Journal of Diabetes and Its Complications xxx (2015) xxx–xxx

Contents lists available at ScienceDirect

Journal of Diabetes and Its Complications

j o u r n a l h o m e p a g e : W W W. J D C J O U R N A L . C O M

Prevalence of depression in type 2 diabetes patients in German primary

care practices
Louis Jacob a, Karel Kostev b,⁎
a
Department of biology, Ecole Normale Supérieure de Lyon, Lyon, France
b
IMS HEALTH, Frankfurt, Germany

a r t i c l e i n f o a b s t r a c t

Article history: Aims: To analyse depression in German type 2 diabetes patients with or without diabetes complications
Received 16 November 2015 Methods: Longitudinal data from nationwide general practices in Germany (n = 1,202) were analysed.
Received in revised form 11 December 2015 People initially diagnosed with type 2 diabetes (2004–2013) were identified and 90,412 patients were
Accepted 13 December 2015 included (age: 65.5 years, SD: 11.7). The main outcome measure was the first diagnosis of depression (ICD 10:
Available online xxxx
F32, F33) within ten years after index date in patients with and without diabetes complications. Cox
proportional hazards models were used to adjust for confounders.
Keywords:
Diabetes
Results: At baseline, most patients had diabetes complications and 6.4% of them had private insurance. Ten
Psychosocial stressors years after type 2 diabetes diagnosis, 30.3% of patients showed symptoms of depression. The prevalence of
Primary care depression was higher in women than in men (33.7% versus 26.8%), in patients with high HbA1c levels (31.3%
Prevalence when Hb1Ac ≥ 9 versus 27.5% when HbA1c b 7) and in patients with diabetes complications (37.7% when
Macrovascular disease there were more than two complications versus 29.1% when there were no complications). Women and
Microvascular disease patients without private health insurance were at a higher risk of developing depression. Retinopathy,
neuropathy, nephropathy, coronary heart disease, stroke and HbA1c levels higher than 7 were also positively
associated with depression.
Conclusions: Diabetes complications and high HbA1c levels had a substantial impact on depression in primary
care patients with type 2 diabetes.
© 2015 Elsevier Inc. All rights reserved.

1. Introduction studies aimed at the estimation of depression prevalence in people

Diabetes and depression are highly prevalent in Europe. There are
about 60 million adults with diabetes in this region of the world
(10.3% of men and 9.6% of women) and prevalence of the chronic
condition is increasing across all age groups, in parallel to an increase
in overweight and obesity, unhealthy diet and physical inactivity
(WHO, 2015a). Millions of European people, the majority of them
women, suffer from serious depression during their lives and 50% of
these cases remain untreated (WHO, 2015a,b). As diabetes and
depression are common disorders in Europe and as the associated
costs for European countries already exceed millions of euros, the
relationship between the two warrants careful examination.
A number of works have already shown an association between
diabetes and depression (Snoek, Bremmer, & Hermanns, 2015). In
2001, Anderson, Freedland, Clouse, and Lustman (2001) analysed 42
Funding sources: None.
Conflict of interest: None.
⁎ Corresponding author at: IMS Health, Epidemiology, Darmstädter Landstr. 108,
60598 Frankfurt am Main, Germany.
E-mail address: kkostev@de.imshealth.com (K. Kostev).
with type 1 and type 2 diabetes. They showed that the presence of
diabetes doubled the odds of comorbid depression and their finding
was later confirmed by other studies on the topic (Roy & Lloyd, 2012).
They also demonstrated that the prevalence of depression was even
higher in people with diabetes when the chronic condition was
reported by the patient him/herself rather than by clinicians (Snoek et
al., 2015). More recently, another meta-analysis indicated a significant
link between treatment non-adherence in diabetes and depression
(Gonzalez et al., 2008), underlining the tenuous link between the
mental disorder and treatments regulating glycaemia, at least in cases
of type 2 diabetes (Zhang et al., 2015). Finally, the association
between the two disorders is not unidirectional; depression is also
known to predispose individuals to diabetes (Pan et al., 2010), and the
association is therefore considered bidirectional.
Despite these works, the relationship between depression and
diabetes is still poorly understood (Snoek et al., 2015), with no real
consensus as to whether it is causal or merely coincidental. Although
depression usually appears before the ages of 25–30, type 1 diabetes
and type 2 diabetes often arise in childhood and later in life
respectively. Therefore, risk factors related to depression may not be
the same for both forms of diabetes. Although depression is more

http://dx.doi.org/10.1016/j.jdiacomp.2015.12.013
1056-8727/© 2015 Elsevier Inc. All rights reserved.

Please cite this article as: Jacob, L., & Kostev, K., Prevalence of depression in type 2 diabetes patients in German primary care practices, Journal
of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.12.013
2 L. Jacob, K. Kostev / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx
prevalent in people with diabetes, it was recently shown that patients
newly diagnosed with type 2 diabetes do not display an increased risk
of developing depression (Skinner et al., 2010). Another interesting
result is that patients exhibit low levels of distress and anxiety during
the first years of the chronic condition (Thoolen, de Ridder, Bensing,
Gorter, & Rutten, 2006), suggesting that early and intensive
treatments can influence the occurrence of depression. Intriguingly,
people with diabetes also reported high distress upon diagnosis
(85.2% of patients felt shocked, guilty, angry, anxious, depressed, or
helpless) (Peyrot et al., 2005). Finally, several authors have shown
that complications related to diabetes are additional risk factors for
depression (Badawi et al., 2013; Pouwer et al., 2003). The goal of the
present study was to analyse depression in German patients with type
2 diabetes, in the presence or absence of diabetes complications.
2. Patients and methods
2.1. Database
The Disease Analyzer database (IMS HEALTH) compiles drug
prescriptions, diagnoses, basic medical and demographic data
obtained directly and in anonymous format from computer systems
used in the practices of general practitioners (Becher, Kostev, &
Schröder-Bernhardi, 2009). Diagnoses (ICD-10), prescriptions (Ana-
tomical Therapeutic Chemical (ATC) Classification System) and the
quality of reported data have been monitored by IMS based on a
number of criteria (e.g. completeness of documentation, linkage
between diagnoses and prescriptions).
In Germany, the sampling method used for the selection of
physicians' practices is appropriate for obtaining a representative
database of primary care practices. The sampling is based on summary
statistics from all doctors in Germany published yearly by the German
Medical Association. IMS uses these statistics to determine the panel
design according to the strata including specialist group, German
federal state, community size category and age of physician (Becher et
al., 2009).
This database was shown to be representative of general practice
in Germany from the perspective of regional, gender and age
stratification (Becher et al., 2009).
Prescription statistics for several drugs were very similar to data
available from pharmaceutical prescription reports (Becher et al.,
2009). The age groups for given diagnoses in Disease Analyzer also
agreed well with those in corresponding disease registries (Becher et
al., 2009).
2.2. Study population
Patients initially diagnosed with type 2 diabetes mellitus (ICD 10:
E11) between January 2004 and December 2013 (index date) were
identified by 1202 general practitioners (GPs) in the IMS Disease
Analyzer database. Patients were included in the analysis only if: (i)
they did not suffer from depression prior to index date, (ii) their
follow-up lasted more than a year, (iii) they were more than 40 years
old. Selected patients were observed for up to ten years after the index
date, the latest follow-up date for any patient being March 31, 2015. A
total of 90,412 patients were available for analysis.
2.3. Study outcome
The main outcome measure was the first diagnosis of depression
(ICD 10: F32, F33) within ten years after index date. Only confirmed
diagnoses were included, meaning that depression was documented
by general practitioners after a first diagnosis either performed by a
psychiatrist or a general practitioner. The share of patients with
depression was estimated in presence and in absence of different
diabetes complications.
Please cite this article as: Jacob, L., & Kostev, K., Prevalence of depression in type 2 diabetes patients in German primary care practices, Journal
of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.12.013
2.4. Independent variables
Demographic data included age, gender and health insurance type
(private or statutory). Several complications related to diabetes and
co-morbid conditions were determined based on primary care
diagnoses (ICD-10 codes): retinopathy (E11.5), neuropathy (E11.4),
nephropathy including renal insufficiency (E11.2, N18, N19), coronary
heart disease (I20, I24, I25), myocardial infarction (I21, I22, I23),
peripheral artery disease (E11.5, I73.9) and stroke (I63, I64, G45).
These complications and conditions could occur throughout the entire
follow-up period prior to initial diagnosis of depression or, when
there was no depression diagnosis, prior to the end of follow-up. In
addition, diagnosed hypertension (I10), lipid disorders (E78) and
obesity (E66) were assessed for each study individual. Mean HbA1c
values for the follow-up time of study patients were calculated and
included as an independent variable. Finally, prescriptions of oral
antidiabetic drugs and insulin treatments were determined for each
patient.
2.5. Statistical analyses
Descriptive analyses were obtained for all demographic variables
and diagnoses and mean ± SD were calculated for normally distrib-
uted variables. Depression-free survival analyses were carried out
using Kaplan–Meier curves and log-rank tests. Kaplan–Meier curves
were stratified by gender, HbA1c levels and presence of diabetes
complications. Multivariate Cox proportional hazards models (de-
pendent variable: incident depression) were used to adjust for
confounders (gender, private insurance, diabetes complications,
co-diagnoses and prescriptions). Diabetes duration is an important
factor both in the development of diabetes complications and in the
development of depression. Yet according to our study, diabetes
duration is automatically considered as the follow-up time, since we
start on the day of the first diabetes diagnosis. Since we present
Kaplan–Meier curves showing time to development of depression,
they also automatically indicate the correlation between diabetes
duration and depression incidence.
P-values b 0.05 were considered statistically significant. The
analyses were carried out using SAS version 9.3.
3. Results
3.1. Patient characteristics
A total of 90,412 primary care patients were diagnosed with diabetes
in German practices between January 2004 and December 2013. The
clinical characteristics of these patients are shown in Table 1. As
expected, the mean age was 65.5 years and most of these older patients
had diabetes complications or co-diagnoses, most commonly hyper-
tension, lipid metabolism and coronary heart disease (79.7%, 56.0% and
28.8% respectively). 19.7% of them also had high levels of Hb1Ac,
indicating poor glycaemic control. 5786 patients (6.4%) had private
insurance. Finally, 75.0%, 5.5% and 12.5% of patients were treated with
oral antidiabetic drugs, insulin, and both medications, respectively (7.0%
of them did not receive any antihyperglycaemic therapy).
3.2. Shares of patients with depression
The Kaplan–Meier curve for time to diagnosis of depression in
patients newly diagnosed with type 2 diabetes is shown in Fig. 1. 5.9%,
17.7% and 30.3% of patients displayed depression one, five and ten
years after the diabetes diagnosis, respectively. The same analyses
were performed for gender, mean HbA1c value and number of
complications and co-diagnoses (Figs. 2, 3 and 4 respectively). The
prevalence of depression was higher in women (33.7%) than in men
(26.8%) ten years after diagnosis of type 2 diabetes. We also showed
 L. Jacob, K. Kostev / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx 3

Table 1 gender, private health insurance, retinopathy, neuropathy, nephrop-

Baseline characteristics of primary care patients with type 2 diabetes: Disease Analyzer athy, coronary heart disease, stroke and HbA1c levels higher than or
database, Germany.
equal to 7. Depression was less common in men (HR = 0.75) and in
Variables Value individuals with private health insurance (HR = 0.72). By contrast,
N 90,412 the six other variables were positively associated with depression (HR
Age (years) 65.5 (11.7) between 1.11 and 1.44 for retinopathy, neuropathy, nephropathy,
Age ≤65 (%) 48.0 coronary heart disease and stroke, and equal to 2.17 for HbA1c N 9).
Age N65 (%) 52.0
Peripheral vascular disease, myocardial infarction, hypertension, lipid
Men (%) 50.2
Private health insurance (%) 6.4 metabolism, obesity and age had no effect on the prevalence of
Diabetes complicationsa (%): depression. Finally, patients treated with oral antidiabetic drugs,
Coronary heart disease 28.8 insulin, and both medications simultaneously, did not have a
Myocardial infarction 5.1 significant increased or decreased depression risk, compared to
Stroke 9.6
patients who did not receive an antihyperglycaemic therapy (OR
Peripheral vascular disease 11.7
Retinopathyb 4.7 between 0.97 and 1.16).
Nephropathy 14.3
Neuropathy 13.4
Hypertension 79.7 4. Discussion
Lipid metabolism 56.0
Obesity 22.5
Antihyperglycaemic therapy
In our study, depression was more common in women and in
No therapy 7.0 individuals without private health insurance. Prevalence also in-
Oral drugs 75.0 creased with the number of diabetes complications. Five of them were
Insulin 5.5 associated with a higher risk of depression development: retinopathy,
Oral drugs and insulin 12.5
neuropathy, nephropathy, coronary heart disease and stroke. Fur-
HbA1c in % 6.5 (0.9)
HbA1c b7 80.3 thermore, high levels of HbA1c had an important impact on
HbA1c 7–b8 13.5 depression, in particular when they were higher than 9, as they
HbA1c 8–b9 3.9 were associated with an HR of 2.17. HbA1c thus had the strongest
HbA1c ≥9 2.3 effect on the risk of developing depression in type 2 diabetes patients.
Data are means (SD) or proportions (%). Myocardial infarction, peripheral vascular disease, hypertension, lipid
a
Primary care diagnoses prior to diagnosis of depression or end of follow-up. metabolism, obesity and age had no significant effect on depression in
b
Figures used in the present study do not accurately reflect the situation in Germany
this study. Finally, we demonstrated that the use of oral antidiabetic
as the diagnosis and therapy are usually undertaken by ophthalmologists.
drugs and insulin did not modify the chance of developing depression.
Although recent studies have shown that poor glycaemic control
that the prevalence of depression increased with HbA1c levels, rising and high levels of HbA1c in patients with type 2 diabetes have a
from 27.5% when levels were lower than 7 to 31.3% when levels were negative effect on various cognitive functions (Abbatecola et al., 2006;
higher than 9. The number of complications/co-diagnoses had also an Chen et al., 2011; Feinkohl, Price, Strachan, & Frier, 2015), their roles
effect on the occurrence of depression. 37.7% of individuals with more with regard to depression are still under debate (Fisher, Glasgow, &
than two complications/co-diagnoses were diagnosed as depressed Strycker, 2010; Lustman & Clouse, 2005; Lustman et al., 2000; Zhang
versus 29.1% with no diabetes complications/co-diagnoses. et al., 2015). In 2010, Fisher et al. (2010) performed a study on the
relationship between glycaemic control and distress and clinical
depression in 463 patients with type 2 diabetes. Although glycaemic
3.3. Association with depression control was associated with distress to a significant extent, it was not
linked to depression, suggesting that there was no statistical
The results of the Cox regression analysis are shown in Table 2. 8 relationship or that the study was not suitably designed to
variables were associated with depression to a significant extent: demonstrate the presence of such a relationship. By contrast, Lustman

Fig. 1. Kaplan–Meier curve for time to diagnosis of depression in primary care patients newly diagnosed with type 2 diabetes.

Please cite this article as: Jacob, L., & Kostev, K., Prevalence of depression in type 2 diabetes patients in German primary care practices, Journal
of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.12.013
4 L. Jacob, K. Kostev / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx

Fig. 2. Kaplan–Meier curves for time to diagnosis of depression in primary care patients newly diagnosed with type 2 diabetes by gender.

Fig. 3. Kaplan–Meier curves for time to diagnosis of depression in primary care patients newly diagnosed with type 2 diabetes by HbA1c value.

Fig. 4. Kaplan–Meier curves for time to depression diagnosis in primary care patients newly diagnosed with type 2 diabetes patients by number of complications.

Please cite this article as: Jacob, L., & Kostev, K., Prevalence of depression in type 2 diabetes patients in German primary care practices, Journal
of Diabetes and Its Complications (2015), http://dx.doi.org/10.1016/j.jdiacomp.2015.12.013
 L. Jacob, K. Kostev / Journal of Diabetes and Its Complications xxx (2015) xxx–xxx 5

Table 2 Moreover, we found no difference in the prevalence of depression

Association of depression with defined outcomes in primary care patients with diabetes in patients older and younger than 65. In the general population, the
in Germany: Cox regression analyses.
association between age and depression is not well understood and
Outcome Variables Hazard Ratio 95% CI p-value the various studies on the topic have yielded contradictory results,
Men 0.75 0.72–0.78 b0.0001 suggesting that the relationship may be artificial (Akhtar-Danesh &
Private health insurance 0.72 0.65–0.80 b0.0001 Landeen, 2007; Stordal, Mykletun, & Dahl, 2003). The literature also
Retinopathy 1.44 1.21–1.70 b0.0001 displays some conflicting findings for patients with type 2 diabetes
Neuropathy 1.25 1.17–1.33 b0.0001
(Alonso-Morán, Satylganova, Orueta, & Nuño-Solinis, 2014; Wang et
Nephropathy 1.13 1.06–1.21 0.0004
CHD 1.11 1.05–1.17 0.0002 al., 2015). Although Alonso-Morán et al. (2014) discovered, in their
Stroke 1.18 1.09–1.27 b0.0001 study of 12,392 men and women displaying this chronic condition,
HbA1c 7–b8a 1.29 1.16–1.42 b0.0001 that patients older than 65 had a higher risk of developing depression,
HbA1c 8–b9 1.43 1.22–1.68 b0.0001 Wang et al. (2015) did not find any age-related effect in their recent
HbA1c N9 2.17 1.82–2.58 b0.0001
study of 865 Chinese patients. Interestingly, our work also showed
Age N65b 0.98 0.91–1.04 0.4647
Oral drugsc 0.97 0.87–1.07 0.5087 that the prevalence of depression was not associated with age when
Insulinc 1.16 0.98–1.38 0.0921 potential biases, such as diabetes complications, were taken into
Oral drugs and insulinc 1.08 0.95–1.23 0.2224 account in the statistical analyses.
a
Reference group is HbA1c b7. We also found a link between depression and private health
b
Reference group age ≤65. insurance, which is an indirect indicator of high income and
c
Reference group: no antihyperglycaemic therapy. education. It is already known that lack of education and low salaries
increase the risk of developing depression in patients with type 2
diabetes (Blazer, Moody-Ayers, Craft-Morgan, & Burchett, 2002;
et al. (2000) previously analysed 24 studies and found that depression Peyrot & Rubin, 1997; Sweileh, Abu-Hadeed, Al-Jabi, & Zyoud,
was linked with hyperglycaemia in patients with type 1 and type 2 2014). Our results confirm these data and underscore the need for
diabetes, although the directional nature of this relationship remained both medical and patient education for people with previously little
unclear. These results were confirmed in 2015 in a study of 2,538 knowledge in order to prevent both diabetes and depression.
patients with type 2 diabetes in China (Zhang et al., 2015). By way of In general, retrospective primary care database analyses are
corroborating these data further in a population with diabetes in limited by the validity and completeness of the data on which they
German primary care, our study showed that high levels of HbA1c had are based. The present study is subject to several limitations, which
a strong effect on the risk of developing depression, which was one of should be mentioned at this point. First, no valid information was
Lustman’s hypotheses in 2000 (Lustman & Clouse, 2005). provided on diabetes duration. Additionally, the assessment of
Retinopathy also had a strong effect on the risk of developing complications and co-diagnoses relied solely on ICD codes by primary
depression, with an HR of 1.44. Diabetic retinopathy is the most frequent care physicians. In addition to the fact that diagnostic criteria for
cause of new cases of blindness among adults aged 20–74 (Fong et al., depression were unknown, depression might have been under-
2004). Ruta et al. (2013) recently analysed 72 studies, showing that the diagnosed, as patients do not always consult for this psychiatric
average prevalence of retinopathy in patients with type 2 diabetes from condition. This study also does not analyse blindness, amputations
developed countries was 27.9% in those with known diabetes and 10.5% and sexual dysfunction, which have been identified in several studies
in those with newly diagnosed diabetes. Therefore, the high prevalence as the complications that are most troublesome for patients.
of retinopathy in patients with type 2 diabetes and its strong effect on Furthermore, the tight association between depression and
the development of depression constitute a compelling argument in diabetes distress might have impacted our results. Data on socioeco-
favour of early treatment for patients. nomic status (e.g. education, income) and lifestyle-related risk factors
Another interesting finding of our study was that several diabetes (e.g. smoking, alcohol, physical activity) were lacking. Unfortunately,
complications/co-diagnoses were not associated with depression. the documentation of hypoglycaemia was also underestimated and
This applies in particular to myocardial infarction, although this result could not be used. Finally, one must remember that depression is
remains controversial (Poongothai et al., 2011; Wang, Song, Chen, underdiagnosed in primary care environments (Rouchell, 2000;
Wang, & Ling, 2015) and despite the fact that coronary heart disease Sheehan, 2004), underlying the fact that we may have under-
had an effect on the development of this mental disorder in patients estimated its prevalence in our work.
with type 2 diabetes (HR: 1.11). One hypothesis that could explain The main strengths of this study are the large nationwide database
this intriguing result may be the difference in the prevalence of these on which it is based and its unbiased assessment of diagnoses and
two diabetes complications among our patients: 28.8% of them prescriptions.
suffered from coronary heart disease whereas only 5.1% had As a brief conclusion, it is important to remember that diabetes
myocardial infarction. Indeed, this latter complication itself common- and depression are common disorders and often occur together.
ly results from a pre-existing heart condition, explaining why its Therefore, there is a need for personalised treatments and manage-
prevalence is low. ments, in order to prevent the development of depression in patients
We further demonstrated that the use of insulin and oral with type 2 diabetes. Such strategies need to ensure the patient is
antidiabetic medications did not have a significant effect on actively involved in his/her own therapy.
depression risk. This result must be carefully discussed, since the
impact of insulin therapies on the quality of life of patients has been
Acknowledgements
the centre of an abundant literature. A recent review has analysed
several works and has found that there are important limitations
Professional English language editing services were provided by
making their interpretation difficult: i) quality of life is a complex
Claudia Jones, MA, Radford, Virginia, United States.
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various forms of insulin, and each of them may have a particular effect
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