Original researchSex Differences in Cardiovascular Disease Risk in Adolescents With Type 1 Diabetes
Introduction
Cardiovascular mortality is increased in patients with diabetes.1 Patients with type 1 diabetes have a cumulative mortality of 35% from coronary artery disease compared with 4% to 8% in the general population.2 However, women with both type 1 and type 2 diabetes have a higher relative risk of cardiovascular disease (CVD) than men. In a diabetes cohort of almost 24,000 patients in the United Kingdom diagnosed with diabetes before age 30 years, female patients had much higher standardized mortality ratios compared with male patients.3 Data from Alleghany county in Pennsylvania show a similar trend, with a standardized mortality ratio in women more than triple that seen in men.4 The higher relative risk in female patients with type 1 diabetes compared with male patients with type 1 diabetes is seen across all ages, with the highest relative risk seen in younger populations.5 In contrast, this sex difference is not evident in individuals without diabetes. These data suggest that women with diabetes lose the protection enjoyed by premenopausal women without diabetes.
The reasons for increased susceptibility to coronary artery disease in women with diabetes are not clear. Different risk factors contribute to CVD in men and women. In women with type 1 diabetes, waist-to-hip ratio, physical activity, and depressive symptomatology predicted coronary artery disease, whereas renal disease was a better predictor in men.6, 7 A study using electron beam computer tomography showed that women with diabetes have a significantly higher risk of coronary calcification compared with women without diabetes.8 For men there was no significant difference in the coronary calcification score between those with and without diabetes. Also in men the strongest predictor of death due to CVD was a previous history of CVD irrespective of diabetes status. Women with diabetes had a higher cardiovascular mortality even without a history of previous CVD compared with women without diabetes who have had a previous cardiovascular incident.9 These and other data suggest that diabetes somehow increases the cardiovascular burden in a gender-specific manner. The exact pathophysiology is yet to be elucidated.
Our study was done to examine the sex differences in cardiovascular disease risk factors (ie, body composition, vascular elasticity, lipid profile, and levels of apolipoprotein B [apo B] and apoliporotein C-III [apo C-III]) in adolescents with type 1 diabetes between ages 13 and 20 years. The control population consisted of adolescents without diabetes across the same age range. We hypothesized that female adolescents with type 1 diabetes will have more risk factors for cardiovascular disease than male adolescents with type 1 diabetes, whereas girls without type 1 diabetes will be relatively protected, as evident by fewer risk factors compared with their male counterparts.
Section snippets
Patients
This was a cross-sectional study of adolescents with and without type 1 diabetes between ages 13 and 20 years. Children across all weight ranges were recruited. Patients with type 1 diabetes were primarily recruited from diabetes clinics at the University of Oklahoma Health Sciences Center, and healthy subjects were recruited through recruitment fliers and campuswide E-mail messages. A total of 77 children were enrolled, and 68 completed the study. Data from 2 participants were not included in
Results
Twenty-nine adolescents and young adults with type 1 diabetes and 37 children without type 1 diabetes were recruited. The demographic information is given in Table I. There was no significant difference (P > 0.05) in age, HbA1C, weight, or BMI between boys and girls with type 1 diabetes. Similarly there was no sex difference in these demographic variables in subjects without type 1 diabetes.
There was no significant difference in total lean and fat mass between boys and girls with and without
Discussion
Our study demonstrates a higher trunk fat percentage in girls with type 1 diabetes compared with boys, but this sex difference was not present in subjects without type 1 diabetes. A study done by Inberg et al14 using DXA measurements, showed higher BMI and fat mass in girls with type 1 diabetes compared with control subjects tracked over a period of 6 years. However this group did not find any difference in regional adiposity between girls with and without type 1 diabetes. That study did not
Conclusions
Female adolescents and young adults with type 1 diabetes have more centrally distributed fat than their male counterparts, which may contribute to their relatively higher cardiovascular disease risk. Attenuation of the central distribution of fat through exercise and dietary modifications may help ameliorate their subsequent cardiovascular disease burden.
Conflicts of Interest
This work was supported by an investigator-initiated grant from Novo-Nordisk (No. C7042301). The study sponsor did not have any role in the study design, data analysis, or any other aspect of the manuscript. The authors have indicated that they have no other conflicts of interest regarding the content of this article.
Acknowledgments
This work was supported by a General Clinical Research Center grant (No. M01-RR-14467) from the National Institutes of Health National Center for Research Resources. Dr. Krishnan was involved in study design, data collection, data interpretation, literature search, and writing. Dr. Fields helped with study design, data collection, and writing. Drs. Copeland and Blackett helped with study design and writing. Dr. Anderson helped with statistical analysis. Dr. Gardner provided mentorship in study
References (25)
- et al.
The effect of type 1 diabetes mellitus on the gender difference in coronary artery calcification
J Am Coll Cardiol
(2000) - et al.
Regional adiposity and risk for coronary artery disease in type 1 diabetes: does having greater amounts of gluteal-femoral adiposity lower the risk?
Diabetes Res Clin Pract
(2010) - et al.
Apolipoprotein C-III protein concentrations and gene polymorphisms in type 1 diabetes: associations with microvascular disease complications in the DCCT/EDIC cohort
J Diabetes Complications
(2005) - et al.
Apolipoprotein a phenotypes and plasma lipoprotein a concentration in patients with diabetes mellitus
Clin Biochem
(2003) - et al.
Diabetes abolishes the vascular protective effects of estrogen in female rats
Life Sci
(1999) - et al.
The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus
Diabet Med
(1999) - et al.
Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus
Circulation
(2005) - et al.
The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus
Diabet Med
(1999) - Nishimura R, LaPorte RE, Dorman JS, et al. Mortality trends in type 1 diabetes: the Allegheny County (Pennsylvania)...
- et al.
Mortality during 25 years of follow-up of a cohort with diabetes
Int J Epidemiol
(1996)
Coronary artery disease in IDDMGender differences in risk factors but not risk
Arterioscler Thromb Vasc Biol
Cause-specific mortality in a population with diabetes: South Tees Diabetes Mortality Study
Diabetes Care
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