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Gender Differences of Regional Abdominal Fat Distribution and Their Relationships with Insulin Sensitivity in Healthy and Glucose-Intolerant Thais

Division of Endocrinology and Metabolism, Department of Medicine, Prince of Songkhla University, Hadyai, Songkhla 90110 Thailand

Address all correspondence and requests for reprints to: Chatchalit Rattarasarn, M.D., Division of Endocrinology and Metabolism, Department of Medicine, Prince of Songkhla University, Hadyai, Songkhla 90110, Thailand. E-mail: rchatcha{at}medicine.psu.ac.th.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
To determine gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais, 44 subjects, 22 men and 22 body mass index-matched women, with normal and abnormal glucose tolerance, which included subjects with impaired glucose tolerance and diabetes, were studied. Total body fat and total abdominal fat (TAF) at L₁-L₄ were measured by dual-energy x-ray absorptiometry. Regional abdominal fat, which consists of sc abdominal fat and visceral abdominal fat, was determined by single-slice computerized tomography of the abdomen at L₄-L₅ disc space level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp and expressed as glucose infusion rate (GIR). With comparable body mass index, visceral abdominal fat was most strongly correlated with GIR after adjustment with percent total body fat in both healthy (r = –0.8155; P = 0.007) and glucose-intolerant women (r = –0.7597; P = 0.011), whereas TAF was most strongly correlated with GIR in both healthy (r = –0.8114; P = 0.008) and glucose-intolerant men (r = –0.6194; P = 0.101). By linear regression analysis, visceral abdominal fat accounted for 35.0% (ß = –3.53 x 10^–2; P = 0.001) of GIR variance in women, whereas TAF accounted for 39.3% (ß = –1.28 x 10^–4; P < 0.0001) of GIR variance in men. We conclude that there are gender differences in the relationships of regional abdominal fat and insulin sensitivity in slightly obese healthy and glucose-intolerant Thais, the difference of which may possibly be in part due to the difference of abdominal fat patterning between genders.

	Introduction

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IT IS WELL KNOWN that there are ethnic and gender differences in body fat amount and its distribution. Data from most Caucasian populations indicate that men have less body fat and a greater amount of abdominal fat than women of the same body mass index (BMI), and abdominal fat, particularly visceral or intraabdominal fat, is the strong negative predictor of insulin sensitivity in both genders. The accumulation of visceral abdominal fat is associated with not only the increase risk of diabetes but also several cardiovascular risk factors in both those with and without diabetes.

However, the anthropometric data comparing body fat distribution between Asian (mostly Chinese) and Caucasian populations demonstrate that Asians have a greater amount of total body fat as well as sc abdominal fat than Caucasians (1). Therefore, it is possible that body fat distribution and its relationships with insulin sensitivity in Asians may differ from those of Caucasians. The study of gender differences of body fat distribution and insulin sensitivity in Asians by using standard tools of measurement has not been well determined. Our study in nonobese, nondiabetic Thais indicates that nonobese men have less total body fat (TBF) and greater proportion of abdominal fat than nonobese women, and TBF, but not abdominal fat, is most strongly associated with insulin sensitivity in nonobese subjects (2). However, the study in nonobese and obese type 2 diabetic Thai women demonstrates the strong negative association of visceral abdominal fat and insulin sensitivity (3). Whether such associations of visceral abdominal fat (VAF) and insulin sensitivity could be demonstrated in diabetic Thai men and obese, nondiabetics are unknown. The objectives of this study were to determine gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in generally obese healthy and glucose-intolerant Thai subjects.

	Subjects and Methods

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Twenty-two women, 11 healthy and 11 glucose-intolerant subjects, with respective mean age 38.8 ± 8.9 (SD) and 41.5 ± 5.2 yr and mean BMI 26.6 ± 3.6 and 27.0 ± 4.0 kg/m², and 22 BMI-matched men, 11 healthy and 11 glucose-intolerant subjects with respective mean age 41.4 ± 7.1 and 48.4 ± 6.2 yr and mean BMI 26.4 ± 1.8 and 27.6 ± 2.9 kg/m², were studied. Glucose-intolerant subjects included patients with known and newly diagnosed type 2 diabetes by oral glucose tolerance test as well as impaired glucose-tolerant subjects. Of 22 glucose-intolerant subjects, 12 (four women, eight men) had impaired glucose tolerance. Healthy subjects were defined as having normal glucose tolerance and no known underlying chronic medical illnesses.

All subjects gave written informed consent before the beginning of the study. The study was reviewed and approved by Prince of Songkhla University Hospital Ethics Committee.

Body composition measurements

TBF and total abdominal fat (TAF) at L₁-L₄ level were measured by dual-energy x-ray absorptiometry (version 4.7, DPX-MD Lunar Corp., Madison, WI) software. TBF was calculated by standard software, whereas TAF measurement was undertaken by manually defining the area of measurement from the top of L₁ to the bottom of L₄. The measurement of TAF was performed by the same operator (R.L.), three times for each subject, the mean value of which was used for the study. The respective coefficients of variation (CVs) of TBF and TAF measurements were 3.3 and less than 2.0%.

Subcutaneous abdominal fat (SAF) and VAF areas were determined by single-slice computerized tomography (CT) scan (Tomoscan AV, Philips, Best, The Netherlands) of the abdomen at the L₄-L₅ disk space level. Scanning was performed at 120 kV. Fat tissue density was determined according to flexible attenuation ranges derived from sc fat density of each individual. SAF area was determined by subtracting the non-sc fat from TAF area. Non-sc fat was defined as intraabdominal and retroperitoneal fat, including the abdominal wall muscles, paraspinal muscles, and vertebral column. VAF area was defined as intraabdominal fat area bound by parietal peritoneum excluding the vertebral column and the paraspinal muscles. The retroperitoneum fat was included in VAF measurement. The measurements of SAF and VAF were performed by the same operator as in TAF measurement, three times in each subject, and the mean value was used for the study. The intraobserver CV of the measurements were less than 3.0%.

Euglycemic hyperinsulinemic clamp

Intravenous catheters were retained in an antecubital vein for infusion of insulin and glucose and in a contralateral dorsal hand vein for blood sampling. A prime continuous infusion of regular insulin (Actrapid HM; Novo Nordisk, Copenhagen, Denmark) was given at a rate of 50 mU/m² body surface area per minute from 0 to 120 min together with 20% dextrose solution to maintain plasma glucose at the level of 90 mg/dl (5 mmol/liter) throughout the clamp period. Blood samples were obtained every 5 min from the hand vein kept in a thermoregulated box at 55–60 C for determination of arterialized plasma glucose. Plasma glucose was measured by the glucose oxidase method (Synchron CX-3 Delta; Beckman Coulter, Fullerton, CA) with interassay CV of 0.9–2.3%. Insulin sensitivity was determined from the glucose infusion rate (GIR) during the last 40 min of the clamp and expressed as milligrams of glucose per kilogram body weight per minute.

Statistical analysis

The unpaired Student’s t test was used for mean comparison. Data that were not normally distributed were log transformed before analysis. Correlation coefficients were determined by Pearson’s product moment. Multiple linear regression analysis was performed to identify the independent contribution of body fat depot to variances of insulin sensitivity in each gender. All statistical analyses were performed using SPSS for Windows (version 9, SPSS Inc., Chicago, IL). P < 0.05 was considered statistically significant.

	Results

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Differences of regional abdominal fat and insulin sensitivity between genders in healthy and glucose-intolerant subjects were shown in Table 1. With comparable BMI, there were no differences of the amount and percent of TBF and TAF between healthy and glucose-intolerant subjects in both women and men. As shown in Table 1, the greater ratio of VAF/SAF in glucose-intolerant women and the greater areas of SAF combined with VAF in glucose-intolerant men were the only differences observed between healthy and glucose-intolerant subjects. Although VAF areas per se were larger in glucose-intolerant subjects than healthy control of both genders, but they did not reach statistically significant differences. TAF measured by dual-energy x-ray absorptiometry was correlated well with areas of SAF combined with VAF measured by CT scan in healthy (r = 0.892; P = 0.001) and glucose-intolerant (r = 0.896; P < 0.0001) women as well as men (r = 0.76; P = 0.011 and r = 0.819; P = 0.007, respectively). GIR was significantly lower in glucose-intolerant subjects in both women and men. When the regional abdominal fat distribution was examined across genders after adjustment with the differences in percent TBF, it was found that healthy men had greater amount of TAF (P = 0.001), larger areas of VAF (P < 0.0001), and greater VAF to SAF ratio (P = 0.001) than healthy women, whereas glucose-intolerant men had greater amount of TAF (P < 0.0001), larger areas of VAF (P = 0.007), SAF (P = 0.011), and combined SAF and VAF (P = 0.003) than glucose-intolerant women. The latter differences still persisted after further adjusting with age, which was significantly greater in glucose-intolerant men. SAF areas of healthy men were greater than those of healthy women, but the difference was not statistically significant.

View larger version (10K): [in this window] [in a new window]   FIG. 1. Relationships between insulin sensitivity and TAF in healthy () (unadjusted r = –0.908) and glucose-intolerant (•) (unadjusted r = –0.560) men and between insulin sensitivity and VAF in healthy () (unadjusted r = –0.596) and glucose-intolerant () (unadjusted r = –0.664) women. To convert glucose to millimoles per liter, divide by 18.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

The studies of the relationship of regional abdominal fat and insulin sensitivity, mostly from Caucasian population, indicate VAF as the major predictor of insulin sensitivity in both obese nondiabetic and diabetic subjects (4, 5, 6, 7), although some studies disagree with those findings. Goodpaster et al. (8) reported that SAF had as strong an association with insulin sensitivity as VAF in nondiabetic men and women. Abate et al. (9) reported a stronger association of SAF and insulin sensitivity than that VAF in diabetic men. Whether such a relationship is different between genders in that study is unknown. It appears that SAF, if any, has been shown to be associated with insulin sensitivity only in men, particularly those of diabetic subjects (9, 10, 11, 12). The discrepancy of those study results with ours may be due to the differences in population ethnic and methodology employed.

This study, to our knowledge, is the first study in an Asian population in which the differences in the relationships of regional abdominal fat and insulin sensitivity are explored in BMI-matched men and women with normal and abnormal glucose tolerance. The poor relationship of VAF and insulin sensitivity in men in this study is in contrast with other studies previously reported. Despite similar methods of abdominal fat and insulin sensitivity measurement, why the relationships of regional abdominal fat and insulin sensitivity in Thai men differ from several others is uncertain. It should be noted that although SAF or VAF per se had poorer correlation with insulin sensitivity than TAF as a whole in men, such a correlation of VAF was stronger than that of SAF, particularly in glucose-intolerant subjects (Table 2); therefore, VAF might be the major abdominal fat depot that determines insulin sensitivity in men. It is possible that the relationship of VAF and insulin sensitivity in men could have been demonstrated if the larger number of subjects were included. The intrasubject variability of VAF distribution measured by single-slice CT abdomen may also contribute. Multislice CT abdomen has been shown to be more precise than single-slice CT for determination of total VAF volume (13, 14). However, Borkan et al. (15) reported that intraabdominal fat from single-slice CT at umbilical level (approximately at L₄ level as in our study), compared with other sites, was closest to the mean of intraabdominal fat measured by multislice CT in men. This is consistent with the study by Greenfield et al. (13) in premenopausal women. Therefore, VAF in this study more or less represents total VAF better than other sites. Furthermore, given the demonstration of the strong relationship of VAF and insulin sensitivity in women with as small number of subjects as in men, it therefore indicates that VAF per se has a less important role as the determinant of insulin sensitivity in Thai men.

One of the things that our study differs from the others is the inclusion of TAF measurement by dual-energy x-ray absorptiometry in addition to the measurements of SAF and VAF by CT scan. Several studies in which the relationship of VAF and insulin sensitivity could be demonstrated did not include TAF as the body fat composition in their studies. This study agrees with and supports the study by Bavenholm et al. (12) in Swedish men that with similar amount of total fat mass, glucose-intolerant men have greater truncal fat mass than healthy men, the difference of which is due to the greater accumulation of both SAF and VAF in the former. As in this study, truncal fat mass measured by dual-energy x-ray absorptiometry correlated best with insulin sensitivity in both healthy and glucose-intolerant men in Bavenholm’s study. Nevertheless, the result of this study disagrees with the study by Park et al. (16), who demonstrated the association of VAF and insulin sensitivity in healthy young Korean men. Of note, TAF was not measured in that study. This study also demonstrated that glucose-intolerant men had larger areas of SAF than glucose-intolerant women, even though the TBF of glucose-intolerant men was smaller and this finding could not be observed in healthy subjects. Taken together, this may indirectly indicate that the increase in SAF in addition to VAF mass may in part contribute to the increase of insulin resistance in glucose-intolerant men in this study. This study was in contrast with our previous study in lean, healthy Thai subjects (2), in which the correlation of TAF and GIR could not be demonstrated. This is likely due to much less amounts of TAF in lean subjects.

The ethnic difference of abdominal fat patterning between Asians and Caucasians may possibly in part explain the discrepancy of the relationship of abdominal fat and insulin sensitivity between our study and the others. Healthy Asians appear to have larger truncal fat than those of Caucasians particularly in men (1, 17, 18), and this difference is observed from the prepubertal period (19). SAF, at least in healthy Caucasians, has been shown in vitro to have not only larger capacity for but also greater response to lipolysis than sc fat of the other sites including VAF (20, 21). The mobilization of free fatty acid from fat depot would induce the increase in gluconeogenesis, impair insulin action, and increase lipoprotein synthesis. Therefore, our finding of the increases of TAF in both healthy and glucose-intolerant men and its association with the decrease in insulin sensitivity is logical. However, it is intriguing why, despite larger VAF in men than women, the relationship of VAF and insulin sensitivity could not be demonstrated in men in this study. Although the in vivo study demonstrates that the contribution of visceral lipolysis to hepatic free fatty acid delivery is greater in relation to visceral fat in women than men (22), but this is in contrast with the in vitro lipolysis study in which VAF of obese men is shown to be more sensitive to catecholamine-induced lipolysis than that of obese women (23). Whether there is the ethnic difference of the adipose tissue sensitivity to catecholamine-induced lipolysis is unanswered. Recently, Kanaya et al. (24) reported a gender difference of VAF effect on diabetes prevalence in elderly subjects. They found that, after adjusting for BMI, VAF in women was more strongly associated with diabetes than that of men (odds ratio 3.0 vs. 1.3), although men had larger VAF (by single-slice CT abdomen at L_4–5) than women. Because diabetes (type 2 diabetes) is strongly associated with insulin resistance, it may indirectly indicate that VAF in women, by uncertain mechanism, has greater effect on insulin resistance than men VAF.

In conclusion, this study demonstrates that there are gender differences in the relationships of regional abdominal fat and insulin sensitivity in slightly obese healthy and glucose-intolerant Thais. VAF is most strongly correlated with and best predicts insulin sensitivity in both healthy and glucose-intolerant women, whereas TAF does so in men.

	Footnotes

 
This work was supported in part by a research fund from the Faculty of Medicine, Prince of Songkhla University.

Abbreviations: BMI, Body mass index; CT, computerized tomography; CV, coefficient of variation; GIR, glucose infusion rate; SAF, sc abdominal fat; TAF, total abdominal fat; TBF, total body fat; VAF, visceral abdominal fat.

Received February 6, 2004.

Accepted September 14, 2004.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Wang J, Thornton JC, Russell M, Burastero S, Heymsfield S, Pierson RN 1994 Asians have lower body mass index (BMI) but higher percent body fat than do whites: comparisons of anthropometric measurements. Am J Clin Nutr 60:23–28[Abstract/Free Full Text]
2. Rattarasarn C, Leelawattana R, Soonthornpun S, Setasuban W, Thamprasit A, Lim A, Chayanunnukul W, Thamkumpee N 2003 Relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai men and women. Diabetes Res Clin Pract 60:87–94[CrossRef][Medline]
3. Rattarasarn C, Leelawattana R, Soonthornpun S, Setasuban W, Thamprasit A, Lim A, Chayanunnukul W, Thamkumpee N, Daendumrongsub T 2003 Regional abdominal fat distribution in lean and obese Thai type 2 diabetic women: relationships with insulin sensitivity and cardiovascular risk factors. Metabolism 52:1444–1447[CrossRef][Medline]
4. Bonora E, Del Prato S, Bonadonna RC, Gulli G, Solini A, Shank ML, Ghiatas AA, Lancaster JL, Kilcoyne RF, Alyassin AM, DeFronzo RA 1992 Total body fat content and fat topography are associated differently with in vivo glucose metabolism in nonobese and obese nondiabetic women. Diabetes 41:1151–1159[Abstract]
5. Banerji MA, Chaiken RL, Gordon D, Kral JG, Lebovitz HE 1995 Does intra-abdominal adipose tissue in black men determine whether NIDDM is insulin-resistant or insulin-sensitive? Diabetes 44:141–146[Abstract]
6. Lovejoy JC, de la Bretonne JA, Klemperer M, Tulley R 1996 Abdominal fat distribution and metabolic risk factors: effects of race. Metabolism 45:1119–1124[CrossRef][Medline]
7. Albu JB, Murphy L, Frager DH, Johnson JA, Pi-Sunyer FX 1997 Visceral fat and race-dependent health risks in obese nondiabetic premenopausal women. Diabetes 46:456–462[Abstract]
8. Goodpaster BH, Thaete FL, Simoneau J-A, Kelly DE 1997 Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 46:1579–1585[Abstract]
9. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Adams-Huet B, Grundy SM 1996 Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. Diabetes 45:1684–1693[Abstract]
10. Banerji MA, Lebovitz J, Chaiken RL, Gordon D, Kral JG, Lebovitz HE 1997 Relationship of visceral adipose tissue and glucose disposal is independent of sex in black NIDDM subjects. Am J Physiol 273:E 425–E432
11. Miyazaki Y, Glass L, Triplitt C, Wajcberg E, Mandarino LJ, DeFronzo RA 2002 Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 283:E1135–E1143
12. Bavenholm PN, Kuhl J, Pigon J, Saha AK, Ruderman NB, Efendic S 2003 Insulin resistance in type 2 diabetes: association with truncal obesity, impaired fitness, and atypical malonyl coenzyme A regulation. J Clin Endocrinol Metab 88:82–87[Abstract/Free Full Text]
13. Greenfield JR, Samaras K, Chisholm DJ, Campbell LV 2002 Regional intra-subject variability in abdominal adiposity limits usefulness of computer tomography. Obes Res 10:260–265[Medline]
14. Jensen MD, Kanaley JA, Reed JE, Sheedy PF 1995 Measurement of abdominal and visceral fat with computed tomography and dual energy X-ray absorptiometry. Am J Clin Nutr 61:274–278[Abstract/Free Full Text]
15. Borkan GA, Gerzof SG, Robbins AH, Hults DE, Silbert CK, Silbert JE 1982 Assessment of abdominal fat content by computerized tomography. Am J Clin Nutr 36:172–177[Abstract/Free Full Text]
16. Park KS, Rhee BD, Lee K-U, Kim SY, Lee HK, Koh C-S, Min HK 1991 Intra-abdominal fat is associated with decreased insulin sensitivity in healthy young men. Metabolism 40:600–603[CrossRef][Medline]
17. Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy S 1999 Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab 84:2329–2335[Abstract/Free Full Text]
18. Raji A, Seely EW, Arky RA, Simonson DC 2001 Body fat distribution and insulin resistance in healthy Asian Indians and Caucasians. J Clin Endocrinol Metab 86:5366–5371[Abstract/Free Full Text]
19. He Q, Horlick M, Thornton J, Wang J, Pierson RN, Heshka S, Gallagher D 2002 Sex and race differences in fat distribution among Asian, African-American, and Caucasian prepubertal children. J Clin Endocrinol Metab 87:2164–2170[Abstract/Free Full Text]
20. Jansson P-A, Smith U, Lonnroth P 1990 Interstitial glyceral concentration measured by microdialysis in two subcutaneous regions in humans. Am J Physiol 258:E918–E922
21. Reynisdottir S, Dauzats M, Thorne A, Langin D 1997 Comparison of hormone-sensitive lipase activity in visceral and subcutaneous human adipose tissue. J Clin Endocrinol Metab 82:4162–4166[Abstract/Free Full Text]
22. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD 2004 Splanchnic lipolysis in human obesity. J Clin Invest 113:1582–1588[CrossRef][Medline]
23. Lonnqvist F, Thorne A, Large V, Arner P 1997 Sex differences in visceral fat lipolysis and metabolic complications of obesity. Arterioscler Thromb Vasc Biol 17:1472–1480[Abstract/Free Full Text]
24. Kanaya AM, Harris T, Goodpaster BH, Tylavsky F, Cummings SR, for the Health, Aging, and Body Composition (ABC) Study 2004 Adipocytokines attenuate the association between visceral adiposity and diabetes in older adults. Diabetes Care 27:1375–1380[Abstract/Free Full Text]

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