Changes in Metabolic Syndrome Status are Associated With Altered Risk of Pancreatic Cancer: A Nationwide Cohort Study.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on pancreatic cancer risk is unknown. We aimed to investigate the effects of changes and persistence in MetS status on pancreatic cancer risk. METHODS: This nationwide cohort study included 8,203,492 adults without cancer who underwent 2 consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2012 and were followed up until 2017. MetS was defined as the presence of 3 of its 5 components, which were evaluated at 2 consecutive biennial health screenings. Participants were categorized into the MetS-free, MetS-recovered, MetS-developed, or MetS-persistent group. Multivariable Cox proportional hazards regression models were used. RESULTS: During the 40,464,586 person-years of follow-up (median, 5.1 years), 8010 individuals developed pancreatic cancer. Compared with the MetS-free group, the MetS-persistent group had the highest risk of pancreatic cancer (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.23-1.37), followed by the MetS-developed group (HR, 1.17; 95% CI, 1.09-1.25) and the MetS-recovered group (HR, 1.12; 95% CI, 1.04-1.21) after adjusting for potential confounders (P for trend <.001). The MetS-recovered group was associated with a lower risk of pancreatic cancer than that in the MetS-persistent group (P < .001). The association between changes in MetS status and pancreatic cancer risk did not differ according to sex or obesity (all P for interactions >.05). CONCLUSIONS: In this study, recovering from MetS was associated with a reduced risk of pancreatic cancer compared with persistent MetS, suggesting that pancreatic cancer risk can be altered by changes in MetS.

Risk of Postoperative Gastrointestinal Bleeding and Its Associated Factors: A Nationwide Population-Based Study in Korea.

Postoperative gastrointestinal bleeding (PGIB) is a serious complication with expensive medical costs and a high mortality rate. This study aims to analyze the incidence of PGIB and its associated factors, including its relationship with postoperative analgesic use. Patients aged ≥20 years who received various kinds of surgery from 2013 to 2017 were included (n = 1,319,807). PGIB was defined by admission with ICD-10 codes of gastrointestinal bleeding plus transfusion within 2 months after surgery. A total of 3505 (0.27%) subjects had PGIB, and the incidence was much higher for those who underwent major gastrointestinal and major cardiovascular surgery (1.9% for both), followed by major head and neck (0.7%), major genitourinary (0.5%), and orthopedic surgery (0.45%). On multivariate analysis, older age, male sex, lower income, comorbidities, peptic ulcer disease, and congestive heart failure were associated with a higher risk of gastrointestinal bleeding. Among analgesics, steroid use was associated with increased postoperative bleeding risk (adjusted OR: 1.36, 95% CI: 1.25-1.48). Acetaminophen/nonsteroidal anti-inflammatory drugs, cyclooxygenase 2 inhibitors, anticonvulsants, antidepressants, and opioids were not associated with increased risk. PGIB is considerable for major surgeries, and its risk should be considered, especially for patients with older age and comorbidities and use of steroids.

Association of prediabetes, diabetes, and diabetes duration with biliary tract cancer risk: A nationwide cohort study.

BACKGROUND & AIMS: Population-based evidence of the association between diabetes and biliary tract cancer (BTC) risk is lacking. We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with subsequent risk of BTC, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), in the Korean general population. METHODS: This nationwide cohort study included 9,697,773 adults aged ≥20 years without cancer who underwent national health screening between January and December 2009. Subjects' glycemic status was categorized as normoglycemic, impaired fasting glucose (IFG), newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Incident BTC was identified using claims data. Follow-up continued until December 2017. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% CIs of BTC. RESULTS: During a median follow-up of 7.2 years, 13,022 patients were newly diagnosed with BTC. Compared with the normoglycemic group, the IFG, newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years groups showed the following adjusted hazard ratios (95% CIs) for BTC: 1.08 (1.04-1.12), 1.31 (1.22-1.41), 1.35 (1.27-1.43), and 1.47 (1.39-1.55), respectively. BTC risk significantly increased with deteriorating glycemic status (P for trend <0.001). These results were consistent with those of CCA and GBC analyses. CONCLUSIONS: Both IFG and diabetes were independently associated with an increased risk of BTC, including CCA and GBC. A longer diabetes duration was associated with a further increase in BTC risk. Diabetes and even IFG may be modifiable risk factors for BTC.

Persistent status of metabolic syndrome and risk of cholangiocarcinoma: A Korean nationwide population-based cohort study.

OBJECTIVE: It is unknown whether persistent metabolic syndrome (MetS) is associated with an increased risk of cholangiocarcinoma (CCA). Therefore, we investigated the risk of CCA according to changes in MetS status. RESEARCH DESIGN AND METHODS: This nationwide cohort study included 8,581,407 adults who underwent anthropometric measurements and laboratory tests in two consecutive national health screenings during 2009-2012 and observed the subjects until 2017. Individuals with cancer, or follow-up duration <1 year were excluded (n = 377,915). Subjects were classified into the MetS-free, MetS-developed, MetS-improved, and MetS-persistent groups. The outcome was the incidence of CCA, identified using the claims database. Multivariable Cox proportional hazards regression models were used. RESULTS: Among the 8,203,492 subjects (mean age 48.9 ± 12.8 years; 56.7% male), 7506 CCA patients were newly identified during a median follow-up of 5.1 years. The probability of CCA was consistently higher in the MetS-persistent group than in the MetS-free group (P < 0.001). MetS-persistent status was significantly associated with an increased risk of CCA compared with the MetS-free status (unadjusted hazard ratio [HR] 2.8, 95% confidence interval [CI] 2.66-2.95), even after adjusting for multiple covariates (adjusted HR 1.07, 95% CI 1.01-1.13). Improved or newly developed MetS was not associated with CCA risk in the fully adjusted model (aHR 1.02, 95% CI 0.94-1.10 and aHR 0.99, 95% CI 0.92-1.06, respectively). CONCLUSIONS: MetS was associated with an increased risk of CCA if it persisted for ≥2 years. Our finding suggests that MetS may be a potentially modifiable risk factor for CCA.

Association between menstrual cycle irregularity and tinnitus: a nationwide population-based study.

This population-based cross-sectional study investigated the association between menstrual cycle irregularity and tinnitus in premenopausal Korean women. We used data from the 5th Korea National Health and Nutrition Examination Survey (2010-2012). A total of 4633 premenopausal women were included. Hierarchical multivariable logistic regression analysis was performed. Individuals with tinnitus accounted for 21.6%. Women with tinnitus or menstrual irregularity had significantly higher rates of stress, depressive mood, and suicidal ideation than those without. The proportion of individuals with irregular menstrual cycles with duration of longer than 3 months increased as the severity of tinnitus increased (P = 0.01). After adjusting for confounding variables, the odds of tinnitus increased in individuals with irregular menstrual cycles compared to those with regular menstrual cycles. The odds ratios (ORs) of tinnitus tended to increase as the duration of menstrual irregularity became longer (1.37, 95% confidence interval: 1.06-1.78 for duration of up to 3 months; 1.71, 1.03-2.85 for duration of longer than 3 months, P for trend = 0.002). Our study found a positive association between menstrual cycle irregularity and tinnitus. Menstrual cycle irregularity may be a related factor of tinnitus in women with childbearing age.

Associations of Variability in Blood Pressure, Glucose and Cholesterol Concentrations, and Body Mass Index With Mortality and Cardiovascular Outcomes in the General Population.

BACKGROUND: Variability in metabolic parameters, such as fasting blood glucose and cholesterol concentrations, blood pressure, and body weight can affect health outcomes. We investigated whether variability in these metabolic parameters has additive effects on the risk of mortality and cardiovascular outcomes in the general population. METHODS: Using nationally representative data from the Korean National Health Insurance System, 6 748 773 people who were free of diabetes mellitus, hypertension, and dyslipidemia and who underwent ≥3 health examinations from 2005 to 2012 were followed to the end of 2015. Variability in fasting blood glucose and total cholesterol concentrations, systolic blood pressure, and body mass index was measured using the coefficient of variation, SD, variability independent of the mean, and average real variability. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability parameters (eg, a score of 4 indicated high variability in all 4 metabolic parameters). Cox proportional hazards models adjusting for age, sex, smoking, alcohol, regular exercise, income, and baseline levels of fasting blood glucose, systolic blood pressure, total cholesterol, and body mass index were used. RESULTS: There were 54 785 deaths (0.8%), 22 498 cases of stroke (0.3%), and 21 452 myocardial infarctions (0.3%) during a median follow-up of 5.5 years. High variability in each metabolic parameter was associated with a higher risk for all-cause mortality, myocardial infarction, and stroke. Furthermore, the risk of outcomes increased significantly with the number of high-variability metabolic parameters. In the multivariable-adjusted model comparing a score of 0 versus 4, the hazard ratios (95% CIs) were 2.27 (2.13-2.42) for all-cause mortality, 1.43 (1.25-1.64) for myocardial infarction, and 1.41 (1.25-1.60) for stroke. Similar results were obtained when modeling the variability using the SD, variability independent of the mean, and average real variability, and in various sensitivity analyses. CONCLUSIONS: High variability of fasting blood glucose and total cholesterol levels, systolic blood pressure, and body mass index was an independent predictor of mortality and cardiovascular events. There was a graded association between the number of high-variability parameters and cardiovascular outcomes.

Variability in metabolic parameters and risk of dementia: a nationwide population-based study.

BACKGROUND: Variability in biological parameters has been reported to be associated with adverse health outcomes. We aimed to investigate the composite effect of the visit-to-visit variability in blood pressure, glucose, cholesterol, and body mass index on the risk of dementia. METHODS: A population-based cohort study including 2,930,816 subjects without a history of dementia, hypertension, diabetes mellitus, and dyslipidemia who underwent ≥ 3 health examinations was performed. The coefficient of variation (CV), standard deviation, and variability independent of the mean were calculated as variability indices. High variability was defined as having values in the highest quartile for each parameter. RESULTS: A total of 32,901 (1.12%) participants developed dementia, of which 74.4% and 11.0% were attributable to Alzheimer's disease and vascular dementia, respectively, during the median follow-up of 5.5 years. Individuals with higher variability of each parameter were at higher risk of future dementia. In the multivariable adjusted model, the hazard ratios and 95% confidence intervals of all-cause dementia were 1.22 (1.19-1.26) for one parameter, 1.39 (1.35-1.43) for two parameters, 1.54 (1.48-1.60) for three parameters, and 1.73 (1.60-1.88) for four parameters compared with subjects having no parameters of high variability measured as the CV. Consistent results were noted for Alzheimer's disease and vascular dementia, using other indices of variability and in various sensitivity and subgroup analyses. CONCLUSIONS: There was a linear association between the number of high variability parameters and risk of dementia. Reducing variability of metabolic parameters would be a target to preserve cognitive reserve in the general population.

Association between hemoglobin A1c variability and subclinical coronary atherosclerosis in subjects with type 2 diabetes.

AIMS: We examined the association between hemoglobin A1c (HbA1c) variability and subclinical coronary atherosclerosis in subjects with type 2 diabetes. METHODS: We used the multidetector coronary computed tomography data collected from subjects with type 2 diabetes who did not have a history of cardiovascular disease or angina symptoms. HbA1c measurements preceding the date of cardiac imaging were retrospectively collected, and intraindividual SD (HbA1c-SD), CV and adjusted SD of HbA1c measurements were calculated. Subclinical coronary atherosclerosis was defined as calcium score >400 without any cardiac symptoms. RESULTS: A total of 595 subjects were categorized according to the median value of each HbA1c variability indicators. The prevalence of subclinical coronary atherosclerosis was higher in higher HbA1c variability group compared with lower HbA1c variability group. Multivariable logistic regression analysis showed that higher HbA1c-SD and -CV were associated with the presence of subclinical coronary atherosclerosis, independent of mean HbA1c level in subjects with diabetes duration ≤10 years (OR [95% CI]; HbA1c-SD, 2.894 [1.105-7.584]; HbA1c-CV, 2.540 [1.022-6.316]). CONCLUSIONS: Long-term stabilization of blood glucose level might be important in preventing subclinical coronary atherosclerosis in subjects with earlier period of type 2 diabetes.