Study aims to identify schizophrenics at risk for type 2 diabetes

August 21, 2006

Dissecting the relationship between schizophrenia and an increased risk of type 2 diabetes has physician-scientists reaching across the Atlantic Ocean.

They are looking at newly diagnosed schizophrenics in an upper-middle-class Spanish community to find whether the disease that causes patients to hear voices and smell, feel and even taste unreal objects also increases their risk of diabetes.

Scientists know the drugs that best control the psychosis increase the risk. "We know it's the medicine; I'm asking whether it's the disease as well," says Dr. Brian Kirkpatrick, vice chair of the Medical College of Georgia Department of Psychiatry and Health Behavior and principal investigator on the National Institute of Diabetes & Digestive & Kidney Diseases-funded study.

Dr. Kirkpatrick and colleagues at Hospital Clinic at the University of Barcelona in Spain and the University of Maryland note mounting evidence that developmental problems, resulting from significant maternal stress in the second or early third trimester of pregnancy, may cause schizophrenia and related problems.

"The brain has this incredibly complex development where cells are born here and march over here and send communication over here; that goes wrong from the very beginning probably," says Dr. Kirkpatrick of the complex process of laying down normal communication pathways that apparently goes awry in about 1 percent of people.

"It's kind of a subtle going wrong in the sense that if you look at the brain under a microscope, at first blush, it looks pretty normal, and on MRI (magnetic resonance imaging), it looks pretty normal, but there are subtle differences," he says, and not just in the brain.

Patients can have memory and attention problems, wide palates and subtle abnormalities of their fingertips, ear shape and peripheral nerves in their muscles. Psychotic symptoms typically start in late adolescence or early adulthood. "Although psychosis is what we often treat and what tends to be noticeable and dramatic and bring people to medical attention, it's just part of the problem," says Dr. Kirkpatrick.

Researchers believe developmental changes also do something that increases the risk of diabetes. Doctors who treat schizophrenics say they see a lot of it. Relative diabetes risk depends on factors including age and which medications patients take, Dr. Kirkpatrick says. One recent study - based on data from the Clinical Antipsychotic Trials of Intervention Effectiveness Schizophrenia Trials - showed the prevalence rate of metabolic syndrome, a group of risk factors that include abdominal obesity, high lipid and cholesterol blood levels and insulin resistance, is better than 50 percent in women and about 37 percent in men with schizophrenia.

Dr. Kirkpatrick has a chart of weight gain based on drugs used to treat the psychosis that resembles a stairway to disaster. Patients on olanzapine and clozapine, two of the most effective anti-psychotics, gained about 10 pounds within a few weeks. While weight gain is a major risk factor for type 2 diabetes, previous studies have shown the disease also can appear in schizophrenics shortly after they begin treatment and without weight gain.

Studies predating anti-psychotics also have shown schizophrenics have an increased rate of impaired glucose tolerance or insulin resistance, a hallmark of diabetes. "It's not 100 percent, it just changes your risk; bad things in utero increase the risk of diabetes and ... the risk of schizophrenia. It may be they are going to be associated because the same bad things cause both," says Dr. Kirkpatrick.

The bottom line of the study of newly diagnosed schizophrenics is to see whether the disease itself carries an increased risk of diabetes. Researchers are comparing glucose tolerance in these patients to that of healthy people as well as those with untreated depression and those with a recent major crisis. One reason for comparison is that three of the groups should have increased levels of cortisol, a stress hormone that can mimic diabetes by increasing insulin resistance.

Patient enrollment began in 2005 and researchers hope to enroll 82 people in each arm of the study. After initial testing, schizophrenics will receive olanzapine and be followed. Researchers hope to glean measures clinicians can easily use to predict development of insulin resistance with anti-psychotic treatment. Greater insulin resistance prior to treatment may be the measure, Dr. Kirkpatrick says.

The study's catchment area, the Esquerra Eixample neighborhood in Barcelona, was selected because it has a fairly homogenous population and psychiatric researchers can study patients early in the illness. In this case, the Hospital Clinic of the University of Barcelona where most people go, offers the best psychiatric care in the nation, Dr. Kirkpatrick says.

"We want to better understand the totality of schizophrenia and we want to increase the risk-benefit ratio of treatment," says Dr. Kirkpatrick. "If you come in and I know you are at high risk of diabetes, I am going to suggest that you try one of the medications that has the reduced risk of also causing diabetes."

Medical College of Georgia at Augusta University

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