A startling and worrisome new study conducted at the University of Haifa has found that people who are diagnosed with type-2 diabetes – especially women – face a 50% percent higher risk of developing schizophrenia than those without diabetes. This finding reveals a surprising link between a common metabolic disease and one of the most severe psychiatric disorders.
“Type 2 diabetes is already known to raise the risks of multiple health conditions, including heart disease and dementia. Our findings show it also increases the risk of schizophrenia. This underscores the need to integrate psychiatric follow-up into diabetes care,” said study leader Prof. Stephen Levine from the university’s School of Public Health, an expert in psychiatric epidemiology, clinical trials, psychometrics, schizophrenia, dementia, suicide, and autism spectrum disorder. It has just been published in the journal Schizophrenia Bulletin under the title “The Risk of Very-Late-Onset Schizophrenia Following Diabetes Type 2 Onset: A Nationwide Population-Based Study of Midlife and Old-Age.”
Type-2 diabetes is one of the most common chronic diseases in the world, characterized by high blood-sugar levels and associated with damage to blood vessels, the heart, and the nervous system. In 2022, an estimated 14% of adults aged 18 and older were living with diabetes in Israel and abroad, with some 600 million people around the world suffering from the disease, which is a leading cause of death and damage to health.
Schizophrenia is a severe mental disorder marked by hallucinations, delusions, and a disconnect from reality. Affecting about one percent of the population, it is considered the most severe psychiatric disorder due to its impact on social and occupational functioning, reduced longevity, and disruption of the lives of patients and their families.
In the present study, Levine, Prof. Arad Kodesh from the university’s Department of Community Mental Health, Meuhedet Healthcare Services, and Prof. Abraham Reichenberg from the psychiatry department at New York’s Mount Sinai Hospital sought to examine whether a history of type-2 diabetes in middle and older age increases the risk of developing schizophrenia.
THE STUDY’S population consisted of 99,567 Israelis aged 51 to 71 (born between 1932 and 1952), all members of the Meuhedet Health Fund and without a prior history of type-2 diabetes or schizophrenia. Participants were followed for approximately 17 years, from January 2003 to February 2020. This extensive dataset allowed the researchers to identify long-term links between diabetes and schizophrenia.
The results indicated that people diagnosed with type-2 diabetes were 50% more likely to develop schizophrenia than those without diabetes. The risk was particularly pronounced among women, where the link was statistically significant.
Those with schizophrenia have higher risk of developing type-2
In addition, the team found that patients with schizophrenia have a two- to three-fold higher risk for developing type-2 diabetes compared to the general population, and after developing the metabolic disease, a three- to four-fold higher mortality rate than those with only type-2 diabetes.
LEVINE, WHO came on aliyah from the UK in 1988, told The Jerusalem Post that the findings were the result of a longitudinal study covering almost 20 years of follow-up. He chose to work with Meuhedet Healthcare Services – the third-largest of the four public health funds – because he has “had a good relationship with them for a long time.”
“There are two forms of schizophrenia,” he said, “the most common appearing in late adolescence or early adulthood. But there is another substantial, late-onset subgroup that can begin from age 50. The first type is more common in males and the second type in females.”
Schizophrenia is a serious psychiatric illness that affects how a person thinks, feels, and behaves. Sufferers may seem as though they have lost touch with reality, with delusions (believing in things that aren’t real or true), hallucinations (seeing or hearing things that other people don’t), be very disorganized or have unusual motor behavior, disorganized speech and thinking, and various other negative symptoms.
“Type-2 diabetes was found in the study to more than double the risk of developing schizophrenia over the age of 60, especially among women” Levine explained. “This means that per 100,000 people followed up over time who have diabetes, 26 will develop schizophrenia instead of 12 per year who do not have the metabolic disease. Fully 52.7% of those who developed the mental disease were women. They can be identified by asking them just four or five questions. Often, a member of her/his family also suffers from schizophrenia.
“It can’t be prevented completely, but eating a nutritious diet, carrying out regular physical activity and other evidence-based practices can reduce the risk and severity,” he said. “Old age and diabetes may be linked partly by genetics, but there are environmental factors including sedentary behavior and obesity.”
PSYCHIATRISTS ARE aware that people with schizophrenia are at higher risk of diabetes but few of them know that the opposite may also be true, Levine stated. “I believe that our study is the first of its kind to discover the connection. Physicians should check older people for the two disorders. There may be common genes and lifestyles.”
Treatment includes antipsychotic medications – of which there are several, not one magic pill for everyone. Psychoanalysis is not effective. There is a three- to four-fold higher mortality rate among people suffering from both diseases than those who are only type-2 diabetics.
“This is the most comprehensive study conducted so far on this subject, and it provides new evidence of the link between diabetes and schizophrenia. The findings call on the health system to provide psychiatric follow-up and support for diabetes patients, particularly in older age,” Levine urged.
The researchers suggest that these findings could change how diabetes is approached and may lead to new policies that include psychiatric monitoring as an integral part of patient care. Implementing such measures could allow early identification of high-risk individuals and help prevent considerable suffering for patients and their families.
Among the widely discussed reasons proposed for this association are atypical antipsychotic medication use, and the increased presence of known risk factors for diabetics in those with schizophrenia, especially obesity, poor diet, and sedentary lifestyle.
Nevertheless, several lines of evidence suggest that the association between diabetes and schizophrenia may also be reversed: T2D may be associated with an increased risk of schizophrenia. First, in first-ever schizophrenia patients, the prevalence of diabetes is elevated in the year before the diagnosis of schizophrenia. In addition, in first-episode psychosis patients, there is an increased prevalence of various abnormal glucose markers. Third, the risk of diabetes is increased in siblings of individuals with schizophrenia.
Furthermore, family histories of diabetes and schizophrenia were found to be linked, suggesting that shared familial risk factors may be involved, the team wrote.
MEUHEDET PROVIDES nationwide healthcare services to 14% of the Israeli population. Before January 2005, participants with a history of a diabetes diagnosis or medication or a schizophrenia spectrum disorder from 2002 to 2004 were not eligible for inclusion in the study. The background information was age, neighborhood socioeconomic status, and smoking status.
“Our study provides the strongest evidence to date in support of the hypothesis that type-2 diabetes is associated with an increased risk of incident schizophrenia in middle and old age,” they wrote. “One possible explanation is that there are shared genetic factors influencing the risk for both diabetes and schizophrenia. Another possible explanation is through common stress-related processes given that stress is a potential risk factor for schizophrenia and diabetes in adults,” they wrote.
“Furthermore, diabetes is associated with decrements in cognitive function and changes in brain structures known to be associated with schizophrenia. Poor cognitive functioning is a core symptom of schizophrenia, and cognitive decline predates the onset of schizophrenia. Plausibly, in some patients, the onset of diabetes leads to a cascade of downstream changes in the brain that could trigger psychosis.”
Diabetes was associated with a higher risk of late-onset schizophrenia in women, they wrote. “This finding may be of clinical significance since the incidence of old-age schizophrenia is higher among females than males. Multiple tentative mechanisms, such as estrogen loss, may be postulated for this association among females,” the study said.
“Nonetheless, while a signal toward increased risk was observed among males, it was not statistically significant, possibly due to the small number of males with diabetes and schizophrenia,” they said. “Future research with larger samples of males is warranted for firmer conclusions regarding sex differences in the association. Among those with diabetes, additional factors, such as loneliness and social isolation, may also contribute to sex differences in the risk of schizophrenia.”