Erratum. The Incidence of Diabetes Among 2,777,768 Veterans With and Without Recent SARS-CoV-2 Infection. Diabetes Care 2022;45:782-788.

For the article cited above, an issue in the way the outcome (diabetes status) was coded was identified during a follow-up analysis. Participants with ICD-10 codes for diabetes at any time were excluded from the analysis, and incident diabetes was identified based only on laboratory values and glucose-lowering medications. This resulted in a substantial underestimate of the number of cases of incident diabetes in the cohort. The coding issue was corrected, the analysis was repeated, and the corrected code was validated by an independent analyst. After these steps, in agreement with the original article, there remained a statistically significant and positive association of SARS-CoV-2 infection with incident diabetes in the corrected analysis. The largest differences between the original and corrected analysis were seen in the analyses of all male participants in whom the association of SARS-CoV-2 infection with incident diabetes was attenuated in the corrected analysis compared with the original results (odds ratio 120 days: 2.56 [2.32-2.83] original vs. 1.75 [1.63-1.88] corrected; odds ratio all-time: 1.95 [1.80-2.12] original vs. 1.44 [1.36-1.52] corrected). For hospitalized male participants, the differences were smaller. In agreement with the original article, there was no association of SARS-CoV-2 infection with incident diabetes in women in the corrected analysis. Finally, in the corrected models, the P values for the sex * SARS-CoV-2 infection interaction terms were statistically significant except for participants hospitalized in the first 30 days (all available follow-up time). The authors apologize for the error. The online version of the article (https://doi.org/10.2337/dc21-1686) has been updated with the corrected data.

SARS-CoV-2 infection is associated with higher odds of insulin treatment but not with hemoglobin A1c at 120 days in U.S. Veterans with new-onset diabetes.

Aims: To examine associations of SARS-CoV-2 infection/COVID-19 with insulin treatment in new-onset diabetes. Methods: We conducted a retrospective cohort study using Veterans Health Administration data (March 1, 2020-June 1, 2022). Individuals with ≥1 positive nasal swab for SARS-CoV-2 (n = 6,706) comprised the exposed group, and individuals with no positive swab and ≥1 laboratory test of any type (n = 20,518) the unexposed group. For exposed, the index date was the date of first positive swab, and for unexposed a random date during the month of the qualifying laboratory test. Among Veterans with new-onset diabetes after the index date, we modeled associations of SARS-CoV-2 with most recent A1c prior to insulin treatment or end of follow-up and receipt of >1 outpatient insulin prescription starting within 120 days. Results: SARS-CoV-2 was associated with a 40% higher odds of insulin treatment compared to no positive test (95%CI 1.2-1.8) but not with most recent A1c (ß 0.00, 95%CI -0.04-0.04). Among Veterans with SARS-CoV-2, ≥2 vaccine doses prior to the index date was marginally associated with lower odds of insulin treatment (OR 0.6, 95%CI 0.3-1.0). Conclusions: SARS-CoV-2 is associated with higher odds of insulin treatment but not with higher A1c. Vaccination may be protective.

Associations of statin use with 30-day adverse outcomes among 4 801 406 US Veterans with and without SARS-CoV-2: an observational cohort study.

OBJECTIVE: To estimate associations of statin use with hospitalisation, intensive care unit (ICU) admission and mortality at 30 days among individuals with and without a positive test for SARS-CoV-2. DESIGN: Retrospective cohort study. SETTING: US Veterans Health Administration (VHA). PARTICIPANTS: All veterans receiving VHA healthcare with ≥1 positive nasal swab for SARS-CoV-2 between 1 March 2020 and 10 March 2021 (cases; n=231 154) and a comparator group of controls comprising all veterans who did not have a positive nasal swab for SARS-CoV-2 but who did have ≥1 clinical lab test performed during the same time period (n=4 570 252). MAIN OUTCOMES: Associations of: (1) any statin use, (2) use of specific statins or (3) low-intensity/moderate-intensity versus high-intensity statin use at the time of positive nasal swab for SARS-CoV-2 (cases) or result of clinical lab test (controls) assessed from pharmacy records with hospitalisation, ICU admission and death at 30 days. We also examined whether associations differed between individuals with and without a positive test for SARS-CoV-2. RESULTS: Among individuals who tested positive for SARS-CoV-2, statin use was associated with lower odds of death at 30 days (OR 0.81 (95% CI 0.77 to 0.85)) but not with hospitalisation or ICU admission. Associations were similar comparing use of each specific statin to no statin. Compared with low-/moderate intensity statin use, high-intensity statin use was not associated with lower odds of ICU admission or death. Over the same period, associations of statin use with 30-day outcomes were significantly stronger among individuals without a positive test for SARS-CoV-2: hospitalisation OR 0.79 (95% CI 0.77 to 0.80), ICU admission OR 0.86 (95% CI 0.81 to 0.90) and death 0.60 (95% CI 0.58 to 0.62; p for interaction all <0.001). CONCLUSIONS: Associations of statin use with lower adverse 30-day outcomes are weaker among individuals who tested positive for SARS-CoV-2 compared with individuals without a positive test, indicating that statins do not exert SARS-CoV-2 specific effects.

Associations of statin use with 30-day adverse outcomes among 4 801 406 US Veterans with and without SARS-CoV-2: an observational cohort study

Objective To estimate associations of statin use with hospitalisation, intensive care unit (ICU) admission and mortality at 30 days among individuals with and without a positive test for SARS-CoV-2. Design Retrospective cohort study. Setting US Veterans Health Administration (VHA). Participants All veterans receiving VHA healthcare with ≥1 positive nasal swab for SARS-CoV-2 between 1 March 2020 and 10 March 2021 (cases;n=231 154) and a comparator group of controls comprising all veterans who did not have a positive nasal swab for SARS-CoV-2 but who did have ≥1 clinical lab test performed during the same time period (n=4 570 252). Main outcomes Associations of: (1) any statin use, (2) use of specific statins or (3) low-intensity/moderate-intensity versus high-intensity statin use at the time of positive nasal swab for SARS-CoV-2 (cases) or result of clinical lab test (controls) assessed from pharmacy records with hospitalisation, ICU admission and death at 30 days. We also examined whether associations differed between individuals with and without a positive test for SARS-CoV-2. Results Among individuals who tested positive for SARS-CoV-2, statin use was associated with lower odds of death at 30 days (OR 0.81 (95% CI 0.77 to 0.85)) but not with hospitalisation or ICU admission. Associations were similar comparing use of each specific statin to no statin. Compared with low-/moderate intensity statin use, high-intensity statin use was not associated with lower odds of ICU admission or death. Over the same period, associations of statin use with 30-day outcomes were significantly stronger among individuals without a positive test for SARS-CoV-2: hospitalisation OR 0.79 (95% CI 0.77 to 0.80), ICU admission OR 0.86 (95% CI 0.81 to 0.90) and death 0.60 (95% CI 0.58 to 0.62;p for interaction all <0.001). Conclusions Associations of statin use with lower adverse 30-day outcomes are weaker among individuals who tested positive for SARS-CoV-2 compared with individuals without a positive test, indicating that statins do not exert SARS-CoV-2 specific effects.

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

BACKGROUND: We aimed to assess efficacy and safety, with a special focus on cardiovascular safety, of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications. METHODS: This open-label, parallel-group, phase 3 study was done in 187 sites in 14 countries on five continents. Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m2 or greater, and established cardiovascular disease or a high risk of cardiovascular events. Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL. The primary endpoint was non-inferiority (0·3% non-inferiority boundary) of tirzepatide 10 mg or 15 mg, or both, versus glargine in HbA1c change from baseline to 52 weeks. All participants were treated for at least 52 weeks, with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events (MACE). Safety measures were assessed over the full study period. This study was registered with ClinicalTrials.gov, NCT03730662. FINDINGS: Patients were recruited between Nov 20, 2018, and Dec 30, 2019. 3045 participants were screened, with 2002 participants randomly assigned to tirzepatide or glargine. 1995 received at least one dose of tirzepatide 5 mg (n=329, 17%), 10 mg (n=328, 16%), or 15 mg (n=338, 17%), or glargine (n=1000, 50%), and were included in the modified intention-to-treat population. At 52 weeks, mean HbA1c changes with tirzepatide were -2·43% (SD 0·05) with 10 mg and -2·58% (0·05) with 15 mg, versus -1·44% (0·03) with glargine. The estimated treatment difference versus glargine was -0·99% (multiplicity adjusted 97·5% CI -1·13 to -0·86) for tirzepatide 10 mg and -1·14% (-1·28 to -1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses. Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase. The percentage of participants with hypoglycaemia (glucose <54 mg/dL or severe) was lower with tirzepatide (6-9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1-3% vs glargine 16%). Adjudicated MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) occurred in 109 participants and were not increased on tirzepatide compared with glargine (hazard ratio 0·74, 95% CI 0·51-1·08). 60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) occurred during the study. INTERPRETATION: In people with type 2 diabetes and elevated cardiovascular risk, tirzepatide, compared with glargine, demonstrated greater and clinically meaningful HbA1c reduction with a lower incidence of hypoglycaemia at week 52. Tirzepatide treatment was not associated with excess cardiovascular risk. FUNDING: Eli Lilly and Company.

COVID-19, Hyperglycemia, and New-Onset Diabetes.

Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the ß-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.

Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19.

OBJECTIVE: To identify preinfection risk factors for adverse outcomes among veterans with diabetes and coronavirus disease 2019 (COVID-19) infection. RESEARCH DESIGN AND METHODS: We identified all Veterans Health Administration patients with diabetes and one or more positive nasal swab(s) for severe acute respiratory syndrome coronavirus 2 (1 March 2020-10 March 2021) (n = 64,892). We examined associations of HbA1c and glucose-lowering medication use with hospitalization, intensive care unit (ICU) admission, and mortality at 30 days using logistic regression models and during 4.4 months of follow-up (range <1-13.1) using proportional hazards models. RESULTS: Compared with HbA1c <7.0%, HbA1c ≥9.0% was associated with higher odds of hospitalization, ICU admission, and death at 30 days (odds ratio [OR] 1.27 [95% CI 1.19-1.35], 1.28 [95% CI 1.15-1.42], 1.30 [95% CI 1.17-1.44], respectively) as well as higher risk of death over 4.4 months (hazard ratio [HR] 1.22 [95% CI 1.12-1.32]). Insulin use was associated with higher odds of hospitalization, ICU admission, and death (OR 1.12 [95% CI 1.07-1.18], 1.12 [95% CI 1.04-1.22], and 1.18 [95% CI 1.09-1.27], respectively) and higher risk of death (HR 1.12 [95% CI 1.07-1.18]). Sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonist (GLP1-RA), or angiotensin receptor blocker use were associated with lower odds of hospitalization (OR 0.92 [95% CI 0.85-0.99], 0.88 [95% CI 0.81-0.96], and 0.94 [95% CI 0.89-0.99], respectively). Metformin and SGLT2i use were associated with lower odds (OR 0.84 [95% CI 0.78-0.91], 0.82 [95% CI 0.72-0.94], respectively) and risk of death (HR 0.84 [95% CI 0.79-0.89], 0.82 [95% CI 0.74-0.92], respectively). CONCLUSIONS: Among veterans with diabetes and COVID-19, higher HbA1c and insulin use were directly associated with adverse outcomes, while use of a GLP1-RA, metformin, and SGLT2i was inversely associated.

Changes in mood and health-related quality of life in Look AHEAD 6 years after termination of the lifestyle intervention.

OBJECTIVE: The Action for Health in Diabetes (Look AHEAD) study previously reported that intensive lifestyle intervention (ILI) reduced incident depressive symptoms and improved health-related quality of life (HRQOL) over nearly 10 years of intervention compared with a control group (the diabetes support and education group [DSE]) in participants with type 2 diabetes and overweight or obesity. The present study compared incident depressive symptoms and changes in HRQOL in these groups for an additional 6 years following termination of the ILI in September 2012. METHODS: A total of 1,945 ILI participants and 1,900 DSE participants completed at least one of four planned postintervention assessments at which weight, mood (via the Patient Health Questionnaire-9), antidepressant medication use, and HRQOL (via the Medical Outcomes Scale, Short Form-36) were measured. RESULTS: ILI participants and DSE participants lost 3.1 (0.3) and 3.8 (0.3) kg [represented as mean (SE); p = 0.10], respectively, during the 6-year postintervention follow-up. No significant differences were observed between groups during this time in incident mild or greater symptoms of depression, antidepressant medication use, or in changes on the physical component summary or mental component summary scores of the Short Form-36. In both groups, mental component summary scores were higher than physical component summary scores. CONCLUSIONS: Prior participation in the ILI, compared with the DSE group, did not appear to improve subsequent mood or HRQOL during 6 years of postintervention follow-up.