Epidemiology of Type 1 Diabetes Mellitus in Korea through an Investigation of the National Registration Project of Type 1 Diabetes for the Reimbursement of Glucometer Strips with Additional Analyses Using Claims Data.

BACKGROUND: The aim of this study was to estimate the prevalence and incidence of type 1 diabetes mellitus (T1DM) in Korea. In addition, we planned to do a performance analysis of the Registration Project of Type 1 diabetes for the reimbursement of consumable materials. METHODS: To obtain nationwide data on the incidence and prevalence of T1DM, we extracted claims data from July 2011 to August 2013 from the Registration Project of Type 1 diabetes on the reimbursement of consumable materials in the National Health Insurance (NHI) Database. For a more detailed analysis of the T1DM population in Korea, stratification by gender, age, and area was performed, and prevalence and incidence were calculated. RESULTS: Of the 8,256 subjects enrolled over the 26 months, the male to female ratio was 1 to 1.12, the median age was 37.1 years, and an average of 136 new T1DM patients were registered to the T1DM registry each month, resulting in 1,632 newly diagnosed T1DM patients each year. We found that the incidence rate of new T1DM cases was 3.28 per 100,000 people. The average proportion of T1DM patients compared with each region's population was 0.0125%. The total number of insurance subscribers under the universal compulsory NHI in Korea was 49,662,097, and the total number of diabetes patients, excluding duplication, was 3,762,332. CONCLUSION: The prevalence of T1DM over the course of the study was approximately 0.017% to 0.021% of the entire population of Korea, and the annual incidence of T1DM was 3.28:100,000 overall and 3.25:100,000 for Koreans under 20 years old.

Effects of dimethyloxalylglycine on wound healing of palatal mucosa in a rat model.

BACKGROUND: Rapid wound healing of oral soft tissue may reduce the opportunity of infection and discomfort of patients. Previous studies have demonstrated that enhancement of angiogenesis is an effective way to accelerate wound repair. In this study, to enhance angiogenesis and healing of palatal wounds, dimethyloxalylglycine (DMOG) was applied to a rat palatal wound model. DMOG is known to inhibit oxygen-dependent degradation of hypoxia inducible factor-1 alpha (HIF-1α), which can lead to up-regulation of angiogenesis markers, favoring wound repair. We also evaluated the effects of DMOG on cell migration and HIF-1α expression of rat palatal (RP) cells. Furthermore, mRNA and protein expression of vascular endothelial growth factor (VEGF) were analyzed in DMOG-treated RP cells. METHODS: Primary cultures of rat palatal (RP) cells were obtained from Sprague-Dawley (SD) rats. Effects of DMOG on cell viability and migration of RP cells were evaluated by using a formazan and culture insert, respectively. VEGF mRNA was observed by real-time PCR, and VEGF and HIF-1α proteins were detected by Western blotting. For the animal study, excisional wounds, 3 mm in diameter, were made at the central part of the palate of SD rats. DMOG with hyaluronic acid ointment was topically applied three times during 1 week, and then wound closures were quantitated photographically and histologically. RESULTS: DMOG was cytotoxic to RP cells at concentrations higher than 2 mM and did not affect cell migration at non-cytotoxic concentrations. mRNA and protein expression of VEGF were significantly stimulated by DMOG treatment. The protein level of HIF-1α was also stabilized in RP cells by DMOG. In the animal study, groups treated with 1 mg/ml DMOG showed an increase of rat palatal wound contractures. CONCLUSIONS: DMOG enhanced wound healing of rat palatal mucosa, which was likely due to the angiogenic effect of the agent.

Effects of thymosin ß4 on wound healing of rat palatal mucosa.

The objective of the present study was to investigate the effect of thymosin ß4 (Tß4) on the wound healing of rat palatal (RP) mucosa and related cellular properties. Cell viability, adhesion and migration of primary cultured RP cells were observed in the presence of Tß4 at various concentrations ranging from 1 to 1,000 ng/ml. The mRNA and protein expression of matrix metalloproteinase 2 (MMP2) and vascular endothelial growth factor (VEGF) in Tß4-treated RP cells was assessed by quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. For the in vivo assay, Tß4 was applied to excisional wounds (3 mm in diameter) that were made in the center of the palate (n=6). Images of the wound areas were captured and assessed histologically one week after surgery. Tß4 did not affect cell viability and adhesion, but RP cell migration was stimulated by Tß4 at concentrations of 100 and 1,000 ng/ml. Tß4 also increased the mRNA and protein expression of MMP2 and VEGF in RP cells. In the animal model, palatal wound closure was significantly enhanced in rats treated with Tß4. The results of the present study indicated that Tß4 promotes the wound healing of RP mucosa. Enhancement of RP cell migration and angiogenesis is likely to be involved in the promotion of wound healing.

The effects of restorative composite resins on the cytotoxicity of dentine bonding agents.

During restoration of damaged teeth in dental clinics, dentin bonding agents are usually overlaid with restorative resin composites. The purpose of this study was to investigate the effects of restorative resin composites on cytotoxicity of dentin bonding agents. Dentin bonding agents were placed on glass discs, pre-cured and uncured resin composite discs. Bonding agents on the glass discs and composite resins discs were light cured and used for agar overlay cytotoxicity testing. Dentin bonding agents on composite resin discs exhibited far less cytotoxicity than that on glass discs. The polymerization of resin composite increased the surface hardness and decreased the cytotoxicity of bonding agents. In conclusion, composite resins in dental restorations are expected to enhance the polymerization of dentin bonding agents and reduce the elution of resin monomers, resulting in the decrease of cytotoxicity.

Effects of the iron-chelating agent deferoxamine on triethylene glycol dimethacrylate, 2-hydroxylethyl methacrylate, hydrogen peroxide-induced cytotoxicity.

Triethylene glycol dimethacrylate (TEGDMA) and 2-hydroxylethyl methacrylate (HEMA) are known to deplete glutathione in mammalian cells, generate reactive oxygen species (ROS), and cause oxidative stress. In this study, we investigated whether hydroxyl radicals (·OH), the most lethal and genotoxic ROS, and the Fenton reaction are involved in the cytotoxicity of resin monomers to four different cell types, namely MC3T3-E1 preosteoblasts, human dental pulp cells (HDPCs), human gingival fibroblasts, and L929 mouse fibroblasts. Deferoxamine (DFO), an iron chelating agent, effectively protected MC3T3-E1 cells from resin monomer-induced cytotoxicity, indicating that cytotoxicity was caused primarily by hydroxyl radicals. However, DFO only had a protective effect against relatively high concentrations of TEGDMA and HEMA in HDPCs and human gingival fibroblasts, and resin monomer-induced cytotoxicity in L929 was not attenuated by DFO. A labile iron pool (LIP) was detectable only in MC3T3-E1 cells among the four cell types. This indicates that the generation of hydroxyl radicals induced by resin monomers is likely dependent on LIP levels. In contrast to resin monomers, hydrogen peroxide (H(2)O(2))-induced cytotoxicity was not prevented by DFO in any of the cell types examined, although hydroxyl radicals were detected in MC3T3-E1 cells and HDPCs on exposure to exogenous H(2)O(2). This result suggests that generation of hydroxyl radicals is not always the primary cause of cytotoxicity in H(2)O(2)-treated cells.

Effects of N-acetylcysteine on TEGDMA- and HEMA-induced suppression of osteogenic differentiation of human osteosarcoma MG63 cells.

Triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are major resinous components of dental restorative materials and dentin bonding adhesives. Resin monomers are known to cause cytotoxicity in mammalian cells via oxidative stress and inhibit differentiation of dental pulp cells and osteoblasts. This study was aimed to investigate whether oxidative stress was involved in the inhibition of TEGDMA- and HEMA-induced differentiation. TEGDMA and HEMA reduced alkaline phosphatase (ALP) activity and the mRNA expression of the osteopontin (OPN) gene in MG63 cells at noncytotoxic concentrations. On the other hand, N-acetylcysteine (NAC) did not affect ALP activity at concentrations below 10 mM. Reduced ALP activity and OPN mRNA expression by TEGDMA were partially recovered via cotreatment with NAC. However, NAC did not exhibit significant effects in HEMA-treated cells. Glutathione (GSH) levels were also down-regulated by both TEGDMA and HEMA. The addition of NAC induced the partial recovery of GSH in cells treated with 0.5 mM TEGDMA. On the other hand, the levels of GSH in HEMA-treated cells were not affected by NAC. These results suggest that oxidative stress is involved in the suppression of differentiation by TEGDMA. Translocation of Nrf2 from the cytoplasm to the nucleus has been known to play a role in the suppression of osteogenic differentiation by oxidative stress. However, Nrf2 did not move into the nucleus in resin monomer-treated MG63 cells, suggesting the contribution of other signaling pathways to the suppressive effects of resin monomers.

Enhancement of the ALP activity of C3H10T1/2 cells by the combination of an oxysterol and apatite.

Biomimetic apatite coating has been used to load osteogenic biomolecules onto the surface of titanium implants. Apatite on the surface of biomaterials is thought to function as a reservoir of biomolecules as well as enhancing osteoconductivity. In this study, 20alpha-hydroxycholesterol (20alpha-HC), an osteogenic oxysterol, was used to induce differentiation of a mouse embryo fibroblast cell line (C3H10T1/2) by loading the oxysterol on biomimetically coated apatite of titanium discs. We found that the phosphatase (alkaline phosphatase (ALP)) activity of 20alpha-HC was significantly higher with ascorbic acid than alone, suggesting a need for ascorbic acid as a co-factor. When 20alpha-HC was added into the apatite coating solution, the ALP activity of the C3H10T1/2 cells did not increase on the apatite surface, even in the presence of ascorbic acid. However, ALP activity increased dramatically when 20alpha-HC was loaded by volatilization of EtOH from the apatite coat after dipping discs in 20alpha-HC-dissolved EtOH. Interestingly, ascorbic acid was not needed for this increase in ALP activity, suggesting a synergistic effect of 20alpha-HC and apatite. The concentration of calcium ions, a major component of apatite, affected the osteogenic effect of 20alpha-HC, and the increase in ALP activity was attenuated by L-type calcium channel inhibitors, verapamil and nifedipine. These results demonstrate that calcium ions released from apatite are important in the synergistic effect of 20alpha-HC and apatite.