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Carbohydrate-restricted diets and intermittent fasting (IF) have been rapidly gaining interest among the general population and patients with cardiometabolic disease, such as overweight or obesity, diabetes, and hypertension. However, there are limited expert recommendations for these dietary regimens. This study aimed to evaluate the level of scientific evidence on the benefits and harms of carbohydrate-restricted diets and IF to make responsible recommendations. A meta-analysis and systematic literature review of 66 articles on 50 randomized controlled trials (RCTs) of carbohydrate-restricted diets and 10 articles on eight RCTs of IF was performed. Based on the analysis, the following recommendations are suggested. In adults with overweight or obesity, a moderately-low carbohydrate or low carbohydrate diet (mLCD) can be considered as a dietary regimen for weight reduction. In adults with type 2 diabetes mellitus, mLCD can be considered as a dietary regimen for improving glycemic control and reducing body weight. In contrast, a very-low carbohydrate diet (VLCD) and IF are recommended against in patients with diabetes. Furthermore, no recommendations are suggested for VLCD and IF in adults with overweight or obesity, and carbohydrate-restricted diets and IF in patients with hypertension. Here, we describe the results of our analysis and the evidence for these recommendations.

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1,862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥40 was considered indicative of high distress. Individuals with high distress (n=589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, longer duration of diabetes, and higher homeostatic model assessment for insulin resistance level (all p

The impaired insulin secretion and increased insulin resistance (or decreased insulin sensitivity) play a major role in the pathogenesis of all types of diabetes mellitus (DM). It is very important to assess the pancreatic β-cell function and insulin resistance/ sensitivity to determine the type of DM and to plan an optimal management and prevention strategy for DM. So far, various methods and indices have been developed to assess the β-cell function and insulin resistance/sensitivity based on static, dynamic test and calculation of their results. In fact, since the metabolism of glucose and insulin is made through a complex process related with various stimuli in several tissues, it is difficult to fully reflect the real physiology. In order to solve the theoretical and practical difficulties, research on new index is still in progress. Also, it is important to select the appropriate method and index for the purpose of use and clinical situation. This review summarized a variety of traditional methods and indices to evaluate pancreatic β-cell function and insulin resistance/sensitivity and introduced novel indices.

The accumulation of advanced glycation end products (AGEs) causes metabolic dysfunction and neuronal cell damage. Methylglyoxal (MG) is a major glycating agent that reacts with basic residues present in proteins and promotes the formation of AGEs. Sciadopitysin, a type of biflavonoid, exerts protective effects against neuronal cell damage; however, the underlying mechanisms have not been studied. This study aimed to investigate the mechanisms underlying the protective effects of sciadopitysin against MG-mediated cytotoxicity in SK-N-MC neuroblastoma cells. Our results demonstrated that pretreatment of SK-N-MC cells with sciadopitysin improved the cell viability that was inhibited by MG and inhibited the apoptosis induced by MG. Sciadopitysin attenuated intracellular Ca2+ , NOX4 levels, oxidative stress, and MG-protein adduct levels, and increased nuclear Nrf2 and glyoxalase 1 levels in the presence of MG. These results suggest that sciadopitysin exerts neuroprotective effects against MG-induced death of human SK-N-MC cells via its antioxidative action. This study highlights sciadopitysin as a promising candidate for antioxidant therapy and designing natural drugs against AGE-induced neurodegenerative disorders.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an endocrine disrupting compound and persistent organic pollutant that has been associated with diabetes in several epidemiological studies. Oleuropein, a major phenolic compound in olive fruit, is a superior antioxidant and radical scavenger. This study aimed to examine the effects of oleuropein against TCDD-induced stress response in a pancreatic beta cell line, INS-1 cells. Cells were pre-incubated with various concentrations of oleuropein and then stimulated with TCDD (10 nM) for 48 hrs. When treated with TCDD, INS-1 cells produced robust amounts of prostaglandin E

The screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.

Background/Aims We examined the concordance rate among fasting plasma glucose (FPG), 2-hour post-challenge glucose (2hr PG), and hemoglobin A1c (HbA1c) in the diagnosis of diabetes in a population with a high-risk for type 2 diabetes mellitus (T2DM) in Korea. Methods Among the participants from the Korean Diabetes Prevention Study, individuals with FPG ≥ 100 mg/dL, body mass index (BMI) ≥ 23.0 kg/m2, and no previous history of T2DM were consecutively enrolled after a 75 g glucose tolerance test. We analyzed the differences in the clinical characteristics in subjects with stage 1 (FPG, 100 to 109 mg/dL) and stage 2 (FPG, 110 to 125 mg/dL) impaired fasting glucose (IFG). Results Of 1,637 participants, 27.2% had T2DM and 59.3% had IFG and/or impaired glucose tolerance (IGT). The mean age was 55.0 ± 8.1 years and the mean BMI was 26.3 ± 2.7 kg/m2. Based on FPG criteria, 515 (31.4%) and 352 (21.5%) subjects were classified as having stage 1 and stage 2 IFG, respectively. The 19.0% of stage 1 and 43.5% of stage 2 subjects showed 2hr PG levels in the diabetic range. Even for those in the normal FPG range, 63 (9.5%) participants showed a 2hr PG level of ≥ 200 mg/dL. Of 446 subjects with newly-diagnosed diabetes, 340 (76.2%) showed FPG levels < 126 mg/dL. Conclusions The oral glucose tolerance test should be actively considered for Korean adults who are overweight or obese with the IFG range (FPG, 100 to 125 mg/ dL) to allow for early detection of diabetes and prompt intervention.

We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea. People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values. The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/m2, and 87.5 ± 18.8 kg, respectively. Body weight and BMI decreased after initiation of liraglutide treatment: −2.94 kg and −1.08 kg/m2 at 2 months; −4.23 kg and −1.55 kg/m2 at 4 months, and −5.14 kg and −1.89 kg/m2 at 6 months (all P

BackgroundInterstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis.MethodsSeventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes.ResultsPatients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P ConclusionsUrinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that produces a wide variety of adverse effects in humans. Catalpol, a major bioactive compound enriched in the dried root of Rehmannia glutinosa, is a major iridoid glycoside that alleviates bone loss. However, the detailed mechanisms underlying the effects of catalpol remain unclear. The present study evaluated the effects of catalpol on TCDD-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Catalpol inhibited TCDD-induced reduction in cell viability and increases in apoptosis and autophagic activity in osteoblastic MC3T3-E1 cells. Additionally, pretreatment with catalpol significantly decreased the nitric oxide and nitrite levels compared with a control in TCDD-treated cells and significantly inhibited TCDD-induced increases in the levels of cytochrome P450 1A1 and extracellular signal-regulated kinase. Pretreatment with catalpol also effectively restored the expression of superoxide dismutase and extracellular signal-regulated kinase 1 and significantly enhanced the expression of glutathione peroxidase 4 and osteoblast differentiation markers, including alkaline phosphatase and osterix. Taken together, these findings demonstrate that catalpol has preventive effects against TCDD-induced damage in MC3T3-E1 osteoblastic cells.

Background/Aim Although alcohol consumption is known to affect the incidence of diabetes mellitus (DM), reports on the effects of moderate alcohol consumption on DM incidence have been inconsistent. This community-based prospective cohort study was performed to investigate the incidence of DM in male Korean moderate alcohol drinkers. Methods The Ansan and Ansung cohort was used for the analysis. The study population included a total of 3,492 men with no history of DM. The subjects were classified as mild (1–14 g/d), moderate (15–29 g/d), and heavy (≥30 g/d) drinkers based on their amount of alcohol consumption. The incidence rates of DM in the three groups were compared and analyzed over a 10 year follow-up period. Results The hazard ratios (HRs) for DM incidence were 25.12 (95% confidence interval [CI], 21.73–28.90) per 1,000 person years (PY) in mild drinkers, 31.13 (26.11–36.83) per 1,000 PY in moderate drinkers, and 31.68 (26.81–37.18) per 1,000 PY in heavy drinkers (p for trend, p = 0.043). Multivariate regression analysis showed that the HRs (95% CI) for DM were 1.25 (0.97–1.61, p = 0.086) in moderate drinkers and 1.30 (1.01–1.68, p = 0.045) in heavy drinkers compared to mild drinkers. The changes in pancreatic insulin secretion were more remarkable than those in insulin resistance in all three groups. Conclusions The incidence of DM in male Korean moderate drinkers did not increase significantly over the observation period. However, the incidence of DM tended to increase with increasing alcohol consumption. Pancreatic insulin secretion may play a more important role than insulin resistance in the relationship between alcohol and incidence of DM.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant. TCDD accumulates in the food chain, mainly in the fatty tissues of the human body where it causes various toxic effects. Biochanin A is a natural organic compound in the class of phytochemicals known as flavonoids. We investigated whether biochanin A suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. In the present study, biochanin A suppressed TCDD-induced loss of lipid accumulation. Pretreating the cells with biochanin A increased the levels of the adipogenesis-associated factors peroxisome proliferator-activated receptor γ and adiponectin, which were inhibited by TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with biochanin A. Biochanin A also inhibited the TCDD-driven decrease in production of insulin receptor substrate-1 and glucose transporter 4. These results suggest a preventive effect of biochanin A against TCDD in the development of insulin resistance and diabetes. TCDD increased production of intracellular calcium ([Ca2+]i), prostaglandin E2, cytosolic phospholipase A2, and cyclooxygenase-1, while reducing the level of peroxisome proliferator-activated receptor gamma coactivator 1-alpha. However, biochanin A inhibited these TCDD-induced effects. We conclude that biochanin A is an attractive compound for preventing TCDD-induced wasting syndrome.

Background and objective: The effects of age and related factors on insulin sensitivity have not been definitively evaluated in East Asian populations. We proposed a reference range for the glucose disposal rate (M-value) on hyperinsulinemic-euglycemic study and its association with other parameters. Methods: Healthy, non-diabetic young (n=10) and elderly (n=13) male subjects with normal body mass index were eligible for this study. Subjects who passed the oral glucose tolerance test (OGTT) underwent hyperinsulinemic-euglycemic clamp with high-dose (80 mU/m2·min) insulin infusion. Results: M-values were normalized to body weight (MBW) and fat-free mass (MFFM). Neither M-value was significantly different between age groups (P=0.458 and P=0.900, respectively). An inverse correlation was observed between MFFM and baseline insulin (r=-0.418; P=0.047), baseline C-peptide (r=-0.426; P=0.043) and OGTT 2-hour glucose (r=-0.452; P=0.030). Regarding correlations with other insulin sensitivity indices, M-values were positively associated with the Matsuda index but not with homeostasis model assessment of insulin resistance. Conclusion: Our results suggest that age is not a critical determinant of insulin sensitivity, while fasting insulin and C-peptide levels, OGTT 2-hour glucose level, and Matsuda index are predictable markers of insulin sensitivity in healthy Koreans.

Methylglyoxal (MG), a highly reactive dicarbonyl compound, is a major cell-permeant precursor of advanced glycation end-products, which are associated with several conditions, including diabetes and degenerative diseases. Crocin, a constituent of saffron, is involved in many pharmacological activities. Recent studies have reported that crocin exerts protective effects against bone diseases. Osteoclasts are multinucleated cells derived from hematopoietic stem cells that are responsible for bone resorption. The up- or down-regulation of their proliferation and differentiation is often associated with many bone-related diseases. The present study aimed to investigate the effects of crocin on osteoclast differentiation and to clarify its mechanism of action in the presence of MG. We demonstrated that crocin reversed MG-induced inhibition of tartrate-resistant acid phosphatase activity and bone resorption activity in osteoclasts. Quantitative reverse transcription-polymerase chain reaction analysis indicated that crocin treatment decreased the expression of TNF receptor-associated factor-6 (TRAF6), Akt2, extracellular-signal-regulated kinase-1 (ERK1), osteopetrosis-associated transmembrane protein 1 (OSTM1), and matrix metalloproteinase 9 (MMP-9) genes in the presence of MG. Crocin pretreatment also reversed MG-induced changes in mitochondrial mass, mitochondrial membrane potential, mitochondrial superoxide, and glyoxalase I levels. Taken together, our data suggest that crocin may be a useful therapeutic agent for the treatment of diabetic bone disorders.

Background/aims Due to recent increases in the disease burden of diabetes mellitus, the Health Insurance Review and Assessment Service (HIRA) of Korea implemented a quality assessment of the treatment of diabetes to improve patient care. The present study was conducted to identify any changes after the implementation of the diabetes quality assessment (DQA). Methods The present study evaluated eight quality assessment indicators that were proposed by the HIRA in all patients with diabetes who visited a university hospital in Korea between 2009 and 2014. The indicators were statistically compared according to the characteristics of the subjects. Results There were several significant differences in the indicators among the subjects according to their demographic characteristics. Female patients had a higher continuity of treatment (COT) than that of male patients, and the insulin-treated group had a higher COT than that of the non-treated group, as well as a higher rate of undergoing the diabetes complication tests (DCTs). Patients between 40 and 80 years of age had the highest COT, while patients under 40 years of age had the lowest COT but the highest rate of taking the DCTs. Patients receiving treatment from an endocrinologist exhibited higher numbers of DCTs performed but displayed lower proportions for the prescription indicators. Conclusion The present analysis of the DQA findings revealed that endocrinologists combine prevention and management of diabetes complications with measures for glycemic control. Thus, the effective management of diabetes likely entails systematic joint treatment regimens that involve an endocrinologist.

Methylglyoxal (MG) is a reactive dicarbonyl compound produced by glycolytic processing, which has been identified as a precursor of advanced glycation end products. Elevated MG levels in patients with diabetes are believed to contribute to diabetic complications, including bone defects. The objective of this study was to evaluate the effect of MG on RANKL-induced osteoclast differentiation in RAW264.7 cells, a murine macrophage cell line. RAW264.7 cells were cultured in medium containing 50 ng/mL RANKL and different concentrations of MG. Tartrate-resistant acid phosphatase (TRAP) activity and osteoclast bone resorbing activity were assessed and changes in intracellular calcium concentration, mitochondrial mass, mitochondrial membrane potential, and glyoxalase I level were examined. In addition, real-time RT-PCR assay was used to analyse osteoclast-associated genes. MG markedly inhibited RANKL-induced TRAP activity. MG treatment resulted in a significant decrease in intracellular calcium concentration, mitochondrial mass, mitochondrial membrane potential, and glyoxalase I level during osteoclastogenesis. In addition, MG increased the formation of mitochondrial superoxide. Quantitative reverse transcriptase-polymerase chain reaction revealed increased expression of the TRAF6, GAB2, ERK1, c-Fos, NFATc1, CLCN7, and OSTM1 genes, decreased expression of TCIRG and carbonic anhydrase II, and unchanged expression of cathepsin K and MMP-9 upon MG treatment. MG had no effect on the bone resorbing activity of osteoclasts. Our findings indicate that MG inhibits TRAP and glyoxalase I activity and impairs mitochondrial function in osteoclasts. Further validation of the underlying pathway is necessary.

Objective: To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 yrs.Subjects and Methods: An elderly cohort of T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort.Results: From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957).Conclusions: Our study suggests that multi-biomarkers may be useful for predicting DME in elderly T2DM patients.

Persistent organic pollutants(POPs) are suggested to be potential risk factors for gestational diabetes mellitus(GDM). We examined the hypothesis that the aryl hydrocarbon receptor trans-activating(AhRT) activity, a potential biomarker for the presence of POPs, could be a GDM risk factor in pregnant women. A total of 390 GDM and 100 normal pregnant(non-GDM) subjects in the Korea National Diabetes Program cohort voluntarily participated. We measured AhRT activity and concentrations of ATP and reactive oxygen in the serum collected at the screening of the participants for GDM using recombinant Hepa1c1c7 cells. Odds ratios(ORs) and 95% confidence intervals(CIs) were estimated using multivariable logistic regression models. The sensitivity and specificity of AhRT activity for GDM diagnostics were measured by receiver operating characteristic(ROC) analysis. Body mass index at pre-pregnancy and delivery and systolic blood pressure were significantly higher in the GDM group. AhRT activity was higher, and ATP concentrations were lower in the GDM group than the non-GDM group(P P 2 = 0.387) and negatively correlated with ATP production(r2 = −0.650). In the ROC curve, AhRT activity had 70.9% sensitivity and 90.0% specificity for glucose-50, a GDM screening method. In conclusion, this study suggests that serum AhRT activity is positively associated with the risk of GDM.

Hepatic hepcidin is a well-known major iron regulator and has been reported to be closely related to hepatitis C virus (HCV) replication. However, pharmacological targeting of the hepcidin in HCV replication has not been reported. A short-chain fatty acid, 4-Phenyl butyrate (4-PBA), is an acid chemical chaperone that acts as a histone deacetylase inhibitor (HDACi) to promote chromosomal histone acetylation. Here, we investigated the therapeutic effect of 4-PBA on hepcidin expression and HCV replication. We used HCV genotype 1b Huh 7.5-Con1 replicon cells and engraftment of NOD/SCID mice as in vitro and in vivo models to test the effect of 4-PBA. It was found that 4-PBA inhibited HCV replication in Huh7.5-Con1 replicon cells in a concentration- and time-dependent manner through the induction of hepcidin expression by epigenetic modification and subsequent upregulation of interferon-&alpha, signaling. HCV formed a membranous web composed of double-membrane vesicles and was utilized for RNA replication. Moreover, 4-PBA also disrupted the integrity of the membranous web and interfered with the molecular interactions critical for the assembly of the HCV replication complex. These findings suggest that 4-PBA is a key epigenetic inducer of anti-HCV hepatic hepcidin and might at least in part play a role in targeting host factors related to HCV infection as an attractive complement to current HCV therapies.

Aim: Many studies suggest that the persistent organic pollutants (POPs) is a risk factor of type 2 diabetes. The relationship between dietary factors and POPs has been explored recently. POPs are fat-soluble substances that accumulate through the consumption of high fat diets, fish, meat and dairy products. Vegetables and fruits are known to prevent the accumulation of POPs. We aimed to examine the associations between dietary factors and serum cumulative bioactivity of AhR ligand mixture (AhRB) as a biomarker of POPs in subjects at high risk for type 2 diabetes. Methods: We performed a cross-sectional analysis of 304 prediabetic subjects using the Korea National Diabetes Program cohort data. AhRB was divided into quartiles according to the concentrations. (Q1 (the lowest quartile): (Q1 (the lowest quartile): 1.7±0.3, Q2: 2.4±0.2, Q3:3.1±0.2, Q4 (the highest quartile): 3.9±0.2). Socio-demographic, health related-behaviors, and dietary factors were assessed. Dietary factors were collected from the 3-day dietary records and food frequency questionnaire. Results: Starting with the Q1 of AhRB, adjusted mean concentrations of serum triglycerides were 147.06±12.97, 151.30±12.64, 125.80±13.19 and 166.78±13.76 mg/dL for ascending quartiles, respectively (P< 0.05). In the 3Q of AhRB, the highest consumption of sugars (Q3: 13.6±11.6g, P=0.016) and dairy products (Q3: 117.0±126.6g, P=0.032) were shown compared to those of other three groups. On multiple linear regression analysis, high consumption of dairy products (P< 0.05) and fried fish with oil (P < 0.05) were significantly positive associated with serum AhRB concentration after adjusting covariates. Conclusion: This study found an association between dietary factors and AhRB level, however, further longitudinal studies are needed to clarify the effects of these dietary factors on POP levels. Disclosure S. Chon: None. H. Lim: None. J. Kim: None. S. Oh: None.

We investigated the efficacy and safety of liraglutide 3 mg daily in combination with diet and exercise 2, 4, and 6 months after initiation in real-world settings in Korea.People first using liraglutide starting in 2018 were recruited from ten sites in Korea. Body weight and body mass index (BMI) were measured after 2, 4, and 6 months and compared with baseline values.The full cohort comprised 769 participants: 672 in the 2-month group, 427 in the 4-month group, and 219 in the 6-month group. The baseline mean ± standard deviation of BMI and body weight were 32.2 ± 5.1 kg/mIn real-world settings in Korea, daily treatment with liraglutide 3 mg was associated with clinically meaningful weight loss without serious adverse events.

Background The prevalence of diabetes mellitus (DM) continues to increase, and the disease burden is the highest of any medical condition in Korea. However, large-scale clinical studies have not yet conducted to establish the basis for diabetes prevention in Korea. Methods The hospital-based Korean Diabetes Prevention Study (H-KDPS) is a prospective, multi-center, randomized, open-label controlled study conducted at university hospitals for the purpose of gathering data to help in efforts to prevent type 2 DM. Ten university hospitals are participating, and 744 subjects will be recruited. The subjects are randomly assigned to the standard care group, lifestyle modification group, or metformin group, and their clinical course will be observed for 36 months. Results All intervention methodologies were developed, validated, and approved by Korean Diabetes Association (KDA) multi-disciplinary team members. The standard control group will engage in individual education based on the current KDA guidelines, and the lifestyle modification group will participate in a professionally guided healthcare intervention aiming for ≥5% weight loss. The metformin group will begin dosing at 250 mg/day, increasing to a maximum of 1,000 mg/day. The primary endpoint of this study is the cumulative incidence of DM during the 3 years after randomization. Conclusion The H-KDPS study is the first large-scale clinical study to establish evidence-based interventions for the prevention of type 2 DM in Koreans. The evidence gathered by this study will be useful for enhancing the health of Koreans and improving the stability of the Korean healthcare system (Trial registration: CRIS KCT0002260, NCT02981121).

The aim of this study was to investigate possible relationships among hematologic factors, psychological dimensions, the presence of self-reported sleep problems, and clinical characteristics in patients with burning mouth syndrome (BMS).Twenty-five postmenopausal female patients with primary BMS (aged 55.2 ± 9.6 years) were included. All participants underwent clinical and psychological evaluations and blood sampling. The patients were subdivided according to the absence or presence of the self-reported sleep problems.Pain intensity of BMS patients with sleep problems was significantly higher than those without sleep problems, and the severity of oral complaints was correlated with the presence of depression, anxiety, hostility, phobia, and psychosis. Estradiol levels were significantly lower, and FSH and LH levels were higher in BMS patients with sleep problems than those without sleep problems.BMS patients with sleep problems may suffer inharmonious psychoneuroendocrinological interactions that might worsen oral BMS symptoms.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has various toxicological effects in adipose tissue. Evidence is accumulating that glabridin, a flavonoid extracted from licorice, has beneficial effects on the regulation of glucose homeostasis. In this study, we investigated whether glabridin suppresses TCDD-induced loss of adipogenic action using 3T3-L1 adipocytes as a cell culture model of wasting syndrome. Glabridin effectively suppressed TCDD-induced loss of lipid accumulation in this model. Pretreating cells with glabridin increased the gene expression of not only the adipogenesis-associated key transcription factors peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha, but also lipoprotein lipase in the presence of TCDD. TCDD decreased insulin-stimulated glucose uptake, which was effectively restored by pretreatment with glabridin. Glabridin also inhibited the TCDD-driven decreased production of insulin receptor substrate 1 and glucose transporter 4. TCDD increased the production of mitochondrial superoxides, prostaglandin E2 , phospholipase A2 , cyclooxygenase-1 and intracellular calcium concentrations, while reducing the production of PPARγ coactivator 1 alpha and glycolysis. However, glabridin treatment reduced these TCDD-induced effects. We conclude that glabridin suppresses the TCDD-induced loss of lipid accumulation in 3T3-L1 adipocytes by regulating the levels of PPARγ, CCAAT/enhancer binding protein alpha, lipoprotein lipase, glucose uptake, prostaglandin E2 and energy metabolism. These results also provide in vitro evidence of the effects of glabridin on adipocyte metabolism, which suggests a protective effect against dioxin exposure in the development of insulin resistance and diabetes.

AIM To evaluate the efficacy and safety of ipragliflozin vs placebo as add-on therapy to metformin and sitagliptin in Korean patients with type 2 diabetes mellitus (T2DM). METHODS This double-blind, placebo-controlled, multi-centre, phase III study was conducted in Korea in 2015 to 2017. Patients were randomized to receive either ipragliflozin 50 mg/day or placebo once daily for 24 weeks in addition to metformin and sitagliptin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to end of treatment (EOT). RESULTS In total, 143 patients were randomized and 139 were included in efficacy analyses (ipragliflozin: 73, placebo: 66). Baseline mean (SD) HbA1c levels were 7.90 (0.69)% for ipragliflozin add-on and 7.92 (0.79)% for placebo. The corresponding mean (SD) changes from baseline to EOT were -0.79 (0.59)% and 0.03 (0.84)%, respectively, in favour of ipragliflozin (adjusted mean difference -0.83% [95% CI -1.07 to -0.59]; P < .0001). More ipragliflozin-treated patients than placebo-treated patients achieved HbA1c target levels of

Background: Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial in dex (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is un clear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD). Methods: This was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed. Results: Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT af ter adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-AS CVD group into three subgroups according to the CAVI score (

Increased glycation of macromolecules via the reactive dicarbonyl and α-oxoaldehyde methylglyoxal (MG) has shown an association with diabetes and its complications. In the present study, the protective effects of sciadopitysin against MG-induced oxidative cell damage were investigated in the insulin-producing pancreatic β-cell line, RIN-m5F cells. When exposed to MG for 48 hours, RIN-m5F cells experienced significant loss of viability and impaired insulin secretion; however, treatment with sciadopitysin protected RIN-m5F cells against MG-induced cell death and decreased insulin secretion. Treatment of RIN-m5F cells with sciadopitysin prevented MG-induced production of interleukin-1β, intracellular reactive oxygen species and cardiolipin peroxidation. Furthermore, sciadopitysin increased adenosine monophosphate-activated protein kinase phosphorylation of RIN-m5F cells. Treatment of cells with sciadopitysin increased the activity of glyoxalase I and decreased the levels of MG-protein adducts, indicating that sciadopitysin protects against MG-induced protein glycation by increasing MG detoxification. Taken together, the results indicated the potential utility of sciadopitysin as an intervention against MG-induced cell damage in pancreatic β-cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3-E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca2+ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased. TCDD treatment increased the mRNA levels of extracellular signal-regulated kinase 1 and nuclear factor kappa B, and significantly decreased the level of protein kinase B (AKT) in MC3T3-E1 osteoblastic cells. However, the presence of xanthohumol alleviated the pathological effects of TCDD. In addition, xanthohumol treatment significantly increased the expression of genes associated with osteoblast differentiation (alkaline phosphatase, osteocalcin, osteoprotegerin and osterix). We conclude that xanthohumol has a beneficial influence and may antagonize TCDD toxicity in osteoblastic cells.

Methylglyoxal (MG) is a potent protein glycating agent and an important precursor of advanced glycation end products, which are involved in the pathogenesis of diabetic osteopathy. In this study, we investigated the effects of limonene on MG-induced damage in osteoblastic MC3T3-E1 cells. Pretreating cells with limonene prevented MG-induced protein adduct formation, tumor necrosis factor alpha and interleukin-6 release, mitochondrial superoxide production, and cardiolipin peroxidation. In addition, limonene increased glyoxalase I activity, and glutathione and heme oxygenase-1 levels in the presence of MG. Pretreatment with limonene prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate loss, and reduced the levels of adenosine monophosphate-activated protein kinase, peroxisome proliferator activated receptor γ coactivator 1α, and nitric oxide. These results demonstrate that limonene may prevent the development of diabetic osteopathy.

Bergenin, an active component of plants in the genus Bergenia, has multiple biological activities, including anti-inflammatory and immunomodulatory properties. We investigated the effects of bergenin on MC3T3-E1 osteoblasts. Bergenin treatment significantly elevated collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis, and mineralization in the cells (p

Background: This is part of a prospective study carried out as a national project to secure standardized public resources for type 2 diabetes mellitus (T2DM) patients in Korea. We compared various characteristics of long-standing T2DM patients with diabetic retinopathy (DR) and macular edema (ME). Methods: From September 2014 to July 2015, T2DM patients with disease duration of at least 15 years were recruited at a single university hospital. Clinical data and samples were collected according to the common data elements and standards of procedure developed by the Korean Diabetes Association Research Council. Each participant was assessed by ophthalmologists for DR and ME. Results: Among 220 registered patients, 183 completed the ophthalmologic assessment. DR was associated with longer disease duration (odds ratio [OR], 1.071; 95% confidence interval [CI], 1.001 to 1.147 for non-proliferative diabetic retinopathy [NPDR]) (OR, 1.142; 95% CI, 1.051 to 1.242 for proliferative diabetic retinopathy [PDR]) and the use of long-acting insulin (OR, 4.559; 95% CI, 1.672 to 12.427 for NPDR) (OR, 4.783; 95% CI, 1.581 to 14.474 for PDR), but a lower prevalence of a family history of cancer (OR, 0.310; 95% CI, 0.119 to 0.809 for NPDR) (OR, 0.206; 95% CI, 0.063 to 0.673 for PDR). ME was associated with higher glycosylated hemoglobin levels (OR, 1.380; 95% CI, 1.032 to 1.845) and the use of rapid-acting insulin (OR, 5.211; 95% CI, 1.445 to 18.794). Conclusion: Various clinical features were associated with DR and ME. Additional epidemiological and biorepository-based studies using this cohort are being conducted to deepen our understanding of diabetic complications in Korea.

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to affect bone metabolism. We evaluated the protective effects of the triterpene glycoside actein from the herb black cohosh against TCDD-induced toxicity in MC3T3-E1 osteoblastic cells. We found that TCDD significantly reduced cell viability and increased apoptosis and autophagy in MC3T3-E1 osteoblastic cells (P

Methylglyoxal (MG) is one of the major precursors of advanced glycation end products (AGEs), which are considered to be one of the causes of diabetes and its complications. The root and rhizomes of black cohosh (Cimicifuga racemosa) have long been used medicinally, and deoxyactein is one of its major constituents. In the present study, the protective effects of deoxyactein against MG-induced oxidative cell damage were investigated in insulin-producing pancreatic β-cells. We found that deoxyactein protected the pancreatic β-cells against MG-induced cell death. Pre-treatment with deoxyactein significantly reduced the levels of intracellular reactive oxygen species (ROS), interleukin-1β (IL-1β), cardiolipin peroxidation, and protein adduct accumulation induced by MG. Pre-treatment of the cells with deoxyactein restored glyoxalase I activity and insulin secretion which were reduced by MG, and increased the mRNA expression of insulin 2 (INS2) and pancreatic and duodenal homeobox protein-1 (PDX-1). It also increased the levels of endogenous antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GPX). Furthermore, treatment with deoxyactein increased the levels of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). These findings indicate that deoxyactein may exert beneficial effects on pancreatic β-cells via the upregulation of mitochondrial biogenesis. Taken together, these results suggest that deoxyactein may be used for the prevention of pancreatic β-cell damage.

Limonene is a common natural terpene with powerful antioxidative properties. This study investigated the effects of limonene, a terpene found in citrus fruits, on the function of the murine pre-osteoblast cell line, MC3T3-E1 cells. The results showed that limonene treatment significantly elevated collagen synthesis, alkaline phosphatase activity, osteocalcin synthesis, and mineralization in osteoblastic cells. Methylglyoxal (MG), a highly reactive dicarbonyl metabolite, is a major precursor of advanced glycation end products, which are involved in the pathogenesis of diabetic osteopathy. We therefore investigated the effects of limonene on MG-induced cytotoxicity. Pre-treatment of MC3T3-E1 cells with limonene prevented MG-induced cell death and apoptosis. Limonene also reduced MG-triggered endoplasmic reticulum (ER) stress, as indicated by decreases in the levels of the ER-localized transmembrane signal transducers ATF-6 and IRE1. Furthermore, limonene treatment significantly reduced MG-induced au...

Several environmental contaminants have been linked to the development of diabetes and increased diabetes‑associated mortality. Perfluorooctanoic acid (PFOA) is a widely used perfluoroalkane found in surfactants and lubricants, and in processing aids used in the production of polymers. Furthermore, PFOA has been detected in humans, wildlife and the environment. The present study investigated the toxic effects of PFOA on rat pancreatic β‑cell‑derived RIN‑m5F cells. Cell viability, apoptosis, reactive oxygen and nitrogen species, cytokine release and mitochondrial parameters, including membrane potential collapse, reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release were assessed. PFOA significantly decreased RIN‑m5F cell viability and increased apoptosis. Exposure to PFOA increased the formation of reactive oxygen species, mitochondrial superoxide, nitric oxide and proinflammatory cytokines. Furthermore, PFOA induced mitochondrial membrane potential collapse and reduced adenosine triphosphate levels, cardiolipin peroxidation and cytochrome c release. These results indicate that PFOA is associated with the induction of apoptosis in RIN-m5F cells, and induces cytotoxicity via increased oxidative stress and mitochondrial dysfunction.

Background The primary aim of this study was to assess the utility of fasting plasma glucose (FPG) and HbA1c to identify diabetes by the 2-hour plasma glucose (PG) criterion in the Korean population at high risk for diabetes. Methods A total of 1646 participants with a body mass index of ≥23 kg/m2 without having a history of diabetes were recruited in this study. The cut-off values of FPG and HbA1c for detecting diabetes were identified using the Youden index using receiver operating characteristic (ROC) analysis. The gold standard for diabetes prediction was defined by the 2-hour PG level of ≥200 mg/dL. Results The participants comprised 54.0% women, and the mean age of all participants was 55.0 ± 8.1 years. At baseline, FPG was 104.1 ± 14.2 mg/dL, the 2-hour PG value was 162.9 ± 55.3 mg/dL, and HbA1c was 5.9% ± 0.5%. Four hundred and forty-six subjects (27.1%) were diagnosed with diabetes and 976 subjects (59.3%) were determined to be at prediabetes. The area under the ROC curve (AUC) of FPG and HbA1c for diabetes were 0.776 and 0.802, while the AUC of FPG and HbA1c for prediabetes were 0.515 and 0.477. The optimal cut-off value for diagnosing diabetes of FPG and HbA1c were 104.5 mg/dL (sensitivity 75.8%, specificity 67.5%) and 5.9% (sensitivity 80.6%, specificity 63.8%), respectively. Conclusions FPG of 104.5 mg/dL and HbA1c value of 5.9% (41 mmol/mol) can be used as an optimal screening value for diabetes by 2-hour PG criterion in the Korean population at high risk for diabetes.

OBJECTIVE To investigate the sex differences in clinical features, including salivary flow rate, psychological distress and hypothalamic-pituitary-adrenal axis response and their inter-relationships in patients with burning mouth syndrome. SUBJECTS AND METHODS Eighteen men and 37 postmenopausal women with burning mouth syndrome underwent a comprehensive questionnaire evaluation, psychological evaluation and salivary flow rate measurement. Laboratory tests were performed to investigate the function and integrity of the hypothalamic-pituitary-adrenal axis. RESULTS Both unstimulated and stimulated salivary flow rates were higher in men than in women (unstimulated: 0.58 ± 0.32 vs. 0.37 ± 0.15 ml/min, p

Background There have been equivocal results in studies of the effects of dipeptidyl peptidase-4 inhibitors (DPP-4i) on fractures. In this study, we analyzed the effect of DPP-4i on bone fracture risk in a Korean population. Methods We extracted subjects (n = 11,164) aged 50 years or older from the National Health Insurance Service–National Sample Cohort 2.0 from 2009 to 2014. Our control group included subjects without diabetes (n = 5,582), and our treatment groups with diabetes included DPP-4i users (n = 1,410) and DPP-4i non-users (n = 4,172). The primary endpoint was the incidence of a composite outcome consisting of osteoporosis diagnosis, osteoporotic fractures, vertebral fractures, non-vertebral fractures, and femoral fractures. The secondary endpoint was the incidence of each individual component of the composite outcome. Survival analysis was performed with adjustment for age, gender, diabetes complications severity index, Charlson comorbidity index, hypertension medication, and dyslipidemia treatment. Results The incidence of the composite outcome per 1,000 person-years was 0.089 in DPP-4i users, 0.099 in DPP-4i non-users, and 0.095 in controls. There was no significant difference in fracture risk between DPP-4i users and DPP-4i non-users or controls after the adjustments (P > 0.05). The incidences of osteoporosis diagnosis, osteoporotic fractures, vertebral fractures, non-vertebral fractures, and femoral fractures were not significantly different between DPP-4i users and non-users. The results of subgroup analyses by gender and age were consistent. Conclusion DPP-4i had no significant effect on the risk of fractures in a Korean population., Graphical Abstract

Background Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. Methods RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. Results The presence of 20 μM TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 μM TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. Conclusion This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production., Graphical Abstract

Methylglyoxal (MG), a reactive sugar-derived metabolite, exerts harmful effects by inducing oxidative stress, which aggravates a series of diabetic complications, including osteoporosis. The present study was performed to examine the effects of luteolin, a dietary polyphenolic flavonoid, on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. Pretreatment of MC3T3-E1 osteoblastic cells with luteolin prevented MG-induced cell death and production of tumor necrosis factor-alpha, intracellular reactive oxygen species, mitochondrial superoxide, and cardiolipin peroxidation. In addition, luteolin increased the levels of glutathione and nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased the inhibition of heme oxygenase-1 activity by MG. Pretreatment with luteolin prior to MG exposure reduced MG-induced mitochondrial dysfunction and increased the peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) and nitric oxide levels, suggesting that luteolin may induce mitochondrial biogenesis. Taken together, these observations indicated that luteolin has potential as a preventive agent against the development of diabetic osteopathy related to MG-induced oxidative stress in diabetes.

Methylglyoxal (MG) is an endogenous product of glucose metabolism known to be toxic to cells and to be present in elevated concentrations under certain pathophysiological conditions. In the present study the effect of actein isolated from black cohosh on MG-induced cytotoxicity was investigated in MC3T3-E1 osteoblastic cells. RESULTS Treatment of MC3T3-E1 osteoblastic cells with actein prevented MG-induced cell death and the production of intracellular reactive oxygen species (ROS), mitochondrial superoxide, inflammatory cytokines and soluble receptor for advanced glycation end-products (sRAGE). In addition, actein increased the activity of glyoxalase I and levels of reduced glutathione (GSH) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). These findings suggest that actein protects against MG-induced cell damage by reducing oxidative stress and increasing MG detoxification. Treatment with actein prior to MG exposure reduced MG-induced mitochondrial dysfunction by preventing mitochondrial membrane potential dissipation and adenosine triphosphate (ATP) loss. Additionally, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and nitric oxide (NO) levels were significantly increased by actein, suggesting that actein may induce mitochondrial biogenesis. CONCLUSION This study demonstrates that actein reduces MG-induced damage in osteoblastic MC3T3-E1 cells by enhancing antioxidant defenses, the glyoxalase system and mitochondrial biogenesis. ? 2016 Society of Chemical Industry

BACKGROUND Gastrointestinal (GI) symptoms are common in patients with type 2 diabetes mellitus (T2DM). Rebamipide is an effective gastric cytoprotective agent, but there are few data on its usefulness in T2DM. The aim of this study is to evaluate the improvement of GI symptoms after rebamipide treatment in patients with T2DM. METHODS Patients with T2DM and atypical GI symptoms were enrolled. They took rebamipide (100 mg thrice daily) for 12 weeks and filled out the diabetes bowel symptom questionnaire (DBSQ) before and after rebamipide treatment. The DBSQ consisted of 10 questions assessing the severity of GI symptoms by a 1 to 6 scoring system. Changes in the DBSQ scores before and after rebamipide treatment were analyzed to evaluate any improvements of GI symptoms. RESULTS A total of 107 patients were enrolled, and 84 patients completed the study. The mean age was 65.0±7.8, 26 patients were male (24.8%), the mean duration of T2DM was 14.71±9.12 years, and the mean glycosylated hemoglobin level was 6.97%±0.82%. The total DBSQ score was reduced significantly from 24.9±8.0 to 20.4±7.3 before and after rebamipide treatment (P

Methylglyoxal (MG) contributes to the pathogenesis of age- and diabetes-associated complications. The present study investigated the effects of glabridin on MG-induced cytotoxicity in MC3T3-E1 osteoblastic cells. MC3T3-E1 cells were treated with glabridin in the presence of MG, and markers of mitochondrial function and oxidative damage were examined. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin prevented MG-induced cell death, the production of intracellular reactive oxygen species and mitochondrial superoxides, cardiolipin peroxidation, and the production of inflammatory cytokines. The soluble form of receptor for advanced glycation end products (sRAGEs)/RAGE ratio increased upon MG treatment, but less so after pretreatment with glabridin, which also increased the level of reduced glutathione and the activities of glyoxalase I and heme oxygenase-1, all of which were reduced by MG. In addition, glabridin elevated the level of nuclear factor erythroid 2-related factor 2. These findings suggest that glabridin protects against MG-induced cell damage by inhibiting oxidative stress and increasing MG detoxification. Pretreatment of MC3T3-E1 osteoblastic cells with glabridin reduced MG-induced mitochondrial dysfunction. Additionally, the nitric oxide level significantly increased upon glabridin pretreatment. Together, these data show that glabridin may potentially serve to prevent the development of diabetic bone disease associated with MG-induced oxidative stress.