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

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

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