Mortality trends from all causes and diabetes mellitus according to sex between 1998 and 2021

1 Introduction

The differences between males and females permeate various spheres of individual life. Among them, biological, social, and behavioral differences stand out [1]. This means that each sex presents certain particularities throughout its life course and also at its death time [1]. Consequently, differences in mortality between men and women can be widely observed, both concerning all causes and from specific conditions related to diabetes mellitus (DM) [1].

A recent review, including data from 13 European countries and the United States, did not observe differences in all-cause mortality rates between men and women [1]. Alternatively, the Global Burden of Disease noted a higher women mortality when evaluating individuals over 80 years old, but higher men mortality when evaluating individuals next to their fourth life decade [2]. In Brazil, official data launched by the Health Ministry found similar results, that is, a higher women mortality in older individuals and higher men mortality in younger individuals [3,4]. These differences would be explained by differences in mortality trends presented between men and women, which take into account local-regional, economic, and age factors [5].

Considering mortality rates due to DM, the data are also conflicting. A Brazilian study observed higher rates in women [6]. However, the Global Burden of Disease study showed higher DM mortality rates in men [2]. Finally, other studies point out that DM mortality rates in a given sex vary depending on age, as it tends to be higher in men around 30 years of age but higher in women after 50 years of age [7]. These differences may be explained by differences in mortality trends presented by women and men that are determined by the health access that each sex has. They may also differ by care and treatment provided by each sex that take into account a series of social factors [8,9,10,11].

Therefore, there is no consensus in the literature on the influence of sex on mortality from all causes and DM. So, this study aimed to analyze mortality trends from all causes and DM according to sex in Bauru, São Paulo, Brazil, between 1998 and 2021.

2 Methods

This was an epidemiological, observational, retrospective, and population-based study that evaluated trends in mortality from all causes and DM according to sex in Bauru, São Paulo, Brazil, between 1998 and 2021.

This study included data on all deaths that occurred from January 1998 to December 2021 among people living in Bauru, State of São Paulo, Brazil, registered in the Brazilian Mortality Information System (SIM). The data are available in the Brazilian public and freely accessible database DATASUS, which is supplied by official mortality records that occur in Brazil and notified by doctors from all over the country [12].

The data collected comprised the year of death, age at the time of death, sex (male or female), and the underlying cause of death. In this case, codes E10–E14, corresponding to the DM codes in the 10th version of the International Classification of Diseases (ICD-10), were utilized to filter deaths related to DM. The platform does not allow the identification of ICD subtypes, that is, it is not possible to identify particular types of DM, but only the ICD that encompasses them as a whole. People of unknown age and undetermined sex were excluded from the study, which was represented by an amount of 92 (1.02%) people across the entire studied timespan. To collect data on mortality from all causes, the option “all causes”, presented on the SIM, was chosen to filter the data [12].

Bauru is the most populous city in the central-western region of the interior of the state of São Paulo, the richest and most populous state in Brazil [13]. Bauru presents a total territorial area of 667.658 square kilometers, with a resident population of 379.146 inhabitants, of which 338.891 (89.38%) live in urban areas and 5.148 (10.62%) in rural areas according to the last demographic Brazilian census made in 2022 [13]. Among these inhabitants, 195.826 individuals (51.65%) are women and 183,320 (48.35%) are men [13]. Furthermore, the city has 65.931 (17.39%) individuals aged 0–14 years, 238.517 (70.02%) aged between 15 and 64 years, and 47.698 (12.59%) individuals aged over 65 years [13]. All these classifications follow the color-race self-declaration proposed by the Instituto Brasileiro de Geografia e Estatística (IBGE) in the Brazilian demographic census [13]. The Human Development Index is 0.801 and the Gini coefficient is 0.438 [13]. According to the provision presented by Bauru city hall, the city has 1.046 hospitalization beds, including nurseries and intensive care units, being 465 public and 581 private [13]. The city has 16 public primary health clinics and 7 family health units, which together make up local primary health care, as well as 5 emergency care units. It also has eight tertiary hospitals, four of which are public and four are private [13].

It is estimated that the incidence of type 1 diabetes mellitus (T1DM) has been increasing in the city of Bauru, as the incidence rates of this condition increased from 2.80/100.000 in 1987 to 25.60/100.000 in 2013 [14]. There are no precise data from other DM types, such as type 2 DM and gestational DM [14,15]. Nonetheless, some estimates suggest that such conditions are highly prevalent in the city and that their incidence is progressively increasing, as well as all over Brazil [15].

Data between 1998 and 2021 were evaluated because only these years, among those available in the utilized databases, contained all the data analyzed in this study.

The total number of deaths was obtained and classified as due to all causes and DM according to the 10th Edition of the ICD, by sex and year of death during the analyzed period. Subsequently, mortality rates were calculated by dividing the number of deaths by the total number of inhabitants of Bauru each year, according to IBGE [16]. Age was considered an adjustment variable, and the 2010 population was considered the standard population since it was a population census year and also the intermediate year in the analyzed period. Other variables, such as ethnicity and marital status, were not included in the analysis, as the IBGE censuses did not contain data on these variables in all years of the analyzed period.

Initially, the Kolmogorov–Smirnov test was performed to verify the distribution of the data, which was not normal (p-value <0.05). After that, the Student’s t-test with resampling technique (bootstrapping) was used to verify the difference in the average mortality values between men and women, using the IBM Statistical Package for the Social Science, version 25.0 software.

Finally, a time series of age-adjusted rates was performed for a segmented analysis. The annual percentage change (APC) and the average annual percentage change (AAPC) were calculated with a 95% confidence interval (CI), the interpretation of which was: for significant p values (p < 0.05), an APC positive suggests an increasing trend, while a negative APC indicates a decreasing trend; in parallel, a non-significant p-value (p ≥ 0.05) suggests a stationary trend. This analysis was carried out using the Joinpoint Regression software, version 5.0.2 [17].

This study used public data with unrestricted access. Therefore, registration and approval by the Research Ethics Committee (CEP) were not necessary following Article 1 of Resolution No. 510/2016 of the National Health Council.

3 Results

The total number of people who died from all causes in Bauru in 1998 was 2.086 and rose to 3.803 in 2021, representing an increase of 82.31%. The total number of deaths over the 24 years was 58.440 with a stationary AAPC (−0.70; 95% CI −1.70; 0.30) when adjusted for age. The number of people who died from DM in Bauru in 1998 was 84 and rose to 168 in 2021, representing a 100% increase. The total sum over 24 years was 2.779 deaths with a stationary AAPC (−0.90; 95% CI −1.90; 0.10) when adjusted for age.

Data regarding the sex of individuals who died from all causes and from DM, in each year, can be seen in Tables 1 and 2. Figures 1–3 show the average age-adjusted mortality rates from all causes and DM by sex and year.

Figure 1

All-cause mortality by sex in Bauru from 1998 to 2021.

Figure 2

Diabetes-related mortality by sex occurred in Bauru annually from 1998 to 2021.

Figure 3

Variation in mortality rates by sex in Bauru, São Paulo, Brazil, in the period 1998–2021.

The average annual mortality rate from all causes was 720.92/100.000, while the average annual mortality rate from DM was 31.95/100.000, which represents 4.46% of the causes of mortality in the period analyzed. All-cause mortality in men had the lowest rate in 2018 (629.30/100.000) and the highest rate in 1999 (1039.60/100.000) with a stationary trend throughout the analyzed period (AAPC: −0.70; 95% CI −1.90; 0.40) and average mortality from all causes 26.50% higher compared to women. All-cause mortality in women had the lowest rate in 2016 (518.20/100.000) and the highest rate in 1999 (824.30/100.000) with a stationary trend (AAPC: −0.70; 95% CI −2.00; 0.50) throughout the period.

DM mortality in men had the lowest rate in 2007 (18.3/100.000) and the highest rate in 2003 (44.20/100.000), with a stationary trend throughout the analyzed period (AAPC: −0.50; IC95 % −1.70; 0.30) DM mortality in women had the lowest rate in 2019 (23.30/100.000) and the highest rate in 2000 (47.20/100.000), with a decrease of 1.30% per year (AAPC: −1.30; 95% CI −2.40; −0.20) throughout the analyzed period, but still with average mortality related to DM (25%) higher compared to men. A summary of the main results may be observed in Figure 4.

Figure 4

Summary of the obtained findings.

4 Discussion

The total number of people who died in Bauru between 1998 and 2021 from all causas was 58.440 and from DM was 2.779, representing an increase of 82.31% and 100% in the annual counts, respectively. After adjusting for age, mortality rates showed a stationary trend for both conditions. Mortality rates from all causes showed a stationary trend in men and women. However, these rates were 26.50% higher in men compared to women. DM mortality rates also showed a stationary trend in men but with a decrease of 1.30% per year in women. However, DM mortality rates were still 25% higher in women compared to men.

In an initial analysis, our study found a stationary trend in all-cause mortality. It is hypothesized that, although the population ages and the absolute number of deaths would increase, the relatives’ rates would remain stationary [18]. In this case, the death number would increase because health systems would be unable to meet the growing demand for the prevention and management of many diseases [18]. Nonetheless, as the population number would be higher, the proportion of deaths would remain stable [18]. Other studies assumed that there would be a reduction in mortality rates in most countries over the years, in parallel with socioeconomic development, which would strengthen their health systems [19].

A study conducted with data from 195 countries observed that DM has shown increasing mortality rates, possibly due to population aging, increased sedentary lifestyle, and high rates of alcohol and tobacco consumption [20]. Our study observed stationary trends in DM-related mortality rates for men, and decreasing trends for women [20]. A stabilization and even reduction in DM mortality rates was observed in Brazil between 2000 and 2011, possibly due to comprehensive health programs offered by the Brazilian Federal Government, covering the management of chronic non-communicable diseases [21].

Among these programs, two stand out: “Farmácia Popular” and “HiperDia” [22,23]. They aim to subsidize, facilitate, and expand the distribution of medicines and provide greater control and care for chronic conditions, such as hypertension and DM. Evidence suggests that these programs significantly expanded the population’s access to medicines and helped reduce hospitalization and mortality rates [22,23]. Despite this, these programs still face a series of difficulties, related to limited access by a large part of the population, especially those most in need, generally presenting educational and cultural limitations, with many patients having difficulties in using these medications appropriately [24,25,26].

Health education plays a fundamental role. It is not enough to provide medicines. Patients must be educated on how to use them properly. A recent meta-analysis that included data from 70 locations in 59 countries, including Brazil, concluded that education improves life expectancy and reduces mortality without a differential effect on all-cause mortality by sex [27]. Health education for females may have a stronger intergenerational effect than education for males, perhaps suggesting that either girls are more aware of their self-care in preventing or treating illness, or men are least reached by educational strategies, or both [28].

The current study has found higher all-cause mortality rates in men. This is in line with several studies carried out in Brazil and abroad, which found that men had higher mortality rates [24,25,27,28,29]. Possibly, this is explained by the fact that men tend to present worse lifestyle habits, which include higher consumption of alcohol, tobacco, and other drugs, as well as greater exposure to potentially fatal situations or conditions that generate greater morbidity [27,29]. Furthermore, men tend to be generally less concerned about their health in general, being less adherent to preventive measures, early diagnosis of diseases, and search for effective treatment for already existing illnesses [24,25]. Some studies argue that this behavior derives from social prejudices that associate health care with individual fragility [24,25,28]. A recent review has shown a similar perspective of higher all-cause mortality rates in men, in all countries, in all years, from 2006 onwards, which could be due to a complex combination of biological, behavioral, and social elements [1].

This study found higher mortality rates from DM in women. This is in line with several studies, which have highlighted women with DM as being more prone to present higher mortality rates than men, as they generally have poorer glycemic control and also higher rates of vascular complications [26,30]. These factors are possibly due to hormonal factors. In this case, during post-menopause, there is a reduction in serum estrogen levels, which reduces peripheral insulin sensitivity and worsens patients’ glycemic control [30]. Furthermore, greater exposure to social stressors derived from double shift work, the need to head family care, and other social forms of pressure may impact the time women spend looking for qualified professionals to monitor their chronic conditions [30]. This includes DM as well as the quality of treatment they receive for such conditions [30]. Additionally, doctors may be applying clinical guidelines differently to men and women due to gender bias, or there may also be gender differences in following medical prescriptions [26].

However, there is no consensus about these perspectives in the literature. Some studies indicate that in certain countries, men have increasingly sought healthcare services [27,29]. Furthermore, it is argued that the number of women who consume various types of drugs and expose themselves to life-threatening situations has been progressively increasing [24,27,28,29]. Nonetheless, other studies point out that women are more frequently concerned about their health status, have earlier disease diagnoses than men, and are more compliant with medical treatments, in addition to better monitoring their chronic health conditions, such as DM [29].

Brazil is currently going through a process of demographic transition [31]. In the 1950s, the country had a demographic pattern characterized by high birth rates, high infant and general mortality, with a low average life expectancy [31]. However, at the beginning of this century, an evident trend towards reducing birth rates was noted, with a significant reduction in infant and general mortality, as well as an increase in life expectancy, resulting in a significant aging of the population [31]. These fluctuations mean that a transversal and specific assessment of mortality rates loses much of its meaning, as it does not allow observing the real dynamics of the population. Therefore, the present longitudinal analysis of the variation in the Brazilian population is important, considering its epidemiological profile and defining the best public health measures that should be issued, according to age and sex groups [31].

As a consequence of the demographic transition, Brazil faces a significant process of epidemiological transition [32]. Currently, Brazil faces a triple burden of disease, characterized by the persistence of high mortality rates due to infectious diseases and external causes – found mainly in developing countries, associated with high mortality rates associated with chronic and non-communicable diseases – found mainly in developed countries and among older people [32]. This scenario has profound impacts on mortality rates and requires assessment, taking into account some variables, such as gender and age [32].

In general, men tend to have higher mortality rates from infectious and external causes, especially at younger ages, especially around the second and third decades of life, as a result of a complex interaction between social, biological, and behavioral variables [33]. Consequently, the predominance of sudden, unforeseen deaths, often without medical supervision, leads to higher mortality rates in men, being classified as undefined conditions [33]. At the same time, women over 50 tend to have higher mortality rates from chronic non-communicable diseases, such as cardiovascular complications and cancer [4]. This may be due to the fact that women have a longer life expectancy than men, which would increase the chance of having such chronic conditions, and they tend to be more frequently reported on their death certificates [33].

It was observed that, between 1998 and 2019, mortality rates due to all causes showed a decreasing trend. However, between 2019 and 2021, it was noted that trends in mortality rates became stationary and even increased for men. This difference may be due to the COVID-19 pandemic, which led to an increase in the number of deaths worldwide [34].

On the other hand, mortality due to DM showed a decreasing trend throughout the entire period evaluated, regardless of the analyzed group. Possibly, the maintenance of decreasing DM rates during the pandemic period was because COVID-19 generated an overreporting of deaths caused by this condition and an underreporting of other conditions such as DM. Consequently, DM was less reported and its trends continued to decrease [35].

However, some studies suggest that COVID-19 would be a potential driver of DM-related deaths [36,37,38,39]. In this sense, some studies have observed that COVID-19 is associated not only with an increase in the number of DM cases but also with greater severity of them [36,37,38,39].

From this perspective, a systematic review and meta-analysis published in 2022 noted that COVID-19 was associated with a 66% higher risk of incident DM among COVID-19’s survivors (risk ratio: 1.66; 95% CI: 1.38–2.00) [38]. Although the pathophysiological mechanisms of this association are not yet fully understood, it is believed that this derives from a complex process [38]. This involves hyperglycemia generated by infectious stress mediated by increased steroid levels in individuals, as well as the direct and indirect effects of the virus on pancreatic β cells [38].

Furthermore, COVID-19 was associated with a higher case gravity for a series of reasons. COVID-19 virus could act synergistically with DM, favoring inflammatory and vascular dysfunctions and leading to a greater number of poor outcomes [36]. Furthermore, COVID-19 could be related to an increase in the frequency and severity of diabetic ketoacidosis in patients with DM, which is associated with higher mortality rates [37]. This is possibly explained by direct viral damage, metabolic dysfunction, and immune action involving the body’s responses to COVID-19 and DM pathophysiology [39].

Interestingly, most studies have observed an association between COVID-19 and cases of T1DM [36,37,38,39]. However, it is suggested that COVID-19 is also associated with an increase in cases of type 2 diabetes mellitus (T2DM) [40]. In this sense, an Italian study pointed out that the incidence rate of T2DM doubled during the COVID-19 pandemic when compared to the pre-pandemic period [40]. This increase is possibly justified by several factors related to changes in lifestyle and health conditions imposed by the pandemic context [40]. In this case, during periods of social isolation, the reduction in physical activity associated with an increased consumption of ultra-processed foods contributed to the population’s weight gain and increased obesity [40]. Furthermore, the chronic stress, anxiety, and depression generated by isolation and COVID-19’s deaths may have triggered hormonal imbalances and increased insulin resistance [40]. Finally, the SARS-CoV-2 infection itself may predispose to the development of T2DM in susceptible individuals, possibly due to mechanisms of inflammation and pancreatic dysfunction induced by the virus [40].

In Brazil, the completion of the death certificate follows strict guidelines established by the Brazilian Ministry of Health [41]. This guideline is periodically updated and widely shared to ensure consistency and accuracy in reporting all causes of death [41]. The death certificate is a legal document that plays a crucial role in public health surveillance and the formulation of health policies [41]. So, training programs for healthcare professionals have been implemented to improve the accuracy of death reporting and reduce errors in certifying deaths, particularly in cases involving multiple comorbidities [41].

Nonetheless, the accuracy and quality of the data are still the subject of widespread debate in Brazil [42]. Some studies indicate that many diseases, such as DM, are underreported, which contributes to a poorer understanding of their real epidemiological impact in the country [42]. Furthermore, there are errors in the way that documents are filled out, since non-immediately lethal conditions, such as DM, tend to appear as the main cause of death [42].

Other variables that were not possible to be evaluated in our study could interfere with the mortality rates presently analyzed. It should be noted that smoking is a well-established risk factor for all-cause mortality and also for DM-related deaths [43]. Smoking exacerbates chronic inflammation and vascular dysfunction leading to an increase in cardiovascular events, which are highly prevalent in patients with DM [43]. Excessive alcohol consumption may also increase the risk of cardiovascular diseases, liver damage, and neuropathy [44]. Alcohol acts as a trigger for a chronic inflammatory process through the production of free radicals and other toxic substances during its metabolization [44].

The strengths of this study include the broad period evaluated, which increases the sample size and the robustness of the analysis. The use of public databases ensures high population representation, since it includes all deaths in the local population, eliminating sampling biases and ensuring statistical robustness. The inclusion of age as an adjustment variable increases the validity of the results since age-adjusted mortality rates are more accurate and comparable across different periods and age groups.

This study cannot distinguish between DM subtypes (T1DM, T2DM, and gestational diabetes) due to limitations of the available ICD-10 codes. This could interfere with data interpretation, since risk factors, prognoses, and mortality patterns differ between DM subtypes. Furthermore, this study did not include variables such as ethnicity and marital status, which could provide a more in-depth analysis of the social determinants of health. These variables could also influence the results, especially in a country such as Brazil, where racial and socioeconomic inequalities significantly affect health outcomes. Although SIM and DATASUS data are widely used, they are subject to quality issues and underreporting, particularly in less developed areas of Brazil. Data quality and accuracy may vary by location and year, which may impact the reliability of the results. Excluding deaths without age or sex information may result in an underestimation of mortality, especially if these individuals belong to vulnerable demographic groups.

5 Conclusions

Despite a stationary trend in both all-cause and DM-related mortality rates, the absolute increase in deaths from DM by 100% and from all causes by 82.31% highlights the growing burden of this disease. This is especially concerning in light of the fact that DM contributed to 4.46% of all deaths during the study period. The higher mortality rates observed in women for DM (25%) higher than in men suggest a need for gender-specific strategies in managing DM.