Introduction

Diabetes mellitus is a chronic metabolic disease characterized by persistent hyperglycemia. It is one of the largest global health problems. The number of adults (20–79 years) with diabetes is expected to increase from 537 million currently to 783 million by the year 2045 [1]. Type 2 diabetes (T2D) is the most common form of diabetes, which is mainly caused by insulin deficiency and insulin resistance [2]. Despite the significant global burden of diabetes, limited attention has been given to women of reproductive age (15–49 years), whose health not only affects their own survival but also family and social development [3]. More than 199 million living women have diabetes all over the world [4], and a large proportion of them are of reproductive age [4,5].

Moreover, there has been a growing trend in the prevalence of T2D among younger individuals [6], and women of reproductive age are particularly affected. Because the onset of T2D occurs mostly during the reproductive years, it is thought to have adverse effects on fertility and pregnancy [7]. It is becoming increasingly apparent that women with T2D are at high risk for reproductive disorders, an area that has not been well studied [8]. The pathophysiology behind reproductive dysfunction in women with diabetes is complex and related to other conditions such as obesity, polycystic ovary syndrome (PCOS), and endogenous or exogenous hyperinsulinemia [9]. Moreover, T2D in women has implications for intergenerational disease transmission [10] and children born to diabetic women have a greater risk of developing T2D themselves [11–13]. Therefore, a comprehensive understanding of the health status of women of reproductive age will provide important clues to help prevent and manage T2D in women of reproductive age.

Comprehensive studies have shed light on the global prevalence and trends of diabetes between 1990 and 2017. Additionally, investigations into diabetes-related mortality among individuals under the age of 25 spanning from 1990 to 2019 have been conducted [14]. Nevertheless, a significant portion of the existing research on T2D forecasting has been limited to individual countries, such as China and Syria’s economic burden research [15,16] or has predominantly addressed the global economic burden of diabetes in the adult population and lack cross regional and cross Socio-demographic Index (SDI) stratified analysis for women of childbearing age [17], without a detailed cross-country or continental analysis. It is worth noting that the disparities in disease burden among countries with varying socioeconomic statuses remain largely unexplored.

We hypothesize that T2D exhibits different epidemiological characteristics among women of reproductive age in various regions globally. The Global Burden of Disease (GBD) 2021 data was used to compare the status of T2D among women of reproductive age between 1990 and 2021 in terms of age-standardized incidence rates (ASIR), Disability-Adjusted Life Years (DALYs), and Estimated Annual Percentage Change (EAPC) and identified the accelerated growth of disease burden in low and middle SDI regions (such as North Africa, the Middle East) and young women (25–29 years old). This analysis is essential for guiding public health policy and formulating effective strategies to alleviate the T2D burden in this key demographic.

Materials and methods

Statistical analysis

In this study, we report both confidence intervals (CI) and uncertainty intervals (UI) as measures of variability around our estimates. CI are statistical ranges derived from sample data, representing the likelihood that the true population parameter lies within the specified bounds (e.g., 95% CI). In contrast, UI, as used in the GBD framework, account for multiple sources of uncertainty, including sampling error, model uncertainty, and data quality limitations. UI provide a more comprehensive assessment of the potential range of true values for each estimate. Age-standardized rates (ASRs) and 95% CI were computed using the world standard population of GBD 2021 and expressed per 100,000 population. We used the age-standardization method suggested by WHO:

Where α_i is the age-specific rate, and w_i is the weight of the corresponding age group in the chosen standard population (where i denotes the i-th age group).

The EAPC is an established indicator of the trends in ASRs in a regression model [20,21]. It measures the average percentage change in the ASR across all time intervals. Linear regression was used to determine the EAPC based on the equation , where and . The EAPC was calculated using the formula , and the 95% CI was calculated using the linear regression model. UI for each incidence and DALYs number were calculated based on 1000 iterations, with the 2.5th and 97.5th percentile values defining the 95% UI limits.

We performed correlation analysis between ASRs of T2D and the SDI using data of 2021. Spearman’s rank correlation was used to find out the association between these two variables, which would help to understand the relationship between the burden of T2D with the socio-economic status across all districts.

All statistical analyses were conducted using the R program version 4.0.4, with values < 0.05 was considered statistically significant.

Result

Trends in the burden of Type 2 diabetes mellitus (T2DM) among women of reproductive age, 1990–2021

The global trend of T2D among women of reproductive age was substantially increased from 1990 to 2021. The number of new cases of T2D worldwide nearly doubled from 1.07 million in 1990 to 3.03 million in 2019 (S3 Table), and the global DALYs for T2D dramatically rose from 1.17 million to 2.98 million (S3 Table). The ASIR of T2D in women of reproductive age was 101.01/100,000 (95% UI: 100.82, 101.20) in 1990, and it increased to 205.17/100,000 (95% UI: 204.93, 205.40; Table 1) in 2021. Additionally, the age-standardized DALY rate significantly rose from 113.25/100,000 (95% UI: 113.05, 113.46) in 1990 to 198.41/100,000 (95% UI: 198.19, 198.64; Table 1 and Fig 1) in 2021, indicating that the overall disease burden of T2D has substantially increased over the past 30 years.

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Table 1. The ASIR and age-standardized DALY rate of Type 2 diabetes burden in women of reproductive age from 1990 to 2021 in different regions.

https://doi.org/10.1371/journal.pone.0322787.t001

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Fig 1. The ASRs of global burden of Type 2 diabetes mellitus among women of childbearing age by region in 1990 and 2021.

https://doi.org/10.1371/journal.pone.0322787.g001

When categorized by SDI, we observed the highest ASIR and age-standardized DALY rate in regions with a low-middle SDI (ASIR 104.44, 95% UI 104.00 to 104.88; age-standardized DALY rate 136.78, 136.27 to 137.29), while regions with a low SDI demonstrated the lowest ASIR (85.11, 84.49 to 85.73; Table 1). The relationship between ASIR, age-standardized DALY rate, and SDI exhibited an inverse U-shaped curve, where countries with a low-middle and middle SDI experienced higher ASIR and age-standardized DALY rates compared to those with a low SDI (all models, P < 0.01; S2 Fig).

Furthermore, the EAPC (Fig 1) showed that both ASIR and age-standardized DALY rates for T2D were increasing, and the increase rate of incidence was slightly higher than the age-standardized DALY rate, which is indicative of the changing burden of T2D among women of reproductive age (S1, S2 Tables and S1 Fig).

Age distribution of the global burden of T2DM among women of reproductive age in 2019

The incidence and DALY rates of T2D among women of reproductive age in 2021 increased with age. The increase was more rapid, starting from age 25–29 years, especially for the global burden (Fig 2).

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Fig 2. Global Heatmap of incidence of Type 2 diabetes mellitus rates among women of childbearing age in 2021 by country and age group.

https://doi.org/10.1371/journal.pone.0322787.g002

The age group-wise analysis showed that the incidence rate of T2D among women of reproductive age had a slow increase in the youngest group (15–19 years) and then increased rapidly, reaching a peak in the 25–29 years’ age group (S3 Fig). Thereafter, it declined slightly in older groups of 35–39 years (Fig 2).

Discussion

While this study provides valuable insights into the global burden and trends of T2DM among women of reproductive age, it is important to note that the findings primarily identify associations and trends rather than establishing direct causal relationships. The observed increases in ASIR and DALYs across different regions and socioeconomic groups highlight potential correlations with factors such as urbanization, lifestyle changes, and healthcare access. However, these associations do not imply causation. This trend is closely associated with adverse lifestyle choices, Similarly, the pronounced increase in T2DM incidence among younger women aged 25–29 years underscores the potential role of adverse lifestyle factors, such as poor dietary habits, physical inactivity, and obesity [22], leading to interrelated health issues such as insulin resistance, PCOS, and obesity [22].

The risk factors for T2D in women of reproductive age are diverse, encompassing traditional factors such as age, and emerging ones like lifestyle-related obesity and sedentary behavior [23]. Additionally, gestational diabetes mellitus (GDM), PCOS, hypertension, dyslipidemia, and racial/ethnic predispositions also play significant roles [24]. Insulin resistance and beta-cell dysfunction are central to the pathogenesis of T2DM, particularly in women of childbearing age, where female-specific hormonal changes further complicate their roles. Insulin resistance, often driven by obesity and sedentary lifestyles, is exacerbated during specific phases of the menstrual cycle, such as the luteal phase, when progesterone levels are elevated, potentially impairing insulin sensitivity [7]. Additionally, conditions like PCOS, which is closely linked to insulin resistance, disproportionately affect this demographic, creating a vicious cycle of metabolic dysregulation and reproductive dysfunction [9]. Pregnancy introduces another layer of complexity, as gestational hormones, including human placental lactogen and progesterone, induce physiological insulin resistance to ensure fetal nutrient supply, but this can precipitate GDM in predisposed individuals [24]. Beta-cell dysfunction, on the other hand, reflects an inability to compensate for increased insulin demands, particularly during pregnancy, leading to hyperglycemia [10]. The interplay between these mechanisms underscores the heightened vulnerability of women of childbearing age to T2DM, emphasizing the need for targeted interventions that consider hormonal fluctuations and reproductive health [8].

Lifestyle interventions play a pivotal role in the management and treatment of T2DM among women of childbearing age, addressing both prevention and disease control. Dietary control, regular physical activity, and weight management are foundational strategies that can significantly improve glycemic control, reduce insulin resistance, and mitigate the risk of diabetes-related complications in this demographic [23]. For instance, adopting a balanced diet rich in whole grains, lean proteins, healthy fats, and fiber while limiting processed foods and added sugars has been shown to lower blood glucose levels and improve metabolic outcomes [24]. Similarly, regular exercise, including both aerobic and resistance training, enhances insulin sensitivity and aids in weight management, which is particularly critical given the rising prevalence of obesity—a major risk factor for T2DM—among younger populations [25]. Weight management, especially in women with PCOS, not only improves reproductive health but also reduces the overall burden of metabolic disorders [26]. Furthermore, lifestyle modifications are cost-effective and empower women to take an active role in managing their health, which is crucial during reproductive years when the implications extend to future generations [27]. Despite these benefits, adherence to lifestyle interventions remains a challenge, necessitating culturally tailored public health strategies and increased awareness campaigns to address barriers such as socioeconomic constraints, lack of education, and limited access to resources [28]. By prioritizing lifestyle interventions, healthcare systems can foster long-term improvements in the health outcomes of women with T2DM, ultimately reducing the global burden of the disease.

The WHO Global Action Plan on Diabetes and the WHO Global Diabetes Compact formulated in 2021, are a part of a global response to address this growing concern [25]. Our findings suggest more than a two-fold increase in incident cases of T2D in 17 out of 21 regions between 1990 and 2021 signifying its increasing burden. At the same time, the rise in incidence and DALYs of T2D globally, emphasizes the growing challenge of this disease [26]. The striking rise in the T2D ASIR suggests an increase in new cases due to better diagnosis and/or a real increase in disease burden. The GBD 2021 Diabetes Collaborators projected that by 2050, 89 (43.6%) of 204 countries and territories will have an age-standardized prevalence > 10% [27]. In contrast to the ASIR, the relatively slower increase in DALYs suggests improvements in the management and care of T2D. As demonstrated in a previous publication [28], huge strides have been made in the treatment of hyperglycemia in recent years with the availability of many new agents which have widened the therapeutic options for T2D. These developments are likely to have led to better outcomes for the disease as is suggested by the slower increase in DALYs.

The incorporation of innovative glucose-lowering medications, such as GLP-1 receptor agonists and SGLT2 inhibitors, represents a promising advancement in the management of T2DM among women of childbearing age. These therapeutic agents not only effectively lower blood glucose levels but also offer additional benefits that are particularly relevant to this demographic. GLP-1 receptor agonists have been shown to promote weight loss and reduce cardiovascular risk, addressing two critical concerns in women with T2DM who often face obesity and heightened cardiovascular vulnerability [28]. Similarly, SGLT2 inhibitors have demonstrated significant cardioprotective and renoprotective effects, which are crucial given the increased risk of cardiovascular and renal complications in women with T2DM [29]. Furthermore, these medications may mitigate some of the reproductive health challenges associated with T2DM, such as PCOS, by improving insulin sensitivity and reducing hyperandrogenism [30]. However, careful consideration is required when prescribing these agents to women of childbearing age, particularly during pregnancy, as their safety profiles in gestational contexts remain under investigation [31]. Despite these challenges, the potential of GLP-1 receptor agonists and SGLT2 inhibitors to improve long-term health outcomes underscores the importance of personalized treatment strategies tailored to the unique physiological and reproductive needs of this population.

The inverse U-shaped relationship between SDI and T2DM burden suggests that socioeconomic development may initially exacerbate the disease burden before improvements in healthcare and preventive measures lead to a decline in high-income settings. While this pattern aligns with existing literature on the epidemiological transition [29], further research is needed to explore the underlying mechanisms driving these trends. Health outcomes and disease burden were strongly linked to socioeconomic development as measured by the SDI [29]. Our analysis further suggests strong geographical heterogeneity of the T2D trends for women of reproductive age across various SDI categories, showing an inverted-U-shaped relationship between SDI and ASIR, age-standardized DALY rate. This suggests that age standardized rates of T2D initially deteriorate with countries’ development but fall in the later stages of development suggesting possibly improved access to care. High-income North America, North Africa and Middle East, East Asia, Western Europe had the largest annual increases in ASIR and age-standardized DALY rates. In 2021, four Oceanian countries (Solomon Islands, Kiribati, Marshall Islands, American Samoa) had the highest age-standardized DALY rates and ASIR. The findings are consistent with the Lancet report that some regions have experienced high diabetes prevalence rates in 2021 [27]. These high prevalence rates of type 2 diabetes may be due to the genetic susceptibility of certain populations such as South Asians [30]. Meanwhile, the diabetes burden in low- middle-income countries (LMICs) is exacerbated by economic and sociopolitical factors [31], such as limited health budgets for diabetes control and lack of subsidization for pharmacological treatments. In LMICs, less than 10% of people with diabetes are estimated to be receiving full treatment coverage. For example, Oceania has the lowest medication coverage globally despite experiencing extremely high prevalence rates [32].

But, we observed fast increase in T2D burden among reproductive aged women in Turkmenistan, Mauritius. These countries have witnessed a remarkable increase in T2D prevalence and therefore request immediate public health approaches to reduce the ambient pollution [33]. Our results suggest region-specific approaches with local socioeconomic conditions to combat the rising T2D burden.

Our study observed a pronounced upsurge in both incidence and DALYs among women of reproductive age, predominantly in the 35–39 age bracket globally. This concurs with existing literature that underscores age as a notable risk factor for T2D [34,35]. The heightened peaks were recorded among those aged between 25 and 29 years. Suboptimal glycemic control during the typical reproductive period for women (i.e., aged 25–29 years) may precipitate hyperglycemia during pregnancy and detrimental outcomes for offspring. Consequently, there is an imperative need to bolster the prevention and management of type 2 diabetes among women within this age range [36].

The strength of this study is that it used data from GBD 2021 to analyze the trends of T2D from 1990 to 2021, which allowed us to globally examine the trends of T2D among women of reproductive age. In addition, ASIR, DALY and EAPC indicators make our results more representative of T2D in different regions and age groups. However, there are still some limitations in our research. First, because this analysis is based on the GBD 2021, our results are affected by the methodological flaws of this study. For example, when there is a lack of data, the results depend on the predictive validity of modeling. When there was data, differences in definitions and measurement methods (for example, different case definitions from different sources) may have led to bias. Although the researchers of GBD 2021 study have used many methods to reduce bias and error, residual bias is still possible. In addition, we estimated CI instead of UI for rates after standardization by age. Second, gestational diabetes is not included in our study because it is classified into other maternal disorders in GBD. Therefore, our conclusions need to be carefully interpreted and further studies are needed to confirm our results.

Conclusion

This study highlights a significant increase in the global burden of T2DM among women of reproductive age from 1990 to 2021, with marked rises in ASIR and DALYs. Our findings reveal complex associations between T2DM burden and socioeconomic development, emphasizing the need for age-specific and region-specific public health strategies. By focusing on these priorities, policymakers and healthcare providers can develop comprehensive, context-sensitive strategies to effectively address the growing challenge of T2DM among women of reproductive age, particularly in regions like North Africa, the Middle East, East Asia, and Oceania

The escalating prevalence of T2DM, particularly among younger women aged 25–29 years, underscores the urgent need for targeted interventions addressing lifestyle factors such as dietary control, physical activity, and weight management. While our analysis points to potential drivers of the increasing burden, including socioeconomic transitions and adverse lifestyle changes, further research is required to confirm causal relationships and refine intervention strategies. Future studies should employ robust methodologies, including longitudinal designs and real-world data, to provide deeper insights into the causal pathways underlying the observed trends.

Supporting information

Acknowledgments

The authors would like to thank all participants who participated in the study.