Insulin resistance, insulin response, and obesity as indicators of metabolic risk.
BACKGROUND
Insulin resistance (IR) and obesity, especially abdominal obesity, are regarded as central pathophysiological features of a cluster of cardiovascular risk factors (CVRFs), but their relative roles remain undefined. Moreover, the differential impact of IR viz. insulin response has not been evaluated.


OBJECTIVE
The objective of this study was to dissect out the impact of obesity, abdominal obesity, and IR/insulin response on CVRF.


METHODS
This was a cross-sectional study.


METHODS
The study was conducted at 21 research centers in Europe.


METHODS
The study included a cohort of 1308 nondiabetic subjects [718 women and 590 men, age 30-60 yr, body mass index (BMI) 17-44 kg.m(-2)].


METHODS
We measured IR (by a standardized euglycemic insulin clamp), waist girth, insulin response to an oral glucose tolerance test, and major CVRF, and analyzed their associations by multivariate models and factor analysis.


RESULTS
BMI was positively related to all CVRFs. Waist circumference was related to higher blood pressure and serum triglycerides and lower high-density lipoprotein-cholesterol, IR to reduced glucose tolerance, higher free fatty acids, triglyceride and low-density lipoprotein-cholesterol, and lower high-density lipoprotein-cholesterol, and insulin response to higher heart rate, blood pressure and fasting glucose, and the same dyslipidemic profile as IR (P < or = 0.05 for all). By factor analysis, three main factors (related to IR, age, and fatness, respectively) appeared to underlie this pattern of associations. Each of BMI, waist girth, IR, and insulin response was independently associated with total CVRF load (all P < 0.001).


CONCLUSIONS
When IR, fat mass and distribution, and insulin response are measured simultaneously in a large cohort, no one factor stands out as the sole driving force of the CVRF cluster, each being associated with one or more physiological pathways according to known cause-effect relationships.
Ferrannini
Ele
E
Department of Internal Medicine, University of Pisa, Via Roma, 67-I-56100 Pisa, Italy. ferranni@ifc.cnr.i
Balkau
Beverley
B
Coppack
Simon W
SW
Dekker
Jacqueline M
JM
Mari
Andrea
A
Nolan
John
J
Walker
Mark
M
Natali
Andrea
A
Beck-Nielsen
Henning
H
D050153:Abdominal Fat / Q000502:physiology; D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D008297:Male; D008659:Metabolic Diseases / Q000453:epidemiology / Q000503:physiopathology*; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000453:epidemiology; D010808:Physical Examination; D011446:Prospective Studies; D012307:Risk Factors; D012727:Sex Characteristics; D049629:Waist-Hip Ratio
D007328:Insulin; D008055:Lipids