Both Subcutaneous and Visceral Adipose ... - Wiley Online Library

Both Subcutaneous and Visceral Adipose Tissue Correlate Highly with Insulin Resistance in African Americans Marshall K. Tulloch-Reid,* Robert L. Hanson,* Nancy G. Sebring,† James C. Reynolds,‡ Ahalya Premkumar,§ David J. Genovese,¶ and Anne E. Sumner¶

Abstract TULLOCH-REID, MARSHALL K., ROBERT L. HANSON, NANCY G. SEBRING, JAMES C. REYNOLDS, AHALYA PREMKUMAR, DAVID J. GENOVESE, AND ANNE E. SUMNER. Both subcutaneous and visceral adipose tissue correlate highly with insulin resistance in African Americans. Obes Res. 2004;12:1352–1359. Objective: The contribution of visceral adipose tissue (VAT) to insulin resistance is well-established; however, the role of subcutaneous abdominal adipose tissue (SAT) in insulin resistance remains controversial. Sex may determine which of these two components of abdominal obesity is more strongly related to insulin resistance and its consequences. The aim of this study was to determine whether both VAT and SAT contribute to insulin resistance in African Americans and to examine the effects of sex on this relationship. Research Methods and Procedures: This was a crosssectional study of 78 nondiabetic African-American volunteers (44 men, 35 women; age 33.8 ⫾ 7.3 years; BMI 30.9 ⫾ 7.4 kg/m2). VAT and SAT volumes were measured using serial computerized tomography slices from the dome of the diaphragm to the iliac crest. The insulin sensitivity

Received for review November 13, 2003. Accepted in final form June 16, 2004. According to U.S. code, all journals requesting payment of author page charges in order to defray the cost of publication are required to publish a disclaimer. This article must, therefore, be marked ‘‘advertisement’’ in compliance with U.S.C. Section 1734 solely to indicate this fact. *Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona; †Nutrition, ‡Nuclear Medicine, and §Diagnostic Radiology Departments, Clinical Center, National Institutes of Health, Bethesda, Maryland; and ¶Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland. Address correspondence to Anne E. Sumner, Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 8S 235D, MSC 1770, Bethesda, MD 20892-1770. E-mail: [email protected] Copyright © 2004 NAASO

1352

OBESITY RESEARCH Vol. 12 No. 8 August 2004

index (SI) was determined from the minimal model using data obtained from the frequently sampled intravenous glucose tolerance test. Results: In men, both VAT and SAT were negatively correlated with SI (r for both correlations ⫽ ⫺0.57; p ⬍ 0.01). In women, the correlation coefficient between VAT and SI was ⫺0.50 (p ⬍ 0.01) and between SAT and SI was ⫺0.67 (p ⬍ 0.01). In women, the correlation coefficient for SI with SAT was significantly greater than the correlation coefficient with VAT (p ⫽ 0.02). Discussion: Both SAT and VAT are strongly correlated with insulin resistance in African Americans. For AfricanAmerican women, SAT may have a greater effect than VAT on insulin resistance. Key words: abdominal obesity, colinearity, insulin resistance complications, African American

Introduction Obesity, particularly abdominal obesity, is strongly associated with insulin resistance and its complications such as hypertriglyceridemia, low high-density lipoprotein (HDL)1cholesterol, altered lipoprotein metabolism, elevated serum glucose, and hypertension (1,2). Several studies have shown a strong association between visceral adiposity and insulin resistance and its metabolic consequences (3–5). However, other studies have shown that subcutaneous abdominal adipose tissue (SAT) may have an equally strong or even superior relationship to insulin resistance than visceral adipose tissue (VAT) (5–7). The portal theory for the pathogenesis of the insulin resistance syndrome suggests that the syndrome is caused by increased delivery of free fatty acids to the liver from

1 Nonstandard abbreviations: HDL, high-density lipoprotein; SAT, subcutaneous abdominal adipose tissue; VAT, visceral adipose tissue; WHR, waist-to-hip ratio; TG, triglyceride; LDL, low-density lipoprotein; apo B, apolipoprotein B; CT, computerized tomography; SI, insulin sensitivity index; LR, likelihood ratio.

Central Obesity in African Americans, Tulloch-Reid et al.

intraabdominal fat (8). According to this theory, free fatty acids are more easily mobilized from VAT and are delivered directly into the portal circulation resulting in altered hepatic metabolism and insulin resistance. Therefore, VAT should be a stronger determinant of the metabolic anomalies associated with insulin resistance than SAT. However, it has also been hypothesized that an increase in free fatty acid delivery to the liver from SAT could produce a similar effect on hepatic metabolism (9,10). SAT in women is considerably larger than VAT; therefore, on the basis of size alone, SAT is likely to contribute to insulin resistance by the release of free fatty acids into the systemic circulation (9). Furthermore, systemic free fatty acids may be an especially important contributor to insulin resistance in the presence of upper abdominal obesity [defined as a waist-to-hip ratio (WHR) ⬎ 0.85] (10). Due to well-described racial differences in central body fat distribution between VAT and SAT compartments, assumptions made in whites about the association between insulin sensitivity and VAT and insulin sensitivity and SAT need to be independently established in African Americans. For example, African-American men and women have lower VAT but greater insulin resistance than whites and Hispanic Americans (5,11–15). Additionally, African Americans have greater SAT than whites (12,16,17). Therefore, it is especially important to examine the effect of SAT on insulin resistance in African Americans. The aim of this study was to evaluate the relationship in African Americans among VAT, SAT, and insulin resistance. Additionally, we wanted to determine the clinical impact of the relationship among insulin resistance and each of these fat depots by examining the correlations of both VAT and SAT with the consequences of insulin resistance, specifically, lower HDL-cholesterol, higher triglycerides (TGs), increased lowdensity lipoprotein (LDL) particle number, small LDL and HDL particle size, higher systolic and diastolic blood pressure, and increased fasting glucose (18–20).

Research Methods and Procedures Subjects Seventy-eight African-American men and women participated in a protocol to evaluate cardiovascular risk in normal healthy volunteers at NIH (Bethesda, MD). All participants were born in the United States and identified both parents as being of African descent. All women were premenopausal and were studied in the follicular phase of the menstrual cycle. The volunteers were recruited by advertisements in the local newsletters, posters, and the NIH web site. The study was approved by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases. Informed consent was obtained from each subject. Methods Subjects made four visits to the Clinical Center over a 3-month period. At Visit 1, a history and physical exami-

nation were performed. Visits 2 to 4 occurred in the morning after the subject had fasted for 12 hours. At each of these visits, a fasting lipid profile was obtained. The lipid results reported for TG, HDL, and apolipoprotein B (apo B) are the mean of these three measurements. At Visit 2, a 2-hour, 75-gram oral glucose tolerance test (Trutol 75; Custom Laboratories, Baltimore, MD) was performed, with glucose determined at 0 and 2 hours. Blood was also collected for LDL particle size and number and HDL particle size. At Visit 3, an abdominal computerized tomography (CT) scan and DXA were obtained. At Visit 4, an insulin-modified frequently sampled intravenous glucose tolerance test was performed. The Frequently Sampled Intravenous Glucose Tolerance Test Intravenous lines were placed in each antecubital vein. The arm used for phlebotomy was wrapped in a heating blanket. At time 0, glucose (0.3 g/kg) was injected over 1 minute. Insulin (4 mU/kg per minute) was administered from 20 to 25 minutes. Samples were taken at: ⫺10, ⫺1, 0, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 minutes. Glucose and insulin levels were measured in all samples. Glucose was determined at the bedside, and blood for insulin determination was drawn into serum separator tubes. Insulin resistance was determined from the insulin sensitivity index (SI) calculated using the minimal model equations (21). SI is the incremental change in insulin required to increase fractional glucose disappearance (22). Anthropometric Measurements Anthropometric measurements were performed according to standard procedures (23). Body weight was measured to the nearest 0.1 kg using a platform digital scale, and standing height was obtained to the nearest 0.1 cm using a stadiometer. The circumference measurements were performed by a single observer (N.G.S.) using a nonstretch tape. The waist circumference was measured just above the anterior iliac crest. The hip circumference was measured at the level of maximum extension of the buttocks. Circumference measurements were performed three times and the mean value reported. Visceral and Subcutaneous Adipose Tissue Measurement CT was performed with a HiSpeed Advantage CT/i scanner (GE Medical Systems, Milwaukee, WI) and analyzed using the MEDx image analysis software package (Sensor System, Inc., Sterling, VA) on a SUN workstation. VAT and SAT volumes were measured with images from 10-mm contiguous slices from the dome of the diaphragm to the iliac crest. Each subject had 20 to 25 slices performed, with the exact number dependent on height. A cursor was placed OBESITY RESEARCH Vol. 12 No. 8 August 2004

1353

Central Obesity in African Americans, Tulloch-Reid et al.

on the abdominal wall, which allowed the tracing of the periphery of the abdominal cavity to be automatically performed using edge detection techniques. The perimeter of the visceral cavity below the subcutaneous fat was then traced manually. A density mask inclusive of pixels with attenuation values ranging from ⫺150 to ⫺50 Hounsfield units (which includes adipose tissue without including other soft tissue, bone, and air) was used to measure the areas. The system calculated the visceral and subcutaneous fat areas separately for each slice. The results from the contiguous slices were added to give the VAT and SAT volumes. Percentage Body Fat Measurement Percentage body fat was determined with a Hologic QDR 4500A DXA (Hologic, Inc., Bedford, MA) in the array mode using software version 5.71A. Five subjects (three men and two women) who were above the weight limits for the DXA machine (136 kg) had their percentage fat determined from a regression equation derived in this population (24) using the percentage body fat calculation (Weight Manager software, version 2.2, RJL Systems, Detroit MI) from the bioelectrical impedance measurement (Quantum II BIA Analyzer, RJL Systems). Laboratory Analytic Methods Glucose was measured using the glucose oxidase method (Glucostat; Yellow Springs Instrument, Yellow Springs, OH). Insulin assays were performed using the double antibody chemiluminescent sandwich assay (Diagnostic Products, Los Angeles, CA). TG was analyzed using standard enzymatic methods by an automated analyzer (Boehringer Mannheim/Hitachi 917, Roche Diagnostic, Indianapolis, IN). HDL-cholesterol was isolated according to the method of Warnick (25). Coefficients of variation for the TG and HDL-cholesterol assays were 1.5% and 2.2%, respectively. Apo B was assayed turbidimetrically using commercial antibodies (Beckman kit/Beckman Array; Beckman Coulter, Fullerton, CA). The LDL particle number and the LDL and HDL particle diameters were determined by LipoScience (Raleigh, NC) using nuclear magnetic spectroscopy (26,27). The technique involves measurement of the plasma nuclear magnetic resonance spectrum for each lipoprotein particle followed by computer deconvolution of the spectral data and calculation of the subclass fractions (27). Normal values for LDL particle number and size of LDL and HDL particles are not yet established. Based on studies performed in the Framingham Offspring Study, the normal mean ⫾ SD for the LDL particle number is 1483 ⫾ 432 nM and for LDL and HDL particle size are 20.9 ⫾ 0.5 and 9.2 ⫾ 0.5 nM, respectively (J.D. Otvos, personal communication). Statistical Analysis Unpaired Student’s t tests were used to detect sex differences. Variables without a normal distribution were log 1354

OBESITY RESEARCH Vol. 12 No. 8 August 2004

transformed before this analysis. The Spearman rank correlation coefficient was used to examine the relationship among the obesity measurements (VAT and SAT), SI, and the lipid and glucose consequences of insulin resistance. To determine whether the difference in the correlation coefficients among SI, VAT, and SAT was significant, a z statistic was generated (28). This statistic was derived in each sex from the correlation coefficients among SI, VAT, and SAT, as well as the correlation coefficient between VAT and SAT. Using a 95% confidence limit, the difference between coefficients was significantly different if the z statistic was either less than ⫺1.96 or more than 1.96 (corresponding to p ⬍ 0.05). The correlation coefficients between VAT and SAT and each of the consequences of insulin resistance were similarly compared using this method. The WHR was used to explore whether upper abdominal obesity (WHR ⬎ 0.85) might modify the relationship between VAT or SAT and SI. An interaction term consisting of the product of WHR and VAT or SAT was included in sex-specific regression models containing age and using SI as the dependent variable. The likelihood ratio (LR) test was used to compare models with the main effects and the interaction term with models containing the main effects alone. All statistical tests were considered significant for p ⱕ 0.05. Analysis was performed using SAS (version 8, SAS Corporation, Cary, NC).

Results The anthropometric and metabolic characteristics of the 78 subjects (44 men and 34 women) are presented in Table 1. Fourteen men (32%) and five women (15%) had glucose intolerance. All analyses were performed including and excluding the glucose intolerant subjects. Because the results did not vary significantly, the findings from the analysis of the combined population are presented in this paper. The BMI of the subjects studied ranged from 21.9 to 54.7 kg/m2 in men and 20.9 to 49.7 kg/m2 in women. There were no sex differences in age, waist circumference, or BMI. Women had a higher percentage body fat (p ⬍ 0.01) and a lower WHR than men (P ⴝ 0.01). Women also had lower VAT (p ⬍ 0.01) and higher SAT (p ⫽ 0.02) than men. Despite the sex differences in WHR, VAT, and SAT, the mean SI of the men and women studied was similar (p ⫽ 0.71). The mean fasting glucose, systolic blood pressure, and TG were all significantly higher in men than women; however, there was no sex difference in the proportion of men or women with impaired glucose tolerance. There were no sex differences in LDL particle number and apo B; however, women had a higher HDL and LDL particle size compared with men. VAT and SAT were highly correlated with each other in men (r ⫽ 0.82; p ⬍ 0.01) and women (r ⫽ 0.84; p ⬍ 0.01).

Central Obesity in African Americans, Tulloch-Reid et al.

Table 1. Anthropometric and metabolic characteristics of the participants*

Age (years) BMI (kg/m2) Percentage body fat Waist circumference (cm) WHR VAT volume (mm3) SAT volume (mm3) SI (L/mU per minute) Fasting insulin (pM) Fasting glucose (mM) Cholesterol (mM) HDL-cholesterol (mM) TGs (mM) Apo B (g/L) LDL particle number (nM) LDL particle size (nm) HDL particle size (nm) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Number with IGT (%)

Men (n ⴝ 44)

Women (n ⴝ 34)

p value

35.1 ⫾ 7.9 30.6 ⫾ 6.4 22.9 ⫾ 6.5 99.1 ⫾ 16.2 0.90 ⫾ 0.07 1580 ⫾ 1030 4085 ⫾ 2960 3.52 ⫾ 1.98 55.1 ⫾ 11.0 5.0 ⫾ 0.6 4.5 ⫾ 1.0 1.21 ⫾ 0.25 0.93 ⫾ 0.33 0.89 ⫾ 0.27 1253 ⫾ 410 21.0 ⫾ 0.6 8.8 ⫾ 0.5 119 ⫾ 11 70 ⫾ 10 14 (32%)

32.1 ⫾ 6.2 30.9 ⫾ 8.6 36.9 ⫾ 9.0 96 ⫾ 16 0.86 ⫾ 0.06 939 ⫾ 776 6237 ⫾ 4563 3.77 ⫾ 2.86 63.3 ⫾ 40.5 4.6 ⫾ 0.5 4.4 ⫾ 1.0 1.39 ⫾ 0.26 0.66 ⫾ 0.38 0.83 ⫾ 0.25 1250 ⫾ 422 21.3 ⫾ 0.6 9.2 ⫾ 0.4 112 ⫾ 14 69 ⫾ 8 5 (15%)

0.07 0.97 ⬍0.01 0.37 0.01 ⬍0.01 0.02 0.71 0.30 ⬍0.01 0.56 ⬍0.01 ⬍0.01 0.34 0.98 0.04 ⬍0.01 0.01 0.65 0.11

* Mean ⫾ SD. IGT, impaired glucose tolerance.

Sex-Specific Correlations for VAT and SAT with Insulin Resistance and Its Consequences The sex-specific correlation coefficients for VAT and SAT with insulin resistance and its consequences are presented in Table 2. In African-American men, VAT and SAT were negatively correlated with SI and HDL particle size.

VAT and SAT were positively correlated with TG and fasting glucose. VAT but not SAT was also positively correlated with LDL particle number and apo B. There was no correlation between blood pressure and either VAT or SAT. In African-American women, both VAT and SAT were negatively correlated with SI, HDL-cholesterol, HDL parti-

Table 2. Age-adjusted Spearman correlations in men and women for insulin resistance and its consequences

Variable Men VAT SAT Women VAT SAT

SI

TG

HDL

HDL particle size

LDL particle size

LDL particle number

apo B

Fasting glucose

Systolic blood pressure

Diastolic blood pressure

⫺0.57* ⫺0.57*

0.51* 0.40*

⫺0.14 ⫺0.15

⫺0.50* ⫺0.44*

⫺0.14 0.05

0.31† 0.20

0.37† 0.24

0.50* 0.40*

0.08 0.14

0.04 ⫺0.04

⫺0.50* ⫺0.67*

0.57* 0.47*

⫺0.41* ⫺0.34†

⫺0.66* ⫺0.59*

⫺0.38† ⫺0.40†

0.50* 0.48*

0.62* 0.55*

0.53* 0.47*

0.40† 0.34†

0.13 ⫺0.06

* p ⬍ 0.01. † p ⬍ 0.05.

OBESITY RESEARCH Vol. 12 No. 8 August 2004

1355

Central Obesity in African Americans, Tulloch-Reid et al.

Figure 1: (A) Men: relationship between SI and VAT (Œ) and SI and SAT (⽧). (B) Women: data presented as described for men. All values are log-transformed (Ln). Age-adjusted Spearman correlation coefficients (r) and p values are provided on each panel.

cle size, and LDL particle size. VAT and SAT were positively correlated with TG, LDL particle number, apo B, and the fasting glucose. Positive correlations were noted between systolic blood pressure and VAT and SAT in women. Neither VAT nor SAT was correlated with the diastolic blood pressure. Comparison of Sex-Specific Correlation Coefficients for VAT and SAT Figure 1 presents by sex the relationship between SI and VAT and SI and SAT. In men, when correlation coefficients for VAT vs. SI and SAT vs. SI were compared, neither measurement was more highly correlated statistically with SI (difference in r ⫽ 0; p ⫽ 0.50). In women, SAT was more highly correlated with SI than VAT (difference in r ⫽ 0.17; p ⫽ 0.02). In African-American men and women, no significant difference in the correlation coefficients for VAT and SAT with the glucose and lipid consequences of insulin resistance was detected (data not shown). Insulin Sensitivity, VAT, SAT, and Upper Body Obesity The presence or absence of upper body obesity (assessed by WHR) did not modify the relationship between either VAT or SAT and SI. In women, the LR test from the inclusion of an interaction term between WHR and VAT or SAT was not significant (p for LR test for regression models 1356

OBESITY RESEARCH Vol. 12 No. 8 August 2004

with and without either the VAT-WHR or SAT-WHR interaction term were 0.85 and 0.83, respectively). In men, interaction terms for VAT, SAT, and SI were also not significant (p for LR test for difference in model with inclusion of VAT-WHR interaction term was 0.49 and 0.70 for the SAT-WHR interaction term). There was no improvement in the regression models when the waist circumference was used instead of WHR to generate the interaction terms in both sexes.

Discussion SAT and VAT volumes were both highly correlated with SI in African Americans. In men, the correlation coefficients for SAT with SI and VAT with SI were similar, whereas in women, the correlation between SAT and SI was significantly greater than the correlation between SI and VAT. Furthermore, SI was similar in men and women, despite the significant sex differences in WHR, SAT, and VAT. In women, both VAT and SAT were correlated with most of the consequences of insulin resistance: higher TG, LDL particle number, fasting glucose, and systolic blood pressure, lower HDL, and smaller LDL and HDL particle size. In men, both VAT and SAT were correlated only with higher TG and fasting glucose and smaller LDL particle size.

Central Obesity in African Americans, Tulloch-Reid et al.

Insulin Resistance and Central Body Fat Distribution The medical literature suggests that both SAT and VAT contribute to insulin resistance. Abate et al. (6), in a study of middle-aged men, showed that the SAT had a stronger correlation with the glucose disposal rate than VAT did. Goodpaster et al. (7), in a study of men and premenopausal women, concluded that even though both VAT and SAT areas had strong correlations with insulin sensitivity, SAT had an independent effect on insulin sensitivity. In contrast, other investigators have found stronger associations between the VAT and insulin resistance compared with SAT (4,29 –31). Cnop et al. (31), in a study of men and pre- and postmenopausal women, concluded that the VAT (compared with SAT, BMI, and WHR) was the strongest predictor of SI. When lean and obese insulin resistant subjects from this study were matched for sex and VAT area, there was no difference in SI among the subjects. The absence of a difference in SI among subjects matched for VAT area has been demonstrated in other studies (29,30), whereas matching subjects for SAT area has not been shown to remove differences in SI (29,30). None of these studies described the effect of race on their findings. Banerji et al., in a study of 52 African Americans (32 men and 20 women, mean age 48 and 54 years, respectively) with type 2 diabetes, found a significant correlation between VAT and insulin-mediated glucose disposal, a measure of insulin sensitivity (32). In contrast to our study, the correlation between SAT and insulin-mediated glucose disposal was not statistically significant in either sex despite similarities in the technique used to measure intraabdominal fat. This study differs from ours in a number of areas. We studied a younger population of African Americans, all of the women were premenopausal, and none of the subjects had type 2 diabetes. The significant heterogeneity among our study populations may explain the differences in our conclusions. Similar to our work, Lovejoy et al. (5) found a significant association between SI and both VAT and SAT in AfricanAmerican women. However, these investigators found that in African-American women, both VAT and SAT areas were equally correlated with the SI. However, we determined that although SI in African-American women was associated with VAT and SAT, the association between SI and SAT was significantly greater than the association between SI and VAT. There may be a methodological reason to account for why we found a relatively greater association between SI and SAT than Lovejoy et al. First, we had a more optimal measure of VAT and SAT. Specifically, we measured total VAT and SAT volume, whereas the other investigators had access to only a single CT area measurement at L4 to L5. Having only area measurements may have reduced the ability to detect a difference in the correlation between VAT and SAT with SI. To compare our data with Lovejoy et al., we looked at the CT slice at L4 to

L5 and calculated the areas for VAT and SAT. When we did this, we also found that the correlation coefficients for SI with VAT and SAT areas at L4 to L5 were similar (data not shown). Importantly, the results of our study are consistent with the findings of the recently published Insulin Resistance Atherosclerosis Study Family Study (15). This population, which consisted of African Americans and Hispanic Americans, also demonstrated that, independent of ethnicity and sex, both SAT and VAT areas had a negative association with SI. In fact, the SI was lowest in the subjects with the largest VAT and SAT areas. In our study, upper abdominal obesity, assessed using the WHR, did not modify the relationship of either VAT or SAT with SI in African-American women. This suggests that in African-American women, SAT contributes to SI regardless of the amount of upper abdominal obesity. In African-American men, SAT and VAT contributed equally to SI regardless of upper abdominal obesity. Insulin Resistance and Disorders of Glucose and Lipoprotein Metabolism In subjects of a variety of racial backgrounds, disorders of glucose and lipoprotein metabolism have been strongly associated with insulin resistance (19,33). Most studies that have examined the association between the metabolic consequences of insulin resistance and VAT and SAT have concluded that VAT is the more important contributor (34 – 36). However, in our study of African Americans, both VAT and SAT volumes were found to be highly correlated with fasting glucose, HDL particle size, and serum TGs. When these correlation coefficients were compared, there was no significant statistical difference among them. VAT and SAT were not correlated with all of the complications of insulin resistance in African-American men. However, in African-American women, both VAT and SAT were equally correlated with all of the consequences of insulin resistance (with the exception of diastolic blood pressure). Therefore, we suggest that in African Americans, SAT has an important role in the pathogenesis of insulin resistance and its metabolic consequences. Our findings also suggest that SAT may be of potentially greater importance to insulin resistance than VAT in African-American women. We are unaware of any other metabolic study of African Americans that has examined the relationship between intraabdominal fat and lipoprotein particle size and number. The sexual dimorphism in the relationship between VAT, SAT, and LDL particle number and apo B is of particular interest. In men, the VAT but not SAT was correlated with these variables. This suggests a stronger relationship between VAT and dyslipoproteinemia than SAT and dyslipoproteinemia in African-American men despite both abdominal fat depots being equally correlated with SI. It OBESITY RESEARCH Vol. 12 No. 8 August 2004

1357

Central Obesity in African Americans, Tulloch-Reid et al.

would be interesting to see whether this relationship is replicated in other studies of African-American men. The strong correlation between VAT and SAT presents a significant problem if one attempts to simultaneously compare the effect of these measurements on any dependent variable in a regression model or by using partial Spearman analysis because of colinearity (37). To avoid this difficulty, we quantified the correlation of both VAT and SAT with SI and consequences of insulin resistance, and we assessed the statistical significance of the difference among the correlation coefficients using the method suggested by Olkin (28). Other advantages of our study include the availability of direct measurements of VAT and SAT volumes (superior to area measurements performed at a single lumbar vertebrae) and the ability to examine the effect of VAT and SAT on some of the newer markers of insulin resistance. Kelley et al. (38) has demonstrated the importance of divisions of subcutaneous adipose tissue to insulin resistance in lean and obese glucose-tolerant men and women. Given the importance of SAT to SI in African Americans, the contribution of deep and superficial subcutaneous fat to insulin resistance and its metabolic consequences will need further exploration in future studies. In African Americans, both SAT and VAT contribute to insulin resistance and its complications. In African-American women, because insulin resistance is more highly correlated with SAT than VAT, SAT may be an even greater contributor to the development of insulin resistance than VAT. Therefore, further investigations are needed to determine the metabolic significance of SAT in African Americans, particularly African-American women.

Acknowledgments We thank all of the study participants, Aramesh Saremi for her assistance with the data analysis, and Jonathan Krakoff for his thoughtful review of the manuscript. This study was supported by intramural funding from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. References 1. Okosun IS, Liao Y, Rotimi CN, Prewitt TE, Cooper RS. Abdominal adiposity and clustering of multiple metabolic syndrome in white, black and Hispanic Americans. Ann Epidemiol. 2000;10:263–70. 2. Karter AJ, Mayer-Davis EJ, Selby JV, et al. Insulin sensitivity and abdominal obesity in African-American, Hispanic, and non-Hispanic white men and women: the Insulin Resistance and Atherosclerosis Study Diabetes. Diabetes. 1996;45: 1547–55. 3. Hayashi T, Boyko EJ, Leonetti DL, et al. Visceral adiposity and the risk of impaired glucose tolerance: a prospective study among Japanese Americans. Diabetes Care. 2003;26:650 –5. 1358

OBESITY RESEARCH Vol. 12 No. 8 August 2004

4. Ross R, Fortier L, Hudson R. Separate associations between visceral and subcutaneous adipose tissue distribution, insulin and glucose levels in obese women. Diabetes Care. 1996;19: 1404 –11. 5. Lovejoy JC, de la Bretonne JA, Klemperer M, Tulley R. Abdominal fat distribution and metabolic risk factors: effects of race. Metabolism. 1996;45:1119 –24. 6. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy SM. Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest. 1995;96: 88 –98. 7. Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes. 1997;46:1579 – 85. 8. Bjo¨rntorp P. “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 1990;10:493– 6. 9. Wajchenberg BL, Giannella-Neto D, Da Silva ME, Santos RF. Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm Metab Res. 2002;34:616 –21. 10. Jensen MD. Adipose tissue and fatty acid metabolism in humans. J R Soc Med. 2002;95(suppl)42:3–7. 11. Conway JM, Yanovski SZ, Avila NA, Hubbard VS. Visceral adipose tissue differences in black and white women. Am J Clin Nutr. 1995;61:765–71. 12. Hill JO, Sidney S, Lewis CE, Tolan K, Scherzinger AL, Stamm ER. Racial differences in amounts of visceral adipose tissue in young adults: the CARDIA (Coronary Artery Risk Development in Young Adults) study. Am J Clin Nutr. 1999; 69:381–7. 13. Perry AC, Applegate EB, Jackson ML, et al. Racial differences in visceral adipose tissue but not anthropometric markers of health-related variables. J Appl Physiol. 2000;89:636 – 43. 14. Haffner SM, D’Agostino R, Saad MF, et al. Increased insulin resistance and insulin secretion in nondiabetic AfricanAmericans and Hispanics compared with non-Hispanic whites: the Insulin Resistance Atherosclerosis Study. Diabetes. 1996;45:742– 8. 15. Wagenknecht LE, Langefeld CD, Scherzinger AL, et al. Insulin sensitivity, insulin secretion, and abdominal fat: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes. 2003;52:2490 – 6. 16. Ryan AS, Nicklas BJ, Berman DM. Racial differences in insulin resistance and mid-thigh fat deposition in postmenopausal women. Obes Res. 2002;10:336 – 44. 17. Kanaley JA, Giannopoulou I, Tillapaugh-Fay G, Nappi JS, Ploutz-Snyder LL. Racial differences in subcutaneous and visceral fat distribution in postmenopausal black and white women. Metabolism. 2003;52:186 –91. 18. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486 –97.

Central Obesity in African Americans, Tulloch-Reid et al.

19. Howard BV, Mayer-Davis EJ, Goff D, et al. Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study. Metabolism. 1998; 47:1174 –9. 20. Garvey WT, Kwon S, Zheng D, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes. 2003;52:453– 62. 21. Pacini G, Bergman RN. MINMOD: a computer program to calculate insulin sensitivity and pancreatic responsivity from the frequently sampled intravenous glucose tolerance test. Comput Methods Programs Biomed. 1986;23:113–22. 22. Steil GM, Volund A, Kahn SE, Bergman RN. Reduced sample number for calculation of insulin sensitivity and glucose effectiveness from the minimal model: suitability for use in population studies. Diabetes. 1993;42:250 – 6. 23. Lohman TG, Roche AF, Martorell R. Anthropometric Standardization Reference Manual. Champaign, IL: Human Kinetics Books; 1998. 24. Sumner AE, Farmer NM, Tulloch-Reid MK, et al. Sex differences in visceral adipose tissue volume among African Americans. Am J Clin Nutr. 2002;76:975–9. 25. Warnick GR, Benderson J, Albers JJ. Dextran sulfateMg2⫹ precipitation procedure for quantitation of high-densitylipoprotein cholesterol. Clin Chem. 1982;28:1379 – 88. 26. Otvos JD, Jeyarajah EJ, Bennett DW, Krauss RM. Development of a proton nuclear magnetic resonance spectroscopic method for determining plasma lipoprotein concentrations and subspecies distributions from a single, rapid measurement. Clin Chem. 1992;38:1632– 8. 27. Otvos JD. Measurement of lipoprotein subclass profiles by nuclear magnetic resonance spectroscopy. Clin Lab. 2002;48: 171– 80. 28. Olkin I. Correlation revisited. In: Stanely JC, ed. Improving Experimental Design and Statistical Analysis. Chicago, IL: Rand McNally; 1967.

29. Ross R, Aru J, Freeman J, Hudson R, Janssen I. Abdominal adiposity and insulin resistance in obese men. Am J Physiol Endocrinol Metab. 2002;282:E657– 63. 30. Ross R, Freeman J, Hudson R, Janssen I. Abdominal obesity, muscle composition, and insulin resistance in premenopausal women. J Clin Endocrinol Metab. 2002;87:5044 –51. 31. Cnop M, Landchild MJ, Vidal J, et al. 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. 2002;51:1005–15. 32. Banerji MA, Lebowitz J, Chaiken RL, Gordon D, Kral JG, Lebovitz HE. Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects. Am J Physiol. 1997;273:E425–32. 33. Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fujimoto WY. Visceral adiposity, fasting plasma insulin, and lipid and lipoprotein levels in Japanese Americans. Int J Obes Relat Metab Disord. 1996;20:801– 8. 34. DeNino WF, Tchernof A, Dionne IJ, et al. Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care. 2001;24:925–32. 35. Marcus MA, Murphy L, Pi-Sunyer FX, Albu JB. Insulin sensitivity and serum triglyceride level in obese white and black women: relationship to visceral and truncal subcutaneous fat. Metabolism. 1999;48:194 –9. 36. Pouliot MC, Despres JP, Nadeau A, et al. Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes. 1992;41:826 –34. 37. Kleinbaum DG, Kupper KL, Muller KE, Nizam A. Regression Diagnostics: Applied Regression Analysis and Multivariable Methods. Pacific Grove, CA: Duxbury Press; 1998, pp. 212– 80. 38. Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab. 2000;278: E941– 8.

OBESITY RESEARCH Vol. 12 No. 8 August 2004

1359