help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Abate, N.
Right arrow Articles by Grundy, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Abate, N.
Right arrow Articles by Grundy, S. M.
The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 6 2750-2755
Copyright © 2004 by The Endocrine Society

Adipose Tissue Metabolites and Insulin Resistance in Nondiabetic Asian Indian Men

Nicola Abate, Manisha Chandalia, Peter G. Snell and Scott M. Grundy

Department of Internal Medicine (N.A., M.C., P.G.S., S.M.G.), Division of Endocrinology and Metabolism (N.A., M.C.), and Center for Human Nutrition (N.A., M.C., S.M.G.), University of Texas Southwestern Medical Center, Dallas, Texas 75390

Address all correspondence and requests for reprints to: Nicola Abate, M.D., Center for Human Nutrition, University of Texas Southwestern Medical Center, 6011 Harry Hines Boulevard, Dallas, TX 75390-9169. E-mail: Nicola.Abate{at}UTSouthwestern.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Obesity-related insulin resistance is associated with changes in adipose tissue release of leptin, adiponectin, and nonesterified fatty acids (NEFAs). We have previously described that persons originating from the Indian subcontinent (Asian Indians) manifest excessive insulin resistance even in the absence of obesity. Therefore, in this study, we tested the hypothesis that nondiabetic, insulin-resistant Asian Indians differ from less insulin-resistant Caucasians of similar age and body composition in adipose tissue production of leptin and adiponectin, and in suppression of plasma NEFA concentrations during hyperinsulinemia. Seventy-nine Asian Indian men were compared with 61 Caucasian men. Higher plasma NEFAs and leptin in Asian Indians (P < 0.0001 and P = 0.003 for NEFAs and leptin, respectively) and lower plasma concentrations of adiponectin (P = 0.009) were not explained by body fat content and distribution. Oral glucose tolerance test studies revealed that Caucasian men had greater suppression of plasma NEFAs than Asian Indian men. We conclude that plasma concentrations of the adipose tissue metabolites leptin and NEFAs are higher and that of adiponectin is lower in insulin-resistant Asian Indians compared with more insulin-sensitive Caucasians. These differences may contribute to the excessive prevalence of type 2 diabetes and cardiovascular disease in nonobese Asian Indians.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
INSULIN RESISTANCE, MEASURED as decreased insulin-mediated glucose disposal, is considered to play a major role in the pathogenesis of both type 2 diabetes (1, 2, 3, 4) and cardiovascular disease (CVD) (5, 6, 7, 8). A common factor contributing to insulin resistance is obesity, which may suppress insulin sensitivity in several ways. One of these is through excess lipolysis, i.e. through release of large amounts of nonesterified fatty acids (NEFAs) into the circulation. Resulting high levels of NEFA seemingly raise triglyceride concentrations in skeletal muscle, thereby suppressing glucose uptake (9, 10). Obesity may impair insulin action in other ways as well, through release of abnormal amounts of various other products from adipose tissue, notably, cytokines, leptin, and adiponectin (11, 12). Obese persons often exhibit high plasma levels of high-sensitive C-reactive protein (CRP), which is one manifestation of high levels of circulating cytokines (13, 14). Moreover, obesity is accompanied by high plasma levels of leptin and a low level of adiponectin, both of which suppress insulin action.

Insulin resistance and its associated excessive risk for both diabetes and CVD also may occur in absence of obesity. One example of this phenomenon may occur in populations originating in South Asia, i.e. Asian Indians. When individuals from these populations undergo urbanization or migration they manifest a high prevalence of premature type 2 diabetes (15, 16, 17) and CVD (18, 19, 20, 21, 22) at body weights much lower than typically found in Caucasians with these conditions. We and other investigators have shown high frequency of insulin resistance (23, 24, 25), even in the presence of a relative low body mass index (BMI), when compared with individuals of European descent. Although Asian Indians are known to be prone to upper body obesity, which is commonly associated with insulin resistance, we have observed that insulin resistance in Asian Indians is commonly present even in the absence of excessive body fat content or abdominal obesity (23). Moreover, we have further reported that such nonobese Asian Indians typically exhibit high levels of CRP, suggestive of a proinflammatory state. Because obese persons commonly have high CRP levels, it is possible that adipose tissue metabolism is abnormal in persons with primary insulin resistance. However, at present, it is not known whether nonobese Asian Indians have features seen in obese Caucasians, namely, high levels of plasma NEFA and leptin or low levels of adiponectin. If they do, such findings would point to abnormalities of adipose tissue as contributors to insulin resistance in this population. In other words, in insulin-resistant Asian Indians, an abnormal function of adipose tissue could exist independently of body fat content, which could predispose them to type 2 diabetes and CVD.

The hypothesis of this study was that healthy nondiabetic, insulin-resistant men of Asian Indian origin will have higher plasma levels of NEFA and leptin and lower levels of adiponectin than will less insulin-resistant Caucasian men of similar age and body composition who are less insulin resistant. To test this hypothesis, we designed a cross-sectional study that compared parameters of body composition, insulin resistance, and plasma levels of NEFAs, leptin, and adiponectin in two groups of young, nondiabetic volunteers of Caucasian and Asian Indian ethnicity.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Subjects were recruited through public advertisement and were screened for hematological and blood chemistry abnormalities. The study was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center at Dallas. All subjects signed a written informed consent. Subjects with diabetes mellitus and other endocrine disorders, coronary heart disease, and liver function test abnormalities, and those receiving any form of therapies, were excluded from the study. At the time of enrollment, each volunteer was administered a health history questionnaire. The questionnaire did not include a report on length of stay in the United States. Height, weight, and blood pressure measurements were taken on all of the subjects.

Oral glucose tolerance test (OGTT)

After 12 h of fasting, subjects had an iv catheter placed in a forearm vein to collect blood. A solution containing 75 g glucose was administered orally to the subjects (Tru-Glu 100; Fisher Scientific, Pittsburgh, PA). Blood was collected at times –30, –15, 0, 30, 60, 90, 120, 150, and 180 min for measurement of glucose, insulin, leptin, adiponectin, and NEFA concentrations. Plasma was separated rapidly from the remaining blood by centrifugation at 4 C and stored immediately at –80 C. Results at times –30, –15, and 0 min were averaged as baseline measurements for analysis.

Biochemical analyses

Plasma glucose concentration was assayed using a glucose oxidase method. Plasma insulin and leptin were measured by RIA at Linco Research, Inc. (St. Louis, MO). Plasma adiponectin was measured by ELISA at Linco Research. The plasma concentrations of free fatty acids were measured by enzymatic colorimetric assay (Roche Diagnostics, Mannheim, Germany).

Anthropometry

Anthropometric measurements were taken on all of the subjects. Height and weight were measured by standard procedures. Waist circumference was measured at the umbilical level. The average of two measurements was used for analysis. Skinfold thickness was measured at nine different anatomical sites (subscapular diagonal and vertical, chest, midaxillary, abdominal horizontal and vertical, suprailiac diagonal and vertical, triceps, biceps, thigh, and calf) using a Lange skinfold caliper (Cambridge Scientific Instruments, Inc., Cambridge, MD), as previously reported (23). Body density was calculated from measurements of body volume determined by hydrostatic weighing with adjustment for residual volume measured by helium dilution during the underwater weighing. Percentage of body fat was calculated using the Siri equation (26) assuming a fat-free density of 1.10 g/cc for men and 1.097 g/cc for women.

Statistical analysis and calculations

Area under the curve (AUC) during OGTT was calculated for glucose and insulin using the trapezoidal rule. Homeostasis model assessment of insulin resistance was calculated from insulin and glucose concentrations using the following equation: insulin (milliunits per milliliter) x [glucose (nanomoles per liter)/22.5] (27). Mann-Whitney U test was used to compare the Asian Indian and Caucasian groups. For skewed variables (leptin, adiponectin, AUCinsulin, and AUCNEFA), the data were log transformed before analysis. Adjusted means were derived and compared using analysis of covariance models. Spearman correlation coefficients were used to assess associations between continuous variables. Statistical analysis was performed using SAS version 8.2 (SAS Institute, Cary, NC).


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The general characteristics of Asian Indian men are compared with those of the Caucasian men in Table 1Go. Seventy-nine Asian Indians and 61 Caucasians participated in this study. We have no information on length of stay in the United States of either study group. The two groups were of similar age, and all were healthy without any acute or chronic illness. Asian Indians had lower mean BMI than Caucasians (24 ± 3 and 26 ± 4 kg/m2, respectively; P = 0.004). Systolic but not diastolic blood pressure was higher in Caucasians. Plasma lipid levels were similar in the two groups. As shown in Table 2Go, Asian Indians had less total body fat mass. However, body fat content, expressed as percentage of total body weight, was similar to that of the Caucasians. Truncal skinfold thickness was greater in Asian Indians, indicating a tendency to store body fat in truncal sc adipose tissue. However, the average waist circumference was lower in Asian Indians. No differences were noted for hip circumference or peripheral skinfold thickness.


View this table:
[in this window]
[in a new window]
  		TABLE 1. General characteristics of the study subjects

 

View this table:
[in this window]
[in a new window]
  		TABLE 2. Body composition of the study subjects

 
Fasting levels of plasma glucose were not different between the two groups (95 ± 9 and 94 ± 7 mg/dl in Asian Indians and Caucasians, respectively; P = 0.16), but fasting plasma insulin was significantly higher in Asian Indians (16 ± 12 vs. 13 ± 6 µU/ml; P = 0.01), suggesting greater insulin resistance. This findings were confirmed using homeostasis model assessment of insulin resistance (4.0 ± 3.5 and 2.9 ± 1.6 for Asian Indians and Caucasians, respectively; P = 0.018). As shown in Fig. 1Go, fasting plasma NEFA levels were significantly higher in Asian Indians. Asian Indians also had significantly higher plasma leptin concentrations and lower plasma adiponectin concentrations compared with Caucasians (Fig. 1Go). These differences remained highly significant even after adjustment for total body fat content, waist, and truncal skinfold thickness; adjusted P values were 0.001, <0.0001, and 0.02, for group differences in fasting plasma NEFA, leptin and adiponectin, respectively.



View larger version (20K):
[in this window]
[in a new window]
  		FIG. 1. Fasting plasma concentrations of NEFA, leptin, and adiponectin in Asian Indians and Caucasians. The results are reported as median, 25th to 75th percentiles, and 5th to 95th percentiles for the Asian Indians () and Caucasians ({square}). P value was determined with independent-samples t test.

 
Table 3Go shows the relationships between body fat and parameters of fat distribution with plasma concentrations of NEFA, leptin, adiponectin, and AUCinsulin. In both groups, increasing generalized (total body fat) and central adiposity (waist and truncal skinfold thickness) was accompanied by higher levels of leptin, AUCinsulin, and AUCNEFA. Increasing generalized and central adiposity was also associated with reduced plasma concentrations of adiponectin. Some apparent differences in correlations between the two ethnic groups could be related to small variability of studied parameters within each group. Table 4Go is a summary of Spearman correlation coefficients between metabolic variables including leptin, adiponectin, AUCNEFA, and AUCinsulin. Small variability of studied parameters may account for apparent differences in r values between the two study groups.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Relationship between body composition and fat distribution with leptin, adiponectin, AUCNEFA, and AUCinsulin

 

View this table:
[in this window]
[in a new window]
  		TABLE 4. Relationship between metabolic variables studied

 
Asian Indians had higher plasma glucose concentrations and higher plasma insulin concentrations during the OGTT (Fig. 2Go). Plasma concentrations of NEFAs were significantly higher at baseline in the Asian Indians (Fig. 1Go), and they remained significantly higher throughout the duration of the OGTT (Fig. 2Go). Despite higher insulin levels, Asian Indian men had less suppression of plasma NEFA concentrations for the last 20 min of the OGTT-induced hyperinsulinemia compared with the Caucasian group (Fig. 2Go). Percentage of suppression of plasma NEFA concentrations at time 120 min of OGTT was 90 ± 14% for the Asian Indians and 94 ± 14% for the Caucasians (P = 0.003). These differences in NEFA levels during the OGTT persisted even after statistical adjustments for total body fat content and central adiposity parameters (adjusted value of P = 0.0005).



View larger version (24K):
[in this window]
[in a new window]
  		FIG. 2. Plasma glucose, insulin, and NEFA concentrations during OGTT are compared for Asian Indians (•) and Caucasians ({circ}) at different time points. The results on the AUC are reported as median, 25th to 75th percentiles, and 5th to 95th percentiles for the Asian Indians () and Caucasians ({square}). P values were determined with independent-samples t test after log transformation. SI conversion for glucose is 0.0555 mmol/liter, and for insulin is 6.945 pmol/liter.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
There are three salient findings in this study. First, plasma concentrations of NEFAs are higher and insulin-mediated plasma NEFA suppression is impaired in Asian Indian men compared with Caucasians; second, plasma leptin concentrations are higher in Asian Indian men compared with Caucasians; and third, plasma adiponectin concentrations are lower in Asian Indian men compared with Caucasians. These differences are found to be unrelated to body fat content or distribution.

High levels of plasma NEFA concentrations have been proposed to be an important link between adipose tissue and defective insulin-mediated glucose disposal primarily occurring in the skeletal muscle cells. Several mechanisms of how elevated NEFAs decrease insulin sensitivity have been proposed; these include a modification of the glucose-fatty acid cycle of Randle et al. (28) and/or inhibition of proximal insulin-signaling pathways (29). Adipose tissue is the only major tissue in which triacylglycerol clearance from lipoproteins and fatty acid trapping are specifically up-regulated during hyperinsulinemia (30, 31). Furthermore, adipose tissue is the only site of release of NEFAs. The finding that, despite relative hyperinsulinemia, Asian Indians have higher fasting plasma NEFA concentrations points to a higher release of NEFAs from the adipose tissue of Asian Indians. In addition, during the hyperinsulinemia induced by oral glucose administration, Asian Indians failed to manifest complete suppression of plasma NEFAs. Reasons for defective insulin action in the adipose tissue are not evident from our study. Nonetheless, a concomitant high concentration of plasma leptin and a low level of plasma adiponectin further point to an abnormality in adipose tissue metabolism of Asian Indians.

Leptin is produced in adipocytes. Increasing body fat content, particularly increasing sc abdominal fat content, is often accompanied by higher plasma leptin concentrations (32, 33, 34). In our study, plasma leptin concentrations were strongly correlated with total body fat content and measures of truncal fat distribution (Table 3Go). In the Asian Indians of this study, there was no increase in overall body fat content. However, there was an increased thickness of truncal skinfolds. When the comparison of the study groups was done with statistical adjustment for truncal skinfold thickness, Asian Indians still had significantly higher plasma leptin concentrations than Caucasians (Fig. 1Go). This supports excessive leptin production from adipocytes of Asian Indians regardless of the degree of overall obesity or abdominal/truncal obesity. High plasma leptin concentrations in obesity seem to be accompanied by leptin resistance (35) and may be involved in the pathogenesis of obesity-related insulin resistance through peripheral effects of leptin on fatty acid metabolism. Leptin promotes fatty acid oxidation in cells (36). Decreased leptin action may predispose to triglycerides accumulation in skeletal muscle cells, a condition associated with impaired insulin-mediated glucose use (9). However, the mechanistic link between insulin resistance and hyperleptinemia is not completely elucidated. Because prolonged experimental hyperinsulinemia can induce an increase in plasma leptin concentration (36), it is also possible that insulin resistance and hyperinsulinemia contribute to hyperleptinemia. In our study, plasma leptin concentrations were significantly correlated with AUCinsulin during OGTT, both in Asian Indians and Caucasians. In the Asian Indians, insulin levels were clearly elevated and thus might have contributed to the higher plasma leptin concentrations of this ethnic group.

Adiponectin is another product of adipocytes. Lower plasma levels of adiponectin have been reported in obesity-related insulin resistance, and there is an inverse relationship between plasma concentrations of adiponectin and leptin (37, 38, 39, 40). The role of adiponectin on the pathogenesis of insulin resistance is at this time incompletely understood. In this study, we could confirm for the Asian Indians the relationships between adiponectin and parameters of obesity, fat distribution, and insulin resistance previously reported in other ethnic groups. In both of our study groups, increasing truncal skinfold thickness was the strongest correlate of decreased plasma adiponectin concentrations (Table 3Go). Because Asian Indians had higher truncal skinfold thickness, we evaluated the differences between Asian Indians and Caucasians, after statistical adjustment for body fat content, waist circumference, and truncal skinfold thickness. Similar to the findings for leptin, this analysis shows that Asian Indians have significantly higher plasma adiponectin concentrations independently of obesity and fat distribution (Fig. 1Go). Imaging studies with direct measurement of visceral adipose tissue and sc abdominal adipose tissue may be required to confirm our findings using anthropometric measurements of fat distribution.

Taken together, the findings of our study point to a defect in adipose tissue metabolism of Asian Indians, which occurs independently of obesity or abdominal fat distribution. These abnormalities of adipose tissue metabolism are concomitant with insulin resistance. Therefore, it is not possible to determine causal sequence, i.e. whether a primary defect in the insulin signaling pathway is responsible for abnormal metabolism in adipose tissue, or vice versa. If the former, a vicious cycle might be established in which primary insulin resistance engenders abnormal adipose tissue metabolism, which in turn enhances insulin resistance in muscle by abnormal release of various products including NEFA, inflammatory cytokines, leptin, and adiponectin. In any case, increased plasma NEFA and leptin concentrations, and decreased plasma adiponectin concentrations in Asian Indians appear to be part of a complex clustering of metabolic abnormalities that includes insulin resistance that is characteristic of this ethnic group, even in absence of obesity. Nonetheless, once some degree of obesity intervenes, these abnormalities likely will be accentuated. Thus, regardless of the precise molecular underpinning of this metabolic pattern, its presence seemingly represents a genetic susceptibility to insulin resistance that, when combined with increasing obesity, can account for the increasing prevalence of type 2 diabetes and CVD in this ethnic group.


   Acknowledgments
 
We thank Marjorie Whelan, Alan Cabo-Chan, M.D., Pankaj Satija, M.D., Rincy Varughese, and Munira Abbas for technical assistance; the nursing and dietetic services of the General Clinical Research Center; and Beverley Adams-Huet for biostatistical assistance.


   Footnotes
 
This work was supported by National Institutes of Health Grants K23-RR16075, HL-29252, DK-42582, DK-02700, and MO1-RR-00633 (National Institutes of Health/National Center for Research Resources–Clinical Research.

Abbreviations: AUC, Area under the curve; BMI, body mass index; CRP, C-reactive protein; CVD, cardiovascular disease; NEFA, nonesterified fatty acid; OGTT, oral glucose tolerance test.

Received October 22, 2003.

Accepted February 19, 2004.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Reaven GM 1998 The role of insulin resistance in human disease. Diabetes 37:1595–1607[CrossRef]
  2. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, Knowler WC, Bennett PH, Bogardus C 1993 Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329:1988–1992[Abstract/Free Full Text]
  3. Haffner SM, Stern MP, Mitchell BD, Hazuda HP, Patterson JK 1990 Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Diabetes 39:283–288[Abstract]
  4. Charles MA, Fontbonne A, Thibult N, Warnet JM, Rosselin GE, Eschwege E 1991 Risk factors for NIDDM in white population. Paris Prospective Study. Diabetes 40:796–799[Abstract]
  5. Fontbonne AM, Eschwege EM 1991 Insulin and cardiovascular disease. Paris Prospective Study. Diabetes Care 14:461–469[Abstract]
  6. Pyorala M, Miettinen H, Laakso M, Pyorala K 1998 Hyperinsulinemia predicts coronary heart disease risk in healthy middle-aged men: the 22-year follow-up results of the Helsinki Policemen Study. Circulation 98:398–404[Abstract/Free Full Text]
  7. Pyorala K, Savolainen E, Kaukola S, Haapakoski J 1985 Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9 1/2-year follow-up of the Helsinki Policemen Study population. Acta Med Scand Suppl 701:38–52[Medline]
  8. Despres JP, Lamarche B, Mauriege P, Cantin B, Dagenais GR, Moorjani S, Lupien PJ 1996 Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 334:952–957[Abstract/Free Full Text]
  9. Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, Ma YZ, Savoye M, Rothman DL, Shulman GI, Caprio S 2002 Assessment of skeletal muscle triglyceride content by 1H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes 51:1022–1027[Abstract/Free Full Text]
  10. Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, Bergeron R, Kim JK, Cushman SW, Cooney GJ, Atcheson B, White MF, Kraegen EW, Shulman GI 2002 Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 277:50230–50236[Abstract/Free Full Text]
  11. Havel PJ 2002 Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 13:51–59[CrossRef][Medline]
  12. Matsuzawa Y, Funahashi T, Nakamura T 1999 Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann NY Acad Sci 892:146–154[Abstract/Free Full Text]
  13. Leinonen E, Hurt-Camejo E, Wiklund O, Hulten LM, Hiukka A, Taskinen MR 2003 Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes. Atherosclerosis 166:387–394[CrossRef][Medline]
  14. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW 1999 C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19:972–978[Abstract/Free Full Text]
  15. Ramachandran A, Snehalatha C, Dharmaraj D, Viswanathan M 1992 Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity. Diabetes Care 15:1348–1355[Abstract]
  16. McKeigue PM, Marmot MG, Syndercombe Court YD, Cottier DE, Rahman S, Riemersma RA 1988 Diabetes, hyperinsulinaemia, and coronary risk factors in Bangladeshis in east London. Br Heart J 60:390–396[Abstract/Free Full Text]
  17. Mather HM, Keen H 1985 The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans. Br Med J 291:1081–1084
  18. Hughes K 1989 Mortality from cardiovascular diseases in Chinese, Malays and Indians in Singapore, in comparison with England and Wales, USA and Japan. Ann Acad Med Singapore 18:642–645[Medline]
  19. Balarajan R 1991 Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. BMJ 302:560–564
  20. Anand SS, Yusuf S, Vuksan V, Devanesen S, Teo KK, Montague PA, Kelemen L, Yi C, Lonn E, Gerstein H, Hegele RA, McQueen M 2000 Differences in risk factors, atherosclerosis, and cardiovascular disease between ethnic groups in Canada: the Study of Health Assessment and Risk in Ethnic groups (SHARE). Lancet 356:279–284[CrossRef][Medline]
  21. Lee J, Heng D, Chia KS, Chew SK, Tan BY, Hughes K 2001 Risk factors and incident coronary heart disease in Chinese, Malay and Asian Indian males: the Singapore Cardiovascular Cohort Study. Int J Epidemiol 30:983–988[Abstract/Free Full Text]
  22. Chandalia M, Deedwania PC 2001 Coronary heart disease and risk factors in Asian Indians. Adv Exp Med Biol 498:27–34[Medline]
  23. Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM 1999 Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab 84:2329–2335[Abstract/Free Full Text]
  24. McKeigue PM, Pierpoint T, Ferrie JE, Marmot MG 1992 Relationship of glucose intolerance and hyperinsulinaemia to body fat pattern in south Asians and Europeans. Diabetologia 35:785–791[Medline]
  25. Laws A, Jeppesen JL, Maheux PC, Schaaf P, Chen YD, Reaven GM 1994 Resistance to insulin-stimulated glucose uptake and dyslipidemia in Asian Indians. Arterioscler Thromb 14:917–922[Abstract/Free Full Text]
  26. Siri WE 1961 Body composition from fluid spaces and density. In: Techniques for measuring body composition. Washington, DC: National Academy of Sciences; 223–224
  27. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC 1985 Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419[CrossRef][Medline]
  28. Randle J, Garland PB, Hales CN, Newsholme EA 1963 The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1:785–789[Medline]
  29. Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI 1999 Free fatty acid-induced insulin resistance is associated with activation of protein kinase C{theta} and alterations in the insulin signaling cascade. Diabetes 48:1270–1274[Abstract]
  30. Frayn KN, Shadid S, Hamlani R, Humphreys SM, Clark ML, Fielding BA, Boland O, Coppack SW 1994 Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition. Am J Physiol 266:E308–E317
  31. Sniderman AD, Cianflone K, Arner P, Summers LK, Frayn KN 1998 The adipocyte, fatty acid trapping, and atherogenesis. Arterioscler Thromb Vasc Biol 18:147–151[Free Full Text]
  32. Staiger H, Tschritter O, Machann J, Thamer C, Fritsche A, Maerker E, Schick F, Haring HU, Stumvoll M 2003 Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans. Obes Res 11:368–372[Medline]
  33. Banerji MA, Faridi N, Atluri R, Chaiken RL, Lebovitz HE 1999 Body composition, visceral fat, leptin, and insulin resistance in Asian Indian men. J Clin Endocrinol Metab 84:137–144[Abstract/Free Full Text]
  34. Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DR, Wang F, Hull RL, Boyko EJ, Retzlaff BM, Walden CE, Knopp RH, Kahn SE 2002 The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 51:1005–1015[Abstract/Free Full Text]
  35. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL, Caro JF 1996 Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334:292–295[Abstract/Free Full Text]
  36. Wang MY, Lee Y, Unger RH 1999 Novel form of lipolysis induced by leptin. J Biol Chem 274:17541–17544[Abstract/Free Full Text]
  37. Kolaczynski JW, Nyce MR, Considine RV, Boden G, Nolan JJ, Henry R, Mudaliar SR, Olefsky J, Caro JF 1996 Acute and chronic effects of insulin on leptin production in humans: studies in vivo and in vitro. Diabetes 45:699–701[Abstract]
  38. Ryan AS, Berman DM, Nicklas BJ, Sinha M, Gingerich RL, Meneilly GS, Egan JM, Elahi D 2003 Plasma adiponectin and leptin levels, body composition, and glucose utilization in adult women with wide ranges of age and obesity. Diabetes Care 26:2383–2388[Abstract/Free Full Text]
  39. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ, Retzlaff BM, Knopp RH, Brunzell JD, Kahn SE 2003 Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 46:459–469[Medline]
  40. Matsubara M, Maruoka S, Katayose S 2002 Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women. Eur J Endocrinol 147:173–180[Abstract]



This article has been cited by other articles:


Home page
 Diabetes CareHome page
M. Martin, L. P. Palaniappan, A. C. Kwan, G. M. Reaven, and P. D. Reaven
Ethnic Differences in the Relationship Between Adiponectin and Insulin Sensitivity in South Asian and Caucasian Women
Diabetes Care, April 1, 2008; 31(4): 798 - 801.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
R. S. Beaser and P. Levy
A Work in Progress, but a Useful Construct
Circulation, April 3, 2007; 115(13): 1812 - 1818.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
R. Retnakaran, A. J.G. Hanley, and B. Zinman
Does Hypoadiponectinemia Explain the Increased Risk of Diabetes and Cardiovascular Disease in South Asians?
Diabetes Care, August 1, 2006; 29(8): 1950 - 1954.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
S. M. Grundy
Does the Metabolic Syndrome Exist?
Diabetes Care, July 1, 2006; 29(7): 1689 - 1692.
[Full Text] [PDF]

Home page
 CirculationHome page
M. Gupta, N. Singh, and S. Verma
South Asians and Cardiovascular Risk: What Clinicians Should Know
Circulation, June 27, 2006; 113(25): e924 - e929.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
R. Retnakaran, A. J.G. Hanley, P. W. Connelly, G. Maguire, M. Sermer, and B. Zinman
Low Serum Levels of High-Molecular Weight Adiponectin in Indo-Asian Women During Pregnancy: Evidence of ethnic variation in adiponectin isoform distribution.
Diabetes Care, June 1, 2006; 29(6): 1377 - 1379.
[Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
L. J Martin, J. G Woo, S. R Geraghty, M. Altaye, B. S Davidson, W. Banach, L. M Dolan, G. M Ruiz-Palacios, and A. L Morrow
Adiponectin is present in human milk and is associated with maternal factors
Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1106 - 1111.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. M. Grundy, J. I. Cleeman, S. R. Daniels, K. A. Donato, R. H. Eckel, B. A. Franklin, D. J. Gordon, R. M. Krauss, P. J. Savage, S. C. Smith Jr, et al.
Diagnosis and Management of the Metabolic Syndrome: An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement
Circulation, October 25, 2005; 112(17): 2735 - 2752.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
H. E. Lebovitz and M. A. Banerji
Point: Visceral Adiposity Is Causally Related to Insulin Resistance
Diabetes Care, September 1, 2005; 28(9): 2322 - 2325.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Abate, N.
Right arrow Articles by Grundy, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Abate, N.
Right arrow Articles by Grundy, S. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals