Gut hormones and appetite regulation.

PURPOSE OF REVIEW: Various gut hormones interact with the brain through delicate communication, thereby influencing appetite and subsequent changes in body weight. This review summarizes the effects of gut hormones on appetite, with a focus on recent research. RECENT FINDINGS: Ghrelin is known as an orexigenic hormone, whereas glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin (CCK), postprandial peptide YY (PYY), and oxyntomodulin (OXM) are known as anorexigenic hormones. Recent human studies have revealed that gut hormones act differently in various systems, including adipose tissue, beyond appetite and energy intake, and even involve in high-order thinking. Environmental factors including meal schedule, food contents and quality, type of exercise, and sleep deprivation also play a role in the influence of gut hormone on appetite, weight change, and obesity. Recently published studies have shown that retatrutide, a triple-agonist of GLP-1, GIP, and glucagon receptor, and orforglipron, a GLP-1 receptor partial agonist, are effective in weight loss and improving various metabolic parameters associated with obesity. SUMMARY: Various gut hormones influence appetite, and several drugs targeting these receptors have been reported to exert positive effects on weight loss in humans. Given that diverse dietary and environmental factors affect the actions of gut hormones and appetite, there is a need for integrated and largescale long-term studies in this field.

Non-alcoholic fatty liver disease is associated with hyperandrogenism in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53-6.63) in FT; 1.12 (1.04-1.22) in FAI), FLI (OR 2.68 (95% CI 1.43-5.03) in FT; 1.13 (1.06-1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08-5.21) in FT; 1.5 (1.09-1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Clinical features of COVID-19 among patients with end-stage renal disease on hemodialysis in the context of high vaccination coverage during the omicron surge period: a retrospective cohort study.

BACKGROUND: We determined the clinical presentation and outcomes of the Omicron variant of severe acute respiratory syndrome coronavirus 2 infection in hemodialysis patients and identified the risk factors for severe coronavirus disease (COVID-19) and mortality in the context of high vaccination coverage. METHODS: This was a retrospective cohort study involving hemodialysis patients who were vaccinated against COVID-19 during March-September 2022, when the Omicron variant was predominant, and the COVID-19 vaccination rate was high. The proportion of people with severe COVID-19 or mortality was evaluated using univariate logistic regression. RESULTS: Eighty-three (78.3%) patients had asymptomatic/mild symptoms, 10 (9.4%) had moderate symptoms, and 13 (12.3%) had severe symptoms. Six (5.7%) patients required intensive care admission, two (1.9%) required mechanical ventilation, and one (0.9%) was kept on high-flow nasal cannula. Of the five (4.7%) mortality cases, one was directly attributed to COVID-19 and four to pre-existing comorbidities. Risk factors for both severe COVID-19 and mortality were advanced age; number of comorbidities; cardiovascular diseases; increased levels of aspartate transaminase, lactate dehydrogenase, blood urea nitrogen/creatinine ratio, brain natriuretic peptide, and red cell distribution; and decreased levels of hematocrit and albumin. Moreover, the number of COVID-19 vaccinations wasa protective factor against both severe disease and mortality. CONCLUSIONS: Clinical features of hemodialysis patients during the Omicron surge with high COVID-19 vaccination coverage were significant for low mortality. The risk features for severe COVID-19 or mortality were similar to those in the pre-Omicron period in the context of low vaccination coverage.

Relationship between age at menarche and metabolic diseases in Korean postmenopausal women: The Korea National Health and Nutrition Examination Survey 2016-2018.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Early menarche may be associated with an increased risk of metabolic diseases such as diabetes and cardiovascular disease. This study aimed to investigate the effect of menarche age and the risk of diabetes and metabolic syndrome in Korean postmenopausal women. METHODS: We analyzed 4,933 postmenopausal women (mean age: 64.7 years) using the Korean National Health and Nutritional Examination Survey 2016-2018. Subjects were divided into three groups according to menarche age (early menarche: ≤ 12 years (n = 451), reference: 13-16 years (n = 3,421), and late menarche: ≥ 17 years (n = 1,061)). Logistic regression analysis was used to estimate the odds ratio (OR) for diabetes and metabolic syndrome. RESULTS: Women with an early menarche age were younger, more educated, and had higher income than the other groups (p-value < 0.001). There were no differences in body mass index, blood pressure, fasting glucose, HbA1c, and cholesterol levels among the three groups. After adjusting for potential confounding factors, early menarche age was significantly associated with the risk of diabetes (OR 1.435, 95% confidence interval (CI): 1.069-1.928). The prevalence of metabolic syndrome in all subjects was 41.1%. After adjusting for potential confounding factors, the OR of metabolic syndrome in the early menarche group was 1.213 (95% CI: 0.971-1.515). CONCLUSION: The risk of diabetes was 1.43 times higher in postmenopausal Korean women with early menarche. Although the risk of metabolic syndrome was not statistically significant, it showed a tendency to increase in the early menarche group. Our results suggest that age at menarche may be helpful in diabetes risk stratification and early interventions for postmenopausal women.

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.

Combination of Statin and Ezetimibe versus Statin Monotherapy on Cardiovascular Disease and Type 2 Diabetes Incidence among Adults with Impaired Fasting Glucose: a Propensity-Matched Nationwide Cohort Study.

OBJECTIVE: We investigated the effects of statin-ezetimibe combination therapy compared with statin-only treatment on the hazard of incident type 2 diabetes (T2D), myocardial infarction (MI), and stroke among adults with impaired fasting glucose (IFG) in a real-world setting. METHODS: The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this propensity-matched nationwide cohort study. Among 56,633 IFG patients without baseline cardiovascular disease (CVD) and/or T2D who initiated statin therapy with or without ezetimibe, 1,155 with statin-ezetimibe combination therapy were matched based on a propensity score at a 1:5 ratio with 5,775 patients who received statin monotherapy. The hazards of T2D, MI, and stroke were compared between these treatment groups. RESULTS: The incidence rate per 1,000 person-years was 19.62 (statin monotherapy group) and 21.02 (combined treatment group) for T2D, 1.53 (statin monotherapy group) and 1.70 (combined treatment group) for MI, and 1.99 (statin monotherapy group) and 2.06 (combined treatment group) for stroke. The hazards of T2D, MI, and stroke were not significantly different between the statin monotherapy group and the statin-ezetimibe combination therapy group. CONCLUSION: The combination of ezetimibe in addition to statin treatment was not associated with a significantly different risk of T2D and CVDs compared with statin monotherapy in Korean adults with IFG.

Glycemic variability and the risk of nonalcoholic fatty liver disease : A nationwide population-based cohort study.

AIM: Although few recent studies have reported the association between the glycemic variability and the development of type 2 diabetes mellitus and cardiovascular disease in individuals without diabetes mellitus, the impact of the long-term variability in fasting plasma glucose (FPG) levels on the incident nonalcoholic fatty liver disease (NAFLD) has not been evaluated. METHODS: The study included 57,636 Korean men and women without NAFLD and diabetes mellitus from the Korean National Health Insurance System cohort. FPG variability was calculated using the coefficient of variation (FPG-CV), standard deviation (FPG-SD), variability independent of the mean (FPG-VIM), and average successive variability (FPG-ASV). RESULTS: The cumulative incidence of NAFLD demonstrated progressively increasing trends according to the higher quartiles of FPG variability in Kaplan-Meier curves. A multivariable Cox proportional hazard analysis revealed that the hazard ratio for incident NAFLD was 1.15 (95% confidence interval, 1.06-1.24) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for various confounding factors, including mean FPG levels. When using FPG-SD, FPG-VIM, and FPG-ASV, the results were similar. The 10-unit increase in FPG variability was associated with a 14% increased risk of NAFLD in the fully adjusted model. Moreover, this effect remained consistent in the subgroup and sensitivity analyses. CONCLUSION: Increased long-term FPG variability is associated with the development of NAFLD, independent of confounding risk variables including mean FPG levels.

Association of Vitamin D Deficiency with Diabetic Nephropathy.

BACKGROUND: Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM. METHODS: This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay. RESULTS: The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables. CONCLUSION: Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy.

Association of the triglyceride and glucose index with low muscle mass: KNHANES 2008-2011.

The triglyceride-glucose (TyG) index is a simple surrogate marker of insulin resistance. We evaluated the association of the TyG index with low muscle mass using a nationwide population-based representative data. This is a cross-sectional study that included 9477 participants aged ≥ 40 years from the Korea National Health and Nutrition Examination Survey between 2008 and 2011. The TyG index was calculated as ln[triglyceride (mg/dL) × fasting plasma glucose (mg/dL)/2]. Dual-energy X-ray absorptiometry was used to measure appendicular lean mass (ALM). Low muscle mass was defined an ALM/weight of 2 standard deviations (SD) below of young participants. The overall prevalence of low muscle mass was 4.7%. The prevalence of low muscle mass increased linearly with the quartiles of the TyG index, 2.5%, 4.2%, 5.6%, and 6.7% in Q1-Q4, respectively. The TyG index was negatively associated with ALM/weight both in men (r = - 0.302) and women (r = - 0.230). The odds ratio (OR) for low muscle mass was 2.08 in the highest quartile compared to the lowest quartile. High TyG index was associated with an increased risk of low muscle mass (OR for 1SD increase: 1.13). Increased TyG index was associated with the risk of low muscle mass independent of confounding factors.

Optimal blood pressure for patients with chronic kidney disease: a nationwide population-based cohort study.

The effect of blood pressure (BP) on the incident cardiovascular events, progression to end-stage renal disease (ESRD) and mortality were evaluated among chronic kidney disease (CKD) patients with and without antihypertensive treatment. This nationwide study used the Korean National Health Insurance Service-Health Screening Cohort data. The hazards of outcomes were analysed according to the systolic BP (SBP) or diastolic BP (DBP) among adults (aged ≥ 40 years) with CKD and without previous cardiovascular disease or ESRD (n = 22,278). The SBP and DBP were ≥ 130 mmHg and ≥ 80 mmHg in 10,809 (48.52%) and 11,583 (51.99%) participants, respectively. During a median 6.2 years, 1271 cardiovascular events, 201 ESRD incidents, and 1061 deaths were noted. Individuals with SBP ≥ 130 mmHg and DBP ≥ 80 mmHg had higher hazards of hypertension-related adverse outcomes compared to the references (SBP 120-129 mmHg and DBP 70-79 mmHg). SBP < 100 mmHg was associated with hazards of all-cause death, and composite of ESRD and all-cause death during follow-up only among the antihypertensive medication users suggesting that the BP should be < 130/80 mmHg and the SBP should not be < 100 mmHg with antihypertensive agents to prevent the adverse outcome risk of insufficient and excessive antihypertensive treatment in CKD patients.

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.

Age- and Sex-Related Differential Associations between Body Composition and Diabetes Mellitus.

Background: The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain. Methods: The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex. Results: In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups. Conclusion: Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.

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.

Ginsenoside compound-Mc1 attenuates oxidative stress and apoptosis in cardiomyocytes through an AMP-activated protein kinase-dependent mechanism.

BACKGROUND: Ginsenoside compound-Mc1 (Mc1) is a member of the deglycosylated ginsenosides obtained from ginseng extract. Although several ginsenosides have a cardioprotective effect, this has not been demonstrated in ginsenoside Mc1. METHODS: We treated H9c2 cells with hydrogen peroxide (H2O2) and ginsenoside Mc1 to evaluate the antioxidant effects of Mc1. The levels of antioxidant molecules, catalase, and superoxide dismutase 2 (SOD2) were measured, and cell viability was determined using the Bcl2-associated X protein (Bax):B-cell lymphoma-extra large ratio, a cytotoxicity assay, and flow cytometry. We generated mice with high-fat diet (HFD)-induced obesity using ginsenoside Mc1 and assessed their heart tissues to evaluate the antioxidant effect and the fibrosis-reducing capability of ginsenoside Mc1. RESULTS: Ginsenoside Mc1 significantly increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the H9c2 cells. The expression levels of catalase and SOD2 increased significantly after treatment with ginsenoside Mc1, resulting in a decrease in the production of H2O2-mediated reactive oxygen species. Treatment with ginsenoside Mc1 also significantly reduced the H2O2-mediated elevation of the Bax:Bcl2 ratio and the number of DNA-damaged cells, which was significantly attenuated by treatment with an AMPK inhibitor. Consistent with the in vitro data, ginsenoside Mc1 upregulated the levels of catalase and SOD2 and decreased the Bax:B-cell lymphoma-extra large ratio and caspase-3 activity in the heart tissues of HFD-induced obese mice, resulting in reduced collagen deposition. CONCLUSION: Ginsenoside Mc1 decreases oxidative stress and increases cell viability in H9c2 cells and the heart tissue isolated from HFD-fed mice via an AMPK-dependent mechanism, suggesting its potential as a novel therapeutic agent for oxidative stress-related cardiac diseases.

Body Weight Variability Increases Dementia Risk Among Older Adults: A Nationwide Population-Based Cohort Study.

Background: Recent growing evidences suggest that body weight (Bwt) variability, a repeated loss and regain of weight within a specific period, causes metabolic disturbances and can be a marker for poor homeostasis. Although there have been many studies about the association between Bwt variability and various health status, its association with the incidence of dementia among elderly people has not been examined. Methods: We performed a retrospective elderly cohort study from 19,987 participants with mean age 73 years old in the Korean National Health Insurance Service. We examined the risk of incident dementia, including Alzheimer's dementia and vascular dementia, according to the quartile of Bwt variability, represented as coefficient of variation (Bwt-CV), SD (Bwt-SD), and variability independent of the mean (Bwt-VIM). Results: In fully adjusted model, the group with the highest Bwt variability (Bwt-VIM Q4) showed an increased risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.206-1.603) and Alzheimer's dementia (HR 1.46, CI 1.240-1.724) compared to the lowest quartile (Bwt-VIM Q1). We also found that subjects with the highest Bwt variability (Q4) and underweight BMI had a significantly increased risk of developing dementia (HR 1.994, 95% CI 1.302-3.054), while subjects with low Bwt variability (Q1 and Q2) and obese BMI had decreased risk of dementia (HR 0.664, 95% CI 0.505-0.872 and HR 0.648, 95% CI 0.493-0.852, respectively) compared to reference group (lowest Bwt variability (Q1) with normal baseline BMI). The effect of Bwt variability on the incidence of dementia was more prominent in subjects <75 years old and abnormal BMI groups (P for interaction < 0.05). Conclusion: The present study revealed that high Bwt variability was associated with an increased risk of dementia in the elderly.

Relationship between the characteristic traits of polycystic ovary syndrome and susceptibility genes.

Polycystic ovary syndrome (PCOS) is a highly complex disorder influenced by genetic and environmental factors. Previous genome-wide association studies (GWAS) on Han Chinese, Korean, and European populations identified multiple PCOS-susceptible loci; however, only a few studies reported the association of susceptibility genes with disease phenotypic traits. This cross-sectional study aimed to investigate the association between PCOS susceptibility genes from GWAS and disease-related clinical features. A total of 1,810 reproductive-aged women were recruited, including 927 control women and 883 women with PCOS, diagnosed based on the European Society for Human Reproduction and Embryology criteria. Genomic DNA was extracted and genotyped, and a Bonferroni test was performed to determine the association between 12 independent SNPs and the clinical features of PCOS. In women with PCOS, rs11031006, nearest to FSHB, was significantly associated with free testosterone (P = 1.94 × 10-3) and luteinizing hormone (P = 1.96 × 10-3) levels. The menstruation number per year, ovarian follicular number, ovarian volume, and insulin sensitivity index were not associated with any SNP. In the control group, no SNPs were associated with any PCOS traits. Collectively, our results suggest that FSHB may play an important role in the development and progression of PCOS.

Ginsenoside Mc1 improves liver steatosis and insulin resistance by attenuating ER stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside, a major pharmacologically active ingredient in ginseng, has been known to exhibit beneficial properties such as antioxidant and anti-inflammatory effects. Ginsenoside compound Mc1 is one of the newly identified de-glycosylated ginsenosides. Endoplasmic reticulum (ER) stress has implicated in the development of non-alcoholic fatty liver disease (NAFLD) through apoptosis and lipid accumulation. AIM OF THE STUDY: We aimed to examine the protective effects of Mc1 treatment on ER stress-induced cell death and impaired insulin signaling in HepG2 human hepatoblastoma cells and ER stress-induced liver steatosis and insulin resistance in a diet-induced obesity (DIO) mouse model. MATERIALS AND METHODS: HepG2 cells were treated with palmitate and Mc1 to evaluate the effects of Mc1 on ER stress-induced damage. C57BL/6 mice were fed with a high-fat diet (HFD) for 4 weeks and received an intraperitoneal injection of either vehicle or Mc1 (10 mg/kg/day). The control mice were fed with a chow diet and injected with vehicle for the same period. ER stress, cell death, and degree of steatosis were evaluated in the liver tissues of mice. The effect of Mc1 treatment on glucose metabolism was also determined. RESULTS: Mc1 co-treatment reduced the palmitate-induced ER stress and death of HepG2 cells. The palmitate-induced insulin resistance improved after Mc1 co-treatment. Consistent with the in vitro data, chronic Mc1 supplementation reduced ER stress and apoptotic damage in the liver of obese mice. Mc1 treatment ameliorated glucose intolerance and insulin resistance through the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. In addition, Mc1 treatment reduced obesity-induced lipogenesis and prevented fat accumulation in the liver of DIO mice. CONCLUSIONS: Mc1 exerted protective effects against ER stress-induced apoptotic damage, insulin resistance and lipogenesis in palmitate-treated hepatocytes and in the liver of DIO mice. Therefore, Mc1 supplementation could be a potential therapeutic strategy to prevent NAFLD in patients with obesity and insulin resistance.

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.

Variability in estimated glomerular filtration rate and the incidence of type 2 diabetes: a nationwide population-based study.

OBJECTIVE: Variability in estimated glomerular filtration rate (eGFR) has been associated with adverse outcomes in patients with diabetes or chronic kidney disease (CKD). However, no previous study has explored the relationship between eGFR variability and type 2 diabetes incidence. RESEARCH DESIGN AND METHODS: In this nationwide, longitudinal, cohort study, we investigated the association between eGFR variability and type 2 diabetes risk using the Korean National Health Insurance Service datasets from 2002 to 2017. eGFR variability was calculated using the variability independent of the mean (eGFR-VIM), coefficient of variation (eGFR-CV), standard deviation (eGFR-SD) and average real variability (eGFR-ARV). RESULTS: Within 7 673 905.58 person-years of follow-up (mean follow-up: 3.19 years; n=2 402 668), 11 981 cases of incident type 2 diabetes were reported. The HRs and 95% CIs for incident type 2 diabetes increased according to advance in quartiles of eGFR-VIM (HR (95% CI): Q2, 1.068 (1.009 to 1.130); Q3, 1.077 (1.018 to 1.138); Q4, 1.203 (1.139 to 1.270)) even after adjusting for confounding factors including mean eGFR and mean fasting plasma glucose levels. The subgroup analyses according to risk factors as well as analyses using eGFR-CV, eGFR-SD and eGFR-ARV showed consistent results. The association between increased eGFR variability and type 2 diabetes risk was more prominent in men, individuals with dyslipidemia and those with CKD as shown in the subgroup analysis (p for interaction <0.001). CONCLUSIONS: Increased eGFR variability may be an independent predictor of type 2 diabetes and might be useful for risk stratification of individuals without diabetes.

Gamma-glutamyl transferase variability and the risk of hospitalisation for heart failure.

OBJECTIVE: Gamma-glutamyl transferase (GGT) is associated with oxidative stress, inflammation, cardiovascular disease and mortality. Variability in metabolic parameters has recently emerged as an indicator of adverse health outcomes, including heart failure (HF). METHODS: We investigated whether GGT variability was associated with the incidence of hospitalisation for heart failure (HHF) in a Korean population without previous HF, ischaemic heart disease or liver disease. This longitudinal cohort study analysed 119 201 individuals from the Korean National Health Insurance Service-National Health Screening Cohort. GGT variability was calculated as the coefficient of variation (CV), SD and variability independent of the mean (VIM). RESULTS: During the 8.4 years of follow-up, 1387 cases of HHF (1.16%) developed. In the multivariable-adjusted model, the HR of HHF was 1.22 (95% CI 1.05 to 1.42) in the highest quartile of GGT variability compared with the lowest quartile, as assessed by CV after adjusting for confounding factors, including alcohol consumption and mean GGT levels. Consistent results were obtained using other indices of GGT variability such as SD (HR 1.37, 95% CI 1.16 to 1.62) and VIM (HR 1.29, 95% CI 1.11 to 1.50). In a subgroup analysis stratified by risk factor variables, although a similar relationship was observed, it was more prominent in individuals with dyslipidaemia. CONCLUSIONS: The results of the present study demonstrated that variability in GGT was independently associated with the incidence of HHF. These findings suggest that higher GGT variability may be useful as an indicator of future risk of HF.