Ranking as the eighth leading cause of combined death and disability worldwide, diabetes has risen to prominence as one of the major public health challenges impacting countries globally, including China (1, 2). The International Diabetes Federation (IDF) indicates that 537 million people worldwide was living with diabetes in 2021, and is estimated to increase to 1.31 billion in 2050 (3). This high and increasing prevalence has placed a substantial burden on population and healthcare systems, particularly in areas with low socioeconomic status (SES) and limited healthcare resources. Exploring the risk factors of diabetes is of great significance for prevention and management in these areas.

Type 2 Diabetes Mellitus (T2DM) is the most common form of diabetes that characterized by an elevated blood glucose concentration associated with body’s impaired response to insulin action, and influences individuals of all demographics. Identified risk factors for the development of suboptimal glycaemic control include genetic susceptibility, obesity, sedentary lifestyles, and suboptimal dietary patterns (4, 5). The developmental origins of health and disease (DOHaD) hypothesis suggested that the suboptimal glycaemic control is also associated with environmental exposures during early life (6). In details, nutritional status in the early developmental periods represents a key determinant of long-term health outcomes later in life (7). Sustained exposure to food shortages and undernutrition during this period can increase the risk of suboptimal health conditions in adulthood (8, 9). Previous studies reported significant difference in nutrition between lower and higher SES. The food choices in lower SES areas are likely to be limited, which resulting in residents in these areas tend to select food with higher energy, and also have limited selections for fruit and vegetables (10). This could lead to a dietary pattern with a level of essential nutrients such as vitamin and micro element in the lower SES areas (11).

Famine subjects a significant proportion of a country or region’s population to severe food shortages (12). During the period of 1959–1961, China suffered one of the most severe famines in the world, which was known as “the Great Chinese Famine” (13). Almost all people over 60 years old living in mainland China were impacted, with the total death toll from this famine estimated to be 15–30 million (14, 15). The impact of early-life malnutrition on the risk of T2DM in adulthood has been reported in various countries or regions (7, 16). However, the findings have been inconsistent, whether early malnutrition increases the risk of diabetes in adulthood remains unclear (13, 17).

Among all regions in China, the Northwest area was reported to have inferior SES than the East. For example, the southern regions of Ningxia Hui Autonomous Region (NHAR), the smallest northwestern province of China, were classified as the least accommodating places for humans to live by the United Nations before 1990s (18). The people living in this region not only experienced famine, but also be perceived as at a lower SES for a long time until the beginning of this century. Although the northern portion of NHAR showed a higher socioeconomic status (SES) with a relatively mild degree of severe famine (19) than its southern portion, NHAR as a whole continues to exhibit a lower SES when compared to other areas throughout China.

To the best of our knowledge, no research has thoroughly examined the risk of T2DM in populations from such areas that have historically experienced both severe famine and prolonged poverty. Our study aimed to explore whether (1) famine exposure during infant, childhood and adolescence are associated with a high risk of Type 2 Diabetes Mellitus (T2DM) in adulthood and the role of socioeconomic status (SES) on this effect in such underdeveloped areas compared with an age-balanced control. This research would help understand the health determinants of chronic diseases in vulnerable populations, and guide the development of public health interventions for regions under similar circumstances globally. This would further contribute to reducing health disparities across diverse populations and promoting more equitable health outcomes.

Our study found that when accounting for the age difference between the comparison groups, exposure to famine during early life stages did not demonstrate a correlation with an increased risk of T2DM in adulthood. Uncontrolled age discrepancies between famine births and post famine births is potent to exaggerate the perceived association between early-life exposure to famine and the risk of developing T2DM in later years (22, 23).

While our analysis of combined data of individuals from both mountainous and plain regions did not reveal an association between early-life exposure to famine and risk of T2DM in adulthood, a nuanced examination focusing exclusively on individuals from mountainous regions (those at lower SES) uncovered that exposure to famine during adolescence can increase the risk of developing T2DM later in life (OR 2.46 95% CI:1.61, 3.77). One possible explanation is that the low SES exposes populations in the NHAR mountains to more potential risk factors of T2DM than in the plains where SES is higher. Some prospective population-based studies have also accessed this correlation. In England it was shown that the incidence of T2DM is increased in lower SES even with the adjustment for regular risk factors for T2DM (24). In the USA, based on the data from Women Heath Study, researcher demonstrated an inverse relationship between increasing education and income to diabetes incidence (25). In our study, the southern mountainous areas include Xiji, Haiyuan, and Yanchi counties, also known as XiHaiGu. This region has been recognized as one of the most barren areas in China since ancient times (18). It was once categorized as one of the national contiguous destitute areas and was evaluated by the United Nations Food and Agriculture Organization (FAO) in 1972 as “one of the most unsuitable areas for living” (18). For a long time, this region has faced a “PPE (poor, people, and environment) vicious circle,” presenting a persistent contradiction between population, resources, environment, and socioeconomic development. Furthermore, several studies found that in T2DM, relative insulin deficiency owing to β-cell dysfunction is a key factor for the development of disease (26–28) that often coexists with insulin resistance. Food restriction in the early life might decrease the beta cell mass, and possibly a less favorable gut microbiota may also be related to increase the T2DM rates (29, 30). Previous studies have found a clear association between the socioeconomic gradient in T2DM and the utilization of healthcare resources (31, 32). Miller found that people living with T2DM may demonstrate lower level of adherence to healthcare interventions once they perceive that these interventions these interventions impose a financial burden on their disposable income (33). Reduced consistency in using medications and adhering to recommended guidelines can increase the risk of diabetes-related complications. On the other hand, people who living in the underdeveloped mountain or low SES areas have even less opportunities to access to healthcare services (32), limiting their engagement with the early screening of T2DM or chronic disease screenings, particularly as digital healthcare has not been widespread in these areas (34). There is also evidence that economic conditions in early life can have lasting influences throughout the lifecycle. For example, using historical data from the Netherlands (19), compare individuals born during the economic boom of 1872 to 1876 with individuals born during the recession of 1877 to 1881, they founded that people born during economically prosperous years had life expectancies that were about 1.6 years longer than those born during the economic downturn.

In fact, maternal nutrition may play a key role in their offspring’s risk of non-communicable diseases (NCDs) later in life. This is a profoundly important relationship, particularly in low and lower-middle income countries (LLMICs) who face the double burden of malnutrition, and 80% of the global NCD burden (35). Furthermore, participants in our study who born in the mountain area may have lower birth weight, which may related to the nutritional status of their mother during gestation. They tend to present a higher body fat mass and diabetes risk (36). Previous study also observed that low birth weight is associated with increased rates of obesity, insulin resistance and T2DM (37). A study suggested that low fat deposition leading to thinness at birth and during infancy results in fat acquisition during childhood, with a subsequent increase in the risk of developing T2DM (38). The finding was consistent with our result. After adjusting the covariates, the childhood exposure group had a high risk of T2DM [OR:1.76 95% CI(1.34, 2.31)]. Overall, our results suggest that people born with a low weight should be advised regarding the risks of developing T2DM.

We also observed significant interaction effects in gender in our study that females exposed to famine during the early-life stage had a higher risk of T2DM than males. We speculate that this could be attributed to the relatively poorer health status of Chinese women compared to men over the last century, as reported by Zhao et al. (39). According to the concept of “mortality selection” (40), which was defined as the tendency for individuals with higher levels of exposure to disadvantageous characteristics to be more likely to experience die, female participants in this study appear to have been exposed to a greater degree of disadvantage during the famine.

The study includes several key strengths. It examines the effect of a historical natural event, the Great Chinese Famine, on people’s health status. The unique topography of NHAR provided a natural classification of famine severity in this region. This study is also based on high-quality data, which was derived from a representative sample across nine counties in NHAR. However, this study also has some limitations. The primary challenge is the vague timeline of the Great Chinese Famine, making it difficult to categorize participants accurately based on their birth dates. Potential misclassification of subgroups may presented. Additionally, the lack of follow-up data may limit our ability to account for the direct effects of time intervals on the study’s findings.

No strong evidence demonstrates that exposure to famine during the early life stage can increase the risk of developing T2DM in adulthood. However, populations with lower SES are likely to be exposed to more risk factors for T2DM. It is recommended that future policies and interventions aimed at chronic disease management should pay more attention to vulnerable populations.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

This study was conducted according to the guidelines laid down in the Declaration of Helsinki and all procedures involving human subjects were approved by the Institutional Review Board of the People's Hospital of Ningxia Hui Autonomous (No. 2020-YC-002). Verbal consent was witnessed and formally recorded. Informed consent was confirmed by the IRB the People's Hospital of Ningxia Hui Autonomous.

HS: Conceptualization, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing. DY: Conceptualization, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing. LM: Data curation, Formal analysis, Writing – review & editing. YC: Data curation, Formal analysis, Writing – review & editing. YL: Investigation, Writing – review & editing. JM: Investigation, Writing – review & editing. HT: Investigation, Writing – review & editing. CS: Conceptualization, Funding acquisition, Methodology, Project administration, Supervision, Validation, Visualization, Writing – review & editing, Formal analysis.