LDL particle size in relation to insulin, proinsulin, and insulin sensitivity. The Insulin Resistance Atherosclerosis Study.
OBJECTIVE
LDL particles are heterogeneous in terms of size and density; small dense LDL particles are considered more atherogenic than larger LDL particles. The aim of this study was to investigate the interrelationships among LDL size, insulin, proinsulin (intact and split), and insulin sensitivity in a tri-ethnic population with varying degrees of glucose tolerance (n = 1,549) in the Insulin Resistance Atherosclerosis Study.


METHODS
Insulin sensitivity was assessed by a frequently sampled intravenous glucose tolerance test with minimal model analysis. Proinsulin levels were measured using highly sensitive assays without detectable cross-reactivity with insulin, and LDL size was determined by gradient-gel electrophoresis.


RESULTS
In univariate analyses, LDL size was related to various features of the insulin resistance syndrome, including fasting insulin (r = -0.18), intact proinsulin (r = -0.24), split proinsulin (r = -0.24), the proinsulin-to-insulin ratio (r = -0.14), and insulin sensitivity (r = 0.21; all P < 0.0001). In a multivariate regression model (adjusted for age, BMI, ethnicity, and clinic), triglyceride levels (P = 0.0001), HDL cholesterol (P = 0.0001), sex (P = 0.002), and proinsulin (P = 0.01) were significantly related to LDL size. In the same model stratified by sex, LDL size was significantly inversely related to proinsulin in men (P = 0.005 and P = 0.04 after further adjustment for the glucose tolerance status), but not in women (P > 0.15).


CONCLUSIONS
We found an inverse relation of proinsulin to LDL particle size in a large tri-ethnic population with varying degrees of glucose tolerance. This relation was independent of age, BMI, and triglyceride and HDL cholesterol concentrations, and was more pronounced in men than in women.
Festa
A
A
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7873. festa@uthscsa.edu
D'Agostino
R
R
Mykkänen
L
L
Tracy
R P
RP
Hales
C N
CN
Howard
B V
BV
Haffner
S M
SM
D001161:Arteriosclerosis / Q000453:epidemiology*; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004739:England; D005006:Ethnicity; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D015999:Multivariate Analysis; D011384:Proinsulin / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors; D012727:Sex Characteristics; D014280:Triglycerides / Q000097:blood; D014481:United States
D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D008077:Lipoproteins, LDL; D014280:Triglycerides; D011384:Proinsulin; D002784:Cholesterol