Insulin resistance as a major determinant of increased coronary heart disease risk in postmenopausal women with Type 2 diabetes mellitus.
OBJECTIVE
To investigate the risk factors associated with clinically defined coronary heart disease (CHD) in women with Type 2 diabetes mellitus (DM).


METHODS
CHD status was assessed via standard history and resting electrocardiogram in 41 postmenopausal diabetic and 41 age- and body mass index-matched normoglycaemic women recruited from a community-based cohort. The following parameters were assessed: body composition by dual energy X-ray absorptiometry, blood pressure, metabolic and lipoprotein profile and haemostatic factors.


RESULTS
Diabetic women with CHD (n = 14) had greater insulin resistance, calculated by homeostasis model assessment (10.2 (7.0-14.8) vs. 6.5 (5.5-7.7), P = 0.010), and higher plasminogen activator inhibitor-1 (PAI-1) levels (45 (29-69) vs. 24 (19-32) ng/ml, P = 0.013), than those without CHD. They also had higher triglycerides (2.9 (2.2-3.8) vs. 2.1 (1.8-2.4) mmol/l, P = 0.016) and a trend towards reduced low-density lipoprotein particle size (25.5 +/- 0.6 vs. 25.8 +/- 0.5 nm, P = 0.097). In a logistic regression model, insulin resistance was a significant independent predictor of CHD status (odds ratio = 1.33, 95% confidence interval = 1.06-1.68, P = 0.015). In contrast, in normoglycaemic women the major risk factors for CHD were elevated cholesterol, apolipoprotein(a), apolipoprotein B and systolic blood pressure (P = 0.018, P = 0.016, P = 0.006 and P = 0.049, respectively).


CONCLUSIONS
Increased insulin resistance in association with elevated PAI-1 and dyslipidaemia appears to underpin the increased risk of CHD in women with Type 2 DM. Therapeutic approaches that increase insulin sensitivity may serve to reduce CHD risk in this vulnerable group. Diabet. Med. 18, 476-482 (2001)
Stoney
R M
RM
Nutrition Department, Alfred Hospital, Melbourne, Australia.
O'Dea
K
K
Herbert
K E
KE
Dragicevic
G
G
Giles
G G
GG
Cumpston
G N
GN
Best
J D
JD
D015502:Absorptiometry, Photon; D000273:Adipose Tissue / Q000033:anatomy & histology; D000368:Aged; D000419:Albuminuria; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D003327:Coronary Disease / Q000453:epidemiology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000503:physiopathology; D004562:Electrocardiography; D005167:Factor VII / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008875:Middle Aged; D008954:Models, Biological; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017698:Postmenopause / Q000502:physiology*; D011384:Proinsulin / Q000097:blood; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D005167:Factor VII; D005340:Fibrinogen; D011384:Proinsulin; D002784:Cholesterol