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Although hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers.

Aims To describe and compare the health system responses for type 1 diabetes in Kyrgyzstan, Mali, Peru and Tanzania. Methods The Rapid Assessment Protocol for Insulin Access, a multi-level assessment of the health system, was implemented in Kyrgyzstan, Mali, Peru and Tanzania using document reviews, site visits and interviews to assess the delivery of care and access to insulin. Results Despite the existence of noncommunicable or diabetes strategies and Universal Health Coverage policies including diabetes-related supplies, this has not necessarily translated into access to insulin or diabetes care for all. Insulin and related supplies were often unavailable and unaffordable. Across the four countries test strips and insulin, when paid for by the individual, represented respectively 48-82% and 25-36% of total costs. Care was mainly delivered at tertiary-level hospitals by specialists. Only Kyrgyzstan had data collection systems integrated into the Ministry of Health structure. In addition, issues with healthcare worker training and education and empowerment of people with diabetes were present in these health systems. Conclusions People with type 1 diabetes in these countries face different barriers, including the cost of insulin and care. Given the renewed attention to diabetes on the global health agenda tailored health system responses for type 1 diabetes are needed. Insulin should be prioritized as it is the foundation of type 1 diabetes care, but other elements of care and support need to be fostered by different actors.

Non-governmental organizations play a vital part in the achievement of the Sustainable Development Goals as defined by the United Nations. These Goals also include targets related to noncommunicable diseases. However, non-governmental organizations have played a limited role in this area despite such diseases causing the bulk of morbidity and mortality worldwide. Through their activities, non-governmental organizations should aim to strengthen health systems, yet they often only support these for a single disease. Mali, like many other low- and middle-income countries, is facing an increasing burden of diabetes and a health system not adapted to address this challenge. Santé Diabète, a non-governmental organization based in Mali since 2003, has been working specifically on diabetes, and has developed a wide range of activities to improve the national health system. This paper describes changes in the diabetes environment in Mali between 2004 and 2018 based on two health system assessments carried out using a Rapid Assessment Protocol. Over this period, the health system was strengthened with regard to financing and access to medical products. Leadership and governance, service delivery and health workforce were all improved but still partially rely on sustained support from Santé Diabète. The key lesson from this study is that to be effective in changing the management of noncommunicable diseases in a low- and middle-income country, non-governmental organizations need to play a variety of roles, many of which may change over time.

OBJECTIVE Glycemic regression is common in real-world settings, but the contribution of regression to the mean (RTM) has been little investigated. We aimed to estimate glycemic regression before and after adjusting for RTM in a free-living cohort of adults with newly ascertained diabetes and intermediate hyperglycemia (IH). RESEARCH DESIGN AND METHODS The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a cohort study of 15,105 adults screened between 2008 and 2010 with standardized oral glucose tolerance test and HbA1c, repeated after 3.84 ± 0.42 years. After excluding those receiving medical treatment for diabetes, we calculated partial or complete regression before and after adjusting baseline values for RTM. RESULTS Regarding newly ascertained diabetes, partial or complete regression was seen in 49.4% (95% CI 45.2–53.7); after adjustment for RTM, in 20.2% (95% CI 12.1–28.3). Regarding IH, regression to normal levels was seen in 39.5% (95% CI 37.9–41.3) or in 23.7% (95% CI 22.6–24.3), depending on use of the World Health Organization (WHO) or the American Diabetes Association (ADA) definition, respectively; after adjustment, corresponding frequencies were 26.1% (95% CI 22.4–28.1) and 19.4% (95% CI 18.4–20.5). Adjustment for RTM reduced the number of cases detected at screening: 526 to 94 cases of diabetes, 3,118 to 1,986 cases of WHO-defined IH, and 6,182 to 5,711 cases of ADA-defined IH. Weight loss ≥2.6% was associated with greater regression from diabetes (relative risk 1.52, 95% CI 1.26–1.84) and IH (relative risk 1.30, 95% CI 1.17–1.45). CONCLUSIONS In this quasi–real-world setting, regression from diabetes at ∼4 years was common, less so for IH. Regression was frequently explained by RTM but, in part, also related to improved weight loss and homeostasis over the follow-up.

Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or "vasocrine" signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery (GA) diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring heat shock proteins 90ab1 and 70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV and V. These data highlight the importance of PVAT in vascular and metabolic physiology, and are likely relevant for obesity and diabetes.

Background. Personalizing medical treatment often requires practitioners to compare multiple treatment options, assess a patient’s unique risk and benefit from each option, and elicit a patient’s preferences around treatment. We integrated these 3 considerations into a decision-modeling framework for the selection of second-line glycemic therapy for type 2 diabetes. Methods. Based on multicriteria decision analysis, we developed a unified treatment decision support tool accounting for 3 factors: patient preferences, disease outcomes, and medication efficacy and safety profiles. By standardizing and multiplying these 3 factors, we calculated the ranking score for each medication. This approach was applied to determining second-line glycemic therapy by integrating 1) treatment efficacy and side-effect data from a network meta-analysis of 301 randomized trials ( N = 219,277), 2) validated risk equations for type 2 diabetes complications, and 3) patient preferences around treatment (e.g., to avoid daily glucose testing). Data from participants with type 2 diabetes in the U.S. National Health and Nutrition Examination Survey (NHANES 2003–2014, N = 1107) were used to explore variations in treatment recommendations and associated quality-adjusted life-years given different patient features. Results. Patients at the highest microvascular disease risk had glucagon-like peptide 1 agonists or basal insulin recommended as top choices, whereas those wanting to avoid an injected medication or daily glucose testing had sodium-glucose linked transporter 2 or dipeptidyl peptidase 4 inhibitors commonly recommended, and those with major cost concerns had sulfonylureas commonly recommended. By converting from the most common sulfonylurea treatment to the model-recommended treatment, NHANES participants were expected to save an average of 0.036 quality-adjusted life-years per person (about a half month) from 10 years of treatment. Conclusions. Models can help integrate meta-analytic treatment effect estimates with individualized risk calculations and preferences, to aid personalized treatment selection.

Reduced vasodilator properties of insulin in obesity are caused by changes in perivascular adipose tissue and contribute to microvascular dysfunction in skeletal muscle. The causes of this dysfunction are unknown. The effects of a short-term Western diet on JNK2-expressing cells in perivascular adipose tissue (PVAT) on insulin-induced vasodilation and perfusion of skeletal muscle were assessed. In vivo, 2 wk of Western diet (WD) reduced whole body insulin sensitivity and insulin-stimulated muscle perfusion, determined using contrast ultrasonography during the hyperinsulinemic clamp. Ex vivo, WD triggered accumulation of PVAT in skeletal muscle and blunted its ability to facilitate insulin-induced vasodilation. Labeling of myeloid cells with green fluorescent protein identified bone marrow as a source of PVAT in muscle. To study whether JNK2-expressing inflammatory cells from bone marrow were involved, we transplanted JNK2−/− bone marrow to WT mice. Deletion of JNK2 in bone marrow rescued the vasodilator phenotype of PVAT during WD exposure. JNK2 deletion in myeloid cells prevented the WD-induced increase in F4/80 expression. Even though WD and JNK2 deletion resulted in specific changes in gene expression of PVAT; epididymal and subcutaneous adipose tissue; expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, or protein inhibitor of STAT1 was not affected. In conclusion, short-term Western diet triggers infiltration of JNK2-positive myeloid cells into PVAT, resulting in PVAT dysfunction, nonclassical inflammation, and loss of insulin-induced vasodilatation in vivo and ex vivo. NEW & NOTEWORTHY We demonstrate that in the earliest phase of weight gain, changes in perivascular adipose tissue in muscle impair insulin-stimulated muscle perfusion. The hallmark of these changes is infiltration by inflammatory cells. Deletion of JNK2 from the bone marrow restores the function of perivascular adipose tissue to enhance insulin’s vasodilator effects in muscle, showing that the bone marrow contributes to regulation of muscle perfusion.

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There exists a level of glycaemia defined by WHO as ‘intermediate hyperglycaemia (IH).’ Over the last 20 years, however, the term ‘prediabetes’ has dominated both the scientific literature and the media. At the PODC in 2014, this author argued that the epidemic of ‘prediabetes’ was a classic example of overdiagnosis, driven by the agendas of professional associations and the medical-industrial complex. This presentation will update the literature on ‘prediabetes,’ and report evidence from a recent piece of investigative journalism supporting this contention. The definition of IH recognised by WHO is based on a glucose tolerance test, and termed Impaired Glucose Tolerance (IGT). In 2005, the prevalence of IGT in US adults was 13.7%. Successive changes to the diagnostic criteria applied by the American Diabetes Association (ADA) included: Using fasting plasma glucose–based criteria (‘Impaired Fasting Glucose’ (IFG)); Lowering the cut–point for IFG from 6.1mmol/l to 5.6mmol/l; Adding a category based on levels of glycated haemoglobin (HbA1c); and Lowering the cut–point of HbA1c from 6.0% to 5.7%. Defining ‘Pre–Diabetes’ as comprising any of these 3 abnormalities. Other bodies have not adopted these changes, and generally oppose the use of the term ‘Pre-Diabetes,’ mainly because most such people never progress to develop diabetes. But the consequence of these successive changes is that the prevalence of ADA-defined ‘Pre-Diabetes’ in US adults, is now 33.9%, or 84 million people. In China, using the WHO criterion of IGT, this proportion is 8.3% (82 million adults). With the ADA criteria, however, the prevalence is estimated to be 50.1% (493 million adults). The American Diabetes Association publishes annual Standards of Care, advising weight loss and physical activity as the mainstay of management. In 2007 it started recommending using metformin to treat high-risk people with ‘Pre-Diabetes’ whose measures did not respond to such treatment. More recently, however, the recommendations have included use of a range of more expensive drugs. All such treatments would be ‘off-label,’ as none has been approved for such use by the US Food and Drug Administration. In a recent article in Science, Piller has reported the origin of the ADA’s use of the term ‘Pre-Diabetes.’ He describes a meeting in 2001 between the Public Relations chief of the ADA and its then Chief Scientific Officer Richard Kahn to explore ways to engage the public in taking seriously slight elevations of glucose levels. At a meeting at the National Institutes of Health, they came up with the idea of using the little-used term ‘Pre-Diabetes’ in place of IFG and IGT in all their literature. The article also used the Open Payments database to explore Conflicts of Interest among the ADA advisers. One senior clinical academic, who has authored studies, such as ACT NOW and STOP DIABETES, of off-label treatments has received $5million from pharmaceutical companies for research funding and $1.3million in consultation fees and travel between 2013 and 2017. Furthermore, during the period covered by this database, 41% of the authors of ADA Standards of Care received at least $10,000 in funding from pharmaceutical companies. Objectives To document the corporate drivers of the epidemic in pre diabetes. Method Literature review and interviews with key informants. Results The term pre diabetes was coined at a 2001 meeting between public relations experts and a scientist working for the American Diabetes Association. Many of the panel who advise on standards of care for the American Diabetes Association have substantial funding from the manufacturers of the drugs recommended for off-label use. Conclusions There is new evidence supporting the contention that the ‘epidemic of pre diabetes‘ is at least in part commercially driven.

OBJECTIVE We sought to validate Risk Equations for Complications of Type 2 Diabetes (RECODe) among diverse populations. RESEARCH DESIGN AND METHODS We compared risk predictions from RECODe equations and from two alternative risk models (UK Prospective Diabetes Study Outcomes Model 2 [UKPDS OM2] and American College of Cardiology/American Heart Association Pooled Cohort Equations) to observed outcomes in two studies: the Multi-Ethnic Study of Atherosclerosis (MESA, n = 1,555 adults with type 2 diabetes, median follow-up 9.1 years) and the Jackson Heart Study (JHS, n = 1,746 adults with type 2 diabetes, median follow-up 8.0 years). Outcomes included nephropathy by multiple measures (microalbuminuria, macroalbuminuria, renal failure, end-stage renal disease, and reduction in glomerular filtration rate), moderate to severe diabetic retinopathy by Airlie House classification, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, congestive heart failure, and all-cause mortality. RESULTS RECODe equations for microvascular and cardiovascular outcomes had C-statistics for discrimination ranging from 0.71 to 0.85 in MESA and 0.64 to 0.91 in JHS for alternative outcomes. Calibration slopes in MESA ranged from 0.62 for a composite nephropathy outcome, 0.83–1.04 for individual nephropathy outcomes, 1.07 for retinopathy, 1.00–1.05 for cardiovascular outcomes, and 1.03 for all-cause mortality. Slopes in JHS ranged from 0.47 for retinopathy, 0.97–1.16 for nephropathy, 0.72–1.05 for cardiovascular outcomes, and 1.01 for all-cause mortality. The alternative models had C-statistics 0.50–0.72 and calibration slopes 0.07–0.60. CONCLUSIONS RECODe equations improved risk estimation for diverse patients with type 2 diabetes, as compared with two commonly used alternatives.

Obesity is a global epidemic, accompanied by increased risk of type 2 diabetes and cardiovascular disease. Adipose tissue hypertrophy is associated with adipose tissue inflammation, which alters secretion of adipose tissue-derived bioactive products, known as adipokines. Adipokines determine vessel wall properties such as smooth muscle tone and vessel wall inflammation. Exercise is a mainstay of prevention of chronic, non-communicable diseases, type 2 diabetes and cardiovascular disease in particular. Aside from reducing adipose tissue mass, exercise has been shown to reduce inflammatory activity in this tissue. Mechanistically, contracting muscles release bioactive molecules known as myokines, which have been shown to alter adipose tissue metabolic phenotype. In adipose tissue, myokines induce browning, enhance fatty acid oxidation and improve insulin sensitivity. In the past years, so-called perivascular adipose tissue surrounding the vasculature (PVAT) has been shown to control vascular tone and inflammation through local release of adipokines. In obesity, an increase in mass and inflammation of PVAT culminate in dysregulation of adipokine secretion, which contributes to vascular dysfunction. This review describes our current understanding of the mechanisms by which active muscles interact with adipose tissue and improve vascular function. Aside from the exercise-dependent regulation of canonical adipose tissue function, we will focus on interaction between skeletal muscle and PVAT and the role of novel myokines, such as interleukin-15, fibroblast growth factor 21 and irisin, in this cross talk.

Background. Patients and clinicians are often required to make tradeoffs between the relative benefits and harms of multiple treatment options. Combining network meta-analysis results with user preferences can be useful when choosing among several treatment alternatives. Objective. Using cholesterol-lowering statin drugs as a case study, we aimed to determine whether an interactive web-based platform that combines network meta-analysis findings with patient preferences had an effect on the decision-making process in a general population sample. Method. This was a pilot parallel randomized controlled trial. We used Amazon’s Mechanical Turk to recruit adults residing in the United States. A total of 349 participants were randomly allocated to view either the interactive tool (intervention) or a series of bar charts (control). The primary endpoint was decisional conflict, and secondary endpoints included decision self-efficacy, preparation for decision making, and the overall ranking of statins. Results. A total of 258 participants completed the trial and were included in the analysis. On the primary outcome, participants randomized to the interactive tool had significantly lower levels of decisional conflict than those in the control group (difference, –8.53; 95% confidence interval [CI], −12.96 to −4.11 on a 100-point scale; P = 0.001). They also appeared to have higher levels of preparation for decision making (difference, 4.19; 95% CI, –0.24 to 8.63 on a 100-point scale; P = 0.031). No difference was found for decision self-efficacy, although groups were statistically significantly different in how they ranked different statins. Conclusion. The findings of our proof-of-concept evaluation suggest that an interactive web-based tool combining published clinical evidence with individual preferences can reduce decisional conflict and better prepare individuals for decision making.

Aims Registries and health plans estimate insulin need for population health metrics. We sought to identify how such estimates affect population- and individual-level estimates of over- and under-treatment. Methods We developed a microsimulation comparing estimated insulin need to dispensation using the National Health and Nutrition Examination Survey (NHANES, 2005–2016, N= 2832) and Medical Expenditure Panel Survey (MEPS, 2005–2016, N = 29,615). Results From NHANES, ~21.6% of people with type 2 diabetes would require insulin to achieve a HbA1c target of 7% after maximum titration of two non-insulins (60.7 IU/person/day, or 84,629,833 vials of 1000 IU in the US). From MEPS, we observed 57.4 IU/person/day of insulin dispensed (81,585,842 vials). About 29% of people were dispensed at least two standard deviations less than their estimated need, and 22% at least two standard deviations more than estimated need. Population-level need estimates reduced 39.4% if liberalizing HbA1c targets to 8% for people ≥75 years old. Conclusions Estimated insulin needs of people with type 2 diabetes in the U.S. are consistent with their dispensed insulin at the population level, but are sensitive to HbA1c targets for older adults, and conceal under- and over-treated subpopulations.

Background— The World Health Organization aims to reduce mortality from chronic diseases including cardiovascular disease (CVD) by 25% by 2025. High blood pressure is a leading CVD risk factor. We sought to compare 3 strategies for treating blood pressure in China and India: a treat-to-target (TTT) strategy emphasizing lowering blood pressure to a target, a benefit-based tailored treatment (BTT) strategy emphasizing lowering CVD risk, or a hybrid strategy currently recommended by the World Health Organization. Methods and Results— We developed a microsimulation model of adults aged 30 to 70 years in China and in India to compare the 2 treatment approaches across a 10-year policy-planning horizon. In the model, a BTT strategy treating adults with a 10-year CVD event risk of ≥10% used similar financial resources but averted ≈5 million more disability-adjusted life-years in both China and India than a TTT approach based on current US guidelines. The hybrid strategy in the current World Health Organization guidelines produced no substantial benefits over TTT. BTT was more cost-effective at $205 to $272/disability-adjusted life-year averted, which was $142 to $182 less per disability-adjusted life-year than TTT or hybrid strategies. The comparative effectiveness of BTT was robust to uncertainties in CVD risk estimation and to variations in the age range analyzed, the BTT treatment threshold, or rates of treatment access, adherence, or concurrent statin therapy. Conclusions— In model-based analyses, a simple BTT strategy was more effective and cost-effective than TTT or hybrid strategies in reducing mortality.

[No abstract]

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland.

The purpose of this review is to highlight the key issues with regard to the value, affordability, and availability of diabetes treatments. Many of the medicines needed to manage diabetes are available as generics and, if purchased appropriately, can be made affordable to many individuals and systems. With new treatments for diabetes, additional costs to individuals and systems need to be assessed in terms of added clinical benefit and financial impact. As healthcare finances are limited, increased spending on diabetes medicines means fewer resources for other areas of diabetes care or for the population as a whole. This increased expenditure is driven by rising prevalence as well as the cost of newer treatments. With an increasing burden of disease and changing patterns of medicines in the market, we stress the need to focus attention on ensuring access for individuals to essential medicines. Universal health care offers unique opportunity to address the issue of access to medicines and the wider issues surrounding access to diabetes care, but this will require concerted action bringing together governments, civil society and the private sector.

Insulin was discovered in 1921 and soon became widely available in high-income countries. However, many people currently in need of this life-saving medicine are unable to access it. This is a global phenomenon, impacting not only populations of low- and middle-income countries but low-income populations in the U.S. In the U.S., the rate of diabetic ketoacidosis remains high in certain subpopulations, the cost of insulin being the main precipitating factor. On a global level the main cause of mortality for a child with type 1 diabetes is a lack of access to insulin, and in sub-Saharan Africa the life expectancy of a child with type 1 diabetes can be as low as 1 year. One lens for considering the issue of access to health and medicines is to consider society as a three-legged stool. In this paradigm, the role of the public sector is to provide “protections” to the population it serves; the private sector is made up of “responsible businesses” that supply many of the goods and services people need; and the plural sector comprises communities and not-for-profits providing the “social affiliations” that are needed. For HIV/AIDS, each of these “legs” played a role in improving access. Civil society raised awareness of the issue and advocated for access to treatment. Governments provided funding and responses both nationally and globally. Finally, the private sector played its role, under pressure from civil society and governments, in lowering the price of medicines and developing programs to expand access. Here, we use this framework to describe the shortcomings in access to insulin from a U.S. and global perspective.

Early life stunting may have long-term effects on body composition, resulting in obesity-related comorbidities. We tested the hypothesis that individuals stunted in early childhood may be at higher cardiometabolic risk later in adulthood. 1753 men and 1781 women participating in the 1982 Pelotas (Brazil) birth cohort study had measurements of anthropometry, body composition, lipids, glucose, blood pressure, and other cardiometabolic traits at age 30 years. Early stunting was defined as height-for-age Z-score at age 2 years below -2 against the World Health Organization growth standards. Linear regression models were performed controlling for sex, maternal race/ethnicity, family income at birth, and birthweight. Analyses were stratified by sex when p-interaction

Background: Several studies have reported on associations of size at birth and early growth with general and central obesity; however, few have examined the potential effects of birth weight and postnatal growth on separate abdominal fat compartments. We investigated the effects of size at birth, linear growth and relative weight gain from birth to adulthood on visceral (VFT) and subcutaneous abdominal (SAFT) fat thicknesses at age 30 years. Methods: A total of 2663 participants from the 1982 Pelotas (Brazil) birth cohort study had complete information on ultrasound measures of abdominal fat at age 30 years, and anthropometric measurements for at least five visits (0/2/4/23/30 years). We estimated weight and height Z-score changes, conditional relative weight gain and conditional height at several ages. Results: In both men and women, VFT and SAFT showed positive associations with conditional relative weight gain during all age periods beyond 2 years and birth, respectively (all P⩽0.01). Women born with intrauterine growth restriction (IUGR) had greater VFT than other women (difference=0.15 s.d., 95% CI: 0.01–0.29), and they showed a stronger positive influence of infant weight gain 0–2 years on VFT (IUGR: β=0.17 s.d., 95% CI: 0.05–0.29; non-IUGR: β=0.01 s.d., 95% CI: −0.04 to 0.06; Pinteraction=0.02). Stunting at 2 years was associated with lower SAFT but not VFT, and it modified the influence of weight gain 2–4 years on SAFT in both sexes (both Pinteraction

Background and aims: Cardiovascular and all-cause mortality in relation to various anthropometric measures of obesity is still controversial. Methods and results: Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), A Body Shape Index (ABSI) and waist-to-hip-to-height ratio (WHHR) were measured at baseline in a cohort of 46,651 European men and women aged 24-99 years. The relationship between anthropometric measures of obesity and mortality was evaluated by the Cox proportional hazards model with age as a time-scale and with threshold detected by a piecewise regression model. Over a median follow-up of 7.9 years, 2381 men and 1055 women died, 1071 men (45.0%) and 339 women (32.1%) from cardiovascular disease (CVD). BMI had a J-shaped relationship with CVD mortality, whereas anthropometric measures of abdominal obesity had positive linear relationships. BMI, WC and WHtR showed J-shaped associations with all-cause mortality, whereas WHR, ABSI and WHHR demonstrated positive linear relationships. Accordingly, a threshold value was detected at 29.29 and 30.98 kg/m(2) for BMI, 96.4 and 93.3 cm for WC, 0.57 and 0.60 for WHtR, 0.0848 and 0.0813 m(11/6) kg(-2/3) for ABSI with CVD mortality in men and women, respectively; 29.88 and 29.50 kg/m(2) for BMI, 104.3 and 105.6 for WC, 0.61 and 0.67 for WHtR, 0.95 and 0.86 for WHR, 0.0807 and 0.0765 for ABSI in men and women, respectively, and 0.52 for WHHR in women with all-cause mortality. Conclusion: All anthropometric measures of abdominal obesity had positive linear associations with CVD mortality, whereas some showed linear and the others J-shaped relationships with all-cause mortality. BMI had a J-shaped relationship with either CVD or all-cause mortality. Thresholds detected based on mortality may help with clinical definition of obesity in relation to mortality.

Summary Background In view of substantial mis-estimation of risks of diabetes complications using existing equations, we sought to develop updated Risk Equations for Complications Of type 2 Diabetes (RECODe). Methods To develop and validate these risk equations, we used data from the Action to Control Cardiovascular Risk in Diabetes study (ACCORD, n=9635; 2001–09) and validated the equations for microvascular events using data from the Diabetes Prevention Program Outcomes Study (DPPOS, n=1018; 1996–2001), and for cardiovascular events using data from the Action for Health in Diabetes (Look AHEAD, n=4760; 2001–12). Microvascular outcomes were nephropathy, retinopathy, and neuropathy. Cardiovascular outcomes were myocardial infarction, stroke, congestive heart failure, and cardiovascular mortality. We also included all-cause mortality as an outcome. We used a cross-validating machine learning method to select predictor variables from demographic characteristics, clinical variables, comorbidities, medications, and biomarkers into Cox proportional hazards models for each outcome. The new equations were compared to older risk equations by assessing model discrimination, calibration, and the net reclassification index. Findings All equations had moderate internal and external discrimination (C-statistics 0·55–0·84 internally, 0·57–0·79 externally) and high internal and external calibration (slopes 0·71–1·31 between observed and estimated risk). Our equations had better discrimination and calibration than the UK Prospective Diabetes Study Outcomes Model 2 (for microvascular and cardiovascular outcomes, C-statistics 0·54–0·62, slopes 0·06–1·12) and the American College of Cardiology/American Heart Association Pooled Cohort Equations (for fatal or non-fatal myocardial infarction or stroke, C-statistics 0·61–0·66, slopes 0·30–0·39). Interpretation RECODe might improve estimation of risk of complications for patients with type 2 diabetes. Funding National Institute for Diabetes and Digestive and Kidney Disease, National Heart, Lung and Blood Institute, and National Institute on Minority Health and Health Disparities, National Institutes of Health, and US Department of Veterans Affairs.

We aimed to identify the independent associations of genomic ancestry and education level with abdominal fat distributions in the 1982 Pelotas birth cohort study, Brazil. In 2,890 participants (1,409 men and 1,481 women), genomic ancestry was assessed using genotype data on 370,539 genome-wide variants to quantify ancestral proportions in each individual. Years of completed education was used to indicate socio-economic position. Visceral fat depth and subcutaneous abdominal fat thickness were measured by ultrasound at age 29-31y; these measures were adjusted for BMI to indicate abdominal fat distributions. Linear regression models were performed, separately by sex. Admixture was observed between European (median proportion 85.3), African (6.6), and Native American (6.3) ancestries, with a strong inverse correlation between the African and European ancestry scores (ρ = -0.93; p

SummaryObjectives We postulated the mechanism for the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and insulin sensitivity might relate to changes in blood flow regulation. We studied the association of this polymorphism with insulin action, and insulin-mediated changes in limb blood flow (LBF), under conditions of high and low salt intake. We also studied effects of genotype and salt loading on renin–angiotensin–aldosterone system (RAAS) activity. Materials/Methods Twenty people with (10 I/I; 10 D/D) and 23 without (10 I/I; 13 D/D), type 2 diabetes were studied during 6 days of 40 mmol/day and 220 mmol/day sodium diet in a randomized, double-blind cross-over fashion. On the sixth day of each condition, we measured 24-h blood pressure, plasma volume, LBF and insulin sensitivity during hyperinsulinaemic clamp at low (40 mU/m2/min) and high (600 mU/m2/min) dose insulin infusion. Results Salt intake variation produced greater effects on the renin–angiotensin–aldosterone system than ACE genotype. Diabetes status and insulin infusion were associated with differences in the metabolic clearance rate of glucose, (P

Body mass index (BMI) is the most commonly used surrogate marker for evaluating the risk of cardiovascular disease (CVD) mortality in relation to general obesity, while abdominal obesity indicators have been proposed to be more informative in risk prediction.A prospective cohort study consisting of 46 651 Europeans aged 24-99 years was conducted to investigate the relationship between CVD mortality and different obesity indicators including BMI, waist circumference (WC), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), A Body Shape Index (ABSI) and waist-to-hip-to-height ratio (WHHR). Hazard ratio (HR) was estimated by the Cox proportional hazards model using age as timescale, and compared using paired homogeneity test.During a median follow-up of 7.9 years, 3435 participants died, 1409 from CVD. All obesity indicators were positively associated with increased risk of CVD mortality, with HRs (95% confidence intervals) per standard deviation increase of 1.19 (1.12-1.27) for BMI, 1.29 (1.21-1.37) for WC, 1.28 (1.20-1.36) for WHR, 1.35 (1.27-1.44) for WSR, 1.34 (1.26-1.44) for ABSI and 1.34 (1.25-1.42) for WHHR in men and 1.37 (1.24-1.51), 1.49 (1.34-1.65), 1.45 (1.31-1.60), 1.52 (1.37-1.69), 1.32 (1.18-1.48) and 1.45 (1.31-1.61) in women, respectively. The prediction was stronger with abdominal obesity indicators than with BMI or ABSI (P0.05 for all paired homogeneity tests). WSR appeared to be the strongest predictor among all the indicators, with a linear relationship with CVD mortality in both men and women.Abdominal obesity indicators such as WC, WHR, WSR and WHHR, are stronger predictors for CVD mortality than general obesity indicator of BMI.

Objective The mechanisms underlying obesity-related hypertension are incompletely understood. Microvascular dysfunction might play a role by increasing peripheral vascular resistance (PVR). Metabolic and microvascular effects of insulin are impaired in obesity, but how these impairments contribute to disturbed blood pressure homeostasis is unclear. Specifically, it is unknown whether local microvascular vasoactive effects of insulin play a role in determining systemic vascular resistance. The aim of this study was to investigate the association between PVR and local microvascular effects of insulin. Design and Methods Thirty-seven healthy, overweight subjects (age 25-55 years, BMI 25-30 kg/m2) were cross-sectionally studied. Local insulin-mediated vasodilation was measured using skin laser Doppler fluxmetry combined with transcutaneous iontophoresis of insulin. For comparison, local vasodilatory effects of acetylcholine and sodium nitroprusside were measured. PVR was calculated from mean arterial pressure and cardiac output, assessed by pulse-dye densitometry. Results PVR was inversely correlated with insulin-mediated vasodilation (r = −0.50; P < 0.01). This finding was maintained after adjustment for age, sex, blood pressure, and smoking. PVR was not associated with local microvascular effects of acetylcholine. Conclusions Our study in overweight subjects suggests that insulin's role in the microvasculature may contribute to blood pressure control.

Summary Background Optimal prescription of blood pressure, lipid, and glycaemic control treatments for adults with type 2 diabetes remains unclear. We aimed to compare the effectiveness and cost-effectiveness of two treatment approaches for diabetes management in five low-income and middle-income countries. Methods We developed a microsimulation model to compare a treat-to-target (TTT) strategy, aiming to achieve target levels of biomarkers (blood pressure 1c Findings The TTT strategy recommended treatment to a larger number of people—who were generally at lower risk of diabetes complications—than the BTT. The BTT strategy recommended treatment to fewer people at higher risk. Compared with the TTT strategy, the BTT strategy would be expected to avert 24·4–30·5% more complications and be more cost-effective from a societal perspective (saving US$4·0–300·0 per disability-adjusted life-year averted in the countries simulated). Alternative treatment thresholds, matched by total cost or population size treated, did not change the comparative superiority of the BTT strategy, nor did titrating treatment using fasting plasma glucose (for areas without HbA 1c testing). However, if insulin were unavailable, the BTT strategy would no longer be superior for preventing microvascular events and was superior only for preventing cardiovascular events. Interpretation A BTT strategy is more effective and cost-effective than a TTT strategy in low-income and middle-income countries for prevention of both cardiovascular and microvascular complications of type 2 diabetes. However, the superiority of the BTT strategy for averting microvascular complications is contingent on insulin availability. Funding Rosenkranz Prize for Healthcare Research in Developing Countries and US National Institutes of Health (U54 MD010724, DP2 MD010478).

The category of “prediabetes” defined by the American Diabetes Association comprises a range of intermediate hyperglycemia based on fasting or 2-h postload glucose or on HbA1c. Over the recent past, the “cut points” identifying this stage have changed, i.e., a lower fasting glucose level is used. On one hand, it can be argued that the change to a lower cut point identifies a group of individuals still at higher risk and provides heightened awareness for a condition associated with higher risk for cardiovascular disease. In addition, identification of individuals at this stage may represent a chance of earlier intervention in the disease. However, the argument against this definition of “prediabetes” is that it disguises the differences in the three subcategories and creates problems in interpreting observations on interventions and outcomes. In addition, it can be argued that the enormous numbers of people identified with the criteria far exceeds the capacity of health care systems to respond through individual care, particularly without evidence that interventions benefit any category other than impaired glucose tolerance. Thus, there does not appear to be consensus on the definition using the cut points identified. Controversy also remains as to whether there are glycemic metrics beyond HbA1c that can be used in addition to HbA1c to help assess risk of an individual developing diabetes complications. Given the current controversy, a Point-Counterpoint debate on this issue is provided herein. In the point narrative below, Dr. Yudkin provides his argument that there are significant problems with this label. In the counterpoint narrative that follows Dr. Yudkin’s contribution, Dr. Cefalu argues that the cut points are appropriate and do provide useful and important information in trying to reduce the future burden of diabetes. —William T. Cefalu Editor in Chief, Diabetes Care

Background Systematic reviews suggest that the incidence of diagnosed tuberculosis is two- to- three times higher in those with diabetes mellitus than in those without. Few studies have previously reported the association between diabetes or hyperglycaemia and the prevalence of active tuberculosis and none in a population-based study with microbiologically-defined tuberculosis. Most have instead concentrated on cases of diagnosed tuberculosis that present to health facilities. We had the opportunity to measure glycaemia alongside prevalent tuberculosis. A focus on prevalent tuberculosis enables estimation of the contribution of hyperglycaemia to the population prevalence of tuberculosis. Methods A population-based cross-sectional study was conducted among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Prevalent tuberculosis was defined by the presence of a respiratory sample that was culture positive for M. tuberculosis. Glycaemia was measured by random blood glucose (RBG) concentration. Association with prevalent tuberculosis was explored across the whole spectrum of glycaemia. Results Among 27,800 Zambian and 11,367 Western Cape participants, 4,431 (15.9%) and 1,835 (16.1%) respectively had a RBG concentration ≥7.0 mmol/L, and 405 (1.5%) and 322 (2.8%) respectively had a RBG concentration ≥11.1 mmol/L. In Zambia, the prevalence of tuberculosis was 0 · 5% (142/27,395) among individuals with RBG concentration

Summary Background Despite widespread recognition that the burden of diabetes is rapidly growing in many countries in sub-Saharan Africa, nationally representative estimates of unmet need for diabetes diagnosis and care are in short supply for the region. We use national population-based survey data to quantify diabetes prevalence and met and unmet need for diabetes diagnosis and care in 12 countries in sub-Saharan Africa. We further estimate demographic and economic gradients of met need for diabetes diagnosis and care. Methods We did a pooled analysis of individual-level data from nationally representative population-based surveys that met the following inclusion criteria: the data were collected during 2005–15; the data were made available at the individual level; a biomarker for diabetes was available in the dataset; and the dataset included information on use of core health services for diabetes diagnosis and care. We first quantified the population in need of diabetes diagnosis and care by estimating the prevalence of diabetes across the surveys; we also quantified the prevalence of overweight and obesity, as a major risk factor for diabetes and an indicator of need for diabetes screening. Second, we determined the level of met need for diabetes diagnosis, preventive counselling, and treatment in both the diabetic and the overweight and obese population. Finally, we did survey fixed-effects regressions to establish the demographic and economic gradients of met need for diabetes diagnosis, counselling, and treatment. Findings We pooled data from 12 nationally representative population-based surveys in sub-Saharan Africa, representing 38 311 individuals with a biomarker measurement for diabetes. Across the surveys, the median prevalence of diabetes was 5% (range 2–14) and the median prevalence of overweight or obesity was 27% (range 16–68). We estimated seven measures of met need for diabetes-related care across the 12 surveys: (1) percentage of the overweight or obese population who received a blood glucose measurement (median 22% [IQR 11–37]); and percentage of the diabetic population who reported that they (2) had ever received a blood glucose measurement (median 36% [IQR 27–63]); (3) had ever been told that they had diabetes (median 27% [IQR 22–51]); (4) had ever been counselled to lose weight (median 15% [IQR 13–23]); (5) had ever been counselled to exercise (median 15% [IQR 11–30]); (6) were using oral diabetes drugs (median 25% [IQR 18–42]); and (7) were using insulin (median 11% [IQR 6–13]). Compared with those aged 15–39 years, the adjusted odds of met need for diabetes diagnosis (measures 1–3) were 2·22 to 3·53 (40–54 years) and 3·82 to 5·01 (≥55 years) times higher. The adjusted odds of met need for diabetes diagnosis also increased consistently with educational attainment and were between 3·07 and 4·56 higher for the group with 8 years or more of education than for the group with less than 1 year of education. Finally, need for diabetes care was significantly more likely to be met (measures 4–7) in the oldest age and highest educational groups. Interpretation Diabetes has already reached high levels of prevalence in several countries in sub-Saharan Africa. Large proportions of need for diabetes diagnosis and care in the region remain unmet, but the patterns of unmet need vary widely across the countries in our sample. Novel health policies and programmes are urgently needed to increase awareness of diabetes and to expand coverage of preventive counselling, diagnosis, and linkage to diabetes care. Because the probability of met need for diabetes diagnosis and care consistently increases with age and educational attainment, policy makers should pay particular attention to improved access to diabetes services for young adults and people with low educational attainment. Funding None.

Health system reform in Kyrgyzstan is seen as a relative success story in central Asia. Initially, most attention focused on structural changes, and it is only since 2006 that the delivery of care and the experience of health service users have risen on the agenda. One exception from the earlier period was a rapid appraisal of the management of diabetes, undertaken in 2002. Using that study as a baseline, we describe the findings of a new evaluation of diabetes management, undertaken in 2009, using the Rapid Assessment Protocol for Insulin Access, now implemented in seven countries. Access to care has improved through the creation of the Family Medical Centres and the deployment of endocrinologists to them. Another improvement is the access to insulin and related medicines, although assessment of the procurement system reveals that the government is getting very poor value for money. Looking ahead, there are grounds for optimism that the passage of the law on diabetes may progressively have a greater impact. Although the law is not yet fully implemented, it has enabled the diabetes associations to defend the rights of their members. This increased capacity is credited with some improvements in diabetes care.

We fully support the views expressed in The Lancet Diabetes & Endocrinology's Editorial about ensuring affordable access to insulin and the proposal to add analogue insulin to the WHO Essential Medicines list. The International Insulin Foundation in its 2011 position statement called for “the universal access for persons with type 1 diabetes to life-saving and life-preserving insulin”. In 2012, we launched the 100 Campaign, which sets the target of 100% affordability and 100% availability of insulin worldwide by the year 2022 (100 years after the introduction of insulin for people with diabetes).

Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. Adipose tissue-derived substances (adipokines) and especially inflammatory products of adipose tissue control insulin sensitivity and vascular function. In the past years, adipose tissue associated with the vasculature, or perivascular adipose tissue (PAT), has been shown to produce a variety of adipokines that contribute to regulation of vascular tone and local inflammation. This review describes our current understanding of the mechanisms linking perivascular adipose tissue to vascular function, inflammation, and insulin resistance. Furthermore, we will discuss mechanisms controlling the quantity and adipokines secretion by PAT.

Background Although there is longstanding evidence of the short-term benefits of promoting rapid growth for young children in low-income settings, more recent studies suggest that early weight gain can also increase the risk of chronic diseases in adults. This paper attempts to separate the effects of early life weight and length/height gains on blood pressure, body mass index (BMI), sum of skin folds and subscapular/triceps skin fold ratio at 14–15 years of age. Methods The sample comprised 833 members of a prospective population-based birth cohort from Brazil. Conditional size (weight or height) analyses were used to express the difference between observed size at a given age and expected size based on a regression, including all previous measures of the same anthropometric index. A positive conditional weight or height indicates growing faster than expected given prior size. Results Conditional weights at all age ranges were positively associated with most outcomes; each z-score of conditional weight at 4 years was associated with an increase of 6.1 mm in the sum of skin folds (95% CI 4.5 to 7.6) in adolescence after adjustment for conditional length/height. Associations of the outcomes with conditional length/height were mostly negative or non-significant—each z-score was associated with a reduction of 2.4 mm (95% CI −3.8 to −1.1) in the sum of skin folds after adjustment for conditional weight. No associations were found with the skin fold ratio. Conclusion The promotion of rapid length/height gain without excessive weight gain seems to be beneficial for long-term outcomes, but this requires confirmation from other studies.

Insulin's indispensible nature is recognised by its inclusion in the World Health Organization's Essential Medicines List. Despite this insulin is still not available on an uninterrupted basis in many parts of the developing world. The International Insulin Foundation has conducted in-country assessments and based on these findings, the barriers to access to insulin were more to do with problems linked distribution, tendering and government policies than purely accessibility and affordability issues. Lack of insulin leads to poor outcomes for people with diabetes, but access to medicines alone cannot improve levels of health in resource poor settings. Aspects such as strong political will and local champions, data, trained healthcare workers and diabetes associations are just as necessary. Strengthening health systems and developing sustainable and locally owned solutions are vital to improve health and health care for people with diabetes and other chronic conditions in resource poor settings.