Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017–2019 and 2020

OBJECTIVE To estimate diabetes-related mortality in Mexico in 2020 compared with 2017–2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017–2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017–2019 rates. RESULTS We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017–2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017–2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018–2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020.

Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury.

Patient Determinants of Mortality with Severe DKA and/or HHS during the COVID Pandemic Differ from the Prepandemic

Background: SARS CoV-2 has been linked to higher mortality rate among DM patients who present with diabetic ketoacidosis (DKA) and/or hyperosmolar hyperglycemic state (HHS) . The Riverside University Health System Medical Center (RUHS-MC) -DKA Outcomes Group initiated a study to determine outcomes and risk factors before and during the pandemic in patients hospitalized at RUHS-MC with DKA and/or HHS. Methods: This was a retrospective cohort study reviewing medical records of non-pregnant adults age 18 or older admitted to the RUHS-MC for DKA and/or HHS from 03/2020 to 02/2021 ("pandemic") compared to 3 years before the pandemic ("pre-pandemic") . Descriptive statistics were used to determine the clinical characteristics. Logistic regression was used to assess the impact of the parameters on the death rate. Results: The mortality rate of DKA and/or HHS was 9% (30/335) during pandemic vs. 1.8% (15/855) during pre-pandemic. Six out of 30 patients died without COVID-19 infection, consistent with the pre-pandemic mortality rate. Pre-existing myocardial infarction and lower beta-hydroxybutyrate level were associated with increased mortality (Table 1) . Discussion: At our institution, the mortality rate of DKA and/or HHS during pandemic was significantly higher, specifically associated with COVID-19 infection. Our study suggests concomitant COVID-19 is a highly lethal and independent factor in patients that develop DKA. The gender disparity in mortality is unexplained and requires additional studies.

Mortality among People with Diabetes Experiencing Hypoglycemic and Hyperglycemic Crises

Severe hypoglycemia and hyperglycemia (ketoacidosis, hyperglycemic hyperosmolar state) are common yet potentially preventable acute complications of diabetes. Our objectives were to use national data from OptumLabs® Data Warehouse, 2011-2020, to 1) characterize trends in all-cause mortality among adults with type 1 diabetes (T1D) and type 2 diabetes (T2D) experiencing emergency department visits or hospitalizations for hypoglycemia and hyperglycemia;2) extend analyses through 2020 to assess the impact of the COVID-pandemic;and 3) examine racial/ethnic and gender disparities in subsequent mortality adjusted for relevant patient characteristics. Among 4,164 adults with T1DM experiencing hypoglycemia, 30-day and 1-year mortality increased from 0.5% to 0.9% and 4.7% to 6.1%. Among 49,931 adults with T2DM experiencing hypoglycemia, 30-day and 1-year mortality were stable at 2.1-2.0% and 16.2-16.1%. Among 4,698 adults with T1DM experiencing hyperglycemia, 30-day and 1-year mortality increased from 0.4% to 1.0% and 2.7% to 5.9%, respectively. Among 17,123 adults with T2DM experiencing hyperglycemia, 30-day and 1-year mortality increased from 2.5% to 3.0% and 11.5% to 13.1%. Table shows differences in mortality rates by age, race/ethnicity, gender. These results call for proactive engagement of high risk individuals experiencing severe hypoglycemia and hyperglycemia to reduce their risk of death.

The Impact of COVID-19 Vaccination on Development of Hyperglycemic Crisis

Hyperglycemic crisis (HC) has been reported in patients with COVID-19 infection, but there is little data about HC following COVID-19 vaccination, with 10 patients described to date. We performed a retrospective observational study examining the correlation between COVID-19 vaccination and HC in adult patients admitted from 1/1/21-7/1/21 at our institution. There were 91 admissions for HC during the study period. Forty-one were admissions for diabetic ketoacidosis (DKA) in patients with type 1 diabetes (T1D) , 2 of which also had hyperglycemic hyperosmolar state (HHS) . In patients with type 2 diabetes (T2D) , there were 49 admissions for DKA, 6 of which also had HHS, and 1 admission for HHS alone. In patients with T1D, 17 admissions occurred following COVID-19 vaccination, ranging from <24 hours to more than 3 months after, including 1 new diagnosis of T1D. All cases had a trigger of insulin omission or other medical illness, including 7 with admission for COVID-19 infection. In patients with T2D, 20 DKA or overlap admissions and 1 HHS admission occurred following COVID-19 vaccination, ranging from 1 to 40 days after. Six of these patients had no clear trigger of medical illness or insulin omission, 3 of which were new diagnoses of T2D. Two were following the first vaccination and 4 following the second vaccination. Hemoglobin A1c at admission was >11% in all 6 of these patients. Among patients with T1D, there were no cases of HC that appeared to be attributable to COVID-19 vaccination. In patients with T2D, while there were six cases following vaccination with no other clear trigger, the degree of hemoglobin A1C elevation at the time of admission was suggestive of longer duration of poor glycemic control. Three of these cases did have acute symptom onset following vaccination within one week of presentation, so it is possible that HC was provoked by vaccination in these patients. While it is not clear that COVID vaccination leads to HC in T1D, it may be an acute trigger for HC in patients with T2D who have poor underlying glycemic control. Large scale population studies are needed to better assess rates of HC following COVID-19 vaccination.