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.

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.

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.

The subject characteristics are shown in Table 1.

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).

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 × adiponectin group interactions for insulin sensitivity was observed within each racial group.

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).

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-α (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 β-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.

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.

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.

Close modal
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.

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.

Close modal
Table 1—

Subject characteristics

African AmericansCaucasians
n (male/female) 41/42 41/37 
Age (years) 12.2 ± 2.0 (8.5–16.8) 12.3 ± 2.1 (8.0–17.2) 
Tanner stage   
    I 22 20 
    II–V 61 58 
Weight (kg) 60.5 ± 25.9 (27.6–128.8) 61.5 ± 30.1 (25.3–139.1) 
BMI (kg/m224.8 ± 8.2 (14.7–49.6) 24.6 ± 8.5 (13.9–47.1) 
Fat mass (kg)"* 18.3 ± 14.5 (2.7–51.0) 17.5 ± 14.3 (3.1–50.6) 
Total fat (%)"* 27.7 ± 13.3 (6.1–51.1) 27.7 ± 12.4 (9.2–51.1) 
Viseral adipose tissue (cm232.2 ± 26.5 (3.2–108.1) 43.3 ± 39.5 (5.2–161.4) 
Abdominal subcutaneous adipose tissue (cm2231.1 ± 222.2 (7.0–890.1) 247.6 ± 228.5 (20.8–822.6) 
Leptin (ng/ml) 18.3 ± 14.6 (1.5–61.6) 16.3 ± 14.0 (1.9–65.2) 
Adiponectin (μg/ml) 10.2 ± 5.5 (2.7–28.4) 12.1 ± 6.0 (1.6–30.4) 
Fasting glucose (mg/dl) 95.0 ± 5.4 (83.0–108.0) 96.5 ± 6.4 (84.3–117.7) 
Fasting insulin (μU/ml) 24.5 ± 16.0 (8.1–91.1) 24.6 ± 16.0 (6.8–95.5) 
Proinsulin (pmol/l) 19.7 ± 20.5 (3.2–112.0) 23.1 ± 21.2 (3.2–108.0) 
Insulin sensitivity (mg · kg FFM−1 · min−1)"* 11.0 ± 5.9 (1.1–24.2) 13.2 ± 8.0 (1.9–40.1) 
Total cholesterol§ 157.0 ± 28.8 (76.0–232.0) 166.3 ± 31.6 (84.0–258.0) 
Triglycerides§ 76.8 ± 33.3 (32.0–164.0) 112.6 ± 65.7 (36.0–395.0) 
HDL§ 48.0 ± 11.7 (27.0–97.8) 46.6 ± 10.3 (28.8–78.7) 
LDL§ 93.7 ± 26.6 (22.0–167.0) 97.0 ± 27.6 (35.0–189.0) 
African AmericansCaucasians
n (male/female) 41/42 41/37 
Age (years) 12.2 ± 2.0 (8.5–16.8) 12.3 ± 2.1 (8.0–17.2) 
Tanner stage   
    I 22 20 
    II–V 61 58 
Weight (kg) 60.5 ± 25.9 (27.6–128.8) 61.5 ± 30.1 (25.3–139.1) 
BMI (kg/m224.8 ± 8.2 (14.7–49.6) 24.6 ± 8.5 (13.9–47.1) 
Fat mass (kg)"* 18.3 ± 14.5 (2.7–51.0) 17.5 ± 14.3 (3.1–50.6) 
Total fat (%)"* 27.7 ± 13.3 (6.1–51.1) 27.7 ± 12.4 (9.2–51.1) 
Viseral adipose tissue (cm232.2 ± 26.5 (3.2–108.1) 43.3 ± 39.5 (5.2–161.4) 
Abdominal subcutaneous adipose tissue (cm2231.1 ± 222.2 (7.0–890.1) 247.6 ± 228.5 (20.8–822.6) 
Leptin (ng/ml) 18.3 ± 14.6 (1.5–61.6) 16.3 ± 14.0 (1.9–65.2) 
Adiponectin (μg/ml) 10.2 ± 5.5 (2.7–28.4) 12.1 ± 6.0 (1.6–30.4) 
Fasting glucose (mg/dl) 95.0 ± 5.4 (83.0–108.0) 96.5 ± 6.4 (84.3–117.7) 
Fasting insulin (μU/ml) 24.5 ± 16.0 (8.1–91.1) 24.6 ± 16.0 (6.8–95.5) 
Proinsulin (pmol/l) 19.7 ± 20.5 (3.2–112.0) 23.1 ± 21.2 (3.2–108.0) 
Insulin sensitivity (mg · kg FFM−1 · min−1)"* 11.0 ± 5.9 (1.1–24.2) 13.2 ± 8.0 (1.9–40.1) 
Total cholesterol§ 157.0 ± 28.8 (76.0–232.0) 166.3 ± 31.6 (84.0–258.0) 
Triglycerides§ 76.8 ± 33.3 (32.0–164.0) 112.6 ± 65.7 (36.0–395.0) 
HDL§ 48.0 ± 11.7 (27.0–97.8) 46.6 ± 10.3 (28.8–78.7) 
LDL§ 93.7 ± 26.6 (22.0–167.0) 97.0 ± 27.6 (35.0–189.0) 

Data are means ± SD (range).

*

Obtained from n = 80 and n = 72 in African Americans and Caucasians, respectively.

P < 0.05;

P = 0.05;

§

n = 82 in African Americans. FFM, fat free mass.

Table 2—

Stepwise multiple regression to quantify the independent contribution of adiponectin, viseral adipose tissue, and leptin to insulin sensitivity

Dependent variableStepIndependent variablePR2
Insulin sensitivity Tanner stage <0.001  
  Sex 0.320  
  Race 0.233 0.21 
     
 Tanner stage <0.001  
  Sex 0.045  
  Race 0.744  
  Adiponectin <0.001 0.48 
     
 Tanner stage <0.001  
  Sex 0.037  
  Race 0.255  
  Adiponectin <0.001  
  VAT <0.001 0.60 
     
 Tanner stage <0.001  
  Sex 0.896  
  Race 0.686  
  Adiponectin <0.001  
  VAT 0.125  
  Leptin <0.001 0.64 
Dependent variableStepIndependent variablePR2
Insulin sensitivity Tanner stage <0.001  
  Sex 0.320  
  Race 0.233 0.21 
     
 Tanner stage <0.001  
  Sex 0.045  
  Race 0.744  
  Adiponectin <0.001 0.48 
     
 Tanner stage <0.001  
  Sex 0.037  
  Race 0.255  
  Adiponectin <0.001  
  VAT <0.001 0.60 
     
 Tanner stage <0.001  
  Sex 0.896  
  Race 0.686  
  Adiponectin <0.001  
  VAT 0.125  
  Leptin <0.001 0.64 

Insulin sensitivity, adiponectin, viseral adipose tissue, and leptin were log transformed to normalize their distribution. VAT, viseral adipose tissue.

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.

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
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
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
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
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
6.
Bjorntorp P: “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes.
Arteriosclerosis
10
:
493
–496,
1990
7.
Pittas AG, Joseph NA, Greenberg AS: Adipocytokines and insulin resistance.
J Clin Endocrinol Metab
89
:
447
–452,
2004
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
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
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
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
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
13.
Bacha F, Saad R, Gungor N, Arslanian SA: Adiponectin in youth: relationship to visceral adiposity, insulin sensitivity, and β-cell function.
Diabetes Care
27
:
547
–552,
2004
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
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
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
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
18.
Strauss RS, Pollack HA: Epidemic increase in childhood overweight, 1986–
1998
. JAMA
286
:
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
20.
Gower BA, Nagy TR, Goran MI: Visceral fat, insulin sensitivity, and lipids in prepubertal children.
Diabetes
48
:
1515
–1521,
1999
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
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
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
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
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
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
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
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
29.
Hotamisligil GS, Spiegelman BM: Tumor necrosis factor α: a key component of the obesity-diabetes link.
Diabetes
43
:
1271
–1278,
1994
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
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
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
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
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
35.
Hulver M, Saleh O, MacDonald K, Pories W, Barakat H: Ethnic differences in adiponectin levels.
Metabolism
53
:
1
–3,
2004
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

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.