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The Korean National Health Information Database (NHID) contains big data combining information obtained from the National Health Insurance Service and health examinations. Data are provided in the form of a cohort, and the NHID can be used to conduct longitudinal studies and research on rare diseases. Moreover, data on the cause and date of death are provided by Statistics Korea. Research and publications based on the NHID have increased explosively in the field of endocrine disorders. However, because the data were not collected for research purposes, studies using the NHID have limitations, particularly the need for the operational definition of diseases. In this review, we describe the characteristics of the Korean NHID, operational definitions of endocrine diseases used for research, and an overview of recent studies in endocrinology using the Korean NHID.

This study aimed to investigate the effect of using a combination of ipguk (koji) and zeolite, as an alternative to the traditional nuruk fermented agents and rice and rice husks combination, on off-flavor suppression in solid fermented spirits. In alcohol production from solid fermented mash, the traditional brewing combination (nuruk + rice husks) produced over 1.3 times more alcohol than that obtained using the alternative combination (ipguk + zeolite). The levels of acetic, butyric, isovaleric acids, and methyl mercaptan, the components causing the offensive odor of distilled liquor (25% alcohol), were significantly reduced upon using the alternative combination as compared to that by the traditional combination. The acetic acid level decreased from 99.38 mg/L to 19.34-24.12 mg/L when using the alternative combination. Butyric acid, isovaleric acid, and methyl mercaptan levels decreased from 95.90, 5.37, and 426.78 mg/L, respectively, to undetectable levels. The furfural content decreased up to 4.3 times. In contrast, acetaldehyde levels increased from 228.04 mg/L to 529.74-578.71 mg/L when using the alternative combination. As the moisture content of the solid-fermented mash prepared with the alternative combination increased (from 40 to 55%), the alcohol production also increased proportionally, and the alcohol content of the distillate was elevated (from 37.14 to 43.74%).

Metformin as an oral glucose-lowering drug is used to treat type 2 diabetic mellitus. Considering the relatively high incidence of cardiovascular complications and other metabolic diseases in diabetic mellitus patients, a combination of metformin plus herbal supplements is a preferrable way to improve the therapeutic outcomes of metformin. Ginseng berry, the fruit of Panax ginseng Meyer, has investigated as a candidate in metformin combination mainly due to its anti-hyperglycemic, anti-hyperlipidemic, anti-obesity, anti-hepatic steatosis and anti-inflammatory effects. Moreover, the pharmacokinetic interaction of metformin via OCTs and MATEs leads to changes in the efficacy and/or toxicity of metformin. Thus, we assessed how ginseng berry extract (GB) affects metformin pharmacokinetics in mice, specially focusing on the effect of the treatment period (i.e., 1-day and 28-day) of GB on metformin pharmacokinetics. In 1-day and 28-day co-treatment of metformin and GB, GB did not affect renal excretion as a main elimination route of metformin and GB therefore did not change the systemic exposure of metformin. Interestingly, 28-day co-treatment of GB increased metformin concentration in the livers (i.e., 37.3, 59.3% and 60.9% increases versus 1-day metformin, 1-day metformin plus GB and 28-day metformin groups, respectively). This was probably due to the increased metformin uptake via OCT1 and decreased metformin biliary excretion via MATE1 in the livers. These results suggest that co-treatment of GB for 28 days (i.e., long-term combined treatment of GB) enhanced metformin concentration in the liver as a pharmacological target tissue of metformin. However, GB showed a negligible impact on the systemic exposure of metformin in relation to its toxicity (i.e., renal and plasma concentrations of metformin).

Background Diabetes mellitus is a major risk factor for heart failure. A recent consensus statement recommended annual cardiac biomarker testing (e.g. natriuretic peptide or high-sensitivity cardiac troponin) for all patients with diabetes. We aimed to identify patients at a higher risk of hospitalization for heart failure among patients with type 2 diabetes to prioritize those who would require screening. Methods Overall, 1,189,113 patients who underwent two medical health checkup cycles (2009–2012 and 2011–2014) and had stable diabetic kidney disease (DKD) phenotype in the Korean National Health Insurance Service database were included in this study. After excluding those with concurrent proteinuria (PU) and reduced estimated glomerular filtration rate, three groups (no-DKD, PU+DKD, and PU−DKD) were identified. A fatty liver index of ≥ 60 was defined as metabolic dysfunction–associated fatty liver disease (MAFLD). Patients were followed up until December 2018 or until outcomes developed. The Cox proportional hazard model was used to compare the risk of hospitalization for heart failure across groups. Results During an average of 6.6 years of follow-up, 5781 patients developed hospitalization for heart failure. After adjusting for covariates, the risk of hospitalization for heart failure was highest in the PU+DKD group [HR 3.12, 95% CI (2.75–3.55)], followed by the PU−DKD group [HR 1.85, 95% CI (1.73–1.99)] using the no-DKD group as the reference category. The risk of hospitalization for heart failure was comparable regardless of MAFLD status in patients who already had DKD. However, in the no-DKD group, the risk of hospitalization for heart failure was 1.4 times higher in patients with MAFLD than in those without [HR 1.41, 95% CI (1.31–1.52)]. Conclusions In lines with the international consensus statement, we suggest that annual cardiac biomarker testing should be conducted at least in patients with DKD and/or MAFLD.

Background : The increasing prevalence of type 2 diabetes mellitus (T2DM) has led to a significant health burden. Technological advancements have highlighted the benefits of digital therapeutics for chronic diseases. In this study, we aimed to investigate the effects of a mobile application on weight reduction in patients with T2DM. Methods : A total of 48 patients with T2DM was included in this single-center, randomized, controlled trial. In addition to conventional treatment, participants in the intervention group used a mobile application-based self-management system for diet, exercise, and medication adherence. The primary outcome of this study was weight change after 3 months of intervention, and secondary outcomes were metabolic parameters. Results : After 12 weeks, no significant differences in body weight change were observed between the intervention and control groups (P=0.229). However, a significant difference was found in waist circumference (WC) between the two groups, wherein the control group showed an increase in WC (from 95.00±8.89 cm to 95.76±9.72 cm), while the intervention group showed a reduction (from 91.93±6.25 cm to 90.75±6.01 cm) with a significant time by group interaction (P=0.016). Additionally, participants with good compliance exhibited a more evident reduction in WC (P=0.037). However, no significant differences were found in other metabolic parameters between the two groups. Conclusion : Lifestyle modification using short-term mobile applications effectively reduced WC, especially in patients with good adherence to the application. However, weight reduction was not achieved.

To enhance the flavor of solid-state fermented spirits, the effects of powdered milk on the composition of the distillation fractions obtained by two different distillation methods were evaluated. In the solid-state fermented product, the addition of whole milk powder did not affect alcohol production. However, the addition of milk increased the amino acid content and reducing sugar content, and decreased the formic, acetic, and succinic acid contents. Distillation using a microwave was four times faster than distillation using steam; however, the resulting number of fractions was high, with a wide range of alcohol flow rates. After the addition of whole milk powder, the contents of ethyl acetate and ethyl caproate were 2 times and 16-27 times higher, respectively, in the fraction, and the contents of butyric, valeric, and hexanoic acids among the volatile organic acids increased. In addition, the content of furfural, an odor component, increased 3.45 times from 1,393.73 mg/L to 4,801.93 mg/L. The microwave distillation method resulted in a 1.46-fold higher ethyl caproate content in the distillate compared with that obtained by steam distillation. However, as the temperature of the solid-state fermented mash was raised to over 300°C, the content of furfural increased by 3.29 times. These results support the use of milk powder in distilled spirits and may guide the development of optimized methods.

This study aimed to identify the phytochemical compounds in purple wheat bran ‘Arriheuk’ extract, with water, 50% ethanol and 70% ethanol and determine its physiological activities. Six types of flavonoids were identified in ‘Arriheuk’ extract using a HPLC analysis. The highest total polyphenol content was observed in the 70% ethanol extract, while the highest total flavonoid content was obtained both from the water and the 70% ethanol extracts of ‘Arriheuk’. 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity was significantly high in the 48-h water extract and the 12-h 70% ethanol extract, while the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) free radical scavenging activity was not significantly different between the two extracts. Cell viability, determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, was high for cells treated with 70% ethanol extract. The apoptosis protective effect, confirmed by Hoechst staining, showed that the morphological features were significantly reduced in cells treated with the 70% ethanol extract. Oil-Red-O staining was used to confirm the protective effect of ‘Arriheuk’ extracts on the intracellular lipid accumulation in cells, and the results showed the best inhibitory effect was observed at the 70% ethanol extract. However, the effect decreased in a concentration dependent manner. These results may improve the usage of ‘Arriheuk’ as a food material in the future.

Background: The role of gut microbiota in metabolic diseases has recently been widely verified. Thyroid hormones are essential for the regulation of energy homeostasis and metabolic processes. However, the relationship between thyroid function and host gut microbial communities is not properly understood. Method: To determine whether and how gut microbiota is associated with thyroid function, metagenomics analysis of the bacterial population in fecal samples of rat models of hyperthyroidism (induced by levothyroxine) and hypothyroidism (induced by propylthiouracil or thyroidectomy) was conducted through 16SrRNA gene sequencing. Finding: Our results revealed that all thyroid dysfunction models were definitely established and gut microbial composition varied according to different thyroid functional status. The relative abundance of Ruminococcus was significantly higher in the hyperthyroidism group (HE) vs both the normal and hypothyroidism (HO) groups while S24-7 was significantly higher in the HO group compared to both the normal and HE groups. The relative abundance of Prevotellaceae and Prevotella were significantly lower in the HO group vs the normal. Firmicutes and Oscillospira was significantly higher in the SHO (surgery-induced hypothyroidism) group than the SHAM group, while Prevotellaceae andPrevotella showed lower abundance in the SHO group compared to the SHAM group. Interpretation: This is the first perspective study of the relationship between thyroid gland and gut microbiota using Next Generation Sequencing-based microbial identification technology. We demonstrated that thyroid status and function influenced the gut microbial composition, and the results presented here can be used as reference in future studies to identify potential mechanism(s) by which thyroid modulates gut microbial population. Funding Statement: This work was supported by a National Research Foundation (NRF) of Korea Grant funded by the Korean Government (NRF- 2019R1A2B5B01070365). This work was also supported by the Main Research Program (E0170602-02) of the Korea Food Research Institute (KFRI) funded by the Ministry of Science and ICT. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal experimental protocol was approved by the Institutional Animal Care and Use Committee of Dongguk University (approval no. 2015-08128) and all experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.

Type 2 diabetes is a risk factor for Parkinson's disease (PD). Recently, it has been reported that proteinuria without reduced estimated glomerular filtration rate (eGFR) can increase the risk of PD development. The objective of this study was to evaluate the risk of PD among Korean adults with type 2 diabetes stratified by proteinuria (PU) and eGFR levels.Using the Korean National Health Insurance Service database, a total of 2,217,326 patients with type 2 diabetes who underwent regular health check-ups from 2009 to 2012 were included. These patients were classified into four groups (no-diabetic kidney disease (DKD) (PUThe prevalence of PUReduced eGFR and/or proteinuria might be independent risk factors for boosting PD development among patients with type 2 diabetes. More attention should be paid to PD in patients with DKD, even in a younger aged population.

Background: Although cardiovascular outcome trials using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) showed a reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effects on stroke risk. Additionally, meta-analysis showed SGLT-2i potentially had an adverse effect on stroke risk. Contrarily, pioglitazone, a type of thiazolidinedione (TZD), has been shown to reduce recurrent stroke risk. Thus, we aimed to compare the effect of SGLT-2i and TZD on the risk of stroke in type 2 diabetes mellitus (T2DM) patients.Methods: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who used SGLT-2i or TZD from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were myocardial infarction (MI), cardiovascular death, 3-point MACE, and heart failure (HF).Results: After propensity-matching, each group included 56,794 patients. Baseline characteristics were well balanced. During the follow-up, 862 patients were newly hospitalized for stroke. The incidence rate of stroke was 4.11 and 4.22 per 1,000 person-years for the TZD and SGLT-2i groups respectively. The hazard ratio (HR) of stroke was 1.054 (95% confidence interval [CI], 0.904 to 1.229) in the SGLT-2i group compared to the TZD group. There was no difference in the risk of MI, cardiovascular death, 3-point MACE between groups. Hospitalization for HF was significantly decreased in SGLT-2i-treated patients (HR, 0.645; 95% CI, 0.466 to 0.893). Results were consistent regardless of prior cardiovascular disease.Conclusion: In this real-world data, the risk of stroke was comparable in T2DM patients treated with SGLT-2i or TZD.

This study aimed to investigate the anti-inflammatory, antioxidant, and anti-atopic dermatitis (AD) effects of haplopine, which is one of the active components in D. dasycarpus. Haplopine (12.5 and 25 μM) inhibited the mRNA expressions of inflammatory cytokines IL-6, TSLP, GM-CSF, and G-CSF and the protein expressions of IL-6 and GM-CSF in TNF-α/INF-γ-stimulated HaCaT cells. In H2O2-induced Jukat T cells, haplopine (25 and 50 μM) suppressed the productions of proinflammatory cytokines (IL-4, IL-13, and COX-2) and increased the mRNA and protein expressions of oxidative stress defense enzymes (SOD, CAT, and HO-1) in a concentration-dependent manner. In vivo, haplopine significantly attenuated the development of AD symptoms in 2,4-dinitrochlorobenzene (DNCB)-stimulated Balb/c mice, as evidenced by reduced clinical dermatitis scores, skin thickness measurements, mast cell infiltration, and serum IgE concentrations. These findings demonstrate that haplopine should be considered a novel anti-atopic agent with the potential to treat AD.

Bone mineral density (BMD) determined by dual-energy X-ray absorptiometry is considered a gold standard for diagnosing osteoporosis. Some people show discordance in BMD values measured at the femur and that at the lumbar spine (LS). The aim of the present study was to investigate whether differences in BMD T-scores between the LS and femur neck (FN) are associated with renal dysfunction in the general population of Korea.We analyzed national data for 17306 adults from the Korean National Health and Nutrition Examination Survey conducted between 2008 and 2011. BMD T-score differences between LS and FN (termed BMD offset) were calculated by subtracting FN T-scores from LS T-scores. Diminished renal function was defined as estimated glomerular filtration rates (eGFR) less than 60 mL/min/1.73 m².Among those aged ≥50 years, BMD offset was negatively associated with eGFR levels. Additionally, eGFR levels decreased linearly across increasing BMD offset quartiles. Men and women with an offset of1.5 showed a 4.79-times and 2.51-times higher risk of renal dysfunction, respectively, compared to individuals with an offset of ≤0, after adjusting for age, body mass index, educational level, current smoking, and physical activity. In contrast, there was little evidence of an association between renal dysfunction and BMD offset in subjects aged50 years.Discordance between LS and FN BMDs was significantly associated with renal dysfunction in subjects aged ≥50 years. When assessing bone health in older chronic kidney disease patients, physicians should consider the possibility of BMD discordance between LS and FN.

Background Long-term glucocorticoid use increases fracture risk by reducing bone mass. This study evaluated the relationship between hip and vertebral fractures and the total amount of systematic glucocorticoid use. Methods We randomly selected 1,896,159 people aged 20 to 100 years who participated in the National Health Checkup program in 2006. The amount of glucocorticoids prescribed was calculated based on the defined daily dose (DDD). The total DDD was obtained by adding oral and parenteral glucocorticoids for 6 months from the index date. Subjects were categorized into four groups according to total glucocorticoid DDDs: non-users (DDDs=0), low users (0< DDDs ≤45), intermediate users (45< DDDs ≤90), and high users (90< DDDs). We followed them for 2 years. A multivariate Cox proportional hazard model was used to evaluate the effects of the total amount of glucocorticoid use on hip and vertebral fractures. Results Higher glucocorticoid use was associated with a higher risk of vertebral fracture. Relative to non-users, the vertebral fracture risk was 1.39 times higher in the low-user group, 1.94 times higher in the intermediate-user group, and 2.43 times higher in the high-user group. The risk of hip fracture was 1.72 times higher in intermediate users and 3.28 times higher in high users than in non-users. Conclusion As the amount of glucocorticoid use for 6 months increased, the risk of hip and vertebral fractures became higher. In order to prevent fractures, it is necessary for doctors to evaluate the total amount of glucocorticoid prescribed to the patient and to provide appropriate treatment.

Although body composition is related to lung function, few studies have reported the effects of sarcopenic obesity on lung function. Thus, the aim of this study was to investigate the associations between lung function and sarcopenia in the presence and in the absence of obesity. We analyzed nationally representative data of 3044 adults aged > 60 years as collated by the ‘Korean National Health and Nutrition Examination Survey 2014–2016. Subjects were classified into four groups: non-sarcopenic non-obese (S−O−), non-sarcopenic obese (S−O+), sarcopenic non-obese (S+O−), and sarcopenic obese (S+O+) according to handgrip strength (GS) and body mass index (BMI). GS was found to be positively associated with forced volume vital capacity (FVC). The S+O+ group had significantly lower FVC values than the S−O− group. Subjects in the S+O+ group were more likely to have restrictive lung disease than those in the S−O− group (odds ratios [ORs] 2.81, 95% confidence interval [CI] 1.72–4.59), and the ORs of restrictive lung disease in S+O+ group were higher than in the S−O+ or S+O− groups. These results were consistent after stratifying by sex and age (61–70 and 71–80). FEV1/FVC ratios (a marker for obstructive lung disease) were not significantly different between S+O+ and S−O− groups. Sarcopenic obesity is associated with a higher risk of restrictive lung disease in Korean elderly.

In this study, we investigated the antibacterial and antioxidative activities of fermented licorice extracts. Aspergillus luchuensis and Aspergillus oryzae were used for licorice, fermentation. The fermentation process was carried out at 35℃, for 7 days. β-Glucosidase activity of koji made by A. luchuensis was 96.74 U/g, which was higher than that of A. oryzae (14.36 U/g). Liquiritin content in licorice fermented with A. luchuensis and A. oryzae respectively decreased to 90.42 mg/L and 43.93 mg/L, while that of liquiritigenin increased to 1,403.49 mg/L and 1,033.63 mg/L. Antibacterial activity of liquiritigenin extract was higher than that of liquiritin. Licorice fermented with A. luchuensis showed stronger antibacterial activities (11.5-14.5 mm) than that fermented with A. oryzae (10.0-11.5 mm). DPPH radical-scavenging activity of a licorice fermented with A. luchuensis, in A. oryzae, and control was 65.35, 43.13, and 25.21%, respectively. The highest ascorbic acid (AA) equivalent antioxidant capacity (AEAC) value (92.22 mg AA eq/g) was obtained for licorice fermented with A. luchuensis (control=2.88 mg AA eq/g). The results showed that fermented licorice extracts contain antibacterial and antioxidant components. Thus, fermented licorice extracts are useful for fermented foods that are difficult to preserve because of lactic acid bacteria.

Inflammatory bowel disease (IBD) is a chronic relapsing disorder modulated by numerous factors. Recent failures of drugs targeting single factors suggest that multitargeting drugs could be useful for the treatment of IBD. Natural medicines may be an alternative option for the treatment of IBD, owing to the complex nature of the disease. However, most natural medicines have poor in vitro and in vivo translational potential because of inadequate pharmacokinetic study. KM1608, a mixture of the medicinal plants Aucklandia lappa, Terminalia chebula, and Zingiber officinale, was examined for its anti-colitis effects and biodistribution using bioimaging. Dehydrocostus lactone, as a marker compound, was analyzed to assess the biodistribution of KM1608. KM1608 significantly attenuated the disease activity of dextran sodium sulfate-induced colitis in mice and suppressed inflammatory mediators such as myeloperoxidase, proinflammatory cytokines (TNF-&alpha, and IL-6), and the Th2-type cytokine IL-4 in the colon. Optical fluorescence imaging revealed that KM1608 was distributed in the intestinal area as a target organ. Collectively, our findings suggest that KM1608 is a potential therapeutic formulation for IBD.

Postsurgical hypoparathyroidism is the most common complication of thyroid surgery. Conventional therapy with high-dose calcium and vitamin D can correct hypocalcemia but can increase the risk of hypercalciuria, renal stones, or ectopic calcification. The aim of the present study was to investigate the efficacy of a calcium-sensing receptor antagonist, also called a calcilytic (AXT914), in rat models of postsurgical hypoparathyroidism. Two postsurgical hypoparathyroidism rat models were made by hemi-parathyroidectomy or total parathyroidectomy with autotransplantation in 10-week-old female Wistar rats. AXT914 or vehicle was administered orally for 2 to 3 weeks. Serum PTH, calcium, and phosphorus levels, and the urinary excretion of calcium were measured. Autotransplanted parathyroid tissues were collected and examined histologically. In the hemi-parathyroidectomy model, the oral administration of the calcilytic AXT914 (5 and 10 mg/kg) for 2 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels and urinary calcium excretion. In the total parathyroidectomy with autotransplantation model, the oral administration of AXT914 (10 mg/kg) for 3 weeks increased serum PTH and calcium levels and decreased serum phosphorus levels. The serum PTH and calcium levels increased by AXT914 were maintained for 1 week, even after discontinuation of the drug. In conclusion, AXT914 increased PTH secretion in rat models of postsurgical hypoparathyroidism, thereby correcting abnormal calcium and phosphorus homeostasis. Furthermore, AXT914 improved the functional recovery of autotransplanted parathyroid tissues.

Background: Influential guidelines recommend using SGLT2i preferentially among antidiabetic drugs in patients with diabetes and ASCVD. Although CVOTs with SGLT2i showed reduction in risk of 3-point major adverse cardiovascular events (MACE), they did not demonstrate beneficial effect on stroke. In addition, a meta-analysis reported adverse effect of SGLT2i for stroke. On the contrary, pioglitazone, a type of TZD, demonstrated the effect in secondary stroke prevention from two large RCTs. The aim of this study was to compare the effect of SGLT2i and TZD on the risk of stroke among patients with type 2 diabetes. Methods: Using the Korean National Health Insurance Service data, we compared a 1:1 propensity score-matched cohort of patients who were new users of SGLT2i (n = 82,044) and TZD (n = 82,044) from January 2014 to December 2018. The primary outcome was stroke. The secondary outcomes were MI, CV death, and 3-point MACE. Results: The incidence rates of stroke were 5.2 and 5.3 per 1000 person-years in SGLT2i-treated patients and TZD-treated patients, respectively. The hazard ratio of stroke was 0.955 (95% CI: 0.841-1.084) in SGLT2i-treated patients compared with TZD-treated patients. There was no clear difference in risk of MI (HR: 1.151, 95% CI: 0.914-1.449), CV death (HR: 0.865, 95% CI: 0.660-1.132), 3-point mace (HR: 0.988, 95% CI: 0.894-1.092) between two groups. Results were consistent regardless of prior CV disease. Conclusions: In this real-world data, the risk of stroke was comparable in patients with type 2 diabetes treated with TZD vs. SGLT2i. Disclosure S. Lee: None. H. Nam: None. H. Choi: None. K. Kim: None.

Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca2+diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.