• Nutrition Research and Practice
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• v.17 no.4
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• pp.789-802
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• 2023

BACKGROUND/OBJECTIVES: Habitual coffee consumption was inversely associated with type 2 diabetes (T2D) and hyperglycemia in observational studies, but the causality of the association remains uncertain. This study tested a causal association of genetically predicted coffee consumption with T2D using the Mendelian randomization (MR) method. SUBJECTS/METHODS: We used five single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with habitual coffee consumption in a previous genome-wide association study among Koreans. We analyzed the associations between IVs and T2D, fasting blood glucose (FBG), 2h-postprandial glucose (2h-PG), and glycated haemoglobin (HbA1C) levels. The MR results were further evaluated by standard sensitivity tests for possible pleiotropism. RESULTS: MR analysis revealed that increased genetically predicted coffee consumption was associated with a reduced prevalence of T2D; ORs per one-unit increment of log-transformed cup per day of coffee consumption ranged from 0.75 (0.62-0.90) for the weighted mode-based method to 0.79 (0.62-0.99) for Wald ratio estimator. We also used the inverse-variance-weighted method, weighted median-based method, MR-Egger method, and MR-PRESSO method. Similarly, genetically predicted coffee consumption was inversely associated with FBG and 2h-PG levels but not with HbA1c. Sensitivity measures gave similar results without evidence of pleiotropy. CONCLUSIONS: A genetic predisposition to habitual coffee consumption was inversely associated with T2D prevalence and lower levels of FBG and 2h-PG profiles. Our study warrants further exploration.

• Journal of Korean Biological Nursing Science
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• v.25 no.1
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• pp.73-85
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• 2023

Purpose: This study focused on identifying the interaction effects of genetic and lifestyle-environmental factors on the development of type 2 diabetes mellitus (T2D). Methods: Study subjects were selected from the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2014. Data on genetic variations, anthropometric measurements, biochemical data, and seven lifestyle factors (diet, physical activity, alcohol drinking, smoking, sleep, depression, and stress) were obtained from 4,836 Koreans aged between 40 and 59 years, including those with T2D at baseline (n = 1,209), newly developed T2D (n= 1,298) and verified controls (n = 3,538). The genetic risk score (GRS) was calculated by using 11 single-nucleotide polymorphisms (SNPs) related to T2D development and the second quartile was used as the reference category. A Cox proportional hazards regression model was used to evaluate the associations of GRS and lifestyle factors with T2D risk, controlling for covariates. Results: Multivariate regression analysis revealed that GRS was the strongest risk factor for T2D, and body mass index (BMI), smoking, drinking, and spicy food preference also increased the risk. Lifestyle/environmental factors that showed significant interactions with GRS were BMI, current smoking, current drinking, fatty food preference, and spicy food preference. Conclusions: Interactions between genetic factors and lifestyle/environmental factors were associated with an increased risk of T2D. The results will be useful to provide a new perspective on genetic profiling for the earlier detection of T2D risk and clues for personalized interventions, which might be more effective prevention strategies or therapies in individuals with a genetic predisposition to T2D.

• Journal of Microbiology and Biotechnology
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• v.33 no.12
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• pp.1657-1670
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• 2023

This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the Lactobacillaceae coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of Corynebacterium and Proteus, which were significantly increased in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ruminococcus_gnavus_group, Desulfovibrio, and Lachnospiraceae_UCG-006. Untargeted metabolomics analysis showed that lotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively correlated with 5-hydroxyindoleacetic acid and 13(S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of Ruminococcus_gnavus_group and Lachnoclostridium to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.

• Journal of Preventive Medicine and Public Health
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• v.49 no.1
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• pp.45-52
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• 2016

Objectives: Previous large-scale cohort studies conducted in Korea have found a positive association between diabetes mellitus (DM) and colorectal cancer (CRC) in men only, in contrast to studies of other populations that have found significant associations in both men and women. Methods: A total of 1070 CRC cases and 2775 controls were recruited from the National Cancer Center, Korea between August 2010 and June 2013. Self-reported DM history and the duration of DM were compared between cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary and polytomous logistic regression models. Results: DM was associated with an elevated risk of CRC in both men (OR, 1.47; 95% CI, 1.13 to 1.90) and women (OR, 1.92; 95% CI, 1.24 to 2.98). This association remained when we controlled for age, body mass index, alcohol consumption, and physical activity level. In sub-site analyses, DM was associated with distal colon cancer risk in both men (multivariate OR, 2.04; 95% CI, 1.39 to 3.00) and women (multivariate ORs, 1.99; 95% CI, 1.05 to 3.79), while DM was only associated with rectal cancer risk in women (multivariate OR, 2.05; 95% CI, 1.10 to 3.82). No significant association was found between DM and proximal colon cancer risk in either men (multivariate OR, 1.45; 95% CI, 0.88 to 2.41) or women (multivariate OR, 1.79; 95% CI, 0.78 to 4.08). Conclusions: Overall, DM was associated with an increased risk of CRC in Koreans. However, potential over-estimation of the ORs should be considered due to potential biases from the case-control design.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4349-4352
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• 2014

Background: Pancreatic cancer has a high mortality rate because it is usually diagnosed late. Since little is known about this cancer in Iran, with the aim of improving this knowledge deficiency, we evaluated clinical, laboratory biomarkers, imaging findings and treatment modalities in Iranian patients with pancreatic adenocarcinoma. Materials and Methods: 131 cases of pancreatic adenocarcinoma in 2010-2013 were obtained from the Taleghani Hospital Record Department. Cases confirmed by histopathology from CT-guided biopsy, EUS-FNA and surgery examination were included. We excluded those with incomplete medical records. Results: The study included 131 subjects between 24 and 97 years of age and a mean age of $63{\pm}13.4$ years. Eighty (61.1%) were male and 51 (38.9%) female. Previous history included diabetes mellitus in 36 (27.5%), alcohol drinking in 5 (3.9%), smoker in 28 (21.4%) and opium addiction in 13 (10%). The common presenting history included weight loss in 79 (60.3%), abdominal pain in 77 (58.8%), fever in 11 (8.4%), nausea in 30 (22.9%), jaundice in 72 (55%), pruritus in 52 (39.7) and anemia in 33 (25.2%). CA19-9 levels with cut offs of 50, 100 and 200 U/ml were increased in 81%, 72% and 66% of patients, respectively. Tumor staging was: stage I, 3 (2.3%); stage II, 10 (7.6%); stage III, 58 (44.3%); and stage IV, 60 (45.8%). From 45 patients, 17 received ERCP inserted metallic stents and 22 plastic stents, the remaining 6 failed that PTC was done. Whipple surgery and chemotherapy were conducted for 10 and 29 patients, respectively. Conclusions: This disease affected older people and there was a male preponderance. The commonest risk factors were diabetes mellitus, smoking and cholelithiasis. The majority of patients presented with loss of appetite, loss of weight, jaundice, abdominal pain and discomfort. Almost all presented at late stages of the disease so that curative surgery was impossible. Also chemotherapy was only performed in a few patients as a neoadjuant treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4265-4269
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• 2014

Purpose: This study aimed at summarizing epidemiological evidence of the association between gestational diabetes mellitus (GDM) and subsequent risk of cancer. Materials and Methods: We searched Medline, Embase, Cancer Lit and CINAHL for epidemiological studies published by February 1, 2014 examining the risk of cancer in patients with history of GDM using highly inclusive algorithms. Information about first author, year of publication, country of study, study design, cancer sites, sample sizes, attained age of subjects and methods used for determining GDM status were extracted by two researchers and Stata version 11.0 was used to perform the meta-analysis and estimate the pooled effects. Results: A total of 9 articles documented 5 cohort and 4 case-control studies containing 10,630 cancer cases and 14,608 women with a history of GDM were included in this review. Taken together, the pooled odds ratio (OR) between GDM and breast cancer risk was 1.01 (0.87-1.17); yet the same pooled ORs of case-control and cohort studies were 0.87 (0.71-1.06) and 1.25 (1.00-1.56) respectively. There are indications that GDM is strongly associated with higher risk of pancreatic cancer (HR=8.68) and hematologic malignancies (HR=4.53), but no relationships were detected between GDM and other types of cancer. Conclusions: Although GDM increases the risk of certain types of cancer, these results should be interpreted with caution becuase of some methodological flaws. The issue merits added investigation and coordinated efforts between researchers, antenatal clinics and cancer treatment and registration agencies to help attain better understanding.

• Journal of the Korean Applied Science and Technology
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• v.36 no.4
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• pp.1268-1280
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• 2019

The purpose of this study was to investigate the effects of combined exercise on irisin, body composition and glucose metabolism in obese elderly women with type 2 diabetes mellitus. The subjects were thirty-six obese elderly women with type 2 diabetes volunteers, aged 65 to 85 years, composed of the combined exercise type 2 diabetes mellitus group (n=20) and non-exercise type 2 diabetes mellitus group (n=16). The 60 minute combined exercise program (outdoor walking exercise & elastic-band exercise) was performed 3 times per week for 12 weeks. Exercise intensity of outdoor walking exercise was performed as medium intensity (RPE 5~6) and elastic-band exercise was progressively increased every four weeks (1-4 weeks: OMNI-RES 3~4, 5-8 weeks: OMNI-RES 5~6, 9-12 weeks: OMNI-RES 7~8). The results of the study in the combined exercise type 2 diabetes mellitus group were as follows; Irisin and skeletal muscle mass had significantly increased (p<.001), percentage of body fat had significantly decreased (p<.001). Further, HbA1c (p=.020) and fasting glucose (p<.001) was significantly decreased, and HOMA-β was significantly increased (p<.001). Correlation results showed that change of irisin had a significant negative correlation between percentage of body fat mass (r=-.423, p=.010), HbA1c (r=-.351, p=.036) and fasting glucose (r=-.424, p=.010). Also, irisin changes showed a positive correlation with aerobic endurance (r=.355, p=.034) and HOMA-β (r=.411, p=.013). In conclusion, the practice of regular combined exercise was found to increase the level of irisin in elderly women with type 2 diabetes and have a positive effect on body composition changes. In addition, HbA1c, fasting glucose and insulin secretion was improved, which helped to regulate glucose metabolism. Walking exercise and elastic band exercise are recommended as effective exercise for the prevention and management of diabetes in obese elderly women with type 2 diabetes mellitus.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4067-4073
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• 2012

Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferator activated receptor$receptor{\gamma}$ ($PPAR{\gamma}$) agonist that induces differentiation in adipocytes and induces growth arrest and/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect of pioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-$A^{\mathcal{Y}}$ obesity and diabetes model mice, and tried to clarify mechanisms by which the $PPAR{\gamma}$ ligand inhibits ACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF/mouse to 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-$A^{\mathcal{Y}}$ mice with significant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines, such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceral fat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cell proliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggest that pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulated adipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNA levels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potential chemopreventive agent against obesity-associated colorectal cancer.

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1078-1087
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• 2020

The current study was carried out to investigate the effect of oral administration for 30 days of the Jijang kimchi extracts on prevention of diabetes, alcoholic liver injury and reduction of blood lipids in laboratory rats with alcoholic liver injury and diabetes induced by streptozotocin. In a diabetic model animals, the blood lipid profile, ALT, and AST levels were lower in kimchi extract groups compared to DC (diabetes control) group, and blood glucose level of DCJK (DC+oral administration with Jijang kimchi extracts) group was lower than that of DCCK (DC+oral administration with commercial kimchi extracts) group. Insulin levels were increased in order of NC (normal control), DCJK > DCCK > DC groups. In alcoholic liver injury model animals, ALT, AST and bilirubin were lowed in order of AC (alcohol group received 1 bottle of soju) > ACCK (1 bottle of soju plus oral administration with commercial kimchi extracts) ACJK (AC plus oral administration with Jijang kimchi extracts) > NC groups. In the clinical pathologic findings of liver tissue, AC group was severely injured, and tended to be improved in groups eating a 1 bottle of soju plus oral administration with kimchi extracts, especially Jijang kimchi extract group. The results suggest that eating Jijang kimchi can improve insulin secretion ability while lowering blood lipid profile, blood sugar and ALT, AST, and bilirubin levles in diabetic and alcoholic liver injury model animals.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8079-8083
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• 2016

Metformin is an oral anti-hyperglycemic agent, which is the most commonly prescribed medication in the treatment of type-2 diabetes mellitus. It is purportedly associated with a reduced risk for various cancers, mainly exerting anti-proliferation effects on various human cancer cell types, such as pancreas, prostate, breast, stomach and liver. This mini-review highlights the risk and benefit of metformin used for cholangiocarcinoma (CCA) prevention and therapy. The results indicated metformin might be a quite promising strategy CCA prevention and treatment, one mechanism being inhibition of CCA tumor growth by cell cycle arrest in both in vitro and in vivo. The AMPK/mTORC1 pathway in intrahepatic CCA cells is targeted by metformin. Furthermore, metformin inhibited CCA tumor growth via the regulation of Drosha-mediated expression of multiple carcinogenic miRNAs. The use of metformin seems to be safe in patients with cirrhosis, and provides a survival benefit. Once hepatic malignancies are already established, metformin does not offer any therapeutic potential. Clinical trials and epidemiological studies of the benefit of metformin use for CCA should be conducted. To date, whether metformin as a prospective chemotherapeutic for CCA is still questionable and waits further atttention.