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Published online October 12, 2007
Diabetes Care 31:170-172, 2008
DOI: 10.2337/dc07-0272
© 2008 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Research

Type 2 Diabetes Without the Atherogenic Metabolic Triad Does Not Predict Angiographically Assessed Coronary Artery Disease in Women

Patricia Blackburn, MSC1,2,3,4, Isabelle Lemieux, PHD1, Benoît Lamarche, PHD, FAHA3,5, Jean Bergeron, MD6, Patrice Perron, MD4, Gérald Tremblay, MD4, Daniel Gaudet, MD4,7 and Jean-Pierre Després, PHD, FAHA1,8

1 Québec Heart Institute, Hôpital Laval Research Centre, Québec, Québec, Canada
2 Division of Physical Activity Sciences, Université du Québec à Chicoutimi, Saguenay, Québec, Canada
3 Department of Food Sciences and Nutrition, Université Laval, Québec, Québec, Canada
4 Chicoutimi Hospital Lipid Clinic, Chicoutimi University Hospital, Saguenay, Québec, Canada
5 Institute on Nutraceuticals and Functional Foods, Université Laval, Québec, Québec, Canada
6 Lipid Research Centre, CHUL Research Centre, Québec, Québec, Canada
7 Community Genomic Medicine Centre, Université de Montréal, Montréal, Québec, Canada
8 Division of Kinesiology, Université Laval, Québec, Québec, Canada

Address correspondence and reprint requests to Jean-Pierre Després, PhD, FAHA, Director of Research, Québec Heart Institute, Hôpital Laval Research Centre, 2725, chemin Ste-Foy, Pavilion Marguerite-D'Youville, 4th Floor, Québec (Québec) Canada G1V4G5. E-mail: jean-pierre.despres{at}crhl.ulaval.ca

Abbreviations: CAD, coronary artery disease • CHD, coronary heart disease


   INTRODUCTION
TOP
 INTRODUCTION
RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 
Evidence suggests that the coronary heart disease (CHD) risk of type 2 diabetes is heterogeneous and affected by the presence/absence of the metabolic syndrome (1). We have previously reported that specific features of the metabolic syndrome (atherogenic metabolic triad) were associated with a 20-fold increase in the risk of developing CHD (2). Considering the costs and lack of standardization of these indexes in clinical practice, we have suggested that the simultaneous measurement and interpretation of waist circumference and fasting triglyceride levels were useful in identifying individuals with the atherogenic metabolic triad and therefore at increased risk for coronary artery disease (CAD) (3). The main objective of the present study was to compare the risk of CAD between nondiabetic and type 2 diabetic women with/without features of the atherogenic metabolic triad.


   RESEARCH DESIGN AND METHODS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
RESULTS
 CONCLUSIONS
 References
 
This cross-sectional study was conducted in a sample of 250 women (56.2 ± 9.1 years) who underwent an angiographic procedure for the investigation of retrosternal pain. Subjects were French Canadians of European origin (Caucasians). Inform written consent was obtained and the study approved by the Chicoutimi Hospital Ethics Committee. CAD was assessed by angiography (4). Anthropometric measurements were performed following standardized techniques (5). Fasting lipid profile, glycemia, and LDL particle size (6–8) were determined according to routine methods. Homeostasis model assessment was used to estimate insulin resistance (fasting insulin x fasting glucose)/22.5 (9). Nondiabetic and diabetic women were classified according to previously established diagnoses of type 2 diabetes or by fasting glucose concentrations (≥7.0 mmol/l). Nondiabetic women without CAD and with a BMI <25 kg/m2 (n = 25) were used to arbitrarily determine the reference value for apolipoprotein B using the 50th percentile of the variable (0.85 g/l). Cutoffs for insulin levels and LDL particle size corresponded to 60 pmol/l and 255 Å, determined from published studies (10,11). Specificity and sensitivity analyses were performed to determine triglycerides and waist girth cutoffs associated with the absence/presence of the atherogenic metabolic triad. A plasma triglyceride cutoff of 1.6 mmol/l combined with a waist circumference of 85 cm gave optimal sensitivity and specificity (66% for both). To keep our algorithm simple for physicians, values of 1.5 mmol/l and 85 cm were selected.

Group differences for continuous variables were examined using Student's unpaired t tests or ANOVA. Fasting triglyceride levels were log transformed. Logistic regression models were used for modeling risk relations considering age, menopausal status, smoking habits, and hormone replacement therapy as possible confounders. Women were classified into two or three groups according to their diabetes status and the presence/absence of the atherogenic metabolic triad. The nondiabetic group or the nondiabetic group characterized by none or 1 feature of the atherogenic metabolic triad were considered the reference group. Comparison of prevalence data among subgroups was performed by the likelihood {chi}2 analysis. Analyses were performed with SAS software.


   RESULTS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
CONCLUSIONS
 References
 
The odds ratio (OR) of being affected by CAD was increased by 3.8-fold (95% CI 1.5–9.2; P < 0.004) among type 2 diabetic compared with nondiabetic women. This association remained significant even after adjustment for confounding variables (OR 3.3 [95% CI 1.0–10.0]; P = 0.04). However, CAD risk in women with type 2 diabetes was only significantly increased among those showing two or three features of the atherogenic metabolic triad (8.0 [1.8–34.9]; P < 0.006), whereas diabetes per se was not predictive of CAD in the absence of the atherogenic metabolic triad (zero to one feature). Adjustment for confounders attenuated this relationship, which nevertheless remained significant (4.7 [1.0–22.1]; P < 0.05).

An increased proportion (71%) of type 2 diabetic women with two to three features of the atherogenic metabolic triad was characterized by hypertriglyceridemic waist (waist circumference ≥85 cm and fasting triglyceride levels ≥1.5 mmol/l), whereas in the absence of the atherogenic metabolic triad (zero to one feature), its prevalence only reached 43% in type 2 diabetic women and 31% in nondiabetic women.

Characteristics of nondiabetic and type 2 diabetic women with/without CAD are shown in Table 1. Type 2 diabetic women with CAD were characterized by a more disturbed fasting plasma lipoprotein-lipid profile compared with type 2 diabetic women without CAD. Among type 2 diabetic women, 68% with CAD had hypertriglyceridemic waist, whereas none of the CAD-negative women had this phenotype.


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  		Table 1— Physical characteristics and fasting metabolic profile of nondiabetic and diabetic women stratified by CAD status

 

   CONCLUSIONS
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
References
 
Using National Health and Nutrition Examination Survey III data, Alexander et al. (1) found that when compared with diabetic patients with the metabolic syndrome, diabetic patients without the metabolic syndrome (using National Cholesterol Education Program–Adult Treatment Panel III criteria [12]) showed a reduced prevalence of CHD (1). These results provided evidence that diabetes is a heterogeneous condition and that diabetic subjects characterized by the metabolic syndrome were at substantially increased risk of CHD. Results of the present study are concordant with these previous results and suggest that physicians may need to go beyond glycemia to properly evaluate/manage CAD risk in their patients with type 2 diabetes.

We have previously suggested that fasting insulin concentrations, apolipoprotein B levels, and LDL size could improve our ability to identify high-risk patients (2). We recognize, however, that these markers are not widely available in clinical practice and therefore suggest that the simultaneous measurement and interpretation of waist circumference and fasting triglyceride levels could help identify high-risk subjects with the atherogenic metabolic triad (3,13–16). A total of 71% of type 2 diabetic women with hypertriglyceridemic waist were characterized by two to three features of the atherogenic metabolic triad, underlining the importance of this phenotype in the initial screening of high-risk CAD patients, even among women with type 2 diabetes.

In the present study, type 2 diabetes was diagnosed using fasting glucose concentrations. Unfortunately, we did not have access to the 2-h glucose criterion, which would have improved the identification of diabetic subjects. Therefore, we acknowledge that the diagnosis of diabetes was probably underestimated. In addition, the number of type 2 diabetic women without CAD was rather small, increasing the probability of a type 2 error (false negative). Thus, results of this angiographic study suggest that diabetes per se is not predictive of CAD in women in the absence of features of the metabolic syndrome. These results provide further support to the notion that abdominal obesity and hypertriglyceridemia as markers of the metabolic syndrome are important CAD risk factors to assess/manage in women with type 2 diabetes.


   Acknowledgments
 
This study was supported by the Canadian Diabetes Association.


   Footnotes
 
Published ahead of print at http://care.diabetesjournals.org on 12 October 2007. DOI: 10.2337/dc07-0272.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received for publication February 9, 2007. Accepted for publication October 6, 2007.


   References
TOP
 INTRODUCTION
 RESEARCH DESIGN AND METHODS
 RESULTS
 CONCLUSIONS
 References
 

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