The Relationship Between Insulin Sensitivity and Serum Adiponectin Levels in Three Population Groups

W. F. Ferris; N. H. Naran; N. J. Crowther; P. Rheeder; L. van der Merwe; N. Chetty

doi:10.1055/s-2005-870580

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2005; 37(11): 695-701
DOI: 10.1055/s-2005-870580

Original Clinical

The Relationship Between Insulin Sensitivity and Serum Adiponectin Levels in Three Population Groups

W. F. Ferris¹ , N. H. Naran² , N. J. Crowther³ , P. Rheeder⁴ , L. van der Merwe⁵ , N. Chetty²

¹Endocrinology and Metabolism Unit, Department of Internal Medicine, University of Stellenbosch, Tygerberg, South Africa
²Department of Haematology and Molecular Medicine, National Health Laboratory Service, University of Witwatersrand, Johannesburg, South Africa
³Department of Chemical Pathology, National Health Laboratory Service, University of Witwatersrand, Johannesburg, South Africa
⁴Clinical Epidemiology Division, University of Pretoria, Pretoria, South Africa
⁵Biostatistics Unit, Medical Research Council, Tygerberg, South Africa

Abstract

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 ± 0.99) and Asian-Indian subjects (HOMA = 3.41 ± 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 ± 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 ± 4.39 µg/ml) compared to black (5.71 ± 2.50 µg/ml) and Asian Indian (5.86 ± 2.50 µg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.

Key words

Obesity - HOMA - HDL - ethnicity

Full Text

References

1 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun. 1996; 221 286-289
2 Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999; 257 79-83
3 Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman M L, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001; 7 941-946
4 Fruebis J, Tsao T S, Javorschi S, Ebbets-Reed D, Erickson M R, Yen F T, Bihain B E, Lodish H F. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U.S.A.. 2001; 98 2005-2010
5 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 25 863-25 866
6 Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002; 8 731-737
7 Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001; 50 2094-2099
8 Hotta K, Funahashi T, Bodkin N L, Ortmeyer H K, Arita Y, Hansen B C, Matsuzawa Y. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes. 2001; 50 1126-1133
9 Stefan N, Bunt J C, Salbe A D, Funahashi T, Matsuzawa Y, Tataranni P A. Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab. 2002; 87 4652-4656
10 Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, Mohlig M, Pfeiffer A F, Luft F C, Sharma A M. Association between adiponectin and mediators of inflammation in obese women. Diabetes. 2003; 52 942-947
11 Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000; 20 1595-1599
12 Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999; 100 2473-2476
13 Lindsay R S, Funahashi T, Hanson R L, Matsuzawa Y, Tanaka S, Tataranni P A, Knowler W C, Krakoff J. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet. 2002; 360 57-58
14 Spranger J, Kroke A, Mohlig M, Bergmann M M, Ristow M, Boeing H, Pfeiffer A F. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003; 361 226-228
15 Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H, Ohnuma H, Igarashi M, Tominaga M, Kato T. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population: the Funagata study. Diabetes Care.. 2003; 26 2015-2020
16 Snehalatha C, Mukesh B, Simon M, Viswanathan V, Haffner S M, Ramachandran A. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian indians. Diabetes Care. 2003; 26 3226-3229
17 Pellme F, Smith U, Funahashi T, Matsuzawa Y, Brekke H, Wiklund O, Taskinen M R, Jansson P A. Circulating adiponectin levels are reduced in nonobese but insulin-resistant first-degree relatives of type 2 diabetic patients. Diabetes. 2003; 52 1182-1186
18 Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003; 289 1799-1804
19 Tsunekawa T, Hayashi T, Suzuki Y, Matsui-Hirai H, Kano H, Fukatsu A, Nomura N, Miyazaki A, Iguchi A. Plasma adiponectin plays an important role in improving insulin resistance with glimepiride in elderly type 2 diabetic subjects. Diabetes Care. 2003; 26 285-289
20 Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol. 2002; 147 173-180
21 Matsubara M, Katayose S, Maruoka S. Decreased plasma adiponectin concentrations in nondiabetic women with elevated homeostasis model assessment ratios. Eur J Endocrinol. 2003; 148 343-350
22 Cnop M, Havel P J, Utzschneider K M, Carr D B, Sinha M K, Boyko E J, Retzlaff B M, Knopp R H, Brunzell J D, Kahn S E. 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
23 Valsamakis G, Chetty R, McTernan P G, Al Daghri N M, Barnett A H, Kumar S. Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab. 2003; 5 131-135
24 Yang W S, Lee W J, Funahashi T, Tanaka S, Matsuzawa Y, Chao C L, Chen C L, Tai T Y, Chuang L M. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab. 2001; 86 3815-3819
25 Chambers J C, Eda S, Bassett P, Karim Y, Thompson S G, Gallimore J R, Pepys M B, Kooner J S. C-reactive protein, insulin resistance, central obesity, and coronary heart disease risk in Indian Asians from the United Kingdom compared with European whites. Circulation. 2001; 104 145-150
26 Whincup P H, Gilg J A, Papacosta O, Seymour C, Miller G J, Alberti K G, Cook D G. Early evidence of ethnic differences in cardiovascular risk: cross sectional comparison of British South Asian and white children. Br Med J. 2002; 324 635-638
27 Laws A, Jeppesen J L, Maheux P C, Schaaf P, Chen Y D, Reaven G M. Resistance to insulin-stimulated glucose uptake and dyslipidemia in Asian Indians. Arterioscler Thromb. 1994; 14 917-922
28 Osei K, Schuster D P. Ethnic differences in secretion, sensitivity, and hepatic extraction of insulin in black and white Americans. Diabet Med. 1994; 11 755-762
29 Haffner S M, D'Agostino R, Saad M F, Rewers M, Mykkanen L, Selby J, Howard G, Savage P J, Hamman R F, Wagenknecht L E, Bergman R N. Increased insulin resistance and insulin secretion in nondiabetic African-Americans and Hispanics compared with non-Hispanic whites. The Insulin Resistance Atherosclerosis Study. Diabetes. 1996; 45 742-748
30 Jialal I, Naidoo C, Rajput M, Joubert S M. Evidence for insulin resistance in Indian patients with non-insulin dependent diabetes in the young. Horm Metab Res. 1984; 16 377-378
31 van der Merwe M T, Crowther N J, Schlaphoff G P, Gray I P, Joffe B I, Lonnroth P N. Evidence for insulin resistance in black women from South Africa. Int J Obes Relat Metab Disord. 2000; 24 1340-1346
32 Zoccali C, Mallamaci F, Tripepi G, Benedetto F A, Cutrupi S, Parlongo S, Malatino L S, Bonanno G, Seminara G, Rapisarda F, Fatuzzo P, Buemi M, Nicocia G, Tanaka S, Ouchi N, Kihara S, Funahashi T, Matsuzawa Y. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol. 2002; 13 134-141
33 Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G. Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care. 2002; 25 971-976
34 Chetty N, Naran N H, Walker A R, Seftel H C, Joffe B I, Raal F J. Plasma fatty acid levels in South African interethnic male high school pupils at different ultimate risks of coronary heart disease. Clin Chim Acta. 1997; 258 31-46
35 Seftel H C. The rise and fall of coronary heart disease in South Africa. S Afr Med J. 1994; 84 (Suppl) 32-33
36 Seftel H C, Asvat M S, Joffe B I, Raal F J, Panz V R, Vermaark W JH, Loock M E, Rajput M C, Omar M A, Jeenah M S. Selected risk factors for coronary heart disease in male scholars from the major South African population groups. S Afr Med J. 1993; 83 891-897
37 Friedewald W T, Levy R I, Fredrickson D S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18 499-502
38 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28 412-419
39 Anderson R L, Hamman R F, Savage P J, Saad M F, Laws A, Kades W W, Sands R E, Cefalu W. Exploration of simple insulin sensitivity measures derived from the frequently sampled intravenous glucose tolerance (FSIGT) tests. The Insulin Resistance Atherosclerosis Study. Am J Epidemiol. 1995; 142 724-732
40 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
41 Hulver M W, Saleh O, MacDonald K G, Pories W J, Barakat H A. Ethnic differences in adiponectin levels. Metabolism. 2004; 53 1-3
42 Abate N, Chandalia M, Snell P G, Grundy S M. Adipose tissue metabolites and insulin resistance in nondiabetic Asian Indian men. J Clin Endocrinol Metab. 2004; 89 2750-2755
43 Retnakaran R, Henley A JG, Raif N, Connelly P W, Sermer M, Zinman B. Hypoadiponectinaemia in South Asian women during pregnancy: evidence of ethnic variation in adiponectin concentration. Diabetic Med. 2004; 21 388-392
44 Degawa-Yamauchi M, Dilts J R, Bovenkerk J E, Saha C, Pratt J H, Considine R V. Lower serum adiponectin levels in African-American boys. Obes Res. 2003; 11 1384-1390
45 Duncan B B, Schmidt M I, Pankow J S, Bang H, Couper D, Ballantyne C M, Hoogeveen R C, Heiss G. Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes. 2004; 53 2473-2478
46 Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, Staiger H, Maerker E, Haring H, Stumvoll M. Plasma adiponectin concentrations predict insulin sensitivity of both glucose and lipid metabolism. Diabetes. 2003; 52 239-243
47 Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley R E, Tataranni P A. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinaemia. J Clin Endocrinol Metab. 2001; 86 1930-1935
48 Ezenwaka C E, Kalloo R, Uhlig M, Eckel J. Relationship between adiponectin and metabolic variables in Caribbean offspring of parents with type 2 diabetes mellitus. Horm Metab Res. 2004; 36 238-242
49 Vikram N K, Misra A, Pandey R M, Dwivedi M, Luthra K. Adiponectin, insulin resistance, and C-reactive protein in postpubertal Asian-Indian adolescents. Metabolism. 2004; 53 1336-1341
50 Kissebah A H, Krakower G R. Regional adiposity and morbidity. Physiol Rev. 1994; 74 761-811
51 van der Merwe M T, Crowther N J, Schlaphoff G P, Boyd I H, Gray I P, Joffe B I, Lönnroth P N. Lactate and glycerol release from the subcutaneous adipose tissue of obese urban women from South Africa; importanat metabolic implications. J Clin Endocrinol Metab. 1998; 83 4084-4091
52 Lovejoy J C, de la Bretonne J A, Klemperer M, Tulley R. Abdominal fat distribution and metabolic risk factors: effects of race. Metabolism. 1996; 45 1119-1124
53 Resnick H E, Valsania P, Halter J B, Lin X. Differential effects of BMI on diabetes risk among black and white Americans. Diabetes Care. 1998; 21 1828-1835
54 Buthelezi E P, van der Merwe M T, Lönnroth P N, Gray I P, Crowther N J. Ethnic differences in the responsiveness of adipocyte lipolytic activity to insulin. Obes Res. 2000; 8 171-178
55 Motoshima H, Wu X, Sinha M K, Hardy V E, Rosato E L, Barbot D J, Rosato F E, Goldstein B J. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab. 2002; 87 5662-5667
56 Walker A R, Adam A, Kustner H G. Changes in total death rate and in ischaemic heart disease death rate in interethnic South African populations, 1978-1989. S Afr Med J. 1993; 83 602-605
57 Kumada M, Kihara S, Sumitsuji S, Kawamoto T, Matsumoto S, Ouchi N, Arita Y, Okamoto Y, Shimomura I, Hiraoka H, Nakamura T, Funahashi T, Matsuzawa Y,. Osaka CAD Study Group . Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003; 23 85-89
58 Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002; 106 2767-2770
59 Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno N H, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003; 423 762-769

W. F. Ferris

Endocrinology and Metabolism Unit · Department of Internal Medicine · Faculty of Health Sciences · University of Stellenbosch

PO Box 19063 · Tygerberg 7505 · South Africa ·

Phone: +27 (21) 938 9448

Fax: +27 (21) 931 7442

Email: Wferris@sun.ac.za