Diabetic Cardiovascular Complications in Women and Young Adults

Abstract

Purpose of Review

Cardiovascular disease (CVD) is the major complication and leading cause of death among individuals with type 2 diabetes (T2D). Women and younger adults with T2D face a disproportionately higher risk of CVD, compared with their male or older counterparts. This review summarizes clinical and epidemiological evidence on the mechanisms underlying these disparities and highlights directions for future research and clinical practice.

Recent Findings

Women with T2D lose the cardioprotection typically seen in the general population and face disproportionately higher cardiovascular risk. This excess risk is influenced by adverse metabolic profiles preceding T2D onset; female-specific factors such as polycystic ovary syndrome and gestational complications; and non-biological contributors, including delayed diagnosis and less optimal healthcare utilization and delivery in women compared with men. Young adults with early-onset T2D also experience a heightened cardiovascular burden, driven by a more aggressive disease course, prolonged exposure to metabolic abnormalities, and distinctive psychosocial stressors that compound their risk. Despite these disparities, both female and young adult patients with T2D remain understudied, hindering the development of precision prevention and management strategies.

Summary

Future mechanistic and interventional research that integrates sex and age as key biological factors will be critical for advancing precision approaches and reducing disparities in diabetes care and outcomes.

Introduction

Type 2 diabetes (T2D) now affects more than 500 million adults worldwide and is projected to surpass 700 million by 2045 [1]. Cardiovascular complications represent the most significant consequences of T2D. Individuals with T2D have a two- to four-fold increased risk of developing atherosclerotic cardiovascular disease (ASCVD), heart failure, and stroke compared with those without diabetes [2]. These cardiovascular diseases (CVD) account for more than half of all deaths among people with T2D, making it the leading cause of morbidity, mortality, and healthcare costs in this population [3]. The pathophysiology linking T2D and CVD is multifactorial, involving insulin resistance, chronic inflammation, endothelial dysfunction, and dyslipidemia [4]. Despite advances in glucose-lowering therapies and cardiovascular risk management, residual CVD risk remains high, particularly among women and younger adults [5–7]. Understanding the mechanisms driving these disparities and improving integrated cardiometabolic care are critical to reducing the risk of CVD in people with T2D. In this review, I synthesized established and emerging evidence on the mechanisms underlying these disparities and underscored key clinical implications and priorities for future research and clinical focus.

Excess CVD Risk in Women with T2D

Accumulating evidence underscores significant and clinically meaningful sex-specific differences in the relationship between T2D and CVD risk. Systematic reviews and meta-analyses have demonstrated that T2D confers a 44% greater excess risk of incident coronary heart disease and a 27% greater excess risk of stroke in women compared with men, independent of sex differences in other major cardiovascular risk factors [8, 9]. The drivers of these sex disparities are multifaceted, encompassing a more adverse metabolic risk profile in women prior to T2D onset, female-specific biological risk factors, and non-biological influences such as disparities in diagnosis, treatment, and social determinants of health, as summarized below.

Worse Metabolic Risk Profile in Women before T2D

Women generally exhibit a more adverse metabolic risk profile than men prior to the diagnosis of T2D (Fig. 1). Studies have shown that women must attain a higher average body mass index (BMI) before receiving a diabetes diagnosis compared with men [10, 11]. One study reported that the age-adjusted mean BMI at diagnosis was approximately 2 kg/m² higher in women than in men, while HbA1c levels within one year of diagnosis were nearly identical between sexes, suggesting that diabetes was detected at a comparable stage of disease progression [11]. Differences in adipose tissue distribution between men and women may explain why women reach overt diabetes with a higher BMI than men [12, 13]. Women typically accumulate more subcutaneous fat, and a greater total fat mass—reflected by higher BMI—is required before these fat stores become saturated and lipids begin to deposit viscerally and ectopically, promoting insulin resistance and the onset of diabetes [14].

Fig. 1.

Risk Factors in the transition from euglycemia to T2D in Women vs. Men

In addition to greater adiposity at diabetes diagnosis, women also tend to have more adverse profiles of other metabolic risk factors—such as blood pressure, lipid levels, and inflammatory markers—compared with men. These factors may deteriorate more rapidly during the prediabetic phase in women than in men [15]. In a previous analysis based on the Atherosclerosis Risk in Communities (ARIC) study, women with pre-diabetes showed more pronounced worsening of metabolic syndrome severity than their male counterparts [15]. Similarly, data from the Bogalusa Heart Study indicate that women who developed T2D accumulated a greater lifetime burden of blood pressure, triglycerides, and LDL cholesterol from young adulthood onward than men [16].

In a recent study of blood metabolome data from the UK Biobank Study (UKB), the authors found that with the development of T2D, there are significant sex differences in changes in lipoproteins, lipids, and inflammatory markers [17]. Among over 100,000 UKB participants with NMR data, women showed higher concentrations of atherogenic lipoprotein/lipid markers, such as total-c, non-HDL-c, remnant-c, VLDL-c, LDL-c, ApoB, and total concentrations of LDL and VLDL in pre-diabetes and newly diagnosed T2D groups, accounting for lipid-lowering medications and other risk factors. Notably, the sex differences become more striking with the advancement of glycemic status. The authors also found unfavorable compositional changes in lipoprotein particles. For example, the constituent TG from VLDL, LDL, and HDL—indicators of increased atherogenic and inflammatory properties of these particles—were higher in men in the euglycemic group. However, in the T2D group, this sex difference reversed, with women showing higher LDL-TG and HDL-TG levels and equivalent VLDL-TG levels compared to men [17]. Marked sex differences in lipoprotein particle sizes were also observed. Euglycemic men typically have higher concentrations of TG-enriched large or medium VLDLs and atherogenic small and medium LDLs, while in the T2D group, the concentrations are either higher in women or show no significant sex difference. Furthermore, with worsening glycemic status, women exhibit significantly higher levels of glycoprotein acetyls (GlycA), a novel inflammatory marker, compared with men [17]. These findings again suggest that women experience earlier and more pronounced metabolic and inflammatory changes before or around the onset of T2D, which could contribute to their increased cardiovascular risk.

Additionally, previous evidence suggests that, during the transition from normal glucose metabolism to the prediabetic stage, women experience greater endothelial dysfunction and more pronounced dysregulation of fibrinolysis and coagulation than men (Fig. 1). [18] Furthermore, women with T2D exhibit more pro-thrombotic compared with men [19]. T2D in women may also elicit a stronger immune response and greater impairment of cellular defenses against oxidative stress [20]. These sex-specific differences in the hemodynamic effects of hyperglycemia may arise from complex interactions between insulin and estrogen signaling and could partially explain the higher excess CVD risk observed in women with T2D. However, further research is needed to confirm these mechanisms [21].

Female-Specific Risk Factors for the Excess CVD Risk

Hormonal and reproductive-related risk factors play an important role in women’s excess CVD risk. The polycystic ovary syndrome (PCOS) describes a female-specific state of androgen excess and hyperinsulinemia related to obesity or T2D, and higher CVD risk [22]. women with preexisting diabetes are more likely to experience early or premature menopause. In an analysis based on three large epidemiological cohorts of more than 9000 women, the authors found that T2D and menopause synergistically increase the risk of CHD, strokes, and the composite ASCVD [23]. Gestational diabetes mellitus (GDM) is an independent risk factor for T2D and subsequent vascular complications, such as CVD. Women with GDM face a more than 70% higher incidence of T2D than prediabetic women do [24, 25]. Women with GDM have a twofold higher risk of cardiovascular events postpartum compared with their peers [26]. Hypertension during pregnancy and preeclampsia increase T2D risk and CVD risk compared to a normotensive pregnancy [27]. Premenopausal women typically have a lower incidence of CVD than men, a cardioprotective advantage attributed to factors such as sex hormone effects and more favorable cardiovascular risk profiles [6]. However, this protection is notably lost in women with T2D [5]. A recent analysis showed that premenopausal women with T2D exhibited lipid and lipoprotein profiles that were comparable to or worse than those of age-matched men with T2D [17]. These findings highlight that T2D may abolish—or even reverse—the inherent cardioprotection in women, exerting a profound detrimental impact on their cardiovascular health.

Sex Differences in Non-Biological Risk Factors

In addition to biological sex differences, disparities in health care utilization and delivery contribute significantly to the observed sex differences in diabetic CVD risk. Historically, women in general have been less likely than men to receive lipid-lowering therapies, aspirin, ACE inhibitors, and beta-blockers, a gap that may reflect under-recognition of cardiovascular risk in women, atypical symptom presentation, and implicit biases in clinical practice [28]. Further evidence indicates that women are also less likely than men to undergo cardiovascular risk factor screening [29]. In a large study of 10,000 individuals with coronary heart disease, secondary prevention and risk factor management were generally less optimal in women compared with men [30].

Despite improvements in diabetes diagnosis overall, women, particularly premenopausal women, continue to experience a rising prevalence of undiagnosed diabetes [31]. Prolonged periods of unmanaged hyperglycemia in these women have been associated with a greater risk of cardiovascular disease compared with men (Fig. 1) [32]. This delay in recognition and treatment may amplify the adverse metabolic and vascular changes already observed in women, further contributing to their heightened cardiovascular vulnerability in the context of T2D.

With respect to T2D management, studies have reported inconsistent results regarding the presence, extent, and direction of sex differences, and definitive conclusions about their impact on cardiovascular outcomes remain elusive. Available evidence suggests that female patients with T2D are generally less likely than men to achieve recommended LDL cholesterol targets, [33, 34] whereas glycemic control, particularly as measured by HbA1c, appears to be largely similar between the sexes [35–38]. In a large population-based study from Italy, women with T2D were less likely than men to undergo kidney function tests, foot examinations, and eye screenings, and they were also less likely to reach target levels for HbA1c and LDL cholesterol despite receiving pharmacologic therapy [39]. When risk factors remained uncontrolled, women were more frequently prescribed insulin or antihypertensive medications but were less likely than men to receive appropriate treatment for micro- or macroalbuminuria [39]. In contrast, a study using data from the U.S. Medical Expenditure Panel Survey household component found that over a nine-year period, women were more likely than men to have annual dilated eye exams, regular blood pressure checks, and physician visits. In contrast, no sex differences were observed for HbA1c testing or foot examinations [40]. Additionally, a Dutch primary care study of patients with diabetes found that women receiving lipid-lowering therapy were less likely than men to achieve LDL cholesterol targets, whereas women prescribed antihypertensive medications were more likely to reach blood pressure goals [41]. These findings suggest that sex differences in risk factor control, potentially driven by variations in medication type, dosage, or adherence, may or may not account for the long-term disparities in cardiovascular complications, highlighting the need for further research.

Excess CVD Risk among Young Adults with T2D

The incidence and prevalence of T2D have risen sharply among adolescents and young adults over recent decades, paralleling the escalating rates of obesity. Early-onset adult T2D—defined as a diagnosis between ages 20 and 40—now accounts for up to 20% of all adult T2D cases [42]. Compared with those with later-onset T2D, young adults with early-onset T2D face a substantially higher risk of complications, including CVD [42]. Although numerous studies have reported declines in major complications of T2D, including CVD and mortality, such improvements have not extended to the young adult patient group [43–45]. Between 1995 and 2015, a marked resurgence of complications, particularly acute myocardial infarction and stroke, was observed among individuals aged 18–44 years [46]. In this review, I focus on the adult form of T2D, recognizing differences in pathophysiology and management strategies between T2D in children and adolescents and in adults [47, 48].

Age at Diabetes Onset Versus Chronologic Aging in Cardiovascular Risk

Disentangling the effects of age at T2D onset from those of the aging process itself on CVD risk is challenging. To address this issue, studies have either adjusted for diabetes duration [49] or compared individuals with different ages of T2D onset at the same duration of disease [50]. A recent meta-analysis of over one million people with T2D worldwide found that each one-year increase in age at diagnosis was associated with a 3%–5% lower risk of cardiorenal disease and all-cause mortality, after adjusting for current age [51]. Excess mortality risk associated with T2D is highest among the youngest individuals and progressively decreases with increasing age [52–54]. In a national registry analysis in Sweden examining mortality and CVD outcomes by age at T2D diagnosis, younger onset was associated with markedly higher risks for all outcomes and the greatest loss of life-years [54]. Nonfatal CVD risks, particularly for coronary heart disease and heart failure, were four- to five-fold higher among those diagnosed at younger ages. These excess risks declined progressively with older age at diagnosis and became negligible or absent in individuals beyond age 80, when adjusted mortality and life-years lost were no longer elevated [54]. Together, these findings underscore that age at T2D diagnosis is a strong prognostic factor for survival and cardiovascular risk, with important implications for determining the timing and intensity of risk-factor interventions in clinical decision-making and guideline-directed care.

Cumulative Burden of Metabolic Risk Factors and Aggressive Disease Course in Young Adult T2D Patients

Several factors may contribute to this elevated CVD risk in young adults with T2D. The cumulative burden of metabolic risk factors plays a critical role in the early development of cardiovascular dysfunction among young adults with T2D. Sustained exposure to hyperglycemia, severe insulin resistance, dyslipidemia, elevated blood pressure, and chronic low-grade inflammation accelerates adverse cardiac remodeling and impairs vascular function [55–57]. Observational cohort studies have demonstrated that these long-standing metabolic disturbances beginning in early adulthood are associated with alterations in cardiac structure and function by midlife, including left ventricular hypertrophy, diastolic dysfunction, and subclinical myocardial injury [56–58]. Such early cardiometabolic derangements substantially increase the risk of premature coronary heart disease and heart failure in individuals with early-onset T2D. Additionally, the higher risk of complications is attributable to a potentially more aggressive trajectory characterized by rapid β-cell decline and poor glycemic durability, as shown in young patient cohorts [59, 60]. These pathophysiologic features contribute to the substantially higher rates of microvascular and macrovascular complications observed in those with early-onset T2D, beyond what would be expected from longer disease duration alone.

Psychosocial Stressors Are Uniquely Impactful among Young Adults with T2D

Psychosocial stressors are a critical but underexplored dimension of CVD risk in people with diabetes, particularly young adults with T2D. Psychosocial stressors are especially salient during young adulthood, a life stage marked by economic transitions, evolving social networks, and the emergence of mental health disorders [61]. These stressors also disproportionately affect subgroups with T2D [62]. Income instability can profoundly affect young adults with T2D by disrupting consistent disease management and worsening long-term outcomes [63, 64]. Fluctuating income is associated with lapses in health insurance coverage, reduced access to medications and glucose-monitoring supplies, and reliance on low-cost, unhealthy foods [64]. Financial uncertainty generates chronic stress, which can exacerbate insulin resistance and increase the risk of depression and anxiety, further undermining diabetes self-care [64, 65]. Moreover, unstable or irregular employment patterns can disrupt routines essential for maintaining glycemic control [63, 64].

Young adulthood is a period marked by significant changes in relationships and social support systems [61, 66]. Shifts in social support can introduce unique sources of stress for young adults with T2D—particularly due to a decline in family involvement in diabetes management and an increased reliance on emotional support from romantic partners [66]. Among young adults with T2D, higher levels of perceived social support, regardless of sources, are associated with better glycemic control and greater engagement in diabetes self-management behaviors [67, 68] Social support is also linked to improved quality of life and may buffer the adverse effects of diabetes distress and depressive symptoms on self-management in both type 1 and type 2 diabetes [69]. Reduced support from family, peers, or partners, however, in young adult patients, has been associated with poorer medication adherence, more risk behaviors, higher stress levels, and increased CVD risk [66].

Although social support interventions hold strong potential to improve key clinical and psychosocial outcomes in individuals with diabetes, most intervention studies have focused on older adults with T2D [66, 70, 71].Among older adult patients, consultations with diabetes care professionals have been associated with lower HbA1c levels, and internet- or telephone-based peer support programs have improved perceived support and physical activity. However, traditional forms of support from spouses, family, or friends have not consistently demonstrated benefits in glycemic control [72]. These findings underscore the potential importance of social support in diabetes management. Still, evidence specific to young adults remains limited and warrants further investigation to determine whether they experience similar benefits [66].

Psychological conditions such as depression and anxiety frequently coexist with T2D in young people. Elevated depressive symptoms and depressive disorders affect one in four patients with diabetes [73]. Previous studies have shown that nearly 40% of hospitalizations among young adults with T2D are related to mental health conditions [74]. In a Swedish population-based study, young adults with T2D had three- to four-fold higher odds of depression, bipolar disorder, anxiety, or stress-related disorders compared with those with later-onset T2D [62]. Another study similarly reported a higher prevalence of depressive symptoms, diabetes distress, and lower self-compassion among younger individuals compared with their older counterparts [75].

Both psychological comorbidities and diabetes-related distress are associated with suboptimal glycemic control and an increased risk of complications and mortality [76–79]. In a recent analysis using data from the UKB, the authors found that an adverse psychosocial risk cluster—characterized by a higher probability of depression or anxiety—was significantly associated with increased CVD risk among individuals with T2D [80]. Notably, the magnitude of this association exceeded that of clusters defined by traditional lifestyle risk factors [80]. The coexistence of mental health conditions and T2D in elevating CVD risk likely reflects the complex interplay of challenges in chronic disease management, genetic predisposition, and shared cardiometabolic risk pathways [81].

Research on mental health conditions in young people with T2D remains limited. A bidirectional relationship likely exists, as psychological distress, depression, and anxiety can contribute to unhealthy behaviors and metabolic dysregulation, while the daily burden of diabetes management may exacerbate emotional distress. Understanding the nuances of these associations is crucial, as the underlying direction and mechanisms have distinct clinical implications for prevention, screening, and the integration of mental health support into diabetes care for young adults.

Conclusions

Cardiovascular complications are a major driver of morbidity and mortality in T2D, with disproportionate burden observed in women and young adults. Women with T2D lose the cardioprotection typically observed in the general population and face higher relative risks of ASCVD, heart failure, and mortality compared with men. This excess risk is likely shaped by adverse metabolic profiles preceding diabetes onset, female-specific risk factors, and behavioral as well as healthcare utilization and delivery differences by sex. Young adults with early-onset T2D also face elevated cardiovascular risk, marked by a more aggressive disease trajectory, longer cumulative exposure to metabolic dysregulation, and distinct psychosocial challenges compared with those diagnosed later in life. Despite these disparities, both groups remain underrepresented in clinical research, limiting the development of targeted prevention and management strategies. Addressing this gap will require mechanistic investigation incorporating sex and age as biological variables, and precision intervention approaches that integrate psychosocial, metabolic, and molecular risk profiles. Such efforts are critical to reduce inequities and improve cardiovascular outcomes among women and young adults living with or at risk for T2D.

Key References

• Regensteiner JG, Reusch JEB. Sex Differences in Cardiovascular Consequences of Hypertension, Obesity, and Diabetes: JACC Focus Seminar 4/7. J Am Coll Cardiol. Apr 19 2022;79(15):1492–1505. doi:10.1016/j.jacc.2022.02.010.

  • ○ This review paper is impactful because it highlights sex differences in cardiovascular consequences of chronic conditions, including diabetes.
• Misra S, Ke C, Srinivasan S, et al. Current insights and emerging trends in early-onset type 2 diabetes. The Lancet Diabetes & Endocrinology. 2023;11(10):768–782. doi:10.1016/S2213-8587(23)00225-5.

  • ○ This paper is important because it provides a comprehensive overview of early-onset type 2 diabetes, highlighting its rising prevalence, unique pathophysiology, increased risk of complications, and emerging research and clinical strategies to improve prevention and management in younger populations.
• Yoshida Y, Li D, Li X, et al. Greater alterations in atherogenic lipids and inflammatory markers in women during type 2 diabetes development and risk of coronary heart disease—findings from two population-based studies. Journal of Clinical Lipidology. 2025/08/22/2025;doi:10.1016/j.jacl.2025.08.010.

  • ○ This paper is important because it leveraged large blood metabolome data and demonstrates that women experience greater changes in atherogenic lipids and inflammatory markers during the development of type 2 diabetes, helping to explain their higher relative risk of coronary heart disease compared with men.
• Yoshida Y, Zu Y, Aguilar D, Ferdinand KC, Fonseca VA. Cumulative effect of hyperglycemia and insulin resistance on cardiac dysfunction: The coronary artery risk development in young adults (CARDIA) study. Am Heart J. Sep 17 2025;292:107276. doi:10.1016/j.ahj.2025.09.008.

  • ○ This paper is important because it shows that cumulative exposure to hyperglycemia and insulin resistance in young adults contributes to early cardiac dysfunction, highlighting the long-term cardiovascular impact of metabolic risk factors from a young age.

Author Contributions

YY is the sole author of the manuscript. YY wrote the manuscript and prepared the figure.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The author declares no competing interests.