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Background: Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown.

Objetivos: Conhecer o perfil dos profissionais capacitados no processo de doação de órgãos sólidos, analisar o resultado de sua aprendizagem antes e após o curso, e correlacionar perfil e atuação do profissional com sua aprendizagem e indicação do curso. Métodos: Estudo retroprospectivo, quantitativo, analítico-descritivo com participantes do curso Processo de Doação de Órgãos Sólidos para Profissionais de Saúde. Utilizaram-se questionários online sobre perfil profissional, atuação na área de doação de órgãos, avaliação de conhecimento e indicação do curso. As análises e correlações foram verificadas com os testes de McNemar, postos de Spearman e ponto-bisserial. Resultados: Dos 130 profissionais, 62% eram enfermeiros, 38% médicos, 35% emergencistas, 26% intensivistas e 42% tinham mais de 10 anos de formação. Para o perfil de atuação na área de doação de órgãos, os profissionais relataram ter participado em até cinco casos em cada uma das seguintes etapas: 44% no protocolo de morte encefálica, 56% na entrevista familiar e 60% no processo de doação de órgãos. A taxa de retenção de conhecimento da turma foi de 26,7%, sendo a dos médicos 29,5% e a dos enfermeiros 24,8%. A indicação do curso foi avaliada seguindo o indicador Net Promoter Score (NPS), estando na zona de promotores. A correlação entre os grupos foi positiva e estatisticamente significante para os atuantes na emergência, com mais de 5 anos de formação e com mais de cinco casos relatados sobre as etapas questionadas na doação de órgãos. Não foi identificada correlação significativa dessas variáveis sobre a indicação do curso. Conclusão: O curso contribuiu para a aprendizagem dos profissionais com maior tempo de formação, maior experiência prévia nas etapas do processo de doação de órgãos e atuantes no setor de emergência.

O objetivo do presente estudo é analisar os determinantes da localização das indústrias de transformação e do emprego industrial nos municípios do estado do Paraná entre 2007 e 2017. Para tal, utilizou-se de métodos de estimação de Dados em Painel. Ademais, variáveis proxies para aglomerações (urbana e emprego), tamanho médio das firmas, despesas municipais em capital humano e rendimento médio do setor no município, foram empregadas nas análises. Pode-se concluir que a aglomeração de emprego nos municípios afetou positivamente tais variáveis. Além disso, destaca-se o papel do capital humano e dos gastos municipais nessa função que, de maneira geral, demonstraram impactar positiva e estatisticamente tanto no número de firmas quanto no emprego no setor industrial dos municípios paranaenses

O presente artigo procura analisar, partir da utilização de métodos de econometria espacial, os principais fatores que levaram à reeleição da presidente Dilma Rousseff nas eleições presidenciais de 2014. Além disso, procura averiguar se a presença de prefeitos e governadores de mesmo partido beneficiou sua candidatura. Os resultados apresentados indicam quea candidata recebeu a maioria dos votos nos municípios menos desenvolvidos, com renda per capita menor, maior taxa de analfabetismo e desemprego, sendo também beneficiada pela presença de governador da mesma coligação. Outro ponto analisado foi, a partir de Regressão Ponderada Geograficamente (RPG), o efeito do programa Bolsa Família em cada município brasileiro. A variável se mostrou estatisticamente significativa, em sua maioria, nos municípios das regiões Sul e Sudeste.

DBH is a candidate gene in Parkinson's disease (PD) and contains a putative functional polymorphism (-1021C-->T) that has been reported to modify PD susceptibility. We examined -1021C-->T in a sample of 1,244 PD patients and 1,186 unrelated control subjects. There was no significant difference in allele (p = 0.14) or genotype (p = 0.26) frequencies between the two groups. A similar result was obtained after pooling our data with those previously published. Furthermore, we found no evidence for an effect of genotype on age at onset among patients. Our findings argue against DBH -1021C-->T as a risk factor or age at onset modifier in PD. [ABSTRACT FROM AUTHOR]

Background and Aims: To prospectively investigate associations of plasma sphingolipids with insulin sensitivity, β-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), β-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., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)

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., (© 2024 by the American Diabetes Association.)

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.

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., (© 2022. W. Montague Cobb-NMA Health Institute.)

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., Competing Interests: The authors have no conflicts of interest to declare

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., Competing Interests: A.J.S. has received travel support from Alkermes, Inc., royalties from UpToDate, Inc., consulting fees from Indivior, Inc., and research support from Medicasafe, Inc. No other authors have conflicts of interest to report., (Copyright © 2022 American Society of Addiction Medicine.)

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/m 2 . 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.

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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/m 2 , respectively. Lower levels of miR-1294 were associated with higher waist circumference (β = -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 (β = -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., (Published by Elsevier B.V.)

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 β cells, either directly by SARS-CoV-2 entry into β 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 β 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 β 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.

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., (© 2022 by the American Diabetes Association.)

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., (© 2022 by the American Diabetes Association.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., (© 2021 The Obesity Society (TOS). This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

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 HbA 1c 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 HbA 1c <7.0%, HbA 1c ≥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 HbA 1c and insulin use were directly associated with adverse outcomes, while use of a GLP1-RA, metformin, and SGLT2i was inversely associated., (© 2021 by the American Diabetes Association.)

Background: Greater visceral fat area (VFA) is associated with cardiometabolic outcomes. We sought to identify cross-sectional and longitudinal associations between amino acid (AA) levels and VFA in Japanese-Americans., Methods: From the cohort of 342 Japanese-American participants (51% men) in a study of diabetes risk factors who were free from diabetes, we measured levels of 20 AA by mass spectrometry, height, weight, waist circumference (WC), VFA, subcutaneous fat area by single-slice CT at the umbilicus. Using AA significantly associated with VFA in univariate analyses, we created a VFA prediction index, termed the 4A index. We compared area under receiver-operating characteristic curve (AUROC) of the 4A index to WC and an existing AA index (Yamakado et al. Clin Obes 2012) in classifying VFA at different cutoff values. We fit age-adjusted linear regression models to evaluate associations between AA levels and change in VFA over 5 years., Results: All 20 AA levels significantly detected VFA excess, but WC was better. The 4A index performed better than Yamakado index at classifying VFA ≥ 100 cm 2 (0.798, 0.807 vs. 0.677, 0.671 for men and women, p < 0.0033) and VFA ≥ sex-specific median values (0.797, 0.786 vs. 0.676, 0.629 for men and women, p < 0.0017). AA significantly associated with change in VFA over 5 years were asparagine, glutamate, glutamine, glycine, methionine, proline, threonine in men; and histidine, isoleucine, tyrosine in women (p < 0.05)., Conclusions: The 4A index can serve as a biomarker for VFA in Japanese-Americans and be considered for this purpose when WC is not available., (Copyright © 2021 Asia Oceania Association for the Study of Obesity. All rights reserved.)

Introduction: Risk factors and mediators of associations of diabetes with COVID-19 outcomes are unclear., Research Design and Methods: We identified all veterans receiving Department of Veterans Affairs healthcare with ≥1 positive nasal swab for SARS-CoV-2 (28 February-31 July 2020; n=35 879). We assessed associations of diabetes (with and without insulin use) with hospitalization, intensive care unit (ICU) admission, or death at 30 days, and with hazard of death until the censoring date. Among participants with diabetes (n=13 863), we examined associations of hemoglobin A1c and antihyperglycemic medication use with COVID-19 outcomes. We estimated mediation between diabetes and outcomes by comorbidities (cardiovascular disease, heart failure, and chronic kidney disease), statin or ACE inhibitor/angiotensin receptor blocker (ARB) use, and cardiac biomarkers (brain natriuretic peptide and troponin)., Results: Diabetes with and without insulin use was associated with greater odds of hospitalization, ICU admission, and death at 30 days, and with greater hazard of death compared with no diabetes (OR 1.73, 1.76 and 1.63, and HR 1.61; and OR 1.39, 1.49 and 1.33, and HR 1.37, respectively, all p<0.0001). Prior sulfonylurea use was associated with greater odds of hospitalization and prior insulin use with hospitalization and death among patients with diabetes; among all participants, statin use was associated with lower mortality and ARB use with lower odds of hospitalization. Cardiovascular disease-related factors mediated <20% of associations between diabetes and outcomes., Conclusions: Diabetes is independently associated with adverse outcomes from COVID-19. Associations are only partially mediated by common comorbidities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Epigenetic changes precede the development of diabetes by many years, providing clues to its pathogenesis. We explored whether the epigenetic markers, circulating microRNAs (miRNAs), were associated with incident diabetes in Japanese Americans. We conducted a pilot study (n = 10) using plasma from age- and sex-matched participants who did or did not develop diabetes in the Japanese American Community Diabetes Study, an observational study of diabetes risk factors. Extraction and high-throughput sequencing of miRNAs were performed using samples collected at baseline. Regression models were fit comparing circulating miRNAs (N = 1640) among individuals who did or did not develop incident diabetes at 10-year follow-up. Participants averaged 51.7 years of age at baseline; 60% were male. We identified 36 miRNAs present at different (10 higher and 26 lower) levels in individuals who developed diabetes compared to those who did not (log 2 fold change ≥1.25 and false discovery rate ≤5%). These included miRNAs with functions in skeletal muscle insulin metabolism (miR-106b and miR-20b-5p) and miRNAs with functions in both skeletal muscle insulin metabolism and cell cycle regulation in endocrine pancreas (miR-15a and miR-17). Circulating miRNAs were associated with subsequent development of diabetes among Japanese Americans over 10 years of follow-up. Results are preliminary. Large-scale miRNA sequencing studies could inform our understanding of diabetes pathogenesis and development of therapies, based on gene expression regulation, that target diabetes.

Objective: We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM)., Research Design and Methods: We monitored 4,372 women with a history of GDM participating in the Nurses' Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women's Health Study., Results: We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83-1.34] for up to 6 months, 0.91 [0.72-1.16] for 6-12 months, 0.85 [0.67-1.06] for 12-24 months, and 0.73 [0.57-0.93] for >24 months, compared with 0 months; P -trend = 0.003) and exclusive breastfeeding ( P -trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA 1c , fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P -trend ≤0.04)., Conclusions: Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined., (© 2020 by the American Diabetes Association.)

Aims: Visceral adiposity measured by computed tomography (CT) as intra-abdominal fat area (IAFA) predicts metabolic diseases. Existing adiposity surrogates have not been systematically compared to a regression-based model derived in individuals of Japanese ancestry. We developed and validated a method to estimate IAFA in individuals of Japanese ancestry and compared it to existing adiposity surrogates., Methods: We assessed age, BMI, waist circumference (WC), fasting lipids, glucose, smoking status, grip strength, mid-thigh circumference (MTC), humeral length, leg length, and IAFA by single-slice CT at the umbilicus for 622 Japanese Americans. We used stepwise linear regression to predict IAFA and termed the predicted value the Estimate of Visceral Adipose Tissue Area (EVA). For men, the final model included age, BMI, WC, high-density lipoprotein cholesterol (HDLc), glucose, and MTC; for women, age, BMI, WC, HDLc, low-density lipoprotein cholesterol, glucose, and MTC. We compared goodness-of-fit (R 2 ) from linear regression models and mean-squared errors (MSE) from k-fold cross-validation to compare the ability of EVA to estimate IAFA compared to an estimate by Després et al., waist-to-height ratio, WC, deep abdominal adipose tissue index, BMI, lipid accumulation product, and visceral adiposity index (VAI). We classified low/high IAFA using area under receiver-operating characteristic curves (AUROC) for IAFA dichotomized at the 75th percentile., Results: EVA gave the least MSE and greatest R 2 (men: 1244, 0.61; women: 581, 0.72). VAI gave the greatest MSE and smallest R 2 (mean 2888, 0.08; women 1734, 0.14)., Conclusions: EVA better predicts IAFA in Japanese-American men and women compared to existing surrogates for adiposity., (Published by Elsevier Inc.)

Aims: Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex., Methods: In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen for potential roles in pregnancy course and complications (miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese (ppBMI≥25kg/m 2 ) or lean (ppBMI<25kg/m 2 ) women, and women with male or female offspring separately., Results: Mean age was 34.3years (cases) and 32.9years (controls). GA-adjusted miR-155-5p (β=0.260/p=0.028) and -21-3p (β=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (β=0.266/p=0.068) and miR-517-5p (β=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses (all p<0.05)., Conclusions: Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy., (Published by Elsevier B.V.)

Purpose: To measure changes in markers of resident well-being over time as progressive work hours limitations (WHLs) were enforced, and to investigate resident perceptions of the 2011 WHLs., Method: A survey study of internal medicine residents was conducted at the University of Washington's multihospital residency program in 2012. The survey included validated well-being questions: the Maslach Burnout Inventory, the two-question PRIME-MD depression screen, and career satisfaction questions. Chi-square tests were used to compare 2012 well-being questionnaire responses against nearly identical surveys conducted in 2001 and 2004 at the same institution. In addition, residents were asked to rate the impact of WHLs on resident well-being and education as well as patient care, and to state preferences for future WHLs., Results: Significantly different proportions of residents met burnout criteria across time, with fewer meeting criteria in 2012 than in 2001 (2001: 76% [87/115]; 2004: 64% [75/118]; 2012: 61% [68/112]; P = .039). Depression screening results also differed across time, with fewer screening positive in 2012 than in 2004 (2001: 45% [52/115]; 2004: 55% [65/118]; 2012 [35/112]: 31%; P = .001). Residents, especially seniors, reported perceived negative impacts of WHLs on their well-being, education, and patient care. Most senior residents favored reverting to the pre-July 2011 system of WHLs. Interns were more divided., Conclusions: Validated measures of resident well-being changed across the three time points measured. Residents had the lowest rates of burnout and depression in 2012. Resident perceptions of the 2011 WHLs, however, were generally negative.

Background: Maternal pre-pregnancy overweight and obese status has been associated with a number of pregnancy complications and adverse offspring outcomes. Mechanisms for observed associations, however, are largely unknown. We investigated associations of pre-pregnancy body mass index with early-mid pregnancy epigenetic biomarkers, circulating microRNAs., Methods: Peripheral blood was collected from participants (16-27 weeks gestation) of two multi-racial pregnancy cohorts, the Omega Study and the Pregnancy Outcomes and Community Health Study. Plasma miRNA expression was characterised using epigenome-wide (319 miRNAs) profiling among 20 pregnant women in each cohort. Cohort-specific linear regression models that included the predictor (pre-pregnancy body mass index), the outcome (microRNA expression), and adjustment factors (maternal age, gestational age at blood collection, and race) were fit., Results: Expression of 27 miRNAs was positively associated with pre-pregnancy body mass index in both cohorts (p-values <0.05). A number of these differentially expressed miRNAs have previously been associated with adipogenesis (e.g. let-7d*, miR-103-2*, -130b, -146b-5-p, -29c, and -26b). Identified miRNAs as well as their experimentally validated targets participate in pathways that involve organismal injury, reproductive system disease, connective tissue disorders, cancer, cellular development, growth and proliferation., Conclusion: Pre-pregnancy body mass index is associated with circulating miRNAs in early-mid pregnancy., (Published by Elsevier Ltd.)

Aim: MicroRNAs (miRNAs) have regulatory functions in organs critical in resuscitation from sudden cardiac arrest due to ventricular fibrillation (VF-SCA); therefore, circulating miRNAs may be markers of VF-SCA outcome., Methods: We measured candidate miRNAs (N=45) in plasma using qRT-PCR among participants of a population-based VF-SCA study. Participants were randomly selected cases who died in the field (DF, n=15), died in hospital (DH, n=15), or survived to discharge (DC, n=15), and, age-, sex-, and race-matched controls (n=15). MiRNA levels were compared using ANOVA, t-tests, and fold-changes., Results: Mean age of groups ranged from 66.9 to 69.7. Most participants were male (53-67%) and white (67%). Comparing cases to controls, plasma levels of 17 miRNAs expressed in heart, brain, liver, and other tissues (including miR-29c, -34a, -122, -145, -200a, -210, -499-5p, and -663b) were higher and three non-specific miRNAs lower (miR-221, -330-3p, and -9-5p). Among DH or DC compared with DF cases, levels of two miRNAs (liver-specific miR-122 and non-specific miR-205) were higher and two heart-specific miRNAs (miR-208b and -499-5p) lower. Among DC vs. DF cases, levels of three miRNAs (miR-122, and non-specific miR-200a and -205) were higher and four heart-specific miRNAs (miR-133a, -133b, -208b, and -499-5p) lower. Among DC vs. DH cases, levels of two non-specific miRNAs (miR-135a and -9-3p) were lower., Conclusions: Circulating miRNAs expressed in heart, brain, and other tissues differ between VF-SCA cases and controls and are related to resuscitation outcomes. Measurement of miRNAs may clarify mechanisms underlying resuscitation, improve prognostication, and guide development of therapies. Results require replication., (Published by Elsevier Ireland Ltd.)

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.

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.

Objective: Conduct of emergency research under waiver of consent produces special challenges. Moreover, the act of performing research may have unintended effects, potentially beneficial or detrimental. The Dispatcher-Assisted Randomized Trial (DART) was designed to compare 2 types of dispatcher cardiopulmonary (CPR) instruction, but not intended to affect the proportion of arrest victims that received bystander CPR. We sought to determine whether odds of receiving bystander CPR were higher during DART than during the periods before and after., Methods: We conducted an observational cohort study of 8626 adults who suffered non-traumatic out-of-hospital cardiac arrest prior to emergency medical services (EMS) arrival in greater King County, Washington, between January 1, 1999, and December 31, 2011. Bystander CPR status was assessed through review of dispatch recordings and EMS reports to classify any bystander CPR (any B-CPR), and further categorized as bystander CPR with or without dispatcher assistance (DA-CPR and B-CPR, no DA). We used multivariable logistic regression to evaluate odds of B-CPR before, during, and after DART., Results: The proportions receiving any B-CPR were 52% before DART (1817/3468), 59% during DART (2093/3527), and 54% after DART (885/1631). Compared to the period before DART, odds of receiving any B-CPR were higher during DART (OR=1.35, 95% CI=1.23-1.49), but no different after (OR=1.10, 0.98-1.24). Compared to the before period, odds of DA-CPR were higher during DART (OR=1.79, 1.59-2.02) but no different after (OR=0.94, 0.80-1.10)., Conclusions: Odds of bystander CPR were higher during the trial, an increase related to higher likelihood of DA-CPR. The finding suggests a possible indirect community-wide benefit due to the interventional trial., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. Although maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed., Methods: A birth cohort of 1400 adults, with data at birth, age 17 and 32 years was used. After genotyping offspring, genetic scores, predictive of exposures and outcome were created, and linear regression models with and without scores were fit to examine the associations of mppBMI and GWG with ΔBMI., Results: A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m² increase in ΔBMI, respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed., Conclusions: This study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health., (Copyright © 2013 The Obesity Society.)

Background: Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown., Methods/results: In 1249 mother-offspring pairs recruited from the Jerusalem Perinatal Study, we used archival data to characterize ppBMI and GWG and follow-up data from offspring to assess CMR, including body mass index (BMI), waist circumference, glucose, insulin, blood pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk. We fit linear regression models to examine the associations of ppBMI and GWG with CMR traits with and without adjustment for GRS. Compared to unadjusted models, the coefficient for the association of a one-standard-deviation (SD) difference in GWG and offspring BMI decreased by 41% (95%CI -81%, -11%) from 0.847 to 0.503 and the coefficient for a 1SD difference in GWG and WC decreased by 63% (95%CI -318%, -11%) from 1.196 to 0.443. For other traits, there were no statistically significant changes in the coefficients for GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits were significantly altered by adjustment for GRS., Conclusions: Maternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.

Objective: Visceral adiposity is an important risk factor for cardiovascular disease and type 2 diabetes. We sought to determine whether change in intraabdominal fat area (IAF) over time predicts subsequent development of diabetes., Research Design and Methods: We followed up 436 nondiabetic Japanese-American subjects (mean age 51.9 years, mean BMI 24.2 kg/m(2), 54% male) for development of diabetes. We fit a logistic regression model to examine the association over a 10-year follow-up between change in IAF at 5-year follow-up and other fat areas (measured by computed tomography) and development of incident diabetes, adjusted for age, sex, family history of diabetes in a first-degree relative, second-generation versus third-generation Japanese American (Nisei vs. Sansei), baseline IAF, BMI, weight change over time, smoking status, physical activity level, and subcutaneous fat (SCF) depot areas., Results: Cumulative incidence of diabetes was 20.4% at 10 years. Mean change in IAF was 10.9 cm(2). An increase of 1 SD in IAF was associated with a 1.65-fold increase in the odds of diabetes over 10 years (OR = 1.65, 95% CI 1.21-2.25) after adjusting for the above covariates. This association was also independent of changes in thoracic, thigh, and abdominal SCF, as well as change in weight., Conclusions: We conclude that baseline IAF and accumulation of fat in this area over time are independent predictors of the development of type 2 diabetes in Japanese Americans.

Aims: Much is known about body composition and type 2 diabetes risk but less about body function such as strength. We assessed whether hand-grip strength predicted incident diabetes., Methods: We followed 394 nondiabetic Japanese-American subjects (mean age 51.9) for the development of diabetes. We fit a logistic regression model to examine the association between hand-grip strength at baseline and type 2 diabetes risk over 10 years, adjusted for age, sex, and family history., Results: A statistically significant (p = 0.008) and negative (coefficient -0.208) association was observed between hand-grip strength and diabetes risk that diminished at higher BMI levels. Adjusted ORs for a 10-pound hand-grip strength increase with BMI set at the 25th, 50th or 75th percentiles were 0.68, 0.79, and 0.98, respectively., Conclusions: Among leaner individuals, greater hand-grip strength was associated with lower risk of type 2 diabetes, suggesting it may be a useful marker of risk in this population., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)