Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Diabetes Care 29:51-56, 2006
DOI: 10.2337/diacare.29.01.06.dc05-0952
© 2006 by the American Diabetes Association
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, S.
Right arrow Articles by Arslanian, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, S.
Right arrow Articles by Arslanian, S. A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Pathophysiology/Complications
Original Article

Racial Differences in Adiponectin in Youth

Relationship to visceral fat and insulin sensitivityv

SoJung Lee, PHD, Fida Bacha, MD, Neslihan Gungor, MD and Silva A. Arslanian, MD

From the Division of Pediatric Endocrinology, Metabolism and Diabetes Mellitus, Weight Management and Wellness Center, Children’s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Address correspondence and reprint requests to Silva A. Arslanian, MD, Children’s Hospital of Pittsburgh, 3705 Fifth Avenue at DeSoto St., Pittsburgh, PA 15213. E-mail: silva.arslanian{at}chp.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
OBJECTIVE—The purpose of this study was to investigate 1) whether adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in African-American and Caucasian youth and 2) whether adiponectin is associated with racial differences in insulin sensitivity.

RESEARCH DESIGN AND METHODS—Total body fat was measured by dual-energy X-ray absorptiometry and abdominal adipose tissue with computed tomography. Insulin sensitivity was measured by a 3-h hyperinsulinemic-euglycemic clamp.

RESULTS—Adiponectin was inversely associated (P < 0.01) with visceral adipose tissue, fasting insulin, and proinsulin and was positively related (P < 0.01) to insulin sensitivity after controlling for Tanner stage and sex independent of race. Stepwise multiple regression revealed that adiponectin was a strong independent predictor of insulin sensitivity, explaining 27% of the variance in insulin sensitivity. When subjects were categorized into tertiles of visceral adipose tissue and further low (≤50th) and high (>50th) adiponectin groups, insulin sensitivity was significantly different across the visceral adipose tissue groups (main effect, P < 0.01) in both races. However, within each visceral adipose tissue group, subjects with high adiponectin had higher insulin sensitivity (main effect, P < 0.05) than subjects with low adiponectin, independent of race. Racial differences in insulin sensitivity remained significant (P < 0.01) after controlling for leptin and visceral adipose tissue but not (P > 0.05) after additional adjustment for adiponectin.

CONCLUSIONS—Adiponectin is associated with insulin sensitivity independent of visceral adipose tissue in both African-American and Caucasian youth. Low adiponectin in African-American youth may be a biological marker that predisposes them to a greater risk of insulin resistance.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
It is well established that visceral adiposity is an independent predictor of cardiovascular disease risk factors (1,2), insulin resistance (3,4), and the metabolic syndrome (5). Visceral adipose tissue exhibits a high lipolytic activity and is drained by the portal circulation, resulting in increased lipoprotein and glucose production and reduced insulin clearance in the liver (6). Although this "portal theory" (6) has long been used to explain the link between abdominal adiposity and metabolic risk, adipose tissue is now recognized as a depot that secretes numerous active proteins, known as adipocytokines (7). Among these, adiponectin is one of the most abundant adipose tissue–specific cytokines that is closely linked to obesity (8). Unlike other adipocytokines, adiponectin concentration is reduced in obesity (8,9) and type 2 diabetes (9) and increases after weight loss (10). Further, it has been reported that adiponectin expression is significantly reduced in visceral adipose tissue of obese subjects with type 2 diabetes, while the decrease in adiponectin expression is less pronounced in abdominal subcutaneous adipose tissue (11).

A growing body of evidence suggests that adiponectin may play a role in the development of insulin resistance. It has been reported that circulating adiponectin level is positively associated with glucose tolerance (9,12) and insulin sensitivity (9,13) and inversely related to future development of type 2 diabetes (14,15). Administration of adiponectin to obese or diabetic rodents is associated with a reduction in endogenous glucose production (16) and an increase in insulin sensitivity (17). Recent findings suggest that the circulating adiponectin level predicts glucose tolerance and insulin sensitivity independent of visceral adiposity in adults (12). Whether this remains true for children and adolescents is currently unknown.

The prevalence of childhood obesity is already high and increasing rapidly in the U.S., particularly among African-American youth (18). African-American youth are hyperinsulinemic (19) and insulin resistant (19,20) by comparison to Caucasians of similar age and total adiposity. Recently, in a small number of prepubertal children, we have demonstrated that adiponectin level is lower in normal-weight African-Americans compared with Caucasian peers (21). This observation is consistent with those of Degawa-Yamauchi et al. (22) who reported that serum adiponectin level is 37% lower in African-American than Caucasian male subjects (aged 12–21 years). Whether this racial difference in adiponectin level explains the racial differences in insulin sensitivity in youth is currently unknown.

The purpose of this study was twofold: 1) to examine whether circulating adiponectin concentration is associated with insulin sensitivity independent of visceral adipose tissue and leptin in African-American and Caucasian youth and 2) to investigate whether adiponectin is associated with racial differences in insulin sensitivity. To examine these questions, we evaluated abdominal adipose tissue and metabolic profiles in 161 African-American and Caucasian youth varying widely in adiposity.


   RESEARCH DESIGN AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
Subjects consisted of healthy African-American (n = 83) and Caucasian (n = 78) youth who participated in various body composition and metabolic studies, some of which have been previously reported (19,21,23). The subjects varied in age (8–17 years) and BMI (14–50 kg/m2). Study participants were recruited via the general media. The investigation was approved by the institutional review board and performed in the General Clinical Research Center of Children’s Hospital of Pittsburgh. Parental informed consent and child assent were obtained from all participants before participation in accordance with the ethical guidelines of Children’s Hospital of Pittsburgh. All participants were in good health on the basis of clinical history, physical examination, and routine hematological and biochemical tests. None of the subjects were taking medications known to affect the primary outcome variables. Pubertal development was assessed by physical examination according to Tanner criteria and was confirmed by measurement of plasma testosterone in male subjects, estradiol in female subjects, and dehydroepiandrosterone sulfate in both.

Anthropometric measurements
Body weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, using standardized equipment.

Body composition
Total body fat was assessed by dual-energy X-ray absorptiometry. A single axial image (10-mm thickness) of the abdomen was obtained at the level of L4-L5 intervertebral disc space using a computed tomography to measure abdominal subcutaneous and visceral adipose tissue. Both dual-energy X-ray absorptiometry and computed tomography methods were previously described (19).

Insulin sensitivity
Each participant underwent a 3-h hyperinsulinemic-euglycemic clamp after 10–12 h of overnight fasting. Briefly, intravenous crystalline insulin (Humulin; Lilly, Indianapolis, IN) was infused at a constant rate of 40 mU · m–2 · min–1 in normal-weight and 80 mU · m–2 · min–1 in obese subjects, as we previously described (24,25), to suppress hepatic glucose production during the clamp. Plasma glucose was clamped at 5.6 mmol/l with a variable rate infusion of 20% dextrose based on arterialized plasma glucose determinations every 5 min. The insulin-stimulated glucose disposal rate was calculated using the average exogenous glucose infusion rate during the final 30 min of the clamp. Insulin sensitivity was calculated by dividing the insulin-stimulated glucose disposal rate by the steady-state insulin levels during the last 30 min of the clamp, as described previously (19).

Biochemical measurements
Adiponectin and leptin were measured using a commercially available radioimmunoassay kit (Linco Research, St. Louis, MO) (13). Plasma glucose was measured by the glucose oxidase method with a glucose analyzer (YSI, Yellow Springs, OH), and the insulin concentration was determined by radioimmunoassay (19). Proinsulin was measured at the Esoterix Endocrinology Laboratory (Calabasas Hills, CA) by immunochemiluminescent assays.

Statistical analyses
Statistical procedures were performed using SPSS (Version 13.0; SPSS, Chicago, IL). Independent t tests were used to compare racial differences in subject characteristics. Log transformations were employed to normalize the distribution for abdominal adipose tissue and metabolic variables. Pearson and partial correlation coefficients were used to determine the associations between abdominal adipose tissue and metabolic variables. A stepwise multiple regression was used to quantify the independent contribution of adiponectin, visceral adipose tissue, and leptin to insulin sensitivity. To further investigate the influence of visceral adipose tissue and adiponectin on insulin sensitivity, subjects were categorized as lowest (<14.2 cm2), moderate (14.2–44.0 cm2), or highest (>44.0 cm2) tertiles of visceral adipose tissue and further classified as low (≤9.7 µg/ml) and high (>9.7 µg/ml) adiponectin groups using the 50th percentile of adiponectin levels derived from all subjects. General linear models were used to determine the influence of adiponectin and visceral adipose tissue groups on insulin sensitivity. Insulin sensitivity was entered as a continuous variable, whereas visceral adipose tissue and adiponectin groups were entered as categorical variables. Racial differences in insulin sensitivity were examined using ANCOVA, with race as the fixed factor, adjusting for Tanner stage, sex, visceral and abdominal adipose tissue, leptin, and adiponectin.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
The subject characteristics are shown in Table 1.


View this table:
[in this window]
[in a new window]
  		Table 1— Subject characteristics

 
Relation of adiponectin and leptin to body composition and metabolic profiles
In African-American and Caucasian youth, adiponectin was inversely associated with abdominal subcutaneous (r = –0.43, r = –0.61) and visceral (r = –0.37, r = –0.61) adipose tissue and fasting insulin (r = –0.49, r = –0.59) and proinsulin (r = –0.51, r = –0.61) and positively related to insulin sensitivity (r = 0.51, r = 0.61), respectively (P < 0.01 for all correlations). By contrast, leptin was positively associated with abdominal subcutaneous (r = 0.89, r = 0.90) and visceral (r = 0.76, r = 0.82) adipose tissue and fasting insulin (r = 0.66, r = 0.77) and proinsulin (r = 0.57, r = 0.71) and inversely related to insulin sensitivity (r = –0.59, r = –0.74), respectively (P < 0.01 for all correlations). These associations remained significant (P < 0.01) after adjusting for Tanner stage and sex independent of race.

Stepwise multiple regression analysis to examine the independent association between adiponectin and insulin sensitivity
Stepwise multiple regression analysis revealed that Tanner stage, sex, and race explained a total of 21% of the variance in insulin sensitivity (Table 2). The addition of adiponetin in the regression model accounted for an additional 27% of the variance in insulin sensitivity, indicating that adiponectin is a strong independent predictor of insulin sensitivity (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 2— Stepwise multiple regression to quantify the independent contribution of adiponectin, viseral adipose tissue, and leptin to insulin sensitivity

 
Influence of adiponectin and visceral adipose tissue on insulin sensitivity
Figure 1 describes the relationships between insulin sensitivity, adiponectin, and visceral adipose tissue. Insulin sensitivity was significantly different across the visceral adipose tissue groups (main effect, P < 0.01) in both African-American and Caucasian youth. However, within each visceral adipose tissue group, subjects with high adiponectin had higher insulin sensitivity than subjects with low adiponectin (main effect, P < 0.05) independent of race. No significant (P > 0.1) visceral adipose tissue x adiponectin group interactions for insulin sensitivity was observed within each racial group.


Figure 1
View larger version (33K):
[in this window]
[in a new window]
  		Figure 1— Influence of adiponectin and visceral adipose tissue (AT) on insulin sensitivity in African-American (A) and Caucasian (B) youth. FFM, fat-free mass.

 
Racial differences in adiponectin and insulin sensitivity
Adiponectin and insulin sensitivity did not differ (P > 0.1) between male and female subjects within each race (data not shown). Despite having similar age, BMI, and total adiposity, African-American youth had lower (P < 0.05) adiponectin and insulin sensitivity compared with Caucasians (Table 1). Racial differences in adiponectin remained significant (P < 0.01) after controlling for Tanner stage, sex, abdominal subcutaneous and visceral adipose tissue, and leptin. Differences in insulin sensitivity between the two racial groups remained significant (P < 0.01) after controlling for Tanner stage, sex, abdominal subcutaneous and visceral adipose tissue, and leptin but not (P > 0.05) after additional adjustment for adiponectin concentration (Fig. 2).


Figure 2
View larger version (19K):
[in this window]
[in a new window]
  		Figure 2— Racial differences in insulin sensitivity before and after adjusting for Tanner stage, sex, visceral and abdominal subcutaneous adipose tissue (VAT and SAT, respectively), leptin, and adiponectin. FFM, fat-free mass.

 

   CONCLUSIONS
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
The primary findings of this study are that 1) adiponectin is a predictor of insulin sensitivity independent of visceral adipose tissue, leptin, and race and 2) racial differences in insulin sensitivity do not remain significant after adjustment for adiponectin. These findings suggest that adiponectin level is a strong marker of insulin sensitivity and that the lower adiponectin level in African-American youth may predispose them to a greater risk of insulin resistance despite lower visceral fat.

Our observation of lower visceral adipose tissue in African-American youth is consistent with other pediatric (26) and adult (27) studies. It is interesting to note that despite lower visceral adipose tissue in African-American youth, adiponectin levels as well as insulin sensitivity are lower compared with Caucasians. Whether this unfavorable metabolic profile in African Americans can be attributable to other fat depots (e.g., skeletal muscle lipid) is unknown and warrants further investigation.

The current data demonstrate that adiponectin explains 27% of the variance in insulin sensitivity independent of race, visceral adipose tissue, and leptin. Our findings in children are consistent with recent findings in adults (9,12). Weyer et al. (9) have shown that a low adiponectin level is a determinant of hyperinsulinemia and insulin resistance independent of total adiposity in both Caucasian and Pima Indians. Further, Cote et al. (12) demonstrated that adiponectin is an independent predictor of HDL cholesterol and glucose tolerance after controlling for visceral adipose tissue in middle-aged men. Together, these observations suggest that hypoadiponectinemia is a strong predictor of insulin resistance independent of total and abdominal obesity in both adults and children.

The underlying mechanism by which adiponectin has a beneficial effect on glucose metabolism has yet to be firmly established. Evidence suggests that adiponectin inhibits the production and action of tumor necrosis factor-{alpha} (28), a cytokine known to interfere with the insulin signaling cascade (29). Others also have shown that adiponectin activates 5'–AMP-activated protein kinase, an insulin-independent mechanism that stimulates glucose transport in skeletal muscle (30). Administration of adiponectin was shown to increase the expression of proteins involved in fatty acid transport and ß-oxidation in rodent skeletal muscle, resulting in decreased skeletal muscle lipid (17). Weiss et al. (31) reported a strong inverse relationship between adiponectin and intramyocellular lipid content (r = –0.73) independent of total and abdominal fat in a limited number of lean and obese adolescents. In that study, a positive association between adiponectin and insulin sensitivity was completely abolished after controlling for intramyocellular lipids. Together, these observations suggest that adiponectin may in part modulate insulin sensitivity by regulating skeletal muscle lipid content, a well-known marker of insulin resistance (32).

Consistent with the metabolic studies, epidemiological findings suggest that adiponectin has a protective effect on the development of type 2 diabetes in Pima Indians (14), Japanese (33), Caucasian (34), and African-American (34) men and women. Recently, Duncan et al. (34) reported that higher adiponectin levels were associated with a lower incidence of type 2 diabetes after controlling for other confounding variables (e.g., BMI, waist-to-hip ratio, and fasting insulin and glucose) in a large representative sample of U.S. African-American and Caucasian adults. In that study (34), individuals in the highest quartile of adiponectin had ~40% lower risk of developing type 2 diabetes than those in the lowest quartile over 9 years of follow-up, a finding that remained true for both men and women independent of race.

The lower adiponectin level in African-American youth compared with their Caucasian peers is consistent with our previous observations in a limited number of prepubertal children (21), others in adolescents (22), and adults (35). Our findings that the racial difference in insulin sensitivity did not remain significant after adjusting for adiponectin level suggest that lower adiponectin level in African-American youth may in part explain the lower insulin sensitivity despite lower visceral adipose tissue. It has been proposed that the association between variants in the adiponectin gene and metabolic profiles may differ between ethnic groups. A recent publication of the HERITAGE (Health, Risk Factors, Exercise Training, and Genetics) Family Study (36) found racial differences between blacks and whites in body composition and lipids according to adiponectin gene sequence variations. In blacks but not in whites, IVS2+G62T polymorphism was associated with adiposity, while in whites Tyr111His polymorphism was associated with insulin sensitivity and secretion (36). Such findings suggest that differences in adiponectin gene polymorphism could underlie the observed racial differences in adiponectin and its association with physical and metabolic parameters between African-American and Caucasian children.

In conclusion, our findings suggest that adiponectin is associated with insulin sensitivity independent of visceral adipose tissue and leptin in both African-American and Caucasian youth. Furthermore, racial differences in insulin sensitivity disappear after adjusting for differences in adiponectin concentration. These findings suggest that adiponectin is a strong independent marker of insulin sensitivity and that a lower adiponectin level in African-American youth may predispose them to a greater risk of insulin resistance and type 2 diabetes. The mechanism(s) responsible for the lower adiponectin levels in African-American youth remain to be determined.


   Acknowledgments
 
This work was supported by U.S. Public Health Service Grants RO1-HD-27503 and K24-HD-01357, General Clinical Research Center (GCRC) Grant MO1-RR-00084, and Eli Lilly and Company.

The authors express their gratitude to the study participants and their parents and to the GCRC staff for their technical assistance.


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

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received for publication May 24, 2005. Accepted for publication September 17, 2005.


   References
TOP
 ABSTRACT
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

  1. Hayashi T, Boyko EJ, Leonetti DL, McNeely MJ, Newell-Morris L, Kahn SE, Fujimoto WY: Visceral adiposity is an independent predictor of incident hypertension in Japanese Americans. Ann Intern Med 140:992–1000, 2004[Abstract/Free Full Text]
  2. Nicklas BJ, Penninx BW, Ryan AS, Berman DM, Lynch NA, Dennis KE: Visceral adipose tissue cutoffs associated with metabolic risk factors for coronary heart disease in women. Diabetes Care 26:1413–1420, 2003[Abstract/Free Full Text]
  3. Ross R, Aru J, Freeman J, Hudson R, Janssen I: Abdominal adiposity and insulin resistance in obese men. Am J Physiol Endocrinol Metab 282:E657–E663, 2002[Abstract/Free Full Text]
  4. Brochu M, Starling RD, Tchernof A, Matthews DE, Garcia-Rubi E, Poehlman ET: Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women. J Clin Endocrinol Metab 85:2378–2384, 2000[Abstract/Free Full Text]
  5. You T, Ryan AS, Nicklas BJ: The metabolic syndrome in obese postmenopausal women: relationship to body composition, visceral fat, and inflammation. J Clin Endocrinol Metab 89:5517–5522, 2004[Abstract/Free Full Text]
  6. Bjorntorp P: "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10:493–496, 1990[Free Full Text]
  7. Pittas AG, Joseph NA, Greenberg AS: Adipocytokines and insulin resistance. J Clin Endocrinol Metab 89:447–452, 2004[Free Full Text]
  8. 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 257:79–83, 1999[Medline]
  9. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA: Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935, 2001[Abstract/Free Full Text]
  10. 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 86:3815–3819, 2001[Abstract/Free Full Text]
  11. Statnick MA, Beavers LS, Conner LJ, Corominola H, Johnson D, Hammond CD, Rafaeloff-Phail R, Seng T, Suter TM, Sluka JP, Ravussin E, Gadski RA, Caro JF: Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res 1:81–88, 2000[Medline]
  12. Cote M, Mauriege P, Bergeron J, Almeras N, Tremblay A, Lemieux I, Despres J-P: Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men. J Clin Endocrinol Metab 90:1434–1439, 2005[Abstract/Free Full Text]
  13. Bacha F, Saad R, Gungor N, Arslanian SA: Adiponectin in youth: relationship to visceral adiposity, insulin sensitivity, and ß-cell function. Diabetes Care 27:547–552, 2004[Abstract/Free Full Text]
  14. 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[Medline]
  15. Cruz M, Garcia-Macedo R, Garcia-Valerio Y, Gutierrez M, Medina-Navarro R, Duran G, Wacher N, Kumate J: Low adiponectin levels predict type 2 diabetes in Mexican children. Diabetes Care 27:1451–1453, 2004[Free Full Text]
  16. Combs TP, Berg AH, Obici S, Scherer PE, Rossetti L: Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 108:1875–1881, 2001[Medline]
  17. 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 ML, 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 7:941–946, 2001[Medline]
  18. Strauss RS, Pollack HA: Epidemic increase in childhood overweight, 1986–1998. JAMA286:2845–2848, 2001
  19. Arslanian SA, Saad R, Lewy V, Danadian K, Janosky J: Hyperinsulinemia in African-American children: decreased insulin clearance and increased insulin secretion and its relationship to insulin sensitivity. Diabetes 51:3014–3019, 2002[Abstract/Free Full Text]
  20. Gower BA, Nagy TR, Goran MI: Visceral fat, insulin sensitivity, and lipids in prepubertal children. Diabetes 48:1515–1521, 1999[Abstract]
  21. Bacha F, Saad R, Gungor N, Arslanian SA: Does adiponectin explain the lower insulin sensitivity and hyperinsulinemia of African-American children? Pediatr Diabetes 6:100–102, 2005[Medline]
  22. Degawa-Yamauchi M, Dilts JR, Bovenkerk JE, Saha C, Pratt JH, Considine RV: Lower serum adiponectin levels in African-American boys. Obes Res 11:1384–1390, 2003[Medline]
  23. Bacha F, Saad R, Gungor N, Janosky J, Arslanian SA: Obesity, regional fat distribution, and syndrome X in obese black versus white adolescents: race differential in diabetogenic and atherogenic risk factors. J Clin Endocrinol Metab 88:2534–2540, 2003[Abstract/Free Full Text]
  24. Arslanian SA, Lewy VD, Danadian K: Glucose intolerance in obese adolescents with polycystic ovary syndrome: roles of insulin resistance and beta-cell dysfunction and risk of cardiovascular disease. J Clin Endocrinol Metab 86:66–71, 2001[Abstract/Free Full Text]
  25. Lewy VD, Danadian K, Witchel SF, Arslanian S: Early metabolic abnormalities in adolescent girls with polycystic ovarian syndrome. J Pediatr 138:38–44, 2001[Medline]
  26. Huang TT, Johnson MS, Gower BA, Goran MI: Effect of changes in fat distribution on the rates of change of insulin response in children. Obes Res 10:978–984, 2002[Medline]
  27. Lara-Castro C, Weinsier RL, Hunter GR, Desmond R: Visceral adipose tissue in women: longitudinal study of the effects of fat gain, time, and race. Obes Res 10:868–874, 2002[Medline]
  28. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y: Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96:1723–1732, 2000[Abstract/Free Full Text]
  29. Hotamisligil GS, Spiegelman BM: Tumor necrosis factor {alpha}: a key component of the obesity-diabetes link. Diabetes 43:1271–1278, 1994[Abstract]
  30. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T: Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295, 2002[Medline]
  31. Weiss R, Dufour S, Groszmann A, Petersen K, Dziura J, Taksali SE, 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[Abstract/Free Full Text]
  32. Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Testolin G, Pozza G, Del Maschio A, Luzi L: Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 48:1600–1606, 1999[Abstract]
  33. 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 26:2015–2020, 2003[Abstract/Free Full Text]
  34. Duncan BB, Schmidt MI, Pankow JS, Bang H, Couper D, Ballantyne CM, Hoogeveen RC, Heiss G: Adiponectin and the development of type 2 diabetes: the Atherosclerosis Risk in Communities Study. Diabetes 53:2473–2478, 2004[Abstract/Free Full Text]
  35. Hulver M, Saleh O, MacDonald K, Pories W, Barakat H: Ethnic differences in adiponectin levels. Metabolism 53:1–3, 2004[Medline]
  36. Ukkola O, Santaniemi M, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bergman R, Kesaniemi YA, Bouchard C: Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study. Ann Med 37:141–150, 2005[Medline]

Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
L. Ibanez, A. Lopez-Bermejo, M. Diaz, M. V. Marcos, and F. de Zegher
Metformin Treatment for Four Years to Reduce Total and Visceral Fat in Low Birth Weight Girls with Precocious Pubarche
J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1841 - 1845.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
R. Weiss and F. R. Kaufman
Metabolic Complications of Childhood Obesity: Identifying and mitigating the risk
Diabetes Care, February 1, 2008; 31(Supplement_2): S310 - S316.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
R. Weiss
Fat distribution and storage: how much, where, and how?
Eur. J. Endocrinol., August 1, 2007; 157(suppl_1): S39 - S45.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. J. G. Hanley, D. Bowden, L. E. Wagenknecht, A. Balasubramanyam, C. Langfeld, M. F. Saad, J. I. Rotter, X. Guo, Y.-D. I. Chen, M. Bryer-Ash, et al.
Associations of Adiponectin with Body Fat Distribution and Insulin Sensitivity in Nondiabetic Hispanics and African-Americans
J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2665 - 2671.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
G. A Martos-Moreno, V. Barrios, and J. Argente
Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids
Eur. J. Endocrinol., September 1, 2006; 155(3): 429 - 434.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, S.
Right arrow Articles by Arslanian, S. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, S.
Right arrow Articles by Arslanian, S. A.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum