Depression Drugs Increase Risk for Diabetes

by Mark Benson on February 5, 2012

Antipsychotic drugs increases diabetes risk

According to statistics in 2008, nearly 14.3 million individuals in the United States have been prescribed and using medication for many emotional disorders such as bipolar disorder, schizophrenia and others. One of the known metabolic side effects of taking these kinds of medication was obesity leading up to diabetes.

This side effect often leaves patients in a dilemma, whether to continue treatment for their mental health issues or damage their physical health. Now, a recent study conducted at the Sanford-Burnham Medical Research Institute found the activating mechanism that psychotherapy drugs trigger leading to the dreaded side effect.

According to the study, which was published in January 31, 2012 in the medical journal Molecular Psychiatry, the drugs activate the protein called SMAD3, an integral part of the transformation of the growth factor beta pathway. This TGFbeta pathway is a cellular level mechanism regulating many of the biological processes, such as cellular growth, inflammation and insulin signaling. The study found the drugs that cause metabolic side effects activated SMAD3 while those not taking the drugs did not have the same side effects.

It was also found that this phenomenon was free and independent from the neurological therapy, begging the question if antipsychotics can be formulated to have beneficial effects for the brain without the dastardly effects on the metabolism of the patient.

According to Fred Levine, MD, PhD, and current Director of the Sanford Children’s Health Research Center at Sanford-Burnham, “We now believe that many antipsychotics cause obesity and diabetes because they trigger the TGFbeta pathway. Of all the drugs we tested, the only two that didn’t activate the pathway were the ones that are known not to cause metabolic side effects.”

Using previous studies to develop new inroads against diabetes, the team of Dr. Levine used the Sanford-Burnham’s high-throughput screening capabilities to find a collection of known drugs for those that modify the body’s ability to create the hormone insulin. This hormone helps the body regulate blood glucose levels in the body. There they observed that antispsychotic drugs altered the activity of the gene that produces insulin. Now, they were able to find the link between the drugs and insulin. They were able to isolate the connection during laboratory experiments through the side effects that activated the TGFbeta pathway. This is where insulin is altered as a result of the use of antipsychotic drugs.

To find the real world applications for their findings, the researchers then analyzed other studies as to the genetic expression patterns in brain tissue from patients suffering from schizophrenia and long-term user of antipsychotics. These findings supported their previous observations, leading to the conclusions found in the published paper.

Dr. Levine further added, “”It’s known that people who have elevated TGFbeta levels are more prone to diabetes. So having a deregulated TGFbeta pathway – whether caused by antipsychotics or through some other mechanism – is clearly a very bad thing. The fact that antipsychotics activate this pathway should be a big concern to pharmaceutical companies. We hope this new information will lead to the development of improved drugs.”


The opinions expressed in this article do not necessarily reflect the views of the DiabetesForum.com Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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