Using big data and genetics to understand how insomnia impact the relationship between depression and type 2 diabetes

Research Spotlight Blog No.4

Dr. Renu Bala is a postdoctoral research associate at the University of Exeter with over eight years of research experience and a background in reproductive genetics. Her research focuses on understanding the causal relationship between major depressive disorder and type 2 diabetes and identifying the risk factors that may explain this link. She primarily uses large-scale genetic data, including genome-wide association studies and individual-level datasets such as the UK Biobank, applying Mendelian Randomization and other statistical genetics approaches. Her current work investigates how sleep disturbances are connected to both depression and type 2 diabetes risk.

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Major depressive disorder (MDD) and type 2 diabetes (T2D) are among the most serious global health challenges of our time and surprisingly, they have a very high degree of co-occurrence. In the UK, around one in six people experiences depression, with women being more commonly affected than men (Reference). Globally, about 11% of people live with depression and 9% with type 2 diabetes, and growing evidence shows that each condition increases the risk of developing the other.

At the University of Exeter, our research group (led by Prof. Jess Tyrell) has been working to understand the aetiology of depression and other severe mental health conditions like bipolar disorder and schizophrenia using large-scale genetic data. Research from our group has previously demonstrated that having a genetic risk of higher body mass index (BMI) (Reference) and being an evening person (Reference) increases your risk of depression.

We have recently shown that there is a bidirectional causal association between depression and T2D, meaning that that having one condition increases the risk of developing the other (Reference). Our work also showed that the risk factors like BMI and insulin-resistance partially contribute to this link, but they don’t fully explain it. This led us to explore other possible contributors, particularly sleep.

The sleep-wake cycle and circadian rhythms help regulate many vital processes in the body, including mood and metabolism. Reduced sleep duration has become increasingly common in modern society due to lifestyle, rising screen time etc., as well as social media use. Studies have consistently shown that poor sleep quality and insomnia (difficulty falling or staying asleep) are linked with both obesity and T2D risk. Inadequate or disrupted sleep is also associated with insulin resistance and higher HbA1c (glycated haemoglobin, often referred to as blood sugar) levels (Reference) - risk factors for T2D.

Illustration showing causal association between MDD and T2D and some plausible risk factors involved in this relationship

Given the established role of sleep-disturbances in both mental and metabolic health, we investigated whether insomnia contributes to the MDD-T2D relationship. We have used both genetic (genome-wide association study (GWAS) and UK Biobank) and longitudinal data to thoroughly investigate this. Genetic analysis showed that the strong genetic correlation between MDD and T2D decreased when adjusted for the effects of insomnia. Using Mendelian randomization (MR) - a technique that uses genetic data to establish causal relationships; we found evidence of a bidirectional causal association (both in GWAS and UK Biobank data), where MDD and T2D both predicted higher insomnia risk, and in reverse insomnia increased the risk of both conditions. Mediation analyses further revealed that insomnia explained around 22.8% of the effect of MDD on T2D, and 28.4% of the effect of T2D on MDD.

Because insomnia is also a common symptom of depression, it can be challenging to determine which comes first. Moreover, using methods like Mendelian Randomization (MR) we can only estimate the lifetime genetic risk to a condition but not at a specific time point. To address this limitation, we also analysed longitudinal electronic health records from the Clinical Practice Research Datalink (CPRD) (this dataset is linked to patient health records from GPs in the UK) to examine whether the timing of insomnia diagnosis influenced diabetes risk in depression patients.

Our preliminary results show that developing insomnia after a diagnosis of depression was linked to a higher risk of T2D, although there was also some evidence of reverse causality (insomnia causing depression in return). Overall, our findings suggest that the relationship between insomnia, depression, and T2D is highly complex. Insomnia may act as a mediator, collider as well as a confounder in this association. Nonetheless, there is consistent evidence supporting insomnia as a partial mediator and an independent risk factor in the MDD-T2D relationship, highlighting its potential as an important clinical target for preventing and managing these conditions.

Support from Circadian Mental Health Network

I am truly grateful to have received the Early Career Researcher Pilot Grant from the Circadian Network. This grant has provided me with an invaluable opportunity to lead project planning and execution, as well as to present my work at several conferences, including Diabetes UK (February 2025, Glasgow) and the Circadian Mental Health Network Conference (June 2025, Edinburgh). Both conferences were incredible experiences that allowed me to engage with fellow researchers, exchange ideas, and learn about the latest developments in related fields. Our work presented at Diabetes UK conference was highly appreciated, nominated for the “Psychological Care Poster Award,” and featured as one of the research highlights of the conference. I have also received an opportunity to present (oral presentation) at the upcoming British Sleep Society Conference (November 2025, Brighton).

Circadian Mental Health Network Conference (Edinburgh, June 2025)

Apart from academic conferences, I had the opportunity to share my research with the public at the “Pint of Science” event, an annual worldwide science outreach programme where researchers discuss their work in informal public spaces such as pubs and cafes. Following this, I was also invited to speak and share my work again at a local science festival in Sidmouth. It was a truly rewarding experience to share my research with the wider community and engage with the audience.

Glimpses of the Pint of Science Event (Exeter, May 2025)

Blog by Renu Bala