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Treating hyperglycaemia and obesity in individuals with type 2 diabetes using multi-receptor agonists can improve short-term and long-term outcomes. LY3437943 is a single peptide with agonist activity for glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptors that is currently in development for the treatment of type 2 diabetes and for the treatment of obesity and associated comorbidities. We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.In this phase 1b, proof-of-concept, double-blind, placebo-controlled, randomised, multiple-ascending dose trial, adults (aged 20-70 years) with type 2 diabetes for at least 3 months, a glycated haemoglobin ABetween Dec 18, 2019, and Dec 28, 2020, 210 people were screened, of whom 72 were enrolled, received at least one dose of study drug, and were included in safety analyses. 15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg. 29 participants discontinued the study prematurely. Treatment-emergent adverse events were reported by 33 (63%), three (60%), and eight (54%) participants who received LY3437943, dulaglutide 1·5 mg, and placebo, respectively, with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events. The pharmacokinetics of LY3437943 were dose proportional and its half-life was approximately 6 days. At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups (least-squares mean difference -2·8 mmol/L [90% CI -4·63 to -0·94] for 3 mg; -3·1 mmol/L [-4·91 to -1·22] for 3/6 mg; and -2·9 mmol/L [-4·70 to -1·01] for 3/6/9/12 mg). Placebo-adjusted sHbAIn this early phase study, LY3437943 showed an acceptable safety profile, and its pharmacokinetics suggest suitability for once-weekly dosing. This finding, together with the pharmacodynamic findings of robust reductions in glucose and bodyweight, provides support for phase 2 development.Eli Lilly and Company.

Obesity is now recognised as a disease that is associated with serious morbidity and increased mortality. One of its main metabolic complications is type 2 diabetes, as the two conditions share key pathophysiological mechanisms. Weight loss is known to reverse the underlying metabolic abnormalities of type 2 diabetes and, as such, improve glucose control; loss of 15% or more of bodyweight can have a disease-modifying effect in people with type 2 diabetes, an outcome that is not attainable by any other glucose-lowering intervention. Furthermore, weight loss in this population exerts benefits that extend beyond glycaemic control to improve risk factors for cardiometabolic disease and quality of life. We review the evidence supporting the role of weight loss in the management of type 2 diabetes and propose that many patients with type 2 diabetes would benefit from having a primary weight-centric approach to diabetes treatment. We discuss the logistical challenges to implementing a new weight-centric primary treatment goal in people with type 2 diabetes.

Summary Background The prevalence of overweight, obesity, and diabetes is rising rapidly in low-income and middle-income countries (LMICs), but there are scant empirical data on the association between body-mass index (BMI) and diabetes in these settings. Methods In this cross-sectional study, we pooled individual-level data from nationally representative surveys across 57 LMICs. We identified all countries in which a WHO Stepwise Approach to Surveillance (STEPS) survey had been done during a year in which the country fell into an eligible World Bank income group category. For LMICs that did not have a STEPS survey, did not have valid contact information, or declined our request for data, we did a systematic search for survey datasets. Eligible surveys were done during or after 2008; had individual-level data; were done in a low-income, lower-middle-income, or upper-middle-income country; were nationally representative; had a response rate of 50% or higher; contained a diabetes biomarker (either a blood glucose measurement or glycated haemoglobin [HbA1c]); and contained data on height and weight. Diabetes was defined biologically as a fasting plasma glucose concentration of 7·0 mmol/L (126·0 mg/dL) or higher; a random plasma glucose concentration of 11·1 mmol/L (200·0 mg/dL) or higher; or a HbA1c of 6·5% (48·0 mmol/mol) or higher, or by self-reported use of diabetes medication. We included individuals aged 25 years or older with complete data on diabetes status, BMI (defined as normal [18·5–22·9 kg/m2], upper-normal [23·0–24·9 kg/m2], overweight [25·0–29·9 kg/m2], or obese [≥30·0 kg/m2]), sex, and age. Countries were categorised into six geographical regions: Latin America and the Caribbean, Europe and central Asia, east, south, and southeast Asia, sub-Saharan Africa, Middle East and north Africa, and Oceania. We estimated the association between BMI and diabetes risk by multivariable Poisson regression and receiver operating curve analyses, stratified by sex and geographical region. Findings Our pooled dataset from 58 nationally representative surveys in 57 LMICs included 685 616 individuals. The overall prevalence of overweight was 27·2% (95% CI 26·6–27·8), of obesity was 21·0% (19·6–22·5), and of diabetes was 9·3% (8·4–10·2). In the pooled analysis, a higher risk of diabetes was observed at a BMI of 23 kg/m2 or higher, with a 43% greater risk of diabetes for men and a 41% greater risk for women compared with a BMI of 18·5–22·9 kg/m2. Diabetes risk also increased steeply in individuals aged 35–44 years and in men aged 25–34 years in sub-Saharan Africa. In the stratified analyses, there was considerable regional variability in this association. Optimal BMI thresholds for diabetes screening ranged from 23·8 kg/m2 among men in east, south, and southeast Asia to 28·3 kg/m2 among women in the Middle East and north Africa and in Latin America and the Caribbean. Interpretation The association between BMI and diabetes risk in LMICs is subject to substantial regional variability. Diabetes risk is greater at lower BMI thresholds and at younger ages than reflected in currently used BMI cutoffs for assessing diabetes risk. These findings offer an important insight to inform context-specific diabetes screening guidelines. Funding Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program.

Metabolic-bariatric surgery delivers substantial weight loss and can induce remission or improvement of obesity-related risks and complications. However, more robust estimates of its effect on long-term mortality and life expectancy-especially stratified by pre-existing diabetes status-are needed to guide policy and facilitate patient counselling. We compared long-term survival outcomes of severely obese patients who received metabolic-bariatric surgery versus usual care.We did a prespecified one-stage meta-analysis using patient-level survival data reconstructed from prospective controlled trials and high-quality matched cohort studies. We searched PubMed, Scopus, and MEDLINE (via Ovid) for randomised trials, prospective controlled studies, and matched cohort studies comparing all-cause mortality after metabolic-bariatric surgery versus non-surgical management of obesity published between inception and Feb 3, 2021. We also searched grey literature by reviewing bibliographies of included studies as well as review articles. Shared-frailty (ie, random-effects) and stratified Cox models were fitted to compare all-cause mortality of adults with obesity who underwent metabolic-bariatric surgery compared with matched controls who received usual care, taking into account clustering of participants at the study level. We also computed numbers needed to treat, and extrapolated life expectancy using Gompertz proportional-hazards modelling. The study protocol is prospectively registered on PROSPERO, number CRD42020218472.Among 1470 articles identified, 16 matched cohort studies and one prospective controlled trial were included in the analysis. 7712 deaths occurred during 1·2 million patient-years. In the overall population consisting 174 772 participants, metabolic-bariatric surgery was associated with a reduction in hazard rate of death of 49·2% (95% CI 46·3-51·9, p0·0001) and median life expectancy was 6·1 years (95% CI 5·2-6·9) longer than usual care. In subgroup analyses, both individuals with (hazard ratio 0·409, 95% CI 0·370-0·453, p0·0001) or without (0·704, 0·588-0·843, p0·0001) baseline diabetes who underwent metabolic-bariatric surgery had lower rates of all-cause mortality, but the treatment effect was considerably greater for those with diabetes (between-subgroup IAmong adults with obesity, metabolic-bariatric surgery is associated with substantially lower all-cause mortality rates and longer life expectancy than usual obesity management. Survival benefits are much more pronounced for people with pre-existing diabetes than those without.None.

Summary Background Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination. Methods In this randomised, placebo-controlled, multiple-ascending dose, phase 1b trial, individuals aged 18–55 years with a body-mass index 27·0−39·9 kg/m2 and who were otherwise healthy were recruited from a single centre in the USA. The trial included six sequential overlapping cohorts, and in each cohort eligible participants were randomly assigned (3:1) to once-weekly subcutaneous cagrilintide (0·16, 0·30, 0·60, 1·2, 2·4, or 4·5 mg) or matched placebo, in combination with once-weekly subcutaneous semaglutide 2·4 mg, without lifestyle interventions. In each cohort, the doses of cagrilintide and semaglutide were co-escalated in 4-week intervals to the desired dose over 16 weeks, participants were treated at the target dose for 4 weeks, and then followed up for 5 weeks. Participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was number of treatment-emergent adverse events from baseline to end of follow-up. Secondary pharmacokinetic endpoints assessed from day of last dose (week 19) to end of treatment (week 20) were area under the plasma concentration-time curve from 0 to 168 h (AUC0–168 h) and maximum concentration [Cmax] of cagrilintide and semaglutide; exploratory pharmacokinetic endpoints were half-life, time to Cmax [tmax], plasma clearance, and volume of distribution of cagrilintide and semaglutide; and exploratory pharmacodynamic endpoints were changes in bodyweight, glycaemic parameters, and hormones. Safety, pharmacokinetic, and pharmacodynamic endpoints were assessed in all participants who were exposed to at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03600480, and is now complete. Findings Between July 25, 2018, and Dec 17, 2019, 285 individuals were screened and 96 were randomly assigned to cagrilintide (0·16–2·4 mg group n=12; 4·5 mg group n=11) or placebo (n=24), in combination with semaglutide 2·4 mg, of whom 95 were exposed to treatment (one patient in 0·60 mg cagrilintide group was not exposed) and included in the safety and full analysis datasets. The mean age was 40·6 years (SD 9·2), 56 (59%) of 95 participants were men and 51 (54%) were Black or African American. Of 566 adverse events reported in 92 participants (69 [97%] of 71 participants assigned to 0·16–4·5 mg cagrilintide and 23 [96%] of 24 assigned to placebo), 207 (37%) were gastrointestinal disorders. Most adverse events were mild to moderate in severity and the proportion of participants with one or more adverse event was similar across treatment groups. Exposure was proportional to cagrilintide dose and did not affect semaglutide exposure or elimination. AUC0–168 h ranged from 926 nmol × h/L to 24 271 nmol × h/L, and Cmax ranged from 6·14 nmol/L to 170 nmol/L with cagrilintide 0·16–4·5 mg. AUC0–168 h ranged from 12 757 nmol × h/L to 15 305 nmol × h/L, and Cmax ranged from 96·4 nmol/L to 120 nmol/L with semaglutide 2·4 mg. Cagrilintide 0·16−4·5 mg had a half-life of 159–195 h, with a median tmax of 24–72 h. Semaglutide 2·4 mg had a half-life of 145–165 h, with a median tmax of 12–24 h. Plasma clearance and volume of distribution for both cagrilintide and semaglutide were similar across treatment groups. At week 20, mean percentage bodyweight reductions were greater with cagrilintide 1·2 and 2·4 mg than with placebo (15·7% [SE 1·6] for cagrilintide 1·2 mg and 17·1% [1·5] for cagrilintide 2·4 mg vs 9·8% [1·2] for pooled placebo cohorts 1–5; estimated treatment difference of −6·0% [95% CI −9·9 to −2·0] for cagrilintide 1·2 mg and −7·4% [−11·2 to −3·5] for cagrilintide 2·4 mg vs pooled placebo), and with cagrilintide 4·5 mg than with matched placebo (15·4% [1·3] vs 8·0% [2·2]; estimated treatment difference −7·4% [−12·8 to −2·1]), all in combination with semaglutide 2·4 mg. Glycaemic parameters improved in all treatment groups, independently of cagrilintide dose. Changes in hormones were similar across treatment groups. Interpretation Concomitant treatment with cagrilintide and semaglutide 2·4 mg was well tolerated with an acceptable safety profile. Future larger and longer trials are needed to fully assess the efficacy and safety of this treatment combination. Funding Novo Nordisk A/S.

The double burden of malnutrition (DBM), defined as the simultaneous manifestation of both undernutrition and overweight and obesity, affects most low-income and middle-income countries (LMICs). This Series paper describes the dynamics of the DBM in LMICs and how it differs by socioeconomic level. This Series paper shows that the DBM has increased in the poorest LMICs, mainly due to overweight and obesity increases. Indonesia is the largest country with a severe DBM, but many other Asian and sub-Saharan African countries also face this problem. We also discuss that overweight increases are mainly due to very rapid changes in the food system, particularly the availability of cheap ultra-processed food and beverages in LMICs, and major reductions in physical activity at work, transportation, home, and even leisure due to introductions of activity-saving technologies. Understanding that the lowest income LMICs face severe levels of the DBM and that the major direct cause is rapid increases in overweight allows identifying selected crucial drivers and possible options for addressing the DBM at all levels.

Actions to address different forms of malnutrition are typically managed by separate communities, policies, programmes, governance structures, and funding streams. In contrast, double duty actions, which aim to simultaneously tackle both undernutrition and problems of overweight, obesity and diet-related non-communicable diseases (DR-NCDs) have been proposed as a way to effectively address malnutrition in all its forms in a more holsitic way. This paper identifies ten double duty actions that have strong potential to reduce the risk of both undernutrition and obesity/DR-NCDs. It does so by : 1) summarizing evidence on common drivers of different forms of malnutrition; 2) documenting examples of unintended harm caused by some undernutrition-focused programmes on obesity/DR-NCDs; and 3) highlighting a few examples of first double duty actions undertaken to tackle multiple forms of malnutrition. We find that undernutrition and obesity/DR-NCDs are intrinsically linked through early life nutrition; dietary quality; food environments; and socioeconomic factors. There is some evidence that undernutrition-focused programs have raised risks of poor quality diets and obesity/DR-NCDs, especially in countries undergoing a rapid nutrition transition. The paper builds on this evidence to develop a framework to guide the design of double duty approaches and strategies, and defines the first steps needed to deliver them. With a clear package of double duty actions now identified, there is an urgent need to move forward with double duty actions to address malnutrition in all its forms.

Summary Observations from many countries indicate that multiple forms of malnutrition might coexist in a country, a household, and an individual. In this Series, the double burden of malnutrition (DBM) encompasses undernutrition in the form of stunting, and overweight and obesity. Health effects of the DBM include those associated with both undernutrition, such as impaired childhood development and greater susceptibility to infectious diseases, and overweight, especially in terms of increased risk of added visceral fat and increased risk of non-communicable diseases. These health effects have not been translated into economic costs for individuals and economies in the form of lost wages and productivity, as well as higher medical expenses. We summarise the existing approaches to modelling the economic effects of malnutrition and point out the weaknesses of these approaches for measuring economic losses from the DBM. Where population needs suggest that nutrition interventions take into account the DBM, economic evaluation can guide the choice of so-called double-duty interventions as an alternative to separate programming for stunting and overweight. We address the evidence gap with an economic analysis of the costs and benefits of an illustrative double-duty intervention that addresses both stunting and overweight in children aged 4 years and older by providing school meals with improved quality of diet. We assess the plausibility of our method and discuss how improved data and models can generate better estimates. Double-duty interventions could save money and be more efficient than single-duty interventions.

Summary Background Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundation.

Summary A caesarean section (CS) can be a life-saving intervention when medically indicated, but this procedure can also lead to short-term and long-term health effects for women and children. Given the increasing use of CS, particularly without medical indication, an increased understanding of its health effects on women and children has become crucial, which we discuss in this Series paper. The prevalence of maternal mortality and maternal morbidity is higher after CS than after vaginal birth. CS is associated with an increased risk of uterine rupture, abnormal placentation, ectopic pregnancy, stillbirth, and preterm birth, and these risks increase in a dose–response manner. There is emerging evidence that babies born by CS have different hormonal, physical, bacterial, and medical exposures, and that these exposures can subtly alter neonatal physiology. Short-term risks of CS include altered immune development, an increased likelihood of allergy, atopy, and asthma, and reduced intestinal gut microbiome diversity. The persistence of these risks into later life is less well investigated, although an association between CS use and greater incidence of late childhood obesity and asthma are frequently reported. There are few studies that focus on the effects of CS on cognitive and educational outcomes. Understanding potential mechanisms that link CS with childhood outcomes, such as the role of the developing neonatal microbiome, has potential to inform novel strategies and research for optimising CS use and promote optimal physiological processes and development.

Background Obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, we evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. Methods We did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m 2 or more. We randomly assigned participants (6:1) to each active treatment group (ie, semaglutide [0·05 mg, 0·1 mg, 0·2 mg, 0·3 mg, or 0·4 mg; initiated at 0·05 mg per day and incrementally escalated every 4 weeks] or liraglutide [3·0 mg; initiated at 0·6 mg per day and escalated by 0·6 mg per week]) or matching placebo group (equal injection volume and escalation schedule to active treatment group) using a block size of 56. All treatment doses were delivered once-daily via subcutaneous injections. Participants and investigators were masked to the assigned study treatment but not the target dose. The primary endpoint was percentage weight loss at week 52. The primary analysis was done using intention-to-treat ANCOVA estimation with missing data derived from the placebo pool. This study is registered with ClinicalTrials.gov, number NCT02453711. Findings Between Oct 1, 2015, and Feb 11, 2016, 957 individuals were randomly assigned (102–103 participants per active treatment group and 136 in the pooled placebo group). Mean baseline characteristics included age 47 years, bodyweight 111·5 kg, and BMI 39·3 kg/m 2. Bodyweight data were available for 891 (93%) of 957 participants at week 52. Estimated mean weight loss was −2·3% for the placebo group versus −6·0% (0·05 mg), −8·6% (0·1 mg), −11·6% (0·2 mg), −11·2% (0·3 mg), and −13·8% (0·4 mg) for the semaglutide groups. All semaglutide groups versus placebo were significant (unadjusted p≤0·0010), and remained significant after adjustment for multiple testing (p≤0·0055). Mean bodyweight reductions for 0·2 mg or more of semaglutide versus liraglutide were all significant (−13·8% to −11·2% vs −7·8%). Estimated weight loss of 10% or more occurred in 10% of participants receiving placebo compared with 37–65% receiving 0·1 mg or more of semaglutide (p

Five Sustainable Development Goals (SDGs) set targets that relate to the reduction of health inequalities nationally and worldwide. These targets are poverty reduction, health and wellbeing for all, equitable education, gender equality, and reduction of inequalities within and between countries. The interaction between inequalities and health is complex: better economic and educational outcomes for households enhance health, low socioeconomic status leads to chronic ill health, and non-communicable diseases (NCDs) reduce income status of households. NCDs account for most causes of early death and disability worldwide, so it is alarming that strong scientific evidence suggests an increase in the clustering of non-communicable conditions with low socioeconomic status in low-income and middle-income countries since 2000, as previously seen in high-income settings. These conditions include tobacco use, obesity, hypertension, cancer, and diabetes. Strong evidence from 283 studies overwhelmingly supports a positive association between low-income, low socioeconomic status, or low educational status and NCDs. The associations have been differentiated by sex in only four studies. Health is a key driver in the SDGs, and reduction of health inequalities and NCDs should become key in the promotion of the overall SDG agenda. A sustained reduction of general inequalities in income status, education, and gender within and between countries would enhance worldwide equality in health. To end poverty through elimination of its causes, NCD programmes should be included in the development agenda. National programmes should mitigate social and health shocks to protect the poor from events that worsen their frail socioeconomic condition and health status. Programmes related to universal health coverage of NCDs should specifically target susceptible populations, such as elderly people, who are most at risk. Growing inequalities in access to resources for prevention and treatment need to be addressed through improved international regulations across jurisdictions that eliminate the legal and practical barriers in the implementation of non-communicable disease control.

Background Restricting advertising of products with high fat, salt, and sugar (HFSS) content has been recommended as a tool to tackle obesity, but the impact on purchases is unknown. This study evaluates the impact of outdoor HFSS advertising restrictions, implemented across the London transport network in February, 2019, on HFSS purchases. Methods Take-home food and drink purchase data (n=5 089 988) from 1970 households (London [intervention] n=977; North of England [control] n=993) from the Kantar Fast Moving Consumer Goods panel were analysed with a controlled interrupted time series design. We estimated average weekly household purchases of energy and nutrients from HFSS products in the postintervention period (Feb 25 to Dec 29, 2019) compared with a counterfactual constructed from the control and preintervention (June 18, 2018, to Feb 24, 2019) series. The London School of Hygiene & Tropical Medicine ethics committee approved the study (16297/RR/11721), and written informed consent was obtained from participants. Findings After adjustment for confounders, average weekly household purchase of energy was reduced by 6·8% (1015·4 kcal, 95% CI 473·6–1557·2) compared with the counterfactual. Reductions in purchases of fat (57·4 g, 95% CI 21·7–93·0), saturated fat (26·4 g, 12·5–40·4) and sugar (85·5 g, 46·7–124·3) from HFSS products were also observed. When stratified by product category, we found a 19·4% reduction in energy purchased from chocolate and confectionery (317·9 kcal, 95% CI 200·0–435·8), along with reductions in fat (13·1 g, 95% CI 7·5–18·8), saturated fat (8·7 g, 5·7–11·7), sugar (41·4 g, 27·4–55·4), and salt (0·2 g, 0·1–0·2) purchased. Interpretation To our knowledge, this was the first UK study to examine the impact of outdoor HFSS advertising restrictions on food and drink purchases. Our findings provide support for policies that restrict HFSS advertising as a tool to reduce purchases of HFSS products. However, the sustainability of the observed effects is unclear. Confounding due to other events occurring at the same time as the intervention in either the intervention or control group cannot be ruled out. However, observed intervention effects were greater among frequent public transport users, and were specific to the week the advertising restrictions were introduced. Funding National Institute for Health Research School for Public Health Research (grant number PD-SPH-2015).

Background The contribution of social determinants, such as deprivation and health-related behaviours, to Black African and Black Caribbean–White differences in cardiovascular risks is uncertain. Methods Primary care records from 44 practices in Lambeth (Lambeth DataNet) from Jan 1, 2000, to Oct 27, 2018, for women aged 40 years or older were analysed using multilevel logistic regression models adjusted for age, income deprivation, lifestyles, health-care access, comorbidities (Quality and Outcome Framework disease registers) and medications, and for clustering of patients within practices. Findings We studied 70 582 women aged 40 years or older from White (n=35 297), Black African (n=11 206), and Black Caribbean (n=9193) ethnic groups. In women aged 40–69 years, smoking levels were similar in White and Black Caribbean groups (approximately 19%), but much lower in Black African groups (6·1%). In both age groups, obesity levels (ie, a body-mass index of ≥30 kg/m2) in Black Caribbean women (44·3%) and Black African women (48·9%) were around double that in White women (20·8%). Levels of missing data were low (2–10%), and were included as a separate category in each variable. Adjusted for age and income deprivation and compared with White women, excess risks observed at age 40–69 years (n=59 132) for Black African women were diabetes (odds ratio [OR] 2·94, 95% CI 2·69–3·20; p Interpretation Deprivation and health-related behaviours made notable contributions to differences in cardiovascular risks between Black African, Black Caribbean, and White ethnic groups, consistent with earlier studies. Funding National Institute of Health Research, Research for Patient Benefit Programme (NIHR202769).

Background Maternal exposures during pregnancy have been linked to offspring adiposity, and the interpregnancy period is an opportunity to intervene on modifiable risk factors. We considered combinations of interpregnancy interventions and effects on rates of childhood obesity (≥95th centile) in second children. Methods We examined records of 5612 women from a population-based cohort of routinely collected antenatal health-care records at University Hospital Southampton (2003–2014), linked to measured child body-mass index (BMI) at age 4–5 years from the National Childhood Measurement Programme. We applied the parametric g-formula to estimate the effects of interventions between first (P1) and second (P2) pregnancies and to calculate estimated second child obesity and population risk ratio reduction (PRRR), compared with the estimated natural-course scenario (without intervention). Analysis was undertaken using the gfoRmula package in R This analysis is part of the SLOPE study which has been approved by the National Health Service Health Research Authority. Findings Observed frequency of obesity in the second child at age 4–5 years was 8·5% (479 of 5612 children). We estimated that if all mothers started P2 with a BMI of 18·5–24·9 kg/m2 and all smokers stopped smoking by confirmation of P2, then, compared with a natural course estimate of 8·3% (95% CI 7·6–9·1), there would be a PRRR of second child obesity of 25·8% (21·0–30·8) to a second child obesity prevalence of 6·2% (5·5–7·0). For mothers who started P1 with BMI 18·5–24·9 kg/m2, if all smokers stopped smoking, then, compared with a natural course estimate of 5·9% (5·0–6·7), there would be a PRRR of second child obesity of 16·6% (10·0–23·2) to a prevalence of 4·9% (4·1–5·7). If BMI was also maintained between 18·5 and 24·9 kg/m2 there would be a PRRR of 21·3% (15·3–28·2) to a prevalence of 4·6% (3·9–5·4). For mothers who started P1 with BMI of 30 kg/m2 or greater, if weight was reduced to being either 18·5–24·9 kg/m2 or 25–29·9 kg/m2 by the start of P2, then, compared with a natural course estimate of 17·7% (15·1–20·9), there would be PRRRs of second child obesity of 29·4% (4·7–53·4) to a prevalence of 12·5% (8·3–17·4) and 17·6% (2·6–35·1) to a prevalence of 14·6% (11·1–17·7), respectively. Interpretation Interventions between pregnancies could reduce obesity rates in the second child, with the most effective interventions varying by maternal BMI during the first pregnancy. Funding NIHR Southampton Biomedical Research Centre, University of Southampton Primary Care, Population Sciences and Medical Education PhD studentship, and an Academy of Medical Sciences and Wellcome Trust grant.

Background Evidence of the effects of lactation on maternal risk of type 2 diabetes is conflicting, with some studies suggesting a protective effect, whereas others report no association. This study aimed to investigate the association between lactation and maternal risk of type 2 diabetes. Methods We did a systematic review and random-effects meta-analysis of observational studies investigating the association between lactation (irrespective of duration, intensity, or mode) and maternal risk of type 2 diabetes. Bibliographic databases MEDLINE and Embase were searched from inception to Feb 28, 2021, with MeSH terms for lactation, breastfeeding, and type 2 diabetes. No restrictions were applied to type of study or language. This search was complemented with hand-searching of reference lists of relevant studies. The methodological quality of eligible studies was assessed using the Newcastle-Ottawa Scale for non-randomised studies. Heterogeneity was quantified using the I2 statistic and tested using Cochran's Q test. Eligible studies were included in the meta-analysis if they had published data on the outcomes of interest in each analysis. This study is registered with PROSPERO, number CRD42020221183. Findings Our search identified 1161 studies, of which 22 (17 cohort and five cross-sectional) were eligible for inclusion in the systematic review (8739 participants), and 16 contributed to the meta-analysis (4372 participants). The studies were conducted in populations from North America, Europe, Asia, and Australia, including multi-ethnic populations and variable sample sizes (range 100–83 000). The five studies that investigated the association of lactation with risk of type 2 diabetes in the first months after birth in women with gestational diabetes reported conflicting results. The 17 studies with longer follow-up (>3 months) showed an incremental (dose–response) protective association between lactation and risk of type 2 diabetes, with a potentially larger risk reduction in women with gestational diabetes than in those without gestational diabetes (risk ratio [RR] 0·66 [95% CI 0·52–0·85] for ever vs never lactation for women with gestational diabetes, and RR 0·81 [0·67–0·98] for ever vs never lactation for women without gestational diabetes; p=0·032 for heterogeneity). Overall, ever versus never lactation was associated with a lower risk of type 2 diabetes (RR 0·73, 95% CI 0·65–0·83; I2=69%, p=0·010). Each additional month of lactation was associated with a 1% lower risk of type 2 diabetes (RR 0·99, 0·98–0·99), irrespective of gestational diabetes. The overall quality of the studies was modest. Interpretation Lactation is associated with a significantly lower risk of maternal type 2 diabetes, particularly in women with gestational diabetes. The protective effect seems to increase with longer duration of lactation. Further research is warranted to understand whether this association is modified by exposure to other risk factors, such as obesity. Breastfeeding-friendly policies might help to reduce the risk of type 2 diabetes among women. Funding None.

Background Overweight and obesity are multifactorial conditions that are spreading fast in both developing and developed countries. They are emerging as a major public health threat among children and adolescents, and present a serious morbidity and mortality burden. Adolescence is a critical period in which lifestyle and dietary behaviours are shaped that persist into adulthood. Therefore, adolescents are an ideal study target in terms of estimating the magnitude of the problem, understanding its risk factors and investigating potential effective intervention programmes. This study assesses the prevalence of overweight, obesity, and associated factors among adolescents in Palestinian schools. Methods Weighted analysis was conducted on data from the Palestinian Micronutrient Survey, a national cross-sectional study carried out in 2013 by the Palestinian Ministry of Health in collaboration with UNICEF. For sample selection, stratified cluster random sampling was used. This school-based survey involved 2400 male and female adolescents aged 15–18 years in government schools in the West Bank and Gaza Strip. Data were analysed at univariate, bivariate, and multivariate levels, by the use of proportions, confidence intervals, and logistic regression. In the original survey, written informed consent was obtained from parents and guardians of the participants. A letter of approval to use the study data was obtained from the Ministry of Health (who own the data). The study was also approved by the Ethics Committee of the Institute of Community and Public Health. Findings The analysis indicates a prevalence of 23·6% (95% CI 20·6–26·5) for overweight and obesity, with a prevalence of 26·1% in the West Bank and 19·5% in the Gaza Strip. The multivariate analysis revealed that the likelihood of overweight and obesity was significantly higher for adolescents from the West Bank than from the Gaza Strip, for those eating two main meals or less than for those eating three meals, for those who reported a high frequency of vegetable intake, and those who observed a diet for weight loss. Interpretation The data suggest that one in every four adolescents is overweight or obese, which is an alarming statistic and calls for attention. The high prevalence can be attributed to different lifestyles, eating behaviours, and dietary intake, which affect energy balance. These factors should be investigated within social, political, and economic contexts, and addressed comprehensively, first at the level of individuals and family, and then at the level of schools and the community. It should be noted that the original study included students in the 10th grade and 11th grade only, whereas adolescence covers a wider age group (10–19 years). Funding None.

Background As of Feb 14, 2014, UNRWA had registered almost 53 000 Palestinian refugees from Syria (PRS) who had fled to Lebanon as the result of the conflict in Syria. Half of the PRS had gone to one of the 12 Palestinian camps, which are overcrowded and of poor infrastructure. Consequently, there is concern for the wellbeing of PRS; in particular, their health status and access to medical care. Little attention has been given to non-communicable diseases (NCDs) in the acute phases of emergencies. Therefore, an assessment of the prevalence of NCDs among PRS, as well as the patterns of use of available health care services by PRS, is warranted. Methods A cross-sectional study was conducted in April, 2018, with 1100 PRS residing inside and outside refugee camps across all governorates of Lebanon. A listing of all PRS families was the sampling frame. A random sample of families was selected and contacted, and then one adult randomly selected from each family was approached for data collection. Pregnant women and participants who were too ill to participate were excluded. After obtaining informed verbal consent, we did face-to-face interviews to collect data on household details (such as type of settlement, source of income) and sociodemographic information, major NCDs (for the household representative), lifestyle behaviours, and health-care use. We invited all participants to UNRWA clinics for physical and biochemical measurements. The study protocol was approved by the Institutional Review Board of the American University of Beirut. Findings We surveyed 959 PRS (59% male [465], 82% married [785], mean age 43 years [SD 12]). A quarter of those interviewed had at least one NCD; the most prevalent were hypertension (23%; 221 of 959), rheumatic diseases (17%; 166), cardiovascular diseases (CVDs, 13%; 126), diabetes (13%; 124), and chronic respiratory diseases (CRDs) (10%; 100). All these NCDs were more prevalent among PRS inside camps than in those residing outside camps, except for diabetes. Most participants who had been diagnosed with NCDs were adhering to their prescribed medications (90–98%). However, of those reporting CVDs, only 56% (71 of 126) had attended at least one follow-up appointment, and of those reporting rheumatic diseases, only 33% (55 of 166) had attended at least one follow-up appointment. About half of participants reported that they checked their blood pressure (55%; 528 of 959) or blood glucose (45%; 430). 111 of 221 (50%) participants with hypertension monitored their blood pressure, and 78 of 124 (63%) participants with diabetes monitored their blood glucose. 133 participants attended UNRWA clinics for measurements; 40% (54) had obesity (>30 kg/cm2), 10% (13) had elevated blood pressure, 12% (16) had stage 1 hypertension, and 8% (10) had stage 2 hypertension. Most participants had normal glucose (67%; 89 of 133), cholesterol (65%; 87), triglyceride (58%; 77), and glycosylated haemoglobin levels (64; 85). A substantial proportion of participants who were tested had undiagnosed diabetes (14%; 33 of 108 reporting no diabetes), undiagnosed hypertension (23%; 19 of 81), uncontrolled diabetes (79% of participants with diabetes; 19 of 24), or uncontrolled hypertension (64% of participants with hypertension; 29 of 45). Interpretation Further study is needed to understand why the prevalence of NCDs among PRS residing in Palestinian camps is higher than among those living outside, and to understand whether and why access to medicines is a problem, particularly outside camps. The burden of NCDs among PRS is high and their access to services is not optimal; therefore UNRWA should pay special attention to NCD services in this population. UNRWA should invest in efforts to increase awareness of free blood pressure and blood glucose monitoring services in its clinics, and could actively offer free testing in public areas inside camps. Doctors at UNRWA clinics should recommend that patients monitor their disease more frequently and educate them on how to do so. A limitation of the study was the low percentage of participants who attended UNRWA clinics for physical and biochemical measurements. Funding UNRWA.

Type 2 diabetes in adolescence manifests as a severe progressive form of diabetes that frequently presents with complications, responds poorly to treatment, and results in rapid progression of microvascular and macrovascular complications. Although overall still a rare disease, adolescent type 2 diabetes now poses major challenges to paediatric and adult diabetes services in many countries. Therapeutic options are heavily curtailed by a dearth of knowledge about the condition, with low numbers of participants and poor trial recruitment impeding research. Together with lifestyle modification, metformin remains the first-line therapy for adolescents with type 2 diabetes, although the majority rapidly progress to treatment failure and insulin therapy. Early bariatric surgery is controversial but has great potential to transform outcomes. Health systems must respond by both concentrating patients in specialist clinical services integrated with translational research programmes, but also by joining up with local health and social care services to improve engagement and uptake of services.

Unprecedented global forces are shaping the health and wellbeing of the largest generation of 10 to 24 year olds in human history. Population mobility, global communications, economic development, and the sustainability of ecosystems are setting the future course for this generation and, in turn, humankind. At the same time, we have come to new understandings of adolescence as a critical phase in life for achieving human potential. Adolescence is characterised by dynamic brain development in which the interaction with the social environment shapes the capabilities an individual takes forward into adult life.3 During adolescence, an individual acquires the physical, cognitive, emotional, social, and economic resources that are the foundation for later life health and wellbeing. These same resources define trajectories into the next generation. Investments in adolescent health and wellbeing bring benefits today, for decades to come, and for the next generation. Better childhood health and nutrition, extensions to education, delays in family formation, and new technologies offer the possibility of this being the healthiest generation of adolescents ever. But these are also the ages when new and different health problems related to the onset of sexual activity, emotional control, and behaviour typically emerge. Global trends include those promoting unhealthy lifestyles and commodities, the crisis of youth unemployment, less family stability, environmental degradation, armed conflict, and mass migration, all of which pose major threats to adolescent health and wellbeing. Adolescents and young adults have until recently been overlooked in global health and social policy, one reason why they have had fewer health gains with economic development than other age groups. The UN Secretary-General's Global Strategy for Women's, Children's and Adolescents' Health initiated, in September, 2015, presents an outstanding opportunity for investment in adolescent health and wellbeing. However, because of limits to resources and technical capacities at both the national and the global level, effective response has many challenges. The question of where to make the most effective investments is now pressing for the international development community. This Commission outlines the opportunities and challenges for investment at both country and global levels (panel 1).

On June 18, 2020, WHO presented a strategic framework to ensure the equitable allocation of scarce COVID-19 resources, including vaccines.1 Health-care workers, people older than 65 years, and people with cardiovascular disease, chronic respiratory disease, cancer, diabetes, or obesity will be prioritised for initial vaccination. Pregnant women do not appear to constitute a high-priority group, despite representing a cohort who are at increased risk for severe complications of COVID-19. A growing body of evidence exists to suggest that pregnant women are at a higher risk of morbidity and mortality from COVID-19, including increased risk of respiratory failure with the need for admission to intensive care and mechanical ventilation, compared with age-matched women who are not pregnant.2, 3 COVID-19 has also been associated with an increased rate of stillbirth.4

Background Geographical inequalities in the prevalence of overweight and obesity among children are well established in cross-sectional research. We aimed to examine how area-level characteristics at birth are related to these outcomes in childhood. Methods Anonymised antenatal and birth data recorded by University Hospital Southampton (2003–18) linked to school-measured weight and height data for children within Southampton, UK were used (14 084 children at ages 4–5 years, and 5 637 at ages 10–11 years). Children's home address at birth was provided at the lower layer super output area level (areas with average populations of 1500). Area-level indices (walkability, unhealthy or healthy food outlets, and spaces for social interaction), natural greenspace coverage, supermarket density, and measures of air pollution (PM2·5, PM10, and NOx) were constructed for lower layer super output areas using data from Ordnance Survey and open sources. Overweight or obesity was defined as a BMI greater than the 85th centile for sex and age. Population-average generalised estimating equations estimated the risk of being overweight or obese for children at both time points. Confounders accounted for included maternal BMI and smoking in early pregnancy, educational attainment, ethnicity, and parity. This project was approved by the NHS Health Research Authority (242031). Findings No significant associations were noted between area characteristics at birth and overweight or obesity at ages 4–5 years. The proportion of the lower layer super output area covered by greenspace was negatively associated with the risk of being overweight or obese at ages 10–11 years (relative risk ratio 0·997, 95% CI 0·995–0·999). This finding was consistent in a subgroup of children who moved residence (between different lower layer super output areas) between birth and time of measurement. Interpretation Local access to natural greenspaces at the time of birth was negatively associated with becoming overweight or obese by the end of primary school, regardless of migration. However, the size of this protective effect is small. Access to and protection of greenspace might have a role in early prevention of childhood obesity. Funding Supported by an Academy of Medical Sciences and Wellcome Trust grant to NAA and the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre.

Background Maternal smoking during pregnancy has been linked to offspring adiposity. We examined interpregnancy changes in maternal smoking behaviour and the risk of age-specific and sex-specific obesity (≥95th centile) in the second child (C2). Methods We used a population-based cohort of antenatal health-care records (August, 2004–August, 2014) at University Hospital Southampton, linked to measured child body-mass index (BMI) at 4–5 years obtained from child health records at two community NHS Trusts (Solent and Southern). We analysed the first two singleton live pregnancies of 6515 women using logistic regression to examine interpregnancy changes in self-reported maternal smoking in relation to C2 obesity (adjusting for maternal age, ethnicity, BMI, educational attainment, employment, folate supplementation, previous losses, infertility treatment, pre-existing and gestational diabetes and hypertension, interpregnancy interval, C2's birthweight, caesarean section delivery, and gestation). Findings Unadjusted C2 obesity prevalence for children whose mothers never smoked, smoked at the start of both pregnancy 1 (P1) and pregnancy 2 (P2), P2 only, P1 only, and stopped smoking when both pregnancies were confirmed was 6·9% (215/3118 children), 12·5% (87/698 children), 12·4% (22/178 children), 10·3% (28/271 children), and 13·1% (29/222 children), respectively. Compared with women who never smoked, smoking at the start of both pregnancies was associated with higher odds of C2 obesity (adjusted odds ratio [aOR] 2·03, 95% CI 1·49–2.78). Women not smoking in P1 who smoked at the start of P2, and those who stopped when each pregnancy was confirmed had increased C2 obesity odds (aOR 1·80 [95% CI 1·09–3·00] and 1·73 [1·11–2·69], respectively). Smokers maintaining cessation having quit by P1 confirmation, P1 smokers who ceased by P2 confirmation, and those who smoked between pregnancies but who quit before C2 conception, did not have higher odds of C2 obesity (aOR 1·21 [95% CI 0·95–1·55], 1·39 [0·89–2·17], and 1·13 [0·78–1·63], respectively). Interpretation A mother smoking at the start of her first two pregnancies has twice the odds of having an obese second child compared with a non-smoker. Smoking in the second pregnancy only and between pregnancies up to the first trimester of P2 is also associated with childhood obesity. The interpregnancy period is an opportunity to intervene on modifiable risk factors such as smoking. Funding NIHR Southampton Biomedical Research Centre and University of Southampton Primary Care and Population Sciences PhD studentship (to EJT) and an Academy of Medical Sciences and Wellcome Trust grant (grant number AMS_HOP001\1060; to NAA).

Background Fruit and vegetable intake can promote health through prevention of diseases including obesity, heart attacks, type 2 diabetes, and cancer. Food security has been identified as a strong determinant of fruit and vegetable intake. Food-insecure households in high-income societies have lower intakes of fruit and vegetables compared with food-secure households. This study aimed to identify the association between food insecurity and fruit and vegetable intake in the UK and examine the role of sociodemographic factors in fruit and vegetable intake. Methods Data from the 2016 Food and You Survey were analysed (n=3118). As the dependent variable, we used two separate questions regarding the frequencies of eating fruit and vegetables. Household food security was measured by ten questions used by the US Department of Agriculture Economic Research Service about experiences associated with difficulties in meeting food needs. Sociodemographic factors, such as sex, area of residence, age, marital status, employment status, and level of education, were used in the analyses. We did statistical analyses, including descriptive analyses, crosstabs, and regressions. Findings The prevalence of high fruit and vegetable intake among families with food insecurity was 33%, compared with 47% in food-secure households. Findings from adjusted binary logistic regression analyses revealed that the probability of having low fruit and vegetable intake increased among food-insecure respondents (odds ratio 1·6, 95% CI 1·3–2·0; p Interpretation Regardless of region, food security positively affects fruit and vegetable consumption. However, sociodemographic factors and, more specifically, education have considerable effects on fruit and vegetable intake. A key strength of this study is the diverse sample provided by the Food and You Survey from different regions of the UK. However, because of the cross-sectional nature of the study, no causal analyses were done and no changes over time were measured. Funding None.

Background Maternal obesity is a major risk factor for childhood obesity. Given the relatively intensive contact with health and care professionals following birth, the interpregnancy period provides an excellent opportunity to focus on preconception and family health. We examined the association between maternal interpregnancy weight change and overweight/obesity in the second child. Methods We used a population-based anonymised linked cohort of antenatal and birth records registered at University Hospital Southampton, Hampshire, UK (August, 2004–August, 2014) and child health records. Change in maternal interpregnancy body-mass index (BMI) was calculated as the difference between BMI (using measured weight) at the first antenatal appointment of each pregnancy. Records of the first two singleton live pregnancies for 6358 women were analysed. Second child's age-adjusted and sex-adjusted BMI at 4–5 years was used to define the outcome of overweight/obesity (≥85th centile). Generalised linear modelling was used to adjust for maternal age, ethnicity, educational qualification, infertility treatment, smoking, employment status, gestational diabetes, BMI at start of the first pregnancy, and interpregnancy interval, then adding second child's birthweight. Findings 18·5% women (1175 of 6358) gained 3 kg/m2 or more and 29·0% (1842 of 6358) gained 1–3 kg/m2 between pregnancies. Unadjusted prevalence of second child overweight/obesity for mothers with 3 kg/m2 or more gain was 27·9% (328 of 1175) compared with 18·6% (427 of 2287) for mothers whose weigh remained stable between pregnancies (–1 to 1 kg/m2). Interpregnancy gain of 3 kg/m2 or more was associated with increased risk of childhood overweight/obesity (adjusted relative risk [aRR] 1·15, 95% CI 1·01–1·32). The relationship was attenuated on adjusting for birthweight of child 2 (1·09, 0·95–1 ·25). This pattern was similar in the subgroup who were obese at the start of their first pregnancy (1·34, 1·00–1·78 and 1·27, 0·96–1·69, respectively). There was no evidence of an association between the other weight change categories and the outcome after adjustment. Interpretation Many women gain a considerable amount of weight between their first and second pregnancies. Children of mothers who have started their second pregnancy with a considerably higher weight than their first were more likely to be overweight/obese at the start of primary school; however, this association was attenuated by accounting for birthweight, which may be on the causal pathway. Funding Academy of Medical Sciences and the Wellcome Trust (grant number AMS_HOP001\1060 to NAA). NAA is also in receipt of research support from and the National Institute for Health Research through the NIHR Southampton Biomedical Research Centre.

Background Many highly cited studies and reviews have interpreted the Chinese famine of 1959–61 as an important driver of current and future epidemics of type 2 diabetes in China. However, few studies used age-balanced controls, and this has caused biased results. We conducted a systematic review and meta-analysis of prenatal famine exposure and type 2 diabetes epidemics in China to examine the effect of prenatal famine with age-balanced controls. Methods We searched PubMed, Embase, Wanfang Data, and the Chinese National Knowledge Infrastructure databases up to January, 2019, for studies that examined the relationship between type 2 diabetes and prenatal exposure to the Chinese famine of 1959–61. From each included study, we abstracted information on the number of type 2 diabetes cases and the populations at risk for type 2 diabetes among individuals born during the famine (famine births), before the famine (pre-famine births), and after the famine (post-famine births). We compared type 2 diabetes outcomes in famine births with those of different control groups: post-famine births, pre-famine and post-famine births combined (age-balanced), and pre-famine births. Fixed-effects models and random-effects models were used to calculate summary estimates. The heterogeneity across studies was assessed. Subgroup analyses were carried out using famine severity, sex, and other reported characteristics. We examined the quality of each eligible study with the modified Newcastle–Ottawa scale. Findings Of 3863 studies identified, 17 studies met our inclusion criteria and data from 12 studies could be used for meta-analysis. All but one study defined famine exposure based on participants' birth year alone. There were between 68 and 1372 type 2 diabetes cases in each study. When post-famine births were used as controls, we found an increased risk of type 2 diabetes (OR 1·47, 95% CI 1·20–1·80) among famine births based on the random-effects model. Using age-balanced controls, we did not find any increased risk of type 2 diabetes (1·08, 0·95–1·24). When pre-famine births were used as controls, famine was associated with a reduction in risk of type 2 diabetes (0·80, 0·66–0·96). Interpretation From the results of our re-analysis, it remains an open question whether the Chinese famine of 1959–61 has contributed substantially to type 2 diabetes epidemics and whether it is likely to cause or affect future epidemics. Definitions of famine exposure and selection of controls need more attention in future studies to better understand this potential association. In view of the conflicting findings, the current public health efforts for type 2 diabetes prevention and treatment in China should focus on the well-established risk factors of overweight and obesity. Funding None.

Summary Background Randomised controlled trials have shown that bariatric surgery is more effective than conventional treatment for the short-term control of type-2 diabetes. However, published studies are characterised by a relatively short follow-up. We aimed to assess 5 year outcomes from our randomised trial designed to compare surgery with conventional medical treatment for the treatment of type 2 diabetes in obese patients. Methods We did our open-label, randomised controlled trial at one diabetes centre in Italy. Patients aged 30–60 years with a body-mass index of 35 kg/m 2 or more and a history of type 2 diabetes lasting at least 5 years were randomly assigned (1:1:1), via a computer-generated randomisation procedure, to receive either medical treatment or surgery by Roux-en-Y gastric bypass or biliopancreatic diversion. Participants were aware of treatment allocation before the operation and study investigators were aware from the point of randomisation. The primary endpoint was the rate of diabetes remission at 2 years, defined as a glycated haemaglobin A 1c (HbA 1c ) concentration of 6·5% or less (≤47·5 mmol/mol) and a fasting glucose concentration of 5·6 mmol/L or less without active pharmacological treatment for 1 year. Here we analyse glycaemic and metabolic control, cardiovascular risk, medication use, quality of life, and long-term complications 5 years after randomisation. Analysis was by intention to treat for the primary endpoint and by per protocol for the 5 year follow-up. This study is registered with ClinicalTrials.gov, number NCT00888836. Findings Between April 27, 2009, and Oct 31, 2009, we randomly assigned 60 patients to receive either medical treatment (n=20) or surgery by gastric bypass (n=20) or biliopancreatic diversion (n=20); 53 (88%) patients completed 5 years' follow-up. Overall, 19 (50%) of the 38 surgical patients (seven [37%] of 19 in the gastric bypass group and 12 [63%] of 19 in the bilipancreatic diversion group) maintained diabetes remission at 5 years, compared with none of the 15 medically treated patients (p=0·0007). We recorded relapse of hyperglycaemia in eight (53%) of the 15 patients who achieved 2 year remission in the gastric bypass group and seven (37%) of the 19 patients who achieved 2 year remission in the biliopancreatic diversion group. Eight (42%) patients who underwent gastric bypass and 13 (68%) patients who underwent biliopancreatic diversion had an HbA 1c concentration of 6·5% or less (≤47·5 mmol/mol) with or without medication, compared with four (27%) medically treated patients (p=0·0457). Surgical patients lost more weight than medically treated patients, but weight changes did not predict diabetes remission or relapse after surgery. Both surgical procedures were associated with significantly lower plasma lipids, cardiovascular risk, and medication use. Five major complications of diabetes (including one fatal myocardial infarction) arose in four (27%) patients in the medical group compared with only one complication in the gastric bypass group and no complications in the biliopancreatic diversion group. No late complications or deaths occurred in the surgery groups. Nutritional side-effects were noted mainly after biliopancreatic diversion. Interpretation Surgery is more effective than medical treatment for the long-term control of obese patients with type 2 diabetes and should be considered in the treatment algorithm of this disease. However, continued monitoring of glycaemic control is warranted because of potential relapse of hyperglycaemia. Funding Catholic University of Rome.

Summary Prevention of obesity requires policies that work. In this Series paper, we propose a new way to understand how food policies could be made to work more effectively for obesity prevention. Our approach draws on evidence from a range of disciplines (psychology, economics, and public health nutrition) to develop a theory of change to understand how food policies work. We focus on one of the key determinants of obesity: diet. The evidence we review suggests that the interaction between human food preferences and the environment in which those preferences are learned, expressed, and reassessed has a central role. We identify four mechanisms through which food policies can affect diet: providing an enabling environment for learning of healthy preferences, overcoming barriers to the expression of healthy preferences, encouraging people to reassess existing unhealthy preferences at the point-of-purchase, and stimulating a food-systems response. We explore how actions in three specific policy areas (school settings, economic instruments, and nutrition labelling) work through these mechanisms, and draw implications for more effective policy design. We find that effective food-policy actions are those that lead to positive changes to food, social, and information environments and the systems that underpin them. Effective food-policy actions are tailored to the preference, behavioural, socioeconomic, and demographic characteristics of the people they seek to support, are designed to work through the mechanisms through which they have greatest effect, and are implemented as part of a combination of mutually reinforcing actions. Moving forward, priorities should include comprehensive policy actions that create an enabling environment for infants and children to learn healthy food preferences and targeted actions that enable disadvantaged populations to overcome barriers to meeting healthy preferences. Policy assessments should be carefully designed on the basis of a theory of change, using indicators of progress along the various pathways towards the long-term goal of reducing obesity rates.

Summary Although the caloric deficits achieved by increased awareness, policy, and environmental approaches have begun to achieve reductions in the prevalence of obesity in some countries, these approaches are insufficient to achieve weight loss in patients with severe obesity. Because the prevalence of obesity poses an enormous clinical burden, innovative treatment and care-delivery strategies are needed. Nonetheless, health professionals are poorly prepared to address obesity. In addition to biases and unfounded assumptions about patients with obesity, absence of training in behaviour-change strategies and scarce experience working within interprofessional teams impairs care of patients with obesity. Modalities available for the treatment of adult obesity include clinical counselling focused on diet, physical activity, and behaviour change, pharmacotherapy, and bariatric surgery. Few options, few published reports of treatment, and no large randomised trials are available for paediatric patients. Improved care for patients with obesity will need alignment of the intensity of therapy with the severity of disease and integration of therapy with environmental changes that reinforce clinical strategies. New treatment strategies, such as the use of technology and innovative means of health-care delivery that rely on health professionals other than physicians, represent promising options, particularly for patients with overweight and patients with mild to moderate obesity. The co-occurrence of undernutrition and obesity in low-income and middle-income countries poses unique challenges that might not be amenable to the same strategies as those that can be used in high-income countries.

Summary With non-communicable conditions accounting for nearly two-thirds of deaths worldwide, the emergence of chronic diseases as the predominant challenge to global health is undisputed. In the USA, chronic diseases are the main causes of poor health, disability, and death, and account for most of health-care expenditures. The chronic disease burden in the USA largely results from a short list of risk factors—including tobacco use, poor diet and physical inactivity (both strongly associated with obesity), excessive alcohol consumption, uncontrolled high blood pressure, and hyperlipidaemia—that can be effectively addressed for individuals and populations. Increases in the burden of chronic diseases are attributable to incidence and prevalence of leading chronic conditions and risk factors (which occur individually and in combination), and population demographics, including ageing and health disparities. To effectively and equitably address the chronic disease burden, public health and health-care systems need to deploy integrated approaches that bundle strategies and interventions, address many risk factors and conditions simultaneously, create population-wide changes, help the population subgroups most affected, and rely on implementation by many sectors, including public–private partnerships and involvement from all stakeholders. To help to meet the chronic disease burden, the US Centers for Disease Control and Prevention (CDC) uses four cross-cutting strategies: (1) epidemiology and surveillance to monitor trends and inform programmes; (2) environmental approaches that promote health and support healthy behaviours; (3) health system interventions to improve the effective use of clinical and other preventive services; and (4) community resources linked to clinical services that sustain improved management of chronic conditions. Establishment of community conditions to support healthy behaviours and promote effective management of chronic conditions will deliver healthier students to schools, healthier workers to employers and businesses, and a healthier population to the health-care system. Collectively, these four strategies will prevent the occurrence of chronic diseases, foster early detection and slow disease progression in people with chronic conditions, reduce complications, support an improved quality of life, and reduce demand on the health-care system. Of crucial importance, with strengthened collaboration between the public health and health-care sectors, the health-care system better uses prevention and early detection services, and population health is improved and sustained by solidifying collaborations between communities and health-care providers. This collaborative approach will improve health equity by building communities that promote health rather than disease, have more accessible and direct care, and focus the health-care system on improving population health.

Background: The prevalence of male obesity is increasing but few men take part in weight loss programmes. We assessed the eff ect of a weight loss and healthy living programme on weight loss in football (soccer) fans. Methods: We did a two-group, pragmatic, randomised controlled trial of 747 male football fans aged 35-65 years with a body-mass index (BMI) of 28 kg/m2 or higher from 13 Scottish professional football clubs. Participants were randomly assigned with SAS (version 9.2, block size 2-9) in a 1:1 ratio, stratifi ed by club, to a weight loss programme delivered by community coaching staff in 12 sessions held every week. The intervention group started a weight loss programme within 3 weeks, and the comparison group were put on a 12 month waiting list. All participants received a weight management booklet. Primary outcome was mean diff erence in weight loss between groups at 12 months, expressed as absolute weight and a percentage of their baseline weight. Primary outcome assessment was masked. Analyses were based on intention to treat. The trial is registered with Current Controlled Trials, number ISRCTN32677491. Findings: 374 men were allocated to the intervention group and 374 to the comparison group. 333 (89%) of the intervention group and 355 (95%) of the comparison group completed 12 month assessments. At 12 months the mean diff erence in weight loss between groups, adjusted for baseline weight and club, was 4.94 kg (95% CI 3.95-5.94) and percentage weight loss, similarly adjusted, was 4.36% (3.64-5.08), both in favour of the intervention (p

Summary Cancer is a global and growing, but not uniform, problem. An increasing proportion of the burden is falling on low-income and middle-income countries because of not only demographic change but also a transition in risk factors, whereby the consequences of the globalisation of economies and behaviours are adding to an existing burden of cancers of infectious origin. We argue that primary prevention is a particularly effective way to fight cancer, with between a third and a half of cancers being preventable on the basis of present knowledge of risk factors. Primary prevention has several advantages: the effectiveness could have benefits for people other than those directly targeted, avoidance of exposure to carcinogenic agents is likely to prevent other non-communicable diseases, and the cause could be removed or reduced in the long term—eg, through regulatory measures against occupational or environmental exposures (ie, the preventive effort does not need to be renewed with every generation, which is especially important when resources are in short supply). Primary prevention must therefore be prioritised as an integral part of global cancer control.

Background Metabolic syndrome is characterised by the presence of several metabolic abnormalities, including hyperglycaemia, central obesity (also known as abdominal obesity), elevated blood pressure, and an abnormal blood lipid profile. The prevalence of metabolic syndrome is rising rapidly around the world as childhood obesity is increasing. The aim of this study is to determine the prevalence of metabolic syndrome in school children aged 6–18 years residing in Ein Alhelwe Refugee camp in Saida, Lebanon. Methods School children aged 6–18 years from the first to twelfth grades from two United Nations Relief and Works Agency (UNRWA) schools were randomly chosen. We used a school-based cross-sectional study design with two stages. The first stage included measurements of weight, height, body mass index (BMI), waist circumference, and blood pressure. In the second stage, blood tests were carried out for fasting blood sugar, triglycerides, and high-density lipoprotein (HDL). Approval was obtained from the ethics committee at Al Hamshari Hospital in Saida, Lebanon. Written permission was obtained from the UNRWA and the principals of the two schools for the first stage, and informed written consent was obtained from parents on behalf of the children involved in the second stage of the study. Findings The first stage of the research included 487 participants (258 female, 229 male) and the second stage included 73 participants (36 overweight participants [12 male, 24 female] and 37 obese participants [19 male, 18 female]). The prevalence of overweight and obesity were 15·2% (74 of 487) and 14·4% (70 of 487) among all age groups, respectively. Among Palestinian refugee school children in Saida aged 10–18 years, the prevalence of metabolic syndrome was more pronounced when the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) definition was used (30·9%; 21 of 68) compared to the International Diabetes Federation (IDF) definition (11·8%; eight of 68), with no statistical differences between male and female participants. Note that the IDF definition can be applied to children aged 10–18 years, of whom there were 68 participants, and for comparison between IDF and NCEP ATP-III, prevalence of metabolic syndrome was calculated for participants in this age range. Low HDL cholesterol (52·1%; 38 of 73), central obesity (46·6%; 34 of 73), and raised blood pressure (42·5%; 31 of 73) were the leading three common metabolic abnormalities among children who were overweight or obese. Interpretation This study has shown that metabolic syndrome is common among children who are obese or overweight, who are aged 10–18 years, living in Ein Al-Helwa Refugee Camp in Saida, Lebanon. These data raise the importance of early prevention and treatment of metabolic syndrome and its components (abdominal obesity, elevated triglycerides, reduced HDL cholesterol, elevated blood pressure, and elevated blood glucose) to reduce the risk of diabetes and cardiovascular complications in susceptible individuals. A potential limitation of this study is that the small sample size may not accurately reflect the prevalence of metabolic syndrome. Funding Palestinian Civil Society Organizations Commission, Life Hope Center, and Palestinian Red Crescent Society Al Hamshari Hospital.

Background Obesity is a global public health issue and worldwide rates of childhood obesity are ten times higher than 40 years ago. A limited number of studies have been conducted to determine the prevalence of preschool obesity and overweight and associated factors in Palestinian children. The aim of this study was to examine sociodemographic and economic factors associated with preschool overweight and obesity in Palestinian children younger than 5 years of age. Methods We used data from the fifth Palestinian Multiple Indicator Cluster Survey (MICS5), a cross-sectional survey of a representative sample of Palestinian households in 2014. The analysis was based on 6853 children (after excluding children whose z-score was out of range or not measured) below 5 years of age (46% [3152 out of 6853] in the Gaza Strip and 54% [3701 out of 6853] in the West Bank), drawn from 7816 completed surveys of a multi-stage cluster sample (99% response rate). The z-scores for BMI-for-age of children were used to evaluate weight status. Underweight, overweight, and obesity were defined as the proportion of preschool children with z-score values of 2 SDs or less, greater than 2 SDs, and greater than 3 SDs, respectively, from the WHO Child Growth Standards. Covariates included gender, age, area and region, number of children per household, mother's level of education, marital status of the mother, mother's age at birth, and wealth quantile (which we used as a composite indicator of wealth, with the first quintile representing the poorest households, and the fifth quintile representing the wealthiest households). We used multiple logistic regression analysis to estimate adjusted odds ratios (AORs) with 95% confidence intervals (CIs). Findings The overall prevalence of overweight and obesity in Palestinian children (birth to 5 years) was 8·8% (95% CI 8·1–9·4); 7·3% were overweight and 1·5% were obese. The prevalence of underweight was 1·4%. The odds of overweight and obesity were lower among children in the Gaza Strip than in the West Bank (AOR=0·74; 95% CI 0·61–0·90). Girls were less likely to be obese and overweight than boys (AOR=0·75; 95% CI 0·63–0·89). Children under 4 years of age had a higher risk of being obese and overweight than children aged 4–5 years. Children who lived in the wealthiest households (fifth quintile) were more likely to be overweight and obese than children in the poorest (first) quintile (AOR=1·36; 95% CI 1·09–1·71). Interpretation The prevalence of obesity and overweight among preschool children in Palestine (8·8%) is higher than the global prevalence (6·7%; derived using the same standardised method as in this study, and using the WHO Child Growth Standards to assess the nutritional status of children). Obesity and overweight were more likely to affect children from wealthier households, children from the West Bank, boys, and younger children. Excessive weight gain in early childhood is a strong predictor of adulthood obesity. Routine assessment of all children needs to become standard clinical practice from very early childhood. Effective management and preventive interventions are needed to tackle the increasing obesity problem in preschool children. Funding None.

Background Diabetes is of growing concern, as the global prevalence of this disease in adults over 18 years of age has risen from 4·7% in 1980 to 8·5% in 2014. Type 2 diabetes makes up approximately 90% of global diabetes cases and is largely the result of unhealthy lifestyle. The aim of this study was to assess the risk factors for developing diabetes in the Palestinian population residing in Lebanon, with the intention of helping to prevent diabetes in this population. Methods A cross-sectional study was conducted in 18 UNRWA centres randomly selected from across Lebanon between April and May, 2016, involving 1162 people aged 18–74 years (all eligible people in this age range who attended the health centres and agreed to be enrolled in this survey). A questionnaire based on a modified version of the Canadian Diabetes Risk Survey was used to collect and score information about BMI, waist circumference, age, gender, physical activity, fruit and vegetable intake, level of education, and family history of diabetes. Informed verbal consent was obtained from all participants. Findings Of the Palestine refugees in Lebanon aged 18–74 years, 25·8% (299 of 1162) were at risk of diabetes. For these individuals, the risk factors were obesity or being overweight (68·4%), large waist circumference (>92 cm for males >80 cm for females; 62·3%), low physical activity (eg, walking for less than 30 minutes per day; 49·9%), low fruit and vegetable intake (46·0% ate fruits and vegetables every day), and family history of diabetes (68·5%). These risk factor levels have been associated with high risk of developing diabetes within 10 years in other populations. In our sample population, the risk of developing diabetes is higher with age (60·6% for people aged 45 years or over vs 3·1% for people under 45 years), male sex (36·9% risk vs 26% for females), and lower level of education (31·2% for people with preparatory and secondary level of education (school grades 1 to 9) vs 12·7% for people with a high school (school grades 10 to 12; pre-university) or university degree. Interpretation Risk factors for developing diabetes are widely present among Palestine refugees in Lebanon, leading to a relatively high risk of developing diabetes (for example, compared to Canada). Awareness campaigns and educational sessions should be conducted at community level. Topics will include simple lifestyle modifications that have been shown to be effective in preventing or delaying the onset of type 2 diabetes and its complications. Funding None.