Low physical activity (LPA) is a prevalent risk factor linked to numerous major non-communicable diseases, such as diabetes and kidney disease (1). LPA and extended sitting durations are linked to metabolic impairments, including diabetes and renal damage, in diabetic patients (2). Research has demonstrated that engaging in physical activity elicits a beneficial effect on inflammation, blood pressure, lipid levels, metabolism, and cardiovascular health, particularly in patients suffering from kidney disease. In addition, it is noteworthy that diabetes serves as the predominant cause of kidney disease (3). This suggests that LPA-induced diabetes may exacerbate the progression of nephropathy. Grouping diabetes and nephropathy, when caused by LPA, under a single category would facilitate a comprehensive evaluation of the enduring impact of diabetes on renal health, as well as the influence of these two diseases individually and collectively. LPA places a substantial economic strain worldwide. The projected global cost of LPA to public healthcare systems from 2020 to 2030 is approximately US$ 300 billion (equivalent to roughly US$ 27 billion annually) if there is no reduction in LPA levels. The annual economic impact of Type 2 diabetes, attributable to physical inactivity, is estimated to be between US$1.9 and US$13.2 billion. It is evident that LPA contributes not only to the global economic burden but also adds to the disease burden by facilitating diabetes and kidney disease. The interplay between LPA-induced diabetes and kidney disease further exacerbates the global disease burden. This suggests that the rise in LPA-induced diabetes and kidney disease, along with their interconnectedness, could potentially precipitate a significant health crisis in the 21st century. An assessment is imperative to comprehend the current state of this disease burden.

LPA is widely regarded as a ignificant modifiable risk factor for numerous diseases (4). Physical activity is crucial for amplifying the effects of renal inflammation, oxidative stress, vascular function, immune response, and macromolecule metabolism (5). Presently, there is a paucity of epidemiological data exploring the relationship between LPA and diabetes, as well as kidney disease, on a global scale. In light of this, it is imperative to conduct an assessment of LPA-induced diabetes and renal disease to contribute to and fill the existing gaps in the literature.

This study leverages data from the global burden of disease to scrutinize trends in the burden of diabetes and kidney disease as attributed to LPA across 204 countries, spanning the period from 1990 to 2021. The findings are tailored to offer policymakers scientifically-grounded insights for optimal resource allocation and policy execution, achieved through a comparative analysis and exploration of potential causative factors.

The study highlights that the global burden of diabetes and kidney disease caused by LPA has increased from 1990 to 2021, with 21 regions showing a sustained upward trend. Incidence is higher in women compared with men, with the fastest growing disease burden in Eastern Europe, the highest ASDR in Southern Sub-Saharan Africa, and the highest Age-Standardized DALY rates in Oceania. The burden of diabetes and kidney disease has been steadily increasing, particularly in Sub-Saharan Africa, Oceania, North Africa, and the Middle East (10, 11). This increase may be related to population aging and LPA-related lifestyle changes. Current projections from the International Diabetes Federation indicate that the prevalence of diabetes is increasing (12). A large number of observational studies have shown that Metabolic risk factors such as diabetes, hypertension, and obesity are the main causes of chronic kidney disease and end-stage renal disease (13). Increases in these metabolic risk factors may explain the significant increases in diabetes-related mortality and kidney disease-related DALYs.

Previous studies have uncovered the mechanisms connecting LPA to diabetes and kidney disease. There are several potential pathways that could explain the relationship between LPA and diabetes. Diabetes mellitus is primarily divided into type 1 and type 2. Type 1 diabetes mellitus, which accounts for 5-10% of cases, is induced by cell-mediated autoimmune defects that lead to the destruction of pancreatic β-cells, resulting in a deficiency in insulin production. On the other hand, type 2 diabetes mellitus, which constitutes 90-95% of cases, is predominantly due to the gradual decline in insulin secretion capacity and is typically accompanied by insulin resistance (14). A sedentary lifestyle, leading to obesity, and the subsequent lack of physical activity are significant risk factors for insulin resistance. This condition expedites beta cell dysfunction and apoptosis, which, in turn, initiate autoimmune responses and beta cell loss in genetically predisposed individuals (15). The pro-inflammatory state, characteristic of obesity, is known to induce insulin resistance in skeletal muscles and the liver, subsequently disrupting their normal metabolic functions (16). Myokines, including irisin, interleukin-6 (IL-6), and interleukin-15 (IL-15), have been demonstrated to be secreted by skeletal muscle in response to exercise. These myokines exert beneficial physiological and metabolic effects on distant tissues such as white adipose tissue, bone, liver, and immune system cells. These effects collectively drive a whole-body anti-inflammatory and insulin-sensitized state, optimizing overall energy expenditure (17). There exist several potential mechanisms underlying the association of LPA with kidney disease. The same physiological processes through which LPA instigates diabetes are operative in kidney disease. Regular physical activity has been shown to improve blood pressure, and it is widely acknowledged that hypertension is a significant contributor to kidney injury and the progression of CKD (18). LPA has the potential to induce insulin resistance, which in turn negatively impacts the glomerular filtration rate, ultimately leading to nephropathy (19). Insulin resistance is believed to be a key factor in the pathogenesis of metabolic syndrome (MS), a condition marked by a range of metabolic abnormalities such as obesity, hyperglycaemia, hypertension, and dyslipidaemia (19). The metabolic syndrome contributes to nephropathy through a variety of mechanisms. These include haemodynamic factors such as hypertension and glomerular hyperfiltration, but also extend to the chronic inflammatory milieu, insulin resistance, and adipokine dysregulation. Moreover, abdominal obesity, which increases intra-abdominal pressure, and the accumulation of free fatty acids and triglycerides in glomerular and tubulointerstitial cells, can contribute to both acute and chronic functional and structural renal injury (20).

The burden of diabetes and kidney disease has been steadily increasing, particularly in Sub-Saharan Africa, Oceania, North Africa, and the Middle East. The Global Burden of Disease 2021 emphasizes that due to poverty and harsh environment in Southern Sub-Saharan Africa and Oceania, the incidence of obesity, hypertension, diabetes, and cardiovascular diseases has increased significantly in the region (21). People with diabetes may develop serious complications such as cardiovascular disease, kidney disease, blindness, and amputation. Environmental toxins and groundwater with high fluoride content further increase the burden of kidney disease (22). Inadequate access to renal replacement therapy can lead to end-stage renal disease and premature death. In Eastern Europe, a shift in economic growth has precipitated an evolution in dietary habits towards high-fat and high-sugar diets. Concurrently, there is an increase in sedentary lifestyles and various psychosocial factors that have a significant impact on the rates of obesity and related morbidities. In Oceania, obesity is a key factor in the rising prevalence of diabetes (23–25), and economic inequality and limited health resources in low-income countries complicate screening and treatment (26, 27). Countries in Sub-Saharan Africa are challenged by shortages of healthcare infrastructure and nephrologists, highlighting the need to strengthen healthcare systems and infrastructure.

Consistent with previous research (28), the impact of physical inactivity in diabetes and kidney disease increased significantly over time in both men and women. Although the overall disease burden is higher in women than men, this increase is more pronounced in men. Possible explanations for this difference include physiological differences between the sexes, the influence of hormone levels and fat distribution patterns (29). Women generally consume more sugar than men, and a high -glycemic index diet can lead to increased abdominal fat, especially in sedentary women. Men tend to do more manual labor or participate in recreational sports, while women may have fewer opportunities to participate in these activities due to family and caregiving responsibilities. Interaction of physical inactivity and increased body mass index contributes to gender trends in disease burden. Mortality and DALY rates related to diabetes and kidney disease increase sharply with age, particularly among those over 90 years of age, which may be attributed to the relationship between physical activity and aging factors gap interaction (30). As older adults age, they increasingly rely on physical activity to maintain blood glucose homeostasis. This highlights the importance of staying physically active, especially for older adults and women who are more health conscious.

In our research, we observed a substantial increase in the burden of LPA-related diabetes and kidney disease in several regions, including Oceania, Southern Sub-Saharan Africa, North Africa and the Middle East, and Eastern Europe. Prior studies have demonstrated that in low-sociodemographic index countries, populations with lower incomes and education levels exhibit higher LPA rates (31, 32). Numerous factors influence physical activity levels, encompassing environmental conditions, support systems, and educational backgrounds (33–35). Notably, the influence of socioeconomic development on these factors is evident, with research indicating that older adults who engage in higher levels of physical activity have a reduced risk of mortality (36). In countries with a high sociodemographic index, factors related to diet may also exert an influence on the prevalence of diabetes and kidney disease, in addition to physical activity (37). Considering the extensive benefits of physical activity, it is imperative for mass media to bolster and enhance support systems for physical activity within communities and workplaces, particularly in low-income countries. Additionally, there is a need for intensified efforts to advocate for physical activity and healthier lifestyles.

We propose several recommendations to address the current state of disease burden. For high-income countries, there is a pressing need for greater understanding of the disease burden associated with diabetes and nephropathy due to LPA. This would facilitate informed decision-making on whether to allocate additional health resources in this area. Moreover, tailored recommendations regarding the types and intensities of physical activity suitable for different populations are required. For low-income countries, there is an urgent need to enhance disease communication. A nuanced understanding of effective health information dissemination channels within each country can lead to successful public health campaigns that increase awareness of LPA as a contributor to diabetes and kidney disease, thereby fostering exercise habits and reducing disease burden. It is imperative that policies be implemented to guarantee research into the appropriate forms of exercise for key demographics such as the elderly and women. Specifically, aerobic, balance, and flexibility exercises may offer feasible options for these groups.

This study offers critical baseline data concerning the global impact of LPA-related diabetes and kidney disease spanning 1990 to 2021. These findings carry significant weight in guiding resource distribution and the execution of intervention strategies. However, there are limitations that warrant consideration. Firstly, updates to GBD data are infrequent, with the most recent information only becoming available in 2021—this potentially fails to reflect current disease trends. Secondly, when evaluating the disease burden linked to LPA, it proves challenging to entirely rule out the potential interactions with other risk factors. Thirdly, while the statistical methodologies employed in GBD studies aid global comparisons between regions, they may contain certain limitations and biases related to data accessibility and processing. Diagnostic precision and confirmation bias at the point of disease registration present potential limitations in estimating cancer incidence and DALYs within GBD. For example, there can be variations in ICD coding practices documenting the underlying cause of death. Research assessing the concordance between death certificates and patient records has identified discrepancies in the reported underlying cause of death (38). These findings, while varying according to location and time, imply that the recording of diabetes as a cause of death may be either over-coded or under-coded, contingent on the specific locale. Fourth, there is a paucity of large-scale, high-quality, population-based studies on disease in certain countries or regions. Consequently, raw data from these areas may invariably contain biased information. It is therefore imperative to exercise caution when interpreting the results of studies, particularly when extrapolating data to countries or regions that are not part of the World Health Organisation and those with underdeveloped health systems. Fifth, the time frame of this study encompassed the COVID-19 pandemic. The pandemic could have potentially impacted data collection, as preventive and control measures such as home confinement might have led to sedentary behaviour and low physical activity (LPA). This in turn could have exacerbated the burden of disease to a certain extent. Therefore, prudence should be exercised when interpreting these results.

Our results show that age-standardized mortality and age-standardized DALY rates increased significantly in 21 regions and showed a continuous upward trend. Of particular concern is the notable escalation in burden, particularly in regions such as Eastern Europe, Sub-Saharan Africa, and Oceania. Our findings highlight the urgent need for targeted health initiatives and increased attention to high-risk groups such as women and the elderly.

The global ASDR and age-standardized DALY rates reveal a significant surge in diabetes and kidney disease attributable to LPA from 1990 to 2021. This escalation is evident across 21 regions, with notable increases observed in Eastern Europe, Sub-Saharan Africa, and Oceania.