the millennium cohort is the largest prospective study using primary data collection ever undertaken by the department of defense ( dod ) .
the study began in 2001 with the objective to collect and evaluate data on health , behavioral risk factors , and occupational characteristics related to military service that may be associated with adverse health outcomes ( 14 ) .
this report includes participants from the first enrollment cycle that spanned 20012003 and comprised 77,047 participants ( 36% of those able to be contacted ) .
approximately 71% of those participants enrolled at baseline responded to follow - up surveys conducted in 2004 and 2007 .
the surveys were administered via paper and the internet and included questions on self - reported provider - diagnosed medical conditions , mental health symptoms , physical and functional status , alcohol and tobacco use , occupational status , military exposures , sleep patterns , and demographic information .
this study was approved by the naval health research center institutional review board , and informed consent was obtained from all study participants .
this research has been conducted in compliance with all applicable federal regulations governing the protection of human subjects in research ( protocol nhrc.2000.0007 ) .
of the 77,047 participants enrolled at baseline , follow - up surveys were completed by 55,021 participants at year 3 and 54,790 at year 6 . since incident diabetes was the outcome of interest , eligible participants included those who were followed until either the outcome was reported to have occurred at year 3 or 6 , or until their last completed follow - up if the outcome was not reported .
exclusions included participants reporting provider - diagnosed diabetes at baseline , missing outcome or exposure data , or if dod outpatient or inpatient medical encounter data contained codes for type 1 diabetes ( n = 72 ) ( icd-9 codes 250.x1 and 250.x3 ) .
the primary data sources were the self - administered millennium cohort surveys and dod electronic personnel files , managed by the defense manpower data center ( dmdc , seaside , ca ) .
for these analyses , electronic records from dmdc provided information on age , sex , race / ethnicity , education , pay grade , service branch , service component , military occupation , dates of separation , and deployment dates .
dmdc information was supplemented with self - reported data to reduce missing values when necessary .
three sleep variables were included in the analyses : 1 ) trouble sleeping , 2 ) sleep duration , and 3 ) sleep apnea .
trouble sleeping was assessed using the sleep items on the prime - md patient health questionnaire ( phq ) and the ptsd checklist  civilian version ( pcl - c ) ( 1720 ) .
the phq asks ,  over the last 4 weeks , how often have you experienced trouble falling asleep or staying asleep ?  the pcl - c asks ,  in the past month , have you had trouble falling asleep or staying asleep ?  participants with trouble sleeping were defined as those who responded 
moderately  or above on the pcl - c sleep item or  several days  or longer on the phq sleep item .
sleep duration was reported as whole number of hours slept in an average 24-h period over the past month .
participants with sleep apnea were identified by self - report as being told by a doctor or other health professional they had sleep apnea .
ptsd was assessed using the pcl - c ( 17 ) , a 17-item self - report screening tool for ptsd symptoms during the past 30 days on a 5-point likert scale , ranging from 1 ( not at all ) to 5 ( extremely ) .
a positive screen for ptsd at baseline was defined as a report of a moderate or higher level of at least one intrusion symptom , three avoidance symptoms , and two hyperarousal symptoms ( criteria established by dsm - iv ) ( 21 ) .
major depressive disorder was assessed using nine items from the phq ( sensitivity = 0.93 ; specificity = 0.89 ) corresponding to the depression diagnosis based on the dsm - iv ( 19 ) .
a positive screen for depression at baseline was defined as 1 ) endorsement of depressed mood or anhedonia and 2 ) response of  more than half the days  or  nearly every day  to at least five items . other anxiety ( 6 items ) and panic ( 15 items ) symptoms
problem drinking was defined using items from the phq on risky behaviors related to alcohol use , such as driving under the influence more than one time over the past year , where endorsement of at least one item indicated problem drinking .
binge drinking was defined as consuming five or more drinks ( men ) or four or more drinks ( women ) in 1 day during the past year .
smokers were identified as those ever smoking 100 cigarettes in their lifetime , with those persisting in this habit defined as current smokers and those having quit as past smokers . in longitudinal models , service branch , service component ,
pay grade , military occupation , birth year , race / ethnicity , and education were assessed at baseline .
smoking status , alcohol use , bmi , combat deployment , ptsd , depression , anxiety , panic , and all sleep variables were assessed at all available time points .
the outcome of interest was incident diagnosed diabetes self - reported on a follow - up survey among people without diabetes at the baseline assessment . at baseline , participants reported if they had ever been told by a doctor or health professional that they had diabetes or
 at follow - up assessments , participants responded to the same question in regard to the previous 3 years .
univariate analyses assessed associations of incident diabetes with sleep , military , demographic , behavioral , and mental health characteristics while accounting for multiple periods of observation per subject . since repeated measurements were available with up to two follow - up assessments per person , generalized estimating equations ( gees ) were used to account for these multiple assessments while adjusting for fixed and time - varying covariates , to estimate adjusted odds of reporting incident diabetes ( 22 )
. incident diabetes was determined at each follow - up assessment , and all covariates were evaluated using data from the previous assessment ( 22 ) . in all multivariable models , adjustments were performed for known type 2 diabetes risk factors captured in the study : age , sex , education , bmi , and race / ethnicity .
the final adjusted models were built using a stepwise backward reduction algorithm that retained all significant variables ( p < 0.10 ) ( table 1 ) while always keeping age , sex , race / ethnicity , education , and bmi in the model .
additionally , mental health variables were added to the final models to determine if this altered the relationship between sleep and diabetes .
first - order interaction terms between retained sleep variables and age , sex , and bmi were tested to determine whether the exposure - outcome associations varied by these characteristics
. possible presence of multicollinearity in multivariable models was considered if the variance inflation factor exceeded 4 .
best - fitting gee models were judged using the quasilikelihood information criterion , the measure developed for gee models analogous to the akaike information criterion .
statistical analyses were performed using sas statistical software , version 9.3 ( sas institute , inc . ,
baseline demographic , military , and behavioral characteristics of millennium cohort participants by development of diabetes at follow - up
of the 77,047 participants enrolled at baseline , follow - up surveys were completed by 55,021 participants at year 3 and 54,790 at year 6 . since incident diabetes was the outcome of interest , eligible participants included those who were followed until either the outcome was reported to have occurred at year 3 or 6 , or until their last completed follow - up if the outcome was not reported .
exclusions included participants reporting provider - diagnosed diabetes at baseline , missing outcome or exposure data , or if dod outpatient or inpatient medical encounter data contained codes for type 1 diabetes ( n = 72 ) ( icd-9 codes 250.x1 and 250.x3 ) .
the primary data sources were the self - administered millennium cohort surveys and dod electronic personnel files , managed by the defense manpower data center ( dmdc , seaside , ca ) .
for these analyses , electronic records from dmdc provided information on age , sex , race / ethnicity , education , pay grade , service branch , service component , military occupation , dates of separation , and deployment dates .
dmdc information was supplemented with self - reported data to reduce missing values when necessary .
three sleep variables were included in the analyses : 1 ) trouble sleeping , 2 ) sleep duration , and 3 ) sleep apnea .
trouble sleeping was assessed using the sleep items on the prime - md patient health questionnaire ( phq ) and the ptsd checklist  civilian version ( pcl - c ) ( 1720 ) .
the phq asks ,  over the last 4 weeks , how often have you experienced trouble falling asleep or staying asleep ?  the pcl - c asks ,  in the past month , have you had trouble falling asleep or staying asleep ?  participants with trouble sleeping were defined as those who responded 
moderately  or above on the pcl - c sleep item or  several days  or longer on the phq sleep item .
sleep duration was reported as whole number of hours slept in an average 24-h period over the past month .
participants with sleep apnea were identified by self - report as being told by a doctor or other health professional they had sleep apnea .
ptsd was assessed using the pcl - c ( 17 ) , a 17-item self - report screening tool for ptsd symptoms during the past 30 days on a 5-point likert scale , ranging from 1 ( not at all ) to 5 ( extremely ) .
a positive screen for ptsd at baseline was defined as a report of a moderate or higher level of at least one intrusion symptom , three avoidance symptoms , and two hyperarousal symptoms ( criteria established by dsm - iv ) ( 21 ) .
major depressive disorder was assessed using nine items from the phq ( sensitivity = 0.93 ; specificity = 0.89 ) corresponding to the depression diagnosis based on the dsm - iv ( 19 ) .
a positive screen for depression at baseline was defined as 1 ) endorsement of depressed mood or anhedonia and 2 ) response of  more than half the days  or  nearly every day  to at least five items . other anxiety ( 6 items ) and panic ( 15 items ) symptoms
problem drinking was defined using items from the phq on risky behaviors related to alcohol use , such as driving under the influence more than one time over the past year , where endorsement of at least one item indicated problem drinking .
binge drinking was defined as consuming five or more drinks ( men ) or four or more drinks ( women ) in 1 day during the past year .
smokers were identified as those ever smoking 100 cigarettes in their lifetime , with those persisting in this habit defined as current smokers and those having quit as past smokers . in longitudinal models , service branch , service component ,
pay grade , military occupation , birth year , race / ethnicity , and education were assessed at baseline .
smoking status , alcohol use , bmi , combat deployment , ptsd , depression , anxiety , panic , and all sleep variables were assessed at all available time points .
the outcome of interest was incident diagnosed diabetes self - reported on a follow - up survey among people without diabetes at the baseline assessment . at baseline , participants reported if they had ever been told by a doctor or health professional that they had diabetes or
 at follow - up assessments , participants responded to the same question in regard to the previous 3 years .
univariate analyses assessed associations of incident diabetes with sleep , military , demographic , behavioral , and mental health characteristics while accounting for multiple periods of observation per subject . since repeated measurements were available with up to two follow - up assessments per person , generalized estimating equations ( gees ) were used to account for these multiple assessments while adjusting for fixed and time - varying covariates , to estimate adjusted odds of reporting incident diabetes ( 22 )
. incident diabetes was determined at each follow - up assessment , and all covariates were evaluated using data from the previous assessment ( 22 ) . in all multivariable models , adjustments were performed for known type 2 diabetes risk factors captured in the study : age , sex , education , bmi , and race / ethnicity .
the final adjusted models were built using a stepwise backward reduction algorithm that retained all significant variables ( p < 0.10 ) ( table 1 ) while always keeping age , sex , race / ethnicity , education , and bmi in the model .
additionally , mental health variables were added to the final models to determine if this altered the relationship between sleep and diabetes .
first - order interaction terms between retained sleep variables and age , sex , and bmi were tested to determine whether the exposure - outcome associations varied by these characteristics
. possible presence of multicollinearity in multivariable models was considered if the variance inflation factor exceeded 4 .
best - fitting gee models were judged using the quasilikelihood information criterion , the measure developed for gee models analogous to the akaike information criterion .
statistical analyses were performed using sas statistical software , version 9.3 ( sas institute , inc . ,
baseline demographic , military , and behavioral characteristics of millennium cohort participants by development of diabetes at follow - up
a total of 47,093 participants were included in this analysis and followed for up to 6 years .
incident diabetes was assessed at each 3-year period separately , with 13,621 participants followed for one 3-year period , and 33,472 participants followed for two 3-year periods .
a total of 383 cases occurred during years 03 and 488 cases occurred during years 36 of follow - up .
the 488 cases that did not occur until years 36 are also present in the first column of table 1 as not having diabetes from year 03 . at baseline ,
participants overall were on average young ( 34.9 years of age , sd 9.0 years ) , slightly overweight ( bmi 26.0 kg / m , sd 3.3 ) , 25.6% female , and more likely than not to be white , non - hispanic race , less than college educated , army service branch , and on active duty ( table 1 ) .
overall , 871 participants newly self - reported diabetes , for a cumulative annual incidence of 3.6/1,000 person - years .
participants who newly self - reported diabetes during follow - up were significantly more likely at baseline to have reported trouble sleeping , sleep duration 5 h , and sleep apnea ( table 1 ) .
sleep duration > 8 h was reported by similar proportions of participants with and without newly self - reported diabetes .
participants with new - onset diabetes were on average older , had a higher bmi , and were more likely of nonwhite race .
characteristics associated with new - onset diabetes included no deployment , having separated from the military since baseline , army or navy / coast guard service branch , reserves / national guard service component , enlisted pay grade , and administration / supply occupation .
binge or problem drinking was less likely to have been reported in people reporting new - onset diabetes , and current and former smoking frequency was similar in groups with and without new - onset diabetes .
all mental health symptoms occurred significantly more frequently among those who newly reported diabetes during follow - up .
factors associated with a higher odds of incident diabetes in models adjusted for sex and known type 2 diabetes risk factors ( age , bmi , education , and race / ethnicity ) included trouble sleeping , sleep duration 5 h compared with 7 h , and sleep apnea ( table 2 )
. several military service characteristics remained significantly related to the outcome , including no deployment , enlisted pay grade , administration / supply occupation , and having separated from the military since baseline ( table 2 ) .
binge or problem drinking remained significantly associated , and current smoking emerged as a risk factor for new - onset diabetes after adjustment . screening positive for depression , panic , other anxiety disorder , and ptsd were all significantly associated with higher odds of new - onset diabetes in these adjusted models ( table 2 ) .
relative odds of incident self - reported diabetes by each baseline characteristic of interest in the multivariable model ( table 3 ) , sleep characteristics remained significantly and independently associated with higher diabetes odds .
the sleep variables that entered the final model included reported trouble sleeping and sleep apnea , which were associated with significant increases in the odds of diabetes of 1.21 to 1.78 , respectively .
these associations were not only independent of each other but also the other covariates adjusted for in the model ( table 3 ) .
military service characteristics significantly associated with diabetes odds included deployment without combat experience , administration or supply occupations , pay grade , and having separated from the military since baseline .
a positive screen for ptsd was significantly associated with higher diabetes odds , independent of sleep characteristics and other covariates in the model , and panic disorder was of borderline significance .
tests for interactions between the sleep variables included in the models in table 3 and age , sex , and bmi were all nonsignificant ( p > 0.10 ) .
no variable had a variance inflation factor > 4 , indicating that collinearity was unlikely .
the model in table 3 was rerun with sleep duration substituted for trouble sleeping but with the other included covariates unchanged .
the quasilikelihood information criterion for the model containing trouble sleeping was slightly lower ( 8,640.9 ) than when sleep duration was included in the model ( 8,646.3 ) .
the sleep duration variable was insignificant overall in this model ( p = 0.1585 ) , although two sleep categories were significantly related to diabetes odds ( < 5-h odds ratio [ or ] 1.52 [ 95% ci 1.092.14 ] ; 5-h or 1.28 [ 1.011.62 ] ) .
several additional modifications of the multivariable model shown in table 3 were conducted . in the first modification , symptoms of depression and anxiety disorder
were included in the model to assess whether adjustment for these additional factors altered the association between sleep and diabetes odds . in the second modification , all
subjects reporting sleep apnea were removed from the model shown in table 3 . in each of these modifications ,
the statistical significance of the associations between the sleep variables and diabetes odds remained unchanged , and the associations were of similar magnitude to those seen in table 3 ( data not shown ) .
longitudinal multivariable regression model of sleep characteristics and mental health symptoms as risk factors for incident self - reported diabetes in the millennium cohort
our study findings confirm that sleep characteristics are associated with subsequent new - onset self - reported diabetes .
these associations persisted after adjustment for multiple mental health conditions known to affect sleep duration and quality , including ptsd and depression ( 1113 ) .
therefore , it is unlikely that sleep simply serves as a surrogate marker for associated mental health conditions previously shown to predict higher diabetes risk ( 9,10 ) . additionally , participants reporting provider - diagnosed sleep apnea were at higher risk of developing self - reported diabetes during follow - up .
although sleep apnea is associated with higher bmi and both altered sleep quality and quantity , adjustment for these variables did not alter the significance of the higher diabetes risk associated with this condition ( 23 ) .
overall , these results suggest that the associations between type 2 diabetes risk and mental health conditions and sleep characteristics , if causal , may involve different pathways . whereas trouble sleeping and shorter sleep duration were associated with higher risk of diabetes in a model adjusted for known diabetes risk factors , longer sleep duration was not , in contrast to findings that others have reported ( 4 ) .
the reason for this discrepancy is unclear , but it may be due to the relatively younger age of our cohort compared with investigations reporting higher diabetes risk with longer sleep duration ( 24,25 ) . the independent role of mental health conditions associated with poor quality and quantity of sleep in predicting risk of diabetes has only been addressed in a limited manner in previous research .
the nurses health study investigators examined sleep as a predictor of incident diabetes in this cohort from 19861996 and adjusted for an assessment of depression based on the short form 36 health survey that was obtained in 1992 , approximately midway through the follow - up period ( 24 ) .
thus , it is unclear whether depression preceded or followed diabetes onset during the first 6 years of follow - up .
an analysis using the national health and nutrition examination survey i epidemiologic follow - up study adjusted for depression while examining the association between sleep and diabetes incidence , although no association was seen between depression and diabetes incidence in this cohort ( 25 ) .
lastly , a prospective study of swedish men assessed the presence of depression with a simple yes / no question ,  do you feel depressed ?  and did not provide information on the accuracy of this question in capturing this condition ( 26 ) . to our knowledge , our study is the first to consider mental health conditions other than depression as potential confounding factors and to measure their occurrence prior to the onset of diabetes .
previous prospective research on sleep characteristics and type 2 diabetes risk has not considered whether sleep duration or quality is related to this outcome independent from sleep apnea , a known cause of sleep disturbance . in our fully adjusted analysis ,
both sleep apnea and trouble sleeping had independent associations with diabetes risk , suggesting that the associations between sleep characteristics and diabetes risk do not merely serve as markers for the presence of sleep - disordered breathing .
in addition to the known higher risk of obesity associated with sleep apnea , other factors associated with sleep - disordered breathing may be involved in higher diabetes risk and include abnormal sympathetic activity and release of proinflammatory mediators such as tumor necrosis factor- and interleukin-6 ( 27 ) . in support of the latter , we observed an independent association between sleep apnea and diabetes risk after adjustment for bmi .
this suggests that manifestations of sleep apnea other than the impact of greater general adiposity may be associated with diabetes risk , although it is possible that incomplete adjustment due to residual confounding occurred due to the inaccuracy of bmi in characterizing body composition .
the association between trouble sleeping or shorter sleep duration and diabetes risk independent of associated weight gain and sleep apnea is not well understood , but it may be related to both changes in insulin sensitivity , secretion , and glucose effectiveness .
one investigation reported significant or borderline - significant reductions in insulin sensitivity , insulin secretion , glucose effectiveness , and the disposition index immediately after a 5-day period of sleep deprivation ( 4 h of sleep per night ) among 11 healthy lean males in a controlled setting ( 28 ) .
all these changes have been associated with higher risk of the development of type 2 diabetes ( 29 ) .
several characteristics of military service were significantly associated with lower diabetes risk in multivariable models , including deployment , officer pay grade , and remaining in military service .
for most comparisons , military deployment with or without combat exposure was related to a lower risk for diabetes , possibly reflecting selection of people medically fit for deployment who are at lower risk for diabetes .
the mental health conditions independently associated with diabetes risk included those characterized by excessive stress , including ptsd and panic disorder .
a review of the literature on stress and diabetes risk concluded that both general emotional and job stress were repeatedly associated with a higher risk of developing diabetes in adults ( 30 ) .
overactivation of the hypothalamic - pituitary axis and abnormal stimulation of the sympathetic nervous system are thought to accompany excessive levels of stress , with accumulation of visceral fat and promotion of an inflammatory state with greater insulin resistance ( 31 ) . a previous analysis of the members of this cohort recruited in 2001 and followed for 3 years similarly demonstrated a higher diabetes risk associated with ptsd symptoms .
first , type 2 diabetes was determined using self - reported data , and it was not confirmed by medical record review .
however , because self - reported diabetes compared with physician diagnosis or medical record data have been shown to have a high sensitivity ( 7099% ; median 81% ) and specificity ( 9299% ) , there is less likelihood for misclassification ( 32 ) .
also , it is possible that individuals self - reporting type 1 diabetes were included in this analysis .
however , individuals with a type 1 diabetes diagnosis in their dod medical records were excluded , although this elimination process would miss those participants no longer receiving care from military treatment facilities after discharge or as reservists . in addition , positive screens for mental disorders were determined from self - report . also , we were unable to adjust for diet or family history , which are known risk factors for diabetes .
we expect these findings to generalize to younger populations who are sufficiently healthy to enter into the u.s .
armed forces , but it is unclear whether the results would apply to dissimilar populations .
self - report of clinician - diagnosed sleep apnea was obtained , and the sensitivity and specificity of this report compared with the medical record are not known .
medical encounter data were not used to confirm diagnoses of diabetes or sleep apnea in this cohort due to the potential for some of its members , particularly those in the reserves or national guard , to have received care in non - dod facilities .
inaccurate classification of sleep apnea and other covariates potentially may have limited our ability to adjust for confounding .
finally , self - reported sleep data were assessed during the prior 4 weeks , and sleep duration was rounded to the nearest whole hour , potentially biasing the estimate of actual sleep time ( 3335 ) .
this is the first study , to our knowledge , to examine baseline sleep characteristics in relation to incident diabetes while adjusting for several mental health conditions known to impair sleep and be associated with type 2 diabetes .
furthermore , this research was conducted in a large population - based study of active duty and reserve / national guard u.s . military personnel from all service branches .
additional strengths include the large sample size and up to 6-year duration of follow - up .
moreover , no association was found between reporting type 2 diabetes at baseline and nonresponse to the first follow - up questionnaire among the first panel of enrollees , suggesting that the development of diabetes was unlikely to have influenced the probability of responding to the follow - up survey ( 36 ) .
finally , previous evaluations of possible biases suggest the cohort is reasonably representative of military personnel in terms of baseline demographic and mental health characteristics , that participants report health and exposure data reliably , and that enrollment in the study is not influenced by health status ( 14,3740 ) .
we conclude that trouble sleeping and sleep apnea predict higher diabetes risk , independent of multiple diabetes risk factors and several mental health conditions . of note
, self - reported sleep apnea was also associated with a significantly higher risk for diabetes even after adjustment for other sleep characteristics , bmi , and mental health conditions .
substitution of sleep duration for trouble sleeping in multivariable modeling yielded nearly identical results , with significantly higher risk seen with < 6 h of sleep .
confirmation of these findings through further analyses may advance our understanding of diabetes pathophysiology and create new opportunities for prevention .
 objectiveresearch has suggested that a higher risk of type 2 diabetes associated with sleep characteristics exists . 
 however , studies have not thoroughly assessed the potential confounding effects of mental health conditions associated with alterations in sleep.research design and methodswe prospectively assessed the association between sleep characteristics and self - reported incident diabetes among millennium cohort study participants prospectively followed over a 6-year time period . 
 surveys are administered approximately every 3 years and collect self - reported data on demographics , height , weight , lifestyle , features of military service , sleep , clinician - diagnosed diabetes , and mental health conditions assessed by the prime - md patient health questionnaire and the ptsd checklist  civilian version . 
 statistical methods for longitudinal data were used for data analysis.resultswe studied 47,093 participants ( mean 34.9 years of age ; mean bmi 26.0 kg / m2 ; 25.6% female ) . during 6 years of follow - up , 871 incident diabetes cases occurred ( annual incidence 3.6/1,000 person - years ) . in univariate analyses , 
 incident diabetes was significantly more likely among participants with self - reported trouble sleeping , sleep duration < 6 h , and sleep apnea . 
 participants reporting incident diabetes were also significantly older , of nonwhite race , of higher bmi , less likely to have been deployed , and more likely to have reported baseline symptoms of panic , anxiety , posttraumatic stress disorder , and depression . after adjusting for covariates , trouble sleeping ( odds ratio 1.21 [ 95% ci 1.031.42 ] ) and sleep apnea ( 1.78 [ 1.392.28 ] ) were significantly and independently related to incident diabetes.conclusionstrouble sleeping and sleep apnea predict diabetes risk independent of mental health conditions and other diabetes risk factors . 
RESEARCH DESIGN AND METHODS
None
Study population and data sources
Outcome
Statistical analyses
RESULTS
CONCLUSIONS