Global burden and influencing factors of chronic kidney disease due to type 2 diabetes in adults aged 20–59 years, 1990–2019

Abstract

Population structure and lifestyles may have contributed to the epidemiological status of Chronic Kidney Disease due to Type 2 Diabetes (CKD-T2D). This study is a secondary data analysis. Using data from the Global Burden of Disease Study, we describe the changes in CKD-T2D burden and its influencing factors in the population aged 20–59 years from 1990 to 2019. Globally, the incidence, death, and Disability Adjusted Life Years (DALYs) rate of CKD-T2D showed an upward trend and increased with age, and the burden in males was higher than that in females. Population growth and aging were important driving factors for the increase of CKD-T2D DALY burden, while high systolic blood pressure and high body-mass index were the primary attributable risk factors. High body-mass index exhibited higher contributions to high Socioeconomic Development Index (SDI) countries, whereas low SDI countries were more impacted by high systolic blood pressure. The population attributable fraction of CKD-T2D DALY caused by high body-mass index was positively correlated with SDI, while high temperature and lead exposure were negatively correlated. Therefore, strengthening disease screening for people aged 20–59 years and formulating early intervention measures based on the level of socioeconomic development may effectively alleviate the burden of CKD-T2D.

Introduction

Diabetic Kidney Disease (DKD) is a prevalent chronic complication of diabetes mellitus, characterized by intermittent or persistent albuminuria and/or progressive decline in the glomerular filtration rate. Without aggressive interventions, DKD ultimately progresses to End-Stage Renal Disease (ESRD)¹. Type 2 Diabetes (T2D) accounts for over 90% of all types of diabetes, and 40–50% of T2D patients may develop Chronic Kidney Disease (CKD)², a leading cause of mortality in the general population^3,4. Elderly patients with T2D, especially those with diabetes for more than 10 years, are more likely to progress to CKD than those without T2D⁵. As the population ages, longer life expectancy⁶, and lifestyles change, the incidence of Chronic Kidney Disease due to T2D (CKD-T2D) continues to rise^7,8 and has become a principal contributor to the global burden of ESRD^9,10,17, and in addition, the incidence and mortality of CKD due to diabetes are closely related to socioeconomic, cultural, and national disease management factors, as well as age¹⁰. Several studies have reported global and regional trends in incidence, prevalence, and mortality of DKD over time and sex differences across all age groups^18,19, Pan and Liu et al. focused on the disease burden of diabetes and DKD in China^20,21, and another study reported mortality and trends in diabetes before 25 years of age²². However, few studies have focused on the epidemiological characteristics of people with DKD under the age of 60 years.

Since it usually takes several years for diabetes mellitus to progress to DKD, and the intervention for DKD needs long-term persistence to benefit²³, the focus should be on early prevention, early recognition, and early intervention within a younger adult demographic. To prevent or delay the disease progression, and further improve the quality of life and survival of the CKD-T2D population²⁴, understanding the global burden of CKD-T2D in the population under 60 years old, especially analyzing the factors affecting the disease burden, is particularly important for seeking strategies to prevent and treat DKD and further reduce the incidence rate.

In this study, we focused on describing the global epidemiological characteristics of CKD-T2D in people aged 20–59 years by analyzing the related data from Global Burden of Disease (GBD) 2019, including trends in disease from 1990 to 2019, differences between countries and regions, gender and age, also, we analyzed the driving factors and attributable risk factors for the increase in CKD-T2D Disability Adjusted Life Years (DALYs), as well as the correlation between attributable risk factors and Socio-Demographic Index (SDI).

Methods

Data source and measures of burden

The GBD 2019 is a multinational collaborative study that estimates the burden of disease associated with 369 diseases and injuries in 204 countries and territories from 1990 to 2019²⁵. The GBD data is obtained for each disease or injury from 7333 national and 24,657 subnational vital registration systems, 16,984 published studies, and 1654 household surveys, as well as other relevant data sources, such as population censuses, health service utilization, satellite imaging, etc²⁵. Annual updates include updates to diseases, data sources, and methods, designed to capture annual changes in the same diseases and injuries by age, gender, country, and region using standard epidemiological and health measures such as incidence, prevalence, death rates, and DALYs²⁵. DALYs are a commonly used measure of disease burden in epidemiological research, representing the total healthy life years lost by patients from disease onset to death, including years of life lost due to premature death from disease and years of healthy life lost due to disability, and can be expressed as a number or rate²⁶.

Study protocol

This study is a secondary data analysis based on the GBD study. Relevant data, inclusive of CKD-T2D incidence, DALY, and mortality spanning the period 1990 to 2019, was sourced from the Global Health Data Exchange (https://ghdx.healthdata.org/gbd-resultstool). This data was stratified by age, region, and gender. The primary aim of the analysis was to elucidate the global epidemiological characteristics of CKD-T2D, with a specific emphasis on the 20–59 age group. We conducted a decomposition analysis (Supplementary Methods) of age structure, population growth, and epidemiological changes to discern the principal drivers of DALY burden attributable to CKD-T2D among the target population. Furthermore, our investigation sought to identify the primary attributable risk factors contributing to CKD-T2D within diverse SDI categories across regions and countries.

Disease criteria

The disease in this study is CKD-T2D (ICD-10 code E11.2-E11.29). In the GBD Study 2019, diabetes was defined as a fasting blood glucose concentration of ≥ 126 mg/dL (7 mmol/L) or diabetes treatment reported¹⁷. Our study findings are consistent with these observations and indicate that age and gender are important factors affecting the burden of CKD-T2D. Therefore, implementing screening and intervention measures for CKD-T2D and its risk factors among the population aged 20–59 years, especially in middle-aged men, may be a crucial public health initiative to mitigate the burden of CKD-T2D.

Prevalent risk factors of CKD-T2D

Adjusting modifiable risk factors to reduce disease burden is a crucial measure in develo** public health policy⁴². Alterations in societal lifestyles have led to an increased number of obese individuals⁴³ and a concomitant rise in the prevalence of CKD caused by type 2 diabetes^{13,44,45,46,47}. DKD has become the primary contributor to the disease burden and medical costs of obese type 2 diabetes patients⁴⁸. The risk of type 2 diabetes patients develo** CKD is related to obesity and hypertension, and they often share common risk factors^49,50,51,52. Sodium is an essential mineral for the human body, with the functions of regulating osmotic pressure, blood volume, and vascular smooth muscle contraction, and is important for maintaining normal physiological functions. Nonetheless, long-term excessive sodium intake can lead to obesity and hypertension, which can in turn cause type 2 diabetes and CKD^53,54,55. Our findings show that globally, the impact of diet high in sodium on CKD-T2D is decreasing, while high systolic blood pressure and high BMI are increasing. This suggests that people may have gradually become aware of the harm of high-sodium diets and have reduced sodium intake in their daily diets. However, the pathogenesis of hypertension is complex and related to various factors such as genetics, environment, metabolism, and exercise, in addition to long-term high-sodium diets^53,56,57. Therefore, it may be an important preventive measure to reduce the burden of CKD-T2D by carrying out promotional education and strengthening management and treatment for hypertensive and high BMI patients.

The Influence of the environment on CKD-T2D should not be underestimated. Lead, a toxic heavy metal, can accumulate in various tissues including the kidneys, brain, and bones via the bloodstream with prolonged exposure, posing a hazard to human health^58,59,60. Our findings show that a decreasing trend in global CKD-T2D DALY attributable to low temperature and lead exposure and an increasing trend in high temperature among the population aged 20–59 years over the past 30 years. It suggests that with the development of society, environmental governance, and improvements in living standards, progress has been made in reducing lead exposure and addressing low-temperature issues through measures such as reducing the use of tobacco, leaded gasoline, and lead-based coatings^61,62 as well as the advancement of insulation materials and renewable energy technologies. Nevertheless, the effects of global warming and high temperatures on CKD-T2D necessitate the continuous strengthening of environmental protection measures, such as reducing deforestation, the use of petroleum and coal as fuels, enhancing garbage sorting and treatment, and reducing the use of non-biodegradable plastics to promote better health outcomes.

Regional difference in attributable risk factors for CKD-T2D

In the present study, we investigated the attributable risk factors for CKD-T2D DALYs in the population aged 20–59 years and found that high systolic blood pressure was the main contributing factor in low SDI countries, while high BMI had a greater impact in high SDI countries. The analysis also revealed a positive association between the PAF of CKD-T2D DALYs due to high BMI and SDI, while high temperature and lead demonstrated a negative correlation. The findings suggest that poor public health infrastructure, limited medical resources, and interventions for hypertension may be responsible for the greater impact of high systolic blood pressure in low SDI countries⁶³. In contrast, advanced economic and educational levels in high SDI countries lead to a greater awareness of environmental factors such as high temperature and lead exposure, and proactive and comprehensive measures to mitigate the risks. However, countries with higher SDI may have greater availability of high energy density diets, more convenient transportation, and less physical activity or exercise, which could elevate the risk of high BMI⁶⁴. Moreover, despite hypertension being a well-established risk factor for CKD-T2D disease progression⁶⁵, our study did not observe any association between high systolic blood pressure and SDI. This may be attributed to the intricate interplay of multiple factors such as genetics, environment, diet, physical activity, access to healthcare, and medication supply, which differ greatly between countries with different levels of SDI⁶⁶.

The epidemiology and risk factors of CKD-T2D exhibit significant variability across different regions and countries²⁵. In countries with higher SDI, which are characterized by pronounced population aging, interventions should focus on addressing this demographic shift and encouraging childbirth⁶⁷. On the other hand, strong evidence shows that longer sedentary time, lower physical activity, and higher red meat consumption are closely related to obesity and T2D^68,69, and the promotion and popularization of health-oriented lifestyles should be strengthened to alleviate the disease burden of CKD-T2D caused by risk factors such as high BMI. In contrast, in countries with lower SDI, the burden of disease has shifted from communicable to non-communicable diseases²⁵, such as CKD-T2D, however, due to constraints in the level of health care coverage and sanitation, changes in health systems are slower than changes in the epidemiologic spectrum³⁶, and the effective coverage index for non-communicable diseases is much lower than that for communicable diseases⁷⁰, interventions should prioritize disease care and treatment, management and improvement of environmental health conditions

Data availability

Data used in the analyses can be obtained from the Global Health Data Exchange Global Burden of Disease Results Tool (https://ghdx.healthdata.org/gbd-results-tool).

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