Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles.

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 concentra- tions 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 insu- lin (1,743±293 pmol/ liter -h) responses to oral glucose com- pared 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.Pat- tern 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. 133±0.17and 0.77±0.05mmol/liter) and lower (P < 0.01-0.001)HDL cholesterol (1.12±0.06 vs. 134±0.05vs. 1.45±0.05mmol/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-cho- lesterol (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.(J.Clin.Invest.1993.92:141-146.)Key words: LDL particle diameter -glucose and insulin responses * resistance to insulin-mediated glucose up- take-lipid and lipoprotein concentrations * blood pressure pattern B LDL 1. Abbreviations used in this paper: BMI, body mass index; SSPG, steady state plasma glucose; SSPI, steady state plasma insulin; TG, triglycerides.Insulin Resistance and Small Low Density Lipoprotein Particles 141 * Mean±SE.INT, intermediate.* INT pattern significantly different (P < 0.05) from pattern A. I Pattern B significantly different (P < 0.05) from pattern A. I I Pattern B significantly different (P < 0.05) from INT pattern.