Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Income variability and incident cardiovascular disease in diabetes: a population-based cohort study.

BACKGROUND AND AIMS: Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). METHODS: Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30-64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. RESULTS: High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22-1.27; Ptrend < .001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35-1.41; Ptrend < .0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70-0.72; Ptrend < .0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. CONCLUSIONS: Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D.

Changes in physical activity and diabetes risk after cancer diagnosis: a nationwide cohort study.

PURPOSE: Physical activity has the potential to reduce the risk of diabetes after cancer diagnosis. However, current evidence supporting its effects is limited. This study aims to examine the associations between changes in physical activity and subsequent risk of diabetes among cancer survivors. METHODS: A total of 264,250 cancer survivors (mean age 56.7 (12.5) years, 44.2% males) without a prior history of diabetes were assessed for adherence to physical activity both before and after their diagnosis. The primary outcome was incident diabetes. The Fine-Gray proportional sub-distribution hazards model was used to calculate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for diabetes risk, considering death as a competing risk. RESULTS: Over a follow-up of 1,065,802 person-years, maintaining regular physical activity from pre-diagnosis was associated with a 10% reduced risk of diabetes after cancer diagnosis (sHR 0.90, 95% CI 0.85-0.96), considering traditional diabetes risk factors, sociodemographics, and primary cancer sites. Cancer survivors who became active and inactive after their cancer diagnosis exhibited a marginally decreased risk of diabetes (sHR 0.98, 95% CI 0.93-1.03; sHR 0.97, 95% CI 0.92-1.03). The strength and direction of the association varied depending on the primary site of cancer. CONCLUSIONS: Regular physical activity starting before a cancer diagnosis is associated with a lower risk of diabetes following the diagnosis, independent of established diabetes risk factors. IMPLICATIONS FOR CANCER SURVIVORS: The study underscores the importance of engaging in sufficient physical activity to mitigate the risk of diabetes in cancer survivors.

Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors.

BACKGROUND: The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment. METHODS: Using data from the Korean Health Insurance Service database (2010-2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities. RESULTS: BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00-1.13), but the association disappeared over time. Younger BCS (age < 40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98-3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older BCS, especially those aged > 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28-1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40-2.69 in those aged ≤ 50 years). CONCLUSIONS: Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS.

Association between healthy dietary patterns and markers of oxidative stress in the Sister Study.

PURPOSE: We assessed the cross-sectional association between healthy dietary patterns [alternate Mediterranean diet (aMED), Dietary Approaches to Stop Hypertension (DASH), alternative Healthy Eating Index (aHEI), and Healthy Eating Index 2015 (HEI-2015)] and urinary biomarkers of oxidative stress. METHODS: Between 2003 and 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35 to 74 (non-Hispanic White, 83.7%). Data were analyzed for 844 premenopausal and 454 postmenopausal women who had urine samples analyzed for F2-isoprostanes and non-missing covariate data. Food frequency questionnaire responses were used to calculate dietary pattern scores. Concentrations of 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were measured in urine samples by GC/MS for premenopausal women and LC/MS for postmenopausal women. Multivariable linear regression models were used to estimate associations between aMED, DASH, aHEI, and HEI-2015 and urinary F2-isoprostanes by menopausal status. Effect modification by sociodemographic, lifestyle, and clinical characteristics was also evaluated. RESULTS: Among premenopausal women, the four dietary indices were inversely associated with 8-iso-PGF2α (aMED ßQ4vsQ1: - 0.17, 95% CI - 0.27, - 0.08; DASH ßQ4vsQ1: - 0.18, 95% CI - 0.28, - 0.08; aHEI ßQ4vsQ1: - 0.20, 95% CI - 0.30, - 0.10; HEI-2015 ßQ4vsQ1: - 0.19, 95% CI - 0.29, - 0.10). In contrast, inverse associations with 8-iso-PGF2α-M were found for the continuous aMED, aHEI, and HEI-2015. Associations between dietary indices and 8-iso-PGF2α were generally stronger among younger women, women with lower income, and women with higher BMI. Similar results were observed among postmenopausal women, though only the continuous DASH and aHEI models were statistically significant. CONCLUSION: Healthy dietary patterns were associated with lower levels of oxidative stress.

Dietary patterns, socioeconomic disparities, and risk of type 2 diabetes in the Sister Study.

AIMS: We investigated the role of socioeconomic disparities in the association between diet and risk of type 2 diabetes (T2D). METHODS: We used prospective data from 40,243 Sister Study participants aged 35 to 74 years who were enrolled in 2003-2009. Scores for healthy eating indices (alternate Mediterranean diet, Dietary Approaches to Stop Hypertension, alternative Healthy Eating Index, and Healthy Eating Index 2015 (HEI-2015)) were calculated using data from a 110-item food frequency questionnaire completed at enrollment. Incident T2D was defined based on self-reported physician's diagnosis or use of anti-diabetic medications. Multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: We observed inverse associations between all four dietary indices and incident T2D after multivariable adjustment. These associations were most pronounced among women with higher educational attainment, higher income, and lower area deprivation index (ADI) (e.g., for the HEI-2015: low ADI, aHRQ4vsQ1: 0.44, 95% CI: 0.35, 0.56 vs high ADI, aHRQ4vsQ1: 0.75, 95% CI: 0.63, 0.90; pinteraction: 0.0007). CONCLUSIONS: Weaker associations among women with lower socioeconomic status and higher neighborhood deprivation suggests that other factors play a larger role in T2D incidence than diet quality among individuals with low SES.

Diabetes Mellitus in the Elderly Adults in Korea: Based on Data from the Korea National Health and Nutrition Examination Survey 2019 to 2020.

BACKGRUOUND: We evaluated the prevalence and management of diabetes mellitus (DM) in elderly Korean patients based on data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: A total of 3,068 adults aged 65 years and older (19.8% of total population) were analyzed using KNHANES from 2019 to 2020. Prevalence, awareness, treatment, and control rates, and comorbidities were analyzed. Lifestyle behaviors and energy intake were also measured. RESULTS: The prevalence of DM and prediabetes was 29.6% and 50.5%, respectively. The awareness, treatment and control rates were 76.4%, 73.3%, and 28.3%, respectively. The control rate was 77.0% if A1C <7.5% criteria was used. The mean A1C value of individuals with known DM was 7.1%, and 14.5% of the known DM patients had A1C ≥8.0%. Abdominal obesity, hypertension, and hypercholesterolemia were combined with DM in 63.9%, 71.7%, and 70.7%, respectively, and the rate of integrated management was 36.0% (A1C <7.5% criteria). A total of 40.1% of those with DM walked regularly. The percentage of energy intake from carbohydrates was higher in those with DM than in those without DM (P=0.044), while those of fat (P=0.003) and protein (P=0.025) were lower in those with DM than in those without DM in women. CONCLUSION: In 2019 to 2020, three of 10 adults aged 65 years and older in Korea had DM, and approximately 70% of them had comorbidities. A strategy for more individualized comprehensive care for the elderly patients with DM is urgently needed.

Association of general and central obesity, and their changes with risk of knee osteoarthritis: a nationwide population-based cohort study.

In this study, we aimed to evaluate the association between general and central obesity, and their changes with risk of knee osteoarthritis (OA) using retrospective cohort data collected from the Korean National Health Insurance Service. We studied 1,139,463 people aged 50 and over who received a health examination in 2009. To evaluate the association between general and/or central obesity and knee OA risk, a Cox proportional hazard models were used. Additionally, we investigate knee OA risk according to the change in obesity status over 2 years for subjects who had undergone health examinations for 2 consecutive years. General obesity without central obesity (HR 1.281, 95% CI 1.270-1.292) and central obesity without general obesity (HR 1.167, 95% CI 1.150-1.184) were associated with increased knee OA risk than the comparison group. Individuals with both general with central obesity had the highest risk (HR 1.418, 95% CI 1.406-1.429). This association was more pronounced in women and younger age group. Remarkably, the remission of general or central obesity over two years was associated with decreased knee OA risk (HR 0.884; 95% CI 0.867-0.902; HR 0.900; 95% CI 0.884-0.916, respectively). The present study found that both general and central obesity were associated with increased risk of knee OA and the risk was highest when the two types of obesity were accompanied. Changes in obesity status have been confirmed to alter the risk of knee OA.

Association between knee osteoarthritis and the risk of cardiovascular disease and the synergistic adverse effects of lack of exercise.

We aimed to determine whether knee OA is associated with CVD risk and all-cause death and to evaluate whether the association differs by exercise behavior. We used Korea National Health Insurance Service (KNHIS) database and included 201,466 participants (7572 subjects diagnosed with knee OA) who underwent health screening between 2009 and 2015. Those who had been diagnosed with knee OA or CVD before the index year were excluded. Cox proportional hazard models were used after adjusting for sociodemographic and CVD risk factors to evaluate the association between knee OA and CVD risk and all-cause death. Stratification analysis was further performed to determine the effect of exercise behavior on this relationship. During a median follow-up of 7.06 ± 2.24 years, 8743 CVD (2510 MI and 6553 stroke) cases developed. Individuals with knee OA had increased risks of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.15-1.38], myocardial infarction (MI) (HR 1.20, 95% CI 1.00-1.44), and stroke (HR 1.29, 95% CI 1.16-1.43) compared with those without knee OA. Those with knee OA who did not exercise had an increased risk of CVD (HR 1.25, 95% CI 1.11-1.40), whereas no significant increased CVD risk was observed in those with knee OA who exercised at least once a week (HR 1.11, 95% CI 0.96-1.28). There was no association between knee osteoarthritis and all-cause death. Knee OA was independently associated with an increased risk of CVD. Lack of exercise might have a synergistic adverse effect on the association between knee OA and CVD.

Comparison of Operational Definition of Type 2 Diabetes Mellitus Based on Data from Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey.

BACKGROUND: We evaluated the validity and reliability of the operational definition of type 2 diabetes mellitus (T2DM) based on the Korean National Health Insurance Service (NHIS) database. METHODS: Adult subjects (≥40 years old) included in the Korea National Health and Nutrition Examination Survey (KNHANES) from 2008 to 2017 were merged with those from the NHIS health check-up database, producing a cross-sectional dataset. We evaluated the sensitivity, specificity, accuracy, and agreement of the NHIS criteria for defining T2DM by comparing them with the KNHANES criteria as a standard reference. RESULTS: In the study population (n=13,006), two algorithms were devised to determine from the NHIS dataset whether the diagnostic claim codes for T2DM were accompanied by prescription codes for anti-diabetic drugs (algorithm 1) or not (algorithm 2). Using these algorithms, the prevalence of T2DM was 14.9% (n=1,942; algorithm 1) and 20.8% (n=2,707; algorithm 2). Good reliability in defining T2DM was observed for both algorithms (Kappa index, 0.73 [algorithm 1], 0.63 [algorithm 2]). However, the accuracy (0.93 vs. 0.89) and specificity (0.96 vs. 0.90) tended to be higher for algorithm 1 than for algorithm 2. The validity (accuracy, ranging from 0.91 to 0.95) and reliability (Kappa index, ranging from 0.68 to 0.78) of defining T2DM by NHIS criteria were independent of age, sex, socioeconomic status, and accompanied hypertension or dyslipidemia. CONCLUSION: The operational definition of T2DM based on population-based NHIS claims data, including diagnostic codes and prescription codes, could be a valid tool to identify individuals with T2DM in the Korean population.

Inflammatory potential of diet and risk of mortality in normal-weight adults with central obesity.

BACKGROUND & AIMS: Inflammatory potential of diet may contribute to poor health outcomes in individuals with metabolic disorders. In a representative sample of the U.S. population, we investigated the association between consuming a pro-inflammatory diet and mortality risk in adults with normal range of body mass index (BMI) but with central obesity. METHODS: This prospective cohort study included 3521 adults 20-90 years of age with normal BMI who participated in the National Health and Nutrition Examination Survey III, 1988-1994 and did not have a history of cardiovascular disease (CVD) or cancer and did not change their dietary intake in the year preceding baseline measurements. Mortality from all causes, CVD, and cancer was ascertained from the National Death Index. Normal-weight central obesity (NWCO, n = 1777) was defined as those with BMI 18.5 to <25 kg/m2 and waist-to-hip ratio (WHR) ≥0.85 in women and ≥0.90 in men. Severe central obesity was defined as WHR ≥0.92 in women and ≥1.00 in men. The dietary inflammatory index (DII®) was computed based on baseline dietary intake using 24-h dietary recalls, and associations with mortality were estimated using multivariable Cox proportional hazards regression. RESULTS: In individuals with NWCO, DII score (i.e., more pro-inflammatory diet) was associated with increased risk of CVD mortality (HRT3 vs T1, 1.89 [95% CI, 1.01-3.53], P trend = 0.04; HR 1 SD increase 1.29 [95% CI, 1.06-1.57]). This association was stronger with more severe central obesity (HRT3 vs T1, 2.79 [95% CI, 1.10-7.03], P trend = 0.03; HR 1 SD increase 1.52 [95% CI, 1.05-2.21]). DII score was not associated with increased risk of mortality in normal-weight individuals without central obesity or with risk of cancer mortality in either group. CONCLUSION: Among individuals in the normal-weight range of BMI, a pro-inflammatory diet assessed by high DII scores was associated with increased risk of CVD mortality in those with central obesity.

Comorbidities associated with high-risk obstructive sleep apnea based on the STOP-BANG questionnaire: a nationwide population-based study.

BACKGROUND/AIMS: We investigated the prevalence, associated factors, and comorbidities of high-risk obstructive sleep apnea (OSA) as determined by the STOP-BANG questionnaire in a Korean adult population. METHODS: Data were obtained from 7,650 adults (aged ≥ 40 years) who participated in the Korea National Health and Nutrition Examination Survey (2019-2020). Multiple logistic regression analyses were used to evaluate the association of socioeconomic status, lifestyle related factors, and comorbidities with high-risk OSA (STOP-BANG score, 5-8). RESULTS: The prevalence of high-risk OSA according to the STOP-BANG questionnaire was 12.0 %. Older age, male, current smoking, heavy alcohol consumption, and more comorbidities were associated with higher STOP-BANG scores. In multivariable adjusted analysis, diabetes mellitus (DM) (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.25 to 1.97), hypertension (OR, 4.81; 95% CI, 3.88 to 5.97), and obesity (OR, 2.02; 95% CI, 1.60 to 2.56) were associated with high risk of OSA, and when hypertension, DM, and obesity were combined, the risk increased synergistically (OR, 3.88; 95% CI, 2.94 to 5.11). CONCLUSION: According to the STOP-BANG questionnaire, the high risk of OSA was more common in males, and was associated with chronic metabolic disease, particularly in those with DM, hypertension, and obesity combined. Active OSA screening, prevention, and management may be beneficial to improving health outcomes related to OSA in these populations.

Duration of diabetes mellitus and risk of kidney and bladder cancer: a longitudinal nationwide cohort study.

Previous studies have suggested that diabetes mellitus (DM) may increase the risk of kidney and bladder cancer; however, little is known about the duration of DM. We aimed to analyze the risk of kidney and bladder cancer according to the duration of DM in a longitudinal nationwide cohort. This study was conducted in a cohort of 9,773,462 participants ≥ 20 years old who underwent a National Health Examination in 2009 and were followed up until December 2017. Cox-proportional hazard models were used to evaluate the risk of kidney and bladder cancer in relation to the duration of DM. During follow-up (mean 7.3 years), kidney and bladder cancer occurred in 11,219 and 13,769 participants, respectively. DM was associated with an increased risk of kidney and bladder cancer (hazard ratio (HR), 95% confidence interval (95% CI); 1.14, 1.09-1.20 and 1.23, 1.17-1.28, respectively). Compared to fasting glucose < 100 mg/dL, impaired fasting glucose (IFG) and longer DM duration were associated with increased risks (HR, 95% CI): IFG (1.05, 1.01-1.10), new-onset DM (1.13, 1.03-1.24), DM < 5 years (1.11, 1.02-1.20), and DM ≥ 5 years (1.25, 1.15-1.36) in kidney cancer; IFG (1.05, 1.01-1.09), new-onset DM (1.10, 1.01-1.19), DM < 5 years (1.26, 1.18-1.35), and DM ≥ 5 years (1.34, 1.26-1.43) in bladder cancer, respectively. Our findings suggest that the subjects with IFG and longer duration of DM had a higher risk for kidney and bladder cancer than those without DM.

Association Between Metabolic Syndrome and Risk of Esophageal Cancer: a Nationwide Population-Based Study.

BACKGROUND: Metabolic syndrome (MetS) is believed to increase the risk of esophageal cancer. However, most studies have been conducted in Western countries, focusing on esophageal adenocarcinoma (EAC). We aimed to investigate the association between MetS and risk of esophageal cancer in nationally representative large dataset in Korea, where esophageal squamous cell carcinoma (ESCC) is predominant. METHODS: We analyzed the health examinations and claims data from the Korean National Health Insurance Service (NHIS). A total of 6,795,738 subjects who received an NHIS provided health examination in 2009 (index year) were included. Cox proportional hazards models were used to estimate multivariable adjusted HRs (aHR) and 95% confidence intervals (CI) for the association of MetS and its components (elevated waist circumference, blood pressure, triglycerides, fasting blood glucose, reduced high-density lipoprotein cholesterol) with the risk of esophageal cancer. RESULTS: During a mean (± SD) follow-up of 8.2 (± 1.1) years, 6,414 cases of esophageal cancer occurred. MetS was associated with an increased risk of esophageal cancer (aHR, 1.11; 95% CI, 1.05-1.18). Among the components of MetS, elevated waist circumference (aHR, 1.24; 95% CI, 1.16-1.33), high blood pressure (aHR, 1.29; 95% CI, 1.22-1.37), and fasting blood glucose (aHR, 1.16; 95% CI, 1.11-1.22) were associated with increased risk of esophageal cancer. CONCLUSIONS: MetS was associated with an increased risk of esophageal cancer. IMPACT: Our findings suggest that individuals with MetS may be at increased risk for esophageal cancer, specifically ESCC. Further studies are needed to establish the relationship between MetS and esophageal cancer.

Association of weight change following smoking cessation with the risk of tuberculosis development: A nationwide population-based cohort study.

BACKGROUND: Smoking or weight loss is a risk of tuberculosis (TB) development. However, the impact of weight change after smoking cessation on the occurrence of TB remains elusive. We aimed to determine the relationship between weight change after smoking cessation and the risk of TB development. METHODS: We conducted a population-based cohort study using the national database in Republic of Korea. Of the 10,490,491 subjects who underwent health check-up in 2009, we enrolled 9,953,124 subjects without a previous TB history and followed them until 2017. We divided all study participants into the following three groups: never, former, and current smokers. The primary endpoint was newly developed TB. RESULTS: Among 9,953,124 subjects analyzed, 5,922,845 (59.5%) were never smokers, 1,428,209 (14.4%) were former smokers, and 2,602,080 (26.1%) were current smokers. The risk of TB development was significantly higher in current smokers than in never smokers (adjusted hazard ratio (aHR) 1.158; 95% confidence interval [CI] 1.131-1.186). Among current smokers, individuals who stopped smoking and maintained weight after baseline evaluation had a significantly lower risk of TB development compared with those who continued to smoke (aHR 0.771; 95% CI 0.741-0.892). However, even after smoking cessation, individuals who lost weight were at a significantly higher risk of TB development compared with those who continued to smoke (aHR 1.327; 95% CI 1.119-1.715). CONCLUSIONS: Our findings suggest that smoking is a risk factor for TB and weight maintenance (neither gaining or losing) after quitting smoking might reduce the risk of TB development.

Adherence to healthy lifestyle behaviors as a preventable risk factor for severe hypoglycemia in people with type 2 diabetes: A longitudinal nationwide cohort study.

AIMS/INTRODUCTION: We investigated the associations between a combination of lifestyle factors and changes to these factors and the subsequent risk of severe hypoglycemia (SH) in type 2 diabetes patients. MATERIALS AND METHODS: Individuals with adult type 2 diabetes who underwent consecutive 2-year interval health screening programs from 2009 to 2012 from the Korean National Health Insurance Service database were included and followed up until 2018. Information on history of smoking status, alcohol consumption and physical activity, as well as changes to these factors, was obtained. The primary outcome was incident SH. RESULTS: Of the 1,490,233 type 2 diabetes patients, 30,539 (2.1%) patients developed SH. Current smokers and heavy drinkers had increased risk of SH, compared with non-smokers and non-drinkers, respectively (hazard ratio 1.28, 95% confidence interval 1.23-1.34; hazard ratio 1.22, 95% confidence interval 1.15-1.30). However, regular physical activity was associated with reduced SH risk (hazard ratio 0.79, 95% confidence interval 0.77-0.82). A combination of unhealthy lifestyle habits was associated with increased SH risk in a dose-dependent fashion (P for trend <0.001). Compared with participants without changes in their unhealthy lifestyles, participants who improved lifestyles had decreased risk of SH. CONCLUSIONS: Greater adherence to healthy lifestyle factors and any improvement in unhealthy lifestyle habits were associated with a substantially lower risk of SH in individuals with type 2 diabetes.

Association of dietary and plasma carotenoids with urinary F2-isoprostanes.

PURPOSE: Carotenoids may protect against chronic diseases including cancer and cardiometabolic disease by mitigating oxidative stress and/or inflammation. We cross-sectionally evaluated associations between carotenoids and biomarkers of oxidative stress or inflammation. METHODS: From 2003 to 2009, the Sister Study enrolled 50,884 breast cancer-free US women aged 35-74. Post-menopausal participants (n = 512) were randomly sampled to measure carotenoids and biomarkers of oxidative stress. Dietary carotenoid consumption was assessed using a validated 110-item Block 1998 food frequency questionnaire; use of ß-carotene-containing supplements was also assessed. Plasma carotenoids were quantified, adjusting for batch. Urinary markers of lipid peroxidation, 8-iso-prostaglandin F2α (8-iso-PGF2α) and its metabolite (8-iso-PGF2α-M) were also measured. Since the biomarker 8-iso-PGF2α can reflect both oxidative stress and inflammation, we used a modeled 8-iso-PGF2α to prostaglandin F2α ratio approach to distinguish effects reflecting oxidative stress versus inflammation. Multivariable linear regression was used to assess the associations of dietary and plasma carotenoids with the estimated biomarker concentrations. RESULTS: Total plasma carotenoids were inversely associated with 8-iso-PGF2α-M concentrations (P for trend across quartiles = 0.009). Inverse trends associations were also seen for α-carotene and ß-carotene. In contrast, lutein/zeaxanthin showed associations with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations. The inverse association for total carotenoids appeared to be specific for oxidative stress (chemical 8-iso-PGF2α; Phighest vs. lowest quartile = 0.04 and P for trend across quartiles = 0.02). The pattern was similar for α-carotene. However, lutein/zeaxanthin tended to have a stronger association with enzymatic 8-iso-PGF2α, suggesting an additional anti-inflammatory effect. Supplemental ß-carotene was inversely associated with both 8-iso-PGF2α and 8-iso-PGF2α-M concentrations, as well as with both chemical and enzymatic 8-iso-PGF2α. Dietary carotenoids were not associated with either biomarker. CONCLUSION: Plasma carotenoids and supplemental ß-carotene were associated with lower concentrations of 8-iso-PGF2α metabolite. Plasma carotenoids associations may reflect antioxidant effects.

Synergistic association between underweight and type 2 diabetes on the development of laryngeal cancer: a national population-based retrospective cohort study.

BACKGROUND: Although cigarette smoking is the most significant risk factor for laryngeal cancer, other risk factors might also be associated with the development of laryngeal cancer. We investigated whether underweight and type 2 diabetes are associated with laryngeal cancer in a Korean population. METHODS: A total of 9,957,059 participants (≥20 years) without prior history of cancer who underwent a National Health Insurance Service health checkup in 2009 were followed up until December 31, 2018. Newly diagnosed laryngeal cancer was identified using claim data, and underweight was defined as body mass index (BMI) < 18.5 kg/m2. A Cox proportional-hazards models with multivariable adjustment were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CIs). RESULTS: During the median follow-up period of 8.3 years, 3504 cases of laryngeal cancer occurred. Underweight was associated with increased risk of laryngeal cancer after adjusting for potential confounders (HR: 1.43, 95% CI: 1.22-1.69) compared to those who were not underweight. Underweight and type 2 diabetes were synergistically associated with higher risk of laryngeal cancer (HR: 2.33, 95% CI: 1.54-3.51), compared to those without either condition. This relationship was stronger in those with an age < 65 years (HR: 3.33, 95% CI: 1.88-5.87) and alcohol consumption (HR: 2.72, 95% CI: 1.64-4.53). CONCLUSIONS: These results suggest that underweight may be a significant risk factor for laryngeal cancer and that underweight and type 2 diabetes might synergistically increase the risk of laryngeal cancer.

Association of Metabolic Parameter Variability with Esophageal Cancer Risk: A Nationwide Population-Based Study.

Introduction: Certain metabolic parameters increase the risk of esophageal cancer. This study investigated the association between the variability in metabolic parameters and esophageal cancer incidence using large nationally representative data. Methods: Using the health checkup and claims data provided by the Korean National Health Insurance Service (NHIS), we included 8,376,233 subjects who underwent NHIS-provided health checkups between 2009 and 2010 (index year) and two or more health checkups within five years before the index year. Hazard ratios (HRs) and 95% confidence intervals (CIs) for esophageal cancer were obtained using Cox proportional hazards models according to the quartiles of variability of each metabolic parameter: fasting blood glucose (FBG), weight, systolic blood pressure (SBP), and total cholesterol (TC) as well as a cumulative number of high-variability parameters. Results: A total of 6,455 cases of esophageal cancer occurred during a mean (±SD) follow-up of 8.8 (±1.1) years. The following metabolic parameters were used, with an adjusted HR and 95% CI: FBG (1.11, 1.03-1.18), weight (1.15, 1.07-1.23), SBP (1.08, 1.01-1.16), and TC (1.23, 1.15-1.32). The risk of esophageal cancer was higher in the highest quartile of variability than the lower quartiles. The risk of esophageal cancer gradually increased with a greater number of high-variability parameters: 1.08 (1.02-1.15), 1.22 (1.14-1.31), and 1.33 (1.21-1.46) for 1, 2, and 3-4 high-variability parameters (vs. none). Conclusions: A high variability of metabolic parameters was associated with an increased esophageal cancer risk. Further studies are needed to replicate our findings in other populations.