Adults with diabetes may be at higher risk for developing mild cognitive impairment, a condition that is often seen as a precursor to Alzheimer’s disease, new research found.
“There is mounting evidence that diabetes is bad for cognition,” said Dr Jose A. Luchsinger, the lead author of the study and an assistant professor of medicine at Columbia University. “The mechanisms need to be elucidated. Type 2, or adult-onset diabetes, which the study refers to, is increasing in the US and in the world. The consequences of the potential cognitive complications of diabetes could be devastating from a public health standpoint.”
Still, there are perhaps more questions than answers in the new study, which was published Monday in the April issue of Archives of Neurology.
“What is the real message for diabetes control?” asked Dr Larry Deeb, president of medicine and science for the American Diabetes Association. “If the message is that you’re at greater risk for MCI (mild cognitive impairment) no matter what, that’s one thing. If taking good care of blood sugar makes a difference, as seems to be the case for most other complications of diabetes, that’s another thing. One would hope this might be another argument for controlling diabetes.”
Health experts already knew that type 2 diabetes can be a risk factor for Alzheimer’s disease. The evidence has been less clear on whether diabetes is related to a higher risk of mild cognitive impairment, often considered a bridge state between normalcy and Alzheimer’s.
“There are few studies looking at the outcome of mild cognitive impairment,” Luchsinger said.
How the study was conducted
For this study, Luchsinger and his colleagues looked at 918 men and women older than 65 (average age 75.9) who did not have mild cognitive impairment or dementia at the start of the study. The participants, all from northern Manhattan in New York City, were assessed every 18 months with an in-person interview as well as physical and neurological examinations.
Almost one-quarter - 23.9 percent - of the participants had diabetes, 68.2 percent had high blood pressure, 33.9 percent had heart disease, and 15 percent had suffered a stroke.
During follow-up that averaged 6.1 years, 334 of the participants developed mild cognitive impairment. And people with diabetes had a higher risk of having mild cognitive impairment, especially amnestic MCI, which affects memory more than non-amnestic MCI.
Diabetes tied to impairment
Overall, 8.8% of cases of mild cognitive impairment among the study participants could be attributable to diabetes. And the rates were higher for black Americans (8.4 percent) and Hispanics (11 percent) than for non-Hispanic whites (4.6 percent). This makes sense, given that minority populations in the United States have a higher prevalence of diabetes.
What explains t?e possible link between diabetes and impairment?
Diabetes could contribute to plaque build-up in the brain, with such a build-up a hallmark of Alzheimer’s, the study authors said.
But, they added, more research is needed.
“Studies are needed to see if preventing diabetes prevents cognitive impairment and how diabetes treatment affects cognition,” Luchsinger said. “We also need to see how cognitive impairment in persons with diabetes affects their ability to follow their treatment, which is usually complex and involves several medications.”
Other experts applauded even the tentative findings.
This type of research may help target populations who could one day benefit from drugs, said Maria Carrillo, director of medical and scientific relations at the Alzheimer’s Association.
Risk factors are real
“This supports the idea that risk factors are real,” Carrillo added. “The field has now matured to a point where we can start looking at earlier and earlier aspects of the disease. It makes sense to look even earlier than that and try to tease out what the risk factors look like in that population, in case we have a disease-modifying drug coming up in near future.”
“This is documenting what we know a little bit better and emphasising that patients should control their blood sugar as well as they can early in the disease,” added Dr Joel Zonszein, director of the Clinical Diabetes Centre at Montefiore Medical Centre in New York City. “This is another piece of information, more wood to the fire.” – (HealthDayNews)
A new charity-biz collaboration is testing proteins that could prevent the immune system from destroying insulin secreting cells and help prevent the onset of diabetes.
MediGene has signed a two year deal with the Juvenile Diabetes Research Foundation (JDRF). The charity will pay €250,000 to help the Germany-headquartered biotech company advance its monoclonal T cell receptor (mTCR) therapeutics towards clinical trials. The soluble proteins are engineered to recognise intracellular antigens and block an immune system response by T cells.
These antigens are inaccessible for traditional monoclonal antibodies and so, the soluble T cell receptor technology opens a new field of options to target cancer, autoimmune, allergic and infectious diseases, according to the company.
Normally in Type I diabetics, receptors on the surface of T cells bind to antigens on pancreatic islet cells, which are responsible for the production of insulin. This marks them for destruction.
In its diabetes programme, MediGene has manufactured specific mTCRs which could bind to islet cell antigens, blocking them and preventing real T cell receptors from attacking the cells - “somewhat like taping over a keyhole to prevent a door from being unlocked,” according to the company.
MediGene also hopes the mTCRs could target known immunosuppressive agents to the islet cell’s local environment.
“Provided autoimmune destruction can be tamed, both the early diagnosis of pre-diabetic individuals and the recent advances in islet transplantation therapy offer the prospect of patients being able to maintain endogenous insulin production, with consequent improvements in quality of life,” said Dr Ulrich Delvos, chief operating officer at MediGene.
“MediGene’s mTCR technology holds the promise of tackling the underlying cause of this autoimmune disease.”
Dr Neill MacKenzie, MediGene’s head of commercial strategy and business development, explained to DrugResearcher.com that strategies to replace the body’s insulin directly or improve its ability to produce and use insulin do not prevent many side effects such as blindness, heart attacks, loss of limbs and kidney function.
MediGene hope to overcome this by creating a “therapy that tries to maintain some level of islet functioning,” said Dr MacKenzie. He explained that the mTCRs are currently in preclinical testing and it would be “at least a couple of years before first-in-man trials.” That is partly because animal models of diabetes take time to generate and this slows research down: “First we have to generate diabetes, and then cure it,” said Dr MacKenzie.
Dr MacKenzie explained that the technology’s main other application is in cancer where it could be used in exactly the opposite way - to activate an immune response and kill tumour cells. He also said that early on, MediGene had looked at using mTCRs as a drug delivery mechanism but it is not looking into it anymore because it “doesn’t think it has enough power”.
If, in the future, they decided to resurrect this research, Dr MacKenzie pointed to Wyeth’s Mylotarg (gemtuzumab ozogamicin) product as an example of how it might be achieved. Mylotarg is an anticancer drug composed of an antibody attached to a toxic antitumor antibiotic.
JDRF also supports other industry diabetes research, including studies at AGTC, Develogen, ESI, Genzyme, Novocell, Macrogenics and Tolerx. The last two are the most advanced research sponsored by the charity with both companies conducting Phase II trials of antibodies that target the CD3 T cell receptor called CD3. Both therapies aim to disarm T cells once they have become activated to attack islet cells.
“Targeted delivery of therapeutics is an attractive prospect,” said Dr Richard Insel, head of research at JDRF.
“This collaboration between MediGene and JDRF provides an exciting opportunity to validate the concept, and hopefully identify a lead compound for entry into the clinic.”
Talking about the JDRF support, Dr MacKenzie said: “It could hopefully lead to a much bigger grant - if we’re successful.”