Chul Sik Kim

Effects of Pro12Ala polymorphism of peroxisome proliferator‐activated receptor γ2 gene on rosiglitazone response in type 2 diabetes

The aim of this study was to examine the effects of the Pro12Ala polymorphism of the peroxisome proliferator‐activated receptor (PPAR) γ2 gene on the response to rosiglitazone in patients with type 2 diabetes mellitus.

Insulin dose titration system in diabetes patients using a short messaging service automatically produced by a knowledge matrix.

BACKGROUND We designed a system for diabetes patients treated with glargine, a long-acting insulin, to make an automatic adjustment of insulin dose based on glucose level data and to provide the patients with the needed insulin dose by using a short message service (SMS). We also compared diabetes patients who used our system with patients who received the conventional titration scheme. METHODS Included were 100 type 2 diabetes patients whose blood glucose was suboptimally controlled on their previous antidiabetes treatment. Each participant was assigned to either the intervention or control group, each with 50 patients, using adaptive randomization. We applied our system to the intervention group for 12 weeks, whereas the control group received a conventional titration scheme, seeking a target fasting blood glucose of <120 mg/dL. RESULTS The fasting and postprandial glucose levels of the intervention group declined earlier than those of the control group. Lastly, a greater (P = 0.023) reduction in hemoglobin A(1C) from baseline to the end point was observed in the intervention group (from 9.8 +/- 1.3% to 7.4 +/- 0.7%) than in the control group (from 9.8 +/- 1.2% to 7.8 +/- 0.8%). The incidence of symptomatic, asymptomatic, and nocturnal hypoglycemia was similar in both groups. There was a small increase in body weight from baseline to the end point with both the intervention (2.4 +/- 3.0 kg) and control (2.2 +/- 2.8 kg) groups. CONCLUSIONS This study demonstrated that SMS based on our specialized Internet-supported system is an effective and safe approach to long-acting insulin dose adjustments in patients with type 2 diabetes.

Effects of growth hormone on insulin resistance and atherosclerotic risk factors in obese type 2 diabetic patients with poor glycaemic control

Objective  We aimed to evaluate the combined effects of GH treatment and diet restriction on lipolysis and anabolism, insulin resistance and atherosclerotic risk factors in obese patients with type 2 diabetes mellitus (T2DM).

Usefulness of brachial-ankle pulse wave velocity as a predictive marker of multiple coronary artery occlusive disease in Korean type 2 diabetes patients

Multiple coronary artery occlusive disease (multiple CAOD) is the most fatal and frequently observed coronary artery disease in type 2 diabetes patients, but no simple, non-invasive screening tool is available yet. The aim of this study is to evaluate the arterial stiffness in type 2 diabetes patients using brachial-ankle pulse wave velocity (baPWV), to demonstrate the correlation between arterial stiffness and multiple CAOD, and to suggest the cutoff point of baPWV for predicting multiple CAOD in Korean type 2 diabetes patients. One hundred and eighty-one diabetes and 262 non-diabetes patients were enrolled in the study. Routine anthropometric and serologic data were collected. baPWV was measured the day before coronary angiography, and the severity of CAOD was assessed with Gensini score after angiography. baPWV and Gensini score were significantly increased in diabetes patients and Gensini score had a positive correlation with baPWV. Subjects in the highest tertile of baPWV showed odds ratio of 3.06 for multiple CAOD compared to the lowest tertile. In ROC curve, baPWV at 1635 cm/s showed 73% sensitivity and 75% specificity with AUC 0.76 in diabetes patients in detecting multiple CAOD. Therefore, baPWV may be utilized a screening tool for predicting multiple CAOD, especially in type 2 diabetes patients.

Dose-related cytoprotective effect of α-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells

α-Lipoic acid (α-LA), an antioxidant used for diabetic polyneuropathy, was reported to induce AMP-activated protein kinase activation and reductions in insulin secretion in pancreatic beta-cells at high concentrations (≥ 500 µmol/l). This study investigated whether α-LA has a protective role under oxidative stress in beta-cells and its effect is dose-related. In INS-1 cells treated with α-LA (150-1200 µmol/l) for 24 h, α-LA itself (≥300 µmol/l) induced apoptotic death dose-dependently. However, pre-treatment with 150 and 300 µmol/l α-LA reduced the hydrogen peroxide-induced apoptosis in INS-1 cells and isolated islets. α-LA alleviated hydrogen peroxide-induced reactive oxygen species production, mitochondrial membrane depolarization and c-JNK activation in beta-cells. α-LA induced phosphoinositide 3-kinase-dependent Akt phosphorylation in INS-1 cells. While α-LA is harmful to beta-cells at high concentrations in vitro, it has potential cytoprotective effects on beta-cells under oxidative stress as in diabetes by its antioxidant properties and possibly by Akt phosphorylation at clinically relevant concentrations.

Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation

For gene transfer strategies to improve islet engraftment, vascular endothelial growth factor (VEGF) expression should be regulated in a way that matches the transient nature of revascularization with simultaneously avoiding undesirable effects of overexpression. The aim of this study was to investigate the effects of hypoxia‐inducible VEGF gene transfer using the RTP801 promoter on islet grafts. We implanted pSV‐hVEGF transfected, pRTP801‐hVEGF transfected or nontransfected mouse islets under the kidney capsule of streptozotocin‐induced diabetic syngeneic mice. Human VEGF immunostaining of day 3 grafts revealed that the pRTP801‐hVEGF transfected group had higher hVEGF expression compared with the pSV‐hVEGF transfected group. BS‐1 staining of day 3 grafts from the pRTP801‐hVEGF transfected group showed the highest vascular density, which was comparable with day 6 grafts from the nontransfected group. In 360 islet equivalent (IEQ)‐transplantation which reverted hyperglycemia in all mice, the area under the curve of glucose levels during intraperitoneal glucose tolerance test 7 weeks post‐transplant was lower in mice transplanted with pRTP801‐hVEGF transfected grafts compared with mice transplanted with nontransfected grafts. In 220 IEQ‐transplantations, diabetic mice transplanted with pRTP801‐hVEGF islets became normoglycemic more rapidly compared with mice transplanted with pSV‐hVEGF or nontransfected islets, and diabetes reversal rate after 50 days was 90%, 68%, and 50%, respectively. In conclusion, our results indicate that regulated overexpression of hVEGF in a hypoxia‐inducible manner enhances islet vascular engraftment and preserves islet function overtime in transplants.

Apigenin induces c-Myc-mediated apoptosis in FRO anaplastic thyroid carcinoma cells.

Apigenin promotes apoptosis in cancer cells. We studied the effect of apigenin on cell survival and c-Myc expression in FRO anaplastic thyroid carcinoma (ATC) cells. Apigenin caused apoptosis via the elevation of c-Myc levels in conjunction with the phosphorylation of p38 and p53. In the c-Myc siRNA-transfected and apigenin-treated cells, compared with the apigenin-treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated. In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c-Myc levels. In conclusion, our results indicate that apigenin induces apoptosis mediated via c-Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells. These findings suggest that augmented c-Myc acts as a core regulator and is necessary for apigenin-induced apoptosis in FRO ATC cells.

Effects of α-lipoic acid on transforming growth factor β1–p38 mitogen-activated protein kinase–fibronectin pathway in diabetic nephropathy

In diabetic nephropathy, transforming growth factor beta1 (TGFbeta1) is related to p38 mitogen-activated protein kinase (MAPK) that induces production of fibronectin in mesangial cells. We investigated the effects of alpha-lipoic acid (ALA), a potent antioxidant, on proteinuria and TGFbeta1-p38 MAPK-fibronectin pathway in diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After ALA treatment for 5 weeks in OLETF rats at 30 weeks of age, plasma malondialdehyde, urinary protein excretion, renal cortical TGFbeta1, and fibronectin protein levels were decreased; and urinary protein excretion was positively correlated with renal cortical TGFbeta1 and fibronectin protein levels. Phospho-form but not total-form levels as well as fold activations of each protein consisting of p38 MAPK pathway were also attenuated. These results suggest that ALA ameliorates proteinuria by attenuating expressions of TGFbeta1 and fibronectin proteins, and these favorable effects are related to inhibition of phosphorylating activation of p38 MAPK pathway in renal cortex of OLETF rats.

The relationship of thyroid hormone status with myocardial function in stress cardiomyopathy

OBJECTIVE This study aimed to investigate thyroid hormone (TH) status and its relationship with myocardial function as well as clinical and biochemical parameters in stress cardiomyopathy (CMP). METHODS Forty-five patients with stress CMP (the patient group), 31 patients without stress CMP (the control II group), and 58 healthy subjects (the control I group) were included. Sick euthyroid syndrome (SES) was defined as low total triiodothyronine (T(3)) with normal TSH levels. RESULTS In the patient group at admission, prevalence of SES was 62.2%. Compared with the control I group, the patient group had a decrease in left ventricular ejection fraction (LVEF) and systolic blood pressure (BP) and an increase in troponin-I, CK-MB, and B-type natriuretic peptide (BNP) levels. Total T(3) levels were reduced, and anti-thyroid peroxidase antibody (anti-TPO Ab) positivity, C-reactive protein (CRP) and cortisol levels were elevated. Total T(3) levels were associated with acute physiology and chronic health evaluation II (APACHE II) score, LVEF, systolic BP, and cortisol levels in multivariate analysis. In the control II group, total T(3) levels were not associated with any variables. In the SES (n=28) and myocardial dysfunction (MDys, n=27) subgroups, increased APACHE II score and BNP levels as well as decreased LVEF and systolic BP were significant. Total T(3) levels were reduced, and CRP, cortisol and catecholamines levels were elevated. In the MDys subgroup, anti-TPO Ab positivity and titer were increased. CONCLUSION These results suggest that total T(3) levels may be associated with myocardial contractility, clinical severity, and cortisol levels. Thyroid autoimmunity may influence myocardial contractility in stress CMP.

Does birthweight predict adolescent adiponectin levels

Objective Low birthweight is associated with insulin resistance later in life, and adiponectin is known to play an important role in insulin resistance. We have investigated whether birthweight has a relationship with adiponectin levels in adolescence.