A comparison of the associations between adiposity and lipids in Malawi and the United Kingdom.

BACKGROUND: The prevalence of excess adiposity, as measured by elevated body mass index (BMI) and waist-hip ratio (WHR), is increasing in sub-Saharan African (SSA) populations. This could add a considerable burden of cardiovascular and metabolic diseases for which these populations are currently ill-prepared. Evidence from white, European origin populations shows that higher adiposity leads to an adverse lipid profile; whether these associations are similar in all SSA populations requires further exploration. This study compared the association of BMI and WHR with lipid profile in urban Malawi with a contemporary cohort with contrasting socioeconomic, demographic, and ethnic characteristics in the United Kingdom (UK). METHODS: We used data from 1248 adolescents (mean 18.7 years) and 2277 Malawian adults (mean 49.8 years), all urban-dwelling, and from 3201 adolescents (mean 17.8 years) and 6323 adults (mean 49.7 years) resident in the UK. Adiposity measures and fasting lipids were assessed in both settings, and the associations of BMI and WHR with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were assessed by sex and age groups in both studies. RESULTS: Malawian female adults were more adipose and had more adverse lipid profiles than their UK counterparts. In contrast, Malawian adolescent and adult males were leaner and had more favourable lipid profiles than in the UK. Higher BMI and WHR were associated with increased TC, LDL-C and TG and reduced HDL-C in both settings. The magnitude of the associations of BMI and WHR with lipids was mostly similar or slightly weaker in the Malawian compared with the UK cohort in both adolescents and adults. One exception was the stronger association between increasing adiposity and elevated TC and LDL-C in Malawian compared to UK men. CONCLUSIONS: Malawian adult women have greater adiposity and more adverse lipid profiles compared with their UK counterparts. Similar associations of adiposity with adverse lipid profiles were observed for Malawian and UK adults in most age and sex groups studied. Sustained efforts are urgently needed to address the excess adiposity and adverse lipid profiles in Malawi to mitigate a future epidemic of cardio-metabolic disease among the poorest populations.

Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi.

BACKGROUND: The emerging burden of cardiovascular disease and diabetes in sub-Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed. RESULTS: Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors. CONCLUSIONS: It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males.

Mental Imagery to Reduce Alcohol-related harm in patients with alcohol use disorder and alcohol-related liver damaGE: the MIRAGE randomised pilot trial results.

OBJECTIVE: The healthcare burden of alcohol-related liver disease (ARLD) is increasing. ARLD and alcohol use disorder (AUD) is best managed by reduction or cessation of alcohol use, but effective treatments are lacking. We tested whether people with ARLD and AUD admitted to hospital could be recruited to and retained in a trial of Functional Imagery Training (FIT), a psychological therapy that uses mental imagery to reduce alcohol craving. We conducted a multicentre randomised pilot trial of treatment as usual (TAU) versus FIT+TAU in people admitted to hospital with ARLD and AUD. DESIGN: Participants were randomised to TAU (a single session of brief intervention) or FIT+TAU (TAU with one hospital-based FIT session then eight telephone sessions over 6 months). Pilot outcomes included recruitment rate and retention at day 180. Secondary outcomes included fidelity of FIT delivery, alcohol use, and severity of alcohol dependence. RESULTS: Fifty-four participants (mean age 49; 63% male) were recruited and randomised, 28 to TAU and 26 to FIT+TAU. The retention rate at day 180 was 43%. FIT was delivered adequately by most alcohol nurses. 50% of intervention participants completed FIT sessions 1 and 2. There were no differences in alcohol use or severity of alcohol dependence between treatment groups at day 180. CONCLUSION: Participants with ARLD and AUD could be recruited to a trial of FIT versus FIT+TAU. However, retention at day 180 was suboptimal. Before conducting a definitive trial of FIT in this patient group, modifications in the intervention and recruitment/retention strategy must be tested. TRIAL REGISTRATION NUMBER: ISRCTN41353774.

Iron supplementation in HIV-infected Malawian children with anemia: a double-blind, randomized, controlled trial.

BACKGROUND: It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV disease progression, and morbidity. METHODS: HIV-infected Malawian children aged 6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A, C, and D) or multivitamins alone for 3 months. Participants were followed for 6 months. RESULTS: A total of 209 children were randomly assigned to treatment, and 196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated with greater increases in hemoglobin concentrations (adjusted mean difference [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the risk of anemia persisting for up to 6 months follow-up (adjusted prevalence ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04), especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68 [95% CI, 1.08-6.63]; P = .03). CONCLUSIONS: Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin, anemia, and immunity but increases the risk of malaria. Thus, iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria. CLINICAL TRIALS REGISTRATION: ISRCTN-62947977.

Dietary Patterns and Practices and Leucocyte Telomere Length: Findings from the UK Biobank.

BACKGROUND: Shorter telomere length (TL) is associated with risk of several age-related diseases and decreased life span, but the extent to which dietary patterns and practices associate with TL is uncertain. OBJECTIVE: This study aimed to investigate the association of dietary patterns and practices and leucocyte TL (LTL). DESIGN: This was a cross-sectional study. PARTICIPANTS AND SETTING: Data collected voluntarily from up to 422,797 UK Biobank participants, during 2006-2010. MAIN OUTCOME MEASURES: LTL was measured as a ratio of the telomere repeat number to a single-copy gene and was loge-transformed and standardized (z-LTL). STATISTICAL ANALYSES PERFORMED: Adherence a priori to a Mediterranean-style diet was assessed through the MedDietScore. Principal component analysis was used to a posteriori extract the "Meat" and "Prudent" dietary patterns. Additional dietary practices considered were the self-reported adherence to "Vegetarian" diet, "Eating 5-a-day of fruit and vegetables" and "Abstaining from eggs/dairy/wheat/sugar." Associations between quintiles of dietary patterns or adherence to dietary practices with z-LTL were investigated through multivariable linear regression models (adjusted for demographic, lifestyle, and clinical characteristics). RESULTS: Adherence to the "Mediterranean" and the "Prudent" patterns, was positively associated with LTL, with an effect magnitude in z-LTL of 0.020 SD and 0.014 SD, respectively, for the highest vs the lowest quintile of adherence to the pattern (both P values < 0.05). Conversely, a reversed association between quintile of the "Meat" pattern and LTL was observed, with z-LTL being on average shorter by 0.025 SD (P = 6.12×10-05) for participants in the highest quintile of the pattern compared with the lowest quintile. For adherents to "5-a-day" z-LTL was on average longer by 0.027 SD (P = 5.36×10-09), and for "abstainers," LTL was shorter by 0.016 SD (P = 2.51×10-04). The association of LTL with a vegetarian diet was nonsignificant after adjustment for demographic, lifestyle, and clinical characteristics. CONCLUSIONS: Several dietary patterns and practices associated with beneficial health effects are significantly associated with longer LTL. However, the magnitude of the association was small, and any clinical relevance is uncertain.

The effectiveness of interventions that support penicillin allergy assessment and delabeling of adult and pediatric patients by nonallergy specialists: a systematic review and meta-analysis.

OBJECTIVES: Penicillin allergy records are often incorrect and may result in harm. We aimed to systematically review the effectiveness and safety of nonallergist health care worker delivery of penicillin allergy delabeling. METHODS: We searched EMBASE/MEDLINE/CINAHL (Ovid), PsycInfo, Web of Science, and Cochrane CENTRAL from inception to January 21, 2022 and unpublished studies and gray literature. The proportion of patients allergic to penicillin delabeled and harmed was calculated using random-effects models. RESULTS: Overall, 5019 patients were delabeled. Using allergy history alone, 14% (95% confidence interval [CI], 9-21%) of 4350 assessed patients were delabeled without reported harm. Direct drug provocation testing resulted in delabeling in 27% (95% CI, 18-37%) of 4207 assessed patients. Of the 1373 patients tested, 98% were delabeled (95% CI, 97-99%), and nonserious harm was reported in 1% (95% CI, 0-2%). Using skin testing, followed by drug provocation testing, 41% (95% CI, 24-59%) of 2890 assessed patients were delabeled. Of the 1294 tested patients, 95.0% (95% CI, 90-99%) were delabeled, and the reported harm was low (0%; (95% CI 0-1%). CONCLUSION: Penicillin allergy delabeling by nonallergists is efficacious and safe. The proportion of assessed patients who can be delabeled increases with the complexity of testing method, but substantial numbers can be delabeled without skin testing.

Practitioners' ability to remotely develop understanding for personalised care and support planning: a thematic analysis of multiple data sources from the feasibility phase of the Dementia Personalised Care Team (D-PACT) intervention.

Practitioner understanding of patients' preferences, wishes and needs is essential for personalised health care i.e., focusing on 'what matters' to people based on their individual life situation. To develop such an understanding, dementia practitioners need to use communication practices that help people share their experiences, preferences, and priorities. Following the COVID-19 pandemic, dementia support is likely to continue to be delivered both remotely and in-person. This study analysed multiple sources of qualitative data to examine the views of practitioners, people living with dementia and carers, and researchers on how an understanding of what matters to people living with dementia can be developed remotely via telephone and video call. Access to environmental stimuli, the remote use of visual tools, peoples' tendency to downplay or omit details about their troubles and carers' ability to disclose privately were interpreted, through thematic analysis, to be factors affecting how practitioners sought to develop understanding remotely. Cumulatively, findings show that while remote support created unique challenges to practitioners' ability to develop understanding for personalised care, practitioners developed adaptive strategies to overcome some of these challenges. Further research should examine how, when and for whom these adapted practices for remote personalised care work, informing the development of evidence-based guidance and training on how practitioners can remotely develop the understanding required for personalised care.

Longitudinal realist evaluation of the Dementia PersonAlised Care Team (D-PACT) intervention: protocol.

BACKGROUND: Different dementia support roles exist but evidence is lacking on which aspects are best, for whom, and in what circumstances, and on their associated costs and benefits. Phase 1 of the Dementia PersonAlised Care Team programme (D-PACT) developed a post-diagnostic primary care-based intervention for people with dementia and their carers and assessed the feasibility of a trial. AIM: Phase 2 of the programme aims to 1) refine the programme theory on how, when, and for whom the intervention works; and 2) evaluate its value and impact. DESIGN & SETTING: A realist longitudinal mixed-methods evaluation will be conducted in urban, rural, and coastal areas across South West and North West England where low-income or ethnic minority populations (for example, South Asian) are represented. Design was informed by patient, public, and professional stakeholder input and phase 1 findings. METHOD: High-volume qualitative and quantitative data will be collected longitudinally from people with dementia, carers, and practitioners. Analyses will comprise the following: 1) realist longitudinal case studies; 2) conversation analysis of recorded interactions; 3) statistical analyses of outcome and experience questionnaires; 4a) health economic analysis examining costs of delivery; and 4b) realist economic analysis of high-cost events and 'near misses'. All findings will be synthesised using a joint display table, evidence appraisal tool, triangulation, and stakeholder co-analysis. CONCLUSION: The realist evaluation will describe how, why, and for whom the intervention does or does not lead to change over time. It will also demonstrate how a non-randomised design can be more appropriate for complex interventions with similar questions or populations.

Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length.

Walking pace is a simple and functional form of movement and a strong predictor of health status, but the nature of its association with leucocyte telomere length (LTL) is unclear. Here we investigate whether walking pace is associated with LTL, which is causally associated with several chronic diseases and has been proposed as a marker of biological age. Analyses were conducted in 405,981 UK Biobank participants. We show that steady/average and brisk walkers had significantly longer LTL compared with slow walkers, with accelerometer-assessed measures of physical activity further supporting this through an association between LTL and habitual activity intensity, but not with total amount of activity. Bi-directional mendelian randomisation analyses suggest a causal link between walking pace and LTL, but not the other way around. A faster walking pace may be causally associated with longer LTL, which could help explain some of the beneficial effects of brisk walking on health status. Given its simple measurement and low heritability, self-reported walking pace may be a pragmatic target for interventions.

Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank.

Background: Telomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences. Methods: In this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait ß coefficients with the age ß coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL. Findings: 422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10-4) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL. Interpretation: Although several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit. Funding: UK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.

Association of shorter leucocyte telomere length with risk of frailty.

BACKGROUND: Frailty is a multidimensional syndrome of decline that affects multiple systems and predisposes to adverse health outcomes. Although chronological age is the major risk factor, inter-individual variation in risk is not fully understood. Leucocyte telomere length (LTL), a proposed marker of biological age, has been associated with risk of many diseases. We sought to determine whether LTL is associated with risk of frailty. METHODS: We utilized cross-sectional data from 441 781 UK Biobank participants (aged 40-69 years), with complete data on frailty indicators and LTL. Frailty was defined as the presence of at least three of five indicators: weaker grip strength, slower walking pace, weight loss in the past year, lower physical activity, and exhaustion in the past 2 weeks. LTL was measured using a validated qPCR method and reported as a ratio of the telomere repeat number (T) to a single-copy gene (S) (T/S ratio). Association of LTL with frailty was evaluated using adjusted (chronological age, sex, deprivation, smoking, alcohol intake, body mass index, and multimorbidity) multinomial and ordinal regression models, and results are presented as relative risk (RRR) or odds ratios (OR), respectively, alongside the 95% confidence interval (CI). Mendelian randomization (MR), using 131 genetic variants associated with LTL, was used to assess if the association of LTL with frailty was causal. RESULTS: Frail participants (4.6%) were older (median age difference (95% CI): 3 (2.5; 3.5) years, P = 2.73 × 10-33 ), more likely to be female (61%, P = 1.97 × 10-129 ), and had shorter LTL (-0.13SD vs. 0.03SD, P = 5.43 × 10-111 ) than non-frail. In adjusted analyses, both age and LTL were associated with frailty (RRR = 1.03 (95% CI: 1.02; 1.04) per year of older chronological age, P = 3.99 × 10-12 ; 1.10 (1.08; 1.11) per SD shorter LTL, P = 1.46 × 10-30 ). Within each age group (40-49, 50-59, 60-69 years), the prevalence of frailty was about 33% higher in participants with shorter (-2SD) versus longer telomeres (+2SD). MR analysis showed an association of LTL with frailty that was directionally consistent with the observational association, but not statistically significant (MR-Median: OR (95% CI): 1.08 (0.98; 1.19) per SD shorter LTL, P = 0.13). CONCLUSIONS: Inter-individual variation in LTL is associated with the risk of frailty independently of chronological age and other risk factors. Our findings provide evidence for an additional biological determinant of frailty.

Shorter leukocyte telomere length is associated with adverse COVID-19 outcomes: A cohort study in UK Biobank.

Background Older age is the most powerful risk factor for adverse coronavirus disease-19 (COVID-19) outcomes. It is uncertain whether leucocyte telomere length (LTL), previously proposed as a marker of biological age, is also associated with COVID-19 outcomes. Methods We associated LTL values obtained from participants recruited into UK Biobank (UKB) during 2006-2010 with adverse COVID-19 outcomes recorded by 30 November 2020, defined as a composite of any of the following: hospital admission, need for critical care, respiratory support, or mortality. Using information on 130 LTL-associated genetic variants, we conducted exploratory Mendelian randomisation (MR) analyses in UKB to evaluate whether observational associations might reflect cause-and-effect relationships. Findings Of 6775 participants in UKB who tested positive for infection with SARS-CoV-2 in the community, there were 914 (13.5%) with adverse COVID-19 outcomes. The odds ratio (OR) for adverse COVID-19 outcomes was 1·17 (95% CI 1·05-1·30; P = 0·004) per 1-SD shorter usual LTL, after adjustment for age, sex and ethnicity. Similar ORs were observed in analyses that: adjusted for additional risk factors; disaggregated the composite outcome and reduced the scope for selection or collider bias. In MR analyses, the OR for adverse COVID-19 outcomes was directionally concordant but non-significant. Interpretation Shorter LTL is associated with higher risk of adverse COVID-19 outcomes, independent of several major risk factors for COVID-19 including age. Further data are needed to determine whether this association reflects causality. Funding UK Medical Research Council, Biotechnology and Biological Sciences Research Council and British Heart Foundation.

Polygenic basis and biomedical consequences of telomere length variation.

Telomeres, the end fragments of chromosomes, play key roles in cellular proliferation and senescence. Here we characterize the genetic architecture of naturally occurring variation in leukocyte telomere length (LTL) and identify causal links between LTL and biomedical phenotypes in 472,174 well-characterized UK Biobank participants. We identified 197 independent sentinel variants associated with LTL at 138 genomic loci (108 new). Genetically determined differences in LTL were associated with multiple biological traits, ranging from height to bone marrow function, as well as several diseases spanning neoplastic, vascular and inflammatory pathologies. Finally, we estimated that, at the age of 40 years, people with an LTL >1 s.d. shorter than the population mean had a 2.5-year-lower life expectancy compared with the group with ≥1 s.d. longer LDL. Overall, we furnish new insights into the genetic regulation of LTL, reveal wide-ranging influences of LTL on physiological traits, diseases and longevity, and provide a powerful resource available to the global research community.

Investigating associations between rural-to-urban migration and cardiometabolic disease in Malawi: a population-level study.

BACKGROUND: The extent to which rural-to-urban migration affects risk for cardiometabolic diseases (CMD) in Africa is not well understood. We investigated prevalence and risk for obesity, diabetes, hypertension and precursor conditions by migration status. METHODS: In a cross-sectional survey in Malawi (February 2013-March 2017), 13 903 rural, 9929 rural-to-urban migrant and 6741 urban residents (≥18 years old) participated. We interviewed participants, measured blood pressure and collected anthropometric data and fasting blood samples to estimate population prevalences and odds ratios, using negative binomial regression, for CMD, by migration status. In a sub-cohort of 131 rural-urban siblings-sets, migration-associated CMD risk was explored using conditional Poisson regression. RESULTS: In rural, rural-to-urban migrant and urban residents, prevalence estimates were; 8.9, 20.9 and 15.2% in men and 25.4, 43.9 and 39.3% in women for overweight/obesity; 1.4, 2.9 and 1.9% in men and 1.5, 2.8 and 1.7% in women for diabetes; and 13.4, 18.8 and 12.2% in men and 13.7, 15.8 and 10.2% in women for hypertension. Rural-to-urban migrants had the greatest risk for hypertension (adjusted relative risk for men 1.18; 95% confidence interval 1.04-1.34 and women 1.17: 95% confidence interval 1.05-1.29) and were the most screened, diagnosed and treated for CMD, compared with urban residents. Within sibling sets, rural-to-urban migrant siblings had a higher risk for overweight and pre-hypertension, with no evidence for differences by duration of stay. CONCLUSIONS: Rural-to-urban migration is associated with increased CMD risk in Malawi. In a poor country experiencing rapid urbanization, interventions for the prevention and management of CMD, which reach migrant populations, are needed.

Sex and area differences in the association between adiposity and lipid profile in Malawi.

BACKGROUND: Evidence from high-income countries shows that higher adiposity results in an adverse lipid profile, but it is unclear whether this association is similar in Sub-Saharan African (SSA) populations. This study aimed to assess the association between total and central adiposity measures and lipid profile in Malawi, exploring differences by sex and area of residence (rural/urban). METHODS: In this cross-sectional study, data from 12 096 rural and 12 847 urban Malawian residents were used. The associations of body mass index (BMI) and waist to hip ratio (WHR) with fasting lipids (total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG)) were assessed by area and sex. RESULTS: After adjusting for potential confounders, higher BMI and WHR were linearly associated with increased TC, LDL-C and TG and reduced HDL-C. BMI was more strongly related to fasting lipids than was WHR. The associations of adiposity with adverse lipid profile were stronger in rural compared with urban residents. For instance, one SD increase in BMI was associated with 0.23 mmol/L (95% CI 0.19 to 0.26) increase in TC in rural women and 0.13 mmol/L (95% CI 0.11 to 0.15) in urban women. Sex differences in the associations between adiposity and lipids were less evident. CONCLUSIONS: The consistent associations observed of higher adiposity with adverse lipid profiles in men and women living in rural and urban areas of Malawi highlight the emerging adverse cardio-metabolic epidemic in this poor population. Our findings underline the potential utility of BMI in estimating cardiovascular risk and highlight the need for greater investment to understand the long-term health outcomes of obesity and adverse lipid profiles and the extent to which lifestyle changes and treatments effectively prevent and modify adverse cardio-metabolic outcomes.

How does the association of general and central adiposity with glycaemia and blood pressure differ by gender and area of residence in a Malawian population: a cross-sectional study.

BACKGROUND: In high-income settings, body mass index (BMI) and measures of central adiposity, such as waist-to-hip ratio (WHR) are associated with cardiometabolic risk, but evidence from low-income settings, particularly sub-Saharan Africa (SSA), is limited. We assessed whether there are differences between central and general adiposity in their associations with fasting glucose, diabetes, systolic and diastolic blood pressures and hypertension, and whether these associations differ with gender or rural/urban setting in Malawi. METHODS: We used data from a population-based study of 27 880 Malawian adults aged ≥18 years, from both rural and urban areas. We used age-standardized z-scores of the means of BMI and WHR to directly compare their associations with glycaemic and blood pressure outcomes. RESULTS: Mean fasting glucose and blood pressure values and odds of hypertension increased linearly across fifths of BMI and WHR, with stronger associations with BMI. For both BMI and WHR, the associations with outcomes were stronger in urban versus rural residents. The association with diabetes was stronger in women than men, whereas for blood-pressure related outcomes a stronger association was seen in men. CONCLUSIONS: BMI is more strongly associated with cardiometabolic risk in SSA, and might be a more useful measure than WHR, in this population. The greater positive association of adiposity with cardiometabolic outcomes in urban residents (where rates of overweight/obesity are already high) highlights the particular importance of addressing obesity within urban SSA populations.

Glycated haemoglobin A1c (HbA1c) for detection of diabetes mellitus and impaired fasting glucose in Malawi: a diagnostic accuracy study.

OBJECTIVES: To examine the accuracy of glycated haemoglobin A1c (HbA1c) in detecting type 2 diabetes and impaired fasting glucose among adults living in Malawi. DESIGN: A diagnostic validation study of HbA1c. Fasting plasma glucose (FPG) ≥7.0 mmol/L was the reference standard for type 2 diabetes, and FPG between 6.1 and 6.9 mmol/L as impaired fasting glucose. PARTICIPANTS: 3645 adults (of whom 63% were women) recruited from two demographic surveillance study sites in urban and rural Malawi. This analysis excluded those who had a previous diagnosis of diabetes or had history of taking diabetes medication. RESULTS: HbA1c demonstrated excellent validity to detect FPG-defined diabetes, with an area under the receiver operating characteristic (AUROC) curve of 0.92 (95% CI 0.90 to 0.94). At HbA1c ≥6.5% (140 mg/dL), sensitivity was 78.7% and specificity was 94.0%. Subgroup AUROCs ranged from 0.86 for participants with anaemia to 0.94 for participants in urban Malawi. There were clinical and metabolic differences between participants with true diabetes versus false positives when HbA1c was ≥6.5% (140 mg/dL). CONCLUSIONS: The findings from this study provide justification to use HbA1c to detect type 2 diabetes. As HbA1c testing is substantially less burdensome to patients than either FPG testing or oral glucose tolerance testing, it represents a useful option for expanding access to diabetes care in sub-Saharan Africa.

Prevalence of obesity, hypertension, and diabetes, and cascade of care in sub-Saharan Africa: a cross-sectional, population-based study in rural and urban Malawi.

BACKGROUND: Sub-Saharan Africa is in rapid demographic transition, and non-communicable diseases are increasingly important causes of morbidity and mortality. We investigated the burden of diabetes, overweight and obesity, hypertension, and multimorbidity, their treatment, and their associations with lifestyle and other factors in Malawi, a very poor country with a predominantly rural-but rapidly growing urban-population, to identify high-risk populations and inform appropriate interventions. METHODS: In this cross-sectional, population-based study, we enrolled all adults (≥18 years) residing in two defined geographical areas within Karonga District and Lilongwe city. All adults self-defining as usually resident in the study areas were eligible, and recruited at household level. Participants were interviewed, had anthropometry and blood pressure measured, and had fasting blood samples collected. The study outcomes were prevalence estimates and risk ratios for diabetes (defined as fasting blood glucose of at least 7·0 mmol/L or self-report of a previous diagnosis of diabetes), hypertension (systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or self-report of current antihypertensive medication), overweight (BMI of 25·0-29·9 kg/m2) and obesity (BMI of 30·0 kg/m2 or more), and multimorbidity (two or more of the above conditions) by location-specific (urban vs rural), age-specific, and sex-specific groups, calculated using negative binomial regression. We used χ2 likelihood ratio tests to assess heterogeneity by age, location, and sex. FINDINGS: Between May 16, 2013, and Feb 8, 2016, we enrolled 15 013 (62%) of 24 367 eligible urban adults in Lilongwe and 13 878 (88%) of 15 806 eligible rural adults in Karonga District. Overweight and obesity, hypertension, and diabetes were highly prevalent, more so in urban residents, the less poor, and better educated than in rural, the poorest, and least educated participants. 18% of urban men (961 of 5211 participants) and 44% (4115 of 9282) of urban women, and 9% (521 of 5834) of rural men and 27% (2038 of 7497) of rural women were overweight or obese; 16% (859 of 5212), 14% (1349 of 9793), 13% (787 of 5847), and 14% (1101 of 8025) had hypertension; and 3% (133 of 3928), 3% (225 of 7867), 2% (84 of 5004), and 2% (124 of 7116) had diabetes, respectively. Of 566 participants with diabetes, 233 (41%) were undiagnosed, and of 4096 participants with hypertension, 2388 (58%) were undiagnosed. Fewer than half the participants on medication for diabetes or hypertension had well controlled diabetes (84 [41%] of 207 participants) or blood pressure (440 [37%] of 1183 participants). Multimorbidity was highest in urban women (n=519, 7%). INTERPRETATION: Overweight and obesity, hypertension, and diabetes are highly prevalent in urban and rural Malawi, yet many patients are undiagnosed and management is limited. Local-evidence-informed multisectoral, innovative, and targeted interventions are needed urgently to manage the already high burden. FUNDING: Wellcome Trust.

Accessing clinical services and retention in care following screening for hypertension and diabetes among Malawian adults: an urban/rural comparison.

OBJECTIVE: Interventions to impact on the burden of chronic noncommunicable diseases, such as hypertension and diabetes, include screening of asymptomatic adults, but little is known about the subsequent course of clinical care. We report on the uptake of referral for clinical assessment and retention in care, following a large urban/rural population screening program in Malawi. METHODS: Adult residents were screened for raised blood pressure and raised fasting blood glucose at a demographic surveillance site in rural Karonga District and in urban Area 25, Lilongwe with well supported chronic care clinics. Successful uptake was defined as presenting for clinical assessment within 6 weeks of referral, and nonattenders were followed at home. Logistic regression was used to examine association of uptake with demographic and clinical factors. Retention was assessed using survival analysis techniques. RESULTS: A total of 27 305 participants were screened for hypertension and diabetes between May 2013 and September 2015. Of these, 4075 (14.9%) were referred for suspected hypertension (3640), diabetes (172), or both (263). Among those referred, 2480 (60.9%), reported for clinical assessment. Factors associated with uptake of care included being female, rural residency, older age, unemployment, prior medication, and diabetes. Retention, for those enrolled in care following a formal clinical assessment, was associated with the final diagnosis following clinical assessment, rural residency, and older age. CONCLUSION: Screening for hypertension and diabetes identifies large numbers of individuals who need further clinical assessment, but strategies are needed to ensure better linkage and retention into care.