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Original Article for Chronobiology International
Morningness Eveningness Questionnaire score and metabolic parameters in
patients with type 2 diabetes mellitus
Yusuke Osonoi MD1, Tomoya Mita MD, PhD 1,4, Takeshi Osonoi MD, PhD6, Miyoko 5
Saito MD, PhD6, Atsuko Tamasawa MD, PhD6, Shiho Nakayama MD, PhD 1, Yuki
Someya1, Hidenori Ishida MD6, Akio Kanazawa MD, PhD 1,3, Masahiko Gosho, PhD7,
Yoshio Fujitani MD, PhD 1,2, Hirotaka Watada MD, PhD 1-5
1Department of Metabolism & Endocrinology, 2Center for Beta-Cell Biology and 10
Regeneration, 3Center for Therapeutic Innovations in Diabetes, 4Center for Molecular
Diabetology, 5Sportology Center, Juntendo University Graduate School of Medicine,
Tokyo, Japan, 2-1-1 Hongo, Bunkyoku, Tokyo 113-8421, Japan. Phone:
+81-3-5802-1579. Fax: +81-3-3813-5996
6 Naka Memorial Clinic, 745-5, Nakadai, Naka City, Ibaraki 311-0113, Japan. Phone: 15
+81-29-353-2800. Fax: 81-295-5400
7Unit of Biostatistics, Advanced Medical Research Center, Aichi Medical University,
1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan. Phone: +81-561-61-1925.
Fax: 81-561-61-1896
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Running head: Lifestyle patterns and biochemical parameters
Word count, text 2,994, abstract 191, number of reference 28, number of tables 3
2
Correspondence: Dr. Tomoya Mita, Department of Metabolism and Endocrinology,
Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyoku, Tokyo 25
113-8421, Japan. Phone: +81-3-5802-1579. Fax: +81-3-3813-5996
E-mail: tom-m@juntendo.ac.jp
3
Abstract
“Morningness” and “Eveningness” represent lifestyle patterns including sleep-wake 30
patterns. Although previous studies described a relationship between the
morningness-eveningness trait and glycemic control in patients with type 2 diabetes
mellitus (T2DM), the mechanism underlying this association remains unknown. The
study participants comprised 725 Japanese T2DM outpatient free of history of
cardiovascular diseases. Various lifestyles were analyzed using self-reported 35
questionnaires, including morningness-eveningness questionnaire. The relationships
between morningness-eveningness trait and various biochemical parameters were
investigated by linear regression analysis and logistic regression analysis. We
classified the study patients into three groups, morning type (n=117), neither type
(n=424), and evening type (n=184). Subjects of the evening type had high levels of 40
alanine aminotransferase, triglyceride, fasting blood glucose and HbA1c and low HDL
level in a model adjusted for age and gender. Furthermore, multivariate analysis
showed that the evening type was associated with high HbA1c and eGFR even after
adjustment for other lifestyle factors known to affect metabolic control. The results
suggest that T2DM patients with eveningness trait are under inadequate metabolic 45
control independent of other lifestyle factors. Thus, the evening trait classified by
morningness-eveningness questionnaire of T2DM patients represents an important
target for intervention to ensure appropriate metabolic function.
Key words: morningness-eveningness questionnaire, type 2 diabetes mellitus, 50
4
Abbreviations:
BDI, Beck Depression inventory;
BDHQ, brief, self-administered diet history questionnaire;
CVD, cardiovascular disease; 55
HDL, high-density lipoprotein-cholesterol;
IPAQ, International Physical Activity Questionnaire;
MEQ, morningness-eveningness questionnaire;
NGSP, National Glycohemoglobin Standardization Program;
OHA, oral hypoglycemic agents; 60
PSQI, Pittsburg Sleep Quality Index;
T2DM, type 2 diabetes mellitus ;
5
Introduction
The onset of type 2 diabetes mellitus (T2DM) is associated with numerous lifestyle
problems. Furthermore, the incidences of cardiovascular disease (CVD) and 65
microvasuclar events correlate with lifestyle factors in patients with T2DM (Stevens,
Kothari et al., 2001; Balkau, Hu et al., 2004). Recent studies have highlighted the
importance of morningness-eveningness trait, in addition to other life styles, in
glycemic control in patient with T2DM (Iwasaki, Hirose et al., 2013; Reutrakul, Hood
et al., 2013). The morningness-eveningness trait reflects the timing of the sleep-wake 70
pattern and other activities, which are quite variable among individuals. The
preferential timing of wake and bedtime is regulated by mainly endogenous circadian
clock in the suprachiasmatic nucleus of the hypothalamus together with various
environmental cues (Klerman, 2005).
With regard to the circadian clock, early studies on plants confirmed that 75
various 24-hour periodic phenomena arise from biological oscillators that internally
track the rotation of Earth. These clocks are entrained by light and synchronize
energy-harvesting and utilization processes with the rising and setting of the sun (Bass
& Takahashi, 2010). In addition, animal experiments showed that endogenous rhythms
are optimally synchronized to the environment by sunlight, physical activity, sleep and 80
feeding behavior and play important roles in the regulation of energy intake and
consumption, metabolism and hormone secretion, in addition to the sleep-wake
pattern (Turek, Joshu et al., 2005; Salgado-Delgado, Angeles-Castellanos et al., 2010;
Huang, Ramsey et al., 2011).
Humans living in modern industrialized societies have easier access to light 85
6
and are often forced to be awake by social norms against their preferred times
independent of the master circadian rhythm. These environmental stimuli eventually
lead to the disruption of the circadian system. Thus, both genetic variations in clock
genes and environmental elements affect the distribution of chronotype.
Evening-type individuals show large differences between social rhythms and 90
the circadian clock. These subjects tend to have unhealthy eating habits, behavioral
health problems, sleep complains, more frequently than individuals of the
morning-type (Ostberg, 1973; Broms, Kaprio et al., 2011). These data suggest that
evening-type individuals could have potentially impaired metabolism based on
abnormal circadian rhythm. Indeed, cross-sectional study demonstrated higher 95
prevalence of T2DM and atrial hypertension in the evening-type individuals than in
the general population (Merikanto, Lahti et al., 2013). Furthermore, more recently, we
and other groups reported the relationships between evening type in 101 male
Japanese workers with T2DM and inadequate glycemic control, and between latter
chronotype among 194 non-shift workers with T2DM, and inadequate glycemic 100
control (Iwasaki, Hirose et al., 2013; Reutrakul, Hood et al., 2013).
These limited data suggest that chronotype could potentially affect glucose
metabolism in patients with T2DM. However, the mechanism or the factors that
mediate the association between the morningness-eveningness classified by The
Morning Evening Questionnaire (MEQ) score and biomedical parameters of glycemic 105
control, dyslipidemia, and renal function remains largely unknown in patients with
T2DM. Here, we investigated the relationship between morningness and eveningness
trait classified by MEQ score and various biochemical parameters in patients with
7
T2DM.
110
Research Design and Methods
Subjects. The subjects of this cohort study were recruited from the Diabetes
Outpatient Clinic of Juntendo University, (Tokyo, Japan) Naka kinen Clinic (Naka,
Japan) or Secomedic Hospital (Funabashi, Japan). The subjects were mainly treated
their diabetes and lifestyle related disease including hypertension, hyperlipidemia and 115
so on. The inclusion criteria were as follows: 1) T2DM patients, 2) ≥25 years of age
and <70 years of age (regardless of gender), and 3) signing consent form for
participation in the study. The following exclusion criteria were also applied: 1) type 1
or secondary diabetes, 2) presence of severe infectious disease, before or after surgery,
or severe trauma, 3) history of myocardial infarction, angina pectoris, cerebral stroke, 120
or cerebral infarction, 4) chronic renal failure requiring hemodialysis, 5) liver cirrhosis,
6) moderate or severe heart failure (NYHA/New York Heart Association stage III or
higher), 7) active malignancy, 8) pregnant, lactating, or possibly pregnant women, or
those planning to become pregnant during the study period, 9) patients judged as
ineligible by the clinical investigators. 125
A total of 1,032 consecutive subjects were screened. Among them, 906 patients
who met the above eligibility criteria were invited to participate in the present study.
After providing information on the purpose and procedures of the study, 736 patients
with T2DM were recruited for this study between June 2013 and January 2014. Blood
and urine samples were taken from the participants and questionnaire surveys were 130
conducted. Data of brachial-ankle pulse wave velocity (baPWV) within about 6
8
months from the day when questionnaire and blood sample tests were conducted were
used for analysis.
The study was approved by the Institutional Review Board of Juntendo
University Hospital and conducted in accordance with the principles described in the 135
Declaration of Helsinki. All patients provided written informed consent prior to
participation. The study was registered on the University Hospital Medical
Information Network Clinical Trials Registry (UMIN000010932).
Questionnaire survey. The MEQ (Hone & Ostberg, 1976) is a self-assessment 140
questionnaire developed primarily for screening candidates for sleep-related
experiments to evaluate morningness and eveningness in individuals. It consists of 19
items on sleep habits and fatigue. Scoring was based on the original questionnaire by
Östberg (Hone & Ostberg, 1976). The MEQ has a good validity and test-retest
reliability (Hone & Ostberg, 1976) (Taillard, Philip et al., 2004) (Ishihara K, 145
Miyashita A et al., 1986) (Lee, Kim et al., 2014). Briefly, 11 questions allowed for
choice and scored from 1 to 4. Two questions allowed for choice and scored 0, 2, 4
and 6. One question allowed for choice and scored 0, 2, 3 and 5. The remaining 5
questions allowed for choice of time scales and scored from 1 to 5. The sum of all
scores was converted into a three point MEQ scales as follow. scores 16-52: Evening 150
type, scores 53-64: Neither type, scores 65-86: Morning type, as reported previously
(Taillard, Philip et al., 2004).
The Pittsburg Sleep Quality Index (PSQI) (Buysse, Reynolds et al., 1989) is a
self-administered questionnaire designed to evaluate sleep quality and consists of 18
9
items that in turn are comprised of 7 components, which include subjective sleep 155
quality, sleep duration, sleep onset, habitual sleep efficiency, sleep disturbances, use of
sleeping medications, and daytime dysfunction, with each weighted equally on a 0-3
scale, to be summed to yield the global PSQI score ranging from 0 to 21, where the
higher the scores, the worse the sleep quality. The PSQI has a high test-retest
reliability and a good validity (Backhaus, Junghanns et al., 2002). 160
The BDI (Beck Depression inventory)-II is a 21-item questionnaire that
assesses hopelessness, irritability, cognition, guilt, fatigue, weight loss, and sexual
interest, representing depression-related symptoms in adults and adolescents (Beck,
Steer et al., 1996). Each of the 21 items measures the presence and severity of somatic
or cognitive symptom of depression, rated on a 4-point scale ranging from 0 to 3. The 165
ratings are summed, yielding a total score ranging from 0 to 63. A high score
represents depressive state. The BDI-II has been validated as a sensitive, specific, and
predictive tool for quantitative assessment of the severity of depression (Beck, Steer et
al., 1996) and has been reliable (Kojima, Furukawa et al., 2002).
Dietary habits during the preceding month were assessed with the validated, 170
Brief, self-administered Diet History Questionnaire (BDHQ). The BDHQ is a 4-page
structured questionnaire that asks about consumption frequency of selected foods to
estimate the dietary intake of 56 food and beverage items with specified serving size
described in terms of consumption in general Japanese populations. The dietary intake
of energy, including alcohol and selected nutrients, were estimated using an ad hoc 175
computer algorithm for the 56 foods and beverages of the BDHQ and the Standard
Tables of Food Composition in Japan (Agency, 2005). The BDHQ has a good validity
10
(Kobayashi, Murakami et al., 2011) and a test-retest reliability (Beliard, Coudert et al.,
2012).
Physical activity level was assessed with the International Physical Activity 180
Questionnaire (IPAQ) that comprises 4 simple questions on physical activity (Craig,
Marshall et al., 2003). The IPAQ has a good validity a high test-retest reliability
(Murase N, Katsumura T et al., 2002) (Hallal & Victora, 2004).The IPAQ results are
expressed as metabolic equivalent scores (METs-hour-week−1).
Workers were defined as full-time employees or shift workers. The work 185
schedule of the subjects was determined by a question in the questionnaire “Which is
your usual work schedule, day, evening, shift, or permanent night work?” Regular
daytime workers were defined as subjects without any evening or night work in their
usual work schedule. We defined shift working as working patterns that differed from
regular daytime working, including irregular or unspecified shifts, mixed schedules, 190
evening shifts, night shifts and rotating shift.
Subjects were asked whether they were currently smokers, had smoked, had
stopped smoking, the date of stopping smoking, and the number of cigarettes smoked
per day. The subjects were classified according to the smoking status into
non-smokers, former smokers or current smokers. Former smokers were those who 195
had not smoked during the month receding the study.
Biochemical tests. Blood samples were obtained at outpatient visits after
overnight fast. Liver and renal function tests, lipids, HbA1c, and glucose (National
Glycohemoglobin Standardization Program) were measured with standard techniques. 200
11
Urinary albumin excretion (UAE) was measured by latex agglutination assay using a
spot urine sample. The estimated glomerular filtration rate (eGFR) was calculated by
the formula: eGFR (ml/min per 1.73 m2) =194× Age-0.287× serum creatinine-0.1094
(×0.739 for females) (Matsuo, Imai et al., 2009).
205
Measurement of baPWV. baPWV was measured using an automatic
waveform analyzer (BP-203RPE; Colin Medical Technology, Komaki, Japan).
baPWV is a useful independent predictor of mortality and cardiovascular morbidity
even in subjects with T2DM (Maeda, Inoguchi et al., 2014). Briefly, measurement was
performed with the patients in the supine position after resting for five minutes. 210
Occlusion and monitoring cuffs were placed snugly around both areas in the upper
and lower extremities. The pressure waveforms were then recorded simultaneously
from the brachial arteries by the oscillometric method. All scans were automatically
conducted by well-trained investigators who were blinded to the clinical information.
The validity and reproducibility of baPWV measurements are confirmed to be 215
considerably high (Yamashina, Tomiyama et al., 2002).
Statistical analysis. Results are presented as mean±SD or median (interquartile
range: 25% to 75%) for continuous variables or number (proportion) of patients for
categorical variables. Some parameters were logarithmically transformed to 220
approximate normal distribution. Trend association across three groups was evaluated
by linear regression analysis for continuous variables and logistic regression analysis
for categorical variables. We developed three models to evaluate the trend. The first
12
model was unadjusted, the second was adjusted for age and gender, and third model
was adjusted for age, gender, body mass index, PSQI including sleep duration, BDI-II, 225
energy intake, smoking pattern, alcohol consumption and IPAQ. Statistical tests were
two-sided with 5% significant level. All analyses were performed using the SAS
software version 9.3 (SAS Institute, Cary, NC).
Results 230
Among the 736 participating patients, 11 did not complete the questionnaires and they
were thus excluded from analysis. The clinical characteristics of the 725 Japanese
patients with T2DM who were being treated on an outpatient basis are summarized in
Table 1. The mean age was 57.8±8.6 years, 62.9% male and HbA1c was 7.0±1.0%,
estimated duration of T2DM was 9.9±7.2 years. The majority of the subjects had 235
previously attended educational programs about diet and exercise therapy and
received appropriate medical treatments at our hospital. These factors were considered
to have contributed to the well-controlled glucose, lipids, and blood pressure in our
subjects.
The MEQ results showed that 117 individuals were “morning type”, 424 240
“neither type”, and 184 “evening type” as shown in Table 2. Subjects of the evening
type tended to be young, female, obese, workers and shift workers, and have high
PSQI, high BDI-II and low alcohol consumption in the unadjusted model. In the age-
and gender-adjusted model, the subjects were still shift workers with high PSQI and
high BDI-II. On the other hand, there were no significant trends in other lifestyles, 245
including energy intake, smoking consumption, alcohol consumption and IPAQ. In
13
addition, those patients were likely to go to bed late, wake up late and sleep for shorter
time, in both the unadjusted model, and age- and gender-adjusted model. Also, they
tended to have late dinner and late breakfast, frequently have late evening snacks, and
less frequently have breakfast, in both the unadjusted model, and age- and 250
gender-adjusted model. In the model adjusted for age, gender, BMI, PSQI, BDI-II,
energy intake, smoking consumption, alcohol consumption and IPAQ, the subjects
were likely to go to bed late, wake up late, and have late dinner, and late breakfast,
frequently have late evening snacks, and less frequently have breakfast.
With regard to biochemical parameters and baPWV, significantly higher levels 255
of alanine aminotransferase (ALT), triglyceride, fasting blood glucose, HbA1c, and
eGFR and lower HDL levels characterized the subjects in the unadjusted model (Table
3). Furthermore, patients of the evening type had significantly high levels of ALT,
triglyceride, fasting blood glucose and HbA1c, and low HDL level even in the model
adjusted for age and gender. Furthermore, HbA1c and eGFR were higher in the model 260
adjusted for age, gender, BMI, PSQI, BDI-II, energy intake, smoking consumption,
alcohol consumption and IPAQ.
Discussion
Recent small sample sized studies showed that evening or later chronotype adversely 265
were associated with poor glycemic control (Iwasaki, Hirose et al., 2013; Reutrakul,
Hood et al., 2013). Our data extended those previous results by demonstrating that the
evening type classified by MEQ score was associated with high ALT and triglyceride,
and low HDL, in addition to poor glycemic control in the age- and gender-adjusted
14
model. Notably, in those previous studies, other lifestyle factors, including sleep 270
quality, energy intake, physical activity, alcohol consumption and smoking were not
fully taken into consideration. Here, we demonstrated that the evening type classified
by MEQ score was associated with poor glycemic control in the model adjusted for
those other lifestyle factors (Table 3). Therefore, our results suggest that the evening
type classified by MEQ score is an important target for intervention in order to 275
achieve appropriate metabolic control among patients with T2DM.
In this study, total daily energy intake was similar among groups classified by
MEQ score. However, patients of the evening type were considered to consume a
greater amount of daily energy intake at late time of the day, because the evening type
tended to have late dinners, frequently late evening snacks, and less frequent breakfast. 280
Recent clinical studies have suggested that late dinner time promotes high
postprandial glucose levels after breakfast in the following morning, compared to
usual dinner time condition, through a greater effect of late dinners on carbohydrate
digestion and absorption of dietary carbohydrates (Tsuchida, Hata et al., 2013). In
addition, a recent study showed that evening intake of macronutrients and intake 285
before sleep may enhance weight gain in healthy volunteers (Baron, Reid et al., 2013).
Thus, late eating seems to worsen metabolic control.
Patients of the evening type classified by MEQ score were more likely to be
employed as workers including shift workers, with higher frequency of overtime work
beyond 21:00 PM. Such workers may be often forced to stay awake through social 290
cues against their preference regulated at least in part by the master circadian rhythm,
eventually leading to disruption of the circadian system. In this regard, a previous
15
study demonstrated that short-period circadian misalignment in healthy volunteers
could lead to increase postprandial glucose and insulin levels (Scheer, Hilton et al.,
2009). In addition, it could result in low serum leptin levels, which may increase 295
appetite and reduce energy expenditure, leading, in turn, to the development of obesity
and deterioration of metabolism. Finally, such misalignment could also results in
complete inversion of cortisol profile.
In this study, subjects with the evening type classified by MEQ score tended to
have poor sleep quality and more depression-related symptoms. Recent studies 300
reported that both sleep duration and/or quality affect glucose and lipid metabolism in
patients with T2DM (Knutson, Ryden et al., 2006; Williams, Hu et al., 2007; Ohkuma,
Fujii et al., 2013; Wan Mahmood, Draman Yusoff et al., 2013). Also, depressive status
may also negatively affect glucose metabolism through increased counter-regulatory
hormones (Musselman, Betan et al., 2003). However, we showed that the evening type 305
classified by MEQ score was still associated with poor glycemic control even after
adjustment for the above factors. Thus, the poor glycemic control observed in the
evening type is likely to be independent of sleep quality and depression-related
symptoms.
Despite the large number of risk factors for atherosclerosis, subjects with the 310
evening type did not show increased atrial stiffness. This result may be influenced by
exclusion of patients with history of CVD who are considered increased arterial
stiffness. Additionally, we have to consider the possibility that the state of
atherosclerosis in certain artery including carotid artery and coronary artery may not
reflect the results of baPWV. Alternatively, we are conducting long-term follow-up 315
16
study that focuses on lifestyle and onset of primary CVD, in the same cohort. On the
other hand, we found that eGFR was higher in subjects with the evening type, which
could reflect hyperglycemia-induced hyperfiltration.
The present study has certain limitations. First, the cross-sectional design does
not allow inference of causal relationship between evening type and metabolic control. 320
Second, we evaluated lifestyles including MEQ by self-reported questionnaires,
although they have been widely used in many studies. The results could be influenced
by social desirability and recall bias. Third, the validity and reproducibility of the
lifestyle patterns identified in this study were not confirmed, although we used
self-reported questionnaires which have good validity and reliability. Forth, we did 325
not evaluate the compliance of drugs, which may affect the anthropometric data, while
there were no significant differences in types of administered drugs including diabetes,
hypertension and hyperlipidemia among groups (data not shown). Finally, there may
be other lifestyle patterns including nap time that should be considered. Thus, further
sample sized studies across the nation are required. 330
In conclusion, the present study demonstrated that evening patients with T2DM
classified by MEQ score suffered inadequate metabolic control among T2DM patients
free of history of CVD. Therefore, our data suggest that the evening type classified by
MEQ score is an important target for intervention in order to achieve appropriate
metabolic function in patients with T2DM. 335
Declaration of Interest
17
T.M. received research funds from MSD, Takeda and Eli Lilly. T.O. has received
lecture fees from Boehringer Ingelheim, Sanofi-Aventis, Ono Pharmaceutical Co.,
Novo Nordisk Pharma, Kissei Pharma, Mitsubishi Tanabe Pharma, Novartis 340
Pharmaceuticals, Sanwakagaku Kenkyusho, Daiichi Sankyo Inc., Takeda
Pharmaceutical Co., MSD, Dainippon Sumitomo Pharm., Kowa Co. and research
funds from Novo Nordisk Pharma, Dainippon Sumitomo Pharma. A.K. has received
lecture fees from Kissei Pharma, Sanofi-Aventis and Takeda Pharmaceutical Co. M.G.
has received lecture fees from Novartis Pharmaceuticals. Y.F. has received lecture fees 345
from Novartis Pharmaceuticals and Eli Lilly, research funds from Novartis
Pharmaceuticals , MSD and Takeda Pharmaceutical Co. H.W. has received lecture
fees from Boehringer Ingelheim, Sanofi-Aventis, Ono Pharmaceutical Co., Novo
Nordisk Pharma, Novartis Pharmaceuticals, Eli Lilly, Sanwakagaku Kenkyusho,
Daiichi Sankyo Inc., Takeda Pharmaceutical Co., MSD, Dainippon Sumitomo Pharm., 350
Kowa Co. and research funds from Boehringer Ingelheim, Pfizer, Mochida
Pharmaceutical Co., Sanofi-Aventis, Novo Nordisk Pharma, Novartis Pharmaceuticals,
Sanwakagaku Kenkyusho, Terumo Corp. Eli Lilly, Mitsubishi Tanabe Pharma, Daiichi
Sankyo Inc., Takeda Pharmaceutical Co., MSD, Shionogi, Pharma, Dainippon
Sumitomo Pharma, Kissei Pharma, and Astrazeneca. 355
Acknowledgments
The authors thank the following staff who participated in this trial: Ms. Risa
Yamamoto and Ms. Emi Ito (Department of Metabolism and Endocrinology, Juntendo
University Graduate School of Medicine), Ms. Satako Douguchi, Ms. Chiyoko Sato, 360
18
Ms. Yoko Ono, Mr. Tadanori Koibuchi, Ms. Norie Shiina, Ms. Nana Shiozawa, Ms.
Mariko Kobori, Ms. Misato Ojima, Ms. Akiko Haginoya, Ms. Kumiko Fujisaku and
Mr. Katuhiro Kawauchi (Naka Memorial Clinic) for the excellent technical support.
19
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1
Table 1. Patients characteristics (n = 725).
Age (years) 57.8±8.6
Gender (male) 456 (62.9)
Estimated history of diabetes (years) 9.9±7.2
Body mass index (kg/m2) 24.6±4.1
HbA1c (%) 7.0±1.0
HbA1c (mmol/mol) 52.5±10.8
Fasting blood glucose (mg/dl) 134±31
Systolic blood pressure (mmHg) 127±14
Diastolic blood pressure (mmHg) 77±11
Total cholesterol (mg/dL) 185±28
HDL-cholesterol (mg/dL) 59±14
Triglyceride (mg/dL) 100 [70,152]
AST (U/L) 21 [18,27]
ALT (U/L) 22 [16,33]
-GTP (U/L) 25 [17,39]
Uric Acid (mg/dl) 5.5±1.2
eGFR (ml/min/ 1.73 m2) 78±18
UAE (mg/g creatinine) 10 [6,23]
baPWV (cm/s) 1543±279
Morningness-Eveningness Questionnaire 57.4±7.3
Pittsburg Sleep Quality Index 5.1±3.0
Beck Depression inventory -II 9.9±7.6
Energy intake (kcal/day) 1713±582
Physical activity (Mets/h/week) 42.8±70.5
Sleep duration (hours) 6.4±1.2
Number of cigarettes 335±458
Current smoker (yes) 174 (24.0)
Alcohol (g/day) 12.3±21.5
On treatment for (n/%)
Diabetes 620 (85.5)
Hypertension 346 (47.7)
Hyperlipidemia 442 (61.0)
Data are mean±SD or number (proportion) of patients.
ALT: alanine aminotransferase; AST: aspartate aminotransferase; baPWV: 5
brachial-ankle pulse wave velocity; eGFR: estimated glomerular filtration rate,
HDL-C: high-density lipoprotein-cholesterol, UAE, urinary albumin excretion, -GTP,
-glutamyl transpeptidase.
2
Table 2. Characteristics of each group classified by MEQ score.
Variable Evening type Neither type Morning type Est Est1 Est2 MEQ 47.8± 3.8 58.6 ± 3.3 67.9 ± 2.7 - - - PSQI 6.2 ± 3.5 5.0 ± 2.7 3.9 ± 2.7 -6.72¶ -5.80¶ - BDI 11.6 ± 7.5 9.6 ± 7.7 8.5 ± 7.4 -3.76¶ -2.79† - Energy intake (kcal/day) 1683 ± 567 1743 ± 613 1652 ± 476 -0.16 -1.05 - Current smoking (yes) 48 (26.1) 98 (23.1) 28 (23.9) -0.53 -0.04 - Alcohol 11.0 ± 21.5 11.2 ± 19.9 18.6 ± 25.8 2.66† 1.53 - Physical activity (kcal/day) 33.0 ± 51.7 47.2 ± 81.4 42.3 ± 48.8 1.45 0.96 - Age (years) 53.9 ± 9.6 58.4 ± 57.9 61.8 ± 6.2 8.91¶ - - Gender (male) 108 (58.7) 264 (62.3) 84 (71.8) 2.18¶ - - Body mass index (kg/m2) 25.9 ± 4.5 24.3 ± 3.9 23.7 ± 3.4 -4.91¶ -1.89 - Estimated history of diabetes (years) 9.3±6.8 9.9±7.4 10.6±7.2 1.54 -0.66 -0.20 Anti-diabetes medications (yes) 156(84.8) 360 (84.9) 104 (88.9) 0.88 0.77 0.94 Anti-hypertension medications (yes) 85(46.2) 200 (47.2) 61 (52.1) 0.93 0.19 0.62 Anti-hyperlipidemia medications (yes) 114(62.0) 259 (61.1) 69 (59.0) -0.50 -1.06 -0.87 Working (yes) 149(81.0) 306 (72.2) 78 (66.7) -2.85† -1.21 -0.80 Shift worker (yes) 31(16.8) 43 (10.1) 4 (3.4) -3.67¶ -2.53† -2.42† frequency of overtime work beyond 21:00 PM 1.4±1.1 1.1±0.9 0.9±0.6 -5.41¶ -3.35¶ -2.79† Sleep duration (hours) 6.2±1.2 6.4±1.1 6.9±1.3 4.97¶ 3.47¶ 0.21 Wake time, A.M. 6:30 [6:00,7:18] 6:00 [5:30,6:30] 5:00 [5:00,5:45] -9.53¶ -9.40¶ -8.74¶ Bedtime, P.M. 24:00 [23:00,25:00] 23:00 [22:00,23:30] 22:00 [21:00,22:30] -13.45¶ -11.10¶ -11.31¶ Breakfast time, A.M. 7:30 [7:00,8:00] 7:00 [6:30,7:30] 6:30 [6:00,7:00] -9.29¶ -9.31¶ -8.69¶ Dinner time, P.M. 19:30 [19:00,20:00] 19:00 [18:30,19:30] 19:00 [18:00,19:30] -8.11¶ -6.25¶ -5.90¶ Number of breakfasts (/week) 6.0±1.9 6.8±1.0 6.9±0.4 7.07¶ 6.04¶ 5.53¶ Late evening snack (yes) 80 (43.5) 179 (42.2) 29 (24.8) -2.89† -3.01† -2.49*
Data are meanSD or median (range: 25% to 75%) or number of subjects. 10
EST and EST. P trend values for linear trends across quintiles are based on linear regression analysis for continuous variables or logistic
regression analysis for categorical variables. EST1 and EST1. Ptrend values for linear trends across quintiles are based on linear regression
analysis for continuous variables or logistic regression analysis for categorical variables adjusted for age and gender. EST2 and EST2. Ptrend
values for linear trends across quintiles are based on linear regression analysis for continuous variables or logistic regression analysis for
categorical variables adjusted for age, gender, BMI, PSQI, BDI-II, energy intake, alcohol intake, current smoking, and physical activity. 15
*P<0.05, †P<0.01, ¶P<0.001. BDI: Beck Depression inventory, MEQ: morningness-eveningness questionnaire PSQI: Pittsburg Sleep Quality
Index.
3
Table 3. Cardio-renal-metabolic parameter according among each group classified by MEQ
score.
Variable Evening type Neither type Morning type Est Est1 Est2
AST (U/L) 22 [18,28] 21 [18,26] 22 [18,28] -0.48 -0.58 -0.18
ALT (U/L) 26 [18,40] 21 [16,31] 21 [16,32] -3.88† -2.36* -1.28
GTP (U/L) 29 [19,46] 24 [17,36] 26 [17,38] -1.77 -1.40 -1.45
Uric Acid (mg/dl) 5.5±1.3 5.4±1.3 5.6±1.1 -0.01 0.26 0.47
eGFR (ml/min/ 1.73 m2) 81±18 77±17 76±18 -2.62† - -2.26*
Total cholesterol (mg/dl) 183±28 186±28 186±27 0.91 1.31 1.50
HDL-C (mg/dl) 58±12 59±15 63±14 3.19 2.38 1.87
Triglycerides (mg/dl) 107 [83,160] 100 [67,152] 89 [66,140] -2.93† -2.05* -1.57
Fasting blood glucose (mg/dl) 142±37 131±28 132±30 -3.07† -1.97* -1.42
HbA1c 7.3±1.3 6.9±0.9 6.7±0.8 -4.99¶ -3.53¶ -2.94†
Systolic BP (mmHg) 127±13 126±14 126±15 -0.75 -0.99 -0.15
Diastolic BP (mmHg) 79±10 76±10 77±15 -1.79 -0.33 0.11
UAE (mg/g creatinine) 11 [6,23] 10 [5,22] 11 [6,24] 0.39 0.02 0.27
baPWV (cm/s) 1493±265 1556±282 1578±285 2.78† -0.96 -0.71
20
Data are meanSD or median (range: 25% to 75%). EST and EST. Ptrend values for linear trends across quintiles are based on linear regression analysis for continuous variables or logistic regression analysis for categorical variables. EST1 and EST1. Ptrend values for linear trends across quintiles are based on linear regression analysis for continuous variables or logistic regression analysis for categorical 25
variables adjusted for age and gender. EST2 and EST2. Ptrend values for linear trends across quintiles are based on linear regression analysis for continuous variables or logistic regression analysis for categorical variables adjusted for age, gender, BMI, morningness-eveningness questionnaire, Pittsburg Sleep Quality Index, Beck Depression inventory, energy intake, alcohol intake, current smoking, and physical activity. 30
4
*P<0.05, †P<0.01, ¶P<0.001. Abbreviations: see Tables 1 and 2.
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