Office of Research & Development

Diabetes

diabetes icon

Diabetes is a chronic disease in which the body cannot produce or properly use insulin. Normally, insulin brings sugar out of the bloodstream and into cells. If the body cannot make insulin or does not respond to it, the sugar stays in the bloodstream. As a result of high blood sugar levels, damage eventually occurs to blood vessels and organs.

More than 20 million Americans have diabetes, and more than 40 million more Americans are at risk to develop the disease. Many Veterans have the disease, including some who developed it as a result of being exposed to herbicides while serving in Vietnam. About one in five VA patients has the condition.

Symptoms of diabetes include blurry vision, excessive thirst, fatigue, frequent urination, hunger, and weight loss. Persons with diabetes need to have their hemoglobin A1C levels checked every three to six months.

A1c is a measure of average blood glucose during the previous two to three months. It is one of the markers, along with blood pressure and cholesterol control, of good diabetes care.

VA researchers are studying innovative strategies and technologies, including group visits, telemedicine, peer counseling, and Internet-based education and case management, to enhance access to diabetes care and to improve outcomes for patients.

In addition, VA researchers are working to develop better ways to prevent or treat diabetes, especially in special populations such as the elderly, amputees, minorities, spinal cord injured patients, and those with kidney or heart disease.

VA's Diabetes Quality Enhancement Research Initiative (QUERI), located in Ann Arbor, Mich., is committed to research and collaborations that promote the use of effective care strategies to help Veterans with diabetes, and those at risk for the disease, to live longer and better lives.

Selected Major Accomplishments

  • VA researcher Rosalyn Yalow, PhD, received the Nobel Prize in physiology or medicine for developing a new way to measure insulin and other hormones in the blood.
  • The VA Diabetes Trial found that intensively controlling insulin does not significantly reduce the risk of heart disease.
  • VA researchers have learned there is a link between low blood sugar and dementia in older adults.
  • Sleep apnea and poor sleep quality predict diabetes, independent of other diabetes risk factors or mental health, according to the VA-Department of Defense Millennium Cohort Study.

Selected Milestones and Major Events

Overview

Diabetes is a chronic disease in which the body cannot produce or properly use insulin. Normally, insulin brings sugar out of the bloodstream and into cells. If the body cannot make insulin or does not respond to it, the sugar stays in the blood where it damages blood vessels and organs.

There are three major types of diabetes. Type 1 diabetes is usually diagnosed in childhood. In this type of diabetes the body makes little or no insulin, so daily injections of insulin are needed.

Type 2 diabetes usually occurs in adults. In this type of diabetes, the pancreas does not make enough insulin to keep blood glucose levels normal, often because the body does not respond well to insulin. More than 90 percent of adults with diabetes have type 2 diabetes. More are at risk due to overweight or obesity.

The third type of diabetes is gestational diabetes, high blood glucose that develops during pregnancy in a woman who does not have diabetes.

Diabetes affects about one million Veterans within the VA health care system, nearly 20 percent of VA's patient population. The disease is also the leading cause of blindness, end-stage renal disease, and amputation for VA patients.

VA researchers are seeking better ways to prevent and treat diabetes, especially in special populations such as the elderly, minorities, those with amputations or spinal cord injuries, and those with kidney or heart disease.

Work of Nobel laureates

Two of VA's three Nobel laureates have done important work to benefit Veterans with diabetes. The late Rosalyn S. Yalow, PhD, received the Nobel Prize for Physiology or Medicine in 1977 for her work in discovering the radioimmunoassay, an extremely sensitive way to measure insulin and other hormones in the blood. The technique made possible major advances in diabetes research and in diagnosing and treating hormonal problems related to growth, thyroid function, and fertility.

Andrew V. Schally , PhD, MDhc, DSc, who also received the Nobel Prize in Physiology or Medicine in 1977 for his discovery that the hypothalamus links the nervous system to the endocrine system via the pituitary gland, is currently doing research, along with teams of national and international researchers, on growth hormone-releasing hormone (GHRH). Among other possibilities opened up by Schally's work with GHRH is the possibility of reducing or eliminating the need for diabetics to regularly inject insulin.

In 2013, an international research team of which Schally was a part devised a way to transplant healthy cells into the body without the usual risk of rejection. The study involved a middle-aged man with diabetes, but it may be relevant to a range of other diseases as well. The researchers developed what amounts to an artificial pancreas (the place where the body makes insulin), which the patient tolerated well without taking drugs to suppress the immune system.

The VA Diabetes Trial

For seven and a half years, researchers involved in a VA cooperative study (CSP 465) looked at nearly 1,800 patients with diabetes. The study's researchers examined cardiovascular disease, the cause of death in nearly two-thirds of all patients with diabetes.

Researchers attempted to determine whether intensive glucose control (using medication and other methods to reduce the level of sugar in the blood in diabetic patients to levels that would be normal in patients without diabetes) reduced heart attacks, strokes, and death from cardiovascular disease.

It had been previously shown that improvements in blood pressure and cholesterol levels can reduce cardiovascular disease in patients with diabetes, but no previous study had shown the beneficial effects of glucose control on cardiovascular disease.

VADT researchers showed that intensive glucose control in patients whose type 2 diabetes had previously been poorly controlled had no significant effect on the rates of major cardiovascular events such as coronary artery disease and stroke, compared to those who were using standard glucose control measures.

The research team also found that the two groups of patients had similar death rates, and that both groups had similar levels of complications such as diabetic neuropathy and retinopathy, except that patients using standard glucose control measures had higher levels of albumin in their urine. (Albumin in the urine is a possible indicator of kidney disease.)

Trial researchers concluded that both very high and very low blood sugar levels can be dangerous, and that big swings between high and low levels are also potentially harmful.

Other completed studies

In 1996, a team of VA researchers conducted a test that determined an implantable insulin pump offers better blood sugar control, weight control, and quality of life for adult-onset diabetes than multiple daily injections. They found that both therapies reduced total cholesterol and C-peptide (a byproduct created when insulin is introduced) levels similarly.

In 2012, researchers from the San Francisco VA Medical Center, the University of California, San Francisco (UCSF), and the Kaiser Permanente Division of Research found that almost half of the 13,000 adults with type 2 diabetes they studied reported acute and chronic pain, and close to one-quarter reported neuropathy (nerve damage), fatigue, depression, sleep disturbance, and physical and emotional disability.

Another San Francisco VAMC/UCSF study, completed in 2013, found that diabetics with an episode of low blood sugar (hypoglycemia) were twice as likely than other older adults to be later diagnosed with dementia, and that those who developed dementia were three times as likely to later experience low blood sugar. Stroke, heart attack, and high blood pressure did not factor into the relationship.

A study conducted by researchers at the Puget Sound VA medical center that was part of the joint VA-Department of Defense Millennium Cohort Study on the health of service members and Veterans, found that sleep apnea and poor sleep quality predicted diabetes, independent of other diabetes risk factors or mental health status.

Sleep apnea increased the risk of diabetes by 78 percent, and simply having trouble sleeping increased the risk of diabetes by 21 percent. The study included more than 47,000 service members and Veterans who were an average age of about 49.

Finally, VA researchers in 2013 stopped a large multicenter study, part of the Veterans Affairs Nephropathy in Diabetes Study (NEPHRON-D), before its scheduled conclusion. They found that the combination of an angiotensin-converting enzyme (ACE) inhibitor and an angiotensin-receptor blocker (ARB) increases the risk for serious adverse effects in patients with diabetic nephropathy, the leading cause of chronic kidney disease in the United States.

The significant increase in risk caused by taking the combination of drugs overshadowed any benefits taking the drugs may have in reducing the progression of kidney disease.

Ongoing studies

A team of VA and Stanford University researchers is conducting a point-of-care study involving more than 3,000 Veterans with diabetes. In a point-of-care study, volunteers are enrolled within the framework of their visits to their regular health care providers.

The providers draw on data from electronic medical records to determine if a patient is right for a study. Patients who consent to take part are randomly placed into one of two groups, and continue to receive care from their usual providers.

The current study compares two methods of administering insulin to hospitalized Veterans, and it is fully integrated into VA's electronic health system. The system is tracking which of the two treatments is associated with shorter hospital stays.

Eventually, the system's software will begin to direct more patients into the treatment that is proving more effective, allowing evidence from the trial to be incorporated into everyday practice quickly and inexpensively.

VA researchers are participating in a five-year National Institutes of Health study to compare the long-term benefits and risks of four diabetes drugs in combination with metformin. The study, called the Glycemic Reduction Approaches in Diabetes (GRADE) trial, is expected to include some 5,000 participants nationwide.

Metformin is the first medication doctors typically use when treating type 2 diabetes. If metformin does not control the disease, doctors may add one of several other drugs, all of which have been shown to lower blood sugar levels in studies. However, no previous long-term study has focused on which drug combination works best and has the least side effects.

The four drugs being studied are sulfonylurea, dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 agonist, and long-acting insulin. Patients are currently being enrolled for the study at VA medical centers in Atlanta, Cincinnati, Cleveland, Denver, Honolulu, Miami, Omaha, San Diego, and Seattle.

More on our Website

Video: Diabetes Research

Understanding the complex link between diabetes and cognitive health. VA Research news feature.

Treating high blood pressure for those with diabetes: Finding the right balance, VA Research news feature.

VA enrolling participants for groundbreaking diabetes study, VA Research Currents, Spring 2014

Miami VA part of international breakthrough in cell therapy, VA Research Currents, Winter 2013-14

VA Diabetes Quality Enhancement Research Initiative (QUERI), Ann Arbor, MI

Selected Scientific Articles by our Researchers

The Veterans Affairs Implantable Insulin Pump Study; effect on cardiovascular risk factors. Duckworth WC, Saudek CD, Giobbie-Hurder A, Henderson WG, Henry RR, Kelley DE, Edelman SV, Zieve FJ, Adler RA, Anderson RJ, Hamilton BP, Donner TW, Kirkman MS, Morgan NA. Implantable insulin pump therapy in insulin-requiring patients with type 2 diabetes has advantages over multiple-dose insulin therapy in decreasing the requirement for antihypertensive therapy and for decreasing total and free insulin and insulin antibodies. Diabetes Care, 1998 Oct;21(10):1596-602.

Glucose control and vascular complications in Veterans with type 2 diabetes. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, Zieve FJ, Marks J, Davis SN, Hayward R, Warren SR, Goldman S, McCarren M, Vitek ME, Henderson WG, Huang GD, VADT investigators. Intensive glucose control in patients with poorly controlled type 2 diabetes had no significant effect on the rates of major cardiovascular events, death, or microvascular complications with the exception of progression of albuminuria. N Engl J Med. 2009 Jan 8;360(2):129-39.

Agonist of growth hormone-releasing hormone as a potential effector for survival and proliferation of pancreatic islets . Ludwig B, Ziegler CG, Schally AV, Richter C, Steffen A, Jabs N, Funk RH, Brendel MD, Block NL, Ehrhart-Bornstein M, Bornstein SR. Evidence that agonists of GHRH represent a promising pharmacological therapy aimed at promoting islet graft growth and proliferation in diabetic patients. Proc Natl Acad Sci USA, 2010 Jul 13;107(28);12623-8.

Symptom burden of adults with type 2 diabetes across the disease course: diabetes and aging study . Sudore RL, Karter AJ, Juang ES, Moffet HH, Laiterrapong N, Schenker Y, Adams A, Whitmer RA, Liu JY, Miao Y, John PM, Schillinger D. n a diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were common among all patients, not only among those near the end of life. However, symptoms were more prevalent among patients with shorter survival. J Gen Intern Med. 2012 Dec;27(12):1674-81.

Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus . Yaffe K, Falvey CM, Hamilton N, Harris TB, Simonsick EM, Strotmeyer ES, Shorr RI, Metti A, Schwartz AV; Health ABC study. Among older adults with diabetes mellitus, there seems to be a bidirectional association between hypoglycemia and dementia. JAMA Intern Med. 2013 Jul 22;173(14):1300-6.

Sleep characteristics, mental health, and diabetes risk: a prospective study of U.S. military service members in the Millennium Cohort Study. Boyko EJ, Seelig AD, Jacobson IG, Hooper TI, Smith B, Smith TC, Crum-Cianflone NF; Millennium Cohort Study Team. Trouble sleeping and sleep apnea predict diabetes risk independent of mental health conditions and other diabetes risk factors. Diabetes Care. 2013 Oct;36(10):3154-61.

Transplantation of human islets without immunosuppression . Ludwig B, Reichel A, Steffen A, Zimerman B, Schally AV, Block N, Colton CK, Ludwig S, Kersting S, Bonifacio E, Solimena M, Gendler Z, Rotem A, Barkai U, Bornstein SR. Transplantation of pancreatic islets is emerging as a successful treatment for type 1 diabetes. Proc Natl Acad Sci USA, 2013 Nov 19;110(47):19054-8

Combined angiotensin inhibition for the treatment of diabetic nephropathy. Fried LF, Emanuele N, Zhang JH, Brophy M, Connor TA, Duckworth W, Leehey DJ, McCullogh PA, O'Connor T, Palevsky PM, Reilly RF, Seliger SL, Warren SR, Watnick S, Peduzzi P, Guarino P; VA NEPHRON-D investigators. Combination therapy with an angiotensin-converting-enzyme (ACE) inhibitor and an angiotensin-receptor-blocker (ARB) was associated with an increased risk of adverse events among patients with diabetic nephropathy. N Engl J Med. 2013 Nov 14;369(20); 1892-903.

VA and other U.S. Government Online Resources

Diabetes Mellitus Type 2 and Agent Orange, VA Office of Public Health

Diabetes Public Health Resource, Centers for Disease Control and Prevention, National Institutes of Health

National Diabetes Education Program, Centers for Disease Control and Prevention, National Institutes of Health

Diabetes Information, U.S. Food and Drug Administration

Women and Diabetes, U.S. Food and Drug Administration

National Diabetes Information Clearinghouse, U.S. Department of Health and Human Services

Diabetes, U.S. Department of Health and Human Services

Diabetes, Medline Plus, the U.S. National Library of Medicine, National Institutes of Health