ABSTRACT
Objective
To estimate the disease burden of type 2 diabetes (T2D) in early‐onset (age < 40) and late‐onset (age ≥ 40) in the U.S.
Methods
Data obtained from the National Health and Nutrition Examination Survey 2003–2018. Prevalence, number, and disability‐adjusted life years (DALYs) in early‐onset and late‐onset T2D were assessed.
Results
There was a clear and steady upward trend in early‐onset T2D, although the prevalence and number of late‐onset T2D were higher than early‐onset. The average loss of DALYs per capita (DALYs/per) in the early‐onset T2D was higher than that in the late‐onset. DALYs/per is higher in males than females in both early‐ and late‐onset T2D groups. People living at or below the poverty line and those with education of high school and below had a higher DALYs/per of early‐onset T2D. Among individuals with early‐onset T2D, the DALYs/per loss was higher in the non‐obesity group.
Conclusion
There was a clear upward trend in the prevalence of early‐onset T2D, and the loss of DALYs/per in early‐onset T2D was higher than that in late‐onset T2D. The attribution risk factors, like sex, education levels, income levels, and body mass index, for the burden of early‐onset T2D varied, and measures need to be taken to target different populations.
Keywords: Disability‐adjusted life years, Early‐onset, Type 2 diabetes
There was a clear upward trend in the prevalence of early‐onset T2D. The loss of DALYs/per in early‐onset T2D was higher than that in late‐onset T2D. Young people (age < 40) with early‐onset T2D, especially males, lower educational attainment, poorer income, and non‐high BMI need to pay more attention to interventions.
INTRODUCTION
Diabetes represents a major global health issue 1 . Among the different types of diabetes, type 2 diabetes(T2D) is considered a severe public health problem, with a significant impact on human life and health expenditures 2 . In 2019, there were 437.9 million cases of T2D globally, and since 1990, the age‐standardized point prevalence and mortality rates of T2D globally have increased by 49% and 10.8%, respectively 3 . T2D was previously thought to be a metabolic disorder affecting middle‐aged and older people and was rarely seen in adolescents and young adults. However, the increasing number of younger adults with T2D in recent years also contributes to the increase in overall T2D prevalence. The incidence and prevalence of T2D in young individuals (aged < 40 years) have significantly increased, approximating a two‐ to threefold increase in the respective rates 4 .
A study based on the Global Burden of Disease (GBD) reported the global burden of T2D among adolescents and young people from 1990 to 2019, and reported the secular trends and variations by several factors (age, sex, and region, categorized by sociodemographic index). The results showed that early‐onset T2D is a growing global health problem among adolescents and young people, especially in countries with a low‐middle and middle sociodemographic index. A greater disease burden in women (aged < 30 years) was found 5 . People with early‐onset T2D have more obvious genetic predispositions and metabolic disorders, and the progression of their diseases may be faster. Their needs in disease management and treatment may differ from those of patients with late‐onset T2D. However, there is no research that specifically compared the disease burden between early‐onset T2D and late‐onset T2D, which may limit the development of effective measures to address this issue at the regional and national levels.
Therefore, we aimed to distinguish whether people with early‐onset T2D bear a higher disease burden than that of late‐onset. We compared the prevalence and number of T2D and the disability‐adjusted life years (DALYs) between the early‐onset and late‐onset T2D groups, based on the National Health and Nutrition Examination Survey (NHANES).
METHODS
Data source
NHANES is a population‐based cross‐sectional survey designed to collect information on the health and nutritional status of the U.S. household population. The survey examines a nationally representative sample of about 5,000 persons each year and every 2 years for a cycle. The NHANES interview component covers demographic, socioeconomic, dietary, and health‐related questions. The physical examination component includes physiological measurements, laboratory tests, and more. The NHANES program began in the early 1960s and has been conducted as a series of surveys focusing on different population groups or health topics. In 1999, the survey became a continuous program that has a changing focus on a variety of health and nutrition measurements to meet emerging needs. The data on diabetes deaths was derived from the 2019 National Death Index (NDI) records. The Linked Mortality Files (LMF) have been updated with mortality follow‐up data through December 31, 2019. The files include a limited set of mortality variables for adult (age ≥ 18) participants only.
Study population
Our current study was derived from the continuous NHANES database from 2003 to 2018 with 8 cycles and a total of 80,312 participants. Exclusion criteria: a. excluded 73,220 individuals without diabetes; b. excluded 115 individuals without diabetes death data. A total of 6,977 T2D aged 18 and older were eligible for this study, as the LMF only provided information for adults. The specific inclusion and exclusion criteria were presented in Figure 1.
Figure 1.
Flowchart of participants. NHANES, National Health and Nutrition Examination Survey.
Definition of T2D
The age of first notification of diabetes in the questionnaire was the onset age of the study population. If no notification of diabetes was made, T2D was defined as glycosylated hemoglobin ≥ 6.5%. The staging of the included person with diabetes was determined based on the respondent's answer to the physician for examination of foot ulcers and whether diabetes affected eyes or retinopathy. Early‐onset diabetes is defined as a young person with the age of onset <40 years, and late‐onset diabetes with the age of onset 40 years or older 6 .
Definition of disease burden
The prevalence of the early‐onset, late‐onset, and T2D in each cycle was calculated as the number of patients divided by the total number of adults (age ≥ 18) in that cycle, respectively. DALYs were defined as the sum of years of life lost (YLL) due to premature mortality, and years lived with a disability (YLD) 7 . The YLL was defined as the expected number of years remaining at the date of death due to diabetes 8 . The data derived from the 2019 United States Life Tables 9 , in which the age at death from diabetes in the included population, corresponded to the age groups in the life expectancy table. It is possible to roughly calculate the life expectancy lost for each individual and the sum of YLLs. The basic equation for YLD is: YLD = (I × L) × W, where I is the number of incident cases of diabetes, L is the duration of illness, and W is the disability weight for diabetes 10 . The disability weights (DWs) are used to quantify the severity of a disease on a continuum scale from 0 to 1, where 0 represents full health (free from disease and disability) and 1 represents the worst possible health state or death 11 . To calculate the situation where multiple complications occur at the same time in an individual, we apply a comprehensive weighting algorithm: combined DW ij = 1 − (1 − DW i ) × (1 − DW j ), where DW = disability weight of health conditions i and j, which is suitable for explaining the coexistence situation 1 . According to the previous literature 12 , the disease weight of simple diabetes was 0.049, the weight of diabetes foot disease was 0.020, and the weight of retinopathy was 0.247 13 . The weight of diabetes foot combined with retinopathy was 0.262 after the combined weighting algorithm described above. The above formulas were shown in Table S1.
Other variables
Death due to diabetes, gender, age, race, poverty income ratio (PIR), marital status, education level, and body mass index (BMI) were included in the baseline variables.
Causes of death related to the ICD‐10 (international classification of diseases, 10th revision) codes. Race was divided into five categories, including Mexican Americans, other Hispanic, non‐Hispanic white, non‐Hispanic black, and others. PIR was divided into three groups: less than 3.5 was defined as below or near poor, greater than or equal to 3.5 was defined as not poor, and missing values were grouped separately. Marriage status was divided into three categories: married or living with a partner, never married, and either widowed or divorced/separated. Education level was divided into two categories: high school or below, and above high school. BMI was divided into two categories: Less than 30 was defined as non‐obese; 30 or more is defined as obese 14 .
Statistical analysis
Continuous variables were described using median (IQR, interquartile range) for non‐normal distributions and mean ± SD for normal distribution. Categorical variables were described using n (percentages). Analysis of variance was used for normal distribution while Wilcoxon rank‐sum test was used for non‐normal distribution in continuous variables and chi‐square tests were used in categorical variables between early‐onset and late‐onset T2D.
The line plots connecting eight periods were used to assess the magnitude and direction of temporal trends in the number and prevalence of T2D. The DALYs/per was calculated, and a t‐test was used to compare DALYs/per between early‐onset and late‐onset groups, and plotted bar graphs for 8 periods to describe the group with a higher disease burden. We also used bar graphs to describe the DALYs/per burden between the T2D group by sex, poverty income ratio, education level, and BMI groups.
All analyses were conducted using R 4.3.3. A P value <0.05 was considered statistically significant.
RESULT
Characteristics of participants with early‐onset vs late‐onset diabetes
A total of 6,977 participants with T2D were eligible for this study. 1,374 early‐onset T2D participants had a median age of 44.5 (IQR: 36.0–58.0), with 640 (46.6%) male and 104 subjects dying from diabetes. 5,603 late‐onset T2D participants had a median age of 65.0 (IQR: 58.0–74.0), with 2,913 (52.0%) male and 458 subjects dying from diabetes. Compared with the late‐onset T2D group, the early‐onset T2D group had fewer men, a higher proportion of poor people, more obese people, and the proportion of people with above high school education was higher in the early‐onset group (Table 1).
Table 1.
Characteristics of participants with T2D
| Characteristic | Early‐onset (n = 1,374) | Late‐onset (n = 5,603) | P |
|---|---|---|---|
| Death due to diabetes | |||
| Yes | 104 (7.6) | 458 (8.2) | 0.494 |
| Gender | |||
| Female | 734 (53.4) | 2,690 (48.0) | <0.001 |
| Age | 44.5 (36.0–58.0) | 65.0 (58.0–74.0) | <0.001 |
| Race | |||
| Mexican American | 306 (22.3) | 1,035 (18.5) | <0.001 |
| Other Hispanic | 146 (10.6) | 511 (9.1) | |
| Non‐Hispanic White | 394 (28.7) | 1,982 (35.4) | |
| Non‐Hispanic Black | 388 (28.2) | 1,493 (26.6) | |
| Other race—Including multi‐racial | 140 (10.2) | 582 (10.4) | |
| Poverty income ratio | |||
| Not poor | 255 (18.6) | 1,196 (21.3) | 0.009 |
| Below or near poor | 992 (72.2) | 3,805 (67.9) | |
| Missing value | 127 (9.2) | 602 (10.7) | |
| Marital status | |||
| Married, living with partner | 798 (58.9) | 3,281 (58.6) | <0.001 |
| Widowed, divorced, separated | 300 (22.1) | 1917 (34.3) | |
| Never married | 257 (19.0) | 397 (7.1) | |
| Education level | |||
| >High school | 595 (44.1) | 2,223 (39.8) | 0.004 |
| Body mass index | |||
| ≥30 | 828 (64.5) | 2,971 (56.3) | <0.001 |
Data were reported in median (IQR) or number (percentages). Wilcoxon rank‐sum test was used to compare continuous variables between early‐onset and late‐onset T2D, while chi‐square tests were applied for categorical variables. T2D, type 2 diabetes.
Temporal trends in the prevalence and number of early‐onset, late‐onset, and persons with diabetes
The prevalence and number of persons with diabetes and late‐onset T2D showed a significant year‐on‐year upward trend. The prevalence and number of late‐onset T2D were much higher than those of early‐onset (Figure 2). There was a clear and steady upward trend in the prevalence and number of early‐onset T2D (Figures S1 and S2).
Figure 2.
The prevalence and number of T2D. The prevalence of early‐onset and late‐onset T2D and total T2D is shown on the left, and the number is shown on the right.
DALYs/per for diabetes in early‐onset vs late‐onset populations
DALYs/per were significantly different between early‐onset and late‐onset T2D groups (P = 0.03). The bar graph showed that the DALYs/per in the early‐onset group was significantly higher than those in the late‐onset group; the early‐onset group lost 2.06 times more DALYs/per than the late‐onset group (Figure 3 and Table S2).
Figure 3.
DALYs per person for T2D in early‐onset vs late‐onset populations. DALYs, disability‐adjusted life years; T2D, type 2 diabetes. P value derived from t‐test.
DALYs burden in different groups of risk factors
The DALYs/per of males was higher than that of females in both early‐onset and late‐onset T2D groups when comparing by gender. The DALYs/per of early‐onset T2D was higher than that of late‐onset T2D in both males and females (Figures 4 and S3).
Figure 4.
DALYs per person for T2D in early‐onset by sex, PIR, education, and BMI. BMI, body mass index; DALYs, disability‐adjusted life years; F, female; M, male; PIR, poverty income ratio; T2D, type 2 diabetes.
In people with early‐onset T2D, when classified by poverty income ratio, people with PIR less than 3.5 (near poor or below) had a higher DALYs burden; when classified by education level, the DALYs burden was higher in those with an education level of high school and below; when obesity was classified according to BMI, the DALYs burden was higher in people with a BMI less than 30 (Figure 4). We have also provided a visual comparison of the disease burden among different groups of people with late‐onset T2D in Figure S3.
DISCUSSION
Based on data from NHANES of U.S. household population, key findings from this study include: (1) There was a clear upward trend in early‐onset T2D, although the prevalence and number of early‐onset T2D are lower than those of late‐onset T2D. (2) The average loss of DALYs/per in the early‐onset T2D was higher than that in the late‐onset in every cycle. (3) Young people with early‐onset T2D, especially males, those with lower educational attainment, poorer income, and non‐high BMI, experienced a greater DALYs burden.
The prevalence of early‐onset T2D has been increasing worldwide. A study based on the GBD 2019 found that from 1990 to 2019, significant increases in age‐standardized incidence rate and age‐standardized DALY rate were found for T2D in adolescents and young adults globally [5]. The incidence and prevalence of T2D in young individuals (aged < 40 years) have significantly increased in recent years. In a recent systematic review of literature on T2D, incidence among children and adolescents from 25 countries/territories estimated 41,600 new cases of early‐onset T2D globally in 2021 15 . A review of early‐onset diabetes in South Korea presents the prevalence of T2D in Korean adults (aged ≥ 30 years) increased 0.2–0.5% annually 16 . There was also increasing evidence that in clinical practice, early‐onset T2D (including children and young adults) has higher rates of complications and faster beta cell dysfunction compared with T1D of the same age and late‐onset T2D in middle‐aged and older adults 17 . However, there has been no study comparing the burden of early‐ and late‐onset T2D. In our study, there was a clear upward trend in early‐onset T2D, although the prevalence and number of early‐onset T2D are lower than those of late‐onset T2D. In addition, we calculated and compared the DALYs in both early‐onset and late‐onset T2D. The loss of DALYs/per individual in early‐onset T2D was higher than that in late‐onset T2D.
There were different evidences here when comparing sexes in early‐onset populations. A single‐center retrospective study based on Chinese patients with early‐onset diabetes showed that men were more likely to have early‐onset diabetes than women 18 . Women were more likely to be present in Canadian 19 and North Indian 20 with early‐onset T2D. Our study showed that the DALYs burden of men was higher than that of women in both early‐ and late‐onset T2D groups, although there were more females in the early‐onset T2D population. Certainly, individuals with lower levels of education and income were at a higher risk of developing T2D 21 . However, there were no articles comparing the burden of DALYs at different levels of education and income in the early‐onset population. In our study, the DALYs burden of early‐onset T2D was heavier among those with high school and below education levels and PIR less than 3.5 (near poor or below). It might be that people of lower socioeconomic status were at a higher risk of developing T2D due to the high cost of medical care such as routine blood glucose monitoring and regular medical check‐ups 22 . High BMI was known as an important risk factor for persons with diabetes 23 , 24 . A study based on the prevalence of early‐onset T2D in Mexico showed that most patients with early‐onset T2D were obese or overweight 25 . Interestingly, our results showed that the DALYs burden of early‐onset T2D was higher in people with BMI less than 30, although the early‐onset T2D group had more obese people than the late‐onset T2D group. This might be due to the “obesity paradox” in epidemiology, as patients with high BMI received more health concerns or earlier and better medical treatment than those with non‐high BMI 26 , 27 .
Our study had important public health implications. Our study suggested that attention should be paid to the risk of disease in early‐onset T2D populations to achieve early prevention and management of T2D. For different risk factors like gender, income, education, and BMI, a personalized approach in the management of people with T2D can reduce the cost and inefficiencies associated with the algorithmic “one‐size‐fits‐all” approach, to anticipate disease progression and reduce the incidence of complications of diabetes 28 .
This study exhibited strengths. The strength was that we studied the comparison of the disease burden of early‐onset and late‐onset T2D all‐around based on the NHANES in the U.S., which provides a reference for the allocation of resources for T2D prevention and control.
Our study also had several limitations. First, people under the age of 18 are not included in the burden of disease calculations for our early‐onset T2D population because only adults are provided in the public death data file. Secondly, the onset age of T2D in the database was the age of first notification of diabetes in the questionnaire, which might overestimate the prevalence of T2D.
In conclusion, there was a clear upward trend in early‐onset T2D, and the loss of DALYs/per in young people (age < 40) is higher than that in middle‐aged and elderly people (age ≥ 40). Young people with early‐onset T2D, especially males, those with lower educational attainment, poorer income, and non‐high BMI need to pay more attention. More research is needed to explore and verify the risk factors of the disease burden among the population with early‐onset T2D in different countries and regions, so that specific measures can be taken to address the health problems caused by the younger onset age of T2D.
FUNDING
This work was supported by the Scientific Research Program of the Tianjin Education Commission (Natural Science, Grant No: 2023KJ033).
DISCLOSURE
The authors declared no conflict of interest.
Approval of the research protocol: N/A.
Informed consent: N/A.
Registry and the registration no. of the study/trial: N/A.
Animal studies: N/A.
Supporting information
Table S1. Calculation of DALYs.
Table S2. DALYs/per loss in the early‐onset and late‐onset T2D groups.
Figure S1. The prevalence of early‐onset T2D.
Figure S2. The number of early‐onset T2D.
Figure S3. DALYs per person for T2D in early‐onset vs late‐onset populations group by sex, PIR, education, and BMI. BMI, body mass index; DALYs, disability‐adjusted life years; F, female; M, male; PIR, poverty income ratio; T2D, type 2 diabetes.
ACKNOWLEDGMENT
The authors thank all the health professionals of NHANES. HW and JM are the guarantors of this manuscript.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Calculation of DALYs.
Table S2. DALYs/per loss in the early‐onset and late‐onset T2D groups.
Figure S1. The prevalence of early‐onset T2D.
Figure S2. The number of early‐onset T2D.
Figure S3. DALYs per person for T2D in early‐onset vs late‐onset populations group by sex, PIR, education, and BMI. BMI, body mass index; DALYs, disability‐adjusted life years; F, female; M, male; PIR, poverty income ratio; T2D, type 2 diabetes.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.