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Can J Diabetes xxx (2017) 1–5

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Original Research

Nocturia and Prevalence of Depressive Symptoms in Japanese Patients

with Type 2 Diabetes Mellitus: The Dogo Study
Shinya Furukawa MD, PhD a,b,*, Takenori Sakai MD c, Tetsuji Niiya MD, PhD d,
Hiroaki Miyaoka MD, PhD e, Teruki Miyake MD, PhD f, Shin Yamamoto MD f, Sayaka Kanzaki MD f,
Koutatsu Maruyama PhD g, Keiko Tanaka DDS, PhD a,b, Teruhisa Ueda MD, PhD h, Hidenori Senba MD a,f
,
Masamoto Torisu MD, PhD i, Hisaka Minami MD, PhD j, Takeshi Tanigawa MD, PhD g,
Bunzo Matsuura MD, PhD k, Yoichi Hiasa MD, PhD f, Yoshihiro Miyake MD, PhD a,b
a Department of Epidemiology and Preventive Medicine, Ehime University Graduate School of Medicine, Ehime, Japan
b Epidemiology and Medical Statistics Unit, Translational Research Center, Ehime University Hospital, Ehime, Japan
c Department of Internal Medicine, Yawatahama General City Hospital, Ehime, Japan
d Department of Internal Medicine, Matsuyama Shimin Hospital, Ehime, Japan
e Department of Internal Medicine, Saiseikai Matsuyama Hospital, Ehime, Japan
f Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
g Department of Public Health, Juntendo University School of Medicine, Tokyo, Japan
h Department of Internal Medicine, Ehime Central Hospital, Ehime, Japan
i Department of Internal Medicine, SaiseikaiSaijo Hospital, Ehime, Japan
j Department of Internal Medicine, Ehime Niihama Hospital, Ehime, Japan
k Department of Lifestyle-related Medicine and Endocrinology, Ehime University Graduate School of Medicine, Ehime, Japan

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

Article history: Objectives: No studies have investigated the association between nocturia and depressive symptoms in
Received 8 January 2017
patients with type 2 diabetes mellitus. Because nocturia and depressive symptoms are common in patients
Received in revised form
with type 2 diabetes, we examined this association in Japanese patients with type 2 diabetes.
20 February 2017
Accepted 2 March 2017 Methods: We studied 762 Japanese patients with type 2 diabetes. A self-administered questionnaire was
used to collect information about the variables under study. The subjects were divided into 3 groups accord-
ing to their nocturnal micturition: 1) no nocturia; 2) mild nocturia (1 void per night) and 3) moderate
Keywords:
depression to severe nocturia (2 or more voids per night). Depressive symptoms were defined as being present when
Japanese a subject had a Self-Rating Depression Scale score higher than 49.
nocturia Results: The prevalence values of mild nocturia, moderate to severe nocturia and depressive symptoms
diabetes were 39.5%, 41.9% and 16.8%, respectively. Both mild nocturia and moderate to severe nocturia were inde-
type 2 diabetes pendently positively associated with depressive symptoms in all patients; the adjusted ORs were 1.96
(95% CI 1.06 to 3.77) and 2.58 (95% CI 1.38 to 5.04). In female patients, both mild nocturia and moderate
to severe nocturia were independently associated with depressive symptoms; the adjusted ORs were 5.26
(95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15 to 28.54), respectively. In male patients, neither mild noc-
turia nor moderate to severe nocturia was significantly related to depressive symptoms.
Conclusions: In Japanese female patients with type 2 diabetes, nocturia may be positively associated with
depressive symptoms.
© 2017 Diabetes Canada.

r é s u m é
Mots clés :
Objectifs : Aucune étude n’a abordé l’association entre la nycturie et les symptômes dépressifs chez les
dépression
patients atteints de diabète de type 2. Étant donné que la nycturie et les symptômes dépressifs sont courants
Japonais
nycturie chez les patients atteints de diabète de type 2, nous avons examiné cette association chez des patients
diabete japonais présentant ce type de diabète.
diabete de type 2

* Address for correspondence: Shinya Furukawa, MD, PhD, Department of Epidemiology and Preventive Medicine, Ehime University Graduate School of Medicine, Shitsukawa,
Toon, Ehime 791-0295, Japan.
E-mail address: shinya.furukawa@gmail.com

1499-2671 © 2017 Diabetes Canada.

The Canadian Diabetes Association is the registered owner of the name Diabetes Canada.
http://dx.doi.org/10.1016/j.jcjd.2017.03.002
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Méthodologie : Nous avons mené une étude portant sur 762 patients japonais atteints de diabète de type
2. Un questionnaire autoadministré a servi à recueillir des renseignements sur les variables à l’étude. Les
patients ont été divisés en 3 groupes en fonction des critères suivants : 1) absence de nycturie; 2)
nycturielégère (1 miction par nuit); 3) nycturie modérée ou marquée (2 mictions ou plus par nuit). Les
symptômes dépressifs étaient réputés présents lorsqu’un patient obtenait un score supérieur à 49 sur
l’échelle d’autoévaluation de la dépression.
Résultats : La prévalence de la nycturie légère, de la nycturie modérée ou marquée et des symptômes
dépressifs a atteint 39,5 %, 41,9 % et 16,8 %, respectivement. La nycturie légère et la nycturie modérée ou
marquée ont été indépendamment associées de façon positive aux symptômes dépressifs chez tous les
patients; les RC corrigés étaient de 1,96 (IC à 95 % : 1,06-3,77) et de 2,58 (IC à 95 % : 1,38-5,04). Chez les
femmes, la nycturie légère et la nycturie modérée ou marquée ont été indépendamment associées
aux symptômes dépressifs; les RC corrigés étaient de 5,26 (IC à 95 % : 1,73-20,61) et de 6,91 (IC à 95 % :
2,15–28,54), respectivement. Chez les hommes, ni la nycturie légère ni la nycturie modérée ou marquée
n’ont été associées de façon significative à des symptômes dépressifs.
Conclusions : Chez les patientes japonaises atteintes de diabète de type 2, la nycturie peut être associée
de façon positive à des symptômes dépressifs.
© 2017 Diabetes Canada.

Introduction of the Ehime University Graduate School of Medicine. Written

The International Continence Society defines nocturia as the con-
dition of waking up to void once or more during a typical night
(1). In general populations, the bidirectional association between
nocturia and depressive symptoms has been suggested. Nocturia
was significantly positively associated with depressive symptoms
in a Polish study (2), in 4 US studies (3–6) and in a Dutch study (7).
On the other hand, depressive symptoms were significantly posi-
tively associated with nocturia in 2 US studies (8,9), in a Swedish
study (10), in a Finnish cohort study (11) and in a cross-national
(United States, United Kingdom and Sweden) study (12). A close
association between nocturia and depressive symptoms was observed
in the general population. Systematic review showed a bidirec-
tional association between nocturia and depression and recom-
mended the assessment of depression in patients with nocturia (13).
The prevalence of nocturia is higher in patients with diabetes
than in those without diabetes (14–18). Similarly, the prevalence
of depressive symptoms is higher in patients with diabetes than in
those without diabetes (19). In patients with type 2 diabetes, depres-
sive symptoms were positively associated with hyperglycemia
(20) and poor prognoses (21). Nocturia was positively associated
with diabetic retinopathy (22), erectile dysfunction (23) and mor-
tality (24). The assessment of nocturia was easy to make in clinics.
Given a positive association between nocturia and depressive symp-
toms, patients with type 2 diabetes and nocturia may need to be
evaluated for depressive symptoms. To our knowledge, however, no
study has investigated the association between nocturia and depres-
sive symptoms in patients with type 2 diabetes. Thus, we aimed
to evaluate this association in Japanese patients with type 2 diabetes.
Methods
Study population
The Dogo Study was a multicentre prospective cohort study that
recruited, between September 2009 and September 2014, 1051 Japa-
nese patients, both inpatients and outpatients, with previously diag-
nosed type 2 diabetes. The median age at recruitment was 61.6 years
(range, 19 to 88 years); 60.9% were men. Collaborating physicians
who specialize in diabetes mellitus and represent 10 hospitals were
responsible for the diagnoses of type 2 diabetes according to the
Japan Diabetes Society criteria.
Excluded from our current analysis were 289 patients because
of incomplete data on the variables under study. Thus, the final
analysis sample consisted of 762 patients. The present study pro-
tocol received ethical approval from the institutional review board
informed consent was obtained from all patients enrolled in the Dogo
Study.
Measurements
Each participant completed a self-administered questionnaire
that collected data on diabetes duration, current smoking habits,
current drinking habits, use of antihypertensive medication, use of
antihyperlipidemic medication, height and weight. Each patient’s
body mass index (BMI) was calculated as weight (kg) divided by
the square of height (m2). Current smoking was defined as posi-
tive if a study subject reported smoking at least 1 cigarette per day.
Blood pressure was measured in the sitting position with a cuff after
a resting period of more than 5 minutes. Hypertension was defined
as positive if systolic blood pressure was above 140 mm Hg, dia-
stolic blood pressure was above 90 mm Hg, or both, or if the patient
had received antihypertensive medication. Dyslipidemia was defined
as positive if serum total cholesterol concentration was higher than
220 mg/dL, triglyceride concentration was higher than 150 mg/dL,
or high-density lipoprotein cholesterol concentration was below
40 mg/dL, or if the patient was already being treated with lipid-
lowering agents. Stroke and ischemic heart disease were assessed
based on the self-administered questionnaires, medical records
and/or admission data. Use of insulin and oral antihyperglycemic
agents was determined by medical records.
Assessment of nocturia
Study subjects were considered to have nocturia if they answered
“once or more” to the following question: “How many times do you
typically wake up to urinate while sleeping at night until waking
in the morning?” The subjects were divided into 3 groups accord-
ing to their nocturnal micturition: 1) no nocturia, 2) mild noctu-
ria (1 void per night) or 3) moderate to severe nocturia (2 or more
voids per night).
Assessment of depressive symptoms
The Self-Rating Depression Scale (SDS) was used to screen depres-
sive symptoms. The SDS contains 20 items scored from 1 to 4; the
total score was converted to a 20- to 80-point scale. The SDS score,
based on cutoff index of 50, showed 97% sensitivity, 63% specific-
ity and 82% correct classification of depressed patients and
nondepressed control patients. In the present study, depressive
symptoms were defined as SDS scores above 49 (25).
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Assessment of the complications of type 2 diabetes
Microvascular complications of type 2 diabetes included reti-
nopathy, nephropathy and neuropathy. Retinopathy was diagnosed
on the basis of the presence of hemorrhage, microaneurysm, soft or
hard exudates, areas of neovascularization or laser coagulation scars
in at least 1 eye. Diagnosis was conducted using florescence fundos-
copy on dilated pupils within 3 months of recruitment. Several oph-
thalmology specialists were responsible for evaluating the participants’
funduses, and all ophthalmologists were blinded to the diagnoses of
nocturia and depressive symptoms. The definition of diabetic
nephropathy was based on a urine albumin-to-creatinine ratio of
300 mg/g or higher and a creatinine and/or estimated glomerular fil-
tration rate (eGFR) above 30 mL/min/1.73 m2 (26). The definition of
diabetic neuropathy was based on abbreviated diagnosis criteria pro-
posed by the Diabetic Neuropathy Study Group of Japan (27).
Statistical analysis
Estimations of crude odds ratios (ORs) and their 95% confi-
dence intervals (CIs) were performed using logistical regression
analyses for depressive symptoms in relation to nocturnal mictu-
rition. Sex, age, BMI, duration of type 2 diabetes, current smoking,
current drinking, hypertension, dyslipidemia, coronary artery disease,
stroke, glycated hemoglobin levels and diabetic retinopathy were
selected a priori as potential confounding factors. Multiple regres-
sion logistic analyses were used to adjust for potential confound-
ing factors. Multiplicative interaction was estimated by introducing
a multiplicative term into a multiple logistic regression model. All
statistical analyses were performed using SAS software package v.
9.4 (SAS Institute, Cary, North Carolina, United States).
Results
In the 762 patients with type 2 diabetes, the prevalence values
of mild nocturia, moderate to severe nocturia and depressive symp-
toms were 39.5%, 41.9% and 16.8%, respectively (Table 1). The mean
age and BMI and the prevalence values of hypertension and
dyslipidemia in female patients were significantly higher than those
in males. On the other hand, the prevalence values of current
smoking and drinking in male patients were higher than those in
females (data not shown). There were increasing trends in age, male
ratio, duration of diabetes, hypertension, diabetic neuropathy, dia-
betic retinopathy and SDS scores and decreasing trends in BMI and
current smoking. Table 2 shows crude and adjusted ORs and 95% CIs
for depressive symptoms in relation to nocturnal micturition. The
prevalence values of depressive symptoms among patients without
nocturia, with mild nocturia and with moderate to severe noctu-
ria were 11.3%, 17.3%, and 18.8%, respectively. After adjustment for

Table 1
Clinical characteristics according to nocturnal micturition in 762 study participants

Variable Total values (%) No nocturia (n=142) Mild nocturia (n=301) Moderate to severe nocturia (n=319) p for trend

Age, years, mean ± SD 61.6±11.2 54.3 61.1 65.2 0.001

Male gender (%) 483 (63.4) 57.8 61.1 68.0 0.021
Female gender (%) 279 (36.6) 42.2 38.9 32.0
BMI, kg/m2, mean ± SD 25.2±4.8 26.4 25.1 24.7 0.004
A1C, mean 7.9±1.9 7.8 8.0 7.9 0.74
Duration of diabetes, years, 10.9±10.0 7.7 10.8 12.5 0.001
mean ± SD
Current drinking (%) 314 (41.2) 47.2 40.9 38.9 0.11
Current smoking (%) 145 (19.0) 26.1 19.9 15.1 0.005
Hypertension (%) 536 (70.3) 63.4 69.8 74.0 0.022
Dyslipidemia (%) 563 (73.9) 76.1 71.4 75.2 0.89
Diabetic neuropathy (%) 469 (61.6) 49.3 58.8 69.6 0.001
Diabetic retinopathy (%) 220 (28.9) 19.7 30.6 31.4 0.025
Diabetic nephropathy (%) 79 (10.4) 7.8 10.3 11.6 0.22
Stroke (%) 52 (6.8) 3.5 8.0 7.2 0.25
Coronary artery disease (%) 82 (10.8) 7.0 11.3 11.9 0.16
SDS score 40.5±8.9 38.9 39.9 41.7 0.003
Depressive symptoms (%) 128 (16.8) 11.3 17.3 18.8 0.06

A1C, glycated hemoglobin; BMI, body mass index; SDS, Self-rating Depression Scale.
Notes: For continuous variables, a linear trend test was used; for categorical variables, a Mantel-Haenszel chi-square test was used.

Table 2
Crude and adjusted odds ratios and 95% confidence intervals for depressive symptoms in relation to nocturnal micturition

Variable Prevalence (%) Crude OR (95% CI) Adjusted OR (95% CI) R2 value

Nocturnal micturition
All patients
No nocturia 16/142 (11.3) 1.00 1.00
Mild nocturia 52/301 (17.3) 1.65 (0.92 to 3.08) 1.96 (1.06 to 3.77)
Moderate to severe nocturia 60/319 (18.8) 1.82 (1.03 to 3.39) 2.58 (1.38 to 5.08) 5.5%
Male patients
No nocturia 12/82 (14.6) 1.00 1.00
Mild nocturia 27/184 (14.7) 1.00 (0.49 to 2.16) 1.05 (0.49 to 2.39)
Moderate to severe nocturia 39/178 (21.9) 1.28 (0.65 to 2.68) 1.45 (0.66 to 3.36) 5.5%
Female patients
No nocturia 4/60 (6.7) 1.00 1.00
Mild nocturia 25/117 (21.4) 3.80 (1.39 to 13.42) 5.26 (1.73 to 20.61)
Moderate to severe nocturia 21/102 20.6) 3.63 (1.31 to 12.95) 6.91 (2.15 to 28.54) 13.5%
CI, confidence interval; OR, odds ratio.
Notes: Odds ratios were adjusted for sex, age, body mass index, duration of type 2 diabetes, current smoking, current drinking, hypertension, dyslipidemia, coronary artery
disease, stroke, glycated hemoglobin levels and diabetic retinopathy.
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sex, age, BMI, current smoking, current drinking, hypertension,
stroke, coronary artery disease, stroke, glycated hemoglobin levels
and diabetic retinopathy, mild nocturia and moderate to severe noc-
turia were independently positively associated with depressive
symptoms; the adjusted ORs were 1.96 (95% CI 1.06 to 3.77) and
2.58 (95% CI 1.38 to 5.04), respectively. In female patients, mild noc-
turia and moderate to severe nocturia were independently posi-
tively associated with depressive symptoms; the adjusted ORs were
5.26 (95% CI 1.73 to 20.61) and 6.91 (95% CI 2.15 to 28.54), respec-
tively. In male patients, mild nocturia and moderate to severe
nocturia were not associated with depressive symptoms. No mul-
tiplicative interaction was found between sex and moderate to severe
nocturia with regard to nocturia (p=0.17 for homogeneity of OR for
moderate to severe nocturia).
Discussion
This study is the first to show a significant positive association
between nocturia and depressive symptoms in Japanese patients
with type 2 diabetes. Our findings were in agreement with those
of previous epidemiologic studies of general populations, which also
showed a positive association between nocturia and depressive
symptoms.
In an American study of 2890 men aged 40 years old or older,
nocturia (2 or more voids per night) was significantly positively asso-
ciated with moderate to severe depression based on the Patient
Health Questionnaire-9 (PHQ-9) (3). In an American study of 547
male patients in departments of urology, the self-reported noctu-
ria scores in patients with depressive symptoms, based on the Geri-
atric Depression Scale, were higher than those of patients without
depressive symptoms; severe nocturia (5 or more voids per night)
was significantly positively associated with depressive symptoms
(4). In an American study of 5503 subjects, nocturia (3 or more voids
per night) was significantly positively associated with depression
symptoms based on the Center for Epidemiological Studies Depres-
sion Scale (CES-D) in both men and women (5). In an American study
of 5506 adults aged 30 to 79, nocturia was significantly positively
associated with depressive symptoms based on the CES-D (6). In
a Dutch study of 2042 women aged 20 to 70, only nocturia, but not
other urogenital symptoms, was significantly positively associ-
ated with depressive symptoms based on the CES-D (7).
On the other hand, in an American cross-sectional study of
2016 women aged 40 years and older, depressive symptoms, based
on the Hospital Anxiety and Depression Scale (HADS), were sig-
nificantly positively associated with clinically significant nocturia
(2 or more voids per night) (8). In an American study of 5297 men
aged 20 years or older, major depression, based on the PHQ-9,
was significantly positively associated with nocturia (9). In a Swedish
study of 1375 subjects, major depression, based on the Major
Depression Inventory, was significantly associated with nocturia
(2 or more voids per night) (10). In a Finnish cohort study of 1580
men, moderate to severe depressive symptoms, based on the 5-item
Mental Health Inventory screening test, but not mild depressive
symptoms, were positively associated with moderate or severe
nocturia but not mild nocturia, after adjustment for age (11). In a
cross-national (United States, United Kingdom, Sweden) study of
30,000 subjects aged 40 years or older, depression, based on the
HADS was independently positively associated with nocturia (2
or more voids per night) after adjustment for several confounding
factors in men but not in women (12).
In a systematic review, it was found that nocturia poses a greater
risk for depression in men than in women (13). However, our find-
ings were inconsistent with previous results in general popula-
tions. These discrepancies might be explained by the distribution
of age, BMI, race, medications and hyperglycemia.
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The mechanisms linking nocturia and depression are still unclear.
Nocturia can lead to daytime drowsiness, inability to concentrate
and decreased motivation to perform activities because of dis-
turbed sleep (3). Chronic lower urinary tract symptoms, including
nocturia, reduce quality of life and can lead to embarrassment, social
anxiety, demoralization and poor self-esteem (28). The incidence
of depression in men with benign prostatic hyperplasia was higher
in a Polish study of 4035 men (2) and in a Taiwanese study of 16,130
men (29). However, the bidirectional association between noctu-
ria and depressive symptoms was suggested. In experimental
animals, reduction of the serotonin and noradrenaline levels in the
central nervous system can lead to depression, increased urinary
frequency and hyperactive bladders (30). The prevalence of sleep
disturbance in patients with depressive symptoms was higher than
in those without depressive symptoms. Patients with uninter-
rupted sleep due to depressive symptoms might decide not to void
until waking in the morning. Further studies are needed to inves-
tigate the underlying mechanisms.
Limitations
Our study has several limitations. First, because this was a cross-
sectional study, we cannot conclude that there is a causal relation-
ship between nocturia and depressive symptoms. The R2 values in
this study were low, and there is the possibility that many impor-
tant confounding factors were excluded because the etiology of noc-
turia and depressive symptoms are thought to be multifactorial.
Second, we did not use frequency-volume charts to detect the
amount of urine. Therefore, we could not estimate overall urine pro-
duction, an increase in urine production only at night or reduced
nocturnal bladder capacity. The data in our study concerning noc-
turia was self-reported. In previous epidemiologic studies
(2–12,14–16,18,29), however, the definition of nocturia was also
based on self-administered questionnaires. Third, we could not
perform urologic examinations. Fourth, our study could not deter-
mine whether subjects were awakened by the need to urinate or
were already awake as a result of other diseases at the time they
decided to void. Fifth, the prevalence of current smoking and the
male ratio was significant higher than that in the included group.
The prevalence of diabetic neuropathy in the excluded group was
significantly lower than that in the included group. Selection bias
could have influenced our results. Finally, we could not control for
the subjects’ partners or socioeconomic statuses.
Conclusions
Nocturia may be independently positively associated with depres-
sive symptoms in Japanese female patients with type 2 diabetes.
Acknowledgements
We thank Morikazu Onji from Saiseikai Imabari Hospital, Eriko
Kawamoto from University of the Ryukyus, Keiko Kikuchi and Tomo
Kogama from Ehime University, and Eri Furukawa from The
Furukawa Clinic. This study was supported by the Japan Society for
the Promotion of Science KAKENHI Grants 21790583 and 23790697).
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