Abstract
Subjects characterized by a predominance of small LDL particles (pattern B) have changes in plasma triglyceride (TG) and HDL-cholesterol concentrations consistent with the presence of resistance to insulin-mediated glucose uptake. To pursue this issue, plasma glucose and insulin responses to oral glucose, insulin-mediated glucose disposal, and lipoprotein concentrations were measured in subjects categorized on the basis of LDL peak diameter measured by gradient gel electrophoresis. Subjects with pattern B had higher (P < 0.05-0.001) total integrated plasma glucose (20.7 +/- 1.0 mmol/liter.h) and insulin (1,743 +/- 293 pmol/liter.h) responses to oral glucose compared with glucose (16.3 +/- 0.4 and 19.2 +/- 0.8 mmol/liter.h) and insulin (856 +/- 60 and 1,222 +/- 168 pmol/liter.h) responses in those with either pattern A or an intermediate pattern. Pattern B individuals were shown to be more insulin resistant on the basis of higher steady state plasma glucose concentrations (SSPG, 10.4 +/- 1.0, P < 0.002, vs. 7.5 +/- 0.7 and 6.0 +/- 0.4 mmol/liter) after a constant infusion of somatostatin, glucose, and insulin than those with either the intermediate or pattern A subclass. Pattern B subjects also had higher concentrations of (P < 0.001) TG (1.98 +/- 0.15 vs. 1.33 +/- 0.17 and 0.77 +/- 0.05 mmol/liter) and lower (P < 0.01-0.001) HDL cholesterol (1.12 +/- 0.06 vs. 1.34 +/- 0.05 vs. 1.45 +/- 0.05 mmol/liter) than those with either the intermediate or pattern A. Finally, significant (P < 0.001) correlation coefficients existed between LDL diameter and SSPG (r = -0.44); glucose (r = -0.41) and insulin (r = -0.38) responses; TG (r = -0.65) and HDL-cholesterol (r = 0.42) concentrations; and systolic (r = -0.34) and diastolic (r = -0.34) blood pressure. Thus, pattern B subjects are insulin resistant, have higher glucose, insulin, and TG, lower HDL-cholesterol levels, and higher blood pressure than those with pattern A or intermediate.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allain C. C., Poon L. S., Chan C. S., Richmond W., Fu P. C. Enzymatic determination of total serum cholesterol. Clin Chem. 1974 Apr;20(4):470–475. [PubMed] [Google Scholar]
- Austin M. A., Breslow J. L., Hennekens C. H., Buring J. E., Willett W. C., Krauss R. M. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA. 1988 Oct 7;260(13):1917–1921. [PubMed] [Google Scholar]
- Austin M. A., Brunzell J. D., Fitch W. L., Krauss R. M. Inheritance of low density lipoprotein subclass patterns in familial combined hyperlipidemia. Arteriosclerosis. 1990 Jul-Aug;10(4):520–530. doi: 10.1161/01.atv.10.4.520. [DOI] [PubMed] [Google Scholar]
- Austin M. A., King M. C., Vranizan K. M., Krauss R. M. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation. 1990 Aug;82(2):495–506. doi: 10.1161/01.cir.82.2.495. [DOI] [PubMed] [Google Scholar]
- Austin M. A., King M. C., Vranizan K. M., Newman B., Krauss R. M. Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis. Am J Hum Genet. 1988 Dec;43(6):838–846. [PMC free article] [PubMed] [Google Scholar]
- Crouse J. R., Parks J. S., Schey H. M., Kahl F. R. Studies of low density lipoprotein molecular weight in human beings with coronary artery disease. J Lipid Res. 1985 May;26(5):566–574. [PubMed] [Google Scholar]
- Facchini F., Chen Y. D., Hollenbeck C. B., Reaven G. M. Relationship between resistance to insulin-mediated glucose uptake, urinary uric acid clearance, and plasma uric acid concentration. JAMA. 1991 Dec 4;266(21):3008–3011. [PubMed] [Google Scholar]
- 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]
- Fisher W. R., Hammond M. G., Warmke G. L. Measurements of the molecular weight variability of plasma low density lipoproteins among normals and subjects with hyper- -lipoproteinemia. Demonstration of macromolecular heterogeneity. Biochemistry. 1972 Feb 15;11(4):519–525. doi: 10.1021/bi00754a006. [DOI] [PubMed] [Google Scholar]
- HALES C. N., RANDLE P. J. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963 Jul;88:137–146. doi: 10.1042/bj0880137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haffner S. M., Stern M. P., Hazuda H. P., Mitchell B. D., Patterson J. K. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical diabetes? JAMA. 1990 Jun 6;263(21):2893–2898. doi: 10.1001/jama.263.21.2893. [DOI] [PubMed] [Google Scholar]
- Juhan-Vague I., Alessi M. C., Vague P. Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis. Diabetologia. 1991 Jul;34(7):457–462. doi: 10.1007/BF00403280. [DOI] [PubMed] [Google Scholar]
- Juhan-Vague I., Roul C., Alessi M. C., Ardissone J. P., Heim M., Vague P. Increased plasminogen activator inhibitor activity in non insulin dependent diabetic patients--relationship with plasma insulin. Thromb Haemost. 1989 Jun 30;61(3):370–373. [PubMed] [Google Scholar]
- Kraemer F. B., Chen Y. D., Cheung R. M., Reaven G. M. Are the binding and degradation of low density lipoprotein altered in Type 2 (non-insulin-dependent) diabetes mellitus? Diabetologia. 1982 Jul;23(1):28–33. doi: 10.1007/BF00257726. [DOI] [PubMed] [Google Scholar]
- Krauss R. M., Burke D. J. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res. 1982 Jan;23(1):97–104. [PubMed] [Google Scholar]
- Krauss R. M., Burke D. J. Identification of multiple subclasses of plasma low density lipoproteins in normal humans. J Lipid Res. 1982 Jan;23(1):97–104. [PubMed] [Google Scholar]
- Krauss R. M., Lindgren F. T., Williams P. T., Kelsey S. F., Brensike J., Vranizan K., Detre K. M., Levy R. I. Intermediate-density lipoproteins and progression of coronary artery disease in hypercholesterolaemic men. Lancet. 1987 Jul 11;2(8550):62–66. doi: 10.1016/s0140-6736(87)92734-6. [DOI] [PubMed] [Google Scholar]
- Landin K., Tengborn L., Smith U. Elevated fibrinogen and plasminogen activator inhibitor (PAI-1) in hypertension are related to metabolic risk factors for cardiovascular disease. J Intern Med. 1990 Apr;227(4):273–278. doi: 10.1111/j.1365-2796.1990.tb00157.x. [DOI] [PubMed] [Google Scholar]
- Laws A., Reaven G. M. Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations. J Intern Med. 1992 Jan;231(1):25–30. doi: 10.1111/j.1365-2796.1992.tb00494.x. [DOI] [PubMed] [Google Scholar]
- Nishina P. M., Johnson J. P., Naggert J. K., Krauss R. M. Linkage of atherogenic lipoprotein phenotype to the low density lipoprotein receptor locus on the short arm of chromosome 19. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):708–712. doi: 10.1073/pnas.89.2.708. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olefsky J. M., Farquhar J. W., Reaven G. M. Reappraisal of the role of insulin in hypertriglyceridemia. Am J Med. 1974 Oct;57(4):551–560. doi: 10.1016/0002-9343(74)90006-0. [DOI] [PubMed] [Google Scholar]
- Reaven G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988 Dec;37(12):1595–1607. doi: 10.2337/diab.37.12.1595. [DOI] [PubMed] [Google Scholar]
- Reaven G. M., Lerner R. L., Stern M. P., Farquhar J. W. Role of insulin in endogenous hypertriglyceridemia. J Clin Invest. 1967 Nov;46(11):1756–1767. doi: 10.1172/JCI105666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shen D. C., Shieh S. M., Fuh M. M., Wu D. A., Chen Y. D., Reaven G. M. Resistance to insulin-stimulated-glucose uptake in patients with hypertension. J Clin Endocrinol Metab. 1988 Mar;66(3):580–583. doi: 10.1210/jcem-66-3-580. [DOI] [PubMed] [Google Scholar]
- Shen S. W., Reaven G. M., Farquhar J. W. Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes. J Clin Invest. 1970 Dec;49(12):2151–2160. doi: 10.1172/JCI106433. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stalder M., Pometta D., Suenram A. Relationship between plasma insulin levels and high density lipoprotein cholesterol levels in healthy men. Diabetologia. 1981 Dec;21(6):544–548. doi: 10.1007/BF00281546. [DOI] [PubMed] [Google Scholar]
- Steiner G. Altering triglyceride concentrations changes insulin-glucose relationships in hypertriglyceridemic patients. Double-blind study with gemfibrozil with implications for atherosclerosis. Diabetes Care. 1991 Nov;14(11):1077–1081. doi: 10.2337/diacare.14.11.1077. [DOI] [PubMed] [Google Scholar]
- Swislocki A. L., Hoffman B. B., Sheu W. H., Chen Y. D., Reaven G. M. Effect of prazosin treatment on carbohydrate and lipoprotein metabolism in patients with hypertension. Am J Med. 1989 Jan 23;86(1B):14–18. doi: 10.1016/0002-9343(89)90122-8. [DOI] [PubMed] [Google Scholar]
- Zavaroni I., Mazza S., Luchetti L., Buonanno G., Bonati P. A., Bergonzani M., Passeri M., Reaven G. M. High plasma insulin and triglyceride concentrations and blood pressure in offspring of people with impaired glucose tolerance. Diabet Med. 1990 Jul;7(6):494–498. doi: 10.1111/j.1464-5491.1990.tb01430.x. [DOI] [PubMed] [Google Scholar]