Trends in All-Cause and Cause-Specific Mortality Among Individuals With Diabetes Before and During the COVID-19 Pandemic in the U.S.

The International Diabetes Federation reported 6.7 million deaths worldwide among adults with diabetes in 2021, accounting for 12.2% of all deaths globally (1). The age-standardized mortality from diabetes declined from 2007 to 2014 and then stabilized from 2014 to 2017 in the U.S. (2). Recently, U.S. data from National Vital Statistics System demonstrated an increase in deaths with diabetes as the underlying cause of death during the coronavirus disease 2019 (COVID-19) pandemic in most states (3). Diabetes being reported as an underlying cause of death is insufficient to estimate diabetes-related national mortality. In individuals with diabetes during the COVID-19 pandemic, the underlying cause of death may include COVID-19, cardiovascular disease (CVD), cancer, and renal disease. Therefore, we estimated the trends in all-cause diabetes-related mortality and cause-specific mortality in the U.S. before and during the COVID-19 pandemic.

We previously described the methods used in this study in detail (2). To estimate quarterly trends in diabetes-related mortality in American adults aged ≥20 years, we analyzed de-identified national mortality records from NVSS 2017–2020 using death certificates. We defined individuals with diabetes based on the ICD-10 (E10-E14) for underlying or contributing causes of death. Using documentation of underlying cause of death for individuals with diabetes, we defined death related to CVD based on ICD-10 I00–I99, cancer ICD-10 C00–C97, diabetes ICD-10 E10–E14, renal disease ICD-10 N00–N07, N17–N19, and N25–N27, accident V01–X59 and Y85–Y86, and COVID-19 U07.1. To determine the impact of the COVID-19 pandemic on the mortality from diabetes, we calculated quarterly age-specific mortality by dividing the number of deaths by the total U.S. census population for each year, standardized to the 2010 U.S. standard population’s age distribution. We calculated the quarterly percentage change (QPC) and the average QPC, which is a summary measure of trend for explaining transitions within each trend segment, using joinpoint regression to determine secular trends over time.

Out of 11,750,978 deaths from 2017 to 2020 in the U.S., study population consisted of 1,218,968 deaths from all-cause mortality due to diabetes (listed as the underlying or contributing cause of death); 373,802 from CVD, 358,439 from diabetes, 124,881 from cancers, 2,310 from renal disease, and 62,595 from COVID-19 (2020) as the underlying cause of death among individuals with diabetes. Although the quarterly age-standardized all-cause mortality due to diabetes increased with an average QPC of 2.4% (95% CI 0.8–4.1) (Fig. 1A), all-cause mortality for diabetes remained stable from 2017 quarter 1 (2017Q1) to 2019Q3 (QPC −1.0%, 95% CI −2.5 to 0.6) and sharply increased from 2019Q3 to 2020Q4 (QPC 9.6%, 95% CI 4.7–14.6). For cause-specific mortality among individuals with diabetes, quarterly CVD-, diabetes-, or renal disease–related mortality among individuals with diabetes remained stable before and during the COVID-19 pandemic. While cancer-related mortality remained stable before the COVID-19 pandemic (QPC −0.2%, 95% CI −0.7 to 0.2), it increased at a rate of 3.9% (95% CI 1.7–6.2) during the COVID-19 pandemic. COVID-19–related mortality among individuals with diabetes markedly increased from 0.4 per 100,000 people in 2020Q1 to 9.7 per 100,000 people in 2020Q4, matching the increasing gap in all-cause mortality due to diabetes, and accounting for the increase in contributing cause of death due to diabetes, during the COVID-19 pandemic. Trends in the proportion of CVD-, diabetes-, cancer-, and renal disease–related mortality as the underlying cause of death among individuals with diabetes decreased with a quarterly decline of −6.0% to −7.5% during the COVID-19 pandemic, while annual trends in the proportion of cause-specific mortalities remained stable before the COVID-19 pandemic (Fig. 1B). The proportion of COVID-19–related mortality among individuals with diabetes sharply increased from 1.3% in 2020Q1 to 24.7% in 2020Q4, which resulted in an equal proportion of deaths with CVD (24.0%) or diabetes (24.1%) as the underlying cause of death among individuals with diabetes.

COVID-19–related mortality for at-risk populations, such as those with diabetes, who are more susceptible to a dysregulated inflammatory response or cytokine storm, is up to fourfold higher (4,5). Although obtaining the underlying or contributing cause of death from the death certificate may have the potential for underestimation and misclassification, it is unlikely that coding alone accounted for the temporal trends in diabetes-related death. In conclusion, all-cause mortality for diabetes remained stable before the COVID-19 pandemic but surged abruptly during the COVID-19 pandemic. While there was no significant increase in diabetes- or CVD-related mortality among individuals with diabetes, the proportion of COVID-19–related mortality among individuals with diabetes sharply increased to ∼25%, matching the proportion of deaths due to CVD or diabetes.