Yonsei Med J.  2017 Mar;58(2):339-346. 10.3349/ymj.2017.58.2.339.

Impact of Serum Leptin to Adiponectin Ratio on Regression of Metabolic Syndrome in High-Risk Individuals: The ARIRANG Study

• Kang DR
• Yadav D
• Koh SB
• Kim JY
• Ahn SV

• KMID: 2427122
• DOI: http://doi.org/10.3349/ymj.2017.58.2.339

Abstract

PURPOSE
The ratio of serum leptin to adiponectin (L/A ratio) could be used as a marker for insulin resistance. However, few prospective studies have investigated the impact of L/A ratio on improvement of metabolic components in high-risk individuals with metabolic syndrome. We examined the association between L/A ratio and the regression of metabolic syndrome in a population-based longitudinal study.
MATERIALS AND METHODS
A total of 1017 subjects (431 men and 586 women) with metabolic syndrome at baseline (2005-2008) were examined and followed (2008-2011). Baseline serum levels of leptin and adiponectin were analyzed by radioimmunoassay. Area under the receiver operating characteristics curve (AUROC) analyses were used to assess the predictive ability of L/A ratio for the regression of metabolic syndrome.
RESULTS
During an average of 2.8 years of follow-up, metabolic syndrome disappeared in 142 men (32.9%) and 196 women (33.4%). After multivariable adjustment, the odds ratios (95% confidence interval) for regression of metabolic syndrome in comparisons of the lowest to the highest tertiles of L/A ratio were 1.84 (1.02-3.31) in men and 2.32 (1.37-3.91) in women. In AUROC analyses, L/A ratio had a greater predictive power than serum adiponectin for the regression of metabolic syndrome in both men (p=0.024) and women (p=0.019).
CONCLUSION
Low L/A ratio is a predictor for the regression of metabolic syndrome. The L/A ratio could be a useful clinical marker for management of high-risk individuals with metabolic syndrome.

Keyword

Leptin; adiponectin; metabolic syndrome; insulin resistance; prospective study

MeSH Terms

Adiponectin/*blood
Adult
Biomarkers/blood
Female
Humans
Insulin Resistance
Leptin/*blood
Longitudinal Studies
Male
Metabolic Syndrome/*blood
Middle Aged
Odds Ratio
Population Surveillance
Prospective Studies
Adiponectin
Biomarkers
Leptin

Figure

• 

  Fig. 1 Proportion (%) of regression of metabolic syndrome according to baseline leptin (ng/mL) and adiponectin (µg/mL) tertiles. Leptin T1: <2.45 in men, <8.02 in women; Leptin T2: 2.45–3.89 in men, 8.02–12.68 in women; Leptin T3: ≥3.90 in men, ≥12.69 in women; Adiponectin T1: <4.61 in men, <7.69 in women; Adiponectin T2: 4.61–6.95 in men, 7.69–11.12 in women; Adiponectin T3: ≥6.96 in men, ≥11.13 in women.

• 

  Fig. 2 Comparison of predictive powers of serum levels of leptin, adiponectin and L/A ratio for regression of metabolic syndrome. AUROC, area under the receiver operating characteristics curve; L/A ratio, ratio of leptin to adiponectin.

Reference

1. Wang P, Mariman E, Renes J, Keijer J. The secretory function of adipocytes in the physiology of white adipose tissue. J Cell Physiol. 2008; 216:3–13.

2. Bartness TJ, Song CK. Thematic review series: adipocyte biology. Sympathetic and sensory innervation of white adipose tissue. J Lipid Res. 2007; 48:1655–1672.

3. Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol. 2005; 115:911–919.

4. Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann N Y Acad Sci. 1999; 892:146–154.

5. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation. 2000; 102:1296–1301.

6. Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, et al. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun. 2004; 314:415–419.

7. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001; 86:1930–1935.

8. Kim JY, Ahn SV, Yoon JH, Koh SB, Yoon J, Yoo BS, et al. Prospective study of serum adiponectin and incident metabolic syndrome: the ARIRANG study. Diabetes Care. 2013; 36:1547–1553.

9. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998; 395:763–770.

10. Patel SB, Reams GP, Spear RM, Freeman RH, Villarreal D. Leptin: linking obesity, the metabolic syndrome, and cardiovascular disease. Curr Hypertens Rep. 2008; 10:131–137.

11. Segal KR, Landt M, Klein S. Relationship between insulin sensitivity and plasma leptin concentration in lean and obese men. Diabetes. 1996; 45:988–991.

12. Finucane FM, Luan J, Wareham NJ, Sharp SJ, O’Rahilly S, Balkau B, et al. Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals. Diabetologia. 2009; 52:2345–2349.

13. Yoon JH, Park JK, Oh SS, Lee KH, Kim SK, Cho IJ, et al. The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: the Korean Genomic Rural Cohort Study. Clin Chim Acta. 2011; 412:2199–2205.

14. Satoh N, Naruse M, Usui T, Tagami T, Suganami T, Yamada K, et al. Leptin-to-adiponectin ratio as a potential atherogenic index in obese type 2 diabetic patients. Diabetes Care. 2004; 27:2488–2490.

15. 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; 28:412–419.

16. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood Institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009; 120:1640–1645.

17. Lee SY, Park HS, Kim DJ, Han JH, Kim SM, Cho GJ, et al. Appropriate waist circumference cutoff points for central obesity in Korean adults. Diabetes Res Clin Pract. 2007; 75:72–80.

18. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005; 365:1415–1428.

19. Trujillo ME, Scherer PE. Adiponectin--journey from an adipocyte secretory protein to biomarker of the metabolic syndrome. J Intern Med. 2005; 257:167–175.

20. Gannagé-Yared MH, Khalife S, Semaan M, Fares F, Jambart S, Halaby G. Serum adiponectin and leptin levels in relation to the metabolic syndrome, androgenic profile and somatotropic axis in healthy non-diabetic elderly men. Eur J Endocrinol. 2006; 155:167–176.

21. Kumagai S, Kishimoto H, Masatakasuwa , Zou B, Harukasasaki . The leptin to adiponectin ratio is a good biomarker for the prevalence of metabolic syndrome, dependent on visceral fat accumulation and endurance fitness in obese patients with diabetes mellitus. Metab Syndr Relat Disord. 2005; 3:85–94.

22. Zhuo Q, Wang Z, Fu P, Piao J, Tian Y, Xu J, et al. Comparison of adiponectin, leptin and leptin to adiponectin ratio as diagnostic marker for metabolic syndrome in older adults of Chinese major cities. Diabetes Res Clin Pract. 2009; 84:27–33.

23. Kimura K, Tsuda K, Baba A, Kawabe T, Boh-oka S, Ibata M, et al. Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. Biochem Biophys Res Commun. 2000; 273:745–749.

24. Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem. 2003; 278:45021–45026.

25. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem. 2004; 279:1304–1309.

26. Xie D, Bollag WB. Obesity, hypertension and aldosterone: is leptin the link? J Endocrinol. 2016; 230:F7–F11.

27. Carlyle M, Jones OB, Kuo JJ, Hall JE. Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension. 2002; 39(2 Pt 2):496–501.

28. Wolf G, Hamann A, Han DC, Helmchen U, Thaiss F, Ziyadeh FN, et al. Leptin stimulates proliferation and TGF-beta expression in renal glomerular endothelial cells: potential role in glomerulosclerosis [seecomments]. Kidney Int. 1999; 56:860–872.

29. Wannamethee SG, Lowe GD, Rumley A, Cherry L, Whincup PH, Sattar N. Adipokines and risk of type 2 diabetes in older men. Diabetes Care. 2007; 30:1200–1205.

30. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N, Ohishi M, Sugimoto K, et al. Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension. 2004; 43:1318–1323.

31. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab. 2002; 87:2764–2769.

32. Beltowski J. Leptin and atherosclerosis. Atherosclerosis. 2006; 189:47–60.

33. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia. 2003; 46:459–469.

34. McNeely MJ, Boyko EJ, Weigle DS, Shofer JB, Chessler SD, Leonnetti DL, et al. Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans. Diabetes Care. 1999; 22:65–70.

35. Söderberg S, Zimmet P, Tuomilehto J, Chitson P, Gareeboo H, Alberti KG, et al. Leptin predicts the development of diabetes in Mauritian men, but not women: a population-based study. Int J Obes (Lond). 2007; 31:1126–1133.

36. Hellström L, Wahrenberg H, Hruska K, Reynisdottir S, Arner P. Mechanisms behind gender differences in circulating leptin levels. J Intern Med. 2000; 247:457–462.

37. Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes. 2002; 51:2734–2741.

38. Boyne MS, Bennett NR, Cooper RS, Royal-Thomas TY, Bennett FI, Luke A, et al. Sex-differences in adiponectin levels and body fat distribution: longitudinal observations in Afro-Jamaicans. Diabetes Res Clin Pract. 2010; 90:e33–e36.

39. Seino Y, Hirose H, Saito I, Itoh H. High-molecular-weight adiponectin is a predictor of progression to metabolic syndrome: a population-based 6-year follow-up study in Japanese men. Metabolism. 2009; 58:355–360.