For nearly a century, scientists have asked how diabetes affects the aging brain. Now a Long Island medical investigator — with the help of a $4.2 million grant — is beginning the hunt for answers.
Dr. Alan M. Jacobson, chief research officer at NYU Winthrop Hospital in Mineola, has been awarded the money by the National Institutes of Health. He is to lead a consortium of medical centers throughout the United States and Canada with the aim of understanding how Type 1 diabetes affects the most complex organ in the known universe — the human brain.
Participants will be 60 and older, ages when the risk rises for cognitive impairments, with or without diabetes.
Earlier medical investigations have shown that diabetes adversely influences the brain through a telltale triad — uncontrolled blood sugar, high blood pressure and high cholesterol. All three are part of the condition.
The team will be on the lookout for key predictors of cognitive impairments as they collect information on hundreds of people over the next five years. The research is just getting organized, Jacobson said.
His game plan is to delve into every possible nuance about cognitive function under the impact of a lifelong and powerful disease, and employ imaging technology to eavesdrop on each participant’s brain.
“We will be using MRI and a variety of different techniques to study brain structure, brain physiology and changes in vascular blood flow,” Jacobson said. The research will attempt to answer unresolved questions about brain shrinkage, memory loss and cognitive declines in thinking and problem-solving that can occur in some diabetics.
For people with any hints of problems, Jacobson said there is a key strategy to protect the brain: controlling blood sugar — the same strategy that protects the heart, eyes and kidneys, all of which are vulnerable to assault.
Type 1 diabetes is the form of the disease that usually begins in childhood, although not exclusively so, and is marked by a lifelong dependence on insulin to control glucose, or blood sugar.
Type 1 differs from Type 2 diabetes, which is characterized by what doctors call insulin resistance. Those patients generally make some insulin, but their bodies do not utilize the hormone efficiently.
Other scientists have documented memory and cognitive problems in people with Type 2. Jacobson’s research will involve people with Type 1 who have been participating in a large, ongoing research project for more than 30 years. Many of these patients want to know if memory problems will be part of their future.
Questions about diabetes and the brain first emerged nearly 100 years ago, shortly after the discovery of insulin in 1921.
The hormone’s emergence as a medication transformed Type 1 from a death sentence into a manageable chronic disease. Patients were further aided when scientists in the late 1970s produced human insulin through genetic engineering, eliminating the therapeutic use of pig insulin in humans.
As early as the 1980s, research revealed that patients who maintained impeccable glucose control had fewer cognitive problems, said Dr. Gerald Bernstein, an endocrinologist who is not involved in Jacobson’s research.
Bernstein, coordinator of the Friedman Diabetes Program at Lenox Hill Hospital in Manhattan, said “tight control” of glucose aids brain health.
“Glucose is the main fuel for the brain,” Bernstein said. “The brain really doesn’t function without it. But when glucose is elevated, it has an adverse impact on all cells in the body, including the brain.”
Jacobson is well aware of diabetes’ signature on the human brain, which he expects to see in some patients.
“The changes that we are anticipating are decreases in brain volume and alterations in small vessels that manifest as very small bleeds or infarctions — damage to the brain tissue,” he said.
But he also expects that any observations of early adverse signs can pave the way to mitigating the problems.
“We might be able to provide patients with a better sense of what they can do over their lives with Type 1 diabetes to prevent problems in later years [and] avoid cognitive dysfunction,” he said.
A primer on diabetes
Type 1 diabetes. This autoimmune disease occurs when specific components of the immune system attack the insulin-producing beta cells of the pancreas, eliminating the body’s ability to produce insulin and control blood sugar. People with Type 1 are believed to be genetically susceptible to beta cell attack.
Controlling glucose. Blood sugar is monitored around the clock for people with Type 1, usually by way of an insulin pump that is worn. Glucose surveillance occurs via a sophisticated algorithm that detects blood-sugar levels and delivers an appropriate amount of insulin.
Type 2 diabetes. This metabolic disease is caused by insulin resistance, which means the body does not properly utilize the insulin it produces. In early-stage disease, the pancreas makes extra insulin in efforts to control glucose, but over time the beta cells become exhausted and fail.
Insulin resistance. Several factors aggravate resistance: aging, obesity, poor diet and sedentary lifestyle. Medications, diet and lifestyle changes are among the strategies to address Type 2 diabetes. Many people with Type 2 have a genetic predisposition to insulin resistance.
Types 1 and 2 diabetes. Both forms of diabetes can adversely affect kidney function, eye health and the brain. Controlling blood sugar protects the brain, just as tight control also protects the heart, kidneys and eyes.
Sources: Dr. Alan M. Jacobson, Dr. Gerald Bernstein, American Diabetes Association