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As incomes rise around the world, health experts expect a more troubling figure to increase as well: the number of diabetics in developing countries.

In China and India – two of the world’s most populous nations with fast-paced economies – the prevalence of diabetes is expected to double by 2025. Between 15 and 20 percent of their adult population will develop the disease as household budgets increase, diets change to include more calories and new health problems emerge.

But China, India and other developing countries are not fully prepared to deal with the rising trend of diabetes. And a growing number of diabetics aren’t getting the care they need to prevent serious complications, Stanford researchers say.

Even with insurance, many diabetics don’t have essential medications that could help them manage their conditions. In many cases, people are spending a great deal of their household incomes to pay for their treatment, said Jeremy Goldhaber-Fiebert, an assistant professor of medicine who led the research team.

“Public and private health insurance programs aren’t providing sufficient protection for diabetics in many developing countries,” said Goldhaber-Fiebert, a faculty member at Stanford Health Policy at the university’s Freeman Spogli Institute for International Studies. “People with insurance aren’t doing markedly better than those who don’t have it. Health insurance and health systems need to be re-oriented to better address chronic diseases like diabetes.”

Findings from the study are online and will be published in the Jan. 24 edition of Diabetes Care, the journal of the American Diabetes Association. The journal article was co-authored by Jay Bhattacharya, an associate professor of medicine and Stanford Health Policy faculty member; and Crystal Smith-Spangler, an instructor at Stanford’s Department of Medicine and an investigator at the Palo Alto VA Health Care System.

Failure to adequately manage diabetes will lead to more severe health problems like blindness, heart disease and kidney failure. It also harms the otherwise healthy, Goldhaber-Fiebert said.

Diabetes often strikes people at an age when they’re taking care of children and elderly parents. To sideline these primary caretakers as dependants will lead to a heavy burden for communities and create an obstacle for economic growth, he added.

Using responses to a global survey conducted by the World Health Organization in 2002 and 2003, Goldhaber-Fiebert and his colleagues examined data from 35 low- and middle-income countries in Asia, Latin America, Africa and Eastern Europe to determine whether diabetics with insurance were more likely to have medication than those without insurance.

They also wanted to know whether insured diabetics have a lower risk of “catastrophic medical spending,” a term the researchers define as spending more than 25 percent of a household income on medical care.

“Surprisingly, diabetics with insurance were no more likely to have the medications they need than uninsured diabetics,” Goldhaber-Fiebert said. “They were also no less likely to suffer catastrophic medical spending.”

There are many reasons why health insurance may not protect diabetics in developing countries against high out-of-pocket spending. In some cases, there’s a lack of sufficient medication – such as insulin – that regulate glucose levels. Without those drugs, there’s a greater risk of complications that often lead to more hospitalizations and more expenses.

In other cases, co-payments and deductibles are too high. Sometimes, drugs and medical services to prevent diabetes complications are not covered. And doctors and hospitals don’t always accept insurance.

“Better policies are needed to provide sufficient protection and care for diabetics in the developing world,” Goldhaber-Fiebert said.

Without medications to manage diabetes and prevent secondary complications, the condition will worsen and the burden of catastrophic spending will increase, he said.

“It’s important to get ahead of the curve and prepare so there’s an infrastructure in place to deal with these health and cost issues,” he said.

While preventing diabetes in the first place would be ideal, programs and policies must be established to care for the many cases that will surely continue to exist.

“There isn’t a single country that’s managed to entirely arrest or reverse the trend of diabetes,” he said. “Programs that focus on primary prevention are extremely important, but the reality is that the developing world faces hundreds of millions of diabetes cases that are unlikely to all be prevented.”

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The mechanism by which strictly CCR5 using HIV-1 clade C variants exacerbate disease progression in absence of coreceptor switch is not clearly known. We previously reported HIV-1 cladeC envelopes (Env) obtained from late stage Indian patients with expanded coreceptor tropism. Here we compared such Envs (having expanded coreceptor tropism) with strictly CCR5 using Envs also obtained from late stage in their capacity to utilize CD4 and CCR5 for productive entry. We found that while envelopes with low CD4 dependence tend to infect primary CD4(+) T cells better than those required optimum CD4 for entry, no significant association was found between low CD4 usage and infectivity of primary CD4(+) T cells by Env-pseudotyped viruses and theirsensitivity to CCR5 antagonist TAK-779. Interestingly, Envs that readily infected HeLa cells expressing low CD4 showed relative resistance to T20 indicating that conformational intermediates of these envelopes remained for a shorter period of time than is required for efficient inhibition by T20.

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Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped viruses to autologous and heterologous plasma antibodies. When tested against monoclonal antibodies targeting different sites in gp120 and gp41, Envs expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.

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Although the past few decades have seen rising incomes and increased government attention to rural development, many children in rural China still lack regular access to micronutrient-rich diets. Insufficient diets and poor knowledge of nutrition among the poor result in nutritional problems, including irondeficiency anaemia, which adversely affect attention and learning of students in school. Little research has been conducted in China documenting the prevalence of nutritional problems among vulnerable populations, such as school-age children, in rural areas. The absence of programmes to combat anaemia among students might be interpreted as a sign that the Government does not recognize its severity. The goals of this paper were to measure the prevalence of anaemia among school-age children in poor regions of Qinghai and Ningxia, to identify individual-, household- and school-based factors that correlate with anaemia in this region, and to report on the correlation between the anaemic status and the physical, psychological and cognitive outcomes. The results of a cross-sectional survey are reported here. The survey involved over 4,000 fourth and fifth grade students from 76 randomly-selected elementary schools in 10 poor counties in rural Qinghai province and Ningxia Hui Autonomous Region, located in the northwest region of China. Data were collected using a structured questionnaire and standardized tests. Trained professional nurses administered haemoglobin (Hb) tests (using Hemocue finger prick kits) and measured heights and weights of children. The baseline data showed that the overall anaemia rate was 24.9%, using the World Health Organization's blood Hb cut-offs of 120 g/L for children aged 12 years and older and 115 g/L for children aged 11 years and under. Children who lived and ate at school had higher rates of anaemia, as did children whose parents worked in farms or were away from home. Children with parents who had lower levels of education were more likely to be anaemic. The anaemic status correlated with the adverse physical, cognitive and psychological outcomes among the students. Such findings are consistent with findings of other recent studies in poor, northwest areas of China and led to conclude that anaemia remains a serious health problem among children in parts of China. © International Centre For Diarrhoeal Disease Research, Bangladesh.

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Journal of Health, Population and Nutrition
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Grant Miller
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In the present study, we investigated genetic divergence between complete autologous HIV-1 env genes amplified directly from plasma of two anti-retroviral naïve, slow progressing Indian patients with broad neutralizing antibody response. All the envelopes (Env) clones obtained from one patient (LT1) belonged to subtype C; the second patient (LT5) harbored quasispecies comprising of pure B, C and B/C recombinants with distinct breakpoints indicative of dual infection with genetically distinct strains. Further characterization of these Envs would provide insights to the biological properties under strong humoral immune response.

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Abstract HIV-2 group A is predominant in different parts of the world, especially Africa, Portugal, Spain, France, the United Kingdom, the United States, Korea, and India. Among the Asian countries, India accounts for about 95% of all HIV-2 infections. The prevalence of HIV-2 has been reported from various states of India such as Maharashtra, Goa, Tamil Nadu, West Bengal, and Uttar Pradesh. In the present study, we analyzed transmembrane region (gp36) sequences of 10 HIV-2 group A Indian strains, isolated from Indian HIV-2-seropositive individuals. HIV Blast analysis for the 1.0-Kb region of the gp36 transmembrane region has shown that all these sequences belong to HIV-2 group A. Phylogenetic analysis indicated that the sequences cluster with HIV-2 group A sequences of Cameroon and Senegal. The epitope found at position 645-656 (YELQKLNSWDVF), previously reported as a broadly neutralizing determinant, was very well conserved in all 10 study sequences. The percentage similarity between Indian and South African HIV-2 group A gp36 sequences was 90% (range 86-100, SD 2.8) and with other nonsubtype A clades was 84% (range 77-100, SD 6.06) indicating overall less variability among the reported HIV-2 sequences. Similarly, the consensus amino acid sequences of the envelope transmembrane region of HIV-1 (gp41) and HIV-2 (gp36) is quite synonymous, indicating 87% similarity; however, limited information is available about the gp36 transmembrane region of the prevalent HIV 2 group A Indian strain. The rate of synonymous substitutions reported in the gp105 region was significantly higher, suggesting lower virulence of HIV-2, which does translate into a lower rate of evolution, while the dN/dS ratio for the gp36 transmembrane region was less than one, indicating its conservation and significance (p<0.05) in structural and functional constraints.

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Paul Wise is a clinical professor of pediatrics and a CHP/PCOR core faculty member. His work focuses on children's health policy; health disparities by race, ethnicity and socioeconomic status; and the interaction of genetics and the environment as these factors influence child and maternal health.

Before coming to Stanford in July 2004, he was a professor of pediatrics at Boston University and vice-chief of Social Medicine and Health Inequalities at Brigham and Women's Hospital. He previously served as director of emergency and primary care services at the Children's Hospital of Boston, and as director of the Harvard Institute for Reproductive and Child Health at Harvard Medical School. He has also served as a special expert at the National Institutes of Health and as special assistant to the U.S. Surgeon General.

Wise has worked to improve healthcare practices and policies in developing countries. He is involved in child health projects in India, South Africa and Latin America, targeting diseases such as tuberculosis and AIDS. He currently chairs the steering committee of the NIH's Global Network for Maternal and Child Health Research, and he has served on many other boards and committees including the Physicians' Task Force on Hunger and the American Academy of Pediatrics' Consortium on Health Disparities. He has received honors from organizations including the American Public Health Association, the March of Dimes, and the New York Academy of Medicine.

He received a BA in Latin American studies from Cornell University, an MD from Cornell University and an MPH from the Harvard School of Public Health. He completed a residency in pediatrics at Children's Hospital Medical Center in Boston.

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Richard E. Behrman Professor of Child Health and Society
Senior Fellow, Freeman Spogli Institute for International Studies
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Dr. Paul Wise is dedicated to bridging the fields of child health equity, public policy, and international security studies. He is the Richard E. Behrman Professor of Child Health and Society and Professor of Pediatrics, Division of Neonatology and Developmental Medicine, and Health Policy at Stanford University. He is also co-Director, Stanford Center for Prematurity Research and a Senior Fellow in the Center on Democracy, Development, and the Rule of Law, and the Center for International Security and Cooperation, Freeman Spogli Institute for International Studies, Stanford University. Wise is a fellow of the American Academy of Arts and Sciences and has been working as the Juvenile Care Monitor for the U.S. Federal Court overseeing the treatment of migrant children in U.S. border detention facilities.

Wise received his A.B. degree summa cum laude in Latin American Studies and his M.D. degree from Cornell University, a Master of Public Health degree from the Harvard School of Public Health and did his pediatric training at the Children’s Hospital in Boston. His former positions include Director of Emergency and Primary Care Services at Boston Children’s Hospital, Director of the Harvard Institute for Reproductive and Child Health, Vice-Chief of the Division of Social Medicine and Health Inequalities at the Brigham and Women’s Hospital and Harvard Medical School and was the founding Director or the Center for Policy, Outcomes and Prevention, Stanford University School of Medicine. He has served in a variety of professional and consultative roles, including Special Assistant to the U.S. Surgeon General, Chair of the Steering Committee of the NIH Global Network for Women’s and Children’s Health Research, Chair of the Strategic Planning Task Force of the Secretary’s Committee on Genetics, Health and Society, a member of the Advisory Council of the National Institute of Child Health and Human Development, NIH, and the Health and Human Secretary’s Advisory Committee on Infant and Maternal Mortality.

Wise’s most recent U.S.-focused work has addressed disparities in birth outcomes, regionalized specialty care for children, and Medicaid. His international work has focused on women’s and child health in violent and politically complex environments, including Ukraine, Gaza, Central America, Venezuela, and children in detention on the U.S.-Mexico border.  

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Background A growing body of evidence supports the role of type 2 diabetes as an individual-level risk factor for tuberculosis (TB), though evidence from developing countries with the highest TB burdens is lacking. In developing countries, TB is most common among the poor, in whom diabetes may be less common. We assessed the relationship between individual-level risk, social determinants and population health in these settings.

Methods We performed individual-level analyses using the World Health Survey (n = 124 607; 46 countries). We estimated the relationship between TB and diabetes, adjusting for gender, age, body mass index, education, housing quality, crowding and health insurance. We also performed a longitudinal country-level analysis using data on per-capita gross domestic product and TB prevalence and incidence and diabetes prevalence for 1990–95 and 2003–04 (163 countries) to estimate the relationship between increasing diabetes prevalence and TB, identifying countries at risk for disease interactions.

Results In lower income countries, individuals with diabetes are more likely than non-diabetics to have TB [univariable odds ratio (OR): 2.39; 95% confidence interval (CI): 1.84–3.10; multivariable OR: 1.81; 95% CI: 1.37–2.39]. Increases in TB prevalence and incidence over time were more likely to occur when diabetes prevalence also increased (OR: 4.7; 95% CI: 1.0–22.5; OR: 8.6; 95% CI: 1.9–40.4). Large populations, prevalent TB and projected increases in diabetes make countries like India, Peru and the Russia Federation areas of particular concern.

Conclusions Given the association between diabetes and TB and projected increases in diabetes worldwide, multi-disease health policies should be considered.

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International Journal of Epidemiology
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Jeremy Goldhaber-Fiebert
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