LAUSR

Individualswithdiabetes are at increased risk of poor outcomes from coronavirus disease 2019 (COVID-19) (1–4). Whether the excess risk of COVID-19 mortality associated with impaired glucose tolerance and diabetes is different between women and men is uncertain. We used data from the UK Biobank to investigate the sex-specific associations, and sex differences, betweendiabetes status, HbA1c, and risk of COVID-19 mortality. As comparison, we also examined sex-specific associations of death by influenza/pneumonia, a major cause of death from respiratory disease prior to COVID-19, and fatal coronary heart disease (CHD), a condition for which sex differences are well established. TheUKBiobank is a prospective cohort study including ;500,000 participants aged 40–69 years at baseline between 2006 and 2010 (5). Follow-up for causespecific mortality was conducted to 30 June 2020 through linkage with the national death register. Cox regression was used to obtain sex-specific hazard ratios (HRs) and 95% CIs for mortality from COVID-19, influenza/pneumonia, and CHD by diabetes status and HbA1c level. For analyses involving .2 groups, 95% CIs were estimated through floating absolute risks. Adjustments were made for age, BMI, socioeconomic status, smoking, systolic blood pressure, antihypertensive medication, total cholesterol, and lipidloweringmedication.Models for levels of HbA1c (#6.5% [48 mmol/mol],.6.5% to #7.5%, and.7.5% [58mmol/mol])were additionally adjusted for glucose-lowering medication, and models for 1% HbA1c change (irrespective of diabetes) were additionallyadjusted for glucose-lowering medication and diabetes. Interactions between each variable and sex were added to the model to obtain the women-tomen ratio of HRs for each risk factor. Overall, 501,884 participants (54% women) were included. At baseline, 7.1% of men and 3.9% of women were previously diagnosed with diabetes, with medianHbA1c of 7.0% (53mmol/mol) and 6.9% (52 mmol/mol), respectively. Over a mean follow-up of 11.2 years, 408 participants (36% women) died of COVID-19, 549 (36% women) died of influenza/ pneumonia, and 3,347 (19% women) died of CHD. Diabetes was associated with greater excess risk of death from COVID-19, influenza/pneumonia, and CHD inmen andwomen (Table 1). In both sexes, the magnitude of the association was strongest for CHDwith aHRof 3.17 in women and 1.93 in men, followed by influenza/pneumonia (2.06 and 1.80) and COVID-19 (1.52 and 1.73). For COVID-19 and influenza/pneumonia, the magnitude of the association with diabetes was similar between the sexes. For CHD, diabetes was associated with a 64% greater excess risk in women compared withmen. Higher levels of HbA1c were not associated with greater risk of COVID-19 or influenza/pneumonia death in women. In men, an HbA1c .7.5% (58 mmol/mol), compared with no diabetes, was associated with a greater risk of COVID-19 or influenza/pneumonia death. Each 1% higher HbA1c was associated with a 9% greater risk of influenza/pneumonia death in men. By comparison, higher levels of HbA1c were associated with greater risk of fatalCHD inbothsexes,andthemagnitude of the association between 1% higher HbA1c andCHDwas9%stronger inwomen compared with men. This study shows that diabetes is associatedwith a greater risk of fatal COVID19, influenza/pneumonia, andCHD inboth sexes. However, unlike for CHD, there are no sex differences in the association between diabetes and death from COVID-19 or influenza/pneumonia. Our finding that diabetes is associated with higher risk of COVID-19 mortality is consistent with other studies (1–4). A study of 61 million individuals in England showed that over a third of all in-hospital COVID-19–related