© 1997 American Heart Association, Inc.
Articles |
Differences in Insulin Suppression of Free Fatty Acid Levels by Gender and Glucose Tolerance Status
Relation to Plasma Triglyceride and Apolipoprotein B Concentrations
the Department of Medicine (A.L.), Stanford University, Stanford, Calif; the Department of Public Health Sciences (H.M.H), Bowman Gray School of Medicine, Winston-Salem, NC; the Medlantic Research Institute (B.V.H.), Washington, DC; the Division of Research (J.V.S.), Kaiser Permanente, Oakland, Calif; the Department of Medicine (S.M.H.), University of Texas Health Science Center at San Antonio; and the Department of Medicine (M.F.S.), University of Southern California, Los Angeles.
Correspondence to Ami Laws, MD, Stanford Medical Group, 900 Blake Wilbur Dr, Suite W2080, Stanford University, Stanford, CA 94305-2205.
Most discussions of relations of insulin resistance to coronary heart disease risk factors have focused on insulin-stimulated glucose uptake, but insulin suppression of plasma free fatty acid (FFA) levels is also important in lipid and lipoprotein metabolism. To identify groups with impaired insulin suppression of FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non–insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load adjusted for fasting FFAs was used as the measure of insulin suppression. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were significantly higher in men than women and in persons with impaired glucose tolerance and non–insulin-dependent diabetes mellitus versus normal glucose tolerance. The gender difference was largely accounted for by differences in central obesity as measured by waist-hip ratio; the difference by glucose tolerance status was not affected by central obesity, suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and apoB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB and triglyceride concentrations associated with male gender and with glucose intolerance are partly accounted for by differences in the ability of insulin to suppress FFA concentrations.
Key Words: free fatty acids • gender • insulin resistance • triglycerides • apolipoprotein B
This article has been cited by other articles:
 |
|
 |
|
  R. Bitzur, H. Cohen, Y. Kamari, A. Shaish, and D. Harats Triglycerides and HDL Cholesterol: Stars or second leads in diabetes? Diabetes Care, November 1, 2009; 32(suppl_2): S373 - S377. [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Romero-Aleshire, M. K. Diamond-Stanic, A. H. Hasty, P. B. Hoyer, and H. L. Brooks Loss of ovarian function in the VCD mouse-model of menopause leads to insulin resistance and a rapid progression into the metabolic syndrome Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2009; 297(3): R587 - R592. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Stafford, F. Yu, R. Printz, A. H. Hasty, L. L. Swift, and K. D. Niswender Central Nervous System Neuropeptide Y Signaling Modulates VLDL Triglyceride Secretion Diabetes, June 1, 2008; 57(6): 1482 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. L. Wang, L. Zhang, K. Youker, M.-X. Zhang, J. Wang, S. A. LeMaire, J. S. Coselli, and Y. H. Shen Free Fatty Acids Inhibit Insulin Signaling-Stimulated Endothelial Nitric Oxide Synthase Activation Through Upregulating PTEN or Inhibiting Akt Kinase. Diabetes, August 1, 2006; 55(8): 2301 - 2310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Myerson, C. Ngai, J. Jones, S. Holleran, R. Ramakrishnan, L. Berglund, and H. N. Ginsberg Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia J. Lipid Res., December 1, 2005; 46(12): 2735 - 2744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ma, S. Bacci, W. Mlynarski, L. Gottardo, T. Soccio, C. Menzaghi, E. Iori, R. A. Lager, A. R. Shroff, E. V. Gervino, et al. A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians Hum. Mol. Genet., October 1, 2004; 13(19): 2197 - 2205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Iozzo, T. Takala, V. Oikonen, J. Bergman, T. Gronroos, E. Ferrannini, P. Nuutila, and J. Knuuti Effect of Training Status on Regional Disposal of Circulating Free Fatty Acids in the Liver and Skeletal Muscle During Physiological Hyperinsulinemia Diabetes Care, September 1, 2004; 27(9): 2172 - 2177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Valera Mora, A. Scarfone, M. Calvani, A. V. Greco, and G. Mingrone Insulin Clearance in Obesity J. Am. Coll. Nutr., December 1, 2003; 22(6): 487 - 493. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Chen, D. B. Jump, M. B. Grant, W. J. Esselman, and J. V. Busik Dyslipidemia, but Not Hyperglycemia, Induces Inflammatory Adhesion Molecules in Human Retinal Vascular Endothelial Cells Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 5016 - 5022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J.G. Hanley, L. E. Wagenknecht, R. B. D'Agostino Jr., B. Zinman, and S. M. Haffner Identification of Subjects with Insulin Resistance and {beta}-Cell Dysfunction Using Alternative Definitions of the Metabolic Syndrome Diabetes, November 1, 2003; 52(11): 2740 - 2747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. T. Lam, A. Carpentier, G. F. Lewis, G. van de Werve, I. G. Fantus, and A. Giacca Mechanisms of the free fatty acid-induced increase in hepatic glucose production Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E863 - E873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Wolever and C. Mehling Long-term effect of varying the source or amount of dietary carbohydrate on postprandial plasma glucose, insulin, triacylglycerol, and free fatty acid concentrations in subjects with impaired glucose tolerance Am. J. Clinical Nutrition, March 1, 2003; 77(3): 612 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Shah, A. Vella, A. Basu, R. Basu, A. Adkins, W. F. Schwenk, C. M. Johnson, K. S. Nair, M. D. Jensen, and R. A. Rizza Elevated Free Fatty Acids Impair Glucose Metabolism in Women: Decreased Stimulation of Muscle Glucose Uptake and Suppression of Splanchnic Glucose Production During Combined Hyperinsulinemia and Hyperglycemia Diabetes, January 1, 2003; 52(1): 38 - 42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Palaniappan, M. R. Carnethon, and S. P. Fortmann Heterogeneity in the Relationship Between Ethnicity, BMI, and Fasting Insulin Diabetes Care, August 1, 2002; 25(8): 1351 - 1357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Galipeau, L. Yao, and J. H. McNeill Relationship among hyperinsulinemia, insulin resistance, and hypertension is dependent on sex Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H562 - H567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lewis, A. Carpentier, K. Adeli, and A. Giacca Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Endocr. Rev., April 1, 2002; 23(2): 201 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J.G. Hanley, R. D'Agostino Jr., L. E. Wagenknecht, M. F. Saad, P. J. Savage, R. Bergman, and S. M. Haffner Increased Proinsulin Levels and Decreased Acute Insulin Response Independently Predict the Incidence of Type 2 Diabetes in the Insulin Resistance Atherosclerosis Study Diabetes, April 1, 2002; 51(4): 1263 - 1270. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Sniderman, T. Scantlebury, and K. Cianflone Hypertriglyceridemic HyperapoB: The Unappreciated Atherogenic Dyslipoproteinemia in Type 2 Diabetes Mellitus Ann Intern Med, September 18, 2001; 135(6): 447 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Frias, G. B. Macaraeg, J. Ofrecio, J. G. Yu, J. M. Olefsky, and Y. T. Kruszynska Decreased Susceptibility to Fatty Acid-Induced Peripheral Tissue Insulin Resistance in Women Diabetes, June 1, 2001; 50(6): 1344 - 1350. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Hulthe, L. Bokemark, J. Wikstrand, and B. Fagerberg The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis : The Atherosclerosis and Insulin Resistance (AIR) Study Arterioscler Thromb Vasc Biol, September 1, 2000; 20(9): 2140 - 2147. [Abstract] [Full Text] [PDF]
|
|