Yoon-Hee Choi

Epidemic obesity and type 2 diabetes in Asia

The proportions of people with type 2 diabetes and obesity have increased throughout Asia, and the rate of increase shows no sign of slowing. People in Asia tend to develop diabetes with a lesser degree of obesity at younger ages, suffer longer with complications of diabetes, and die sooner than people in other regions. Childhood obesity has increased substantially and the prevalence of type 2 diabetes has now reached epidemic levels in Asia. The health consequences of this epidemic threaten to overwhelm health-care systems in the region. Urgent action is needed, and advocacy for lifestyle changes is the first step. Countries should review and implement interventions, and take a comprehensive and integrated public-health approach. At the level of primary prevention, such programmes can be linked to other non-communicable disease prevention programmes that target lifestyle-related issues. The cost of inaction is clear and unacceptable.

Long-Term Effect of the Internet-Based Glucose Monitoring System on HbA1c Reduction and Glucose Stability A 30-month follow-up study for diabetes management with a ubiquitous medical care system

OBJECTIVE—To investigate the long-term effectiveness of the Internet-based glucose monitoring system (IBGMS) on glucose control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—We conducted a prospective, randomized, controlled trial in 80 patients with type 2 diabetes for 30 months. The intervention group was treated with the IBGMS, while the control group made conventional office visits only. HbA1c (A1C) was performed at 3-month intervals. For measuring of the stability of glucose control, the SD value of A1C levels for each subject was used as the A1C fluctuation index (HFI). RESULTS—The mean A1C and HFI were significantly lower in the intervention group (n = 40) than in the control group (n = 40). (A1C [mean ± SD] 6.9 ± 0.9 vs. 7.5 ± 1.0%, P = 0.009; HFI 0.47 ± 0.23 vs. 0.78 ± 0.51, P = 0.001; intervention versus control groups, respectively). Patients in the intervention group with a basal A1C ≥7% (n = 27) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study (P = 0.022). Control patients with a basal A1C <7% (n = 15) showed the characteristic bimodal distribution of A1C levels, whereas the A1C levels in the intervention group remained stable throughout the study with low HFI. CONCLUSIONS—Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability.

Temperature-dependent properties of the magnetic order in single-crystal BiFeO 3

We report neutron diffraction and magnetization studies of the magnetic order in multiferroic BiFeO3. In ferroelectric monodomain single crystals, there are three magnetic cycloidal domains with propagation vectors equivalent by crystallographic symmetry. The cycloid period slowly grows with increasing temperature. The magnetic domain populations do not change with temperature except in the close vicinity of the N{\P}eel temperature, at which, in addition, a small jump in magneti- zation is observed. No evidence for the spin-reorientation transitions proposed in previous Raman and dielectric studies is found. The magnetic cycloid is slightly anharmonic for T=5 K. The an- harmonicity is much smaller than previously reported in NMR studies. At room temperature, a circular cycloid is observed, within errors. We argue that the observed anharmonicity provides important clues for understanding electromagnons in BiFeO3.

Hyperglycemia and hyperinsulinemia have additive effects on activation and proliferation of pancreatic stellate cells : Possible explanation of islet-specific fibrosis in type 2 diabetes mellitus

Pancreatic islet fibrosis observed in Type 2 diabetes is one of the major factors leading to progressive β‐cell loss and dysfunction. Despite its importance, the mechanism of islet‐restricted fibrogenesis associated with pancreatic stellate cell (PSC) activation and proliferation remains to be defined. Therefore, we studied whether the islet‐specific environment represented by hyperglycemia and hyperinsulinemia had additive effects on the activation and proliferation of cultured rat PSCs. Cells were stimulated to activate and proliferate with glucose and insulin, either individually or concomitantly. Both stimuli promoted PSC proliferation and extracellular signal‐regulated kinase (ERK) 1/2 phosphorylation independently, but an additive effect was also demonstrated. Blockade of ERK signaling by the mitogen‐activated protein kinase kinase (MEK) inhibitor, U0126, suppressed both glucose‐ and insulin‐induced ERK 1/2 phosphorylation and PSC proliferation. Glucose and insulin‐induced ERK 1/2 phosphorylation also stimulated connective tissue growth factor gene expression. Thus, hyperglycemia and hyperinsulinemia are two crucial mitogenic factors that activate and proliferate PSCs, and the presence of both states will amplify this response. J. Cell. Biochem. 101: 665–675, 2007.

Origin of electric-field-induced magnetization in multiferroic HoMnO3.

We have performed polarized and unpolarized small angle neutron scattering experiments on single crystals of HoMnO(3) and have found that an increase in magnetic scattering at low momentum transfers begins upon cooling through temperatures close to the spin reorientation transition at T(SR) approximately 40 K. We attribute the increase to an uncompensated magnetization arising within antiferromagnetic domain walls. Polarized neutron scattering experiments performed while applying an electric field show that the field suppresses magnetic scattering below T approximately 50 K, indicating that the electric field affects the magnetization via the antiferromagnetic domain walls rather than through a change to the bulk magnetic order.

Prevention of diabetes: a strategic approach for individual patients.

The ‘diabetes epidemic’ is an important health and socioeconomic problem worldwide. Type 2 diabetes is a chronic disease with gradual deterioration in glucose metabolism which causes multiple systemic complications. Therefore, early intervention in the prediabetic stage is a valuable approach to reduce diabetes development and related complications. Many clinical trials have suggested that lifestyle intervention, including moderate‐intensity exercise and diet control, and pharmacologic intervention using metformin, α‐glucosidase inhibitors, thiazolidinediones, anti‐obesity drugs and incretin mimics, are effective in preventing diabetes development. However, an individualized approach with careful consideration of the patient’s risk status and health economics is needed to perform a successful intervention programmes. In this review, we will summarize the known evidence on treatment‐ and cost‐effectiveness of drug and lifestyle treatment. Additionally, we will propose a strategic approach algorithm that is applicable to clinical practice.

Transforming growth factor-β induces epithelial to mesenchymal transition and suppresses the proliferation and transdifferentiation of cultured human pancreatic duct cells†‡

Pancreatic duct cells are considered a potential source of β‐cell regeneration, and transforming growth factor‐β (TGF‐β) has been suggested to perform an important role in these processes, but the underlying mechanism of the signal pathways, especially in humans, remains poorly understood. To evaluate the role of TGF‐β1, pancreatic duct cells were isolated from three brain‐dead organ donors. Pancreatic cell clusters harvested after islet isolation were dispersed to single cells and cultured in monolayers, then treated with TGF‐β1. We analyzed the characteristics of the cultured cells, the TGF‐β1 intracellular signaling pathway, the proliferation, and transdifferentiation rates of the duct cells. We also evaluated the genes and protein expression patterns after TGF‐β1 treatment. After TGF‐β1 treatment, typical morphologic changes representative of EMT were observed and Erk1/2, JNK, and AKT phosphorylation, Ras downstream effectors, were increased. β cell‐specific transcription factors including PDX‐1, Beta2/NeuroD, Ist‐1, and NGN3 were markedly suppressed and the rate of transdifferentiation into β cells was also suppressed. Genomic and proteomic analyses suggested that TGF‐β1 induces marked changes in a variety of structural genes and proteins associated with EMT. In conclusion, TGF‐β1 induces EMT in cultured human pancreatic duct cells, but suppresses its proliferation and transdifferentiation into β cells. Our results are the first report of TGF‐β1 effects for EMT and ductal cell transdifferentiation and proliferation at the protein level in human pancreatic duct cells. J. Cell. Biochem. 112: 179–188, 2011.

Proteomic analysis of differential protein expression in response to epidermal growth factor in neonatal porcine pancreatic cell monolayers

We have proposed that porcine neonatal pancreatic cell clusters (NPCCs) may be a useful alternative source of cells for islet transplantation, and that monolayer cultures might provide an opportunity to manipulate the cells before transplantation. In addition we previously identified 10 genes up‐regulated by epidermal growth factor (EGF) in cultured porcine NPCC monolayers. We have now analyzed the intracellular signaling pathways activated by EGF and searched for proteins differentially expressed following EGF treatment of the monolayers, using two‐dimensional gel electrophoresis (2‐DE) and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). EGF treatment resulted in phosphorylation of both Erk 1/2 and Akt, as well as increased cell proliferation. Five unknown and 13 previously identified proteins were differentially expressed in response to EGF. EGF treatment increased the expression of several structural proteins of epithelial cells, such as cytokeratin 19 and plakoglobin, whereas vimentin, the intermediate filament protein of mesenchymal cells, and non‐muscle myosin alkali chain isoform 1, decreased. Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 factor, which promotes epithelial cell proliferation, and hemoglobin alpha I & II also increased, whereas cyclin A1, immunoglobulin heavy chain, apolipoprotein A1, 5,10‐ethylenetetrahydrofolated reductase (5,10‐MTHFR), angiotensin‐converting enzyme 2 (ACE2), co‐lipase II precursor, and NAD+ isocitrate dehydrogenase (NAD+ IDH) alpha chain proteins decreased. Our results show that EGF stimulates proliferation of pancreatic epithelial cells by simultaneously activating the MAPK and PI‐3K pathways. HnRNP A2/B1, hemoglobin, cyclin A1, and ACE2 may play roles in the proliferation of epithelial cells in response to EGF.

Statin Discontinuation after Achieving a Target Low Density Lipoprotein Cholesterol Level in Type 2 Diabetic Patients without Cardiovascular Disease: A Randomized Controlled Study.

Background This study investigated the rate of relapse of dyslipidemia and the factors which could predict relapse following a short-term statin discontinuation after achieving a target low density lipoprotein cholesterol (LDL-C) level in type 2 diabetic patients without cardiovascular disease (CVD). Methods Ninety-nine subjects on rosuvastatin treatment and whose LDL-C level was lower than 100 mg/dL were randomly assigned to discontinue or maintain statin treatment at a 2:1 ratio. The subjects were followed-up after 10 weeks. A relapse of dyslipidemia was defined as a reascent of LDL-C level to greater than 100 mg/dL. Results The statin discontinuation group had a significant rate of relapse compared to the maintenance group (79% vs. 3%, respectively). Pretreatment and baseline lipid levels, their ratios, and hemoglobin A1c level were significantly different between the relapse and nonrelapse groups. The pretreatment and baseline lipid profiles and their ratios were independently associated with relapse. The pretreatment LDL-C level was the most useful parameter for predicting a relapse, with a cutoff of 123 mg/dL. During the follow-up period, no CVD event was noted. Conclusion The relapse rate of dyslipidemia was high when statins were discontinued in type 2 diabetic patients without CVD. Statin discontinuation should be considered carefully based on the pretreatment lipid profiles of patients.

Nutritional Intake of Pregnant Women with Gestational Diabetes or Type 2 Diabetes Mellitus

Adequate intake of nutrients by pregnant women diagnosed with gestational diabetes mellitus (GDM) or type 2 diabetes (T2DM) is very important for appropriate weight gain and maintenance of normoglycemia without ketonuria. The aim of this study was to investigate the nutritional intake of pregnant women with GDM or T2DM who had not been provided with nutritional education regarding blood glucose management. Between June 2008 and May 2010, 125 pregnant women who had been diagnosed with GDM or T2DM and had not received any nutrition education regarding glycemic control and proper diet during pregnancy were interviewed to collect data regarding background characteristics, health-related behaviors, and course of pregnancy and instructed to record their dietary intake using a 24-hour recall method for one day. Using the collected data, the index of nutritional quality, nutrient adequacy ratio, and mean adequacy ratio values of the subjects were calculated. Analysis of the values indicated that the majority of the subjects did not meet recommended intake levels for most micronutrients and consumed an undesirable ratio of macronutrients, specifically a higher percentage of total carbohydrates than the current recommendation level. The GDM and T2DM groups obtained 56.6% and 63.6%, respectively (p = 0.012), of their calories by carbohydrate intake, which exceeded the recommended levels (125.8% in GDM groups, 141.3% in T2DM groups).