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Original Article

pISSN 2233-9019 · eISSN 2233-9116

Korean J Fam Pract. 2015;5(3, suppl. 2):303-308

KJFP

Korean Journal of Family Practice

Original Article

pISSN 2233-9019 · eISSN 2233-9116 Korean J Fam Pract. 2015;5(3, suppl. 2):PB-1

KJFP

Korean Journal of Family Practice

Received February 27, 2015 Revised August 26, 2015 Accepted September 3, 2015 Corresponding Author Dong-Yung Cho

Tel: +82-2-2030-7681, Fax: +82-2-2030-5339 E-mail: dycho@kuh.ac.kr

Copyright © 2015 The Korean Academy of Family Medicine

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

Inadequate sleep is common in modern society. Sleep is an important factor to maintain neurocognitive, behavioral, autonomic, andregulationofmetabolicfunction.1-2)Additionally, short or long sleep duration has been associated with immunosuppression, obesity, cardiovascular diseases, all-cause mortality, insulinresistanceanddiabetes.(3-5)

Diabetes mellitus is a metabolic disorder as a result of insufficient secretion of insulin or disability of normal glucose control function and majorhealthproblem inKorea because of itshighprevalencerate, increasedmorbidityandhighhealthcare

costs. Patients with diabetesrequirefrequent visitto healthcare institutiontopreventandmanagevariouscomplications, andmay also experience episodes of Diabetic emergencies(eg. Diabetic ketoacidosis).

In addition, type 2diabetes mellitus is preceded by insulin resistanceandpre-diabeticconditionsincludingimpairedglucose tolerance. About twenty-five percent of pre-diabetic patients progress to have diabetes over three to five years.6) Many of lifestyleinterventionsuchasregularphysicalactivity, healthydiet, andreducingweighthavebeenrecommendedtothepatients.

Recentcross-sectionalstudiesfound thatinsufficientduration ofsleepwasoneofimportantriskfactorsofpre-diabetes.7, 8)

수면시간과 공복혈당장애의 관계

오희경, 정유진, 안아름, 오은정, 최재경, 권혁중, 조동영*

건국대학교 의학전문대학원 가정의학교실

Sleep duration and pre-diabetes

Hee-Kyung Oh, You-Jin Jung, Ah-Leum Ahn, Eun-Jung Oh, Jae-Kyung Choi, Hyuk-Jung Kweon, Dong-Yung Cho* Department of Family Medicine, Konkuk University Medical Center, Seoul, Korea

Background: Current epidemiologic studies have investigated the association between inadequate sleep and pre-diabetes, but results have been inconsistent. We evaluated the relationship between sleep duration and pre-diabetes in a nationally representative population.

Methods: Participants aged 19~79 years old who were free of diabetes were chosen from the Korea National Health and Nutrition Examination Survey(2010~2012). Sleep duration was self-reported with categories of ≤5, 6, 7(reference), 8 and ≥9 hours/day.

Results: In the total population and the all-female group, very short sleep duration(≤5 hours/day) showed a significantly higher odds ratio for pre-diabetes in the unadjusted model.

However, there was no significant relationship after adjustment for covariates. Both gender groups tended to show increased risk of pre-diabetes with less sleep, although the relationship was not significant(men p=0.281, women p=0.055) in the unadjusted model.

Conclusion: Risk of pre-diabetes was found to increase as subjects’ sleep duration decreased. Thus, sleep duration may be a risk factor for pre-diabetes, but one which has less influence than other well-known risk factors for diabetes. As these results were inconsistent with previous studies, further objective and prospective studies are needed to clarify the relationship between sleep duration and pre-diabetes.

Keywords: Sleep duration; pre-diabetes; Korean; adults; KNHANES

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Hee-Kyung Oh, et al. Sleep duration and pre-diabetes

Korean Journal of Family Practice

KJFP

However, there isalack ofstudy onthe association between average sleepduration and pre-diabetes in Koreanpopulation. The aim of our studywas to evaluatethe association between sleepdurationandpre-diabetesasapartofefforttoreducethe prevalence of pre-diabetes whichis increasing amongKorean adults.

Methods

1. Study population

The study data werecollected from the fifth Korea National Health and Nutrition Examination Survey (KNHANES) 2010~2012 performed by the Korea Ministry of Health and Welfare. We includedaged19~79 years ofadultsbecause older adults may have more underlying diseases and often have a difficulty in maintenance of sleep quality. Participants were excluded if they had a self-reported previous diagnosis of diabetesorafastingplasmaglucoselevelof126mg/dL(7.0mmol/ L) ormoreandhadmissingdataonsleep, covariates, andblood glucoselevel. Aftertheseexclusions, thetotalanalyticsamplesize was9578inourstudy.

2. Study procedure

The numbersofhoursofsleepwasassessedbyself-reported questionnaire. Thequestion formulation wasOnaverage, how many hours do you sleep a day?” The classificationwas5, 6, 7, 8and9hours/day, consistentwithpreviousstudies.5, 8) Becausethemeanhoursofsleepstandarderror) was6.87

0.013), wetreatedsleepduration7hours/dayasreference. Glycemicstatuswasdefinedinaccordancewiththediagnostic criteria of the American Diabetes Association.9) Diabetes mellitus(DM) was defined asa fasting glucose levelof 126mg/ dLormore, pre-diabetes wasdefinedasafastingglucoselevel of100to125mg/dLand normoglycemiawasdefinedasglucose

<100mg/dL andno use of hypoglycemic agents or physician diagnosis.

Hypertensionwasdefinedassystolic140mmHgordiastolic blood pressure90mmHg, or the useof anti-hypertensive medications. BMIwascalculatedasweightinkilogramsdivided by the square of height in meters anda BMI25kg/m2was

regarded as general obesity for Asians form the WorldHealth Organization definition of obesity for Asians.10) Smokingwas classified ascurrent, formerandneversmoker. Harmfulalcohol use was defined as K-AUDIT10 in men, ≥6 in women based on the usual frequency and amountof alcoholintake.11) K-AUDIT wasa translation ofthe AUDIT considering tothe Korean situation which was developed by the World Health Organization(WHO) asan indicatorsofhazardous and harmful alcoholuse, aswellaspossiblealcoholdependence.

Physical activity was assessed using Metabolic Equiva-lent of Task values(METs), according to the International Physical ActivityQuestionnaire(IPAQ); thatis, inactivitywas<600MET- min/week.12) We evaluatedtheaverage dailyenergy intake(kcal/ day) through24-hoursdietrecallincludingtypeandamountof intake food. Participantswho havereceived previousdepression diagnosiswere classified asdepressiongroup. A positive family historyofdiabetes wasdefinedasatleastoneoftheparents or onesiblinghaddiabetes.

3. Statistical analysis

All analyses used weighted values to the raw data of the KNHANES thatconsistedofmultistage, stratified, andclustered sampling. Clinical characteristics of the participants were compared betweenthenormoglycemiaandpre-diabetesgroups using a student t-test forcontinuous variablesand chi-square test forcategorical variables. Multiplelogisticregression analysis was used to determine the association between sleep duration and glycemic status. Odds ratios(OR) and 95% confidence intervals(95% CI) werecalculated.

All statistical analyseswere performedusing complex sample procedure ofSPSSsoftware(version 20, Cary, NC, USA) and a p-value <0.05wasconsideredstatisticallysignificant.

Results

Totalstudypopulationwas9578adultsaged19~79years, men was3990(41.7%) andwomanwas5588 (58.3%).

Table1representsclinicalcharacteristicsaccordingtoglycemic status. Pre-diabetesgroupwasolder (53.94yearsvs. 44.76years, p<0.001), andhadahigherpercentageofmen(55.7% vs. 38.2%,

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오희경 외. 수면시간과 공복혈당장애의 관계 Korean Journal of Family Practice

KJFP

p<0.001).

Also, participants with pre-diabetestendedto be tallerand weigh more, as well as have a higher proportion of general obesity, hypertension, family history ofdiabetes, and lifestyle riskfactorsuchascurrentsmoker, harmfuldrinking, inactivity, higher daily intakecalories. The mean hoursofsleep was6.77 versus6.89(p<0.001) forpre-diabetesandnormoglycemia, sleep duration was shorterin pre-diabetes, significantly. However,

depression wasnot significantlydifferent betweentwo glycemic groups.

Table 2shows the relationship between sleepduration and pre-diabetes by multiple logistic regression analysis. In total population, very short sleep duration(≤5hours/day) group showed higherodds ratiofor pre-diabetessignificantly in the unadjustedmodel(OR=1.29, 95% CI1.01~1.58).

Table3presentpotentialeffectofsleepdurationontheriskof pre-diabetesthroughlogisticregressionanalysisbydividingsex, becausethedifferenceofgendermightinfluencethedevelopment ofdiabetesandmodifythisrelationship. Model1wasadjustedfor age. Additionally, model2wasadjustedforhypertension, general obesity, smoking, alcohol, physicalactivity, nutrition, depression andfamilyhistoryofdiabetes. Infemaleadults, participantswho had 5hoursorlessofsleeptimeweremorelikely tohavepre- diabetes with an oddsratioof 1.45(95% CI 1.18~1.92) inthe unadjusted modelas total population. However, there was no significantrelationshipafteradjustmentforcovariates.

We used linear regression analysisto determine thetrends of risk of pre-diabetes accordingto sleep duration in total population, maleandwoman. Totalpopulationandbothgender groupstendedtoshowincreasedriskofpre-diabeteswithlesser sleep, theseassociation appearedlinearpattern, andPfortrend for total population and female were significant.(P for trend Total=0.0002, men=0.1500, women p=0.0005) although only inunadjustedmodel.

Table 1. Characteristics of the study subjects according to glycemic status

Characteristic Normoglycemia (n= 7689)

Pre-diabetes

(n= 1889) P-value

Male(n,%) 2937(38.2) 1053(55.7) <0.001

Age(y) 44.76± 0.17 53.94± 0.29 <0.001*

Body composition Height(cm) Weight(kg) General obesity(n,%) Hypertension(n,%)

162.81± 0.1 61.28± 0.13 1929(25.1) 1596(20.8)

163.55± 0.21 67.03± 0.27

874(46.3) 847(44.8)

0.001*

<0.001*

<0.001

<0.001 Lifestyle factors

Current smoker(n,%) Harmful drinking(n, %) Inactivity(n, %) Family history of DM (n, %)

Sleep duration (hours/d)

≤ 5 hours/d(n,%) 6 hours/d 7 hours/d 8 hours/d

≥ 9 hours/d

1321(17.2) 2197(28.6) 2777(36.1) 1246(16.2)

6.89± 0.01

903(11.7) 1998(26.0) 2381(31.0) 1860(24.2) 547(7.1)

(20.5) 680(36.0) 632(33.5) 367(19.4)

6.77± 0.03

279(14.8) 518(27.4) 548(29.0) 421(22.3) 123(6.5)

0.001

<0.001 0.031

<0.001

<0.001*

<0.002

Depression(%) 1.9 1.7 0.716

Daily calorie intake

(kcal/d) 2021.33± 9.9 2105.25± 20.76 <0.001*

Values are presented as mean±standard error or number of percentage.

* Analyzed using Student’s t-test.

Analyzed using chi-square test.

Table 2. Relationship between sleep duration and pre-diabetes Sleep duration

(hours/day)

pre-diabetes number(%)

Odds ratio§(95% CI) for pre-diabetes

Unadjusted Model 1 Model 2

Total(n= 9678)

≤ 5 6 7(reference) 8

≥ 9

279(23.6) 518(20.6) 548(18.7) 421(18.5) 123(19.7)

1.29(1.01-1.58)* 1.15(0.98-1.37)

1 0.91(0.76-1.08) 0.83(0.64-1.09)

0.98(0.78-1.23) 1.08(0.91-1.29)

1 0.95(0.78-1.15) 0.83(0.61-1.14)

0.96(0.76-1.22) 1.05(0.88-1.25)

1 0.99(0.81-1.21) 0.93(0.69-1.27)

* p-value <0.05

Model 1, adjusted for age and sex

Model 2, adjusted for the variables in model 1 plus hypertension, and general obesity, smoking, drinking alcohol, physical activity, nutrition, depression and family history of DM.

§ Analyzed using multiple logistic regression analysis.

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Hee-Kyung Oh, et al. Sleep duration and pre-diabetes

Korean Journal of Family Practice

KJFP

Discussion

In our study, nationally representative sample of Korean adults, the significantdifference ofsleepdurationwas observed in two groupsaccording toglycemic status. Intotal population and female group, very short sleep duration(≤5 hours/day) group was associated with pre-diabetes significantly in the unadjustedmodel. Also, the riskof pre-diabetes was found to bemoreinfluentialwhenthesubjectssleptforlesshours, showed linearpattern, althoughinunadjustedmodel.

There are several possible mechanisms to support the hypothesis thatabnormal sleep duration can leadto disability of glucose metabolism. Firstmechanism is through changes in the neurohormonalsecretion. Short sleepalteredmean levelsof the ghrelin andleptin, and consequentlyincreased appetite.13) Second possible pathway is through the activation of the sympathetic nervoussystem. Inseveral experiments, inadequate sleepdurationdecreasedglucosetoleranceandincreasedcortisol levels.14)Moreover, short sleep duration was associatedwith activationofinflammatorypathwaysandinterruptionofglucose regulationandhomeostasis.15)

The cross-sectional study of 2285 participants from the NationalHealthandNutritionExaminationSurvey (2005~2008) found that short sleep duration was one of the risk factors of pre-diabetes.8) Other Swedish cross-sectional survey,

2816 population aged 30~75 years old showed a significant association between insufficient sleep duration and impaired glucose tolerance, after adjustment for confounders.7)Previous studieshaveanalyzedtheassociationbetweeninappropriatesleep durationandpre-diabetesandsomestudiesshowedaU-shaped pattern,16, 17)but in some studies, inconstant results has been found.18, 19)

As compared to the previous studies, demographic characteristics may affect theoutcome and can explainfor this discrepancy. Ethnicand racial differencesinsleeppatterns have beenevaluatedinnumberofstudies. Additionally, differencesof socioeconomic, lifestyle, andcomorbiddiseasesbetweenKorean adultsandothersubjectscanexist.(20) IntheUS, alargecross- sectional study, short sleep duration showed association with pre-diabetes,8)participantswhousedsleepingmedication, orhad sleepingdisorderwereexcluded, buthadapreviousdiagnosisof diabeteswerenotexcluded. Inourstudy, dataonsleepdisorder were not available. We excluded participants with previous diagnosisofdiabetes, sincediabeticpatientshavehadhigherrates of insomnia, disturbance ofsleep, and obstructivesleep apnea, wealsotriedtopreventoverestimatingthepossibleeffectofsleep durationondiabetes.21)

As our results, sleep duration isone of the factors of pre- diabetes clearly, but has lessinfluence thanother well-known risk factors of diabetes. Since the significance of theseresults

Table 3. Relationship between sleep duration and pre-diabetes by sex Sleep duration

(hours/day)

pre-diabetes number(%)

Odds ratio§(95% CI) for pre-diabetes

Unadjusted Model 1 Model 2

Men(n= 3990)

≤ 5 6 7(reference) 8

≥ 9

133(30.9) 302(26.1 321(25.6) 234(25.8) 63(25.9)

1.32(0.97-1.79) 1.10(0.89-1.37)

1 0.93(0.72-1.2) 0.91(0.62-1.34)

0.96(0.69-1.33) 1.09(0.88-1.36)

1 0.91(0.70-1.20) 0.75(0.48-1.18)

0.96(0.68-1.37) 1.07(0.86-1.34)

1 0.95(0.72-1.26) 0.92(0.59-1.44) Women(n= 5588)

≤ 5 6 7(reference) 8

≥ 9

146(19.4) 216(15.9) 227(13.6) 187(13.6) 60(14.1)

1.45(1.18-1.92)* 1.20(0.94-1.55)

1 0.94(0.73-1.21) 0.87(0.60-1.27)

1.01(0.75-1.38) 1.06(0.82-1.37)

1 1.03(0.79-1.34) 0.96(0.65-1.41)

0.97(0.71-1.31) 1.03(0.79-1.35)

1 1.09(0.84-1.42) 0.97(0.63-1.47)

* p-value <0.05

Model 1, adjusted for age

Model 2, adjusted for the variables in model 1 plus hypertension, and general obesity, smoking, drinking alcohol, physical activity, nutrition, depression and family history of DM.

§ Analyzed using multiple logistic regression analysis.

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오희경 외. 수면시간과 공복혈당장애의 관계 Korean Journal of Family Practice

KJFP

disappeared after controlling with sex and age,(model 1) our study alsosuggeststhatdifferences ofgenderandageare major confounderswhichhavemultiplicativeeffectonthisrelationship. Sex-relateddifferencesofsleepwerefoundtobeassociatedwith time use, social roles, menstrualcycle, hormonaldifferences.22) Changes in sleep with normal aging have been explained as a circadian modulation, alteration of cardiopulmonary and endocrine function.23)Thedifferences ofageand sex havebeen found as important risk factors of both sleep and metabolic diseases.24) In addition, sleep duration was related with obesity and high bloodpressure, which are greatrisk factors pre-diabetes,25, 26) through similar mechanisms on glycemic control disorders. And when adjusted for general obesity and hypertension, thecorrelationofsleepdurationwithpre-diabetes grew weak. Thus, for research of the relationship between the sleep durationand pre-diabetes, overall understanding of physiologicalinteractionsandpotentialconfoundingvariablesare required.

Several limitations of our study mustbe considered. First, sleepdurationandotherlifestylefactorswere assessedbyself- report, not objectively measured, which could result in recall bias. Other health behavior alsoassessed by self-report, may havevariationsandleadtobringaboutpotentialconfounders. In addition, we analyzedonlythe sleepdurationbutnotthe sleep quality, because dataof sleeprelated problemsor sleepquality werenotavailableinKNHANES, wecouldntcontroltheresidual confounder effect on sleep qualityon diabetic risk. Lastly, we classified a depressiongroup asprevious depressiondiagnosis, becausedatarelatedtodepressionsymptomsinKNHANESwere notcorrespondtotheexactdefinitionofdepression.

Tothebestofourknowledge, thisisthefirststudytoanalyze the relationship between sleep duration andpre-diabetes in a Korean population. Ourstrength is that studypopulation was large and selected from anationally representative survey. We adjusted for major potential covariates, including well-known diabetesriskfactors, severaldiseasesanalyzedbydividingageand sex group. We usedplasma fastingglucose toestimateglycemic status, notself-report, however, thesamplewascheckedonlyfor onceperparticipant.

Additional objectivemeasured prospectivestudies are needed

tofurtherinvestigationoftherelationshipbetweensleepduration and pre-diabetes, as well as other behavioral and biological pathways.

요 약

연구배경: 최근 임상역학적인 연구들이 부적절한 수면과 공복혈당 장애의 연관성을 밝히고자 하였으나 그 결과가 일관적이지 않았다.

이번 연구는 한국 성인들을 대상으로 수면시간과 공복혈당장애의 연관성을 밝혀보고자 하였다.

방법: 5차 국민건강영양조사(2010~2012)의 데이터를 분석, 19

~79세 성인 9578명을 대상으로 하였다. 대상자가 자가 보고한 수 면시간을 토대로 수면 시간을 하루 5시간 이하, 6시간, 7시간, 8 간, 9시간 이상으로 구분하였고, 복합표본 로지스틱 회귀분석을 시 행하였다.

결과: 전체 대상자와 성인 여성의 공복혈당장애 위험은 수면시간이 7시간일 때에 비해 하루 5시간 이하의 수면(수면 부족)을 취하는 경 우, 교차비(Oddsratio)가 각각 1.29(95% CI1.01~1.58), 1.45(95% CI1.18~1.92)로 높았으나, 여러 교란 변수들을 보정한 후에는 유 의하지 않았다. 남성, 여성 모두 수면시간이 부족할수록 공복혈당 장애의 위험이 커지는 경향성을 확인하였지만, 통계적으로는 유의 하지 않았다.

결론: 본 연구에서 짧은 수면 시간이 공복혈당장애의 위험을 높인 다는 경향성을 확인할 수 있었다. 수면시간이 공복혈당장애의 관련 인자임을 제시할 수 있겠으나, 당뇨병의 잘 알려진 위험인자에 비 하여서는 영향이 적은 것으로 보인다. 이 결과는 이전에 진행된 연 구 결과와는 차이를 보이고 있고, 추후 객관적이고 전향적인 연구 가 더 필요할 것이다.

중심단어: 수면시간, 공복혈당장애, 한국, 성인, 국민건강영양조사

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KJFP

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수치

Table 3 present potential effect of sleep duration on the risk of pre - diabetes through logistic regression analysis by dividing sex ,  because the difference of gender might influence the development of diabetes and modify this relationship
Table 3. Relationship between sleep duration and pre-diabetes by sex Sleep duration

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The influence of age and gender on remifentanil EC 50 for preventing microemulsion propofol injection pain.. - Remifentanil EC 50 on propofol injection

Using the CGE model with endogenous technology progress, this study investigates economic impacts and differences of subsidy and taxation for stimulating

In this study, it can be seen that sex and metabolic syndrome are important for biological factors, and occupation, smoking, and exercise are important