Abstract
Objectives:
We sought to evaluate whether rotating night shift work increases the risk of type 2 diabetes, particularly among women with a history of gestational diabetes mellitus (GDM).
Methods:
We included 50,122 Nurses’ Health Study II participants who were parous at baseline in 1989 or at any time during follow-up through 2019. Using multivariable-adjusted Cox proportional hazards models, we estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between cumulative years of rotating night shift work and incident type 2 diabetes, overall, and by history of GDM.
Results:
Compared with participants who never engaged in rotating night shift work, we observed a graded increase in the risk of type 2 diabetes with cumulative years of rotating night shift work: HR(95%CI)= 1.14(1.04, 1.24) for <5 years, 1.32(1.17, 1.49) for 5-10 years, and 1.32(1.16, 1.50) for >10 years (p-linear trend <0.001). Stratifying by history of GDM, we observed a similar pattern of associations among participants without a history of GDM, but not among those with a history of GDM (p-interaction=0.02). History of GDM was strongly associated with risk of incident type 2 diabetes in all women, including those who never worked rotating night shifts: HR(95%CI)=4.76(3.90, 5.81).
Conclusions/interpretation:
Cumulative years of rotating night shift work was modestly associated with a higher risk of type 2 diabetes, overall, and among nurses without a history of GDM. Rotating night shift work was not associated with risk of type 2 diabetes among individuals with a history of GDM, an exceptionally high-risk sub-group for type 2 diabetes732.
Keywords: Gestational diabetes, Night shift work, Type 2 diabetes
Introduction
Shift work is a common occupational exposure, with 15% of the female US workforce reporting shift work outside of traditional daytime hours (7am-5pm).1 Night shift work, in which the majority of hours fall between midnight and 7am, is particularly common in nursing.2,3 Night shift work may be fixed (e.g. nights only) or rotating (nights in combination with days and evenings). A previous analysis in the Nurses’ Health Study cohorts found that every 5 year increase in rotating night shift work is associated with an 18% (95%CI=14-22%) higher risk of type 2 diabetes.4 Rotating night shift work, which has also been associated with obesity and weight gain,4 chronic hypertension,5 and coronary heart disease,6,7 has been suggested to be more harmful than a fixed night shift work because a changing schedule over the long-term may cause greater circadian disruption than a fixed schedule.8 Indeed, a recent large meta-analysis found the pooled odds ratio for type 2 diabetes was higher for rotating night shift work than fixed night shift work.9
Night shift work has been hypothesized to contribute to metabolic dysregulation via multiple downstream processes including changes in gene expression,10 circulating metabolites,11,12 and hormonal activation.13,14 In controlled experiments among healthy human volunteers, simulated night shift work results in insulin resistance15 and hyperglycemia,16 suggesting a potential direct effect of circadian disruption on impaired glucose metabolism. Night shift work may also contribute to metabolic dysregulation indirectly, via behaviors such as decreased sleep duration, increased total energy intake, irregular meal timing, and smoking,17 all of which are more common among night shift workers.
Identifying populations that are more vulnerable to the health impacts of night shift work is critical to educate at-risk individuals and allow them to make informed choices about their work schedule. This is particularly true in industries that require 24-hour staffing, such as nursing, in which workers are more likely to work nighttime hours.1 Women with a history of gestational diabetes mellitus (GDM) are among the highest risk sub-groups for developing type 2 diabetes.18 Estimates suggest that as many as one-third of parous women with type 2 diabetes have a history of GDM.19 Compared with women with a history of normoglycemic pregnancies, those with prior GDM have more than a 7-fold increased risk of developing type 2 diabetes.3-5 Studies of how modifiable risk factors, such as rotating night shift work, may impact the progression from GDM to type 2 diabetes are not available. In this analysis, we sought to evaluate the extent to which rotating night shift work in female nurses is related to risk of type 2 diabetes and if that association varies by history of GDM.
Methods
Study population and design
We conducted our analyses in the Nurses’ Health Study II (NHS II), a U.S.-based prospective cohort study of 116,429 female nurses aged 25–42 years when enrolled in 1989. As previously described in detail, demographic data from NHS II participants were collected at baseline and information on diet, lifestyle, medical history, and incidence of diseases was updated via biennial questionnaires.20 For this analysis, follow-up was between 1991, the first year that data on recent night shift work was collected, and the return of the 2019 questionnaire. NHS II participants were eligible for inclusion in this analysis if they were parous by the time of the baseline questionnaire in 1991 or if they reported an incident first birth during follow-up. We excluded participants who reported a history of type 2 diabetes, cardiovascular disease, or cancer prior to baseline or first pregnancy. We further excluded participants who were menopausal at baseline and those with missing information on cumulative night shift work. After applying these inclusion and exclusion criteria, our analysis included 50,122 participants (Supplementary Figure 1).
Ascertainment of rotating night shift work
In the 1989 questionnaire, NHS II participants were asked the following question: “What is the total number of years during which you worked rotating night shifts (at least three nights per month in addition to days/evenings in that month)?”, with seven pre-specified response categories (never, 1-2, 3-5, 6-9, 10-14, 15-19, and ≥20 years). Information on shift work was updated in 1991, 1993, 1997, 2001, 2005, 2007, and 2009 in NHS II. The 1991, 1993, 1997, 2007, and 2009 questionnaires collected information on the total number of months during which the nurse had worked rotating night shifts in the previous two years, with pre-specified response categories (none, 1-4, 5-9, 10-14, 15-19, and ≥20 months). Additionally, in 2001 women were asked about duration of rotating night shifts in 1993-95, 1995-97, 1997-99, and 1999-2001. In 2005 we collected data on the duration of rotating night shifts in 2001-03 and 2003-05.
Ascertainment of gestational diabetes
Self-report of a physician’s diagnosis of GDM was captured in the 1989 questionnaire and updated every 2 years through 2001, at which time most NHS II participants had passed reproductive age. Self-reported GDM was previously validated against medical records in a subgroup of NHS II participants reporting GDM on the 1991 questionnaire, with 94% of cases confirmed.21
Ascertainment of type 2 diabetes
The primary outcome of interest was incident type 2 diabetes occurring from baseline through return of the 2019 questionnaire. Participants reporting physician-diagnosed type 2 diabetes on each biennial questionnaire were mailed a supplementary questionnaire regarding symptoms, diagnostic tests, and hypoglycemic therapy to confirm self-reported diagnoses. Confirmed diabetes required at least one of the following reported on the supplementary questionnaire according to the American Diabetes Association (ADA) criteria: (1) one or more classic symptoms (excessive thirst, polyuria, weight loss, hunger, pruritus, or coma) plus elevated glucose levels (fasting plasma glucose concentration ≥ 126 mg/dL or random plasma glucose ≥ 200 mg/dL); or (2) no symptoms reported but two or more elevated plasma glucose concentrations on more than one occasion (fasting ≥ 126 mg/dL, random ≥ 200 mg/dL, 2-hour oral glucose tolerance test ≥ 200 mg/dL); or (3) treatment with insulin or oral hypoglycemic agent. As previously reported, 98% of cases identified by the supplementary questionnaire were reconfirmed after review of medical records.22
Ascertainment of covariates
Participants self-reported their age, race and ethnicity, and recalled weight at age 18 on the 1989 questionnaire. We calculated body mass index (BMI, weight in kilograms divided by height in meters squared) using recalled weight at age 18. Participants updated their parity (pregnancies lasting at least 6 months), home address, husband’s highest level of education, smoking status, and changes in nursing occupation on biennial questionnaires. We derived socioeconomic status score based on the sum of the z-scores of census tract indicators based on each participant’s home address zip code (median household income, home value, percentage with college degree, percentage of families with interest or dividends, percentage occupied housing, percentage living in poverty, percentage white). Participants reported their usual frequency of engaging in common recreational activities on a validated physical activity questionnaire approximately every four years.23 We converted their responses into metabolic equivalent tasks (METs) and summed across activities to calculate total physical activity in METs per week. Participants reported their usual dietary intake approximately every 4 years using a semiquantitative food frequency questionnaire. From this information, we derived alcohol intake and computed a healthy dietary pattern adherence score for each participant according to the 2010 Alternative Healthy Eating Index (AHEI), with a higher score indicating greater overall diet quality.24
Statistical analysis
We calculated cumulative duration of rotating night shift work by assigning and adding together midpoint values of duration of rotating night shift work prior to 1989 and in each questionnaire period. We grouped cumulative duration of rotating night shift work in categories as follows: none, <5 years, 5-10 years, and >10 years. We grouped recent participation in rotating night shift work as follows: none, 1- 19 months, and 20-24 months of rotating night shift work within the last two years. We considered participants to have a history of GDM from the time of their first pregnancy affected by GDM until the end of follow-up. We used Cox proportional hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between categories of cumulative or recent rotating night shift work and incident type 2 diabetes. Participants were eligible to contribute person-time beginning in 1991 if they were parous at baseline, or from the date of their first pregnancy if it occurred during the follow-up period. Participants contributed person-time until report of incident type 2 diabetes, death, or loss to follow-up, or the end of the follow-up period (June 30, 2019). Multivariable-adjusted model 1 included likely confounders: age (continuous), parity (1, 2, ≥3 children), race (non-Hispanic white, Hispanic or non-white, missing), socioeconomic status indicator (quartiles; <−2.7, −2.7 to −0.4, −0.3 to 2.2, >2.2), husband's education (high school or less, some or all college, graduate school, other/missing), currently working as a nurse (yes/no). Multivariable-adjusted model 2 additionally included: body-mass index at age 18 (15 to <25, 25 to <30, 30 to <50 kg/m2), and time-varying smoking status (never, past, current), alcohol use (none, < 1 drink/day, 1 or more drinks/day), physical activity (quartiles; <4.7, 47 to 11.9, 12.0 to 25.6, >25.6 MET-hours/week), and AHEI diet quality score (quartiles; <39.9, 39.9 to 46.8, 46.9 to 54.3, >54.3, missing). We additionally created a mutually-adjusted model that included both cumulative and recent rotating night shift work. As not all variables were collected in each questionnaire cycle, we carried forward data on recent shift work, smoking, alcohol, physical activity, and diet score up to two questionnaire cycles; beyond this we classified variables as missing for that cycle. If participants stopped updating their shift work history completely, we censored for loss to follow-up. We calculated the median values of each exposure category of rotating night shift work, and modeled these as a continuous variable to obtain tests for linear trend.
We tested for effect modification of the association between night shift work and type 2 diabetes according to history of GDM by adding an interaction term (median values of rotating night shift work exposure categories*history of GDM) to the multivariable-adjusted models described above, and by conducting stratified models by history of GDM. Additionally, we calculated the unadjusted incidence rates of type 2 diabetes for the joint strata combining cumulative night shift work and history of GDM (No rotating night shift work/No GDM, <5 years/No GDM, 5-10 years/No GDM, >10 years/No GDM, No rotating night shift work/History of GDM, <5 years/History of GDM, 5-10 years/History of GDM, >10 years/History of GDM). We then modeled the multivariable-adjusted risk of type 2 diabetes among joint exposure categories, compared to the reference category of women with no rotating night shift work/no GDM.
We used 2-sided statistical tests, and considered p-values of <0.05 to indicate statistical significance. We analyzed data with SAS, version 9.4 (SAS Institute).
Results
Among 50,122 participants (mean age 37 years in 1991), 36% did not work rotating night shifts, 48% worked <5 years of rotating night shifts, 11% worked 5-10 years, and 5% worked >10 years. There were 2,548 participants with a history of GDM at baseline or reported during follow-up. There were 2,814 cases of incident type 2 diabetes (n=2,349 in participants without a history of GDM and n=465 in participants with a history of GDM).
Table 1 summarizes the sociodemographic characteristics of participants at baseline by category of cumulative duration of rotating night shift work and by history of GDM. For a description of the sample at baseline that includes BMI and lifestyle variables, see Supplementary Table 1. Participants with a longer cumulative duration of rotating night shift work had, on average, lower socioeconomic status and higher BMI at age 18 than participants without a history of rotating night shift work. Participants with longer cumulative duration of rotating night shift work were also more likely to be past or current smokers, and tended to be more physically active. Participants with a history of GDM had higher parity, lower physical activity, and higher BMI at age 18 compared to participants without a history of GDM.
Table 1.
Baseline (1991) sociodemographic characteristics of 50,122 participants according to cumulative durationa of rotating night shift work and history of gestational diabetes (GDM) in the Nurses’ Health Study II
| Cumulative duration of rotating night shift work |
History of GDM | |||||
|---|---|---|---|---|---|---|
| None (n=18,085) |
<5 years (n=24,166) |
5-10 years (n=5,534) |
>10 years (n=2,337) |
No GDM (n=47,574) |
GDM (n=2,548) |
|
| Characteristics | n/mean (%/SD) |
n/mean (%/SD) |
n/mean (%/SD) |
n/mean (%/SD) |
n/mean (%/SD) |
n/mean (%/SD) |
| Age (years), mean [SD] | 37.6 (4.4) | 37.3 (4.3) | 37.1 (4.3) | 39.1 (3.4) | 37.5 (4.4) | 36.4 (4.2) |
| Self-reported | ||||||
| race/ethnicity | ||||||
| non-Hispanic white | 16932 (93.6) | 22510 (93.2) | 5123 (92.6) | 2122 (90.8) | 44362 (93.3) | 2325 (91.3) |
| Hispanic or non-white | 883 (4.9) | 1295 (5.4) | 335 (6.1) | 175 (7.5) | 2497 (5.3) | 191 (7.5) |
| Missing | 270 (1.5) | 361 (1.5) | 79 (1.4) | 40 (1.7) | 715 (1.5) | 32 (1.3) |
| Parity (pregnancies ≥6 months) | ||||||
| 1 | 3786 (20.9) | 5328 (2.1) | 1341 (24.2) | 501 (21.4) | 10398 (21.9) | 558 (21.9) |
| 2 | 8957 (49.5) | 11796 (48.8) | 2646 (47.8) | 1140 (48.8) | 23356 (49.1) | 1183 (46.4) |
| ≥3 | 5342 (29.5) | 7042 (29.1) | 1547 (28) | 696 (29.8) | 13820 (29.1) | 807 (31.7) |
| Socioeconomic status scoreb | ||||||
| First quartile: <−2.7 | 3877 (21.4) | 5242 (21.7) | 1360 (24.6) | 577 (24.7) | 10515 (22.1) | 541 (21.2) |
| Second quartile: −2.7 to | ||||||
| −0.4 | 5284 (29.2) | 6700 (27.7) | 1678 (30.3) | 758 (32.4) | 13690 (28.8) | 730 (28.6) |
| Third quartile: −0.3 to 2.2 | 4660 (25.8) | 6440 (26.7) | 1338 (24.2) | 564 (24.1) | 12309 (25.9) | 693 (27.2) |
| Fourth quartile: >2.2 | 4264 (23.6) | 5784 (23.9) | 1158 (20.9) | 438 (18.7) | 11060 (23.3) | 584 (22.9) |
| Husband's education | ||||||
| High school | 3213 (17.8) | 3815 (15.8) | 995 (19) | 434 (18.6) | 8029 (16.9) | 428 (16.8) |
| Some college | 8368 (56.3) | 10929 (45.2) | 2491 (45) | 1075 (46) | 21671 (45.6) | 1192 (46.8) |
| College graduate | 4529 (25) | 6773 (28) | 1303 (23.6) | 490 (21) | 12457 (26.2) | 638 (25) |
| Not applicable | 1120 (6.2) | 1450 (6) | 419 (7.6) | 184 (7.9) | 3022 (6.4) | 151 (5.9) |
| Missing | 855 (4.7) | 1199 (5) | 326 (5.9) | 152 (6.6) | 2395 (5) | 138 (5.5) |
Cumulative duration of rotating night shift work was calculated by assigning and adding together midpoint values of duration of rotating night shift work prior to 1989 and in each questionnaire period.
Socioeconomic status score is based on the sum of the z-scores of census tract indicators based on participants’ zip codes (median household income, home value, percentage with college degree, percentage of families with interest or dividends, percentage occupied housing, percentage living in poverty, percentage white)
Table 2 provides the HRs for the associations between cumulative duration of rotating night shift work and incident type 2 diabetes. In the overall population, compared with participants who never engaged in rotating night shift work, we observed a graded increase in the risk of type 2 diabetes with cumulative years of rotating night shift work: HR(95%CI)= 1.14(1.04, 1.24) for <5 years, 1.32(1.17, 1.49) for 5-10 years, and 1.32(1.16, 1.50) for >10 years in the fully-adjusted model (p-linear trend <0.001). We observed a similar pattern of associations between cumulative years of rotating night shift work and risk of type 2 diabetes among participants without a history of GDM, but not among those with a history of GDM (p-interaction=0.02). Among participants without a history of GDM, longer duration of cumulative rotating night shift work was associated with a higher risk of type 2 diabetes: HR(95%CI)= 1.13(1.03, 1.25) for <5 years of rotating night shift work, 1.29(1.13, 1.47) for 5-10 years, and 1.35(1.17, 1.55) for >10 years (p-linear trend <0.001). We did not observe an association between cumulative duration of rotating night shift work and type 2 diabetes among participants with a history of GDM (p-linear trend=0.88).
Table 2.
Risk of incident type 2 diabetes according to cumulative durationa of rotating night shift work in the Nurses’ Health Study II, by history of gestational diabetes (GDM)
| Model | Cumulative duration of rotating night shift worka | ||||
|---|---|---|---|---|---|
| All participants | |||||
| Never | <5 years | 5-10 years | >10 years | p-trend | |
| Type 2 Diabetes, n cases | 752 | 1289 | 424 | 349 | |
| Person-years | 438782 | 673602 | 179066 | 125039 | |
| Model 1b | 1.00 (ref) | 1.13 (1.03, 1.24) | 1.35 (1.20, 1.52) | 1.36 (1.20, 1.55) | <0.001 |
| Model 2c | 1.00 (ref) | 1.14 (1.04, 1.24) | 1.32 (1.17, 1.49) | 1.32 (1.16, 1.50) | <0.001 |
| p-interaction with history of GDM | 0.02 | ||||
| Participants without a history of GDM | |||||
| Never | <5 years | 5-10 years | >10 years | p-trend | |
| Type 2 Diabetes, n cases | 637 | 1069 | 343 | 300 | |
| Person-years | 421287 | 640426 | 169340 | 117899 | |
| Model 1b | 1.00 (ref) | 1.12 (1.02, 1.24) | 1.32 (1.15, 1.50) | 1.39 (1.21, 1.60) | <0.001 |
| Model 2c | 1.00 (ref) | 1.13 (1.03, 1.25) | 1.29 (1.13, 1.47) | 1.35 (1.17, 1.55) | <0.001 |
| Participants with a history of GDM | |||||
| Never | <5 years | 5-10 years | >10 years | p-linear trend |
|
| Type 2 Diabetes, n cases | 115 | 200 | 81 | 49 | |
| Person-years | 17495 | 33176 | 9726 | 7140 | |
| Model 1b | 1.00 (ref) | 1.00 (0.79, 1.25) | 1.22 (0.92, 1.63) | 0.91 (0.65, 1.27) | 0.91 |
| Model 2c | 1.00 (ref) | 0.99 (0.79, 1.24) | 1.21 (0.90, 1.61) | 0.92 (0.65, 1.29) | 0.88 |
Cumulative duration of rotating night shift work was calculated by assigning and adding together midpoint values of duration of rotating night shift work prior to 1989 and in each questionnaire period.
Adjusted for age (continuous), parity (1, 2, ≥3 children), race (non-Hispanic white, Hispanic or non-white, missing), socioeconomic status score quartiles (<−2.7, −2.7 to −0.4, −0.3 to 2.2, >2.2), husband's education (high school or less, some or all college, graduate school, other/missing), currently working as a nurse (yes/no)
Adjusted for Model 1 variables and body-mass index at age 18 (15 to <25, 25 to <30, 30 to <50 kg/m2), and time-varying smoking status (never, past, current), alcohol use (none, < 1 drink/day, 1 or more drinks/day), physical activity quartiles (<4.7, 47 to 11.9, 12.0 to 25.6, >25.6 MET-hours/week), and Alternative Healthy Eating Index quartiles (<39.9, 39.9 to 46.8, 46.9 to 54.3, >54.3, missing)
Table 3 provides the estimated HRs for the association between recent rotating night shift work and incident type 2 diabetes. In the overall population, the risk of type 2 diabetes increased with months of rotating night shift work within the past two years: HR(95%CI)= 1.13(0.96, 1.32) for 1-19 months and 1.22(1.00, 1.49) for 20-24 months in the fully-adjusted model (p-linear trend=0.02). There was no statistically significant effect modification by history of GDM (p-interaction=0.55). However, among participants without a history of GDM, months of recent rotating night shift work was associated with a higher risk of type 2 diabetes: HR(95%CI)= 1.07(0.89, 1.28) for 1-19 months of rotating night shift work within the past 2 years and 1.28(1.03, 1.59) for 20-24 months, compared with no recent rotating night shift work (p-linear trend=0.02). In contrast, we did not observe an association between months of recent rotating night shift work and type 2 diabetes among participants with a history of GDM (p-linear trend=0.86).
Table 3.
Risk of incident type 2 diabetes according to past two year participationa in rotating night shift work in the Nurses’ Health Study II, by history of gestational diabetes (GDM)
| Model | Past two year participation in rotating night shift work |
|||
|---|---|---|---|---|
| All participants | ||||
| None | 1-19 months |
20-24 months |
p-linear trend |
|
| Type 2 Diabetes, n cases | 2373 | 162 | 102 | |
| Person-years | 1184299 | 83532 1.16 (0.99, 1.36) | 46972 1.32 (1.08, 1.62) | |
| Model 1b | 1.00 (ref) | 1.13 (0.96, 1.32) | 1.22 (1.00, 1.49) | 0.002 |
| Model 2c | 1.00 (ref) | 0.02 | ||
| p-interaction with history of GDM | 0.55 | |||
| Participants without a history of GDM | ||||
| None | 1-19 months | 20-24 months |
p-linear trend |
|
| Type 2 Diabetes, n cases | 2000 | 124 | 86 | |
| Person-years | 1130900 | 78620 | 44151 | |
| Model 1b | 1.00 (ref) | 1.10 (0.91, 1.32) | 1.39 (1.12, 1.73) | 0.002 |
| Model 2c | 1.00 (ref) | 1.07 (0.89, 1.28) | 1.28 (1.03, 1.59) | 0.02 |
| Participants with a history of GDM | ||||
| None | 1-19 months | 20-24 months |
p-linear trend |
|
| Type 2 Diabetes, n cases | 373 | 38 | 16 | |
| Person-years | 53399 | 4912 | 2822 | |
| Model 1b | 1.00 (ref) | 1.22 (0.87, 1.71) | 0.91 (0.55, 1.50) | 0.93 |
| Model 2c | 1.00 (ref) | 1.18 (0.84, 1.66) | 0.86 (0.52, 1.43) | 0.86 |
Past two year participation in rotating night shift work was defined based on months of night shift work within the last 24 months.
Adjusted for age (continuous), parity (1, 2, ≥3 children), race (non-Hispanic white, Hispanic or non-white, missing), socioeconomic status score quartiles (<−2.7, −2.7 to −0.4, −0.3 to 2.2, >2.2), husband's education (high school or less, some or all college, graduate school, other/missing), currently working as a nurse (yes/no)
Adjusted for Model 1 variables and body-mass index at age 18 (15 to <25, 25 to <30, 30 to <50 kg/m2), and time-varying smoking status (never, past, current), alcohol use (none, < 1 drink/day, 1 or more drinks/day), physical activity quartiles (<4.7, 47 to 11.9, 12.0 to 25.6, >25.6 MET-hours/week), and Alternative Healthy Eating Index quartiles (<39.9, 39.9 to 46.8, 46.9 to 54.3, >54.3, missing)
Supplementary Table 2 provides the estimated HRs for type 2 diabetes according to night shift work history, from a model in which cumulative duration of rotating night shift work and recent rotating night shift work were mutually-adjusted. In the overall population, and among individuals without a history of GDM, adjustment for recent rotating night shift work did not significantly impact the magnitude or statistical significance of associations between categories of cumulative duration of rotating night shift work and incident type 2 diabetes. However, we no longer observed associations between recent rotating night shift work and type 2 diabetes, in either the overall population or among individuals without a history of GDM, in the mutually-adjusted model. This attenuation of recent rotating night shift work in the mutually-adjusted model suggests that cumulative duration of rotating night shift work may be more important for risk of type 2 diabetes than recent rotating night shift work.
Supplementary Figure 2 shows the unadjusted incidence rates of type 2 diabetes among each of the joint exposure categories for cumulative rotating night shift work and history of GDM. This illustrates the high absolute risk of type 2 diabetes among women with a history of GDM, and a modestly higher risk of type 2 diabetes observed with higher exposure to night shift work. Table 4 provides the estimated HRs for type 2 diabetes for the joint association of cumulative duration of rotating night shift work and history of GDM, compared to women with neither shift work nor a history of GDM. Similarly, Table 5 provides the estimated HRs for type 2 diabetes for the joint association of recent rotating night shift work and history of GDM, with the reference group as participants with no history of rotating night shift work and no history of GDM. For both Tables 4 and 5, the multivariable-adjusted results indicated that GDM was strongly associated with incident type 2 diabetes for all exposure categories of cumulative rotating night shift work (HRs: 3.94-5.75) and recent rotating night shift work (HRs:3.84-5.51). Further, a modest positive association was observed for higher exposure to rotating night shift work and higher risk of type 2 diabetes among women without prior GDM but not for those with a history of GDM, although statistical power was limited in this subset.
Table 4.
Risk of incident type 2 diabetes according to cumulative durationa of rotating night shift work and history of gestational diabetes (GDM) in the Nurses’ Health Study II
| Model | No rotating night shift work, No GDM (reference) |
<5 years, No GDM |
5-10 years, No GDM |
>10 years, No GDM |
No rotating night shift work, History of GDM |
<5 years, History of GDM |
5-10 years, History of GDM |
>10 years, History of GDM |
|---|---|---|---|---|---|---|---|---|
| Type 2 Diabete s, n cases | 637 | 1069 | 343 | 300 | 115 | 220 | 81 | 49 |
| Person-years | 421287 | 640426 | 169340 | 117899 | 17495 | 33176 | 9726 | 7140 |
| Model 1b | xS 1.00 (ref) | 1.12 (102, 1.24) | 1.32 (1.15, 1.50) | 1.41 (1.23, 1.62) | 5.11 (4.19, 6.23) | 5.07 (4.35, 5.92) | 6.25 (4.96, 7.88) | 4.27 (3.19, 5.72) |
| model 2c | 1.00 (ref) | 1.13 (1.03, 1.25) | 1.29 (1.13, 1.48) | 1.37 (1.19, 1.57) | 4.76 (3.90, 5.81) | 4.68 (4.01, 5.46) | 5.75 (4.56, 7.26) | 3.94 (2.94, 5.28) |
Cumulative duration of rotating night shift work was calculated by assigning and adding together midpoint values of duration of rotating night shift work prior to 1989 and in each questionnaire period.
Adjusted for age (continuous), parity (1, 2, ≥3 children), race (non-Hispanic white, Hispanic or non-white, missing), socioeconomic status score quartiles (<−2.7, −2.7 to −0.4, −0.3 to 2.2, >2.2), husband's education (high school or less, some or all college, graduate school, other/missing), currently working as a nurse (yes/no)
Adjusted for Model 1 variables and body-mass index at age 18 (15 to <25, 25 to <30, 30 to <50 kg/m2), and time-varying smoking status (never, past, current), alcohol use (none, < 1 drink/day, 1 or more drinks/day), physical activity quartiles (<4.7, 47 to 11.9, 12.0 to 25.6, >25.6 MET-hours/week), and Alternative Healthy Eating Index quartiles (<39.9, 39.9 to 46.8, 46.9 to 54.3, >54.3, missing)
Table 5.
Risk of incident type 2 diabetes according to past two year participationa in rotating night shift work and history of gestational diabetes (GDM) in the Nurses’ Health Study II
| Model | No rotating night shift work, No GDM |
1-19 months, No GDM |
20-24 months, No GDM |
No rotating night shift work, History of GDM |
1-19 months, History of GDM |
20-24 months, History of GDM |
|---|---|---|---|---|---|---|
| Type 2 Diabetes, n cases | 2000 | 124 | 86 | 373 | 38 | 16 |
| Person-years | 421287 | 640426 | 169340 | 117899 | 17495 | 33176 |
| Model 1b | 1.00 (ref) | 1.08 (0.90, 1.29) | 1.36 (1.09, 1.69) | 4.51 (4.02, 5.03) | 6.17 (4.47, 8.52) | 4.50 (2.75, 7.38) |
| Model 2c | 1.00 (ref) | 1.05 (0.87, 1.26) | 1.26 (1.01, 1.57) | 4.16 (3.72, 4.65) | 5.51 (3.99, 7.61) | 3.84 (2.35, 6.29) |
Past two year participation in rotating night shift work was defined based on months of night shift work within the last 24 months.
Adjusted for age (continuous), parity (1, 2, ≥3 children), race (non-Hispanic white, Hispanic or non-white, missing), socioeconomic status score quartiles (<−2.7, −2.7 to −0.4, −0.3 to 2.2, >2.2), husband's education (high school or less, some or all college, graduate school, other/missing), currently working as a nurse (yes/no)
Adjusted for Model 1 variables and body-mass index at age 18 (15 to <25, 25 to <30, 30 to <50 kg/m2), and time-varying smoking status (never, past, current), alcohol use (none, < 1 drink/day, 1 or more drinks/day), physical activity quartiles (<4.7, 47 to 11.9, 12.0 to 25.6, >25.6 MET-hours/week), and Alternative Healthy Eating Index quartiles (<39.9, 39.9 to 46.8, 46.9 to 54.3, >54.3, missing)
Discussion
In this large cohort of US nurses, parous participants with a longer cumulative duration of rotating night shift work had a higher risk of incident type 2 diabetes. In addition, the frequency of recent rotating night shift work within the past 2 years was also related to higher risk of type 2 diabetes. These associations were pronounced among nurses without a history of GDM, and no association was observed among nurses with a history of GDM. Nurses with a history of GDM were at exceptionally high risk of type 2 diabetes compared to nurses without a history of GDM, regardless of their cumulative or recent exposure to rotating night shift work.
Our results demonstrate an association between cumulative duration of rotating night shift work and incident type 2 diabetes in the overall population and are consistent with prior studies.4,9 The most recent meta-analysis (10 prospective cohorts with 235,800 participants) found that rotating night shift work is associated with a 30% higher risk of type 2 diabetes (95%CI=1.18, 1.43) when comparing night shift workers to non-night shift workers .25 A prior analysis in the Nurses’ Health Studies (that was not restricted to parous participants) also demonstrated a monotonically increasing risk of type 2 diabetes with longer cumulative duration of rotating night shift work.4 Several potential mechanisms for the association between night shift work and type 2 diabetes have been proposed, including that night shift workers may be more likely to engage in unhealthy lifestyle behaviors such as smoking,17 higher total calorie intake,17 shorter sleep duration,26 and sedentary lifestyle27 that contribute to obesity and impaired metabolism. However, we found that associations between cumulative duration of rotating night shift work and type 2 diabetes were robust to adjustment for smoking, diet quality, and physical activity, suggesting a possible direct effect of circadian disruption on impaired metabolism. This is supported by prior controlled experimental studies among healthy human volunteers, in which simulated night shift work has been found to result in insulin resistance15 and hyperglycemia.16
We observed that while rotating night shift work increased risk of developing type 2 diabetes among nurses without GDM, among nurses with a history of GDM, there was no relationship between rotating night shift work and type 2 diabetes. GDM is among the strongest risk factors for type 2 diabetes;18 and, establishing the impact of an additional moderate risk factor for type 2 diabetes in this high-risk subgroup is challenging. Further, our statistical power for analyses of rotating night shift work and type 2 diabetes in the subset of participants with a history of GDM was limited. If a larger study were conducted to confirm our results with more precision, it might be useful to examine risk differences among individuals with and without a history of GDM, to determine the potential impact of reducing night shift work in each group.
We found that mutual adjustment for cumulative and recent rotating night shift work resulted in attenuation of the association between recent rotating night shift work and type 2 diabetes, while the association between cumulative duration of rotating night shift work and type 2 diabetes remained unchanged. One potential mechanism to explain this finding is mediation by weight gain, which may occur slowly over time, and may not be detectable in a two year exposure window.28 However, prior studies in other cohorts have found significant associations between recent rotating night shift work and type 2 diabetes, and inconsistent associations between cumulative duration of rotating night shift work and type 2 diabetes,29,30 suggesting that additional research is needed to clarify underlying relationships.
Strengths of our study include the study population – a large, prospective occupational cohort of US nurses. Nurses are disproportionately women of reproductive age,31 and more likely to participate in night shift work compared to workers in other professions.32 Additional strengths include the study design with repeated measures of shift work exposure over the lifecourse, repeated measures of potential confounders over the lifecourse, and long term follow up.
Our analysis also has several limitations. First, there was potential misclassification of rotating night shift work since recent rotating night shift work was self-reported and ascertained retrospectively. Also, rotating night shift work was not assessed in each questionnaire cycle and was carried forward in our analysis up to four years when missing in a given cycle. Further, we only assessed whether participants were working rotating night shifts, and did not have information on whether participants were working permanent night shifts or other shift schedules – thus, some participants who were working permanent night shifts, with similar type 2 diabetes risk as rotating night shift work, may have been included in the reference group. We anticipate any of the above sources of exposure misclassification, if non-differential, could have biased our results towards the null. In addition, our primary outcome of incident type 2 diabetes was self-reported; however, this outcome has previously been validated and found to have high accuracy.22 Even though we carefully controlled for known and suspected potential confounding factors, confounders were self-reported, and residual and unmeasured confounding is possible. Further, our analysis was conducted among individuals from across the United States, who may have had different workplace policies for night shift scheduling. Finally, our study population consisted of parous nurses, thus the generalizability of our results to other populations or occupations is uncertain.
Our analyses may underestimate the association between rotating night shift work and type 2 diabetes due to the “healthy worker effect.” It is possible that some rotating night shift workers continued to work night shift schedules because they were healthier than those who worked on daytime schedules or switched back to day routines or withdrew from work for health reasons. This self-selection could bias our results towards the null.
In this study, we observed a modest association between cumulative and recent rotating night shift work and risk of type 2 diabetes among nurses without a history of GDM but not among nurses with a history of GDM. Larger studies with more precise information on shift work timing, that investigate shift work changes subsequent to GDM diagnosis, could be considered. Moreover, the field will benefit from future research exploring potential mechanisms by which night shift work may contribute to the risk of type 2 diabetes.
Supplementary Material
Research in Context.
What is already known on this topic
Individuals with a history of gestational diabetes are at exceptionally high risk for type 2 diabetes
Rotating night shift work is a moderate risk factor for type 2 diabetes
What this study adds
Cumulative years of rotating night shift work was modestly associated with a higher risk of type 2 diabetes, overall, and among nurses without a history of gestational diabetes.
Rotating night shift work was not associated with risk of type 2 diabetes among individuals with a history of gestational diabetes, an exceptionally high-risk sub-group for type 2 diabetes.
How this study might affect research, practice or policy
Counseling regarding the metabolic impacts of rotating night shift work is warranted, even among lower risk women without a history of gestational diabetes
Funding:
This research was made possible by the NHSII cohort infrastructure grant (U01 CA176726). Work by IA was supported by the COBRE training grant (2P20GM121301-06A1, PI: Liaw).
Abbreviations:
- GDM
gestational diabetes mellitus
Footnotes
Ethics statement: This study was approved by the MaineHealth Institutional Review Board (1948444) and was considered exempt #4.iii as secondary research for which no new data was collected.
Competing Interest: None
Data availability:
Data from the Nurses’ Health Study is available to collaborators upon request and with the permission of Nurses’ Health Study.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Data from the Nurses’ Health Study is available to collaborators upon request and with the permission of Nurses’ Health Study.