SYMPTOMS OF DEPRESSION BUT NOT ANXIETY ARE ASSOCIATED WITH CENTRAL OBESITY AND CARDIOVASCULAR DISEASE IN PEOPLE WITH TYPE 2 DIABETES: THE EDINBURGH TYPE 2 DIABETES STUDY

Abstract

Aims/hypothesis

To identify risk factors for depression and anxiety in a well-characterised cohort of subjects with type 2 diabetes mellitus.

Methods

We used baseline data from participants (n=1066, 48.7% women, aged 67.9 ± 4.2 years) from the Edinburgh Type 2 Diabetes Study. Symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Obesity was characterised according to both overall (body mass index, fat mass) and abdominal (waist circumference) measurement. Cardiovascular disease was assessed by questionnaire, physical examination and review of medical records. Stepwise multiple linear regression was performed to identify explanatory variables related to either anxiety or depression HADS scores.

Results

Abdominal obesity (waist circumference) and cardiovascular disease (ischaemic heart disease and ankle-brachial pressure index) were related to depression but not anxiety. Lifetime history of severe hypoglycaemia was associated with anxiety. Other cardiovascular risk factors or microvascular complications were not related to either anxiety or depressive symptoms.

Conclusion/interpretation

Depression but not anxiety is associated with abdominal obesity and cardiovascular disease in people with type 2 diabetes mellitus. This knowledge may help to identify depressive symptoms among patients with type 2 diabetes who are at greatest risk.

INTRODUCTION

Although it is recognised that people with type 2 diabetes mellitus often have anxiety and depression [1, 2], the potential risk factors for these conditions have not been well defined. Most studies examining psychological disorders occurring in type 2 diabetes have focused on depression, which has been associated with poorer glycaemic control [3], more metabolic complications [3, 4] including ischaemic heart disease [2, 4], and greater mortality [5]. The poorer prognosis in patients with depression may in part be explained by a lower adherence to medications or dietary recommendations and a higher prevalence of obesity [4] and of other cardiovascular risk factors [4]. Symptoms of anxiety are often reported by people with type 2 diabetes [1], and with depression or obesity [6]. However, it is not known whether anxiety symptoms are related to obesity or cardiovascular risk in type 2 diabetes.

Previous studies [3, 5] exploring the relationship between depression and the metabolic profile in type 2 diabetes have assessed adiposity by body mass index (BMI) but more detailed assessments such as waist circumference or body fat distribution are lacking. The differentiation between central and overall obesity when assessing depression is important as recent studies suggest that central (rather than overall) obesity is associated with depression in non-diabetic populations [7] and is also associated with an adverse metabolic profile [8].

We therefore aimed to identify risk factors for depression and anxiety in a very well-characterised large sample of people with type 2 diabetes. We controlled for both overall (BMI, fat mass) and abdominal obesity (waist circumference) measures.

METHODS

The Edinburgh Type 2 Diabetes Study (ET2DS) is a population-based, prospective cohort study designed to determine the association between potentially modifiable risk factors and cognitive decline in people with type 2 diabetes. Ethical permission was obtained from the Lothian Research Ethics Committee and written informed consent obtained. The complete protocol is described elsewhere [9]. In brief, individuals with type 2 diabetes (WHO criteria) living in Lothian, Scotland, were selected from the Lothian Diabetes Register (LDR). People aged between 60 and 74 years on 1st August 2006 were selected by sex and 5-year age bands from computer-randomised lists of eligible subjects from the LDR. After exclusion of patients with pre-defined criteria [9], 1066 subjects were willing and eligible to take part in the ET2DS.

Clinical assessment

Participants completed a questionnaire at baseline to assess socio-demographic and life-style variables, and clinical information related to their diabetes and cardiovascular status, including questions on medical diagnoses and/or treatment for angina, myocardial infarction, stroke, hypertension and hypercholesterolaemia. Lifetime history of severe hypoglycaemic episodes was defined by self-report as the presence of at least one hypoglycaemic episode needing assistance by another person. Details on the year of cardiovascular diagnosis or event, and hospital or general practice attended, were collected to enable further validation of diagnoses after comparison with data from the LDR and from the Information Service Division (Scotland’s national organisation for health information, statistics and information technology services). The Hospital Anxiety and Depression Scale (HADS) was used to evaluate current anxiety and depressive symptoms. This scale performs well in screening for the separate dimensions of anxiety and depression in patients from non-psychiatric hospital clinics [10].

A complete physical examination was performed including measurement of systolic and diastolic brachial blood pressures, waist circumference and body fat percentage by bio-electrical impedance. As the maximum percentage fat mass that could be recorded was 50%, we categorized this variable into quartiles, using different cut-off points for male and female subjects, due to the known gender differences in fat-mass distribution [7]. A resting 12-lead electrocardiogram was recorded. Assessment of ankle-brachial pressure index (ABPI), neuropathy and retinopathy, as well as further definitions of cardiovascular disease, cardiovascular risk factors and metabolic complications, are detailed in Table 1 (supplementary material).

Blood and urine samples

Venous blood samples were taken after an overnight fast for measurement of HbA1c, and plasma total and high density lipoprotein (HDL) cholesterol. An early-morning specimen of urine was obtained to calculate the albumin to creatinine ratio (ACR).

Statistical analyses

Data were analysed using SPSS 15.0. As HADS anxiety and depression scores were skewed, a square-root transformation was applied. Multiple linear regression was performed to identify explanatory variables related to either anxiety or depression scores (used as continuous variables). Gender was forced to enter the equation in the first step (so all models are adjusted for gender) whereas other independent variables were tested with a forward stepwise procedure: age, employment status, education level, marital status, anxiety or depression HADS score, obesity-related variables (BMI, waist circumference and fat mass), duration of diabetes mellitus, history of severe hypoglycaemia, diabetes treatment, HbA1c, smoking, alcohol consumption, ischaemic heart disease, stroke, ABPI, ACR, neuropathy, retinopathy, hypertension, dyslipidaemia, treatment with thyroxine, antidepressants or glucocorticoids. Interactions between gender and independent variables were tested and significant interactions were included in the final equations. Two analyses were performed, using the square-root transformed HADS scores for anxiety (Analysis 1) or depression (Analysis 2) as the dependent variable.

RESULTS

Clinical characteristics and metabolic complications of the participants are described in Table 1. Results from the multiple linear regression models used to select explanatory variables related to anxiety and depression HADS scores are shown in Table 2. HADS depressive scores were related to anxiety scores. Abdominal obesity and ischaemic heart disease were positively related to depression but not to anxiety. Lower ABPI measurements were also associated with depression. Treatment with insulin was positively related to depression and inversely related to anxiety. History of severe hypoglycaemia was associated with anxiety. Subjects living with a partner reported less anxiety and those with a lower education reported more depression. Female subjects and those taking antidepressants reported more anxiety symptoms. There was however, a gender interaction effect in relation to the antidepressant treatment ( i.e. females taking antidepressants reported less anxiety). No significant gender interaction effects were found in the depression regression model.

Table 1. Baseline clinical variables in the ET2DS (n=1066).

Sociodemographic and life style variables
Female gender	519 (51.3)
Age at assessment (years)	67.9 (4.2)
Current Marital Status
Married	744 (69.9)
Living with long-term partner	54 (5.1)
Single	159 (14.9)
Widowed	107 (10.1)
Education (highest level completed)
University/College	171 (16.0)
Other professional qualification	307 (28.8)
Primary or secondary school	588 (55.2)
Current Employment status
Worker	152 (14.3)
Retired	864 (81.1)
Other: housewife, unemployed	50 (4.7)
Ethnic group
Caucasian	1016 (95.3)
Other	50 (4.7)
Current smoker	148 (13.9)
Alcohol consumption in preceding year (frequency)
Never	218 (20.6)
1-4 drinks per month	463 (43.7)
2-5 drinks per week	268 (25.3)
6 or more drinks per week	110 (10.4)
Diabetes Mellitus (DM) variables
Duration of DM (years)	9.1 (6.5)
HbA1c	7.4 (1.1)
Treatment of DM
Diet alone	201 (18.9)
Oral hypoglycaemic agents	678 (63.6)
Insulin ± Oral hypoglycaemic agents	187 (17.5)
Lifetime history of severe hypoglycaemic episodes (1 or more)	113 (10.8)
Cardiovascular variables and other metabolic complications
Systolic blood pressure (mmHg)	133.3 (16.4)
Diastolic blood pressure (mmHg)	69.1 (9.0)
Hypertension	956 (89.7)
HDL-cholesterol (mmol/L)	1.3 (0.4)
Dyslipidaemia	923 (86.6)
Ischaemic heart disease (angina or MI)	330 (31.0)
Myocardial infarction	150 (14.1)
Angina (lifetime history)	298 (28.0)
Cerebrovascular disease (stroke or TIA)	93 (8.7)
Ankle-Brachial Pressure Index	0.981 (0.207)
Neuropathy	520 (48.8)
Albumin/Creatinine Ratio (mg/mmol)	3.1 (10.0)
Retinopathy	400 (37.5)
Anthropometric measures
Weight (kg)	86.5 (16.2)
BMI (kg/m2)	31.4 (5.7)
Waist (cm)
Males	108.2 (12.1)
Females	105.5 (13.5)
Mood scores
HADS – Anxiety score	5.7 (3.9)
HADS- Depression score	3.9 (2.9)
Treatments
Taking antidepressant	137 (12.9)
Taking glucocorticoids	147 (13.8)
Taking thyroxine	121 (11.4)

Data are mean (SD) or N (%). Sample size may vary for some variables with < 3% missing data.

Table 2. Significant explanatory variables included in the final model for each multiple linear regression analysis testing anxiety or depression scores in male and female patients.

		Analysis 1 (Anxiety)
	R2 Change	ß	SE	95% CI	P value
Female gender	0.067	0.407	0.052	0.305 to 0.509	<0.001
HADS-Depressiona	0.263	0.595	0.032	0.532 to 0.657	<0.001
Lifetime history of severe hypoglycaemia	0.008	0.293	0.082	0.133 to 0.453	<0.001
Marital status (living with partner)	0.005	−0.299	0.116	−0.526 to −0.071	0.010
Taking antidepressant treatment	0.004	0.399	0.114	0.176 to 0.622	<0.001
Treatment with insulin (+-OHA)	0.004	−0.167	0.068	−0.300 to −0.033	0.014
Interaction female gender by antidepressant treatment	0.004	−0.367	0.147	−0.656 to −0.078	0.013
		Analysis 2 (Depression)
	R2 Change	ß	SE	95% CI	P-value
Female gender	0.012	−0.002	0.043	−0.085 to 0.082	0.971
HADS-Anxietya	0.279	0.427	0.023	0.383 to 0.471	<0.001
Waist circumference (in cm)	0.038	0.010	0.002	0.007 to 0.014	<0.001
Ischaemic heart disease	0.023	0.241	0.045	0.153 to 0.329	<0.001
Treatment with insulin (+- OHA)	0.007	0.179	0.055	0.071 to 0.286	0.001
Low education (primary or secondary school)	0.003	0.087	0.041	0.006 to 0.167	0.035
Ankle-Brachial Pressure Index	0.003	−0.208	0.099	−0.402 to −0.013	0.036

DISCUSSION

This is the largest study to investigate the factors predicting symptoms of anxiety and depression in a well-characterised cohort of people with type 2 diabetes. We found a positive association between abdominal obesity and depression but not anxiety. Cardiovascular disease measures (ischaemic heart disease and lower ABPI) were related only to depression.

Our data support an association between depression and obesity in type 2 diabetes, as has been suggested by earlier studies in both non-diabetic [6] and diabetic [3] populations.. When three obesity measures (BMI, fat mass, waist circumference) were examined in the multivariate analysis, only waist circumference was significantly related to depression. These findings are in accord with a recent prospective study [7] in a non-diabetic population where visceral obesity as determined by CT scanning (but not BMI or fat mass) was related to the incidence of depression. However, the effect size was small, explaining only 4% of the variability of the data in the final regression model studying depressive symptoms.

Although it is possible that the relationship between visceral obesity, cardiovascular disease and depression could be explained by differences in cardiovascular risk factors, we found that cardiovascular risk factors were not related to either anxiety or depressive symptoms, albeit that the lack of association with these cardiovascular risk factors may be obscured by treatment effects. In contrast to previous studies in type 2 diabetes which have reported associations between depression and metabolic complications including coronary heart disease only in males [3], no significant gender differences were evident in our study. Interestingly, we found a positive relationship between lifetime history of severe hypoglycaemia and symptoms of anxiety. It is not known whether anxiety per se impairs awareness of hypoglycaemia or interferes with the ability to self-treat a fall in blood glucose, or both.

The main limitation of our study is the cross-sectional design and so a causal relationship between clinical variables and anxiety or depressive symptoms cannot be inferred. Although we did not include a non-diabetic comparison group, we included the full spectrum of people type 2 diabetes ranging from dietary therapy alone to insulin-treated with complications. We used a psychometric scale for assessing anxiety and depression rather than a structured interview for mental disorders, thus clinical diagnoses of anxiety or depressive disorders could not be made and information about current or prior history of depressive disorders was not available. As symptoms of anxiety and depression may be obscured by antidepressant treatment, we repeated all regression analysis after excluding those subjects taking antidepressants, but the final results did not change.

In summary, our results suggest that depression but not anxiety is associated with abdominal obesity and cardiovascular disease in people with type 2 diabetes. This relationship is independent of cardiovascular risk factors. Anxiety is also associated with risk of hypoglycaemia. In the clinical setting, knowledge of these risk factors may help to identify depressive symptoms among people with type 2 diabetes.

Abbreviations

HADS

Hospital Anxiety and Depression Scale