Exercise-induced secreted factors (exerkines) are proposed to coordinate systemic health benefits, yet their human tissue sources and the physiological rules governing transcript-to-serum coupling remain incompletely defined. We integrated multi-tissue transcriptomics with matched serial serum profiling to identify exercise-regulated exerkines and determine whether tissue mass moderates their systemic appearance. Sixteen healthy, sedentary young men performed a single treadmill bout calibrated to expend 300 kcal at 70-75% of maximum heart rate. RNA sequencing was performed on periumbilical subcutaneous adipose tissue, vastus lateralis skeletal muscle and whole blood collected before and immediately after exercise, with serial serum quantification up to 120 min post-exercise. Acute exercise altered adipose and muscle transcriptomes, with a minimal whole-blood response, and upregulated LGALS1 (galectin-1), FSTL1 (follistatin-like 1), OGN (osteoglycin) and C1QTNF3 (C1q and tumour necrosis factor-related protein 3) in both tissues. Serum follistatin-like 1 and galectin-1 concentrations increased significantly immediately after exercise and during recovery. Despite robust transcript induction, OGN and C1QTNF3 did not translate into early circulating increases, indicating candidate-specific kinetics and constraints beyond transcript abundance. Moderation models revealed divergent transcript-to-serum coupling: follistatin-like 1 coupling was moderated by tissue mass in both muscle and adipose depots, whereas galectin-1 followed a muscle-dominant additive profile independent of mass scaling. These findings propose galectin-1 and follistatin-like 1 as human exerkines and indicate that body composition regulates systemic exerkine signatures after exercise, providing a mechanistic framework for understanding physiological variability in exercise-induced adaptations. KEY POINTS: Exercise releases circulating factors that may contribute to health benefits, but the human tissues responsible for their production remain unclear. RNA sequencing was performed in human skeletal muscle, subcutaneous adipose tissue and whole blood, with targeted serum protein quantification over 2 h after a single treadmill bout. Exercise increased LGALS1 and FSTL1 transcripts in skeletal muscle and adipose tissue, with concurrent increases in their circulating protein products immediately post-exercise and during recovery, whereas OGN and C1QTNF3 transcripts increased robustly without an early post-exercise elevation in their circulating protein products. Body composition moderated transcript-to-serum coupling: FSTL1 (follistatin-like 1) showed mass-sensitive coupling, whereas LGALS1 (galectin-1) displayed a muscle-dominant additive profile. Galectin-1 and follistatin-like 1 emerge as exercise-induced exerkines whose circulating responses vary with body composition, supporting their prioritization as candidate mediators of exercise-related health benefits and a framework for interpreting physiological heterogeneity in adaptation.

Diabetes is highly prevalent in individuals with pancreatic ductal adenocarcinoma (PDAC) and even precedes diagnosis of PDAC; however, the mechanisms of pancreatic cancer-associated blood glucose deterioration remain largely unknown. Here, we constructed a prospective cohort of patients undergoing pancreatectomy to investigate the underlying mechanism of PDAC-associated hyperglycemia. A total of 160 patients who underwent pancreatectomy (72 patients with PDAC and 88 patients without PDAC) were enrolled at a tertiary care hospital. Glucometabolic parameters under oral glucose tolerance test were assessed in both pre- and postoperative periods, and patient-derived blood and pancreatic tissue samples were collected. Compared with patients without PDAC, patients with PDAC showed severe hyperglycemia with impaired insulin secretion before surgery. However, despite identical type of pancreatectomy in both groups, hyperglycemia improved more significantly and insulin secretory function declined less after pancreatectomy in patients with PDAC. Plasma Wnt5a and pancreatic islet β-catenin levels were higher in patients with PDAC and correlated with the degree of hyperglycemia and insulin deficiency. Plasma Wnt5a levels also correlated with tumor size and pancreatic islet β-catenin expression in patients with PDAC. In rodent islets, Wnt5a treatment suppressed insulin release, which was recovered by inhibition of β-catenin. Collectively, impaired pancreatic insulin secretion by aberrant Wnt5a/β-catenin activation may underlie the hyperglycemia associated with PDAC. Our finding provides insights into the unique molecular mechanism of pancreatic cancer-associated hyperglycemia, paving the way for the identification of potential biomarker and therapeutic targets for this condition. Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with low survival. Many patients with PDAC also develop diabetes, but the connection between the two is still unclear. Researchers aimed to explore this link by studying 160 patients, including those with PDAC and those without PDAC, who had surgery to remove part of their pancreas. The study involved measuring blood sugar and insulin levels before and after surgery. Patients with PDAC had higher blood sugar levels and lower insulin production than those without PDAC before surgery. After the surgery, patients with PDAC showed greater improvement in blood sugar control and a smaller decrease in insulin secretion than patients without PDAC. A protein called Wnt5a secreted by cancer was higher in patients with PDAC and might be linked to reduced insulin production. This protein could serve as a marker for early detection of PDAC-related diabetes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Metabolic/bariatric surgery is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), with sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) being the most common procedures. However, comparative data on their metabolic benefits in East Asian populations are limited. This multicenter retrospective cohort study assessed outcomes of SG and RYGB in Korean adults (BMI ≥ 30 kg/m²) with T2DM who underwent surgery between January 2019 and June 2021. The primary outcome was complete T2DM remission at 1 and 2 years postoperatively. Follow-up data were available for 271 patients at 1 year and 169 at 2 years. Unadjusted analysis showed lower complete remission rates in the RYGB group than the SG group at both 1 year (51.4

Background Type 2 diabetes mellitus (T2DM) requires stringent glycemic control from an early stage to prevent complications. The most effective treatment regimen for early T2DM remains unclear. The study aimed to compare the efficacy and safety of monotherapies and combination therapies for early T2DM. Methods A systematic review and network meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Randomized controlled trials focused on glycemic control, body weight, and adverse events were included. The primary outcomes were changes in glycosylated hemoglobin (HbA1c) and odds of achieving the target HbA1c after 6 months. Results All combination therapies were more effective than monotherapy. Metformin+glucagon-like peptide-1 receptor agonists (GLP-1RA) (weighted mean difference [WMD] –1.50%; 95% confidence interval [CI] –2.04 to –0.96) and metformin+dipeptidyl peptidase-4 inhibitors (WMD –1.46%; 95% CI, –1.96 to –0.95) were the most effective for change in HbA1c. GLP-1RA and sodium-glucose cotransporter-2 inhibitors led to weight reduction. Apart from the increased risk of hypoglycemia with sulfonylureas, no significant differences in adverse events were observed across regimens. Conclusion Early combination therapy effectively improved glycemic control in patients with early T2DM without significantly increasing adverse risks. Future studies should explore new combinations, including potent GLP-1RA.

Objectives Musclin, recently identified as a myokine, has been recognized for its physiological significance in potentiating the functional properties of natrieutic peptides (NPs) through competitive inhibition of their clearance receptor, natrieutic peptide receptor C (NPR-C). This study, for the first time in the literature, investigated the dynamic response of musclin during and after aerobic exercise in humans, exploring its potential as a myokine and its interaction with NPs and NPR-C in the context of exercise-induced metabolic responses.Methods Twenty-one inactive young males participated, and we assessed changes in serum levels of musclin, atrial natriuretic peptide (ANP), brain natriuretic peptide, epinephrine, and glycerol as indicative of lipid mobilization, during and after moderate-intensity aerobic exercise. Furthermore, we evaluated the gene expression of NPR-C in subcutaneous fat biopsies.Results Serum musclin levels increased significantly during aerobic exercise, followed by a decline during recovery, remaining elevated compared to baseline. Significant correlations were found between musclin responses and lean body mass (LBM), indicating its regulation by skeletal muscle mass and exercise. Exercise-induced changes in musclin positively correlated with those of ANP, potentially preventing ANP degradation. Additionally, a potential interplay between NPR-C expression and musclin dynamics on ANP was suggested. However, musclin's influence on lipid mobilization was not predominant when considering other lipolytic factors during exercise.Discussion Musclin's classification as a myokine is supported by its response to aerobic exercise and its association with LBM. Additionally, its interactions with NPR-C and NPs suggest its physiological relevance and potential clinical implications.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent condition in the general population. Although recent studies have demonstrated a link between NAFLD and lipoprotein(a), a low-density lipoprotein-like particle synthesized in the liver, its precise physiological role and mechanism of action remain unclear. This study aimed to investigate the relationship between lipoprotein(a) levels and development of NAFLD and hepatic fibrosis in Korean adults. A total of 1501 subjects who underwent abdominal ultrasonography at least twice as part of a health checkup program were enrolled. Biochemical and ultrasonography results were analyzed longitudinally, and the degree of hepatic fibrosis was calculated in subjects with NAFLD using serum biomarkers, such as fibrosis-4 (FIB-4). During the 3.36-year follow-up period, 352 patients (23.5%) were diagnosed with NAFLD. The subjects were categorized into 4 groups based on their lipoprotein(a) levels. Remarkably, the incidence of NAFLD decreased as the lipoprotein(a) levels increased. Following logistic regression analysis and adjustment for various risk factors, the odds ratio for the development of NAFLD was 0.625 (95% CI 0.440–0.888; P = .032) when comparing the highest to the lowest tertile of lipoprotein(a). However, no significant association was observed between the occurrence of hepatic fibrosis and lipoprotein(a) levels in subjects with NAFLD. Lipoprotein(a) levels have been identified as a significant predictor of NAFLD development. Additional large-scale studies with extended follow-up periods are required to better understand the effect of lipoprotein(a) on NAFLD and hepatic fibrosis.

Background/Aims: There are no data regarding the association between sarcopenic obesity status and nonalcoholic fatty liver disease (NAFLD) and NAFLD-associated liver fibrosis. Therefore, we aimed to investigate the relationship between sarcopenic obesity status (sarcopenia only, obesity only, and sarcopenic obesity) and NAFLD and liver fibrosis in Korean adults. Methods: In total, 2,191 subjects completed a health checkup program, including abdominal ultrasonography and FibroScan. Subjects were classified into the following four categories: optimal body composition (nonobese and nonsarcopenic), sarcopenia only (nonobese), obesity only (nonsarcopenic), and sarcopenic obesity. Sarcopenic obesity was stratified by the skeletal muscle mass index and body fat using bioelectrical impedance analysis. NAFLD was diagnosed by ultrasonography, and liver fibrosis was assessed using transient elastography in subjects with NAFLD. Results: The prevalence of NAFLD and liver fibrosis significantly increased according to the sarcopenic obesity status. In the logistic regression analysis, after adjusting for multiple risk factors, the odds ratio (OR) for the risk of NAFLD was largest in the sarcopenic obesity group (OR, 3.68; 95% confidence interval [CI], 2.94 to 4.60), followed by the obesity only (OR, 2.25; 95% CI, 1.67 to 3.03) and sarcopenia only (OR, 1.92; 95% CI, 1.30 to 2.84) groups, when compared with the optimal group. Additionally, liver fibrosis was independently associated with sarcopenic obesity status (OR 4.69, 95% CI 1.95 to 11.29; OR 4.17, 95% CI 1.56 to 11.17; OR 3.80, 95% CI 0.86 to 16.75, respectively). Conclusions: These results demonstrated that sarcopenic obesity was independently associated with NAFLD and liver fibrosis and increased the risk of NAFLD and liver fibrosis more than obesity or sarcopenia alone.

Background: To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).Methods: Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.Results: Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.Conclusion: The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

Background We aimed to investigate the association between the triglyceride-glucose (TyG) index and gastric carcinogenesis, including precancerous conditions such as dysplasia, atrophic gastritis, and intestinal metaplasia. Methods Patients who received an upper endoscopic assessment at a medical center were included. The enrolled patients were divided into four categories according to their TyG index quartile (Q). To evaluate the relationship between increase of TyG index and gastric cancer, we analyzed the patients who received a health checkup twice. Moreover, receiver-operating characteristic curve analysis was used to establish cut-off value of the TyG index for gastric cancer. Results Of 127,564 enrolled patients, 43,525 (34.1%) and 186 (0.1%) were diagnosed with precancerous conditions and gastric cancer, respectively. The odds ratios (ORs) of precancerous conditions given TyG index progressively increased across quartiles: using Q1 as the reference: Q2 (OR = 1.403, P < 0.001), Q3 (OR = 1.646, P < 0.001), and Q4 (OR = 1.656, P < 0.001). The ORs of gastric cancer also increased according to the quartiles: Q2 (OR = 1.619, P = 0.045), Q3 (OR = 2.180, P = 0.004), and Q4 (OR = 2.363, P = 0.001). Moreover, the increase in TyG index between baseline and follow-up tests was more significant in gastric cancer group than in control group ( P = 0.001). The optimal cut-off value for predicting gastric cancer was 9.73. Conclusions The TyG index may be a novel predictive biomarker for gastric carcinogenesis. Notably, increase in the TyG index is significantly associated with gastric cancer.

The triglyceride-glucose (TyG) index was proposed as a useful marker of metabolic syndrome. Insulin resistance, the main mechanism underlying metabolic syndrome, is related to gastroesophageal reflux disease (GERD). This study aimed to elucidate the association between the TyG index and GERD/erosive reflux disease (ERD). We retrospectively reviewed the electronic medical records of patients who underwent gastroduodenoscopy at a checkup center. The calculation of TyG index used following formula: ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). We divided the patients into four groups according to the TyG index quartile (Q). We evaluated the relationship between the alteration of the TyG index and GERD in patients who received health checkups two times. Among the 52,605 enrolled patients, 3073 (5.8%) and 434 (0.8%) were diagnosed with GERD and ERD, respectively. The odds ratios (ORs) for GERD in the TyG index progressively increased across quartiles (P < 0.001): Q2 (OR = 2.477), Q3 (OR = 3.013), and Q4 (OR = 4.027) compared with Q1, which was used as a reference, respectively. Those for ERD also progressively increased across quartiles (P < 0.001): Q2 (OR = 4.264), Q3 (OR = 4.841), and Q4 (OR = 7.390) compared with Q1, respectively. Moreover, the degree of TyG index increase during the first and second tests in the GERD group was more prominent than in the control group (P = 0.001). In conclusion, the higher TyG index was significantly associated with GERD. The TyG index may be a novel predictive biomarker of GERD and ERD.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

PURPOSE:Little is known about the relationship between brain-derived neurotrophic factor (BDNF) gene polymorphisms and psychiatric symptoms in diabetes patients. We investigated the effects of BDNF Val/66/Met polymorphism, glucose status, psychological susceptibility, and resilience on anxiety and depression symptoms in patients newly diagnosed with type 2 diabetes mellitus (T2DM).MATERIALS AND METHODS:We examined biochemical factors and BDNF polymorphism in 89 patients who were newly diagnosed with T2DM. Psychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS), and the Connor-Davidson Resilience Scale (CD-RISC) and Impact of Event Scale (IES) were used to assess psychological resilience and susceptibility to psychological distress, respectively. Logistic regression analyses were conducted to investigate factors associated with psychiatric symptoms.RESULTS:We determined that 62 patients (70%) were Met-carriers. No significant differences were found between the Val/Val homozygous and Met-carrier groups regarding age, sex, body mass index, and clinical factors related to glycemic control and lipid profiles. HADS-anxiety and HADS-depression scores and IES factor scores were higher in the Met-carrier than the Val/Val homozygous group. Hemoglobin A1c (HbA1c) level was significantly inversely correlated with the severity of depressive symptoms. Resilience factors showed significant inverse correlations, and IES factors showed positive correlations with depressive symptom severity. In the logistic regression analysis model, depressive symptoms were significantly associated with HbA1c and BDNF polymorphism, whereas only the hyperarousal factor of the IES scale was associated with anxiety.CONCLUSION:Depressive symptoms are associated with the presence of the Met-carriers and lower HbA1c in patients newly diagnosed with T2DM.

We designed a postmarketing surveillance study of linagliptin for patients with type 2 diabetes (T2D) in Korea. This prospective, observational, multicentre study investigated the safety and glycaemic effectiveness of linagliptin as monotherapy or combination therapy with other antidiabetic drugs in routine clinical practice. Endpoints were the incidence of adverse drug reactions (ADRs) and the change in HbA1c. Overall, 3119 and 2171 patients were included in the safety and effectiveness analysis sets, respectively. A total of 56 patients (1.8%) experienced ADRs. The most common ADR was gastrointestinal disorders (0.7%), followed by metabolism and nutrition disorders (0.5%). ADRs of special interest, including pancreatic diseases, cardiac diseases and hypoglycaemia, occurred in 12 patients, 11 of whom had hypoglycaemia, while one had a skin lesion. Mean HbA1c change during the study period was -0.8%. Lower body mass index, shorter diabetes duration and higher baseline HbA1c were independently associated with a better effectiveness, while the presence of diabetic complications, dyslipidaemia and the use of sulphonylureas were associated with a poor response. In conclusion, linagliptin showed an excellent safety profile and glycaemic effectiveness in Korean patients with T2D.

Type 2 diabetes is the fastest growing metabolic disease in the world. Recently, muscle is considered an endocrine organ which secretes various peptides that play an important role in insulin resistance and metabolic syndrome. We assessed 4 different myokines, irisin, interleukin-13 (IL-13), follistatin-related protein-1 (FSTL-1), and fractalkine, in normal, prediabetes, and diabetes patients. A total of 126 participants who visited Gangnam Severance Hospital were enrolled and divided into normal, prediabetes, and diabetes groups based on oral glucose tolerance test and hemoglobin a1c. A cross-sectional study was conducted to measure and compare serum levels of irisin, IL-13, FSTL-1, and fractalkine among the groups. Irisin level showed a tendency to increase in prediabetes group compared to normal group (P < .1) but showed a significant decrease when comparing diabetes from prediabetes group (P < .001). IL-13 decreased in diabetes group compared to prediabetes and normal group (P < .001, P < .05, respectively). FSTL-1 of diabetes group was lower than that of prediabetes group (P < .05), and fractalkine was higher in diabetes group compared to that of prediabetes and normal group (P < .01, P < .01, respectively). Irisin, IL-13, and FSTL-1 levels were reduced in diabetes group compared to normal or prediabetes group while fractalkine showed a progressive increase from normal to diabetes group. Further studies are warranted to study the roles of various myokine in diabetes through a larger prospective study.

Background Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD). Recently, atherogenic index of plasma (AIP) has been proposed as a novel predictive marker for CVD, and there are few cross sectional studies that demonstrated a relationship between AIP and coronary artery disease. We investigated the association between AIP and the progression of coronary artery calcification (CAC) in Korean adults without CVD. Methods A total of 1,124 participants who had undergone CAC measurement at least twice by multi-detector CT in a health care center were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were assessed. The AIP was defined as the base 10 logarithm of the ratio of the concentration of TG to HDL-C. The CAC progression was defined as either incident CAC in a CAC-free population at baseline or an increase of ≥ 2.5 units between the square roots of the baseline and follow-up coronary artery calcium scores (CACS) among subjects with detectable CAC at baseline Results CAC progression was observed in 290 subjects (25.8%) during the mean 4.2 years of follow-up. All subjects were stratified into three groups according to AIP. There were significant differences in cardiovascular parameters among the groups at baseline. The follow-up CAC and the incidence of CAC progression increased gradually with the rising AIP tertiles. In the logistic regression analysis, the odds ratio for CAC progression was 2.27 when comparing the highest to the lowest tertile of the AIP (95% CI: 1.61-3.19; P for trend <0.01). However, this association was attenuated after adjustment for multiple risk factors (P for trend = 0.67). Conclusions There is a significant correlation between AIP and CAC and its progression in subjects without CVD, but AIP is not an independent predictor of CAC progression.