Abstract
Aims: Adiponectin and leptin are adipocytokines associated with insulin resistance. The objective of this study was to evaluate the performance of the adiponectin-leptin ratio as a measure of insulin resistance in comparison with other surrogate measures of insulin resistance based on fasting insulin and glucose levels [homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), fasting glucose/insulin ratio] and with measures based on fasting insulin and triglyceride levels (McAuley index) in Caucasian patients with Type 2 diabetes (T2D). Methods: In 70 patients included in DEMAND (delapril and manidipine for nephroprotection in diabetes) study, fasting samples of plasma insulin and adiponectin were determined by a radioimmunoassay, whereas plasma leptin was determined by an enzyme-linked immunosorbent assay. Insulin resistance estimates were derived by the established equations and compared with the direct measurement of insulin resistance obtained with the euglycemic hyperinsulinemic clamp. Insulin resistance estimates and the clamp derived sensitivity index were compared by correlation analysis. Results: The adiponectin-leptin ratio correlated best with the clamp derived sensitivity index (r=0.553, p<0.001) compared to other surrogate measures of insulin resistance. In multiple linear regression models including different surrogate measures of insulin resistance as independent predictors of the sensitivity index, the model with the adiponectin-leptin ratio accounted for the highest variability of the sensitivity index (r 2=0.336, p<0.001). Conclusions: The adiponectin-leptin ratio is associated with insulin resistance, measured with the euglycemic hyperinsulinemic clamp, in Caucasians with T2D. The association with clamp derived sensitivity index is even stronger than that of HOMA, QUICKI, fasting glucose/insulin ratio or McAuley index and is independent of body mass index or glycemic control. The adiponectin-leptin ratio promises to become a new laboratory marker of insulin resistance in T2D.
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References
Bloomgarden ZT. Insulin resistance, dyslipidemia, and cardiovascular disease. Diabetes Care 2007, 30: 2164–70.
American Diabetes Association. Consensus development conference on insulin resistance. Diabetes Care 1998, 21: 310–4.
Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance. Diabetologia 2003, 46: 1594–603.
Weyer C, Funahashi T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metabol 2001, 86: 1930–5.
Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000, 20: 1595–9.
Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004, 50: 1511–25.
Inoue M, Maehata E, Yano M, Taniyama M, Suzuki S. Correlation between the adiponectin-leptin ratio and parameters of insulin resistance in patients with type 2 diabetes. Metabolism 2005, 54: 281–6.
Inoue M, Yano M, Yamakado M, Maehata E, Suzuki S. Relationship between the adiponectin-leptin ratio and parameters of insulin resistance in subjects without hyperglycemia. Metabolism 2006, 55: 1248–54.
Satoh N, Naruse M, Usui T, et al. Leptin-to-adiponectin ratio as a potential atherogenic index in obese Type 2 diabetic patients. Diabetes Care 2004, 27: 2488–90.
Kotani K, Sakane N, Saiga K, Kurozawa Y. Leptin:adiponectin ratio as an atheroscleroic index in patients with Type 2 diabetes: relationship of the index to carotid intima-media thickness. Diabetologia 2005, 48: 2684–6.
DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979, 237: 214–23.
McAuley KA, Williams SM, Mann JI, et al. Diagnosing insulin resistance in the general population. Diabetes Care 2001, 24: 460–4.
Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte secreted protein ACRP30 enhances hepatic insulin action. Nat Med 2001, 7: 947–53.
Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP 30. Nat Med 2002, 8: 731–7.
Stefan N, Vozarova B, Funahashi T, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 2002, 51: 1884–8.
Musi N, Yu H, Goodyear LJ. AMP-activated protein kinase regulation and action in skeletal muscle during exercise. Biochem Soc Trans 2003, 31: 191–5.
Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003, 423: 762–9.
Minokoshi Y, Kim YB, Peroni OD, et al. Leptin stimulates fatty acid oxidation by activating AMP-activated protein kinase. Nature 2002, 415: 339–43.
Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002, 26: 1407–33.
Sandhofer A, Laimer M, Ebenbichler CF, Kaser S, Paulweber B, Patsch JR. Soluble leptin receptor and soluble receptor-bound fraction of leptin in the metabolic syndrome. Obes Res 2003, 11: 760–8.
Vigoroux C, Maachi M, Nguyen TH, et al. Serum adipocytokines are related to lipodystrophy and metabolic disorders in HIV-infected men under retroviral therapy. AIDS 2003, 17: 1503–11.
Xita N, Papassotiriou I, Georgiou I, Vounatsou M, Margeli A, Tsatsoulis A. The adiponectin-to-leptin ratio in women with polycystic ovary syndrome: relation to insulin resistance and proinflammatory markers. Metabolism 2007, 56: 766–71.
Ouyang Y, Chen H, Chen H. Reduced plasma adiponectin and elevatedleptin in pre-eclampsia. Int J Gynaecol Obstet 2007, 98: 110–4.
Katsuki A, Sumida Y, Urakawa H, et al. Neither homeostasis model assessment nor quantitative insulin sensitivity check indexcan predict insulin resistance in elderly patients with poorly controlled type 2 diabetes mellitus. J Clin Endocrinol Metab 2002, 87: 5332–5.
Prato SD, Pozzilli P. FIRI: fasting or false insulin resistance index? Lancet 1996, 347: 132.
Oda N, Imamura S, Fujita T, et al. Theratio of leptin to adiponectin can be used as an index of insulin resistance. Metabolism 2008, 57: 268–73.
Martin M, Palaniappan LP, Kwan AC, Reaven GM, Reaven PD. Ethnic differences in the relationship between adiponectin and insulin sensitivity in South Asian and Caucasian women. Diabetes Care 2008, 31: 798–801.
Araneta MR, Barrett-Connor E. Adiponectin and ghrelin levels and body size in normoglycemic Filipino, African-American, and white women. Obesity (Silver Spring) 2007, 15: 2454–62.
Radziuk J. Insulin sensitivity and its measurement: structural commonalities among the methods. J Clin Endocrinol Metab 2000, 85: 4426–33.
Ciccone M, Vettor R, Pannacciulli N, et al. Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. Int J Obes Related Metab Disord 2001, 25: 805–10.
Störk S, Bots ML, Angerer P, et al. Low levels of adiponectin predict worsening of arterial morphology and function. Atherosclerosis 2007, 194: 147–53.
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Zaletel, J., Pongrac Barlovic, D. & Prezelj, J. Adiponectin-leptin ratio: A useful estimate of insulin resistance in patients with Type 2 diabetes. J Endocrinol Invest 33, 514–518 (2010). https://doi.org/10.1007/BF03346639
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DOI: https://doi.org/10.1007/BF03346639