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. 1995 Jul;96(1):88–98. doi: 10.1172/JCI118083

Relationships of generalized and regional adiposity to insulin sensitivity in men.

N Abate 1, A Garg 1, R M Peshock 1, J Stray-Gundersen 1, S M Grundy 1
PMCID: PMC185176  PMID: 7615840

Abstract

The relative impacts of regional and generalized adiposity on insulin sensitivity have not been fully defined. Therefore, we investigated the relationship of insulin sensitivity (measured using hyperinsulinemic, euglycemic clamp technique with [3-3H]glucose turnover) to total body adiposity (determined by hydrodensitometry) and regional adiposity. The latter was assessed by determining subcutaneous abdominal, intraperitoneal, and retroperitoneal fat masses (using magnetic resonance imaging) and the sum of truncal and peripheral skinfold thicknesses. 39 healthy middle-aged men with a wide range of adiposity were studied. Overall, the intraperitoneal and retroperitoneal fat constituted only 11 and 7% of the total body fat. Glucose disposal rate (Rd) and residual hepatic glucose output (rHGO) values during the 40 mU/m2.min insulin infusion correlated significantly with total body fat (r = -0.61 and 0.50, respectively), subcutaneous abdominal fat (r = -0.62 and 0.50, respectively), sum of truncal skinfold thickness (r = -0.72 and 0.57, respectively), and intraperitoneal fat (r = -0.51 and 0.44, respectively) but not to retroperitoneal fat. After adjusting for total body fat, the Rd and rHGO values showed the highest correlation with the sum of truncal skinfold thickness (partial r = -0.40 and 0.33, respectively). We conclude that subcutaneous truncal fat plays a major role in obesity-related insulin resistance in men, whereas intraperitoneal fat and retroperitoneal fat have a lesser role.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abate N., Burns D., Peshock R. M., Garg A., Grundy S. M. Estimation of adipose tissue mass by magnetic resonance imaging: validation against dissection in human cadavers. J Lipid Res. 1994 Aug;35(8):1490–1496. [PubMed] [Google Scholar]
  2. Björntorp P. "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis. 1990 Jul-Aug;10(4):493–496. [PubMed] [Google Scholar]
  3. Björntorp P. Obesity and the risk of cardiovascular disease. Ann Clin Res. 1985;17(1):3–9. [PubMed] [Google Scholar]
  4. Bogardus C., Lillioja S., Mott D. M., Hollenbeck C., Reaven G. Relationship between degree of obesity and in vivo insulin action in man. Am J Physiol. 1985 Mar;248(3 Pt 1):E286–E291. doi: 10.1152/ajpendo.1985.248.3.E286. [DOI] [PubMed] [Google Scholar]
  5. Bogardus C., Lillioja S., Mott D., Reaven G. R., Kashiwagi A., Foley J. E. Relationship between obesity and maximal insulin-stimulated glucose uptake in vivo and in vitro in Pima Indians. J Clin Invest. 1984 Mar;73(3):800–805. doi: 10.1172/JCI111274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bogardus C., Ravussin E., Robbins D. C., Wolfe R. R., Horton E. S., Sims E. A. Effects of physical training and diet therapy on carbohydrate metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Diabetes. 1984 Apr;33(4):311–318. doi: 10.2337/diab.33.4.311. [DOI] [PubMed] [Google Scholar]
  7. Bouchard C., Després J. P., Mauriège P. Genetic and nongenetic determinants of regional fat distribution. Endocr Rev. 1993 Feb;14(1):72–93. doi: 10.1210/edrv-14-1-72. [DOI] [PubMed] [Google Scholar]
  8. Carlson L. A., Hallberg D., Micheli H. Quantitative studies on the lipolytic response of human subcutaneous and omental adipose tissue to noradrenaline and theophylline. Acta Med Scand. 1969 Jun;185(6):465–469. doi: 10.1111/j.0954-6820.1969.tb07368.x. [DOI] [PubMed] [Google Scholar]
  9. Casassus P., Fontbonne A., Thibult N., Ducimetière P., Richard J. L., Claude J. R., Warnet J. M., Rosselin G., Eschwège E. Upper-body fat distribution: a hyperinsulinemia-independent predictor of coronary heart disease mortality. The Paris Prospective Study. Arterioscler Thromb. 1992 Dec;12(12):1387–1392. doi: 10.1161/01.atv.12.12.1387. [DOI] [PubMed] [Google Scholar]
  10. Chapman J. M., Coulson A. H., Clark V. A., Borun E. R. The differential effect of serum cholesterol, blood pressure and weight on the incidence of myocardial infarction and angina pectoris. J Chronic Dis. 1971 Feb;23(9):631–645. doi: 10.1016/0021-9681(71)90159-7. [DOI] [PubMed] [Google Scholar]
  11. Chowdhury B., Sjöström L., Alpsten M., Kostanty J., Kvist H., Löfgren R. A multicompartment body composition technique based on computerized tomography. Int J Obes Relat Metab Disord. 1994 Apr;18(4):219–234. [PubMed] [Google Scholar]
  12. Crespin S. R., Greenough W. B., 3rd, Steinberg D. Stimulation of insulin secretion by long-chain free fatty acids. A direct pancreatic effect. J Clin Invest. 1973 Aug;52(8):1979–1984. doi: 10.1172/JCI107382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DOLE V. P. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150–154. doi: 10.1172/JCI103259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. DeFronzo R. A., Tobin J. D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214–E223. doi: 10.1152/ajpendo.1979.237.3.E214. [DOI] [PubMed] [Google Scholar]
  15. Després J. P., Moorjani S., Ferland M., Tremblay A., Lupien P. J., Nadeau A., Pinault S., Thériault G., Bouchard C. Adipose tissue distribution and plasma lipoprotein levels in obese women. Importance of intra-abdominal fat. Arteriosclerosis. 1989 Mar-Apr;9(2):203–210. doi: 10.1161/01.atv.9.2.203. [DOI] [PubMed] [Google Scholar]
  16. Després J. P., Moorjani S., Lupien P. J., Tremblay A., Nadeau A., Bouchard C. Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. Arteriosclerosis. 1990 Jul-Aug;10(4):497–511. doi: 10.1161/01.atv.10.4.497. [DOI] [PubMed] [Google Scholar]
  17. Donahue R. P., Abbott R. D., Bloom E., Reed D. M., Yano K. Central obesity and coronary heart disease in men. Lancet. 1987 Apr 11;1(8537):821–824. doi: 10.1016/s0140-6736(87)91605-9. [DOI] [PubMed] [Google Scholar]
  18. Ducimetiere P., Richard J., Cambien F. The pattern of subcutaneous fat distribution in middle-aged men and the risk of coronary heart disease: the Paris Prospective Study. Int J Obes. 1986;10(3):229–240. [PubMed] [Google Scholar]
  19. Efendić S. Catecholamines and metabolism of human adipose tissue. 3. Comparison between the regulation of lipolysis in omental and subcutaneous adipose tissue. Acta Med Scand. 1970 Jun;187(6):477–483. [PubMed] [Google Scholar]
  20. Evans D. J., Hoffmann R. G., Kalkhoff R. K., Kissebah A. H. Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women. Metabolism. 1984 Jan;33(1):68–75. doi: 10.1016/0026-0495(84)90164-1. [DOI] [PubMed] [Google Scholar]
  21. Evans D. J., Murray R., Kissebah A. H. Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography. J Clin Invest. 1984 Oct;74(4):1515–1525. doi: 10.1172/JCI111565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ferrannini E., Barrett E. J., Bevilacqua S., DeFronzo R. A. Effect of fatty acids on glucose production and utilization in man. J Clin Invest. 1983 Nov;72(5):1737–1747. doi: 10.1172/JCI111133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ferrannini E., Haffner S. M., Mitchell B. D., Stern M. P. Hyperinsulinaemia: the key feature of a cardiovascular and metabolic syndrome. Diabetologia. 1991 Jun;34(6):416–422. doi: 10.1007/BF00403180. [DOI] [PubMed] [Google Scholar]
  24. Finegood D. T., Bergman R. N., Vranic M. Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates. Diabetes. 1987 Aug;36(8):914–924. doi: 10.2337/diab.36.8.914. [DOI] [PubMed] [Google Scholar]
  25. Fujioka S., Matsuzawa Y., Tokunaga K., Tarui S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism. 1987 Jan;36(1):54–59. doi: 10.1016/0026-0495(87)90063-1. [DOI] [PubMed] [Google Scholar]
  26. Golay A., Felber J. P., Meyer H. U., Curchod B., Maeder E., Jéquier E. Study on lipid metabolism in obesity diabetes. Metabolism. 1984 Feb;33(2):111–116. doi: 10.1016/0026-0495(84)90121-5. [DOI] [PubMed] [Google Scholar]
  27. Golay A., Swislocki A. L., Chen Y. D., Jaspan J. B., Reaven G. M. Effect of obesity on ambient plasma glucose, free fatty acid, insulin, growth hormone, and glucagon concentrations. J Clin Endocrinol Metab. 1986 Aug;63(2):481–484. doi: 10.1210/jcem-63-2-481. [DOI] [PubMed] [Google Scholar]
  28. Gordon T., Kannel W. B. The effects of overweight on cardiovascular diseases. Geriatrics. 1973 Aug;28(8):80–88. [PubMed] [Google Scholar]
  29. Haffner S. M., Stern M. P., Hazuda H. P., Pugh J., Patterson J. K. Do upper-body and centralized adiposity measure different aspects of regional body-fat distribution? Relationship to non-insulin-dependent diabetes mellitus, lipids, and lipoproteins. Diabetes. 1987 Jan;36(1):43–51. doi: 10.2337/diab.36.1.43. [DOI] [PubMed] [Google Scholar]
  30. Haffner S. M., Stern M. P., Mitchell B. D., Hazuda H. P., Patterson J. K. Incidence of type II diabetes in Mexican Americans predicted by fasting insulin and glucose levels, obesity, and body-fat distribution. Diabetes. 1990 Mar;39(3):283–288. doi: 10.2337/diab.39.3.283. [DOI] [PubMed] [Google Scholar]
  31. Hartz A. J., Rupley D. C., Rimm A. A. The association of girth measurements with disease in 32,856 women. Am J Epidemiol. 1984 Jan;119(1):71–80. doi: 10.1093/oxfordjournals.aje.a113727. [DOI] [PubMed] [Google Scholar]
  32. Herbert V., Lau K. S., Gottlieb C. W., Bleicher S. J. Coated charcoal immunoassay of insulin. J Clin Endocrinol Metab. 1965 Oct;25(10):1375–1384. doi: 10.1210/jcem-25-10-1375. [DOI] [PubMed] [Google Scholar]
  33. Hubert H. B., Feinleib M., McNamara P. M., Castelli W. P. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983 May;67(5):968–977. doi: 10.1161/01.cir.67.5.968. [DOI] [PubMed] [Google Scholar]
  34. Insel P. A., Liljenquist J. E., Tobin J. D., Sherwin R. S., Watkins P., Andres R., Berman M. Insulin control of glucose metabolism in man: a new kinetic analysis. J Clin Invest. 1975 May;55(5):1057–1066. doi: 10.1172/JCI108006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Jensen M. D., Haymond M. W., Rizza R. A., Cryer P. E., Miles J. M. Influence of body fat distribution on free fatty acid metabolism in obesity. J Clin Invest. 1989 Apr;83(4):1168–1173. doi: 10.1172/JCI113997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kissebah A. H., Vydelingum N., Murray R., Evans D. J., Hartz A. J., Kalkhoff R. K., Adams P. W. Relation of body fat distribution to metabolic complications of obesity. J Clin Endocrinol Metab. 1982 Feb;54(2):254–260. doi: 10.1210/jcem-54-2-254. [DOI] [PubMed] [Google Scholar]
  37. Knowler W. C., Pettitt D. J., Savage P. J., Bennett P. H. Diabetes incidence in Pima indians: contributions of obesity and parental diabetes. Am J Epidemiol. 1981 Feb;113(2):144–156. doi: 10.1093/oxfordjournals.aje.a113079. [DOI] [PubMed] [Google Scholar]
  38. Koester R. S., Hunter G. R., Snyder S., Khaled M. A., Berland L. L. Estimation of computerized tomography derived abdominal fat distribution. Int J Obes Relat Metab Disord. 1992 Aug;16(8):543–554. [PubMed] [Google Scholar]
  39. Kohrt W. M., Kirwan J. P., Staten M. A., Bourey R. E., King D. S., Holloszy J. O. Insulin resistance in aging is related to abdominal obesity. Diabetes. 1993 Feb;42(2):273–281. [PubMed] [Google Scholar]
  40. Krotkiewski M., Björntorp P., Sjöström L., Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983 Sep;72(3):1150–1162. doi: 10.1172/JCI111040. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lafontan M., Dang-Tran L., Berlan M. Alpha-adrenergic antilipolytic effect of adrenaline in human fat cells of the thigh: comparison with adrenaline responsiveness of different fat deposits. Eur J Clin Invest. 1979 Aug;9(4):261–266. doi: 10.1111/j.1365-2362.1979.tb00883.x. [DOI] [PubMed] [Google Scholar]
  42. Landin K., Lönnroth P., Krotkiewski M., Holm G., Smith U. Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio. Eur J Clin Invest. 1990 Oct;20(5):530–535. doi: 10.1111/j.1365-2362.1990.tb01897.x. [DOI] [PubMed] [Google Scholar]
  43. Landin K., Lönnroth P., Krotkiewski M., Holm G., Smith U. Increased insulin resistance and fat cell lipolysis in obese but not lean women with a high waist/hip ratio. Eur J Clin Invest. 1990 Oct;20(5):530–535. doi: 10.1111/j.1365-2362.1990.tb01897.x. [DOI] [PubMed] [Google Scholar]
  44. Lapidus L., Bengtsson C., Larsson B., Pennert K., Rybo E., Sjöström L. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12 year follow up of participants in the population study of women in Gothenburg, Sweden. Br Med J (Clin Res Ed) 1984 Nov 10;289(6454):1257–1261. doi: 10.1136/bmj.289.6454.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Larsson B., Seidell J., Svärdsudd K., Welin L., Tibblin G., Wilhelmsen L., Björntorp P. Obesity, adipose tissue distribution and health in men--the study of men born in 1913. Appetite. 1989 Aug;13(1):37–44. doi: 10.1016/0195-6663(89)90025-1. [DOI] [PubMed] [Google Scholar]
  46. Lillioja S., Mott D. M., Zawadzki J. K., Young A. A., Abbott W. G., Knowler W. C., Bennett P. H., Moll P., Bogardus C. In vivo insulin action is familial characteristic in nondiabetic Pima Indians. Diabetes. 1987 Nov;36(11):1329–1335. doi: 10.2337/diab.36.11.1329. [DOI] [PubMed] [Google Scholar]
  47. Manson J. E., Colditz G. A., Stampfer M. J., Willett W. C., Rosner B., Monson R. R., Speizer F. E., Hennekens C. H. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990 Mar 29;322(13):882–889. doi: 10.1056/NEJM199003293221303. [DOI] [PubMed] [Google Scholar]
  48. Meneilly G. S., Elahi D., Minaker K. L., Rowe J. W. Somatostatin does not alter insulin-mediated glucose disposal. J Clin Endocrinol Metab. 1987 Aug;65(2):364–367. doi: 10.1210/jcem-65-2-364. [DOI] [PubMed] [Google Scholar]
  49. Mårin P., Andersson B., Ottosson M., Olbe L., Chowdhury B., Kvist H., Holm G., Sjöström L., Björntorp P. The morphology and metabolism of intraabdominal adipose tissue in men. Metabolism. 1992 Nov;41(11):1242–1248. doi: 10.1016/0026-0495(92)90016-4. [DOI] [PubMed] [Google Scholar]
  50. OPIE L. H., WALFISH P. G. Plasma free fatty acid concentrations in obesity. N Engl J Med. 1963 Apr 4;268:757–760. doi: 10.1056/NEJM196304042681404. [DOI] [PubMed] [Google Scholar]
  51. Ohlson L. O., Larsson B., Svärdsudd K., Welin L., Eriksson H., Wilhelmsen L., Björntorp P., Tibblin G. The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985 Oct;34(10):1055–1058. doi: 10.2337/diab.34.10.1055. [DOI] [PubMed] [Google Scholar]
  52. Ostman J., Arner P., Engfeldt P., Kager L. Regional differences in the control of lipolysis in human adipose tissue. Metabolism. 1979 Dec;28(12):1198–1205. doi: 10.1016/0026-0495(79)90131-8. [DOI] [PubMed] [Google Scholar]
  53. RANDLE P. J., GARLAND P. B., HALES C. N., NEWSHOLME E. A. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. doi: 10.1016/s0140-6736(63)91500-9. [DOI] [PubMed] [Google Scholar]
  54. Rebuffé-Scrive M., Anderson B., Olbe L., Björntorp P. Metabolism of adipose tissue in intraabdominal depots in severely obese men and women. Metabolism. 1990 Oct;39(10):1021–1025. doi: 10.1016/0026-0495(90)90160-e. [DOI] [PubMed] [Google Scholar]
  55. Rebuffé-Scrive M., Andersson B., Olbe L., Björntorp P. Metabolism of adipose tissue in intraabdominal depots of nonobese men and women. Metabolism. 1989 May;38(5):453–458. doi: 10.1016/0026-0495(89)90198-4. [DOI] [PubMed] [Google Scholar]
  56. Rebuffé-Scrive M., Enk L., Crona N., Lönnroth P., Abrahamsson L., Smith U., Björntorp P. Fat cell metabolism in different regions in women. Effect of menstrual cycle, pregnancy, and lactation. J Clin Invest. 1985 Jun;75(6):1973–1976. doi: 10.1172/JCI111914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Richelsen B., Pedersen S. B., Møller-Pedersen T., Bak J. F. Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2. Metabolism. 1991 Sep;40(9):990–996. doi: 10.1016/0026-0495(91)90078-b. [DOI] [PubMed] [Google Scholar]
  58. Ross R., Shaw K. D., Rissanen J., Martel Y., de Guise J., Avruch L. Sex differences in lean and adipose tissue distribution by magnetic resonance imaging: anthropometric relationships. Am J Clin Nutr. 1994 Jun;59(6):1277–1285. doi: 10.1093/ajcn/59.6.1277. [DOI] [PubMed] [Google Scholar]
  59. STEELE R. Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci. 1959 Sep 25;82:420–430. doi: 10.1111/j.1749-6632.1959.tb44923.x. [DOI] [PubMed] [Google Scholar]
  60. Sato Y., Iguchi A., Sakamoto N. Biochemical determination of training effects using insulin clamp technique. Horm Metab Res. 1984 Sep;16(9):483–486. doi: 10.1055/s-2007-1014825. [DOI] [PubMed] [Google Scholar]
  61. Sparrow D., Borkan G. A., Gerzof S. G., Wisniewski C., Silbert C. K. Relationship of fat distribution to glucose tolerance. Results of computed tomography in male participants of the Normative Aging Study. Diabetes. 1986 Apr;35(4):411–415. doi: 10.2337/diab.35.4.411. [DOI] [PubMed] [Google Scholar]
  62. Svedberg J., Strömblad G., Wirth A., Smith U., Björntorp P. Fatty acids in the portal vein of the rat regulate hepatic insulin clearance. J Clin Invest. 1991 Dec;88(6):2054–2058. doi: 10.1172/JCI115534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. THOMAS L. W. The chemical composition of adipose tissue of man and mice. Q J Exp Physiol Cogn Med Sci. 1962 Apr;47:179–188. doi: 10.1113/expphysiol.1962.sp001589. [DOI] [PubMed] [Google Scholar]
  64. VAGUE J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout, and uric calculous disease. Am J Clin Nutr. 1956 Jan-Feb;4(1):20–34. doi: 10.1093/ajcn/4.1.20. [DOI] [PubMed] [Google Scholar]
  65. Van Itallie T. B. Health implications of overweight and obesity in the United States. Ann Intern Med. 1985 Dec;103(6 ):983–988. doi: 10.7326/0003-4819-103-6-983. [DOI] [PubMed] [Google Scholar]
  66. Welin L., Svärdsudd K., Wilhelmsen L., Larsson B., Tibblin G. Analysis of risk factors for stroke in a cohort of men born in 1913. N Engl J Med. 1987 Aug 27;317(9):521–526. doi: 10.1056/NEJM198708273170901. [DOI] [PubMed] [Google Scholar]
  67. Westlund K., Nicolaysen R. Ten-year mortality and morbidity related to serum cholesterol. A follow-up of 3.751 men aged 40-49. Scand J Clin Lab Invest Suppl. 1972;127:1–24. [PubMed] [Google Scholar]
  68. YALOW R. S., BERSON S. A. Immunoassay of endogenous plasma insulin in man. J Clin Invest. 1960 Jul;39:1157–1175. doi: 10.1172/JCI104130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Zavaroni I., Bonora E., Pagliara M., Dall'Aglio E., Luchetti L., Buonanno G., Bonati P. A., Bergonzani M., Gnudi L., Passeri M. Risk factors for coronary artery disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med. 1989 Mar 16;320(11):702–706. doi: 10.1056/NEJM198903163201105. [DOI] [PubMed] [Google Scholar]
  70. van der Kooy K., Leenen R., Seidell J. C., Deurenberg P., Droop A., Bakker C. J. Waist-hip ratio is a poor predictor of changes in visceral fat. Am J Clin Nutr. 1993 Mar;57(3):327–333. doi: 10.1093/ajcn/57.3.327. [DOI] [PubMed] [Google Scholar]

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