We studied the relation of serum insulin levels to plasma lipid levels and blood pressure in two groups drawn from among 247 healthy, normotensive nonobese subjects with normal glucose tolerance. One group of 32 subjects was defined as having hyperinsulinemia (serum insulin, greater than 2 SD above the mean) and then compared with 32 normoinsulinemic subjects (serum insulin within 1 SD of the mean) matched for age (mean, 39 years), sex (22 men and 10 women), and body-mass index (24.7). The two groups had similar patterns of smoking, drinking, and physical exercise. Plasma glucose levels after an oral glucose challenge were significantly higher (P less than 0.05) in the hyperinsulinemic group. In addition, the mean (+/- SEM) fasting plasma triglyceride levels in subjects with hyperinsulinemia were significantly higher (1.73 +/- 0.2 vs. 1.24 +/- 0.1 mmol per liter) and the plasma high-density lipoprotein cholesterol concentrations were lower (1.21 +/- 0.06 vs. 1.43 +/- 0.06 mmol per liter) than in subjects with normoinsulinemia. Both systolic (126 vs. 119 mm Hg; P less than 0.05) and diastolic (85 vs. 78 mm Hg; P less than 0.01) blood pressures were significantly elevated in the group with hyperinsulinemia. We conclude that healthy persons with hyperinsulinemia and normal glucose tolerance have an increase in risk factors for coronary artery disease, as compared with a well-matched group of healthy subjects with normal insulin levels.
Source Information
General Medicine Clinic, Parma University, Italy.
This article has been cited by other articles:
Shimotoyodome, A., Fukuoka, D., Suzuki, J., Fujii, Y., Mizuno, T., Meguro, S., Tokimitsu, I., Hase, T.
(2009). Coingestion of Acylglycerols Differentially Affects Glucose-Induced Insulin Secretion via Glucose-Dependent Insulinotropic Polypeptide in C57BL/6J Mice. Endocrinology
150: 2118-2126
[Abstract][Full Text]
Eddy, D., Schlessinger, L., Kahn, R., Peskin, B., Schiebinger, R.
(2009). Relationship of Insulin Resistance and Related Metabolic Variables to Coronary Artery Disease: A Mathematical Analysis. Diabetes Care
32: 361-366
[Abstract][Full Text]
Steinfeld, I., Navon, R., Ardigo, D., Zavaroni, I., Yakhini, Z.
(2008). Clinically driven semi-supervised class discovery in gene expression data. Bioinformatics
24: i90-i97
[Abstract][Full Text]
Valtuena, S., Pellegrini, N., Franzini, L., Bianchi, M. A, Ardigo, D., Del Rio, D., Piatti, P., Scazzina, F., Zavaroni, I., Brighenti, F.
(2008). Food selection based on total antioxidant capacity can modify antioxidant intake, systemic inflammation, and liver function without altering markers of oxidative stress. Am. J. Clin. Nutr.
87: 1290-1297
[Abstract][Full Text]
Gur, M., Yilmaz, R., Demirbag, R., Aksoy, N.
(2008). Relation of Serum Uric Acid Levels With the Presence and Severity of Angiographic Coronary Artery Disease. ANGIOLOGY
59: 166-171
[Abstract]
Reaven, G.
(2008). Why a Cluster is Truly a Cluster: Insulin Resistance and Cardiovascular Disease. Clin. Chem.
54: 785-787
[Full Text]
Ashikaga, T., Nishizaki, M., Fujii, H., Ihara, K., Niki, S., Murai, T., Maeda, S., Yamawake, N., Kishi, Y., Isobe, M.
(2008). Coronary Endothelial Dysfunction and Impaired Microcirculation Response to Atrial Natriuretic Peptide in Hyperinsulinemia. J CARDIOVASC PHARMACOL THER
13: 58-63
[Abstract]
Bloomgarden, Z. T.
(2007). Diabetes and Obesity: Part 1. Diabetes Care
30: 3145-3151
[Full Text]
Lorenzo, C., Serrano-Rios, M., Martinez-Larrad, M. T., Gonzalez-Villalpando, C., Gonzalez-Sanchez, J. L., Martinez-Calatrava, M. J., Gabriel, R., Haffner, S. M.
(2007). Is Waist Circumference an Essential Component of the Metabolic Syndrome?. Diabetes Care
30: 2141-2142
[Full Text]
Reaven, G. M.
(2007). The Individual Components of the Metabolic Syndrome: Is There a Raison d'Etre?. J. Am. Coll. Nutr.
26: 191-195
[Full Text]
Forman, J. P., Choi, H., Curhan, G. C.
(2007). Plasma Uric Acid Level and Risk for Incident Hypertension Among Men. J. Am. Soc. Nephrol.
18: 287-292
[Abstract][Full Text]
Blaha, M., Elasy, T. A.
(2006). Clinical Use of the Metabolic Syndrome: Why the Confusion?. Clin. Diabetes
24: 125-131
[Abstract][Full Text]
Reaven, G. M
(2006). The metabolic syndrome: is this diagnosis necessary?. Am. J. Clin. Nutr.
83: 1237-1247
[Abstract][Full Text]
De Caterina, R., Zampolli, A., Del Turco, S., Madonna, R., Massaro, M.
(2006). Nutritional mechanisms that influence cardiovascular disease. Am. J. Clin. Nutr.
83: 421S-426S
[Abstract][Full Text]
Reaven, G.
(2005). Counterpoint: Just Being Alive Is Not Good Enough. Clin. Chem.
51: 1354-1357
[Full Text]
Zheng, Y., Yamada, H., Sakamoto, K., Horita, S., Kunimi, M., Endo, Y., Li, Y., Tobe, K., Terauchi, Y., Kadowaki, T., Seki, G., Fujita, T.
(2005). Roles of Insulin Receptor Substrates in Insulin-Induced Stimulation of Renal Proximal Bicarbonate Absorption. J. Am. Soc. Nephrol.
16: 2288-2295
[Abstract][Full Text]
Apridonidze, T., Essah, P. A., Iuorno, M. J., Nestler, J. E.
(2005). Prevalence and Characteristics of the Metabolic Syndrome in Women with Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab.
90: 1929-1935
[Abstract][Full Text]
Larsen, J. L.
(2004). Pancreas Transplantation: Indications and Consequences. Endocr. Rev.
25: 919-946
[Abstract][Full Text]
Wilkin, T. J, Voss, L. D
(2004). Metabolic syndrome: maladaptation to a modern world. JRSM
97: 511-520
[Full Text]
Karelis, A. D., St-Pierre, D. H., Conus, F., Rabasa-Lhoret, R., Poehlman, E. T.
(2004). Metabolic and Body Composition Factors in Subgroups of Obesity: What Do We Know?. J. Clin. Endocrinol. Metab.
89: 2569-2575
[Abstract][Full Text]
Iwashima, Y., Katsuya, T., Ishikawa, K., Ouchi, N., Ohishi, M., Sugimoto, K., Fu, Y., Motone, M., Yamamoto, K., Matsuo, A., Ohashi, K., Kihara, S., Funahashi, T., Rakugi, H., Matsuzawa, Y., Ogihara, T.
(2004). Hypoadiponectinemia Is an Independent Risk Factor for Hypertension. Hypertension
43: 1318-1323
[Abstract][Full Text]
De Leo, V., la Marca, A., Petraglia, F.
(2003). Insulin-Lowering Agents in the Management of Polycystic Ovary Syndrome. Endocr. Rev.
24: 633-667
[Abstract][Full Text]
Kenkre, P. V., Lindeman, R. D., Lillian Yau, C., Baumgartner, R. N., Garry, P. J.
(2003). Serum Insulin Concentrations in Daily Drinkers Compared With Abstainers in the New Mexico Elder Health Survey. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
58: M960-963
[Abstract][Full Text]
Haffner, S. M., D'Agostino, R. Jr., Festa, A., Bergman, R. N., Mykkanen, L., Karter, A., Saad, M. F., Wagenknecht, L. E.
(2003). Low Insulin Sensitivity (Si = 0) in Diabetic and Nondiabetic Subjects in the Insulin Resistance Atherosclerosis Study: Is it associated with components of the metabolic syndrome and nontraditional risk factors?. Diabetes Care
26: 2796-2803
[Abstract][Full Text]
Robins, S. J., Rubins, H. B., Faas, F. H., Schaefer, E. J., Elam, M. B., Anderson, J. W., Collins, D.
(2003). Insulin Resistance and Cardiovascular Events With Low HDL Cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT). Diabetes Care
26: 1513-1517
[Abstract][Full Text]
(2002). Hypertension, Insulin, and Proinsulin in Participants With Impaired Glucose Tolerance. Hypertension
40: 679-686
[Abstract][Full Text]
Kernan, W. N., Inzucchi, S. E., Viscoli, C. M., Brass, L. M., Bravata, D. M., Horwitz, R. I.
(2002). Insulin resistance and risk for stroke. Neurology
59: 809-815
[Abstract][Full Text]
Colangelo, L. A., Gapstur, S. M., Gann, P. H., Dyer, A. R., Liu, K.
(2002). Colorectal Cancer Mortality and Factors Related to the Insulin Resistance Syndrome. Cancer Epidemiol. Biomarkers Prev.
11: 385-391
[Abstract][Full Text]
Iida, K. T., Suzuki, H., Sone, H., Shimano, H., Toyoshima, H., Yatoh, S., Asano, T., Okuda, Y., Yamada, N.
(2002). Insulin Inhibits Apoptosis of Macrophage Cell Line, THP-1 Cells, via Phosphatidylinositol-3-Kinase-Dependent Pathway. Arterioscler. Thromb. Vasc. Bio.
22: 380-386
[Abstract][Full Text]
Mills, J. D, Grant, P. J
(2002). Insulin resistance, haemostatic factors and cardiovascular risk. British Journal of Diabetes & Vascular Disease
2: 19-26
[Abstract]
Trevisan, M., Browne, R., Ram, M., Muti, P., Freudenheim, J., Carosella, A. M., Armstrong, D.
(2001). Correlates of Markers of Oxidative Status in the General Population. Am J Epidemiol
154: 348-356
[Abstract][Full Text]
Boden, G., Lebed, B., Schatz, M., Homko, C., Lemieux, S.
(2001). Effects of Acute Changes of Plasma Free Fatty Acids on Intramyocellular Fat Content and Insulin Resistance in Healthy Subjects. Diabetes
50: 1612-1617
[Abstract][Full Text]
Wajchenberg, B. L.
(2000). Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome. Endocr. Rev.
21: 697-738
[Abstract][Full Text]
Brynes, A. E, Edwards, C M., Jadhav, A., Ghatei, M. A, Bloom, S. R, Frost, G. S
(2000). Diet-induced change in fatty acid composition of plasma triacylglycerols is not associated with change in glucagon-like peptide 1 or insulin sensitivity in people with type 2 diabetes. Am. J. Clin. Nutr.
72: 1111-1118
[Abstract][Full Text]
Shinozaki, K., Nishio, Y., Okamura, T., Yoshida, Y., Maegawa, H., Kojima, H., Masada, M., Toda, N., Kikkawa, R., Kashiwagi, A.
(2000). Oral Administration of Tetrahydrobiopterin Prevents Endothelial Dysfunction and Vascular Oxidative Stress in the Aortas of Insulin-Resistant Rats. Circ. Res.
87: 566-573
[Abstract][Full Text]
Suzuki, M., Kimura, Y., Tsushima, M., Harano, Y.
(2000). Association of Insulin Resistance With Salt Sensitivity and Nocturnal Fall of Blood Pressure. Hypertension
35: 864-868
[Abstract][Full Text]
Kashiwagi, A., Shinozaki, K., Nishio, Y., Maegawa, H., Maeno, Y., Kanazawa, A., Kojima, H., Haneda, M., Hidaka, H., Yasuda, H., Kikkawa, R.
(1999). Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats. Am. J. Physiol. Endocrinol. Metab.
277: E976-E983
[Abstract][Full Text]
Saku, K., Zhang, B., Shirai, K., Jimi, S., Yoshinaga, K., Arakawa, K.
(1999). Hyperinsulinemic hypoalphalipoproteinemia as a new indicator for coronary heart disease. J Am Coll Cardiol
34: 1443-1451
[Abstract][Full Text]
Rubins, H. B., Robins, S. J., Collins, D., Fye, C. L., Anderson, J. W., Elam, M. B., Faas, F. H., Linares, E., Schaefer, E. J., Schectman, G., Wilt, T. J., Wittes, J., The Veterans Affairs High-Density Lipoprotein Chol,
(1999). Gemfibrozil for the Secondary Prevention of Coronary Heart Disease in Men with Low Levels of High-Density Lipoprotein Cholesterol. NEJM
341: 410-418
[Abstract][Full Text]
Chandalia, M., Abate, N., Garg, A., Stray-Gundersen, J., Grundy, S. M.
(1999). Relationship between Generalized and Upper Body Obesity to Insulin Resistance in Asian Indian Men. J. Clin. Endocrinol. Metab.
84: 2329-2335
[Abstract][Full Text]
Alderman, M. H., Cohen, H., Madhavan, S., Kivlighn, S.
(1999). Serum Uric Acid and Cardiovascular Events in Successfully Treated Hypertensive Patients. Hypertension
34: 144-150
[Abstract][Full Text]
Nestler, J. E., Jakubowicz, D. J., Reamer, P., Gunn, R. D., Allan, G.
(1999). Ovulatory and Metabolic Effects of d-Chiro-Inositol in the Polycystic Ovary Syndrome. NEJM
340: 1314-1320
[Abstract][Full Text]
Festa, A., D'Agostino, R. Jr, Mykkanen, L., Tracy, R. P., Zaccaro, D. J., Hales, C. N., Haffner, S. M.
(1999). Relative Contribution of Insulin and Its Precursors to Fibrinogen and PAI-1 in a Large Population With Different States of Glucose Tolerance : The Insulin Resistance Atherosclerosis Study (IRAS). Arterioscler. Thromb. Vasc. Bio.
19: 562-568
[Abstract][Full Text]
Zavaroni, I., Zuccarelli, A., Gasparini, P., Massironi, P., Barilli, A., Reaven, G. M.
(1998). Can Weight Gain in Healthy, Nonobese Volunteers Be Predicted by Differences in Baseline Plasma Insulin Concentration?. J. Clin. Endocrinol. Metab.
83: 3498-3500
[Abstract][Full Text]
Velloso, L. A., Carvalho, C. R.O., Rojas, F. A., Folli, F., Saad, M. J.A.
(1998). Insulin signalling in heart involves insulin receptor substrates-1 and -2, activation of phosphatidylinositol 3-kinase and the JAK 2-growth related pathway. Cardiovasc Res
40: 96-102
[Abstract][Full Text]
Burchfiel, C. M., Sharp, D. S., Curb, J. D., Rodriguez, B. L., Abbott, R. D., Arakaki, R., Yano, K.
(1998). Hyperinsulinemia and Cardiovascular Disease in Elderly Men : The Honolulu Heart Program. Arterioscler. Thromb. Vasc. Bio.
18: 450-457
[Abstract][Full Text]
Lehto, S., Niskanen, L., Ronnemaa, T., Laakso, M.
(1998). Serum Uric Acid Is a Strong Predictor of Stroke in Patients With Non–Insulin-Dependent Diabetes Mellitus. Stroke
29: 635-639
[Abstract][Full Text]
Batey, L. S., RD, L. S., Goff, D. C. Jr, Tortolero, S. R., Nichaman, M. Z., Chan, W., Chan, F. A., Grunbaum, J., EdD, J., Hanis, C. L., Labarthe, D. R.
(1997). Summary Measures of the Insulin Resistance Syndrome Are Adverse Among Mexican-American Versus Non-Hispanic White Children : The Corpus Christi Child Heart Study. Circulation
96: 4319-4325
[Abstract][Full Text]
Rainwater, D. L., Mitchell, B. D., Mahaney, M. C., Haffner, S. M.
(1997). Genetic Relationship Between Measures of HDL Phenotypes and Insulin Concentrations. Arterioscler. Thromb. Vasc. Bio.
17: 3414-3419
[Abstract][Full Text]
Sinaiko, A. R., Gomez-Marin, O., Prineas, R. J.
(1997). Relation of Fasting Insulin to Blood Pressure and Lipids in Adolescents and Parents. Hypertension
30: 1554-1559
[Abstract][Full Text]
Rajkhowa, M., Neary, R. H., Kumpatla, P., Game, F. L., Jones, P. W., Obhrai, M. S., Clayton, R. N.
(1997). Altered Composition of High Density Lipoproteins in Women with the Polycystic Ovary Syndrome. J. Clin. Endocrinol. Metab.
82: 3389-3394
[Abstract][Full Text]
Mykkanen, L., Haffner, S. M., Rainwater, D. L., Karhapaa, P., Miettinen, H., Laakso, M.
(1997). Relationship of LDL Size to Insulin Sensitivity in Normoglycemic Men. Arterioscler. Thromb. Vasc. Bio.
17: 1447-1453
[Abstract][Full Text]
Sowers, J. R.
(1997). Insulin and Insulin-Like Growth Factor in Normal and Pathological Cardiovascular Physiology. Hypertension
29: 691-699
[Full Text]
Chan, P., Tomlinson, B., Lee, C.-B., Pan, W.-H., Lee, Y.-S.
(1996). Beneficial Effects of Pravastatin on Fasting Hyperinsulinemia in Elderly Hypertensive Hypercholesterolemic Subjects. Hypertension
28: 647-651
[Abstract][Full Text]
Haffner, S. M., Miettinen, H., Gaskill, S. P., Stern, M. P.
(1996). Metabolic Precursors of Hypertension: The San Antonio Heart Study. Arch Intern Med
156: 1994-2001
[Abstract]
DeSouza, C. A., Dengel, D. R., Rogers, M. A., Cox, K., Macko, R. F.
(1996). The Fibrinolytic System Is Not Impaired in Older Men With Hypertension. Hypertension
27: 1053-1058
[Abstract][Full Text]
Despres, J.-P., Lamarche, B., Mauriege, P., Cantin, B., Dagenais, G. R., Moorjani, S., Lupien, P.-J.
(1996). Hyperinsulinemia as an Independent Risk Factor for Ischemic Heart Disease. NEJM
334: 952-958
[Abstract][Full Text]
Konen, J. C., Curtis, L. G., Summerson, J. H.
(1996). Symptoms and Complications of Adult Diabetic Patients in a Family Practice. Arch Fam Med
5: 135-145
[Abstract]
Johnson, J. L., Wolf, S. L., Kabadi, U. M.
(1996). Efficacy of Insulin and Sulfonylurea Combination Therapy in Type II Diabetes: A Meta-analysis of the Randomized Placebo-Controlled Trials. Arch Intern Med
156: 259-264
[Abstract]
Mitchell, B. D., Kammerer, C. M., Mahaney, M. C., Blangero, J., Comuzzie, A. G., Atwood, L. D., Haffner, S. M., Stern, M. P., MacCluer, J. W.
(1996). Genetic Analysis of the IRS : Pleiotropic Effects of Genes Influencing Insulin Levels on Lipoprotein and Obesity Measures. Arterioscler. Thromb. Vasc. Bio.
16: 281-288
[Abstract][Full Text]
Bao, W., Srinivasan, S. R., Berenson, G. S.
(1996). Persistent Elevation of Plasma Insulin Levels Is Associated With Increased Cardiovascular Risk in Children and Young Adults : The Bogalusa Heart Study. Circulation
93: 54-59
[Abstract][Full Text]
Burchfiel, C. M., Curb, J. D., Sharp, D. S., Rodriguez, B. L., Arakaki, R., Chyou, P.-H., Yano, K.
(1995). Distribution and Correlates of Insulin in Elderly Men : The Honolulu Heart Program. Arterioscler. Thromb. Vasc. Bio.
15: 2213-2221
[Abstract][Full Text]
Falkner, B., Kushner, H., Tulenko, T., Sumner, A. E., Marsh, J. B.
(1995). Insulin Sensitivity, Lipids, and Blood Pressure in Young American Blacks. Arterioscler. Thromb. Vasc. Bio.
15: 1798-1804
[Abstract][Full Text]
Kato, H., Takashima, T., Ohmori, K., Sunaga, T.
(1995). Urine C-Peptide and Atherogenic Risk Factors in Diabetes Mellitus: Relevance to "Syndrome X". ANGIOLOGY
46: 915-921
[Abstract]
Clifton, P. M., Abbey, M., Noakes, M., Beltrame, S., Rumbelow, N., Nestel, P. J.
(1995). Body Fat Distribution Is a Determinant of the High-Density Lipoprotein Response to Dietary Fat and Cholesterol in Women. Arterioscler. Thromb. Vasc. Bio.
15: 1070-1078
[Abstract][Full Text]
Salomaa, V., Riley, W., Kark, J. D., Nardo, C., Folsom, A. R.
(1995). Non–Insulin-Dependent Diabetes Mellitus and Fasting Glucose and Insulin Concentrations Are Associated With Arterial Stiffness Indexes : The ARIC Study. Circulation
91: 1432-1443
[Abstract][Full Text]
Jiang, X., Srinivasan, S. R., Webber, L. S., Wattigney, W. A., Berenson, G. S.
(1995). Association of Fasting Insulin Level With Serum Lipid and Lipoprotein Levels in Children, Adolescents, and Young Adults: The Bogalusa Heart Study. Arch Intern Med
155: 190-196
[Abstract]
Cappuccio, F. P., Strazzullo, P., Farinaro, E., Trevisan, M.
(1993). Uric Acid Metabolism and Tubular Sodium Handling: Results From a Population-Based Study. JAMA
270: 354-359
[Abstract]
Wilson, P. W. F., Kannel, W. B.
(1993). Is Baldness Bad for the Heart?. JAMA
269: 1035-1036
[Abstract]
Borkman, M., Storlien, L. H., Pan, D. A., Jenkins, A. B., Chisholm, D. J., Campbell, L. V.
(1993). The Relation between Insulin Sensitivity and the Fatty-Acid Composition of Skeletal-Muscle Phospholipids. NEJM
328: 238-244
[Abstract][Full Text]
Cooper, G. R., Myers, G. L., Smith, S. J., Schlant, R. C.
(1992). Blood Lipid Measurements: Variations and Practical Utility. JAMA
267: 1652-1660
[Abstract]
Selby, J. V., Newman, B., Quiroga, J., Christian, J. C., Austin, M. A., Fabsitz, R. R.
(1991). Concordance for Dyslipidemic Hypertension in Male Twins. JAMA
265: 2079-2084
[Abstract]
Hamsten, A.
(1991). Myocardial infarction at a young age: mechanisms and management. Vasc Med
2: 45-60
Haffner, S. M., Stern, M. P., Hazuda, H. P., Mitchell, B. D., Patterson, J. K.
(1990). Cardiovascular Risk Factors in Confirmed Prediabetic Individuals: Does the Clock for Coronary Heart Disease Start Ticking Before the Onset of Clinical Diabetes?. JAMA
263: 2893-2898
[Abstract]
Iida, K. T., Shimano, H., Kawakami, Y., Sone, H., Toyoshima, H., Suzuki, S., Asano, T., Okuda, Y., Yamada, N.
(2001). Insulin Up-regulates Tumor Necrosis Factor-alpha Production in Macrophages through an Extracellular-regulated Kinase-dependent Pathway. J. Biol. Chem.
276: 32531-32537
[Abstract][Full Text]