How do anxiety/depression and overall perception of health influence the management of type 2 diabetes?

Student: Shaifali Kulkarni
Primary supervisor: Dr Myzoon Ali
Co-supervisor: Professor John Petrie

The prevalence of type 2 diabetes (T2D) across the world is on the rise, with one estimate suggesting that the number of people living with diabetes will increase from 266 million in 2000 to 366 million in 2030. (1) There has been an increasing amount of research exploring the link between T2D and anxiety/depression. The prevalence rate of depression can be almost two-fold more common in patients with diabetes compared to those without. (2)
People with T2D often report feeling burdened by their medications and self-care involved in regulating their blood glucose levels. (3) They report worrying about the complications of diabetes and feeling guilty for mismanaging their diabetic control. Furthermore, they especially express concern regarding managing their diets, obesity and social stigma. (4) Other factors that contribute to anxiety/depression in diabetic patients include female sex, certain ethnic minorities, low socio-economic status and adverse life events. (5)
In type 1 and 2 diabetes patients, African-Americans were shown to be less likely to report symptoms of depression and use of mental health services compared to other ethnicities. (6) Contrastingly, the Multi-Ethnic Study of Atherosclerosis (MESA) study showed that ethnicity did not affect the link between depression and T2D. (7) One study suggests that depression is more likely to occur in young and female T2D patients, and overall younger patients are at an increased risk of depression compared to older patients. (8) There is a need for further research to explore the role of factors such as ethnicity, age and sex in anxiety/depression in T2D.
There is also evidence suggesting that depression is associated with poor glycaemic control; therefore, it is reasonable to suggest that anxiety/depression may increase the risk of serious adverse outcomes such as diabetes complications. (9) Anxiety/depression in diabetes is likely to have varying relationships with these adverse outcomes. (9) The interaction between various biological, social and psychological factors that could lead to a diabetic patient developing anxiety/depression could also be increasing the risk of diabetes complications. However, further research is required to understand the association between glycaemic control and anxiety/depression. (9) Many studies have established why understanding the link between anxiety/depression in T2D is a priority. Based on a James Lind Priority Setting Partnership established by Diabetes UK, certain research topics in this field have been identified. These include the mechanisms underlying depression in diabetes, the social stigma surrounding the disease and improving the language used by healthcare professionals. (10)
Improved identification of people with anxiety and depression and an increased understanding of how anxiety and depression might impact the management of T2D would enable the development of optimum approaches to support people with T2D. This, in turn, can help people to cope with life with T2D and improve wellbeing and self-management, thereby contributing to lower blood glucose levels and fewer complications.

To investigate the relationship between overall health, anxiety and depression and glycaemic control in T2D.

Research Questions
In people with T2D:
1. Do levels of anxiety/depression vary according to age, sex, ethnicity and diabetes duration?
2. Does the number and type of diabetes complications experienced affect anxiety/depression levels?
3. What is the relationship between anxiety/depression, overall wellbeing, and glycaemic control?
4. Do those who experience clinically significant changes in HbA1c (in either direction) over time experience changes in anxiety/depression levels?


Methods
We will query approximately 2700 Individual Participant Data (IPD) from the diabetes subsection of the Virtual International Cardiovascular and Cognitive Trials Archive (VICCTA-Diabetes).
Key variables include:
• Demographics
• Medical history
• Glycated haemoglobin A1c (HbA1c)
• Dependency for activities of daily living (ADLs)
• Quality of life
o EQ-5D scores (European Quality of Life scores) for anxiety & depression
o VAS (Visual Analogue Scale) scores
• Number of medications
• Diabetes complications (diabetic retinopathy, neuropathy, nephropathy and macrovascular disease)

Endpoints
Glycaemic control as assessed using HbA1c. Participant data will be divided as follows:
• suboptimal glycaemic control (HbA1c > 7.5%) and
• optimal glycaemic control (HbA1c < 7.5%), and/or into four groups:
• poor glycaemic control (HbA1c > 9%)
• average glycaemic control (HbA1c of 7.5% - 9%)
• good glycaemic control (HbA1c of 6.5-7.4%)
• very good (HbA1c < 6.5%)
depending on the distribution of the data.

Analyses
Population description
We will describe the analysis population using mean (and SD) or median (and interquartile range) for continuous variables (e.g. age) and frequencies/ proportions for categorical variables (e.g. sex, ethnicities). We will define the presence or absence of anxiety/depression at follow up using the EQ-5D score.
• Absence of anxiety/depression will be defined as a score of 1 (no problems) on the EQ-5D anxiety/depression domain.
• Presence of anxiety/depression will be defined as a score of 2 or 3 (some problems and extreme problems) on the EQ-5D anxiety/depression domain.


In people with T2D:
Do levels of anxiety/depression vary according to age, sex, ethnicity and diabetes duration?
We will the stratify populations by age, diabetes duration (according to the median, or terciles, as appropriate), sex and ethnicity. We will plot the presence of anxiety/depression across each stratum of age, sex, ethnicity and diabetes duration using frequencies and percentages. Where possible, we will describe the trajectory of depression over time from baseline up to 4 years across age, sex, ethnicity and diabetes duration. Chi-squared tests will be used to explore whether there are any statistically significant differences in the proportions of people with anxiety/depression according to age, sex, ethnicity and diabetes duration.

Does the number and type of diabetes complications experienced affect anxiety/depression levels?
We will describe the number and type of serious adverse events experienced by people with depression vs no depression. We will plot the most frequent SAE experienced by both groups.

What is the relationship between anxiety/depression, overall wellbeing, and glycaemic control?
We will describe the profiles of HbA1c, dependency for ADLs, and the VAS scores (by EQ-5D) from baseline up to 4 years for people with and without depression.
We will conduct a regression analysis to examine the relationship between suboptimal glycaemic control (using both definitions of HbA1c > 7.5% and HbA1c > 9%), presence of anxiety/depression and overall perception of health (EQ-5D VAS), adjusting for covariates including age, sex, ethnicity and duration of diabetes.
Odds ratios, 95% confidence intervals and p values will be used (a significant p-value being < 0.05).

Do those who experience clinically significant changes in HbA1c (in either direction) over time experience changes in anxiety/depression levels?
We will examine people with optimal glycaemic control at baseline but who had suboptimal glycaemic control at follow-up (HbA1c increase by >0.5% or >1.0%). We will similarly examine decreases by <0.5% and <1% in HbA1c. Within these groups of individuals, we will describe the proportions with and without anxiety/depression. Additionally, we will compare the number of medications used in individuals with anxiety/depression and individuals without anxiety/depression. We will formally examine these differences using Chi-squared tests.
The statistical software packages Minitab and SPSS will be used.

This study will describe demographic and glycaemic control profiles for people with T2D across a 4-year period and the associations with depression/anxiety and overall perception of health. This could describe potential relationships between diabetes management and emotional health and wellbeing. Furthermore, the study could increase understanding about relationships between different factors (ethnicity, age and sex) and anxiety/depression in patients with T2D.

The use of fully anonymised data from the Virtual Trials Archives for novel research purposes has institutional ethical approval (University of Glasgow, MVLS ethics).

This is an undergraduate student project funded by the University of Glasgow.

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