Associations of plasma sphingolipids with measures of insulin sensitivity, ß-cell function, and incident diabetes in Japanese Americans.

BACKGROUND AND AIMS: To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, ß-cell function, and incident diabetes in the Japanese American Community Diabetes Study. METHODS AND RESULTS: Baseline plasma samples from adults without diabetes (n = 349; mean age 56.7 years, 51 % men) were assayed for circulating ceramide and sphingomyelin species. Adjusted regression models examined cross-sectional and longitudinal associations with insulin sensitivity (HOMA2-%S), ß-cell function (oral disposition index: DIo) and with incident diabetes over 5 years follow-up. Concentrations of four species (Ceramide C16:0, C18:0, C20:0, and C22:0) were inversely associated with HOMA2-%S at baseline (all P values < 0.05, Q values < 0.05) and change in HOMA2-%S over 5 years (all P values < 0.05, Q values < 0.05). No sphingolipids were associated with baseline or change in DIo. Of the four species associated with HOMA2-%S, only Ceramide C18:0 was significantly and positively associated with incident diabetes (RR/1SD 1.44, 95 % CI 1.10-1.80, P = 0.006, Q = 0.024). The association of plasma Ceramide C18:0 with the risk of diabetes was partially mediated by change in HOMA2-%S between baseline and 5 years (mediation proportion: 61.5 %, 95 % CI 21.1%-212.5 %). CONCLUSION: Plasma Ceramide C18:0 was associated with higher risk of incident diabetes which was partially mediated through a decrease in insulin sensitivity between baseline and five years. Circulating Ceramide C18:0 could be a potential biomarker for identifying those at risk of developing diabetes.

A Case for Targeting Th17 Cells and IL-17A in SARS-CoV-2 Infections.

SARS-CoV-2, the virus causing COVID-19, has infected millions and has caused hundreds of thousands of fatalities. Risk factors for critical illness from SARS-CoV-2 infection include male gender, obesity, diabetes, and age >65. The mechanisms underlying the susceptibility to critical illness are poorly understood. Of interest, these comorbidities have previously been associated with increased signaling of Th17 cells. Th17 cells secrete IL-17A and are important for clearing extracellular pathogens, but inappropriate signaling has been linked to acute respiratory distress syndrome. Currently there are few treatment options for SARS-CoV-2 infections. This review describes evidence linking risk factors for critical illness in COVID-19 with increased Th17 cell activation and IL-17 signaling that may lead to increased likelihood for lung injury and respiratory failure. These findings provide a basis for testing the potential use of therapies directed at modulation of Th17 cells and IL-17A signaling in the treatment of COVID-19.

Maternal Leisure Time Physical Activity and Infant Birth Size.

BACKGROUND: Associations of maternal leisure time physical activity with birth size are inconsistent. Roles of infant sex and maternal prepregnancy body mass index (BMI) in these associations have not been studied. METHODS: Participants (N = 3,310) in the Omega study, a cohort in Washington State (1996-2008), reported leisure time physical activity duration and energy expenditure in the year prepregnancy and in early pregnancy (mean 15 weeks gestation). Regression models estimated mean differences in infant head circumference, birthweight, and ponderal index (birthweight/length) across quartiles of pre- or early-pregnancy leisure time physical activity. We assessed effect modification by infant sex or prepregnancy overweight/obese status (BMI ≥ 25 kg/m). RESULTS: We observed positive associations between prepregnancy leisure time physical activity and head circumference overall and among male infants. Among males, each quartile increase in prepregnancy physical activity duration was associated with 0.14 cm (95% confidence interval = 0.046, 0.24; trend P = 0.004) greater head circumference. We did not observe associations between leisure time physical activity and birthweight or ponderal index overall. Each quartile increase in pre- or early-pregnancy physical activity duration was associated with 17-23 g lower birthweight among female infants and among women with normal prepregnancy BMI. CONCLUSIONS: We observed positive associations between prepregnancy leisure time physical activity and head circumference among male infants, and inverse associations of pre- and early-pregnancy physical activity with birthweight among female infants and women with normal prepregnancy BMI. Future studies should confirm results and elucidate mechanisms of observed associations.

Associations of Early and Late Gestational Weight Gain with Infant Birth Size.

OBJECTIVES: Associations of gestational weight gain (GWG) during specific periods of pregnancy with infant birth size have been inconsistent. Infant sex-specific differences in these associations are unknown METHODS: Information on GWG (kg) [total, early (<20 weeks gestation), and late (≥20 weeks gestation)] and indices of infant birth size including birthweight (BW), ponderal index (PI), crown-heel length (CHL), and head circumference (HC) was collected from 3,621 pregnant women. We calculated adjusted mean differences and 95 % confidence intervals (CIs) relating total, early and late GWG to infant birth size using multivariable linear regression procedures. We used stratified analyses and interaction terms to test whether associations differed by infant sex. RESULTS: One-kg increases in total, early or late GWG were associated with BW increases of 17.2 g (95 % CI 13.8-18.9), 14.1 g (95 % CI 10.3-18.0), and 21.0 g (95 % CI 16.7-25.4), respectively. Early GWG-BW and late GWG-BW associations were different (p = 0.026). Sex-stratified total GWG-BW associations were similar to overall results. There were sex-specific differences in early GWG-BW and late GWG-BW associations. Among females, early GWG-BW (12.0 g, 95 % CI 6.7-17.2) and late GWG-BW (24.2 g, 95 % CI 18.2-30.3) associations differed (p = 0.0042); the corresponding associations did not differ among males. Total, early, and late GWG were associated with CHL and HC, but not with PI. Associations did not differ for early or late GWG. CONCLUSIONS FOR PRACTICE: For comparable GWG, late-GWG-related BW increase is greater than early-GWG-related BW increase, particularly among female infants.

Plasma miRNAs and Treatment Failure in Participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) Study.

OBJECTIVE: To identify plasma miRNAs related to treatment failure in youth with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We examined whether a panel of miRNAs could predict treatment failure in training/test data sets among participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study (N = 209). We also examined whether individual miRNAs were associated with treatment failure. RESULTS: Participants were age 14.5 years, and 62% were female. A panel of miRNAs did not predict treatment failure. However, for each doubling, miR-4306 was associated with a 12% decrease (P = 0.040) and miR-483-3p was marginally associated with a 12% increase (P = 0.080) in failure independently of sex, race/ethnicity, BMI, Tanner stage, HbA1c, maternal diabetes, oral disposition index, and treatment arm. The addition of both miRNAs improved model fit (log likelihood without vs. with miRNAs -360.3 vs. -363.5; P = 0.040). CONCLUSIONS: miR-483-3p and miR-4306 may be associated with treatment failure in youth with T2D.

Addiction Services for Veterans: Opportunities in Acute Care.

OBJECTIVE: This study aimed to estimate the proportion of total hospital discharges that involved a primary or secondary substance-related diagnosis code (SubDx) on inpatient medicine, psychiatry, and surgery services as part of a needs assessment for inpatient addiction consultation at our large, academic-affiliated Veterans Affairs (VA) hospital. METHODS: We first calculated the percentage of total and service-specific discharges with a primary or secondary substance-related International Classification of Disease, Tenth Revision , code on all inpatient services (medicine, psychiatry, and surgery) in Fiscal Year 2017, 2018, and 2019, using facility-level data. Second, we calculated the proportion of total discharges that involved alcohol- and opioid-related diagnoses. RESULTS: Over the 3 years studied, 29% of total discharges had a SubDx (4469 of 15,575). The proportion of total discharges that involved a SubDx was 23% (1246 of 5449) in 2017, 31% (1664 of 5332) in 2018, and 33% in 2019 (1559 of 4794), a statistically significant increase ( P < 0.001). As a percentage of service-specific discharges, 65% of discharges from psychiatry (1446 of 2217) had a SubDx, compared with 25% from medicine (2469 of 9713), and 15% from surgery (554 of 3645). Medicine services had the most discharges with SubDx, with a year-over-year increase in the number of discharges with SubDx. The percentage of total discharges that involved alcohol- and opioid-related diagnoses was 14% and 4%, respectively. CONCLUSIONS: Substance-related diagnoses are prevalent at our hospital and are increasing over time. The largest number of discharges with SubDx was found on medicine services. Alcohol-related diagnoses were nearly 4 times more prevalent than opioid-related diagnoses. We found focused need around alcohol use and alcohol withdrawal.

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.

Cross-sectional Associations of Multiracial Identity with Self-Reported Asthma and Poor Health Among American Indian and Alaska Native Adults.

INTRODUCTION: American Indian and Alaska Native (AI/AN) multiracial subgroups are underrecognized in health outcomes research. METHODS: We performed a cross-sectional analysis of Behavioral Risk Factor Surveillance System surveys (2013-2019), including adults who self-identified as AI/AN only (single race AI/AN, n = 60,413) or as AI/AN and at least one other race (multiracial AI/AN, (n = 6056)). We used log binomial regression to estimate the survey-weighted prevalence ratios (PR) and 95% confidence intervals (CI) of lifetime asthma, current asthma, and poor self-reported health among multiracial AI/AN adults compared to single race AI/AN adults, adjusting for age, obesity, and smoking status. We then examined whether associations differed by sex and by Latinx identity. RESULTS: Lifetime asthma, current asthma, and poor health were reported by 25%, 18%, and 30% of multiracial AI/AN adults and 18%, 12%, and 28% single race AI/AN adults. Multiracial AI/AN was associated with a higher prevalence of lifetime (PR 1.30, 95% CI 1.18-1.43) and current asthma (PR 1.36, 95% CI 1.21-1.54), but not poor health. Associations did not differ by sex. The association of multiracial identity with current asthma was stronger among AI/AN adults who identified as Latinx (PR 1.77, 95% CI 1.08-2.94) than non-Latinx AI/AN (PR 1.18, 95% CI 1.04-1.33), p-value for interaction 0.03. CONCLUSIONS: Multiracial AI/AN adults experience a higher prevalence of lifetime and current asthma compared to single race AI/AN adults. The association between multiracial identity and current asthma is stronger among AI/AN Latinx individuals. The mechanisms for these findings remain under-explored and merit further study.

Rates of ICD-10 Code U09.9 Documentation and Clinical Characteristics of VA Patients With Post-COVID-19 Condition.

Importance: A significant proportion of SARS-CoV-2 infected individuals experience post-COVID-19 condition months after initial infection. Objective: To determine the rates, clinical setting, risk factors, and symptoms associated with the documentation of International Statistical Classification of Diseases Tenth Revision (ICD-10), code U09.9 for post-COVID-19 condition after acute infection. Design, Setting, and Participants: This retrospective cohort study was performed within the US Department of Veterans Affairs (VA) health care system. Veterans with a positive SARS-CoV-2 test result between October 1, 2021, the date ICD-10 code U09.9 was introduced, and January 31, 2023 (n = 388 980), and a randomly selected subsample of patients with the U09.9 code (n = 350) whose symptom prevalence was assessed by systematic medical record review, were included in the analysis. Exposure: Positive SARS-CoV-2 test result. Main Outcomes and Measures: Rates, clinical setting, risk factors, and symptoms associated with ICD-10 code U09.9 in the medical record. Results: Among the 388 980 persons with a positive SARS-CoV-2 test, the mean (SD) age was 61.4 (16.1) years; 87.3% were men. In terms of race and ethnicity, 0.8% were American Indian or Alaska Native, 1.4% were Asian, 20.7% were Black, 9.3% were Hispanic or Latino, 1.0% were Native Hawaiian or Other Pacific Islander; and 67.8% were White. Cumulative incidence of U09.9 documentation was 4.79% (95% CI, 4.73%-4.87%) at 6 months and 5.28% (95% CI, 5.21%-5.36%) at 12 months after infection. Factors independently associated with U09.9 documentation included older age, female sex, Hispanic or Latino ethnicity, comorbidity burden, and severe acute infection manifesting by symptoms, hospitalization, or ventilation. Primary vaccination (adjusted hazard ratio [AHR], 0.80 [95% CI, 0.78-0.83]) and booster vaccination (AHR, 0.66 [95% CI, 0.64-0.69]) were associated with a lower likelihood of U09.9 documentation. Marked differences by geographic region and facility in U09.9 code documentation may reflect local screening and care practices. Among the 350 patients undergoing systematic medical record review, the most common symptoms documented in the medical records among patients with the U09.9 code were shortness of breath (130 [37.1%]), fatigue or exhaustion (78 [22.3%]), cough (63 [18.0%]), reduced cognitive function or brain fog (22 [6.3%]), and change in smell and/or taste (20 [5.7%]). Conclusions and Relevance: In this cohort study of 388 980 veterans, documentation of ICD-10 code U09.9 had marked regional and facility-level variability. Strong risk factors for U09.9 documentation were identified, while vaccination appeared to be protective. Accurate and consistent documentation of U09.9 is needed to maximize its utility in tracking patients for clinical care and research. Future studies should examine the long-term trajectory of individuals with U09.9 documentation.

Does diabetes risk after SARS-CoV-2 infection depend on the viral variant?

SARS-CoV-2 infection is associated with an elevated risk of new-onset diabetes. With infections forecast to rise in the coming months, this may exacerbate an existing public health crisis by increasing rates of diabetes worldwide. Much remains to be learned about a causal link between SARS-CoV-2 and incident diabetes. This is complicated by the rapid evolution of new SARS-CoV-2 variants that may have differential effects on development of diabetes. It is possible that some variants confer an increased risk, while others carry little to no risk. Distinguishing between these possibilities could be key in preventing or screening for new-onset diabetes, and could inform care of at-risk individuals with recent SARS-CoV-2 infection.

Going viral in the islet: mediators of SARS-CoV-2 entry beyond ACE2.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Following initial infection of airway epithelia, SARS-CoV-2 invades a wide range of cells in multiple organs, including pancreatic islet cells. Diabetes is now recognised as a risk factor for severe COVID-19 outcomes, including hospitalisation and death. Additionally, COVID-19 is associated with a higher risk of new-onset diabetes and metabolic complications of diabetes. One mechanism by which these deleterious outcomes may occur is via the destruction of insulin-producing islet ß cells, either directly by SARS-CoV-2 entry into ß cells or indirectly due to inflammation and fibrosis in the surrounding microenvironment. While the canonical pathway of viral entry via angiotensin-converting enzyme 2 (ACE2) has been established as a major route of SARS-CoV-2 infection in the lung, it may not be solely responsible for viral entry into the endocrine pancreas. This is likely due to the divergent expression of viral entry factors among different tissues. For example, expression of ACE2 has not been unequivocally demonstrated in ß cells. Thus, it is important to understand how other proteins known to be highly expressed in pancreatic endocrine cells may be involved in SARS-CoV-2 entry, with the view that these could be targeted to prevent the demise of the ß cell in COVID-19. To that end, this review discusses alternate receptors of SARS-CoV-2 (CD147 and GRP78), as well as mediators (furin, TMPRSS2, cathepsin L, ADAM17, neuropilin-1, and heparan sulphate) that may facilitate SARS-CoV-2 entry into pancreatic islets independent of or in conjunction with ACE2.

A retrospective cohort study of race/ethnicity, pre-pregnancy weight, and pregnancy complications.

OBJECTIVE: To examine the relationship between race/ethnicity, pre-pregnancy overweight/obesity status, and pregnancy complications. METHODS: We conducted a retrospective cohort study among mothers with singleton live births using data from hospitals contributing to the Obstetrical Care Outcomes Assessment Program database (N = 72,697). Race was categorized as Non-Hispanic (NH) White, NH African-American, Hispanic, NH Asian, NH American Indian/Alaskan Native, and NH Native-Hawaiian/Other Pacific Islander. Pre-pregnancy overweight/obesity status was defined as body mass index (BMI)≥25 kg/m2. Pregnancy complications evaluated were gestational diabetes, pre-eclampsia, and cesarean delivery. We fitted adjusted and unadjusted stratified Poisson regression models with robust standard errors. Interaction terms were used to assess statistical significance of interactions between race/ethnicity and pre-pregnancy overweight/obesity status. RESULTS: Most women were NH White (52.1%) and more than half had overweight/obesity (54.3%). Among women with overweight/obesity, Hispanics had a lower risk of cesarean delivery as compared to NH White (adjusted relative risk, aRR:0.89; 95%CI:0.84-0.93). Similarly, among women with overweight/obesity, Hispanic and NH Native-Hawaiian/Other Pacific Islander had a lower risk of preeclampsia (aRR:0.74; 95%CI:0.66-0.82 and aRR:0.64; 95%CI:0.44-0.92, respectively) and NH African-American had a greater risk of gestational diabetes (aRR:1.23; 95%CI:1.07-1.42) when compared with NH White women. These associations were not present among normal-weight women. Women with overweight/obesity, when compared with women of normal-weight, had an increased risk of gestational diabetes and cesarean delivery among all race/ethnicities except NH American Indian/Alaskan Native and NH Native-Hawaiian/Other Pacific Islander, respectively (p-values < .05). The multiplicative interaction terms between race/ethnicity and overweight/obesity status were significant for all three complications (interaction p-values < .05). CONCLUSION: Pre-pregnancy overweight/obesity status modifies associations of race/ethnicity with pregnancy complications. Conversely, race/ethnicity modifies associations of pre-pregnancy overweight/obesity status with pregnancy complications. Our findings have implications for public health and clinical practice, supporting the focus on healthy preconception weight and risk stratification across racial/ethnic groups.

Associations of plasma miRNAs with waist circumference and insulin resistance among women with polycystic ovary syndrome - Pilot study.

BACKGROUND: Insulin resistance (IR) and central obesity are common in polycystic ovary syndrome (PCOS), but pathomechanisms for IR in PCOS are not established. Circulating microRNAs (miRNAs) are non-invasive biomarkers of epigenetic regulation that may contribute to the pathogenesis of IR and central adiposity in PCOS. METHODS: We conducted a pilot study to examine associations of circulating miRNAs with IR and central adiposity among women with PCOS (n = 11) using high-throughput miRNA sequencing. We fit generalized linear models examining associations of waist circumference and HOMA-IR with plasma miRNAs. We used false discovery rate (FDR)-adjusted cutoff p < 0.1 to correct for multiple testing. We used miRDB's Gene Ontology (GO) tool to identify predicted pathways for top hits. RESULTS: Mean age and BMI of participants were 27.9 years and 32.5 kg/m2, respectively. Lower levels of miR-1294 were associated with higher waist circumference (ß = -0.10, FDR = 0.095). While no miRNAs were associated with HOMA-IR at our FDR cut off <0.1, 11 miRNAs were associated with waist circumference and 14 miRNAs with HOMA-IR at unadjusted p < 0.01, including members of the highly conserved miR-17/92 cluster and miR-1294 (ß = -0.10, p < 0.001). The GO analysis of miR-1294 identified 54 overrepresented pathways, including "negative regulation of insulin receptor signaling" (FDR = 0.019), and 6 underrepresented pathways. CONCLUSIONS: Plasma miR-1294 along with members of the miR-17/92 cluster and miRNAs involved in insulin signaling may be associated with central obesity and insulin resistance in PCOS. Larger studies among women with and without PCOS are needed to validate these findings.

The Incidence of Diabetes Among 2,777,768 Veterans With and Without Recent SARS-CoV-2 Infection.

OBJECTIVE: To examine associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection/coronavirus disease 2019 with incident diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using Veterans Health Administration data. We defined all patients without preexisting diabetes with one or more nasal swabs positive for SARS-CoV-2 (1 March 2020-10 March 2021; n = 126,710) as exposed and those with no positive swab and one or more laboratory tests (1 March 2020-31 March 2021; n = 2,651,058) as unexposed. The index date for patients exposed was the date of first positive swab and for patients unexposed a random date during the month of the qualifying laboratory test. We fit sex-stratified logistic regression models examining associations of SARS-CoV-2 with incident diabetes within 120 days and all follow-up time through 1 June 2021. A subgroup analysis was performed among hospitalized subjects only to help equalize laboratory surveillance. RESULTS: SARS-CoV-2 was associated with higher risk of incident diabetes, compared with no positive tests, among men (120 days, odds ratio [OR] 2.56 [95% CI 2.32-2.83]; all time, 1.95 [1.80-2.12]) but not women (120 days, 1.21 [0.88-1.68]; all time, 1.04 [0.82-1.31]). Among hospitalized participants, SARS-CoV-2 was associated with higher risk of diabetes at 120 days and at the end of follow-up in men (OR 1.42 [95% CI 1.22-1.65] and 1.32 [1.16-1.50], respectively) but not women (0.72 [0.34-1.52] and 0.80 [0.44-1.45]). Sex ∗ SARS-CoV-2 interaction P values were all <0.1. CONCLUSIONS: SARS-CoV-2 is associated with higher risk of incident diabetes in men but not in women even after greater surveillance related to hospitalization is accounted for.

The Incidence of Adult-Onset Type 1 Diabetes: A Systematic Review From 32 Countries and Regions.

BACKGROUND: The epidemiology of adult-onset type 1 diabetes (T1D) incidence is not well-characterized due to the historic focus on T1D as a childhood-onset disease. PURPOSE: We assess the incidence of adult-onset (≥20 years) T1D, by country, from available data. DATA SOURCES: A systematic review of MEDLINE, Embase, and the gray literature, through 11 May 2021, was undertaken. STUDY SELECTION: We included all population-based studies reporting on adult-onset T1D incidence and published from 1990 onward in English. DATA EXTRACTION: With the search we identified 1,374 references of which 46 were included for data extraction. Estimates of annual T1D incidence were allocated into broad age categories (20-39, 40-59, ≥60, or ≥20 years) as appropriate. DATA SYNTHESIS: Overall, we observed the following patterns: 1) there is a paucity of data, particularly in low- and middle-income countries; 2) the incidence of adult-onset T1D is lowest in Asian and highest in Nordic countries; 3) adult-onset T1D is higher in men versus women; 4) it is unclear whether adult-onset T1D incidence declines with increasing age; and 5) it is unclear whether incidence of adult-onset T1D has changed over time. LIMITATIONS: Results are generalizable to high-income countries, and misclassification of diabetes type cannot be ruled out. CONCLUSIONS: From available data, this systematic review suggests that the incidence of T1D in adulthood is substantial and highlights the pressing need to better distinguish T1D from T2D in adults so that we may better assess and respond to the true burden of T1D in adults.

Adiposity, related biomarkers, and type 2 diabetes after gestational diabetes: The Diabetes Prevention Program.

OBJECTIVE: This study investigated associations of adiposity and adiposity-related biomarkers with incident type 2 diabetes (T2D) among parous women. METHODS: Among women in the Diabetes Prevention Program (DPP) who reported a previous live birth, circulating biomarkers (leptin, adiponectin, sex hormone-binding globulin, and alanine aminotransferase; n = 1,711) were measured at enrollment (average: 12 years post partum). Visceral (VAT) and subcutaneous adipose tissue areas at the L2-L3 region and the L3-L4 region were quantified by computed tomography (n = 477). Overall and stratified (by history of gestational diabetes mellitus [GDM]) adjusted Cox proportional hazards models were fit. RESULTS: Alanine aminotransferase, L2-L3 VAT, and L3-L4 VAT were positively associated (hazard ratio [HR] for 1-SD increases: 1.073, p = 0.024; 1.251, p = 0.009; 1.272, p = 0.004, respectively), and adiponectin concentration was inversely associated with T2D (HR 0.762, p < 0.001). Whereas leptin concentration was not associated with T2D overall, in GDM-stratified models, a 1-SD higher leptin was positively associated with risk of T2D in women without GDM (HR: 1.126, p = 0.016) and inversely in women with a history of GDM (HR: 0.776, p = 0.013, interaction p = 0.002). CONCLUSIONS: Among parous women, alanine aminotransferase and VAT are positively associated with incident T2D, whereas adiponectin is inversely associated. Leptin is associated with higher risk of T2D in women with a history of GDM but a lower risk in women without a history of GDM.

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.

Consensus elements for observational research on COVID-19-related long-term outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its long-term outcomes may be jointly caused by a wide range of clinical, social, and economic characteristics. Studies aiming to identify mechanisms for SARS-CoV-2 morbidity and mortality must measure and account for these characteristics to arrive at unbiased, accurate conclusions. We sought to inform the design, measurement, and analysis of longitudinal studies of long-term outcomes among people infected with SARS-CoV-2. We fielded a survey to an interprofessional group of clinicians and scientists to identify factors associated with SARS-CoV-2 infection and subsequent outcomes. Using an iterative process, we refined the resulting list of factors into a consensus causal diagram relating infection and 12-month mortality. Finally, we operationalized concepts from the causal diagram into minimally sufficient adjustment sets using common medical record data elements. Total 31 investigators identified 49 potential risk factors for and 72 potential consequences of SARS-CoV-2 infection. Risk factors for infection with SARS-CoV-2 were grouped into five domains: demographics, physical health, mental health, personal social, and economic factors, and external social and economic factors. Consequences of coronavirus disease 2019 (COVID-19) were grouped into clinical consequences, social consequences, and economic consequences. Risk factors for SARS-CoV-2 infection were developed into a consensus directed acyclic graph for mortality that included two minimally sufficient adjustment sets. We present a collectively developed and iteratively refined list of data elements for observational research in SARS-CoV-2 infection and disease. By accounting for these elements, studies aimed at identifying causal pathways for long-term outcomes of SARS-CoV-2 infection can be made more informative.

Cumulative Lactation and Clinical Metabolic Outcomes at Mid-Life among Women with a History of Gestational Diabetes.

Lactation is associated with a lower risk of subsequent cardiometabolic disease among parous women; however, the underlying mechanisms are unknown. Further, the potential protective effects of lactation on cardiometabolic risk markers at mid-life among high-risk women with past gestational diabetes (GDM) are not established. Using data from the Diabetes & Women's Health Study (2012−2014; n = 577), a longitudinal cohort of women with past GDM from the Danish National Birth Cohort (1996−2002), we assessed associations of cumulative lactation duration (none, <6 months, 6−12 months, ≥12−24 months, and ≥24 months) with clinical metabolic outcomes (including type 2 diabetes [T2D], prediabetes, and obesity) and cardiometabolic biomarkers (including biomarkers of glucose/insulin metabolism, fasting lipids, inflammation, and anthropometrics) 9−16 years after enrollment when women were at mid-life. At follow-up, women were 43.9 years old (SD 4.6) with a BMI of 28.7 kg/m2 (IQR 24.6, 33.0); 28.6% of participants had T2D, 39.7% had prediabetes, and 41.2% had obesity. Relative risks (95% CI) of T2D for 0−6, 6−12, 12−24, and ≥24 months of cumulative lactation duration compared to none were 0.94 (0.62,1.44), 0.88 (0.59,1.32), 0.73 (0.46,1.17), and 0.71 (0.40,1.27), respectively. Cumulative lactation duration was not significantly associated with any other clinical outcome or continuous biomarker. In this high-risk cohort of middle-aged women with past GDM, T2D, prediabetes, and obesity were common at follow-up, but not associated with history of cumulative lactation duration 9−16 years after the index pregnancy. Further studies in diverse populations among women at mid-age are needed to understand associations of breastfeeding with T2D.