Four soluble factors—putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102—were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45–55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.
People with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular disease, heart failure, chronic kidney disease, and premature death than people without diabetes. Therefore, treatment of diabetes aims to reduce these complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown beneficial effects on cardiorenal and metabolic health beyond glucose control, making them a promising class of drugs for achieving the ultimate goals of diabetes treatment. However, despite their proven benefits, the use of SGLT2 inhibitors in eligible patients with T2DM remains suboptimal due to reports of adverse events. The use of SGLT2 inhibitors is particularly limited in older patients with T2DM because of the lack of treatment experience and insufficient long-term safety data. This article comprehensively reviews the risk-benefit profile of SGLT2 inhibitors in older patients with T2DM, drawing on data from prospective randomized controlled trials of cardiorenal outcomes, original studies, subgroup analyses across different age groups, and observational cohort studies.
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Background The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus.
Methods Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis.
Results During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration.
Conclusion Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Jaehyun Bae, Eonju Jeon, Ji Min Kim, Seon Mee Kang, Jung Hwan Park, Jae-Seung Yun, Bong-Soo Cha, Min Kyong Moon, Byung-Wan Lee
Diabetes Metab J. 2024;48(4):546-708. Published online July 26, 2024
Adherence to the nutritional recommendations according to diabetes status in Korean adults: a cross-sectional study Jong Han Choi, Chen Lulu, Seon-Joo Park, Hae-Jeung Lee BMC Public Health.2024;[Epub] CrossRef
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Diabetes Metab J. 2024;48(6):1160-1168. Published online May 21, 2024
Background Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans.
Methods A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness.
Conclusion A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.
Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee
Diabetes Metab J. 2024;48(4):730-739. Published online May 20, 2024
Background It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
Nam Hoon Kim, Mi-Hae Seo, Jin Hyung Jung, Kyung Do Han, Mi Kyung Kim, Nan Hee Kim, on Behalf of Diabetic Kidney Disease Research Group of the Korean Diabetes Association
Diabetes Metab J. 2024;48(3):463-472. Published online March 19, 2024
Background To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea.
Methods We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 in patients with diabetes mellitus.
Results The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage.
Conclusion DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.
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Endothelial NOX5 Obliterates the Reno-Protective Effect of Nox4 Deletion by Promoting Renal Fibrosis via Activation of EMT and ROS-Sensitive Pathways in Diabetes Karin A. M. Jandeleit-Dahm, Haritha R. Kankanamalage, Aozhi Dai, Jaroslawna Meister, Sara Lopez-Trevino, Mark E. Cooper, Rhian M. Touyz, Christopher R. J. Kennedy, Jay C. Jha Antioxidants.2024; 13(4): 396. CrossRef
Background The effects of excessive ultra-processed food (UPF) consumption on body composition measures or sociodemographic disparities are understudied in Korea. We aimed to investigate the association of UPF intake with percent body fat (PBF) and percent appendicular skeletal muscle mass (PASM) by sociodemographic status in adults.
Methods This study used data from the Korea National Health and Nutrition Examination Survey 2008–2011 (n=11,123 aged ≥40 years). We used a NOVA system to classify all foods reported in a 24-hour dietary recall, and the percentage of energy intake (%kcal) from UPFs was estimated. PBF and PASM were measured by dual-energy X-ray absorptiometry. Tertile (T) 3 of PBF indicated adiposity and T1 of PASM indicated low skeletal muscle mass, respectively. Multinomial logistic regression models were used to estimate odds ratios (OR) with 95% confidence interval (CI) after adjusting covariates.
Results UPF intake was positively associated with PBF-defined adiposity (ORper 10% increase, 1.04; 95% CI, 1.002 to 1.08) and low PASM (ORper 10% increase, 1.05; 95% CI, 1.01 to 1.09). These associations were stronger in rural residents (PBF: ORper 10% increase, 1.14; 95% CI, 1.06 to 1.23; PASM: ORper 10% increase, 1.15; 95% CI, 1.07 to 1.23) and not college graduates (PBF: ORper 10% increase, 1.06; 95% CI, 1.02 to 1.11; PASM: ORper 10% increase, 1.07; 95% CI, 1.03 to 1.12) than their counterparts.
Conclusion A higher UPF intake was associated with higher adiposity and lower skeletal muscle mass among Korean adults aged 40 years and older, particularly in those from rural areas and with lower education levels.
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Food Allergy, Nutrition, Psychology, and Health Elena Gupta, Alexandra E. Conway, Marylee Verdi, Marion Groetch, Aikaterini Anagnostou, Elissa M. Abrams, Anna Nowak-Wegrzyn, Don Bukstein, Juliette C. Madan, Matthew Hand, Sarah L. Garnaat, Marcus S. Shaker The Journal of Allergy and Clinical Immunology: In Practice.2024;[Epub] CrossRef
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Diabetes Metab J. 2024;48(2):279-289. Published online January 26, 2024
Background Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD.
Methods We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study.
Results Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users.
Conclusion The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.
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So Hee Park, You-Bin Lee, Kyu-na Lee, Bongsung Kim, So Hyun Cho, So Yoon Kwon, Jiyun Park, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Kyungdo Han, Jae Hyeon Kim
Diabetes Metab J. 2024;48(2):290-301. Published online January 3, 2024
Background We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM).
Methods For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317).
Results During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status.
Conclusion Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.
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Background Post-transplant diabetes mellitus (PTDM) is one of the most significant complications after transplantation. Patients with end-stage liver diseases requiring transplantation are prone to sarcopenia, but the association between sarcopenia and PTDM remains to be elucidated. We aimed to investigate the effect of postoperative muscle mass loss on PTDM development.
Methods A total of 500 patients who underwent liver transplantation at a tertiary care hospital between 2005 and 2020 were included. Skeletal muscle area at the level of the L3–L5 vertebrae was measured using computed tomography scans performed before and 1 year after the transplantation. The associations between the change in the muscle area after the transplantation and the incidence of PTDM was investigated using a Cox proportional hazard model.
Results During the follow-up period (median, 4.9 years), PTDM occurred in 165 patients (33%). The muscle mass loss was greater in patients who developed PTDM than in those without PTDM. Muscle depletion significantly increased risk of developing PTDM after adjustment for other confounding factors (hazard ratio, 1.50; 95% confidence interval, 1.23 to 1.84; P=0.001). Of the 357 subjects who had muscle mass loss, 124 (34.7%) developed PTDM, whereas of the 143 patients in the muscle mass maintenance group, 41 (28.7%) developed PTDM. The cumulative incidence of PTDM was significantly higher in patients with muscle loss than in patients without muscle loss (P=0.034).
Conclusion Muscle depletion after liver transplantation is associated with increased risk of PTDM development.
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae Jin Kim, Hyun Min Kim, Jung Hae Ko, Nam Hoon Kim, Chong Hwa Kim, Jeeyun Ahn, Tae Jung Oh, Soo-Kyung Kim, Jaehyun Kim, Eugene Han, Sang-Man Jin, Won Suk Choi, Min Kyong Moon, Committee of Clinical Practice Guidelines, Korean Diabetes Association
Diabetes Metab J. 2023;47(5):575-594. Published online September 26, 2023
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.
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Background This study aimed to investigate the association between type 2 diabetes mellitus (T2DM) and shoulder adhesive capsulitis (AC) using a large-scale, nationwide, population-based cohort in the Republic of Korea.
Methods A total of 3,471,745 subjects aged over 20 years who underwent a National Health Insurance Service medical checkup between 2009 and 2010 were included in this study, and followed from the date of their medical checkup to the end of 2018. Subjects were classified into the following four groups based on the presence of dysglycemia and history of diabetes medication: normal, prediabetes, newly diagnosed T2DM (new-T2DM), and T2DM (claim history for antidiabetic medication). The endpoint was new-onset AC during follow-up. The incidence rates (IRs) in 1,000 person-years and hazard ratios (HRs) of AC for each group were analyzed using Cox proportional hazard regression models.
Results The IRs of AC were 9.453 (normal), 11.912 (prediabetes), 14.933 (new-T2DM), and 24.3761 (T2DM). The adjusted HRs of AC in the prediabetes, new-T2DM, and T2DM groups were 1.084 (95% confidence interval [CI], 1.075 to 1.094), 1.312 (95% CI, 1.287 to 1.337), and 1.473 (95% CI, 1.452 to 1.494) compared to the normal group, respectively. This secular trend of the HRs of AC according to T2DM status was statistically significant (P<0.0001).
Conclusion This large-scale, longitudinal, nationwide, population-based cohort study of 3,471,745 subjects confirmed that the risk of AC increases in prediabetic subjects and is associated with T2DM status.
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Background We explored the risk of death from pneumonia according to cumulative duration in low household income state (LHIS) among adults with type 2 diabetes mellitus (T2DM).
Methods Using Korean National Health Insurance Service data (2002 to 2018), the hazards of mortality from pneumonia were analyzed according to duration in LHIS (being registered to Medical Aid) during the 5 years before baseline (0, 1–4, and 5 years) among adults with T2DM who underwent health examinations between 2009 and 2012 (n=2,503,581). Hazards of outcomes were also compared in six groups categorized by insulin use and duration in LHIS.
Results During a median 7.18 years, 12,245 deaths from pneumonia occurred. Individuals who had been exposed to LHIS had higher hazards of death from pneumonia in a dose-response manner (hazard ratio [HR], 1.726; 95% confidence interval [CI], 1.568 to 1.899 and HR, 4.686; 95% CI, 3.948 to 5.562 in those exposed for 1–4 and 5 years, respectively) compared to the non-exposed reference. Insulin users exposed for 5 years to LHIS exhibited the highest outcome hazard among six groups categorized by insulin use and duration in LHIS.
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Background This study aimed to investigate the association between consumption of ultra-processed foods (UPF) and obesity in Korean adults.
Methods We included the Cardiovascular and Metabolic Diseases Etiology Research Center cohort study baseline data of adults aged 30 to 64 years who completed a validated food frequency questionnaire. UPF was defined using the NOVA food classification. Multivariable linear and logistic regression analyses were performed to assess the association of dietary energy contribution of UPF with obesity indicators (body mass index [BMI], obesity, waist circumference [WC], and abdominal obesity).
Results Consumption of UPF accounted for 17.9% of total energy intake and obesity and abdominal obesity prevalence was 35.4% and 30.2%, respectively. Compared with those in the lowest quartile of UPF consumption, adults in the highest quartile had greater BMI (β=0.36; 95% confidence interval [CI], 0.15 to 0.56), WC (β=1.03; 95% CI, 0.46 to 1.60), higher odds of having obesity (odds ratio [OR], 1.24; 95% CI, 1.07 to 1.45), and abdominal obesity (OR, 1.34; 95% CI, 1.14 to 1.57), after adjusting for sociodemographic characteristics, health-related behaviors, and family history of diseases. Dose-response associations between UPF consumption and obesity indicators were consistently found (all P trend <0.01). However, the strength of association was halved for all obesity indicators after further adjustments for total energy intake and overall diet quality score, and the trend toward association for obesity and WC disappeared.
Conclusion Our finding supports the evidence that consumption of UPF is positively associated with obesity among Korean adults.
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