Acculturation, Body Mass Index and Type 2 Diabetes Risk in Asian Americans

Exposure and assimilation to a Western environment (acculturation) might impact the health of Asian immigrants to the US. This hypothesis is supported by the lower prevalence of overweight and diabetes in Asians living in Asia compared to those living in the US, but longitudinal studies are lacking. We conducted a longitudinal analysis on 8,634 Asians using data on acculturation (generational status, length of US residence, age at immigration) and BMI history from the California Men's Health Study (2002-2003) and information on repeated, measured BMI and diabetes diagnoses from electronic health records (2005-2012). We determined: (1) differences in BMI changes in Asians living in Asia versus Asians living in the US; (2) the association between acculturation, overweight and BMI change after immigration to the US; and (3) BMI's role as a mediator of the association between acculturation and incident diabetes. We confirmed that Asians living in Asia experienced smaller increases in BMI over time than those living in the US at the same age. After immigration to the US, first-generation, foreign-born Asians gained weight rapidly during their first 25 years in the US, yet they never reached the same level of overweight as their second- and third-generation, US-born counterparts. Contrary to our expectations, Asians born in Asia had a higher risk of diabetes than those born in the US despite their lower BMI levels. Thus, Asians might be exposed to risk factors, other than BMI, prior to migrating to the US. Less acculturated Asians were at even higher diabetes risk when we considered the effect independent of BMI using mediation analysis. Their lower BMI levels protect less acculturated Asian men from diabetes. These results provide novel insights into the influence of a Western environment on BMI and diabetes risk among Asian immigrants and emphasize the importance of public health efforts in this vulnerable ethnic group, which already has elevated diabetes risk at the time of immigration. Interventions focused on maintaining a healthy weight are needed for Asians immediately after immigration to the US.Doctor of Philosoph

Sources of Food Affect Dietary Adequacy of Inuit Women of Childbearing Age in Arctic Canada

Dietary transition in the Arctic is associated with decreased quality of diet, which is of particular concern for women of childbearing age due to the potential impact of maternal nutrition status on the next generation. The study assessed dietary intake and adequacy among Inuit women of childbearing age living in three communities in Nunavut, Canada. A culturally-appropriate quantitative food-frequency questionnaire was administered to 106 Inuit women aged 19-44 years. Sources of key foods, energy and nutrient intakes were determined; dietary adequacy was determined by comparing nutrient intakes with recommendations. The prevalence of overweight/obesity was >70%, and many consumed inadequate dietary fibre, folate, calcium, potassium, magnesium, and vitamin A, D, E, and K. Non-nutrient-dense foods were primary sources of fat, carbohydrate and sugar intakes and contributed >30% of energy. Traditional foods accounted for 21% of energy and >50% of protein and iron intakes. Strategies to improve weight status and nutrient intake are needed among Inuit women in this important life stage

Body Mass Index at Age 25 and All-Cause Mortality in Whites and African Americans: The Atherosclerosis Risk in Communities Study

Approximately 20% of young adults in the United States are obese, and most gain weight between young and middle adulthood. Few studies have examined the association between elevated BMI in early adulthood and mortality or examined such effects independent of changes in weight. We know of no studies in African American samples

Long- and Short-term Weight Change and Incident Coronary Heart Disease and Ischemic Stroke: The Atherosclerosis Risk in Communities Study

Weight gain increases the prevalence of obesity, a risk factor for cardiovascular disease. Nevertheless, unintentional weight loss can be a harbinger of health problems. The Atherosclerosis Risk in Communities Study (1987–2009) included 15,792 US adults aged 45–64 years at baseline and was used to compare associations of long-term (30 years) and short-term (3 years) weight change with the risks of coronary heart disease (CHD) and ischemic stroke. Age-, gender-, and race-standardized incidence rates were 4.9 (95% confidence interval (CI): 4.6, 5.2) per 1,000 person-years for CHD and 2.5 (95% CI: 2.3, 2.8) per 1,000 person-years for stroke. After controlling for baseline body mass index and other covariates, long-term weight gain (since age 25 years) of more than 2.7% was associated with elevated CHD risk, and any long-term weight gain was associated with increased stroke risk. Among middle-aged adults, short-term (3-year) weight loss of more than 3% was associated with elevated immediate CHD risk (hazard ratio = 1.46, 95% CI: 1.18, 1.81) and stroke risk (hazard ratio = 1.45, 95% CI: 1.10, 1.92). Risk tended to be larger in adults whose weight loss did not occur through dieting. Avoidance of weight gain between early and middle adulthood can reduce risks of CHD and stroke, but short-term, unintentional weight loss in middle adulthood may be an indicator of immediate elevated risk that has not previously been well recognized

Sources of Food Affect Dietary Adequacy of Inuit Women of Childbearing Age in Arctic Canada

Dietary transition in the Arctic is associated with decreased quality of diet, which is of particular concern for women of childbearing age due to the potential impact of maternal nutrition status on the next generation. The study assessed dietary intake and adequacy among Inuit women of childbearing age living in three communities in Nunavut, Canada. A culturally-appropriate quantitative food-frequency questionnaire was administered to 106 Inuit women aged 19-44 years. Sources of key foods, energy and nutrient intakes were determined; dietary adequacy was determined by comparing nutrient intakes with recommendations. The prevalence of overweight/obesity was >70%, and many consumed inadequate dietary fibre, folate, calcium, potassium, magnesium, and vitamin A, D, E, and K. Non-nutrient-dense foods were primary sources of fat, carbohydrate and sugar intakes and contributed >30% of energy. Traditional foods accounted for 21% of energy and >50% of protein and iron intakes. Strategies to improve weight status and nutrient intake are needed among Inuit women in this important life stage

Cardiovascular disease risk by assigned treatment using the 2013 and 1998 obesity guidelines: Evaluation of Obesity Guidelines

The 1998 and the 2013 guidelines on management of overweight and obesity in adults provided algorithms for identification of patients to be treated with weight loss. To date the cardiovascular disease (CVD) risk in the groups recommended or not recommended for weight loss treatment have not been estimated and compared

Mammographic density and epithelial histopathologic markers

<p>Abstract</p> <p>Background</p> <p>We explored the association of mammographic density, a breast cancer risk factor, with hormonal and proliferation markers in benign tissue from tumor blocks of pre-and postmenopausal breast cancer cases.</p> <p>Methods</p> <p>Breast cancer cases were recruited from a case-control study on breast density. Mammographic density was assessed on digitized prediagnostic mammograms using a computer-assisted method. For 279 participants of the original study, we obtained tumor blocks and prepared tissue microarrays (TMA), but benign tissue cores were only available for 159 women. The TMAs were immunostained for estrogen receptor alpha (ERα) and beta (ERβ), progesterone receptor (PR), HER2/neu, Ki-67, and Proliferating Cell Nuclear Antigen (PCNA). We applied general linear models to compute breast density according to marker expression.</p> <p>Results</p> <p>A substantial proportion of the samples were in the low or no staining categories. None of the results was statistically significant, but women with PR and ERβ staining had 3.4% and 2.4% higher percent density. The respective values for Caucasians were 5.7% and 11.6% but less in Japanese women (3.5% and -1.1%). Percent density was 3.4% higher in women with any Ki-67 staining and 2.2% in those with positive PCNA staining.</p> <p>Conclusion</p> <p>This study detected little evidence for an association between mammographic density and expression of steroid receptors and proliferation markers in breast tissue, but it illustrated the problems of locating tumor blocks and benign breast tissue samples for epidemiologic research. Given the suggestive findings, future studies examining estrogen effects in tissue, cell proliferation, and density in the breast may be informative.</p

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)