Schizophenia and Diabetes
Physician-scientists 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."
Contact: Toni Baker
Medical College of Georgia