A global perspective on the issue of access to insulin.

The discovery of insulin in 1921 changed the prognosis for people with type 1 diabetes. A century later, availability and affordability of insulin remain a challenge in many parts of the globe. Using the WHO's framework on understanding the life cycle of medicines, this review details the global and national challenges that affect patients' abilities to access and afford insulin. Current research and development in diabetes has seen some innovations, but none of these have truly been game-changing. Currently, three multinational companies control over 95% of global insulin supply. The inclusion of insulin on the WHO's Prequalification Programme is an opportunity to facilitate entry of new companies into the market. Many governments lack policies on the selection, procurement, supply, pricing and reimbursement of insulin. Moreover, mark-ups in the supply chain also affect the final price to the consumer. Whilst expenses related to diabetes are mostly covered by insurance in high-income countries, many patients from low- and middle-income countries have to pay out of their own pockets. The organisation of diabetes management within the healthcare system also affects patient access to insulin. The challenges affecting access to insulin are complex and require a wide range of solutions. Given that 2021 marks the centenary of the discovery of insulin, there is need for global advocacy to ensure that the benefits of insulin and innovations in diabetes care reach all individuals living with diabetes

Implications of COVID-19 control measures for diet and physical activity, and lessons for addressing other pandemics facing rapidly urbanising countries.

At the time of writing, it is unclear how the COVID-19 pandemic will play out in rapidly urbanising regions of the world. In these regions, the realities of large overcrowded informal settlements, a high burden of infectious and non-communicable diseases, as well as malnutrition and precarity of livelihoods, have raised added concerns about the potential impact of the COVID-19 pandemic in these contexts. COVID-19 infection control measures have been shown to have some effects in slowing down the progress of the pandemic, effectively buying time to prepare the healthcare system. However, there has been less of a focus on the indirect impacts of these measures on health behaviours and the consequent health risks, particularly in the most vulnerable. In this current debate piece, focusing on two of the four risk factors that contribute to >80% of the NCD burden, we consider the possible ways that the restrictions put in place to control the pandemic, have the potential to impact on dietary and physical activity behaviours and their determinants. By considering mitigation responses implemented by governments in several LMIC cities, we identify key lessons that highlight the potential of economic, political, food and built environment sectors, mobilised during the pandemic, to retain health as a priority beyond the context of pandemic response. Such whole-of society approaches are feasible and necessary to support equitable healthy eating and active living required to address other epidemics and to lower the baseline need for healthcare in the long term

The global diet and activity research (GDAR) network: a global public health partnership to address upstream NCD risk factors in urban low and middle-income contexts

Abstract: Background: Non-communicable diseases (NCDs) are the leading cause of death globally. While upstream approaches to tackle NCD risk factors of poor quality diets and physical inactivity have been trialled in high income countries (HICs), there is little evidence from low and middle-income countries (LMICs) that bear a disproportionate NCD burden. Sub-Saharan Africa and the Caribbean are therefore the focus regions for a novel global health partnership to address upstream determinants of NCDs. Partnership: The Global Diet and Activity research Network (GDAR Network) was formed in July 2017 with funding from the UK National Institute for Health Research (NIHR) Global Health Research Units and Groups Programme. We describe the GDAR Network as a case example and a potential model for research generation and capacity strengthening for others committed to addressing the upstream determinants of NCDs in LMICs. We highlight the dual equity targets of research generation and capacity strengthening in the description of the four work packages. The work packages focus on learning from the past through identifying evidence and policy gaps and priorities, understanding the present through adolescent lived experiences of healthy eating and physical activity, and co-designing future interventions with non-academic stakeholders. Conclusion: We present five lessons learned to date from the GDAR Network activities that can benefit other global health research partnerships. We close with a summary of the GDAR Network contribution to cultivating sustainable capacity strengthening and cutting-edge policy-relevant research as a beacon to exemplify the need for such collaborative groups

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Epidemiological studies of the aetiological associations between nutritional biomarkers and cardiometabolic risk factors in Cameroon

Suboptimal diets are among the leading factors fuelling the global rise in the prevalence of type 2 diabetes and other metabolic disorders. Most epidemiological studies of the associations between diet and nutritional factors and metabolic outcomes have relied on self-report instruments. Nutritional biomarkers offer a complementary objective approach but have not been widely applied in African settings to test associations between diet and metabolic outcomes. This thesis aimed to examine the relationship between diet and nutritional factors assessed using a wide range of objectively measured nutritional biomarkers and metabolic outcomes in a population-based study in adults in rural and urban Cameroon (n= 651). I spent the first part of my PhD in the laboratory measuring circulating vitamin D, folate, holotranscobalamin, carotenoids and tocopherol using mass spectrometry techniques. Subsequently, I undertook analyses to describe the patterns and identify factors affecting these nutritional biomarkers reflecting dietary intakes and plasma zinc, which was measured in an external laboratory. Most of the biomarkers showed distinct patterns by age, sex, level of education, physical activity levels and rural/urban area of residence. I then investigated the independent cross-sectional associations of these biomarkers with metabolic risk factors exploring the possibility of both linear and non-linear associations and adjusting for a wide range of potential confounders. Circulating folate and carotenoids, which are associated with intake of fruits and vegetables, showed an inverse association with the metabolic syndrome score and fasting glucose respectively. Holotranscobalamin, a biomarker that reflects intake of animal-sourced foods, was positively associated with the metabolic syndrome score. Circulating zinc, reflecting intake of protein-rich foods, was inversely associated with several markers of glucose homeostasis (fasting and 2-h glucose and homeostatic model assessment for insulin resistance). Higher 25-hydroxy-vitamin D, a marker of vitamin D status, was associated with lower fasting glucose. Finally, I investigated the potential effect modification by rural/urban area of residence, sex and body mass index on the association between the biomarker and metabolic outcomes. Overall this PhD showed 1) Rural and urban differences in the distribution of the nutritional biomarkers in Cameroon 2) Significant associations of the studied biomarkers reflecting dietary intakes with metabolic risk factors. Findings from my PhD advance the understanding of the role of diet and nutritional factors on metabolic health in adults in Cameroon. Diet is modifiable, making it a realistic target for public health intervention to improve metabolic health in this population

Associations of Serum Folate and Holotranscobalamin With Cardiometabolic Risk Factors in Rural and Urban Cameroon

A low intake of fruit and vegetables and a high intake of meat are associated with higher cardiometabolic disease risk; however much prior research has relied on subjective methods for dietary assessment and focused on Western populations. We aimed to investigate the association of blood folate as an objective marker of fruit and vegetable intake and holotranscobalamin (holoTC) as a marker of animal-sourced food intake with cardiometabolic risk factors. We conducted a population-based cross-sectional study on 578 adults (mean ± SD age = 38.2 ± 8.6 years; 64% women). The primary outcome was a continuous metabolic syndrome score. The median serum folate was 12.9 (IQR: 8.6–20.5) nmol/L and the mean holoTC was 75 (SD: 34.3) pmol/L. Rural residents demonstrated higher serum folate concentrations (15.9 (9.8–25.9) nmol/L) than urban residents (11.3 (7.9–15.8) nmol/L), but lower holoTC concentrations (rural: 69.8 (32.9) pmol/L; urban: 79.8 (34.9)) pmol/L, p < 0.001 for both comparisons. There was an inverse association between serum folate and metabolic syndrome score by −0.20 in the z-score (95% CI, −0.38 to −0.02) per 10.8 (1 SD) of folate) in a model adjusted for socio-demographic factors, smoking status, alcohol intake, BMI, and physical activity. HoloTC was positively associated with the metabolic syndrome score in unadjusted analysis (0.33 (95% CI, 0.10 to 0.56)) but became non-significant (0.17 (−0.05 to 0.39)) after adjusting for socio-demographic and behavioural characteristics. In conclusion, serum folate and holoTC were associated with the metabolic syndrome score in opposite directions. The positive association between serum holoTC and the metabolic syndrome score was partly dependent on sociodemographic characteristics. These findings suggest that, based on these biomarkers reflecting dietary intakes, public health approaches promoting a higher intake of fruit and vegetables may lower cardiometabolic risk factors in this population

Associations of Serum Folate and Holotranscobalamin With Cardiometabolic Risk Factors in Rural and Urban Cameroon

OBJECTIVES: Previous studies mostly in Western populations suggest that a low exposure to B-vitamins (folate and vitamin B12 in particular) are associated with increased cardiometabolic disease risk. This study aimed to examine the association of blood concentrations of folate and holotranscobalamin (holoTC) with cardiometabolic risk factors in adults in Cameroon. METHODS: We conducted a cross-sectional population-based study in 497 adults. We measured serum folate and holoTC by liquid chromatography tandem mass spectrometry and “sandwich” ELISA respectively. Total folate was calculated excluding the oxidation product 5-methyltetrahydrofolate. The outcomes were individual cardiometabolic risk factors and a continuous metabolic risk score. We fitted linear regression models to examine the association between B-vitamins and cardiometabolic risk factors and estimated β-coefficients and 95% confidence intervals per standard deviation (SD) difference in each B vitamin variable. RESULTS: Mean age was 38.2 (SD: 8.6) years and 63.5% of the participants were women. Mean serum folate was 15.9 (SD: 10.8) nmol/L and holoTC was 74.1 (SD: 33.7) pmol/L. Rural residents had higher concentrations of serum folate but lower holoTC than urban residents. There was a significant inverse association between serum folate and the metabolic risk score (−0.22 (−0.41 to −0.03)) in a multivariable model adjusted for age, sex, education level, smoking, alcohol intake, rural/urban site and BMI. This association was attenuated to the null after further adjustments for objectively measured physical activity (PAEE) and holoTC. HoloTC was positively associated with the metabolic risk score in unadjusted analysis (0.29 (0.08 to 0.51)) but attenuated to the null after adjusting for socio-demographic characteristics. For individual risk factors, an inverse association was observed between serum folate and diastolic blood pressure, which was unaffected by adjustment for confounders including PAEE and holoTC (−1.18 (−2.16 to − 0.20)). CONCLUSIONS: In Cameroon, serum folate and holoTC were associated with the metabolic risk score in opposite directions, partly depending on potential demographic and socioeconomic characteristics. The inverse association between serum folate and the metabolic risk score was likely driven by the blood pressure component. FUNDING SOURCES: None

Associations of Serum Folate and Holotranscobalamin with Cardiometabolic Risk Factors in Rural and Urban Cameroon

A low intake of fruit and vegetables and a high intake of meat are associated with higher cardiometabolic disease risk; however much prior research has relied on subjective methods for dietary assessment and focused on Western populations. We aimed to investigate the association of blood folate as an objective marker of fruit and vegetable intake and holotranscobalamin (holoTC) as a marker of animal-sourced food intake with cardiometabolic risk factors. We conducted a population-based cross-sectional study on 578 adults (mean &plusmn; SD age = 38.2 &plusmn; 8.6 years; 64% women). The primary outcome was a continuous metabolic syndrome score. The median serum folate was 12.9 (IQR: 8.6&ndash;20.5) nmol/L and the mean holoTC was 75 (SD: 34.3) pmol/L. Rural residents demonstrated higher serum folate concentrations (15.9 (9.8&ndash;25.9) nmol/L) than urban residents (11.3 (7.9&ndash;15.8) nmol/L), but lower holoTC concentrations (rural: 69.8 (32.9) pmol/L; urban: 79.8 (34.9)) pmol/L, p &lt; 0.001 for both comparisons. There was an inverse association between serum folate and metabolic syndrome score by &minus;0.20 in the z-score (95% CI, &minus;0.38 to &minus;0.02) per 10.8 (1 SD) of folate) in a model adjusted for socio-demographic factors, smoking status, alcohol intake, BMI, and physical activity. HoloTC was positively associated with the metabolic syndrome score in unadjusted analysis (0.33 (95% CI, 0.10 to 0.56)) but became non-significant (0.17 (&minus;0.05 to 0.39)) after adjusting for socio-demographic and behavioural characteristics. In conclusion, serum folate and holoTC were associated with the metabolic syndrome score in opposite directions. The positive association between serum holoTC and the metabolic syndrome score was partly dependent on sociodemographic characteristics. These findings suggest that, based on these biomarkers reflecting dietary intakes, public health approaches promoting a higher intake of fruit and vegetables may lower cardiometabolic risk factors in this population

The association between plasma zinc concentrations and markers of glucose metabolism in adults in Cameroon.

An abnormal Zn status has been suggested to play a role in the pathogenesis of type 2 diabetes. However, epidemiological studies of the relationship between plasma Zn concentrations and diabetes are sparse and inconclusive. We aimed to investigate the association between plasma Zn concentrations and glycaemic markers (fasting glucose, 2-h glucose and homeostatic model assessment of insulin resistance) in rural and urban Cameroon. We studied 596 healthy adults (63·3 % women) aged 25-55 years in a population-based cross-sectional study. The mean plasma Zn concentration was 13·7 ± 2·7 µmol/L overall, with higher levels in men (14·4 ± 2·9 µmol/l) than in women (13·2 ± 2·6 µmol/l), P-value < 0·0001. There was an inverse relationship between tertiles of plasma Zn and 2-h glucose concentrations (P-value for linear trend = 0·002). The difference in 2-h glucose between those in the highest tertile of plasma Zn compared to the lowest was -0·63 (95 % CI - 1·02, -0·23) mmol/l. This remained significant after adjusting for age, sex, smoking status, alcohol intake, education level, area of residence, adiposity and objectively measured physical activity -0·43(-0·82, -0·04). Similar inverse associations were observed between plasma Zn concentrations and fasting glucose and homeostatic model assessment of insulin resistance when adjusted for socio-demographic and health-related behavioural characteristics. The current findings of an inverse association between plasma Zn concentrations and several markers of glucose homeostasis, together with growing evidence from intervention studies, suggest a role for Zn in glucose metabolism. If supported by further evidence, strategies to improve Zn status in populations may provide a cheap public health prevention approach for diabetes

Association between circulating 25-hydroxyvitamin D and cardiometabolic risk factors in adults in rural and urban settings

Background: An inverse association between vitamin D status and cardiometabolic risk has been reported but this relationship may have been affected by residual confounding from adiposity and physical activity due to imprecise measures of these variables. We aimed to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk factors, with adjustment for objectively-measured physical activity and adiposity. Methods: This was a population-based cross-sectional study in 586 adults in Cameroon (63.5% women). We assessed markers of glucose homeostasis (fasting blood glucose (BG), 2-h post glucose load BG, HOMA-IR)) and computed a metabolic syndrome score by summing the sex‐specific z‐scores of five risk components measuring central adiposity, blood pressure, glucose HDL cholesterol and triglycerides. Results: Mean±SD age was 38.3±8.6 years, and serum 25(OH)D was 51.7±12.5 nmol/L. Mean 25(OH)D was higher in rural (53.4±12.8 nmol/L) than urban residents (50.2±12.1 nmol/L), p=0.002. The prevalence of vitamin D insufficiency (< 50 nmol/L) was 45.7%. There was an inverse association between 25(OH)D and the metabolic syndrome score in unadjusted analyses (β= -0.30, 95% CI -0.55 to -0.05), which became non-significant after adjusting for age, sex, smoking status, alcohol intake and education level. Serum 25(OH)D was inversely associated with fasting BG (-0.21, -0.34 to -0.08)), which remained significant after adjustment for age, sex, education, smoking, alcohol intake, season of data collection, BMI and physical activity (-0.17, -0.29 to -0.06). There was an inverse association of 25(OH)D with 2-h BG (-0.20, -0.34 to -0.05) and HOMA-IR (-0.12, -0.19 to -0.04) in unadjusted analysis, but these associations became non-significant after adjustment for potential confounders. Conclusion: Vitamin D insufficiency was common in this population. This study showed an inverse association between vitamin D status and fasting glucose that was independent of potential confounders including objectively measured physical activity and adiposity suggesting a possible mechanism through insulin secretion.CMM receives funding from the Cambridge Trust International-Islamic Development Bank Scholarship. NJW, NGF and FI acknowledge funding from the Medical Research Council Epidemiology Unit MC_UU_00006/1 and MC_UU_00006/3; NJW, NGF and AK from NIHR Cambridge Biomedical Research Centre: nutrition, diet, and lifestyle research theme (IS-BRC-1215-20014). NGF is an NIHR Senior Investigator