Author: Hamna Khan - Batterjee Medical College
Diabetes: a condition 99% of us have come across in our lifetime. We often assume that diabetes is a stand-alone condition affecting the elderly and obese. Far from the truth! Surprisingly, it is not widely known that diabetes is present among several patients diagnosed with schizophrenia (I asked around, and no one knew!). Schizophrenia is often comorbidly associated with several physical health issues, like type 2 diabetes mellitus, obesity, and high blood sugar. The concept of diabetes as an illness affecting the body's physical health is now seen paradoxically to have its fair share of effects on mental illnesses. Diabetes among schizophrenic patients is widely known by doctors and is often categorized as an effect of the medications used. This understanding was challenged by researchers in Hungary. By conducting a cross-sectional study, sort of like a single snapshot in time, researchers were able to test the association between type 2 diabetes mellitus (DM), schizophrenia, and metabolic syndrome (MetS). It is essential to note that this study examines the associations, rather than the causal relationship, between the three.
A total of 218 patients from 3 distinct psychiatric institutions were recruited under specific inclusion criteria. Among these, 103 were diagnosed with schizophrenia (SCZ) alone, 62 with schizophrenia plus MetS (SCZ+MetS), and 53 with schizophrenia plus type 2 DM (SCZ+DM). Through a gold-standard cognitive test, called the Repeated Battery for the Assessment of Neuropsychological Status (RBANS), they were able to quantify and provide clear evidence that patients diagnosed with the combination of schizophrenia and diabetes mellitus scored the lowest in terms of attention and delayed memory.
So what could be causing this sharp decline? Researchers further moved their study to determine the underlying cause of this cognitive decline. To trace this inflammation, they measured two key markers in the blood: interleukin-6 (IL6), an inflammation kick-starter, and C-reactive protein.
Generally, all patients presented with high levels of interleukin-6. However, comparatively, amongst themselves, group SCZ+DM resulted in higher levels of interleukin-6. The C-reactive protein levels remain the same in all groups, suggesting IL-6 is the major contributor to this neurocognitive decline. As we know, IL-6 plays a role in inflammation initiation. In addition to this, another recent study published in 2021 also recognised IL-6 levels to be higher in patients with major depressive disorders (MDDs). This suggests that IL-6 may be a common inflammatory thread linking different mental health conditions and metabolic dysfunction.
One may assume that the reason for high IL-6 would be due to a greater level of fat storage in patients with DM, which, although a compelling argument, is inaccurate in terms of this study. A closer examination of this study reveals that total BMI and fat percentage are similar across all patient groups, regardless of diagnosis.
So, if not a higher fat percentage, then what is the underlying cause that makes SCZ+DM patients different from the rest? High blood glucose and insulin resistance are seen predominantly in patients suffering from type 2 DM. This suggests that, alongside fat, an increase in glucose levels and insulin resistance fuels the inflammation caused by IL-6, eventually leading to cognitive decline.
To sum up this cascading pathway: Dysregulated metabolism (the state of diabetes) → Chronic Inflammation (high IL-6) → Brain Dysfunction → Further worsening of attention and delayed memory.
This study thus proposes that diabetes further fuels inflammation, elevating IL-6, which acts as a biological toxin that disrupts the brain's memory and attention networks. So, schizophrenia not only affects the mind of a person but also their physical health. This biologically compelling finding calls for action to be taken by forming interdisciplinary teams of endocrinologists/diabetes specialists and psychiatrists. Treating diabetes through integrated care for these patients is now a brain-preserving strategy. Additionally, the traditional belief that diabetes in schizophrenic patients is “just medications” is challenged, opening upgrounds for discussion regarding everything we know about mental illnesses as a whole.
Furthermore, researchers also call for longitudinal research to be conducted to confirm the effect and causal relationship. Such new findings propel us, as the general public, to ask insightful questions like: Could IL-6 be used as a new biological marker? Could approaching schizophrenia through anti-inflammatory approaches show results?
The fate of schizophrenic patients may change by managing diabetes, which could be a key to protecting their minds.
References:
1. Kancsev, A., Engh, M. A., Horváth, A. A., Hegyi, P., Kelemen, O., & Kéri, S. (2025). Association between metabolic syndrome, diabetes mellitus, inflammation and cognitive dysfunctions in schizophrenia: a cross-sectional analysis. Schizophrenia, 11(1), 148.
2. Roohi, E., Jaafari, N., & Hashemian, F. (2021). On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?. Journal of neuroinflammation, 18(1), 45.