This cross-sectional study was performed to examine the association between alcohol consumption and insulin secretion and sensitivity using the Korean Genome and Epidemiology Study. Alcohol consumption levels were categorized into four groups: (i) abstainers, (ii) low (<5 g/day), (iii) intermediate (<30 g/day), and (iv) high (≥30 g/day) alcohol consumption. β-cell function and insulin sensitivity were estimated using the insulinogenic index (IGI₆₀), and Matsuda insulin sensitivity index (ISI), respectively. IGI₆₀ and ISI were dichotomized into high and low groups using median cut-off values and four groups were defined (G-I: high IGI₆₀/high ISI; G-II: high IGI₆₀/low ISI; G-III: low IGI₆₀/high ISI; and G-IV: low IGI₆₀/low ISI). Men consumed 26.5 g alcohol per day on average, whereas women only consumed 5.7 g/day, so women were excluded from subsequent analyses due to their low drinking levels. Alcohol consumption was positively associated with high-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST), and triglycerides (TG) in men, but was negatively associated with IGI₆₀ (p < 0.05). TG levels were only increased in individuals with decreased insulin sensitivity (G-II) or decreased β-cell function (G-III) with high alcohol consumption. In addition, alcohol consumption increased HDL cholesterol in the four groups (p < 0.001). In subjects with decreased insulin sensitivity (G-II), intermediate and high alcohol consumption increased the risk of high cholesterol and TG. In individuals with decreased β-cell function (G-III), alcohol consumption increased the risk of high TG and high AST levels. High alcohol consumption was significantly associated with reduced insulin secretion. In addition, alcohol consumption was related to some metabolic risk factors depending on insulin secretion or sensitivity.

Background: Glutamate is a major neurotransmitter, although it causes cytotoxicity and inflammation in nonneuronal organs. This study aimed to investigate the metabolic disorders in which glutamate, associated with type 2 diabetes onset, is induced in the liver.Methods: An analysis of Korean community‐based Ansan‐Ansung cohort study data as well as functional research using in vitro and mouse models were performed.Results: Groups with high plasma glutamate levels (T2, T3) had a significantly increased risk of diabetes incidence after 8 years, compared to the group with relatively low glutamate levels (T1). Analysis of the effect of glutamate on diabetes onset in vitro showed that glutamate induces insulin resistance by increasing glucose‐related protein 78 (GRP78) and phosphoenolpyruvate carboxykinase (PEPCK) expression in SK‐Hep‐1 human liver cells. In addition, three different genes, FRMB4B, PLG, and PARD3, were significantly associated with glutamate and were identified via genome‐wide association studies. Among glutamate‐related genes, plasminogen (PLG) levels were most significantly increased in several environments in which insulin resistance was induced, and was also upregulated by glutamate. Glutamate‐induced increase in PLG in liver cells was caused by metabotropic glutamate receptor 5 activation, and PLG levels were also upregulated after extracellular secretion. Moreover, glutamate increased the expression of plasminogen activator inhibitor‐1 (PAI‐1). Thus, extracellular secreted PLG cannot be converted to plasmin (fibrinolytic enzyme) by increased PAI‐1.Conclusions: Increased glutamate is closely associated with the development of diabetes, and it may cause metabolic disorders by inhibiting the fibrinolytic system, which plays an important role in determining blood clots, a hallmark of diabetes.

Background: The current study aimed to screen for relationships and different potential metabolic biomarkers involved between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in adolescents. Methods: The study included 148 obese adolescents aged between 14 and 16. The study participants were divided into MUO and MHO groups based on the age-specific adolescent metabolic syndrome (MetS) criteria of the International Diabetes Federation. The current study was conducted to investigate the clinical and metabolic differences between the MHO and MUO groups. Multivariate analyses were conducted to investigate the metabolites as independent predictors for the odds ratio and the presence of the MetS. Results: There were significant differences in the three acylcarnitines, five amino acids, glutamine/glutamate ratio, three biogenic amines, two glycerophospholipids, and the triglyceride-glucose index between the MUO group and those in the MHO group. Moreover, several metabolites were associated with the prevalence of MUO. Additionally, several metabolites were inversely correlated with MHO in the MUO group. Conclusions: In this study, the biomarkers found in this study have the potential to reflect the clinical outcomes of the MUO group. These biomarkers will lead to a better understanding of MetS in obese adolescents.

Background/Objectives: Childhood overweight/obesity status is a critical risk factor for adverse cardiometabolic outcomes. We aimed to evaluate the sex-specific associations between a maintained childhood overweight status and late-adolescent cardiometabolic risk factors using data from a Korean longitudinal study. Methods: We used data from the Korean Children-Adolescents Study, a prospective cohort of children enrolled at age 7 and followed annually from 2005 to 2020. Among participants who were followed at least once, a total of 899 children (438 boys, 461 girls) with consistent body mass index (BMI) status at ages 7–9 and 10–12 were included in the analysis. Participants were categorized into two groups on the basis of BMI: normal weight maintenance and overweight maintenance. Multivariable linear regression was used to examine the associations between BMI patterns and cardiometabolic risk factors, with adjustments for covariates. Results: Among the 899 children (mean age: 7.1 ± 0.4 years, 48.7% boys), 12.8% of boys and 5.9% of girls were classified into the overweight maintenance group. Boys in the overweight maintenance group had significantly greater BMIs, waist circumferences (WC), body fat percentages, trunk fat mass, and aspartate aminotransferase and alanine aminotransferase levels at ages 15 and 18. Girls in the same group had elevated BMI, WC, body fat percentage, trunk fat mass, and blood pressure and experienced earlier pubertal onset. Conclusions: Maintaining an overweight status during childhood is associated with adverse cardiometabolic profiles in adolescence, with sex-specific differences. These findings highlight the importance of early, sex-specific interventions to prevent long-term health risks associated with childhood obesity.