Non-communicable diseases (NCDs) now account for more than 36 million deaths each year; many of which are premature. Pacific Islanders are some of the worst afflicted by obesity and diabetes with ...prevalence of both diseases rising disproportionately faster in the Pacific region over the past three decades than in the rest of the world. A high burden of disease is also found among enclaves of Pacifican migrants in the USA, Australia, and New Zealand. Urgent action is needed to alleviate the high economic and personal costs now associated with NCDs in Pacific Islanders. In this article, we describe contributors to the temporal trends in obesity and diabetes, discuss the current burden of disease in the Pacific Islands and among migrant communities, and suggest priorities for future research in this area. Finally, we discuss challenges unique to intervention among Pacific Islanders and highlight promising opportunities to reduce the NCD burden.
Samoans are a unique founder population with a high prevalence of obesity, making them well suited for identifying new genetic contributors to obesity. We conducted a genome-wide association study ...(GWAS) in 3,072 Samoans, discovered a variant, rs12513649, strongly associated with body mass index (BMI) (P = 5.3 × 10(-14)), and replicated the association in 2,102 additional Samoans (P = 1.2 × 10(-9)). Targeted sequencing identified a strongly associated missense variant, rs373863828 (p.Arg457Gln), in CREBRF (meta P = 1.4 × 10(-20)). Although this variant is extremely rare in other populations, it is common in Samoans (frequency of 0.259), with an effect size much larger than that of any other known common BMI risk variant (1.36-1.45 kg/m(2) per copy of the risk-associated allele). In comparison to wild-type CREBRF, the Arg457Gln variant when overexpressed selectively decreased energy use and increased fat storage in an adipocyte cell model. These data, in combination with evidence of positive selection of the allele encoding p.Arg457Gln, support a 'thrifty' variant hypothesis as a factor in human obesity.
Tuberculosis (TB) stigma remains a barrier to early diagnosis and treatment completion. Increased understanding of stigma is necessary for improved interventions to minimise TB stigma and its ...effects. The purpose of this study is to quantitatively measure TB stigma and to explore qualitatively its manifestation among TB patients in a rural Kenyan community.
This hospital based study using explanatory sequential mixed methods approach was conducted in 2016. In the quantitative part of the study, a questionnaire containing socio-demographic characteristics and scales measuring perceived TB stigma and experienced TB stigma, was administered to 208 adult pulmonary TB patients receiving treatment in West Pokot County. Respondents with high stigma were purposively selected to take part in in-depth interviews and focus group discussions. The qualitative data were collected through 15 in-depth interviews and 6 focus group discussions with TB patients. Descriptive and bivariate analysis was done for the quantitative data while the thematic analysis was done for qualitative data.
The internal consistency reliability coefficients were satisfactory with Cronbach alphas of 0.87 and 0.86 for the 11-item and 12-item stigma measurement scale. The investigation revealed that TB stigma was high. The key drivers of TB stigma were the association of TB with HIV/AIDS and the fear of TB transmission. TB stigma was exemplified through patients being isolated by others, self-isolation, fear to disclose TB diagnosis, association of TB with human immunodeficiency virus (HIV) and lack of social support. Being a woman was significantly associated with high levels of both experienced stigma (p = 0.007) and perceived stigma (p = 0.005) while age, marital status, occupation and the patient's religion were not.
There is a need to implement stigma reduction interventions in order to improve TB program outcomes.
This paper demonstrates that internal migration may be contributing to rising non-communicable disease risk in low- and middle-income countries in gendered and geographically differentiated ways. ...With 2018 baseline data from the Migrant Health Follow-Up Study, we investigate the relationship between internal migration and elevated blood pressure (BP) among 2163 rural-origin men and women in South Africa, testing for sex differences. To examine the influence of place, we test whether the migration-BP relationship differs by migrants' destination locations, controlling for household composition, social support, prior migration, and housing quality. We find that migration is associated with elevated BP only among women, and that this association is greatest for migrants living in Tembisa township. Our research underscores that gender and migration are important social determinants of noncommunicable disease risk in low-resource, rapidly-urbanizing settings.
•Gender plays an important role in structuring the NCD burden in LMICs.•Migration is associated with elevated blood pressure among women.•Elevations in blood pressure vary by migrants' urban destination locations.•Household headship mediates but does not eliminate the health penalty among women.•Migrant women’s health may be especially sensitive to social and contextual factors.
The A allele of rs373863828 in CREB3 regulatory factor is associated with high Body Mass Index, but lower odds of type 2 diabetes. These associations have been replicated elsewhere, but to date all ...studies have been cross-sectional. Our aims were (1) to describe the development of type 2 diabetes and change in fasting glucose between 2010 and 2018 among a longitudinal cohort of adult Samoans without type 2 diabetes or who were not using diabetes medications at baseline, and (2) to examine associations between fasting glucose rate-of-change (mmol/L per year) and the A allele of rs373863828. We describe and test differences in fasting glucose, the development of type 2 diabetes, body mass index, age, smoking status, physical activity, urbanicity of residence, and household asset scores between 2010 and 2018 among a cohort of n = 401 adult Samoans, selected to have a ~2:2:1 ratio of GG:AG: AA rs373863828 genotypes. Multivariate linear regression was used to test whether fasting glucose rate-of-change was associated with rs373863828 genotype, and other baseline variables. By 2018, fasting glucose and BMI significantly increased among all genotype groups, and a substantial portion of the sample developed type 2 diabetes mellitus. The A allele was associated with a lower fasting glucose rate-of-change (beta = -0.05 mmol/L/year per allele, p = 0.058 among women; beta = -0.004 mmol/L/year per allele, p = 0.863 among men), after accounting for baseline variables. Mean fasting glucose and mean BMI increased over an eight-year period and a substantial number of individuals developed type 2 diabetes by 2018. However, fasting glucose rate-of-change, and type 2 diabetes development was lower among females with AG and AA genotypes. Further research is needed to understand the effect of the A allele on fasting glucose and type 2 diabetes development. Based on our observations that other risk factors increased over time, we advocate for the continued promotion for diabetes prevention and treatment programming, and the reduction of modifiable risk factors, in this setting.
Background. The dual burden of cardiovascular diseases and Human Immunodeficiency Virus (HIV) in sub-Saharan Africa is of public health concern. Persons living with HIV are 1.5–2 times more likely to ...develop CVD risk factors compared to the noninfected individuals. Hypertension is a major risk factor leading to the rising CVD epidemic in SSA. However, the burden of hypertension among HIV patients in Kenya is not well documented. Objective. This study determined the prevalence and the associated factors of hypertension among HIV patients receiving regular care at Thika Level 5 Hospital Comprehensive Care Clinic (CCC), within metropolitan Nairobi, Kenya. Methods. The current cross-sectional study involved review of patients’ records/charts. Charts for adult patients seen in the last 6 months at Thika Level 5 Hospital CCC were included in the study. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on two different readings one month apart, while overweight/obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Results. In a sample of 939 HIV patients, the majority, 68.8% (646), were female. The patients’ ages ranged from 18 to 84 years with a median age of 44 (IQR 37–51) years. The mean BMI was higher for females (25.8 kg/m2) compared to that of males (23.1 kg/m2). However, the prevalence of hypertension was higher among males (25.3%) compared to females (16.9%). Age >40 years (AOR = 2.80, p≤0.001), male sex (AOR = 2.10; p=0.04), history of alcohol consumption (AOR = 2.56, p≤0.001), and being overweight/obese (AOR = 2.77 p≤0.001) were significantly associated with hypertension. The antiretroviral (ARV) regimen and, additionally, the duration of antiretroviral therapy had no association with being hypertensive. Conclusion. The prevalence of hypertension is high among HIV patients. Traditional cardiovascular risk factors were associated with hypertension, but no association was observed with ART regime or duration of ARV use. There is a need to integrate hypertension management into regular HIV care.
This paper investigates the demographic and socio-economic correlates of dietary patterns in South Africa, drawing on a sample of young adults experiencing internal migration and urbanisation. We use ...data from the 2018 baseline survey of the Migrant Health Follow-Up Study, an original longitudinal cohort study consisting of 3,087 internal migrants and rural residents aged 18-40 nested within the Agincourt Health and socio-Demographic Surveillance System in rural northeast South Africa. We employ principal components analysis to identify dietary patterns from food frequency questionnaires and ordinary least squares regression to assess whether migration and other socio-economic characteristics correlate with specific dietary patterns at baseline. We observe five distinct dietary patterns characterised by frequent consumption of processed foods, red meat, fruits and vegetables, diverse foods, and high sugar/fat foods. We find migration to be significantly associated with more frequent consumption of both processed foods and fruits and vegetables; we also find the association between migration status and dietary patterns to be heterogenous depending on migrants' destinations. This paper extends current understanding of changing dietary patterns in the context of nutrition transitions with attention to dynamic migration processes rather than static rural-urban differences.This paper investigates the demographic and socio-economic correlates of dietary patterns in South Africa, drawing on a sample of young adults experiencing internal migration and urbanisation. We use data from the 2018 baseline survey of the Migrant Health Follow-Up Study, an original longitudinal cohort study consisting of 3,087 internal migrants and rural residents aged 18-40 nested within the Agincourt Health and socio-Demographic Surveillance System in rural northeast South Africa. We employ principal components analysis to identify dietary patterns from food frequency questionnaires and ordinary least squares regression to assess whether migration and other socio-economic characteristics correlate with specific dietary patterns at baseline. We observe five distinct dietary patterns characterised by frequent consumption of processed foods, red meat, fruits and vegetables, diverse foods, and high sugar/fat foods. We find migration to be significantly associated with more frequent consumption of both processed foods and fruits and vegetables; we also find the association between migration status and dietary patterns to be heterogenous depending on migrants' destinations. This paper extends current understanding of changing dietary patterns in the context of nutrition transitions with attention to dynamic migration processes rather than static rural-urban differences.
Obesity and diabetes have strong heritable components, yet the genetic contributions to these diseases remain largely unexplained. In humans, a missense variant in Creb3 regulatory factor (CREBRF) ...rs373863828 (p.Arg457Gln); CREBRFR457Q is strongly associated with increased odds of obesity but decreased odds of diabetes. Although virtually nothing is known about CREBRF's mechanism of action, emerging evidence implicates it in the adaptive transcriptional response to nutritional stress downstream of TORC1. The objectives of this study were to generate a murine model with knockin of the orthologous variant in mice (CREBRFR458Q) and to test the hypothesis that this CREBRF variant promotes obesity and protects against diabetes by regulating energy and glucose homeostasis downstream of TORC1. To test this hypothesis, we performed extensive phenotypic analysis of CREBRFR458Q knockin mice at baseline and in response to acute (fasting/refeeding), chronic (low- and high-fat diet feeding), and extreme (prolonged fasting) nutritional stress as well as with pharmacological TORC1 inhibition, and aging to 52 weeks. The results demonstrate that the murine CREBRFR458Q model of the human CREBRFR457Q variant does not influence energy/glucose homeostasis in response to these interventions, with the exception of possible greater loss of fat relative to lean mass with age. Alternative preclinical models and/or studies in humans will be required to decipher the mechanisms linking this variant to human health and disease.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy ...and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19.
We did a randomised, double-blind, placebo-controlled, phase 2 pilot trial at nine UK sites. Adults aged 18 years or older and admitted to hospital with COVID-19 symptoms, with a positive RT-PCR or point-of-care test, or both, were randomly assigned (1:1) to receive SNG001 (6 MIU) or placebo by inhalation via a mouthpiece daily for 14 days. The primary outcome was the change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population (all randomised patients who received at least one dose of the study drug). The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death. Multiple analyses were done to identify the most suitable statistical method for future clinical trials. Safety was assessed by monitoring adverse events for 28 days. This trial is registered with Clinicaltrialsregister.eu (2020-001023-14) and ClinicalTrials.gov (NCT04385095); the pilot trial of inpatients with COVID-19 is now completed.
Between March 30 and May 30, 2020, 101 patients were randomly assigned to SNG001 (n=50) or placebo (n=51). 48 received SNG001 and 50 received placebo and were included in the intention-to-treat population. 66 (67%) patients required oxygen supplementation at baseline: 29 in the placebo group and 37 in the SNG001 group. Patients receiving SNG001 had greater odds of improvement on the OSCI scale (odds ratio 2·32 95% CI 1·07-5·04; p=0·033) on day 15 or 16 and were more likely than those receiving placebo to recover to an OSCI score of 1 (no limitation of activities) during treatment (hazard ratio 2·19 95% CI 1·03-4·69; p=0·043). SNG001 was well tolerated. The most frequently reported treatment-emergent adverse event was headache (seven 15% patients in the SNG001 group and five 10% in the placebo group). There were three deaths in the placebo group and none in the SNG001 group.
Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials.
Synairgen Research.
To estimate associations of HIV status and antiretroviral (ART) regimen with gestational diabetes (GDM) and postpartum glucose metabolism.
Prospective cohort study.
We enrolled pregnant persons with ...HIV (PWH) and without HIV in Cape Town, South Africa who were at least 18 years of age at 24-28 weeks' gestation and followed up to 26 months postpartum. Participants were tested for GDM in pregnancy and for diabetes postpartum using a 75 g 2 h oral glucose tolerance test (OGTT) and diagnosed via WHO criteria. We estimated associations of HIV status and ART regime efavirenz (EFV) versus dolutegravir (DTG) with GDM and postpartum impaired glucose metabolism using multivariable log binomial or linear regression models.
Among 397 participants median age 30 (interquartile range (IQR) 25-34; n = 198 without HIV, n = 199 PWH, the prevalence of GDM was 6% (9 PWH versus 3% without HIV). In multivariable analyses, PWH were at higher risk of GDM risk ratio (RR) 3.9, 95% confidence interval (CI) 1.4-10.7 after adjustment for prepregnancy BMI and other confounders. GDM risk did not differ by ART regimen (unadjusted prevalence 8.1% DTG versus 5.6% EFV, adjusted RR 1.1, 95% CI 0.2-6.6). Few participants had diabetes, impaired glucose tolerance (IGT), or impaired fasting glucose postpartum ( n = 13, 6%) with no differences by HIV or ART status.
In a setting of universal GDM testing, PWH had an increased risk of impaired glucose metabolism during pregnancy but not postpartum. Among PWH, GDM risk was similar regardless of EFV or DTG use. Given concerns about DTG and weight gain, diabetes risk should continue to be monitored.
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