Association between gastrointestinal disorders and sleep-related problems: the mediating effect of depression | BMC Gastroenterology

Study population

The NHANES, administered by the National Center for Health Statistics (NCHS), is a nationally representative program designed to assess the health and nutritional status of the non-institutionalized civilian U.S. population. This study analyzed data from the 2005–2014 NHANES cycles, encompassing 50,965 participants. Exclusion criteria were applied to remove 40,339 individuals for the following reasons: missing data on sleep (n = 18,869), gastrointestinal (GI) disease (n = 4,033), depression (n = 1,959), or key covariates including education, income-to-poverty ratio, BMI, hypertension, smoking, alcohol use, and diabetes (n = 4,010). Participants with a cancer diagnosis (n = 2,305) or missing data on coronary heart disease, heart failure, stroke, physical activity, HEI-2015, or DI-GM (n = 9,163) were also excluded. The final analytical sample consisted of 10,626 participants (Fig. 1).

Fig. 1

Assessment of gastrointestinal disease

GI disease status was determined based on responses from the “Current Health Status”section of the questionnaire. Participants were classified as having a GI disease if they answered “yes”to the question: “During the past 30 days, have you had a stomach or intestinal illness with vomiting or diarrhea?”.

Assessment of sleep-related factors

Sleep duration was assessed via the question: “On average, how many hours of sleep do you usually get on weekdays or workdays?”Trouble sleeping and sleep disorders were identified through affirmative responses to the questions: “Have you ever been told by a doctor that you had trouble sleeping?” and“Have you ever been told by a doctor that you have a sleep disorder?” [17].

Assessment of depression

Depression was evaluated using the Patient Health Questionnaire-9 (PHQ-9), a validated instrument for assessing depressive symptom severity [18]. The PHQ-9 consists of nine items rated on a 4-point Likert scale (0 = “not at all” to 3 = “nearly every day”), yielding a total score from 0 to 27. A score of ≥ 10 was used to indicate depression [19].

Covariates

Covariates included demographic and clinical variables: age, sex, race/ethnicity (Mexican American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Other), education (< 9th grade, 9–11th grade, high school diploma/GED, some college/associate degree, ≥ college graduate), income-to-poverty ratio, BMI, drinking status, smoking status, hypertension, diabetes, physical activity, HEI-2015, DI-GM, caffeine intake, coronary heart disease, heart failure, and stroke. Hypertension was defined as self-reported high blood pressure with current use of antihypertensive medications [20]. Diabetes was defined as physician-diagnosed, fasting glucose ≥ 7.0 mmol/L, or 2-h plasma glucose (OGTT) ≥ 11.1 mmol/L. Prediabetes was defined as fasting glucose 6.1–6.9 mmol/L or OGTT 7.8–11.1 mmol/L, or physician diagnosis [20]. Smoking status was classified as never smokers (never smoked or quit over a year ago) and current smokers (smoked within the past 30 days or resumed smoking ≥ 2 cigarettes per day) [21]. Drinking status was categorized as never drinkers (< 12 drinks in a lifetime) or current drinkers (≥ 12 drinks per year or ≥ 6 occasions in the past 12 months) [20]. Participants were considered positive for specific cardiovascular conditions if they reported a diagnosis of congestive heart failure, coronary heart disease, angina, myocardial infarction, or stroke [21]. Physical activity was assessed using the Global Physical Activity Questionnaire [18]. Total physical activity was calculated using metabolic equivalent of task (MET) values based on reported frequency and duration. Participants were classified as inactive (< 600 MET-min/week) or active (≥ 600 MET-min/week) [18]. BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2).

Statistical analyses

All statistical analyses followed NHANES analytic guidelines. Survey weights were adjusted for the five combined cycles (2005–2014) by dividing the 2-year weight variable (WTMEC2YR) by five. Primary sampling units (SDMVPSU) and strata (SDMVSTRA) were applied to account for the complex sampling design. After weighting, each participant represented 7,826 individuals in the U.S. population. Continuous variables were summarized using means and standard deviations (SD), while categorical variables were expressed as frequencies and weighted percentages. Group comparisons were performed using Student’s t-tests for continuous variables and chi-square tests for categorical variables. Variance inflation factors (VIFs) were used to assess multicollinearity. Multivariable logistic regression models were used to examine the association between gastrointestinal disease and trouble sleeping. Model 1 was unadjusted. Model 2 adjusted for sex, age, race/ethnicity, education, and family income-to-poverty ratio. Model 3 additionally adjusted for BMI, drinking status, smoking status, hypertension, and diabetes. Model 4 further included physical activity, HEI-2015, DI-GM, caffeine intake, coronary heart disease, heart failure, and stroke. Subgroup analyses and interaction terms were included to assess effect modification by demographic and health-related variables. Mediation analysis was conducted using the R package mediation to test whether depression mediated the relationship between GI disease and sleep trouble. Direct, indirect, and total effects were estimated using 5,000 bootstrap iterations. Statistical significance was defined by a 95% confidence interval excluding zero. To address missing data, multiple imputation was performed using the R package mice, preserving statistical power and minimizing bias. All analyses were conducted using IBM SPSS Statistics (version 24.0) and R (version 4.3.0). A two-sided P-value < 0.05 was considered statistically significant.

Sensitivity analyses

To evaluate the robustness of the results, additional multivariable linear and logistic regression analyses were conducted to examine the associations between GI disease and both sleep duration and sleep disorder. Unweighted analyses were also performed to assess the consistency of the association between GI disease and trouble sleeping.

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