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Does Hypoadiponectinemia Explain the Increased Risk of Diabetes and Cardiovascular Disease in South Asians?

  1. Ravi Retnakaran, MD12,
  2. Anthony J.G. Hanley, PHD123 and
  3. Bernard Zinman, MD12
  1. 1Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada
  2. 2Division of Endocrinology, University of Toronto, Toronto, Canada
  3. 3Department of Nutritional Sciences, University of Toronto, Toronto, Canada
  1. Address correspondence and reprint requests to Dr. Bernard Zinman, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Room L5-024, 60 Murray St., Box 21, Toronto, Ontario, Canada, M5T 3L9. E-mail: zinman{at}mshri.on.ca
Diabetes Care 2006 Aug; 29(8): 1950-1954. https://doi.org/10.2337/dc06-0867
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  • CAD, coronary artery disease
  • CVD, cardiovascular disease

A substantial body of evidence has documented the high prevalence of type 2 diabetes and cardiovascular disease (CVD) among people of South-Asian descent, defined on the basis of ancestral origin from the Indian subcontinent comprised of India, Pakistan, Bangladesh, and Sri Lanka (1–7). These observations relate to both native South Asians in urban settings and those living overseas in different countries (including the U.K., Canada, the U.S., South Africa, Singapore, Fiji, and Trinidad), leading to the suggestion that members of this ethnic group may share an underlying predisposition to metabolic and vascular disease (3,4,6–10). It has been postulated that a gene-environment interaction between underlying genetic susceptibility and urbanization-induced lifestyle changes (such as increased caloric intake and decreased energy expenditure) may promote the clinical expression of a high-risk phenotype (7). Clinically, this phenomenon translates to a 1.5- to 10-fold–higher incidence of coronary artery disease (CAD) in immigrant South Asians compared with the general populations of the host countries (2–4,10,11). Furthermore, South Asians exhibit clinical features suggestive of a distinctly aggressive cardiovascular pathophysiology compared with other ethnic groups. These features include significantly higher cardiovascular mortality (4,12) and earlier onset of CAD in young adults (7,13). Thus, identification of the determinants of vascular disease in South Asians may be relevant to both 1) our understanding of the pathophysiology of CVD and 2) preventive health care for the approximately one-fifth of the world’s population that comes from the Indian subcontinent.

A similarly worrisome problem is the rising prevalence of type 2 diabetes in South Asians. India currently has the highest number of cases of diabetes in the world (14). In addition, it has been projected that between 2000 and 2030, the number of patients with diabetes in India will increase from 31.7 to 79.4 million, reflecting the highest national increase within the global diabetes epidemic (14). In the U.K., the prevalence of diabetes in people of South-Asian descent is as high as 16–20% (2,7,15). Furthermore, South Asians develop type 2 diabetes at an earlier age and at lower BMI than Caucasians (16). Even in the absence of overt diabetes, South Asians exhibit higher fasting glucose levels and more glucose intolerance than other ethnic groups (6). Thus, as with CVD, elucidation of the factors underlying abnormal glucose metabolism in South Asians is sorely needed.

The metabolic and vascular phenotype of the South-Asian patient

Studies to date have documented a plethora of metabolic and vascular risk factors and abnormalities in people of South-Asian descent. First, there are significant differences in body composition between South Asians and Caucasians. South Asians typically have thin limbs (suggestive of smaller muscle mass) combined with increased central obesity, as evidenced by higher waist-to-hip ratio and greater subscapular-to-triceps skinfold ratio (7,17). Importantly, visceral fat mass is higher in South Asians compared with Caucasians at the same BMI (11). Consistent with greater visceral obesity, South Asians exhibit increased insulin resistance, as consistently demonstrated by fasting hyperinsulinemia, reduced insulin sensitivity on oral glucose tolerance tests, and reduced glucose disposal during euglycemic-hyperinsulinemic clamp (11,18–22). Similarly, South-Asian ethnicity is associated with lipid abnormalities that are consistent with increased visceral obesity. Specifically, HDL cholesterol concentration is typically lower in South Asians than in Caucasians (5,6). In addition, HDL particle size may be reduced, reflecting a preponderance of smaller, less cardioprotective HDL particles (23). Indeed, in the Framingham Offspring Study, South-Asian men had 1) lower levels of large, protective HDL cholesterol, 2) increased concentration of small HDL cholesterol, and 3) smaller HDL particle size (23). LDL cholesterol particle size may be unfavorable as well. While total LDL levels are typically comparable with those of other ethnic groups, an increased prevalence of atherogenic, small dense LDL particles has been demonstrated in South Asians (24). The regulation of lipolysis is another process that may be abnormal in South Asians, as evidenced by higher plasma levels of nonesterified fatty acids and impaired insulin-mediated suppression of plasma nonesterified fatty acids compared with Caucasians (25). Excessive lipolysis in adipose tissue, the site of release of nonesterified fatty acids, could contribute to lipid deposition in nonadipose tissues. Indeed, increased intramyocellular lipid content has been documented in South-Asian subjects (26). Finally, the endothelium represents yet another tissue in which abnormalities have been noted in individuals of South-Asian descent. Specifically, significant impairment of flow-mediated endothelium-dependent vasodilation has been shown in healthy South Asians (27). This finding is of interest in the current context, given recent evidence (28,29) that markers of endothelial dysfunction may predict the development of type 2 diabetes and CVD.

It is thus apparent that South-Asian ethnicity is associated with multiple risk factors for type 2 diabetes and CVD. Importantly, however, conventional vascular risk factors, such as diabetes and dyslipidemia, do not fully reconcile the excess cardiovascular risk associated with South-Asian ethnicity (2,6,9). As such, additional factors likely contribute to metabolic and vascular risk within this ethnic group. Nontraditional factors studied to date in this context include inflammatory mediators and prothrombotic factors. Increased serum concentrations of the inflammatory biomarker C-reactive protein, correlating with visceral obesity, have been demonstrated in South Asians (30,31), though prospective study of the association of C-reative protein with incident type 2 diabetes or CVD in South Asians is lacking. The same limitation applies to the prothrombotic factor plasminogen activator inhibitor-1, which has also been shown to be upregulated in healthy South Asians (6,21). Other prothrombotic abnormalities reported in South Asians include increased serum levels of fibrinogen, homocysteine, and lipoprotein(a) (6,32). Importantly, however, none of these nontraditional factors have yet reconciled the increased risk of type 2 diabetes and CVD in South Asians.

Adiponectin and South-Asian ethnicity

One candidate factor of particular interest with respect to both diabetes and vascular risk is adiponectin, an adipokine with putative insulin-sensitizing, antiatherogenic, and anti-inflammatory properties (33). Secreted exclusively by adipose tissue, adiponectin circulates at a relatively high concentration in oligomeric complexes, consisting of trimers, hexamers, and high–molecular weight multimers of 12–18 subunits (34). Total serum adiponectin concentration (i.e., consisting of all multimeric isoforms) is inversely proportional to both intra-abdominal fat and insulin resistance, consistent with the observation of hypoadiponectinemia in patients with type 2 diabetes (35,36). Importantly, low serum concentration of adiponectin predicts the future development of 1) insulin resistance in Pima Indians (37) and 2) incident type 2 diabetes in various populations, including Pima Indian, Caucasian, Japanese, and native South-Asian people (38–41). Thus, hypoadiponectinemia has emerged as a potential factor in the pathophysiology of insulin resistance and type 2 diabetes.

Adiponectin has also been proposed as a factor linking adipose tissue and vascular function (33). Indeed, adiponectin accumulates in the walls of injured blood vessels and displays antiatherogenic bioactivity such as attenuation of tumor necrosis factor-α–mediated inflammation, inhibition of vascular smooth muscle cell proliferation, and suppression of macrophage-to-foam cell transformation (33). Consistent with these effects, hypoadiponectinemia has been documented in patients with CAD (42). Furthermore, low serum levels of adiponectin have been shown to predict incident CVD in 1) healthy men participating in the Health Professionals Follow-up Study (43), 2) men with type 2 diabetes (44), 3) young adults with type 1 diabetes (45), and 4) patients with end-stage renal disease (46). As such, hypoadiponectinemia has been implicated as a possible factor in the development of CVD.

Given the increased risk of type 2 diabetes and CVD in South Asians, it is intriguing to note that hypoadiponectinemia within this ethnic group has been consistently observed in clinical studies (Table 1) (21,25,47–50). Although variability exists in the adiponectin levels reported in these studies (likely reflecting differences between the study populations with respect to factors such as sex and pregnancy status), hypoadiponectinemia in South-Asian subjects is a consistent finding in each study (21,25,47–50). Indeed, hypoadiponectinemia in South Asians has been documented in both sexes (21,25,47,49,50) and during pregnancy (48). Furthermore, these differences in adiponectin concentration are of such a substantial magnitude that they are detectable even in modestly sized studies involving as few as 15–31 South-Asian subjects (21,47,48). In healthy young men, Abate et al. (25) reported that plasma adiponectin concentration remained significantly lower in South Asians (n = 79) compared with Caucasians (n = 61), even after adjustment for differences in total body fat content, waist circumference, and truncal skinfold thickeness. Similarly, in a study of 180 pregnant women, South-Asian ethnicity emerged as the strongest independent and negative determinant of adiponectin concentration on multiple linear regression analysis, after adjustment for potential covariates including glucose intolerance, insulin resistance, family history of diabetes, and prepregnancy BMI (48). These data raise the possibility that hypoadiponectinemia may be a generalized phenomenon in South Asians that could contribute to the excess diabetes and vascular risk within this ethnic group.

Hypoadiponectinemia is consistent with several aspects of the metabolic and vascular phenotype of South-Asian patients (Fig. 1). First, given the inverse relationship between serum adiponectin and intra-abdominal fat (35), hypoadiponectinemia is concordant with the increased central obesity and visceral fat observed in South Asians. Second, low adiponectin in South Asians is consistent with the increased insulin resistance in this ethnic group. Indeed, ethnicity-associated hypoadiponectinemia may relate to the finding of insulin resistance in young healthy South Asians (21,25). Third, given that studies have repeatedly shown that adiponectin is independently associated with HDL cholesterol concentration (35,47), hypoadiponectinemia is consistent with the reduced HDL levels seen in South Asians. Fourth, intramyocellular lipid content, previously reported to be increased in South Asians (26), is inversely related to adiponectin concentration (51). Finally, hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation (33), an aspect of endothelial dysfunction that has been demonstrated by reduced flow-mediated dilatation in healthy South Asians (27). Taken together, these data support a model in which the pathologic effects of visceral obesity in South Asians may be mediated by hypoadiponectinemia, leading to the expression of metabolic and vascular risk factors and subsequent disease.

Consistent with the proposed model, hypoadiponectinemia has been associated with metabolic disease in South Asians. In a study of 200 subjects in Chennai, India, low adiponectin was associated with both type 2 diabetes and the metabolic syndrome (52). Furthermore, in a prospective study from Chennai involving 91 subjects with impaired glucose tolerance, Snehalatha et al. (41) found that baseline hypoadiponectinemia independently predicted the future development of type 2 diabetes, after adjustment for covariates including waist circumference. These data support the notion that hypoadiponectinemia in South Asians is clinically significant. Further prospective study of the associations of adiponectin with incident type 2 diabetes and CVD in this ethnic group is needed.

The vast majority of clinical studies to date have evaluated total circulating adiponectin concentrations, as measured by current commercial assays. It has recently emerged, however, that adiponectin circulates in oligomeric complexes, consisting of trimers, hexamers, and high–molecular weight multimers of 12–18 subunits (34,53). The physiologic activity of adiponectin appears to be primarily influenced by the relative distribution of these isoforms, which activate different signal transduction pathways and hence may mediate different functional properties of the protein (53,54). While conflicting results have been reported (55) regarding the precise pathways affected by specific isoforms, the high–molecular weight complex has emerged as a mediator of both glucose-lowering and antiatherogenic activity (56,57). Indeed, high–molecular weight adiponectin exhibits insulin-sensitizing and vasculature-protective effects (56,57). Furthermore, the relative proportion of adiponectin in high–molecular weight form is decreased in patients with type 2 diabetes and CAD, respectively, compared with control subjects (56,57). Lara-Castro et al. (58) reported that the hypoadiponectinemia observed in patients with type 2 diabetes may be entirely attributable to decreased levels of the high–molecular weight isoform. Interestingly, we have recently demonstrated that pregnant South-Asian women exhibit low serum levels of high–molecular weight adiponectin, thereby documenting ethnic variation in adiponectin isoform composition (59). Indeed, on multivariate analysis, South-Asian ethnicity emerged as an independent and negative determinant of the relative proportion of total adiponectin in high–molecular weight form (59). Thus, the hypoadiponectinemia observed in South Asians may reflect selective reduction of the high–molecular weight isoform. This concept is theoretically consistent with the low levels of HDL cholesterol in South Asians, since high–molecular weight adiponectin strongly correlates with HDL and has even emerged as an independent predictor of the change in HDL over time (55). Furthermore, low serum levels of high–molecular weight adiponectin have recently been shown to correlate with other metabolic abnormalities commonly observed in South Asians, including central obesity, insulin resistance, and small HDL particle size (58). Collectively, these data raise the possibility that deficiency of high–molecular weight adiponectin may be a factor contributing to diabetes and vascular risk in South Asians. Further study is needed to 1) determine whether deficiency of high–molecular weight adiponectin is a generalized phenomenon in South Asians and 2) prospectively evaluate its relevance to incident type 2 diabetes and CVD within this ethnic group.

If further clinical studies establish hypoadiponectinemia as a key contributory factor in the development of type 2 diabetes and CVD in South Asians, then therapeutic strategies to increase adiponectin levels may be particularly relevant in this ethnic group. For instance, weight reduction can increase total adiponectin and has been shown to raise levels of the high–molecular weight and hexameric isoforms, while reducing the trimeric form of the protein (55). Similarly, thiazolidinediones can increase total and high–molecular weight adiponectin in both nondiabetic and diabetic subjects (56,60). In this context, one could hypothesize that there may be a unique role for thiazolidinedione therapy in the South-Asian patient. Further clinical study is needed.

In summary, hypoadiponectinemia in South Asians has been consistently demonstrated in clinical studies to date. As low adiponectin relates to several elements of the metabolic and vascular risk profile of this ethnic group, the possibility emerges that hypoadiponectinemia may contribute to the increased risk of type 2 diabetes and CVD in South Asians. Further study of adiponectin biology within this ethnic group may provide important insights into the pathophysiology of metabolic and vascular disease and ideally may identify therapeutic strategies for optimal care of the South-Asian patient.

Figure 1—
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Figure 1—

Visceral obesity–mediated hypoadiponectinemia may contribute to several elements of the metabolic and vascular risk profile of South Asian patients.

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Table 1—

Studies that have compared adiponectin levels in South Asians and Caucasians

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted April 27, 2006.
    • Received April 24, 2006.
  • DIABETES CARE

References

  1. ↵
    Mather HM, Keen H: The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans. Br Med J (Clin Res Ed) 291: 1081–1084, 1985
  2. ↵
    McKeigue PM, Shah B, Marmot MG: Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians. Lancet 337:382–386, 1991
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    McKeigue PM, Miller GJ, Marmot JG: Coronary heart disease in South Asians overseas: a review. J Clin Epidemiol 42:597–609, 1989
    OpenUrlCrossRefPubMedWeb of Science
  4. ↵
    Wild S, McKeigue P: Cross sectional analysis of mortality by country of birth in England and Wales, 1970–92. BMJ 314:705–710, 1997
    OpenUrlAbstract/FREE Full Text
  5. ↵
    Bhopal R: Epidemic of cardiovascular disease in South Asians. BMJ 324:625–626, 2002
    OpenUrlFREE Full Text
  6. ↵
    Anand SS, Yusuf S, Vuksan V, Devanesan S, Teo KK, Montague PA, Kelemen L, Yi C, Lonn E, Gerstein H, Hegele RA, McQueen M: Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups. Lancet 356:279–284, 2000
    OpenUrlCrossRefPubMedWeb of Science
  7. ↵
    Forouhi NG, Sattar N: CVD risk factors and ethnicity: a homogeneous relationship? Atheroscler Suppl 7:11–19, 2006
    OpenUrlPubMedWeb of Science
  8. Reddy KS, Yusuf S: Emerging epidemic of cardiovascular disease in developing countries. Circulation 97:596–601, 1998
    OpenUrlFREE Full Text
  9. ↵
    Aarabi M, Jackson PR: Coronary risk in South Asians: role of ethnicity and blood sugar. Eur J Cardiovasc Prev Rehabil 11:389–393, 2004
    OpenUrlCrossRefPubMedWeb of Science
  10. ↵
    Beckles GLA, Miller GJ, Kirkwood BR, Alexis SD, Carson DC, Byam NTA: High total and cardiovascular disease mortality in adults of Asian Indian descent in Trinidad, unexplained by major coronary risk factors. Lancet 1:1298–1301, 1986
    OpenUrlCrossRefPubMedWeb of Science
  11. ↵
    Raji A, Seely EW, Arky RA, Simonson DC: Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 86:5366–5371, 2001
    OpenUrlCrossRefPubMedWeb of Science
  12. ↵
    Palaniappan L, Wang Y, Fortmann SP: Coronary heart disease mortality for six ethnic groups in California, 1990–2000. Ann Epidemiol14:499–506, 2004
  13. ↵
    McKeigue PM, Ferrie JE, Pierpoint T, Marmot MG: Association of early-onset coronary heart disease in South Asian men with glucose intolerance and hyperinsulinemia. Circulation 87:152–161, 1993
    OpenUrlAbstract/FREE Full Text
  14. ↵
    Wild S, Roglic G, Green A, Sicree R, King H: Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care27:1047–1053, 2004
  15. ↵
    Simmons D, Williams DR, Powell MJ: Prevalence of diabetes in different regional and religious south Asian communities in Coventry. Diabet Med 9:428–431, 1992
    OpenUrlPubMedWeb of Science
  16. ↵
    Mukhopadhyay B, Forouhi NG, Fisher BM, Kesson CM, Sattar N: A comparison of glycaemic and metabolic control over time among South Asian and European patients with type 2 diabetes: results from follow-up in a routine diabetes clinic. Diabet Med 23:94–98, 2006
    OpenUrlCrossRefPubMedWeb of Science
  17. ↵
    Yajnik CS: The insulin resistance epidemic in India: fetal origins, later lifestyle, or both? Nutr Rev 59 (1 Pt. 1):1–9, 2001
  18. ↵
    Liew CF, Seah ES, Yeo KP, Lee KO, Wise SD: Lean, nondiabetic Asian Indians have decreased insulin sensitivity and insulin clearance, and raised leptin compared to Caucasians and Chinese subjects. Int J Obes Relat Metab Disord 27:784–789, 2003
    OpenUrlCrossRefPubMed
  19. Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM: Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab 84:2329–2335, 1999
    OpenUrlCrossRefPubMedWeb of Science
  20. Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE: Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men. J Clin Endocrinol Metab 84:137–144, 1999
    OpenUrlCrossRefPubMedWeb of Science
  21. ↵
    Raji A, Gerhard-Herman MD, Warren M, Silverman SG, Raptopoulos V, Mantzoros CS, Simonson DC: Insulin resistance and vascular dysfunction in nondiabetic Asian Indians. J Clin Endocrinol Metab 89:3965–3972, 2004
    OpenUrlCrossRefPubMedWeb of Science
  22. ↵
    Retnakaran R, Hanley AJ, Connelly PW, Sermer M, Zinman B: Ethnicity modifies the effect of obesity on insulin resistance in pregnancy: a comparison of Asian, South Asian, and Caucasian women. J Clin Endocrinol Metab 91:93–97, 2006
    OpenUrlCrossRefPubMedWeb of Science
  23. ↵
    Bhalodkar NC, Blum S, Rana T, Bhalodkar A, Kitchappa R, Kim KS, Enas E: Comparison of levels of large and small high-density lipoprotein cholesterol in Asian Indian men compared with Caucasian men in the Framingham Offspring Study. Am J Cardiol 94:1561–1563, 2004
    OpenUrlCrossRefPubMedWeb of Science
  24. ↵
    Kulkarni HR, Markovitz JH, Nanda NC, Segrest JP: Increased prevalence of smaller and denser LDL particles in Asian Indians. Arterioscler Thromb Vasc Biol 19:2749–2755, 1999
    OpenUrlAbstract/FREE Full Text
  25. ↵
    Abate N, Chandalia M, Snell P, Grundy SM: Adipose tissue metabolites and insulin resistance in nondiabetic Asian Indian men. J Clin Endocrinol Metab 89:2750–2755, 2004
    OpenUrlCrossRefPubMed
  26. ↵
    Forouhi NG, Jenkinson G, Thomas E, Mullick S, Mierisova S, Bhonsle U, McKeigue PM, Bell JD: Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men. Diabetologia 42:932–935, 1999
    OpenUrlCrossRefPubMedWeb of Science
  27. ↵
    Chambers JC, McGregor A, Jean-Marie J, Kooner JS: Abnormalities of vascular endothelial function may contribute to increased coronary heart disease in UK Indian Asians. Heart 81:501–504, 1999
    OpenUrlAbstract/FREE Full Text
  28. ↵
    Meigs JB, Hu FB, Rifai N, Manson JE: Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 291:1978–1986, 2004
    OpenUrlCrossRefPubMedWeb of Science
  29. ↵
    Luc G, Arveiler D, Evans A, Amouyel P, Ferrieres J, Bard JM, Elkhalil L, Fruchart JC, Ducimetiere P, the PRIME Study Group: Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and incident coronary heart disease: the PRIME Study. Atherosclerosis 170:169–176, 2003
    OpenUrlCrossRefPubMedWeb of Science
  30. ↵
    Chambers JC, Eda S, Bassett P, Karim Y, Thompson SG, Gallimore JR, Pepys MB, Kooner JS: C-reactive protein, insulin resistance, central obesity, and coronary heart diease risk in Indian Asians from the United Kingdom compared with European whites. Circulation 104:145–150, 2001
    OpenUrlAbstract/FREE Full Text
  31. ↵
    Forouhi NG, Sattar N, McKeigue PM: Relation of C-reactive protein to body fat distribution and features of the metabolic syndrome in Europeans and South Asians. Int J Obes 25:1327–1331, 2001
    OpenUrlCrossRefPubMedWeb of Science
  32. ↵
    Kain K, Catto AJ, Grant PJ: Impaired fibrinolysis and increased fibrinogen levels in South Asian subjects. Atherosclerosis 156:457–461, 2001
    OpenUrlCrossRefPubMedWeb of Science
  33. ↵
    Goldstein BJ, Scalia R: Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 89:2563–2568, 2004
    OpenUrlCrossRefPubMedWeb of Science
  34. ↵
    Peake PW, Kriketos A, Campbell L, Shen Y, Charlesworth JA: The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol 153:409–417, 2005
    OpenUrlAbstract/FREE Full Text
  35. ↵
    Cnop C, Havel PJ, Utzschneider K, Carr D, Sinha M, Boyko E, Retzlaff B, Knopp R, Brunzell JD, Kahn SE: Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 46:459–469, 2003
    OpenUrlPubMedWeb of Science
  36. ↵
    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 20:1595–1599, 2000
    OpenUrlAbstract/FREE Full Text
  37. ↵
    Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA: 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 50:1884–1888, 2002
    OpenUrl
  38. ↵
    Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, Knowler WC, Krakoff J: Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 360:57–58, 2002
    OpenUrlCrossRefPubMedWeb of Science
  39. Spranger J, Kroke A, Mohlig M: Adiponectin and protection against type 2 diabetes mellitus. Lancet 361:226–228, 2003
    OpenUrlCrossRefPubMedWeb of Science
  40. Daimon M, Oizumi T, Saitoh T, Kameda W, Hirata A, Yamaguchi H, Ohnuma H, Igarashi M, Tominaga M, Katro T, the Funagata Study: 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 26:2015–2020, 2003
    OpenUrlAbstract/FREE Full Text
  41. ↵
    Snehalatha C, Mukesh B, Simon M, Vishwanathan V, Haffner SM, Ramachandran A: Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 26:3226–3229, 2003
    OpenUrlAbstract/FREE Full Text
  42. ↵
    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: Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol 23:85–89, 2003
    OpenUrlAbstract/FREE Full Text
  43. ↵
    Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB: Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291:1730–1737, 2004
    OpenUrlCrossRefPubMedWeb of Science
  44. ↵
    Schulze MB, Shai I, Rimm EB, Li T, Rifai N, Hu FB: Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 54:534–539, 2005
    OpenUrlAbstract/FREE Full Text
  45. ↵
    Costacou T, Zgibor JC, Evans RW, Otvos J, Lopes-Virella MF, Tracy RP, Orchard TJ: The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia 48:41–48, 2005
    OpenUrlCrossRefPubMedWeb of Science
  46. ↵
    Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, Malatino LS, 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 13:134–141, 2002
    OpenUrlAbstract/FREE Full Text
  47. ↵
    Valsamakis G, Chetty R, McTernan PG, Al-Daghri NM, Barnett AH, Kumar S: Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab 5:131–135, 2003
    OpenUrlCrossRefPubMedWeb of Science
  48. ↵
    Retnakaran R, Hanley AJ, Raif N, Connelly PW, Sermer M, Zinman B: Hypoadiponectinemia in South Asian women during pregnancy: evidence of ethnic variation in adiponectin concentration. Diabet Med 21:388–392, 2004
    OpenUrlCrossRefPubMedWeb of Science
  49. ↵
    Ferris WF, Naran NH, Crowther NJ, Rheeder P, van der Merwe L, Chetty N: The relationship between insulin sensitivity and serum adiponectin levels in three population groups. Horm Metab Res 37:695–701, 2005
    OpenUrlCrossRefPubMedWeb of Science
  50. ↵
    Smith JD, Al-Amri M, Sniderman AD, Cianflone K: Leptin and adiponectin in relation to body fat percentage, waist to hip ratio and the apoB/apoA1 ratio in Asian Indian and Caucasian men and women. Nutr Metab (Lond)3:18, 2006
    OpenUrlCrossRef
  51. ↵
    Weiss R, Dufour S, Groszmann A, Petersen K, Dziura J, Taksali S, Shulman G, Caprio S: Low adiponectin levels in adolescent obesity: a marker of increased intramyocellular lipid accumulation. J Clin Endocrinol Metab 88:2014–2018, 2003
    OpenUrlCrossRefPubMedWeb of Science
  52. ↵
    Mohan V, Deepa R, Pradeepa R, Vimaleswaran KS, Mohan A, Velmurugan K, Radha V: Association of low adiponectin levels with the metabolic syndrome: the Chennai Urban Rural Epidemiology Study (CURES-4). Metabolism 54:476–481, 2005
    OpenUrlCrossRefPubMedWeb of Science
  53. ↵
    Tsao TS, Tomas E, Murrey H, Hug C, Lee D, Ruderman N, Heuser J, Lodish HF: Role of disulfide bonds in Acrp30/adiponectin structure and signalling specificity: different oligomers activate different signal transduction pathways. J Biol Chem 278:50810–50817, 2003
    OpenUrlAbstract/FREE Full Text
  54. ↵
    Wang Y, Lam KS, Xu J, Lu G, Xu L, Cooper G, Xu A: Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem 280:18341–18347, 2005
    OpenUrlAbstract/FREE Full Text
  55. ↵
    Bobbert T, Rochlitz H, Wegewitz U, Akpulat S, Mai K, Weickert M, Mohlig M, Pfeiffer A, Spranger J: Changes of adiponectin oligomer composition by moderate weight reduction. Diabetes 54:2712–2719, 2005
    OpenUrlAbstract/FREE Full Text
  56. ↵
    Pajvani UB, Hawkins M, Combs T, Rajala M, Doebber T, Berger J, Wagner J, Wu M, Knopps A, Xiang A, Utzschneider, Kahn SE, Olefsky J, Buchanan TA, Scherer PE: Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 279:12152–12162, 2004
    OpenUrlAbstract/FREE Full Text
  57. ↵
    Kobayashi H, Ouchi N, Kihara S, Walsh K, Kumada M, Abe Y, Funahashi T, Matsuzawa Y: Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res 94:e27–e31, 2004
    OpenUrlAbstract/FREE Full Text
  58. ↵
    Lara-Castro C, Luo N, Wallace P, Klein RL, Garvey WT: Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 55:249–259, 2006
    OpenUrlAbstract/FREE Full Text
  59. ↵
    Retnakaran R, Hanley AJ, Connelly PW, Maguire G, Sermer M, Zinman B: Low serum levels of high molecular weight adiponectin in Indo-Asian women during pregnancy: evidence of ethnic variation in adiponectin isoform distribution. Diabetes Care 29:1377–1379, 2006
    OpenUrlFREE Full Text
  60. ↵
    Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, Olefsky JM: The effect of thiazolidinediones on plasma adiponectin levels in normal, obese and type 2 diabetic subjects. Diabetes 51:2968–2974, 2002
    OpenUrlAbstract/FREE Full Text
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Diabetes Care: 29 (8)

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August 2006, 29(8)
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Does Hypoadiponectinemia Explain the Increased Risk of Diabetes and Cardiovascular Disease in South Asians?
Ravi Retnakaran, Anthony J.G. Hanley, Bernard Zinman
Diabetes Care Aug 2006, 29 (8) 1950-1954; DOI: 10.2337/dc06-0867

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Does Hypoadiponectinemia Explain the Increased Risk of Diabetes and Cardiovascular Disease in South Asians?
Ravi Retnakaran, Anthony J.G. Hanley, Bernard Zinman
Diabetes Care Aug 2006, 29 (8) 1950-1954; DOI: 10.2337/dc06-0867
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