Diabetes – a chronic disease in which the body cannot produce or properly use the metabolic hormone insulin, resulting in elevated blood glucose – has affected an outsized percentage of veterans. About 25 million Americans have diabetes – about 8 percent of the population – and nearly twice that number are at risk to develop the disease. By comparison, nearly one out of every four veterans using the VA health system has the disease.
The VA’s diabetes research program is aimed at the disease from every angle, investigating the basic science underlying diabetes and its complications, better ways to prevent or treat the disease, and strategies or technologies that can be used by health care providers to maximize access to diabetes care and improve outcomes.
The most common form, accounting for 90 to 95 percent of cases, is type 2 diabetes. It’s a devastating disease, with long-term complications that can affect every part of the body. It’s the leading cause of blindness, end-stage kidney disease, and amputation for VA patients, and often leads to stroke, nerve damage, and cardiovascular disease, which is the leading cause of death among all diabetics.
The VA’s diabetes research program is aimed at the disease from every angle, investigating the basic science underlying diabetes and its complications, better ways to prevent or treat the disease, and strategies or technologies that can be used by health care providers to maximize access to diabetes care and improve outcomes.
For 35 years, Dr. Jim Sowers, a VA investigator and director of the Thomas W. and Joan F. Burns Center for Diabetes and Cardiovascular Research at the University of Missouri-Columbia School of Medicine, has conducted VA-funded research into the basic mechanisms by which diabetes promotes cardiovascular disease. He’s been a practicing endocrinologist for 43 years, currently at the Harry S Truman Memorial Veterans Hospital. “About two-thirds of all patients seen by cardiologists present with either diabetes or impaired glucose metabolism,” he said, “and diabetes is a promoter of atherosclerosis, myocardial infarction, and heart failure … so we’ve been exploring basic fundamental mechanisms underlying the cardiovascular disease that’s associated with diabetes.”
In studies that have focused primarily on rodent models, Sowers has studied the role of insulin resistance in high blood pressure and cardiovascular disease. “We’ve been studying animal models that have been fed Western diets high in fructose and fat,” he said. “We’ve been studying hormonal mechanisms or systems, such as the renin-angiotensin-aldosterone system [RAAS], involved in diabetes-related cardiovascular disease.” The RAAS is the hormone system that regulates blood pressure and blood volume. “We’ve also explored how this diet promotes high blood pressure and cardiac disease.”
These explorations, said Sowers, are laying the groundwork for investigations into interventions – both behavioral and medical – that can improve clinical outcomes for diabetic veterans. For example, in his own work, Sowers has explored the efficacy of diuretics and angiotensin receptor blockers in preserving the insulin response in obese subjects with hypertension.
The relationship between diabetes and cardiovascular disease long has been known, if not completely understood, but VA researchers have also uncovered associations between the disease and other conditions. Researchers from the San Francisco VAMC and the University of California-San Francisco recently found that cognitive decline tended to occur more rapidly, over a nine-year period, among diabetic patients over 70 than among those who did not have diabetes at the outset. In February 2014, a team led by researchers from the VA Puget Sound Health Care System found that service members who suffered from sleep disorders, such as insomnia or sleep apnea, carried a higher risk for diabetes.
Retired U.S. Air Force Master Sgt. Alfredo Alferez undergoes a screening for diabetes, provided by the 61st Medical Group, at the annual Retiree Expo in the Gordon Conference Center, Los Angeles Air Force Base, California, June 26, 2010. U.S. Air Force photo by Joe Juarez
Dr. Leonard Pogach, the VA’s former program director for diabetes and now its national director of medicine, cautions that these observational associations, without a randomized clinical trial to further isolate other variables, cannot imply a cause/effect relationship – and therefore it’s inappropriate to conclude that treating one condition will have any effect on another.
“Clearly there are associations between diabetes and things such as sleep apnea, cognitive dysfunction, and decreased hearing,” Pogach said, “but we have to try to understand the reasons for these associations. For example, cognitive impairment: Is it due to glycemia [blood glucose], or is it due to underlying vascular disease, which is often common with people with type 2 diabetes and may have occurred for many years beforehand? Or do both contribute? … It’s not accurate to state that you need to treat a certain condition because it will prevent X, Y, or Z.”
Exploring Prevention and Treatment
One recent clinical trial that may help refine our understanding of diabetes was reported in the June 12, 2014, New England Journal of Medicine by a team including researchers from the Philadelphia VAMC, the University of Pennsylvania, and Temple University School of Medicine, who explored the effects of treatments for weight loss and sleep apnea – a condition strongly linked to obesity – on 90 patients. To separate the risks obesity poses compared to those posed by sleep apnea, the team divided subjects into three groups: those who were treated only for obesity; those who were treated only for sleep apnea with the use of a continuous positive airway pressure (CPAP) system; and those who were treated for both issues.
VA researchers are also conducting an innovative “point-of-care” study of 3,000 veterans with diabetes, comparing the outcomes for two methods of insulin administration: the sliding-scale regimen and the weight-based protocol.
The team found that a 24-week weight-loss program, whether it was accompanied by CPAP therapy or not, significantly reduced inflammation and insulin resistance. CPAP therapy alone did not provide these benefits – but did reduce blood pressure. The two treatments combined produced the largest declines in blood pressure. In an interview with Reuters after the study was reported, lead author Dr. Julio Chirinos of the Philadelphia VAMC summed up the study’s primary implication: “Whether or not you get CPAP,” he said, “the weight loss is the essential component for reducing cardiovascular risk. It’s obesity that needs to be targeted.”
The treatment for type 2 diabetes involves lifestyle interventions, the reduction of other cardiovascular risk factors, and glycemic control with the use of medication. VA researchers are participating in a five-year National Institutes of Health (NIH) study aimed at expanding our knowledge of diabetic drugs commonly used in combination with Metformin, the first-line treatment used by physicians. The Glycemia Reduction Approaches in Diabetes (GRADE) trial is expected to include 5,000 participants nationwide, and will compare the long-term risks and benefits of four widely used drugs: sulfonylurea, which directly increases insulin levels; DPP-4 inhibitor, which boosts insulin levels indirectly by stimulating the release of an intestinal hormone; GLP-1 agonist, which increases the amount of insulin released in response to nutrients; and long-acting insulin.
VA researchers are also conducting an innovative “point-of-care” study of 3,000 veterans with diabetes, comparing the outcomes for two methods of insulin administration: the sliding-scale regimen and the weight-based protocol. Developed by a team including experts from VA’s Boston Health Care System, Boston University, and Stanford University, the study is significant for the way in which it uses the VA’s electronic health records to identify potential subjects, randomly assign them one of the treatment regimens, and report outcomes in real time.