Long-term Psychiatric and Endocrine Complications Following Hematopoietic Stem Cell Transplantation in Hematologic Disease in Korea: A Nation-Wide Cohort Study.

PURPOSE: Numerous patients experience long-term complications after hematopoietic stem cell transplantation (HSCT). This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses. MATERIALS AND METHODS: We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases, 10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis. RESULTS: A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation-based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, total body irradiation-based conditioning regimen, and non-antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus. CONCLUSION: The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

Clinical validation of a deep-learning-based bone age software in healthy Korean children.

PURPOSE: Bone age (BA) is needed to assess developmental status and growth disorders. We evaluated the clinical performance of a deep-learning-based BA software to estimate the chronological age (CA) of healthy Korean children. METHODS: This retrospective study included 371 healthy children (217 boys, 154 girls), aged between 4 and 17 years, who visited the Department of Pediatrics for health check-ups between January 2017 and December 2018. A total of 553 left-hand radiographs from 371 healthy Korean children were evaluated using a commercial deep-learning-based BA software (BoneAge, Vuno, Seoul, Korea). The clinical performance of the deep learning (DL) software was determined using the concordance rate and Bland-Altman analysis via comparison with the CA. RESULTS: A 2-sample t-test (P<0.001) and Fisher exact test (P=0.011) showed a significant difference between the normal CA and the BA estimated by the DL software. There was good correlation between the 2 variables (r=0.96, P<0.001); however, the root mean square error was 15.4 months. With a 12-month cutoff, the concordance rate was 58.8%. The Bland-Altman plot showed that the DL software tended to underestimate the BA compared with the CA, especially in children under the age of 8.3 years. CONCLUSION: The DL-based BA software showed a low concordance rate and a tendency to underestimate the BA in healthy Korean children.

Long-Term Effect on Ovarian Function After Uterine Artery Embolization During the Postpartum Period: A Nationwide Population-Based Study.

Uterine artery embolization(UAE) is widely used in obstetrical indications, including postpartum bleeding and placental implantation abnormality, to manage many conditions to conserve the uterus. However, physicians are concerned about future fertility or ovarian function due to the occlusion of major pelvic vessels in the uterine artery embolization. However, there are limited data related to UAE usage during the postpartum period. This study was to evaluate the impact of UAE during the postpartum period on primary ovarian failure(POF), menstrual disorders, and infertility in women. Using the Korea National Health Insurance claims database, all pregnant women who delivered between January 2007 and December 2015 and underwent UAE during the postpartum period were identified. The occurrence of POF, female infertility, and menstrual disorders after delivery was evaluated. Using Cox proportional hazards models, the adjusted hazard ratios and 95% confidence intervals were estimated. 779,612 cases were analyzed in the study with 947 women in the UAE group. After delivery, the incidence of POF (0.84% vs.0.27%, P<.0001) and female infertility (10.24% vs. 6.89%, P<.0001) were higher in UAE group than in the control group. After adjusting for covariates, the POF risk was significantly higher in UAE group than in the control group (HR 2.37, 95% CI 1.16-4.82). The risk for the disorder of menstrual frequency (HR 1.28, 95% CI 1.10-1.50) and female infertility (HR 1.37, 95% CI 1.10-1.71) was significantly higher in UAE group than in the control group. This study confirmed UAE during the postpartum period is a risk factor for POF after delivery.

Risk of adverse obstetric outcomes in patients with a history of endometrial cancer: A nationwide population-based cohort study.

OBJECTIVE: To evaluate adverse obstetric outcomes in women with a history of endometrial cancer (EC). DESIGN: Population-based cohort study. SETTING: The Korean National Health Insurance (KNHI) claims database. POPULATION: Women who gave birth between 2009 and 2016, with a history of EC prior to pregnancy. METHODS: The KNHI database was used to compare obstetric outcomes of women with and without a history of EC, using the ICD-10 codes. Multivariable logistic regression models were used to determine the associations between a history of EC and adverse obstetric outcomes. MAIN OUTCOMES MEASURES: Adverse obstetric outcomes. RESULTS: Overall, 248 and 3 335 359 women with and without a history of EC, respectively, gave birth. When adjusted for age, primiparity and comorbidities, an increased risk of multiple gestations (odds ratio [OR] 4.925, 95% confidence interval [CI] 3.394-7.147), caesarean delivery (OR 2.005, 95% CI 1.535-2.62) and preterm birth (OR 1.941, 95% CI 1.107-3.404) was observed among women with a history of EC. We were unable to demonstrate significant differences in the risk of pre-eclampsia, gestational diabetes, vacuum delivery, placenta praevia, placenta accreta spectrum, placental abruption and postpartum haemorrhage between the groups. In the sensitivity analyses excluding multiple gestations, an increased risk of preterm birth was not observed among women with a history of EC (OR 1.276, 95% CI 0.565-2.881). CONCLUSIONS: There is no convincing evidence of an increased risk of adverse obstetric outcomes among women with a history of EC. Our findings would be useful in counselling of patients with EC who are undergoing fertility-sparing treatment.

Statin use in patients with hormone receptor-positive metastatic breast cancer treated with everolimus and exemestane.

BACKGROUND: We analyzed the effect of statins in patients with hormone receptor-positive (HR+) metastatic breast cancer treated with everolimus + exemestane (EverX). MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using the National Health Insurance database with patients who received EverX for metastatic breast cancer between 2011 and 2019. RESULTS: Of 224,948 patients diagnosed with breast cancer, 1749 patients who received EverX for at least 30 days were included. Among them, 500 (28.6%) patients were found to take statins with EverX treatment (statin group), and the median duration of this combination was 5.36 months. The median time to treatment duration (TTD) for EverX and the overall survival (OS) were significantly higher in the statin group than in the no-statin group [7.69 vs. 5.06 months, p < 0.001; 45.7 vs. 26.0 months, p < 0.001, respectively]. Multivariable Cox analysis revealed that the use of statins was associated with prolonged TTD [HR = 0.67 (95% CI, 0.59-0.77)] and OS [HR = 0.57 (95% CI, 0.46-0.70)] for EverX even after adjustment for other covariates. CONCLUSION: Statins may have synergistic effects with endocrine therapy with the mTOR inhibitor everolimus, and improve survival in patients with HR+ metastatic breast cancer.

Long-term risks of coronary heart disease and cerebrovascular disease in ovarian, uterine and cervical cancer survivors: a nationwide study in Korea.

Only few studies have evaluated the incidence of coronary heart disease (CHD) and cerebrovascular disease (CVD) among gynaecologic cancer survivors. We selected 26,880 gynaecologic cancer patients who underwent health check-ups within 2 years after diagnosis using the Korean National Health Insurance Service Database. They were compared with 79,830 non-cancer controls. Cox regression models were used to estimate hazard ratios (HRs). There was no significant relationship between gynaecologic cancer survivors and CHD or CVD events. However, 10 years after diagnosing cancers, the risk of angina increased in cancer survivors (adjusted HR = 1.193, 95% CI: 1.013-1.406). After 1 year of diagnosis, cancer patients with no initial comorbidities showed an increased risk of all CHD and CVD events (adjusted HR = 1.101, 95% CI: 1.020-1.189) and CHD alone (adjusted HR = 1.168, 95% CI: 1.055-1.293) compared with controls. CHD risk was also higher in the cancer group with no comorbidities after 10 years of diagnosis (adjusted HR = 1.284, 95% CI: 1.020-1.615). Overall, the risk of CHD or CVD did not increase in gynaecologic cancer survivors. However, cancer patients without any comorbidities showed a higher risk of CHD compared with control, the risk persisting until 10 years after cancer diagnosis.Impact StatementWhat is already known on this subject? Cardiovascular risk and the incidence of stroke increase after cancer diagnosis.What do the results of this study add? The risk of coronary heart disease (CHD) and cerebrovascular disease did not increase in Asian (especially Korean) gynaecologic cancer survivors compared with the general population. However, cancer patients without any comorbidities showed a higher risk of CHD compared with the non-cancer population.What are the implications of these findings for clinical practice and/or further research? Our results imply the importance of surveillance of cardiovascular risks among patients with gynaecologic cancer without comorbidities.

Pregnancy outcomes of immigrant women living in Korea: A population-based study.

Although there is a high rate of pregnant immigrant women in Korea, little is known regarding their pregnancy outcomes. The aim of this study was to evaluate the pregnancy outcomes of immigrant women in Korea. Data for all pregnant women who gave birth between January 1, 2007 and December 31, 2016 were obtained using the Health Insurance Review and Assessment Service Database. Pregnant women were divided into two groups: Korean and immigrant women. The main outcome measures were adverse pregnancy outcomes including gestational diabetes of mellitus, preeclampsia, cesarean section, placental abrnomalities, and postpartum hemorrhage. The odds of gestational diabetes mellitus, preeclampsia, cesarean section, placental previa, placental abruptio, and postpartum hemorrhage was compared between the two groups. Among 4,439,778 pregnant women who gave birth during the study period, 168,940 (3.8%) were immigrant women. The odds of gestational diabetes mellitus (adjusted OR: 1.24; 95% CI: 1.21, 1.28), and cesarean section (adjusted OR: 1.26; 95% CI: 1.25-1.28)were higher in immigrant women than in Korean women, but the odds of preeclampsia (adjusted OR: 0.84; 95% CI: 0.81-0.86) and postpartum hemorrhage (adjusted OR 0.96, 95% CI 0.94-0.97) was lower in immigrant women than in Korean women. Immigrant women had different pregnancy outcomes. Pregnancy and postpartum management that reflects these characteristics will be necessary for immigrant women.

The risk for future cerebrovascular disease in pregnant women with Moyamoya disease: a nationwide population-based study in South Korea.

BACKGROUND: Physiologic changes during pregnancy affect the development of postpartum cerebrovascular disease (CVD) in women with Moyamoya disease. Due to the rare prevalence of Moyamoya disease and its large regional variations, large-scale based studies on the risk of CVD after delivery have not been conducted. This study aimed to evaluate whether women with Moyamoya disease have an increased risk of CVD after delivery. METHODS: Research data was collected from the National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Patients who delivered in Korea from 2007 to 2014 were enrolled in this study. We classified women as having CVD if they were diagnosed with any of the following conditions between delivery and December 31, 2016; cerebral infarction (I63.X in the International Classification of Diseases-10th Revision [ICD-10]) and/or intracranial hemorrhage (I61.X, I62.X in ICD-10) and/or subarachnoid hemorrhage (I60.X in ICD-10). Women with Moyamoya disease were identified as having I67.5 in ICD-10. We matched the study cohort by the ratio of 1:10 to analyze the risk CVD occurrence. The matching technique applied in this study was based on the variables of age and parity. To evaluate the adjusted hazard ratio (HR) for CVD in women with Moyamoya disease, we used multivariate Cox proportional hazard regression. RESULTS: Among a total of 3,611,216 Korean women who underwent delivered, we identified 412 women with Moyamoya disease diagnosis and 1420 age- and parity-matched women without Moyamoya disease (control). Compared to the control group, women with Moyamoya disease had a significantly higher rate of Cesarean section, overt DM, and essential hypertension (all p < 0.0001). Among women with Moyamoya disease, 55 (13.35%) women developed CVD within the follow-up postpartum period. The presence of Moyamoya disease was associated with an increased risk of CVD after delivery (adjusted HR 37.42; 95% confidence interval (CI) 17.50-80.02 within 2.3 years) after adjusting for pregnancy-induced hypertension, gestational diabetes mellitus, pregestational diabetes, chronic hypertension. CONCLUSION: This population based study showed that the occurrence rate of CVD after delivery was higher in women with Moyamoya disease than in those without. Therefore, careful and long-term postpartum surveillance is required for women with Moyamoya disease.

Pre-pregnancy blood pressure and pregnancy outcomes: a nationwide population-based study.

BACKGROUND: Hypertension has been known to increase the risk of obstetric complications. Recently, the American College of Cardiology endorsed lower thresholds for hypertension as systolic blood pressure of 130-139 mmHg or diastolic blood pressure 80-89 mmHg. However, there is a paucity of information regarding the impact of pre-pregnancy blood pressure on pregnancy outcomes. We aimed to evaluate the effect of pre-pregnancy blood pressure on maternal and neonatal complications. METHODS: In this nationwide, population based study, pregnant women without history of hypertension and pre-pregnancy blood pressure < 140/90 mmHg were enrolled. The primary outcome of composite morbidity was defined as any of the followings: preeclampsia, placental abruption, stillbirth, preterm birth, or low birth weight. RESULTS: A total of 375,305 pregnant women were included. After adjusting for covariates, the risk of composite morbidity was greater in those with stage I hypertension in comparison with the normotensive group (systolic blood pressure, odds ratio = 1.68, 95% CI: 1.59 - 1.78; diastolic blood pressure, odds ratio = 1.56, 95% CI: 1.42 - 1.72). There was a linear association between pre-pregnancy blood pressure and the primary outcome, with risk maximizing at newly defined stage I hypertension and with risk decreasing at lower blood pressure ranges. CONCLUSIONS: 'The lower, the better' phenomenon was still valid for both maternal and neonatal outcomes. Our results suggest that the recent changes in diagnostic thresholds for hypertension may also apply to pregnant women. Therefore, women with stage I hypertension prior to pregnancy should be carefully observed for adverse outcomes.

Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study.

BACKGROUND: We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults. METHODS: The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616). RESULTS: During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up. CONCLUSION: Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

External validation of deep learning-based bone-age software: a preliminary study with real world data.

Artificial intelligence (AI) is increasingly being used in bone-age (BA) assessment due to its complicated and lengthy nature. We aimed to evaluate the clinical performance of a commercially available deep learning (DL)-based software for BA assessment using a real-world data. From Nov. 2018 to Feb. 2019, 474 children (35 boys, 439 girls, age 4-17 years) were enrolled. We compared the BA estimated by DL software (DL-BA) with that independently estimated by 3 reviewers (R1: Musculoskeletal radiologist, R2: Radiology resident, R3: Pediatric endocrinologist) using the traditional Greulich-Pyle atlas, then to his/her chronological age (CA). A paired t-test, Pearson's correlation coefficient, Bland-Altman plot, mean absolute error (MAE) and root mean square error (RMSE) were used for the statistical analysis. The intraclass correlation coefficient (ICC) was used for inter-rater variation. There were significant differences between DL-BA and each reviewer's BA (P < 0.025), but the correlation was good with one another (r = 0.983, P < 0.025). RMSE (MAE) values were 10.09 (7.21), 10.76 (7.88) and 13.06 (10.06) months between DL-BA and R1, R2, R3 BA. Compared with the CA, RMSE (MAE) values were 13.54 (11.06), 15.18 (12.11), 16.19 (12.78) and 19.53 (17.71) months for DL-BA, R1, R2, R3 BA, respectively. Bland-Altman plots revealed the software and reviewers' tendency to overestimate the BA in general. ICC values between 3 reviewers were 0.97, 0.85 and 0.86, and the overall ICC value was 0.93. The BA estimated by DL-based software showed statistically similar, or even better performance than that of reviewers' compared to the chronological age in the real world clinic.

Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study.

CONTEXT: Abnormal thyroid function after thyroidectomy and subsequent thyroid-stimulating hormone suppression can have detrimental effects on glucose homeostasis in patients with thyroid cancer. OBJECTIVE: To investigate whether thyroidectomy increases the risk of type 2 diabetes in patients with thyroid cancer and to explore the association between levothyroxine dosage and type 2 diabetes risk. METHODS: A retrospective population-based cohort study using the Korean National Health Insurance database. We included 36 377 thyroid cancer patients without known diabetes who underwent thyroidectomy between 2004 and 2013. Matched subjects with nonthyroid cancer were selected using 1:1 propensity score matching. The main outcome measure was newly developed type 2 diabetes mellitus. RESULTS: Patients with thyroid cancer who underwent thyroidectomy had a higher risk of developing type 2 diabetes mellitus than the matched controls (hazard ratio [HR] 1.43, 95% CI 1.39-1.47). Among patients with thyroid cancer, when the second quartile group (in terms of the mean levothyroxine dosage; 101-127 µg/day) was considered the reference group, the risk of type 2 diabetes mellitus increased in the first quartile (<101 µg/day; HR 1.45, 95% CI 1.36-1.54) and fourth quartile groups (≥150 µg/day; HR 1.37, 95% CI 1.29-1.45); meanwhile, the risk decreased in the third quartile group (128-149 µg/day; HR 0.91, 95% CI 0.85-0.97). CONCLUSION: Patients with thyroid cancer who underwent thyroidectomy were more likely to develop type 2 diabetes mellitus than the matched controls. There was a U-shaped dose-dependent relationship between the levothyroxine dosage and type 2 diabetes mellitus risk.

Risk of Diabetes in Patients with Long-Standing Graves' Disease: A Longitudinal Study.

BACKGROUND: The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. METHODS: The risk of diabetes in patients with Graves' disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. RESULTS: A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). CONCLUSION: The risk of diabetes was significantly higher in patients with long-standing Graves' disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

Pregnancy Outcomes Following Laparoscopic and Open Surgery in Pelvis during Pregnancy: a Nationwide Population-based Study in Korea.

BACKGROUND: Non-obstetric surgery during pregnancy is associated with adverse obstetric and fetal outcomes. The aim of this study was to investigate the risk of adverse pregnancy outcomes for women who underwent non-obstetric pelvic surgery during pregnancy compared with that of women that did not undergo surgery. METHODS: Study data from women who gave birth in Korea were collected from the Korea National Health Insurance claims database between 2006 and 2016. We identified pregnant women who underwent abdominal non-obstetric pelvic surgery by laparoscopy or laparotomy from the database. Pregnancy outcomes including preterm birth, low birth weight (LBW), cesarean section (C/S), gestational hypertension, gestational diabetes, and postpartum hemorrhage were identified. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the pregnancy outcomes were estimated by multivariate regression models. RESULTS: Data from 4,439,778 women were collected for this study. From 2006-2016, 9,417 women from the initial cohort underwent non-obstetric pelvic surgery (adnexal mass resection, appendectomy) during pregnancy. Multivariate logistic regression analysis indicated that preterm birth (HR, 2.01; 95% CI, 1.81-2.23), LBW (HR, 1.62; 95% CI, 1.46-1.79), C/S (HR, 1.13; 95% CI, 1.08-1.18), and gestational hypertension (HR, 1.35; 95% CI, 1.18-1.55) were significantly more frequent in women who underwent non-obstetric surgery during pregnancy compared to pregnant women who did not undergo surgery. When the laparoscopic and laparotomy groups were compared for risk of fetal outcomes, the risk of LBW was significantly decreased in laparoscopic adnexal resection during pregnancy compared to laparotomy (odds ratio, 0.62; 95% CI, 0.40-0.95). CONCLUSION: Non-obstetric pelvic surgery during pregnancy was associated with a higher risk of preterm birth, LBW, gestational hypertension, placenta previa, placental abruption, and C/S. Although the benefits and safety of laparoscopy during pregnancy appear similar to those of laparotomy in regard to pregnancy outcomes, laparoscopic adnexal mass resection was associated with a lower risk of LBW.

Prepregnancy hemoglobin levels and gestational diabetes mellitus in pregnancy.

AIM: To identify the influence of prepregnancy hemoglobin levels on gestational diabetes mellitus. MATERIALS AND METHODS: Korean women who had given birth between January 1st, 2006 and December 31st, 2015 and who had undergone a biannual national health screening examination within 6 months prior to pregnancy were enrolled. Subjects were divided into three groups according to their hemoglobin levels. Multivariate logistic regression analysis was used to estimate the adjusted odds ratio and 95% confidence interval for GDM. RESULTS: Of the 366,122 participants, GDM developed in 14,799 (4%) women. More specifically, GDM developed in 3.6% of women with prepregnancy anemia (hemoglobin < 11 g/dL), 3.57% with normal hemoglobin levels, and 4.47% with hemoglobin levels higher than 13 g/dL. We did not find any association between prepregnancy anemia and the risk of developing GDM (OR 1.002 [95% CI 0.90-1.11]). After adjusting for potential confounding factors (adjusted odds ratio 1.41; 95% CI 1.29-1.54), high hemoglobin levels were associated with insulin requiring GDM. CONCLUSIONS: Our study identified an association between high prepregnancy hemoglobin levels and GDM risk.

Triglyceride and glucose index and the risk of gestational diabetes mellitus: A nationwide population-based cohort study.

AIMS: Pre-pregnancy insulin resistance is one of the main pathophysiologies of gestational diabetes mellitus (GDM). Triglyceride-glucose (TyG) index is a marker of insulin resistance. We aimed to evaluate the association between pre-pregnancy TyG index and GDM in primipara women. METHODS: A total of 380,208 women who underwent a Korean national health screening exam within 2 years before their first delivery, between January 1, 2012 and December 31, 2015, were included. The TyG index was calculated as ln [triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. RESULTS: Among the 380,208 primipara women, 17,239 women were diagnosed with GDM (4.53%). Multivariate logistic regression analysis adjusted for risk factors showed a higher odds ratio of 1.73 for GDM (95% CI 1.65-1.81) in the highest quartile than that in the lowest quartile. A 1-SD increase in the TyG index increased the risk of GDM (31%) and GDM requiring insulin therapy (82%) in the fully adjusted model. A 1-unit increase in the TyG index significantly increased the risk of GDM and GDM requiring insulin treatment by 1.81 and 3.69 times, respectively.The impact of a high TyG index on the risk of GDM was more profound in the subjects aged ≥ 35 years, with obesity, with impaired fasting glucose, who are current smokers, and with a family history of diabetes mellitus. CONCLUSIONS: Increased pre-pregnancy TyG index is associated with a risk of GDM. Elevation of the TyG index may be an early marker of GDM.

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study.

INTRODUCTION: Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM. METHODS: We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements. RESULTS: In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18-1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend <0.001). A 1-SD increase in FPG variability assessed by VIM was significantly associated with a 10.0% increase in gastric cancer risk in the fully adjusted model. DISCUSSION: In a DM-free population, high variability in visit-to-visit FPG levels was independently associated with an increased risk of gastric cancer.

Secular trends in cesarean sections and risk factors in South Korea (2006-2015).

OBJECTIVE: This study aimed to investigate trends in the rate of cesarean sections (CSs) in South Korea from 2006 to 2015 and identify the risk factors associated with these changes. METHODS: Using the National Health Insurance Corporation dataset, all women who gave birth between 2006 and 2015 were included in the study. We investigated 1) the mode of delivery, 2) the complication rates during pregnancy (i.e., preeclampsia and placenta previa), and 3) pre-pregnancy factors (body mass index, hypertension [HTN], diabetes mellitus [DM], and other pre-existing medical conditions), and their trends during the study period. RESULTS: Over 10 years, the rate of CS increased from 36.3% in 2006 to 40.6% in 2015 (P<0.01). The rate of CS increased in primiparous women, women with multiple pregnancy, and women with preeclampsia. Maternal age and the incidence of placenta previa also increased. In contrast, the rate of vacuum deliveries and vaginal birth after CS decreased during the study period. The rate of women with pre-pregnancy obesity and DM increased, but the rate of women with pre-pregnancy HTN decreased. CONCLUSION: The rate of CS in South Korea increased from 2006 to 2015. This trend may reflect changes in the rate of different risk factors. Identifying the causes of the increasing CS trend observed in this study will allow clinicians to monitor these factors and possibly reduce the rate of CS.

Association of fasting plasma glucose variability with gestational diabetes mellitus: a nationwide population-based cohort study.

OBJECTIVE: Long-term glycemic variability has recently been recognized as another risk factor for future adverse health outcomes. We aimed to evaluate the risk of gestational diabetes mellitus (GDM) according to the prepregnancy long-term fasting plasma glucose (FPG) variability. RESEARCH DESIGN AND METHODS: A total of 164 053 women who delivered their first baby between January 1, 2012 and December 31, 2015, were selected from the Korean National Health Insurance data. All women underwent at least three national health screening examinations, and the last examination should be conducted within 2 years before their first delivery. GDM was defined as the presence of more than four times of claim of GDM (International Classification of Disease, 10th Revision (ICD-10) O24.4 and O24.9) or prescription of insulin under the ICD-code of GDM. FPG variability was assessed by variability independent of the mean (FPG-VIM), coefficient of variation, SD, and average successive variability. RESULTS: Among the 164 053 women, GDM developed in 6627 (4.04%). Those in the higher quartiles of FPG-VIM showed a stepwise increased risk of GDM. In fully adjusted model, the ORs for GDM was 1.22 (95% CI 1.14 to 1.31) in women with the highest FPG-VIM quartile compared with those in the lowest quartile. The risk for GDM requiring insulin therapy was 48% increase in women in the highest quartile of FPG-VIM compared with those in the lowest quartile, while that for GDM not requiring insulin therapy was 19% increase. The association between high FPG variability and the risk of GDM was intensified in the obese and aged more than 35 years women. CONCLUSIONS: Increased FPG variability in the prepregnancy state is associated with the risk of GDM independent of confounding factors. Therefore, prepregnancy FPG variability might be a surrogate marker of the risk of GDM.