Treatment with protease inhibitors associated with peripheral insulin resistance and impaired oral glucose tolerance in HIV-1-infected patients. AIDS 1998, 12:F167-F173.
• [26]Dubé MP, Edmondson-Melançon H, Qian D, Aqeel R, Johnson D, Buchanan TA: Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B-cell function in HIV-infected patients. J Acquir Immune Defic Syndr 2001, 27:130-134.
• [27]Yan Q, Hruz PW: Direct comparison of the acute in vivo effects of HIV protease inhibitors on peripheral glucose disposal. J Acquir Immune Defic Syndr 2005, 40:398-403.
• [28]Florescu D, Kotler DP: Insulin resistance, glucose intolerance and diabetes mellitus in HIV-infected patients. Antivir Ther 2007, 12(2):149-162.
• [29]De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, El-Sadr W, Monforte A, Fontas E, Law MG, Friis-Møller N, Phillips A: Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study. Diabetes Care 2008, 31(6):9-1224. Epub 2008 Feb 11
• [30]Ziemke F, Mantzoros CS: Adiponectin in insulin resistance: lessons from translational research. Am J Clin Nutr 2010, 91(1):258S-261S.
• [31]Fu Y, Luo N, Klein RL, Garvey WT: Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res 2005, 46(7):79-1369. Epub 2005 Apr 16
• [32]Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, Noda T: Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002, 277:25863-25866.
• [33]Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001, 86:1930-1935.
• [34]Deloumeaux J, Maachi M, Sow-Goerger MT, Lamaury I, Velayoudom FL, Cheret A, Batard ML, Muller P, Bastard JP, Chene G, Capeau J, Foucan L: Adiponectin and leptin in Afro-Caribbean men and women with HIV infection: association with insulin resistance and type 2 diabetes. Diabetes Metab 2011 Apr, 37(2):98-104.
• [35]Viganò A, Zuccotti GV, Cerini C, Stucchi S, Puzzovio M, Giacomet V, Mora S: Lipodystrophy, Insulin Resistance, and Adiponectin Concentration in HIV-Infected Children and Adolescents. Curr HIV Res 2011 Jul, 9(5):321-326.
• [36]Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K, Okazaki Y, Ishii T, Nishikai K, Saruta T: Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population. Clin Sci (Lond) 2002, 103:137-142.
• [37]Mynarcik DC, Combs T, McNurlan MA, Scherer PE, Komaroff E, Gelato MC: Adiponectin and leptin levels in HIV-Infected subjects withinsulin resistance and body fat redistribution. JAIDS 2002, 31:514-520.
• [38]Kelesidis T, Kelesidis I, Chou S, Mantzoros CS: Narrative review: the role of leptin in human physiology: emerging clinical applications. Ann Intern Med 2010 Jan 19, 152(2):93-100.
• [39]Azzoni L, Crowther NJ, Firnhaber C, et al.: Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women. J Int AIDS Soc 2010 Sep 7, 13:33. BioMed Central Full Text
• [40]Tao MM, Zhang L, Qiu ZF, Xie J, Han Y, Yu W, Li M, Li TS: Adipokines and highly active antiretroviral therapy related lipodystrophy: clinical study of 52 cases. Zhonghua Yi Xue Za Zhi 2009 Apr 7, 89(13):867-871.
• [41]Nagy GS, Tsiodras S, Martin LD, Avihingsanon A, Gavrila A, Hsu WC, Karchmer AW, Mantzoros CS: Human immunodeficiency virus type 1-related lipoatrophy and lipohypertrophy are associated with serum concentrations of leptin. Clin Infect Dis 2003, 36:795-802.