Shinshu Med J, 69⑵：75～81, 2021

Exploring Hidden Atrial Fibrillation in Patients withType 2 Diabetes Mellitus Admitted to Shinshu University Hospital
Keiko Sekido, Takashi Sekido, Yohsuke Ohkubo, Yusuke Shibata, Iori Kawata
Tomohiko Yamaguchi, Ai Sato, Yoshihiko Sato and Mitsuhisa Komatsu＊
Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine,
Shinshu University School of Medicine

Using the event-triggered recorder, SpiderFlash-t AFIB, which allows us to detect asymptomatic or symp­
tomatic arrhythmia, we examined the prevalence of hidden atrial fibrillation (AF) in patients with type 2 diabe­
tes admitted to our hospital. In total, we enrolled 69 patients with type 2 diabetes mellitus admitted to the hospi­
tal due to hyperglycemia. Averages of HbA1c, age, duration of the disease, and BMI were 8.9 ％, 64.8 years old,14.8 years, and 26.0 kg/m2, respectively. Neuropathy, retinopathy, and nephropathy were found in 37 (53.6 ％), 27(39.1 ％), and 27 (39.1 ％), respectively. Macroangiopathy was found in 13 (18.9 ％). In the first series of surveys
where we attached the recorder for 7 days no sustained AF events were found, and only 2 transient events. We
attached the recorder for 14 days with 39 subjects in the second series of the survey, and fail to find any AFrhythm. This study is the first attempt to reveal the frequency of hidden AF in diabetes. This finding suggeststhat screening of atrial fibrillation with SpiderFlash-t AFIB for patients with type 2 diabetic patients hospital­
ized for glycemic control may not be useful in assessing the prevalence of atrial fibrillation. Shinshu Med J
69 : 75―81, 2021
(Received for publication November 5, 2020 ; accepted in revised form December 28, 2020)
Key words : atrial fibrillation, diabetes mellitus, sinus rhythm, SpiderFlash-t AFIB

Ⅰ

important to identify subclinical or paroxysmal AF in

Introduction

individuals without persistent AF to consider the ap­

Atrial fibrillation (AF) is the most common form ofplication of anti-coagulation therapy. Type 2 diabetes

cardiac arrhythmia in clinical practice. As the aging

mellitus (T2D), which relates to sedentary lifestyleof society proceeds, the number of patients with AFand overeating, has spread rapidly worldwide, and it

is steadily increasing worldwide because aging is ais established as a strong risk factor for atherosclero­

1）strong risk factor for the development of AF . In

sis. Incidence of T2D among AF patients was report­

Japan, it is estimated that over 2 million subjects

ed to be higher than among non-AF individuals3）.

suffer from AF, and it could be a common disease.

Several lines of evidence suggest that there is a

AF is a high risk factor for developing strokes and isstrong correlation between the presence of T2D andlargely preventable with anti-coagulation therapy.

the development of stroke4）. In addition, T2D is gen­

However, approximately 40 ％ of Japanese patients

erally considered one of the risk factors for AF al­2）

with AF remained asymptomatic . Therefore, it isthough the pathophysiological relationship between
diabetes mellitus and AF is unknown. Indeed, in the＊Corresponding author : Mitsuhisa Komatsu

Framingham Heart Study, the presence of diabetes

Division of Diabetes, Endocrinology and Metabolism,

was shown to be associated with a significant in­

Department of Internal Medicine, Shinshu University
School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano
390-8621, Japan
E-mail : mitsuk@shinshu-u.ac.jp

No. 2, 2021

crease in the development of AF with odds ratio
being 1.1 for men and 1.5 for women5）. Accordingly,
it is possible that T2D without apparent AF has75

Sekido K・Sekido T・Ohkubo et al.

hidden paroxysmal AF with no symptoms suchnormal ECG on admission and no history of AF. We

as palpitation. However, the precise prevalence ofanalyzed various clinical parameters of the patients.

paroxysmal AF in patients with T2D has not been

When we identified AF or transient AF rhythms inestablished due to a lack of accurate and feasible

the patients, we performed brain MRI/MRA andequipment for its evaluation.

consulted cardiologists as to whether they needed toIn this study we examined the prevalence of par­receive anticoagulant therapy. The patients wereoxysmal AF in T2D patients who were admitted toadvised to press the button on the recorder if they

our hospital in order to control hyperglycemia, using

felt chest symptoms such as palpitation, chest pain,

an event-triggered recorder, SpiderFlash-t AFIB.

and dizziness. We defined paroxysmal AF as irreg­

Given that this recorder allows us to detect asymp­

ular R-R interval and a lack of P-wave of moretomatic or symptomatic arrhythmia including tran­

than 60 seconds, and supraventricular tachycardia

sient AF over periods of weeks, we will be able to(SVT) as 120 beats per minute or lasting 8 minutes

uncover the clinical importance of searching foror more, and bradycardia as 45 beats per minute or

hidden AF in T2D.

less for more than 20 seconds.

ⅡＡ

Materials and Methods

External loop recorder
For the detection of asymptomatic and symptomaticＣ

Statistical analysis
Values from Periods 1 and 2 were compared withnon-paired Students` T test, and a p value less than
0.05 was considered statistically significant.

arrhythmic events, we used an extended external loop

The protocol of this study was approved by therecorder (SpiderFlash-t AFIB ; Sorin, France, Medi­

ethics committee of Shinshu University School ofcal device approval number : 222AHBZI00013000).

Medicine (Approved number 2702). All patients pro­

The recording consisted of continuous electrocardi­

vided written informed consent.

ography (ECG) recording for the initial 24h, auto-Ⅲ

trigger episodes, and patient-activated episodes for7days or 14 days. The SpiderFlash-t AFIB can record

ＡResults

Characteristics of the subjects
As shown in Table 1, the characteristic features

an ECG for up to 7.5 min before and 15 min after
detection of arrhythmias or patient activation.

of the subjects in Period 1 and Period 2 were essen­Ｂtially similar. As a whole, they had 14.8±11.8 year

Subjects
We attached SpiderFlash-t AFIB for 7 days to 39

duration of type 2 diabetes, and exhibited microvas­

T2D patients admitted to Shinshu University Hospitalcular complications in neuropathy 53.6 ％, retinopa­

from April 1, 2014 to September 30, 2014 (Period 1).

thy 39.1 ％ , nephropathy more than state 2 39.1 ％From April 1, 2015 to September 30, 2015, the secondand macrovascular complications 18.9 ％ . Glycemic

series of the study was performed with 30 T2Dcontrol was poor (HbA1c 8.9±1.8 ％) because most ofadmitted to Shinshu University Hospital (Period 2).

the patients were admitted to the hospital to control

In the second population, we attached SpiderFlash-t

hyperglycemia. Thus our patients were considered

AFIB for 14 days to enhance the possibility of detec­to be a relatively advanced stage population rather

tion of the events. Gladstone et al. reported thatthan newly diagnosed.

the detection rate with SpiderFlash-t AFIB of atrial

Ｂ

Results of SpiderFlash-t FIB

fibrillation increased 7.4 ％ in 7days and 11.6 ％ in 14

In Table 2, we summarize the incidence of arrhyth­days in patients with transient stroke and cerebral

mias in this study. In Period 1, none of the sub­6）

infarction . Based on this finding we decided tojects were detected to have AF with SpiderFlash-t

review again by extending the wearing of the moni­

FIB, and only 2 out of 39 subjects were found totor. The characteristic features of the patients areexperience transitory AF rhythm lasting less than 10

summarized in Table 1. We included T2D withbeats. Both of the events were asymptomatic. Then76

Shinshu Med JVol. 69

Type 2 diabetes and atrial fibrillation
Table 1

Clinical Characteristics of the patients

GenderMale, n (％)
Female, n (％)
Age, median, years
HbA1c (％)
Body mass index (kg/m2)
Time since diagnosis of type 2 diabetes
Neuropathy
Retinopathy
Nephropathy＊
stage1stage2stage3stage4stage5
History of athererosclerotic vascular disease
Coronary
Cereberovascular disease
Pulmonary embolism
Hypertension
Hyperlipidemia
Hyperuricemia

Period 1n＝39

Period 2
n＝30

Total
n＝6926 (67)
13 (33)62.1 (13.7)
8.9 (1.6)

18 (60)12 (40)67.6 (11.7)
9.1 (2.0)

43 (62.3)
26 (37.7)
64.8 (12.6)
8.9 (1.8)

27.1 (6.3)
12.7 (11.9)
12 (35.2)
14 (41.1)

25.3 (4.9)
16.3 (11.6)
15 (50.0)
13 (40.0)26 (5.7)
14.8 (11.8)
37 (53.6)
27 (39.1)

30 (76.9)
3 (7.7)6 (15.4)00

12 (40.0)
9 (30.0)
3 (10.0)
6 (20.0)042 (60.9)
12 (14.5)
9 (13.0)
6 (8.7)0

7 (17.9)
11 (36.6)
2 (5.1)28 (71.7)
18 (46.1)
2 (5.8)6 (20.0)
14 (46.6)
3 (10.0)
21 (70.0)
13 (43.3)
6 (20.0)

13 (18.9)25 (36.2)
5 (7.1)49 (71.0)
31 (44.9)
8 (11.6)

Baseline characteristics of the subjects. Data are n (％) or mean (SD). eGFR=estimated glomerular filtration rate.
＊Stage of nephropathy, stage 1 is normal albuminuria＝UACR＜30 mg/g and eGFR＞30, stage 2 is microalbuminuria＝UACR≧30to≦300mg/g and eGFR＞30, stage 3 is macroalbuminuria＝UACR＞300mg/g and eGFR＞30, Stage 4 iseGFR＜30.
Table 2

event％

Arrthymic patterns detected by the SpiderFlash-t AFIB and the number in 69 cases

AF＊PAC

PVC

PauseBrady

VT

second degree
AV block

2
2.9

56
81.2

37
53.6

12
17.4

453.6

2
2.9

22.9

AF : atrial fibrillation, PAC : premature atrial contraction, PVC : premature ventricular contraction,
VT : ventricular tachycardia ;＊AF rhythm lasted too short to define as AF.

we performed 24-hour Holter electrocardiography intractions were observed in all cases. There were 2both patients, and did not find any evidence of tran­

cases who exhibited 5 sequential ventricular prema­

sitory AF rhythm. In Period 2, where cardiac rhythms

ture contractions, so beta-blocker was started just inwere monitored for 14 days (actual recorded periods

case of serious ventricular arrhythmias. More thanwere 12.03±4.02 days) with SpiderFlash-t AFIB,

triplet supraventricular premature contractions were

there was no AF rhythm recorded, and no transitory

found in 38 cases (55 ％).

AF in all 30 subjects. In total, we only found 2 out of

The 2 patients with AF rhythm underwent MRI/

69 subjects exhibiting transitory AF rhythm. Atrial

MRA and were referred to cardiologists. We describe

extrasystoles and supraventricular premature con­the clinical features of the 2 cases in brief.

No. 2, 2021

77

Sekido K・Sekido T・Ohkubo et al.

Fig. 1

Subclinical AF of about 10 heart beats recognized by SpiderFlash-t AFIB (Case 1).

Fig. 2 MRI revealed that the vicinity of the rightventricle is high (flair image : left).
Right picture is T1WI. Old multiple lacunar
infarction was observed.

ＣCase 1cigaretes a day for 50 years. Past history was cata­

A 68-year-old male was admitted to our hospitalract operation. There was no diabetic neuropathy

to control hyperglycemia. His recent HbA1c wasand diabetic retinopathy, but there was microalbu­

8.5 ％. He had a history of type 2 diabetic mel­minuria compatible with early stage of diabetic ne­litus over 10 years. He had no diabetic neuropathy,phropathy. BMI was 27.8 kg/m2, and blood pressure

diabetic retinopathy or diabetic nephropathy. Hewas 118/69 mmHg. The electrocardiogram at hospi­

smoked 20 cigarets per day for 30 years. Electrocar­

talization was normal. We tried using the event-diogram at hospitalization was normal. We used thetriggered recorder SpiderFlash-t AFIB for 7 days.

event-triggered recorder SpiderFlash-t AFIB for 7

Fig. 3 shows subclinical AF of about 7 ventriculardays. Fig. 1 shows AF rhythms for about 10 heartbeats. We referred him to a cardiologist. Holter ECG

beats. Brain MRI/MRA revealed old multiple lacunar

was done, but AF was not identified. Anticoagulation

infarctions, and an acute phase of cerebral infarction

therapy was not indicated.

was observed in the vicinity of the right ventricle

Ⅳfull angle (Fig. 2). We referred the patient to a cardi­

Discussion

ologist and a neurologist. After that, Holter ECG for

Despite an intensive search for hidden AF in Japa­

24 hours was done, but no AF rhythms were detect­nese patients with T2D, we failed to detect any AF

ed. It was judged that anticoagulation therapy wasevents in the patients who were admitted to ournot indicated in this patient. If there were to be re­hospital for the purpose of glycemic control and edu­

peatability of AF rhythms in the future, it was overcation. Two events of 10 or less beats of irregularpolicy to start anticoagulation therapy. An antiplate­

R-R, which did not reach the criteria of AF, werelet drug was started for acute stage cerebral infarc­

found in two patients. This result was totally unex­

tion.

pected.

ＤCase 2

Recently, by using noninvasive ambulatory ECG

A 71-year-old male was admitted to our hospitalmonitoring, Gladstone et al, found paroxysmal AF in

to control hyperglycemia. He had a history of T2D

7.4 ％ and 11.6 ％ of the patients with cryptogenic

over 40 years. Immediately before addmittion, hisstroke with 1 week and 2 weeks monitoring, respective­

HbA1c was 10.0 ％ . His mother has diabetes, andly5）. Affordability of extended external auto-triggered

cerebral vascular disease. He had been smoking 30

loop recorder monitoring, which is exactly the same78

Shinshu Med JVol. 69

Type 2 diabetes and atrial fibrillation

Fig. 3

Subclinical AF of about 7 heart beats of recognized in SpideFlash-t AFIB (Case 2).

Table 3 AF risk factors raised by Framingham study and Hisayama study, inour survey
risk factor

All patientsagesmoking
diabetes mellitus
left ventricular hypertrophy
hypertention
ischemic heart disease
congestive heart falure
antiarrhythmic drug

64.8 (12.6)
57.9
100
31.9
71
14.5
10.1
7.2

Data are n (％) or mean (SD).

equipment used in our study, had been reported in7）

the Framingham study and Hisayama stydy12） andAF patients after catheter ablation . Several studies

our study patients. As a result, in this study, the rate

have shown that the patients with T2D have an in­of smoking, left ventricular hypertrophy, and blood8）

creased risk of AF . For example, T2D is reportedpressure were high and obviously all of the subjects

as an independent risk factor for AF in the Chinese

had T2D. The percentage of each factor was high,population. Diabetes mellitus is an independent risk

but the detection rate of atrial fibrillation was low. In9）

factor for atrial fibrillation in a general population .

Japan, research on AF prevalence studies includes

Recent meta-analyses of 100 thousand people revealed

nationwide surveillance of cardiovascular disease13）14）,

that the risk of AF is increased by 40 ％ in diabetic

epidemiology survey of Japanese cardiovascular10）

disease15）, and a survey of Kurashiki city16）. Compar­

subjects compared to non-diabetic subjects .

We expected the presence of intermittent and as­

ing the average age in this study, there was no par­ymptomatic AF evading detection under usual

ticular difference. Although there has been no sur­clinical evaluation such as careful physical examina­

vey targeting diabetic patients, this study suggested

tion and a single recording of electrocardiographythat the frequency of latent AF in Japanese diabetic(ECG) in our T2D patients. The T2D patients in thispatients does not change with the prevalence rate instudy included various stages of the disease. Many

the general population in the ages we studied.

of them were advanced and high-risk patients as

Therefore, the lack of episodes of AF even under
prolonged monitoring in this study is not likely dueshown.
The prevalence of paroxysmal AF in the general

to patient profile. Rather, our findings suggest that11）

population was reported to be approximately 3 ％ .

the prevalence of intermittent and paroxysmal AF in

Aging and having heart disease were strong risk

Japanese T2D patients who apparently have no4）

factors for the development of AF . Table 3 shows
the risk factors for atrial fibrillation, as identified in
No. 2, 2021

history and no AF on ECG is low.
To the best of our knowledge, the incidence of79

Sekido K・Sekido T・Ohkubo et al.

paroxysmal, or preclinical, AF in T2D is not previ­

propose an accurate incidence of subclinical AF in

ously reported. To elucidate subclinical AF in a

Japanese T2D. Another limitation of the study is thatpatient without a prior history of AF, it is important

the recordings were performed during admission.

to use proper monitoring techniques. In this sense,

This may be one of the reasons for the decrease in

we consider that our approach with SpiderFlash-t

the occurrence of paroxysmal AF.
In conclusion, we failed to detect any single event

AFIB monitoring for an average of 9.2±3.6 days isof paroxysmal AF compatible with our definition inreasonable enough to detect subclinical AF.
The limitation of our study is obviously the small

69 Japanese T2D patients without a prior episode ofnumber of study individuals. We could not propose

AF. This finding suggests that the screening of atrial

the actual number of the incidence of subclinical AF,

fibrillation with SpiderFlash-t AFIB for patients withrather we could suggest the rare incidence of sub­type 2 diabetic patients hospitalized for glycemic

clinical AF in Japanese T2DM who were admitted tocontrol may not be useful in assessing the preva­

our hospital for controlling their hyperglycemia. Al­

lence of atrial fibrillation.

though an implantable loop recorder allows us toDisclosure

monitor for a longer period of time, it is slightly

None of the authors have any potential conflicts ofinvasive and not suitable for screening of subclinical
AF. Nevertheless, we need both elongation of moni­interest associated with this research.

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