• Genomics & Informatics
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• v.17 no.4
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• pp.47.1-47.12
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• 2019

The achievements of genome-wide association studies have suggested ways to predict diseases, such as type 2 diabetes (T2D), using single-nucleotide polymorphisms (SNPs). Most T2D risk prediction models have used SNPs in combination with demographic variables. However, it is difficult to evaluate the pure additive contribution of genetic variants to classically used demographic models. Since prediction models include some heritable traits, such as body mass index, the contribution of SNPs using unmatched case-control samples may be underestimated. In this article, we propose a method that uses propensity score matching to avoid underestimation by matching case and control samples, thereby determining the pure additive contribution of SNPs. To illustrate the proposed propensity score matching method, we used SNP data from the Korea Association Resources project and reported SNPs from the genome-wide association study catalog. We selected various SNP sets via stepwise logistic regression (SLR), least absolute shrinkage and selection operator (LASSO), and the elastic-net (EN) algorithm. Using these SNP sets, we made predictions using SLR, LASSO, and EN as logistic regression modeling techniques. The accuracy of the predictions was compared in terms of area under the receiver operating characteristic curve (AUC). The contribution of SNPs to T2D was evaluated by the difference in the AUC between models using only demographic variables and models that included the SNPs. The largest difference among our models showed that the AUC of the model using genetic variants with demographic variables could be 0.107 higher than that of the corresponding model using only demographic variables.

• Genomics & Informatics
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• v.9 no.3
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• pp.114-120
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• 2011

Chronic inflammation has been implicated as one of the important etiological factors in insulin resistance and type 2 diabetes mellitus (T2DM). To investigate the role of anti-inflammatory cytokines in the development of T2DM, we conducted a case-control study to assess the association between IL4/IL4R polymorphisms and disease risk. We firstly identified single nucleotide poly-morphisms (SNP) at IL4 and IL4RA loci by sequencing the loci in Korean participants. Case-control studies were conducted by genotyping the SNPs in 474 T2DM cases and 470 non-diabetic controls recruited from community-based cohorts. Replication of the associated signals was performed in 1,216 cases and 1,352 controls. We assessed effect of IL4 -IL4RA interaction on T2DM using logistic regression method. The functional relevance of the SNP associated with disease risk was determined using a reporter expression assay. We identified a strong association between the IL4 promoter variant rs2243250 and T2DM risk (OR=0.77; 95% CI, 0.67~0.88; p=$1.65{\times}10^{－4}$ in the meta-analysis). The reporter gene expression assay demonstrated that the presence of rs2243250 might affect the gene expression level with ~1.5-fold allele difference. Our findings contribute to the identification of IL4 as a T2D susceptibility locus, further supporting the role of anti-inflammatory cytokines in T2DM disease development.

• Journal of Pharmacopuncture
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• v.25 no.2
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• pp.130-137
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• 2022

Objectives: Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. Methods: We divided 60 mice into 12 groups (n = 5 per group): control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. Results: Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. Conclusion: Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.

• BMB Reports
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• v.46 no.12
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• pp.606-610
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• 2013

Glucagon like peptide-1 (GLP-1) regulates glucose mediated-insulin secretion, nutrient accumulation, and ${\beta}$-cell growth. Despite the potential therapeutic usage for type 2 diabetes (T2D), GLP-1 has a short half-life in vivo ($t_{1/2}$ <2 min). In an attempt to prolong half-life, GLP-1 fusion proteins were genetically engineered: GLP-1 human serum albumin fusion (GLP-1/HSA), AGLP-1/HSA which has an additional alanine at the N-terminus of GLP-1, and AGLP-1-L/HSA, in which a peptide linker is inserted between AGLP-1 and HSA. Recombinant fusion proteins secreted from the Chinese Hamster Ovary-K1 (CHO-K1) cell line were purified with high purity (>96%). AGLP-1 fusion protein was resistant against the dipeptidyl peptidase-IV (DPP-IV). The fusion proteins activated cAMP-mediated signaling in rat insulinoma INS-1 cells. Furthermore, a C57BL/6N mice pharmacodynamics study exhibited that AGLP-1-L/HSA effectively reduced blood glucose level compared to AGLP-1/HSA.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.595-600
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• 2015

Background: Accumulating evidence suggests that metformin possesses anticarcinogenic properties, and its use is associated with favorable outcomes in several cancers. However, it remains unclear whether metformin influences prognosis in prostate cancer (PCa) with concurrent type 2 diabetes (T2D). Materials and Methods: We searched PubMed, EMBASE, and the Cochrane Library from database inception to April 16, 2014 without language restrictions to identify studies investigating the effect of metformin treatment on outcomes of PCa with concurrent T2D. We conducted a meta-analysis to quantify the risk of recurrence, progression, cancer-specific mortality, and all-cause mortality. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Publication bias was assessed by Begg's rank correlation test. Results: A total of eight studies fulfilled the eligibility criteria. We found that diabetic PCa patients who did not use metformin were at increased risk of cancer recurrence (RR, 1.20; 95%CI, 1.00-1.44), compared with those who used metformin. A similar trend was observed for other outcomes, but their relationships did not reach statistical significance. Funnel plot asymmetry was not observed among studies reporting recurrence (p=0.086). Conclusions: Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D. Well-designed large studies and collaborative basic research are warranted.

• Korean Journal of Adult Nursing
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• v.22 no.3
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• pp.271-280
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• 2010

Purpose: The purpose of this study was to examine relationships among blood glucose, HbA1c, and self management comparing these with general and illness characteristics of subjects with Type II Diabetes living in the community. Methods: Using a comprehensive survey developed for the study, data were collected from 82 type II diabetes patients who were registered at five community health departments. The variables of self management, blood glucose and HbA1c were assessed by nurses. Data were analyzed with descriptive statistics including t-test, ANOVA and Pearson's correlation coefficient to compare self management and level of HbA1c by subject's general and illness characteristics and to examine the relationships among variables. Results: About 73.2% of the subjects' HbA1c were 7.0% or higher and 54.9% of subjects' blood glucose were 200 mg/dL or higher. The level of self management was moderate. Most frequently perceived reasons for failure of blood glucose control were dietary failure (32.9%). There was significant relationship between self management and HbA1c(r=-.223, p=.040). The mean score of self management were higher among female (t=-2.37, p=.021), who are not on diabetes medication (t=6.70, p=.011). Conclusion: Comprehensive intervention is needed to improve dietary self management, especially for male and those who is on diabetes medication.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.99-103
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• 2010

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.136-145
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• 2010

Natural killer T (NKT) cell is a special type of T lymphocytes that has both receptor of natural killer (NK) cell (NK1.1, CD161c) and T cell (TCR) and express a conserved or invariant T cell receptor called $V{\alpha}14J{\alpha}18$ in mice or Va24 in humans. Invariant NKT (iNKT) cell recognizes lipid antigen presented by CD1d molecules. Marine-sponge-derived glycolipid, ${\alpha}-galactosylceremide$ (${\alpha}-GalCer$), binds CD1d at the cell surface of antigen-presenting cells and is presented to iNKT cells. Within hours, iNKT cells become activated and start to secrete Interleukin-4 and $interferon-{\gamma}$. NKT cell prevents autoimmune diseases, such as type 1 diabetes, experimental allergic encephalomyelitis, systemic lupus erythematous, inflammatory colitis, and Graves' thyroiditis, by activation with ${\alpha}-GalCer$. In addition, NKT cell is associated with infectious diseases by mycobacteria, leshmania, and virus. Moreover NKT cell is associated with asthma, especially CD4+ iNKT cells. In this review, I will discuss the characteristics of NKT cell and the association with inflammatory diseases, especially asthma.

• Korean Journal of Psychosomatic Medicine
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• v.30 no.2
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• pp.155-164
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• 2022

Objectives : A growing body of evidence links type 2 diabetes (T2D) with a neurodegenerative disease (ND) such as Alzheimer's disease and Parkinson's disease. The purpose of this study is to investigate the relationship between NDs and the development of T2D by comparing the incidence of T2D in a group of various NDs (ND group) and control group. Methods : A population-based 10-year follow-up study was conducted using the Korean National Health Information Database for 2002-2015. We used a retrospective cohort study design to investigate the association of ND with T2D occurrence. The study population included ND (n=8,814) and control (n=37,970) groups, all aged 60 years or over. The Kaplan-Meier method was used to estimate the risk of developing T2D as a function of time. Cox proportional hazards regression models were used to evaluate the relationship between ND and T2D. Results : T2D was developed in a significantly higher percentage of patients in the ND group (53.6%) than in the control group (44.7%). The ND group increased the risk of T2D (HR, 1.43; 95% CI, 1.38-1.47). About one-third of patients in both groups were additionally diagnosed with another ND before the occurrence of T2D during a 10-year follow-up period. When compared to those who did not have another ND during the follow-up period, the incidence of T2D in those who were additionally diagnosed with another ND was higher in both the ND and control groups. Conclusions : The ND group had about 1.4 times higher risk of developing T2D than the control group. Our results showed a positive association between ND and T2D.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.283-294
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• 2017

Purpose: This study primarily aimed to investigate the short- and long-term remission rates of type 2 diabetes (T2D) in patients who underwent surgical treatment for gastric cancer, especially patients who were non-obese, and secondarily to determine the potential factors associated with remission. Materials and Methods: We retrospectively reviewed the clinical records of patients with T2D who underwent radical gastrectomy for gastric cancer, from January 2008 to December 2012. Results: T2D improved in 39 out of 70 (55.7%) patients at the postoperative 2-year follow-up and 21 of 42 (50.0%) at the 5-year follow-up. In the 2-year data analysis, preoperative body mass index (BMI) (P=0.043), glycated hemoglobin (A1C) level (P=0.039), number of anti-diabetic medications at baseline (P=0.040), reconstruction method (statistical difference was noted between Roux-en-Y reconstruction and Billroth I; P=0.035) were significantly related to the improvement in glycemic control. Unlike the results at 2 years, the 5-year data analysis revealed that only preoperative BMI (P=0.043) and A1C level (P=0.039) were statistically significant for the improvement in glycemic control; however, the reconstruction method was not. Conclusions: All types of gastric cancer surgery can be effective in short- and long-term T2D control in non-obese patients. In addition, unless long-limb bypass is considered in gastric cancer surgery, the long-term glycemic control is not expected to be different between the reconstruction methods.