Sex-Related Differences in Cardiovascular Disease Risk Profile in Children and Adolescents with Type 1 Diabetes

Abstract

Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profiles; the girls were on the whole more impacted.

Increased prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes and hypertension: The SWEET international database

“…Hormonal causes, worse glycaemic control in females than males, especially during adolescence, psychosocial factors, and CVRFs have been implicated. 29 In this study, girls had a higher prevalence of obesity than boys, which probably contributed to this difference. However, it should be underlined that boys had higher SBP in our cohort than girls, which is consistent with BP normalcy tables showing higher BP values in boys.…”

“…In this study, female patients had a higher prevalence of accumulated risk factors than male patients. Other studies have also shown that girls with T1D have a higher prevalence of individual CVRFs compared with boys, although it is less clear when excess cardiovascular risk begins in female patients with T1D 29,30 . A study in Australia showed that young female participants with T1D had higher SBP, DBP, cholesterol, and albumin excretion rate than male participants, together with a higher risk of developing CVD 31 .…”

“…The reason for this gender difference is not clear. Hormonal causes, worse glycaemic control in females than males, especially during adolescence, psychosocial factors, and CVRFs have been implicated 29 …”

“…Other studies have also shown that girls with T1D have a higher prevalence of individual CVRFs compared with boys, although it is less clear when excess cardiovascular risk begins in female patients with T1D. 29,30 A study in Australia showed that young female participants with T1D had higher SBP, DBP, cholesterol, and albumin excretion rate than male participants, together with a higher risk of developing CVD. 31 Thus, the authors suggested that the loss of the protective effect of female sex on cardiovascular risk in T1D is present from childhood.…”

Cardiovascular Implications of Immune Disorders in Women

“…Compared with healthy controls, the ASCVD mortality ratio for people with type 1 diabetes was 40-fold in women and 10-fold in men—a difference that starts as early as in childhood and adolescence 90 and was not fully attributable to differences in traditional risk factors or glycemic management. 90,135 In people with RA, several studies have established that men have a greater burden of traditional ASCVD risk factors than women, 136,137 while women are at greater risk for left ventricular hypertrophy than men with an odds ratio of 6.56 (95% CI, 1.34–30.96) after controlling for CVD risk factors. 91 In one study, women <40 years old had the same ASCVD event rate as age-matched men, although men versus women in all older age groups had a greater event rate.…”