Rising diabetes rates are raising concern on a global scale
By Steve Halasey
At the beginning of April, the World Health Organization (WHO) commemorated World Health Day and the 68th anniversary of its founding by issuing its first-ever Global Report on Diabetes.1
Noting that the number of people living with diabetes has almost quadrupled since 1980 to 422 million adults, with most living in developing countries, WHO used the occasion of its report to call for global action to halt the rise in diabetes and improve care for people living with the disease. (For more information, see “Key Findings from the WHO Report on Diabetes.)
According to the WHO report, factors driving the dramatic rise in the global incidence of diabetes include excessive weight and obesity. Measures needed to counteract the trend include expanding health-promoting environments to reduce diabetes risk factors, such as physical inactivity and unhealthy diets, and strengthening national capacities to help people with diabetes receive the treatment and care they need to manage their conditions.
“If we are to make any headway in halting the rise in diabetes, we need to rethink our daily lives: to eat healthily, be physically active, and avoid excessive weight gain,” says Margaret Chan, MD, MPH, WHO director-general. “Even in the poorest settings, governments must ensure that people are able to make these healthy choices and that health systems are able to diagnose and treat people with diabetes.”
Global Commitments. Diabetes is a chronic, progressive noncommunicable disease (NCD) characterized by elevated levels of blood glucose. It occurs either when the pancreas does not produce enough of the insulin hormone, which regulates blood sugar, or when the body cannot effectively use the insulin it produces. Undetected and untreated, diabetes typically worsens, causing heart disease, blindness, kidney failure, or death.
There are three main forms of diabetes: type 1, type 2, and gestational diabetes. The cause of type 1 diabetes is unknown and people living with it require daily insulin administration for survival. Type 2 accounts for the vast majority of people living with diabetes globally, and is largely the result of excess body weight and physical inactivity. Once seen only in adults, type 2 diabetes is now increasingly occurring in children and young people. Gestational diabetes is a temporary condition that occurs during pregnancy and carries a long-term risk of type 2 diabetes. Gestational diabetes is present when blood glucose values are above normal but still below those diagnostic of diabetes.
“Many cases of diabetes can be prevented, and measures exist to detect and manage the condition, improving the odds that people with diabetes live long and healthy lives,” says Oleg Chestnov, MD, PhD, WHO assistant director-general for NCDs and mental health. “But change greatly depends on governments doing more, including by implementing global commitments to address diabetes and other NCDs.”
Such tactics include meeting the United Nations’ sustainable development goal (SDG) 3.4, which calls for reducing premature death from NCDs, including diabetes, by 30% by 2030. (For more information, see “WHO Conclusions and Recommendations.”) Governments have also committed to achieving four time-bound national commitments set out in the 2014 UN General Assembly outcome document on NCDs, and attaining the nine global targets laid out in the WHO global action plan for NCDs, which include halting the rise in diabetes and obesity.2–4
“Around 100 years after the insulin hormone was discovered, the Global Report on Diabetes shows that essential diabetes medicines and technologies needed for treatment, including insulin, are generally available in only one in three of the world’s poorest countries,” says Etienne Krug, MD, MPH, director of WHO’s department for the management of NCDs, disability, violence, and injury prevention. “Access to insulin is a matter of life or death for many people with diabetes. Improving access to insulin and NCD medicines in general should be a priority.”
Global efforts are underway to make medicines, including those for NCDs, more available and affordable. Commitments from world leaders—including SDGs, agreements on the management of NCDs, and the UN secretary-general’s high-level panel on access to essential medicines—are aimed at improving the affordability and availability of essential drugs for people living with diabetes.5
HOPE IN INDIA
In partnership with the global health organization Project HOPE, efforts to improve care for diabetic patients are experiencing great success in India through Project Uday (which means “dawn” or “sunrise” in Hindi), a comprehensive diabetes and hypertension prevention and management program supported by Eli Lilly and Company under the Lilly NCD Partnership.6
According to the International Diabetes Federation, India has the world’s second-largest population living with diabetes, second only to China. Higher incomes, more sedentary lifestyles, diets heavy in starches and sugars, and high blood pressure are all factors contributing to the spread of the disorder. While today there are about 65 million people with diabetes in India, that number is expected to increase to 109 million by 2030.
Launched in 2012, Project Uday is led by the Public Health Foundation of India (PHFI), New Delhi, in partnership with Population Services International (PSI) and Project HOPE. Uday comprises a set of five interventions with the overarching goal of preventing, detecting, and reducing the risk of diabetes and hypertension, and improving the management of individuals with either of these conditions. The project’s activities are focused on two geographically and culturally distinct study sites in northern and southern India.
Project HOPE’s main focus is to develop skilled healthcare professionals and NCD patient networks, with an emphasis on advancing knowledge toward early detection, prevention, management, and timely referrals of NCDs. This involves understanding and responding to the specific needs of the community toward NCD care and management.
To maximize learning, Project HOPE’s training methodology uses adult participatory learning, including case scenarios, demonstrations, role-playing, and interactive exercises and games. The methodology creates a technology-independent environment that is conducive to keeping participants engaged for advanced learning. The method enhances the capacity of health workers for community interaction and counseling, and for promoting opportunistic screenings in different sociocultural contexts.
The project’s training efforts have been complemented by advocacy to secure increased government attention to and involvement in scaling up and mainstreaming NCD-related activities. “Project HOPE’s approach in Uday is mobilizing patients through patient networks, and at the same time strengthening the service delivery via healthcare workers,” says Cheena Malhotra, program manager for Project HOPE India. “Project HOPE has been very pleased with the success of the program, where participating health workers showed 95% of improvement in knowledge on the posttest versus 15% at the beginning of the training.”
“Through Uday, we are bringing meaningful, long-term changes that benefit people with diabetes today, and will hopefully prevent its onset with others moving forward,” says Craig Waugh, global leader of the Lilly NCD Partnership. “Our ultimate goal is to use the research coming out of projects like Uday to advocate for wider scale-up in order to positively impact more people in India.”
The challenges identified by WHO may be more intractable in nations where limited funding and other resources restricts patient access to care. But the diabetes equation doesn’t improve much when conditions in the United States are considered.
Nationally, diabetes rates have tripled over the past 30 years. Approximately 1.7 million people in the United States are diagnosed with diabetes each year, and roughly 28 million Americans are now living with type 2 diabetes.
Annual medical spending for people with diabetes is almost twice that for people without diabetes. A person who is diagnosed with diabetes by age 40 will have lifetime medical spending that is $124,600 more than someone who is not. All told, diabetes-related direct healthcare and lost productivity costs in the United States are estimated at about $322 billion annually.
According to a recent study conducted by the UCLA Center for Health Policy Research and commissioned by the California Center for Public Health Advocacy, nearly half of California adults, including one out of every three young adults, have either prediabetes—a precursor to type 2 diabetes—or undiagnosed diabetes.7 The research provides the first analysis and breakdown of California prediabetes rates by county, age, and ethnicity, and offers alarming insights into the future of the nation’s diabetes epidemic.
The study analyzed hemoglobin A1c (HbA1c) and fasting plasma glucose findings from the National Health and Nutrition Examination Survey together with California Health Interview Survey data from more than 40,000 respondents.
The study estimates that some 13 million adults in California, or 46%, have prediabetes or undiagnosed diabetes, while another 2.5 million adults, or 9%, have already been diagnosed with diabetes. Combined, the two groups represent 15.5 million people—55% of the state’s population. Because diabetes is more common among older adults, the study’s finding that 33% of young adults aged 18 to 39 have prediabetes is of particular concern.
“This is the clearest indication to date that the diabetes epidemic is out of control and getting worse,” says Harold Goldstein, DrPH, executive director of the health advocacy center. “With limited availability of healthy food in low-income communities, a preponderance of soda and junk food marketing, and urban neighborhoods lacking safe places to play, we have created a world where diabetes is the natural consequence. If there is any hope to keep health insurance costs from skyrocketing, healthcare providers from being overwhelmed, and millions of Californians from suffering needlessly from amputations, blindness, and kidney failure, the state of California must launch a major campaign to turn around the epidemic of type 2 diabetes.”
Complicating matters is the fact that many people do not get tested for prediabetes because the test often is not covered by insurance, particularly for those under the age of 45. And although there are effective interventions to help people control their weight and adopt a healthier lifestyle, these programs are often not be covered by insurers.
“There are significant barriers not only to people knowing their status, but getting effective help,” says Susan H. Babey, PhD, lead author of the study and codirector of the chronic disease program at the UCLA Center for Health Policy Research. “A simple blood test for diabetes should be covered by all insurers, as should the resources and programs that can make a real difference in stopping the progression of this terrible disease.”
Prediabetes is a condition in which blood glucose levels are higher than normal but not high enough for a diabetes diagnosis. Up to 30% of people with prediabetes will develop type 2 diabetes within 5 years, and as many as 70% of them will develop the disease in their lifetime. To avoid the progression from prediabetes to diabetes, the study’s authors recommend greater participation in the National Diabetes Prevention Program, as well as policy and other changes to increase screening and prevention and encourage healthy, active lifestyles.
“For most people, type 2 diabetes is entirely preventable,” says Goldstein. “If Medi-Cal covered diabetes prevention programs and every health provider screened for prediabetes, we could prevent a large proportion of cases. In exchange for a proactive investment today, we can save billions of dollars in healthcare costs over the next 5 years and beyond, and save thousands of lives.”
California’s experience with diabetes may be typical of national trends, but investigators are looking at the disease from a variety of perspectives. The result is a wide range of new information about what types of treatment programs actually work, as well as discoveries about novel biomarkers that can help clinicians manage patients better.
Access to Care. A 2015 study by researchers at Quest Diagnostics, Madison, NJ, found that people in states that expanded Medicaid under the Patient Protection and Affordable Care Act (PPACA) are far more likely to be newly identified with diabetes than those in states that have elected not to expand the public healthcare program.8 The study was among the first nationally representative analyses of the impact of PPACA on promoting earlier diagnosis of, and potentially better outcomes for, diabetes.
The analysis of deidentified test results of 434,288 people with newly identified diabetes, tested by Quest Diagnostics, found that newly identified diabetes surged 23% among Medicaid-enrolled patients in states that expanded Medicaid, but increased just 0.4% in states that did not expand. The newly identified patients with diabetes were also more likely to be identified at earlier stages of disease in states that expanded Medicaid than in those that did not. (For more information, see “Analysis of Diagnostic Testing Patterns Reveals Trends in Access to Care.”)
“This seminal study demonstrates that PPACA promotes earlier diagnosis of one of the most prevalent and treatable chronic health conditions in the United States,” says study coinvestigator Vivian A. Fonseca, MD, FRCP, professor of medicine at Tulane University School of Medicine and a past president for medicine and science at the American Diabetes Association. “But these benefits were not shared equally across states. This study demonstrates the need for additional debate on the merits of healthcare reform to promote equal access to health services.”
“Our study demonstrates the value of objective insights gleaned from aggregate diagnostic data for informing population health strategies that can promote better health outcomes,” says Jay G. Wohlgemuth, MD, senior vice president and chief scientific officer for research, development, and medical, at Quest Diagnostics. “We hope that the use of our population data in this research enlightens the decisions of policymakers considering reforms in the area of preventive health services.”
Effective January 1, 2014, PPACA expanded Medicaid for uninsured adults with income at or below 138% of the federal poverty level, expanding access to millions of people who were previously excluded from the public health insurance program and who likely did not have private health insurance. At the time of the Quest Diagnostics analysis, 26 states and the District of Columbia had agreed to expand Medicaid, while 24 states had not.
Researchers at Quest Diagnostics analyzed deidentified test results for people between the ages of 19 and 64 of both genders across the United States who met the definition of newly diagnosed diabetes during the first 6 months of 2013 (prior to Medicaid expansion) and the first 6 months of 2014 (following Medicaid expansion). Newly diagnosed diabetes was determined based results for at least one blood test for HbA1c greater than 6.4%, or an ICD-9 code for diabetes mellitus with no prior diagnosis for the preceding year.
“Not only did states with expanded Medicaid programs catch more people with diabetes, they caught them at earlier stages, when the disease is more manageable,” says study lead investigator Harvey W. Kaufman, MD, senior medical director at Quest Diagnostics. “These findings likely apply to other chronic conditions, like heart and chronic kidney disease, for which early diagnosis and treatment strongly correlate with better health outcomes.
“While more research is needed, we theorize that states that have expanded Medicaid may experience fewer diabetes complications and healthcare costs over time than those that did not expand, and that this pattern may apply to other chronic diseases,” adds Kaufman. “We look forward to results of additional research into the long-term health and economic impacts of greater access to healthcare services as a result of Medicaid expansion.”
Lymphatic Barrier Dysfunction. Until recently, the effects of diabetes on the body’s lymphatic vessels has been unknown. But a study by University of Missouri (MU) researchers has identified for the first time how the condition affects lymphatic vessels—a finding that could lay the groundwork for new therapies to improve the lives of people with type 2 diabetes.9
“The lymphatic system’s primary role is to transport lymph—a clear fluid that contains white blood cells that help rid the body of antigens or destroy cancer cells—to lymph nodes where immune responses are activated,” says Joshua Scallan, PhD, a research assistant professor of medical pharmacology and physiology at the MU School of Medicine. “We now know for the first time that when individuals have type 2 diabetes, the walls of their lymphatic vessels are defective and become increasingly permeable, or leaky.”
Scallan likens the permeability of a healthy lymphatic vessel to a porous garden hose, which is designed to allow water to escape through small holes in the hose. By contrast, a lymphatic vessel in a person with type 2 diabetes is like a porous garden hose that has been drilled with large holes, letting too much water escape. When the lymphatic vessel is too permeable, lymph and antigens are not transported to the lymph nodes.
Studying lymphatic vessel function in animals has been a challenge for researchers because, unlike blood vessels, lymph vessels are clear and appear almost invisible. However, Scallan developed a new investigative method to measure lymphatic vessel permeability and found that the vessels in type 2 diabetes produced nitric oxide levels much lower than healthy lymphatic vessels.
“When an individual has type 2 diabetes, cells in the lymphatic vessels aren’t producing enough nitric oxide, which is essential to maintaining the integrity of their endothelial layer so that they function properly,” says Scallan. “We found that by giving the lymphatic vessels L-arginine—an amino acid commonly found in red meat, poultry, dairy products, and nutritional supplements—we were able to boost their nitric oxide production and restore their ability to act as a barrier.”
The authors write that the degree of lymphatic barrier dysfunction resulting from diabetes may be sufficient to reduce lymph flow, thereby trapping lipids and cholesterol in the tissue. “This effect is likely significant because inhibiting lymphatic transport of cholesterol bound to high-density lipoprotein (HDL-C) from the tissues to the liver (ie, reverse cholesterol transport) exacerbates atherosclerosis,” write the authors. “Further, these findings link lymphatic endothelial dysfunction to lymph leakage, which leads to tissue adipose deposition, obesity, fibrosis, and inflammation.”
While more studies are needed, Scallan is hopeful the findings may lead to new treatments or therapies for individuals with type 2 diabetes. “Because diabetic patients are at increased risk for dyslipidemia, atherosclerosis, and edema, treating lymphatic dysfunction may selectively alleviate these risks. Future studies are required to determine whether rescuing lymphatic dysfunction in diabetes reduces atherosclerotic plaque formation,” the authors conclude.
Methylation Biomarker. In another recent study, scientists at Lund University have discovered a new biomarker that may help predict a patient’s risk of developing type 2 diabetes.10 The biomarker detects epigenetic changes in specific genes through a blood test. Its discovery has made it possible to measure the presence of DNA methylations in four specific genes, and thus predict those at risk for type 2 diabetes well before its onset. By measuring HbA1c levels they can then help predict the onset of diabetes.
For the study, Karl Bacos, PhD, an assistant researcher in epigenetics and diabetes at Lund University, and colleagues studied insulin-producing beta cells from 87 deceased persons. They noted that the DNA methylations in the four genes studied increased, depending on the donor’s age, and in turn affected the activity of the genes. When replicated in cultured beta cells, researchers saw a positive effect on insulin secretion.
They then compared blood samples from participants enrolled in Danish and Finnish research projects, with blood samples drawn again from the same participants 10 years later. The Finnish patients with higher levels of DNA methylation in their first sample had a lower risk of type 2 diabetes 10 years later. In the Danish patients, higher DNA methylation in their first sample was linked to higher insulin secretion 10 years later.
All of the Danish patients were healthy on both study points, whereas about one third of the Finnish patients had developed type 2 diabetes.
“Increased insulin secretion actually protects against type 2 diabetes. It could be the body’s way of protecting itself when other tissue becomes resistant to insulin, which often happens as we get older,” wrote the researchers.
The researchers admit that the “predictive potential of this method is modest.” But they hope to continue research to find markers with a stronger predictive potential by implementing so-called epigenetic whole-genome sequencing in a larger cohort.
Fingerstick Practices. The prevalence of fingerstick glucose monitoring offers researchers additional opportunities to study diabetic populations. In March, COLA, a national laboratory accreditor, joined with the Centers for Disease Control and Prevention (CDC) and the Clinical and Laboratory Standards Institute (CLSI) to conduct a study aimed at improving the impact of laboratory practice guidelines (LPGs) on healthcare. The study will identify metrics that can then be used to determine and enhance the overall impact of LPG creation, implementation, and dissemination.
The study is being conducted via an anonymous survey of COLA facilities performing point-of-care fingerstick glucose monitoring. The goal is to gain information to help CLSI improve the dissemination and implementation of its LPGs, and to improve the quality of care provided to all patients in any healthcare setting.
“We are excited to have this opportunity to partner with both CDC and CLSI on this important study,” says Douglas Beigel, CEO at COLA. “COLA is committed to continually promoting excellence in laboratory medicine and patient care. Improving the ability to implement LPGs can have a direct and profound impact on ensuring quality test results and, as a result, positive patient experiences.”
THE PRODUCT EDGE
Manufacturers are acutely aware of the growing diabetes epidemic, and have responded with new and updated systems whose capabilities match the need of laboratories for faster instruments with a simpler workflow. Last October, Roche Diagnostics, Basel, Switzerland, launched a dedicated high-throughput HbA1c testing solution, the Cobas c513 analyzer, for countries accepting the CE mark.
HbA1c is a measure of the amount of glucose attached to hemoglobin in red blood cells over the preceding 2 to 3 months, and is used to determine whether a person is diabetic or at risk of developing diabetes. However, specimens from patients with hemoglobin variants such as HbS (the variant associated with sickle-cell anemia) can produce inaccurate results, depending in part on the method used for testing.11 To ensure that test results are accurate, patients known to have a hemoglobin variant should be tested using an instrument that does not show interference with that variant.
The Cobas c513 analyzer runs the established Tina-Quant HbA1c A1cDx Gen.3 test, which is also used across the Roche laboratory HbA1c portfolio. With no interference from most known HbA1c variants, Roche’s Tina-Quant HbA1c assay delivers accurate monitoring of HbA1c levels. The analyzer complies with current guidelines and recommendations for HbA1c testing, and measures HbA1c as defined by the International Federation of Clinical Chemistry and Laboratory Medicine.
The Cobas c513 analyzer replaces the company’s previous dedicated HbA1c analyzer, the Cobas Integra 800 CTS. “The increasing number of people with diabetes is challenging healthcare providers and is putting a significant strain on healthcare systems,” says Roland Diggelmann, chief operating officer of Roche Diagnostics. “With the Cobas c513, Roche is meeting the dedicated and growing testing needs of our customers.”
The new instrument doubles the throughput of its predecessor from 200 to 400 patient results per hour, while maintaining the same footprint. Moreover, the Cobas c513 analyzer provides a higher onboard test capacity. Enabling laboratories to load the analyzer with more tests at a time saves laboratory space, releases lab resources, and ensures a smooth workflow. The new analyzer also offers closed-tube sampling, which reduces hands-on time, prevents sample contamination, and ensures operator safety.
The Cobas c513 features direct results reporting, thereby minimizing the risk of result misinterpretation and eliminating the need to perform time-consuming, manual results interpretation. This saves valuable time and laboratory resources while ensuring high quality of results.
New to the US Market. Following FDA clearance and CE marking in 2015, earlier this year Bio-Rad Laboratories, Hercules, Calif, launched its new D-100 system, a dedicated HbA1c analyzer. The analyzer is now available in the United States and other global markets.
The D-100 is designed to address the key challenges affecting the current market: a surge in orders for HbA1c tests but not enough time to run them; and many methods requiring lots of preparation and hands-on instrument time, taking away from other tasks in the lab.
“The D-100 was designed taking into account every step in running the instrument that could potentially be arduous or time-consuming, with an eye toward reducing hands-on time and minimizing the number of steps required to produce an error-free HbA1c result,” says Priya Sivaraman, PhD, senior product manager at Bio-Rad Laboratories. “All this has been done without compromising the instrument’s ability to detect variants, which is a key benefit of the high-performance liquid chromatography (HPLC) method used by the instrument. The D-100 produces results at a much faster rate than other platforms currently on the market—just 45 seconds per sample with variant detection.”
According to Sivaraman, the D-100 requires no sample preparation and is virtually unaffected by hemoglobin variants C, D, E, and S, or by carbamylated hemoglobin, labile HbA1c, or fetal hemoglobin (up to 30%). In addition, the instrument can be used as an aid in diagnosing diabetes mellitus, as well as monitoring patients’ long-term glycemic control.
With a throughput of 80 tests per hour, the D-100 is especially suited for medium- to high-volume laboratories. It incorporates an onboard advisor that provides a consistent, thorough review of every test result. Normal results can be released automatically, while flagged results can be held for further review. The advisor helps to reduce errors and simplify the results review process.
Insulin Resistance. Metabolon Inc, Research Triangle Park, NC, recently announced plans to launch its Quantose IR test for insulin resistance through a commercialization collaboration with European laboratory services provider Synlab Group, Augsburg, Germany.
Quantose IR is a laboratory-developed test used to identify insulin resistance, a critical pathophysiological state underlying several chronic conditions, including prediabetes, type 2 diabetes, polycystic ovary syndrome, hypertension, and cardiovascular disease.
The test will initially be made available in Spain, with international expansion planned in 2016. The agreement also provides Synlab Group an option to commercialize new Metabolon precision medicine and diagnostics products as they become available.
“Combining Synlab Group’s expertise and marketing strength in clinical laboratory services with Metabolon’s technology gives physicians and their patients access to advanced, new laboratory medicine,” says John Ryals, PhD, CEO at Metabolon. “This collaboration between our two companies is an important step toward making Quantose IR and future precision medicine and diagnostics products widely available across the globe.”
Insulin resistance status can be a cornerstone of successful disease prevention and management. If caught early, physicians and patients can work together to prevent type 2 diabetes and other serious health conditions. Knowing the unique insulin resistance score for each patient enables physicians to identify and better manage individuals at the greatest risk for disease development or progression.
“Product innovation is key to Synlab’s objective of making medical innovation quickly available to medical experts and their patients. Working with Metabolon and licensing the Quantose IR technology adds another innovative offering to our laboratory services,” says Santiago Valor, MD, chief medical officer at Synlab. “The detection of insulin resistance will enable physicians to identify patients earlier for disease prevention and stratify patients by risk of disease progression.”
Public health authorities across the globe have sounded alarm bells because of the continuing rise in the worldwide incidence of diabetes. But they also agree that the impending crisis is one that can be avoided—if only patients can be convinced to adopt healthier lifestyles, including a better diet and more exercise.
Advanced diagnostic technologies will continue making contributions in this realm, not only by rendering accurate diagnoses of patients’ diabetes status, but also by seeking out markers to identify those at greatest risk—and therefore also most in need of intervention. The role of clinical laboratories will be vital for slowing the increase in diabetes and, with a little luck, perhaps even reversing the trend.
Steve Halasey is chief editor of CLP. He can be reached via [email protected].
- Global report on diabetes. Geneva, Switzerland: World Health Organization, 2016. Available at: http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf?ua=1. Accessed April 6, 2016.
- Transforming our world: the 2030 agenda for sustainable development. United Nations General Assembly resolution A/RES/70/1. New York City: United Nations, 2015. Available at: http://www.un.org/ga/search/view_doc.asp?symbol=A/RES/70/1&Lang=E. Accessed April 6, 2016.
- Outcome document of the high-level meeting of the General Assembly on the comprehensive review and assessment of the progress achieved in the prevention and control of noncommunicable diseases. United Nations General Assembly resolution A/RES/68/300. New York City: United Nations, 2014. Available at: www.who.int/nmh/events/2014/a-res-68-300.pdf. Accessed April 6, 2016.
- Global action plan for the prevention and control of noncommunicable diseases, 2013–2020. Geneva, Switzerland: World Health Organization, 2013. Available at: http://apps.who.int/iris/bitstream/10665/94384/1/9789241506236_eng.pdf?ua=1. Accessed April 6, 2016.
- United Nations secretary-general’s high-level panel on access to medicines [online]. New York City: United Nations, 2016. Available at: www.unsgaccessmeds.org/#homepage. Accessed April 6, 2016.
- About the Lilly NCD partnership [online]. Indianapolis: Eli Lilly and Company, 2015. Available at: www.lillyglobalhealth.com/en/ncd/about-ncd-partnership.aspx. Accessed April 6, 2016.
- Babey SH, Wolstein J, Diamant AL, Goldstein H. Prediabetes in California: nearly half of California adults on path to diabetes. Health Policy Brief. Los Angeles: UCLA Center for Health Policy Research and California Center for Public Health Advocacy, 2016. Available at: http://ucla-dev-web01.reliam.com/publications/Documents/PDF/2016/prediabetes-brief-mar2016.pdf. Accessed April 6, 2016.
- Kaufman HW, Chen Z, Fonseca VA, McPhaul MJ. Surge in newly identified diabetes among Medicaid patients in 2014 within Medicaid expansion states under the Affordable Care Act. Diabetes Care. 2015;38(5):833–837; doi: 10.2337/dc14-2334.
- World 1. Scallan JP, Hill MA, Davis MJ. Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signaling. Cardiovasc Res. 2015;107:89–97; doi: 10.1093/cvr/cvv117.
- Bacos K, Gillberg L, Volkov P, et al. Blood-based biomarkers of age-associated epigenetic changes in human islets associate with insulin secretion and diabetes. Nat Commun. 2016;7:11089; doi: 10.1038/ncomms11089.
- HbA1c assay interferences [online]. Columbia, MO: National Glycohemoglobin Standardization Program, 2016. Available at: www.ngsp.org/interf.asp. Accessed April l6, 2016.