Ki-Ho Song

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.

Vitamin D Deficiency Is Associated with Sarcopenia in Older Koreans, Regardless of Obesity: The Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) 2009

BACKGROUND An association between vitamin D status and sarcopenia has not been shown in a community-dwelling cohort, despite the well-documented relationship between vitamin D status and falls. OBJECTIVE Our objective was to investigate whether vitamin D level is associated with sarcopenia in older Koreans. DESIGN AND SETTING The Fourth Korea National Health and Nutrition Examination Survey in the Korean population was conducted in 2009. PARTICIPANTS Participants included 1380 men and 1789 women aged 50 yr or older. MEASUREMENTS Serum 25-hydroxyvitamin D [25(OH)D] and PTH levels were measured. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight that was less than 2 sd below the sex-specific mean for young adults. Obesity was defined as a body mass index (BMI) of 27.5 kg/m(2) or higher. RESULTS 25(OH)D level correlated negatively with appendicular fat mass and positively with appendicular skeletal mass. The groups with sarcopenic obesity and sarcopenia only had lower 25(OH)D levels than did the nonsarcopenia groups. However, 25(OH)D levels did not differ between the sarcopenic obesity and sarcopenia groups. After adjustment for age, sex, BMI, and lifestyle factors, compared with those in the lowest quartile of 25(OH)D level, participants in the highest quartile had an odds ratio for sarcopenia of 0.47 (95% confidence interval = 0.30-0.73; P for trend = 0.001). There was no association between PTH and sarcopenia after adjustment of BMI. CONCLUSIONS Vitamin D levels were significantly lower in subjects with sarcopenia than in those without, regardless of obesity. We found a strong inverse association between 25(OH)D level and sarcopenia in the older Korean population.

High glucose increases extracellular matrix production in pancreatic stellate cells by activating the renin–angiotensin system

Pancreatic stellate cells (PSCs) are involved in pancreatic inflammation and fibrosis. Recent studies have shown that blocking the renin–angiotensin system (RAS) attenuates pancreatic inflammation and fibrosis. However, there are few data about the direct effects of high glucose on extracellular matrix (ECM) protein synthesis and angiotensin II (Ang II) induction in PSCs. PSCs were isolated from male Sprague–Dawley rats and cultured in medium containing 5.5 mM (LG group) or 27 mM D‐glucose (HG group). Levels of Ang II and transforming growth factor‐β (TGF‐β) in culture media were measured and Ang II‐positive cells were counted. We used real‐time polymerase chain reaction (PCR) to detect Ang II receptor expression and Western blot analysis for the expression of ECM proteins such as connective‐tissue growth factor (CTGF) and collagen type IV. Cells were also treated with an Ang II‐receptor antagonist (candesartan, 10 µM) or angiotensin‐converting enzyme (ACE) inhibitor (ramiprilat, 100 nM). Thymidine uptake by PSCs increased fourfold with high glucose treatment. Ang II levels and the proportion of Ang II‐positive PSCs were significantly increased after 6 h under high‐glucose conditions. TGF‐β concentrations also increased significantly with high glucose. After 72 h, the expression of CTGF and collagen type IV proteins in high‐glucose cultures increased significantly and this increase was effectively attenuated by the candesartan or the ramiprilat. All together, high glucose induced PSCs proliferation and ECM protein synthesis, and these effects were attenuated by an Ang II‐receptor antagonist. The data suggest that pancreatic inflammation and fibrosis aggravated by hyperglycemia, and Ang II play an important role in this pathogenesis. J. Cell. Biochem. 98: 343–355, 2006.

The short-term changes of bone mineral metabolism following bone marrow transplantation

Organ transplantation is now the treatment of choice for many patients with life-threatening chronic diseases. A new set of side effects unique to these groups of patients has become recognized, and bone disease is one of these complications. However, little is known about the effects of myeloablative treatment followed by bone marrow transplantation (BMT) on bone mineral metabolism. We have prospectively investigated 31 patients undergoing BMT for hematologic diseases. Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones, and the biochemical markers of bone turnover were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 year after BMT. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry before BMT and 1 year after BMT. The serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively until 4 weeks after BMT. Thereafter, it began to decrease and reached basal values after 1 year. Serum osteocalcin decreased progressively until 3 weeks after BMT. After that, it increased and reached basal values after 3 months. No distinct differences were observed in the serum biochemical turnover markers between males and females, or between patients who received total body irradiation and those who did not. One year after BMT, lumbar spine BMD had decreased by 2.2%, and total proximal femoral BMD had decreased by 6.2%. Eighty-six percent of the women (12/14) went into a menopausal state immediately after BMT. This was caused by high gonadotropin levels and low estradiol levels. In contrast, gonadotropin levels and testosterone levels did not change significantly in the male patients after BMT. In conclusion, the rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in post-BMT bone loss.

Clinical characteristics of diabetic ketoacidosis in Korea over the past two decades

Aims  The aim of this study was to investigate changes in the clinical characteristics of diabetic ketoacidosis (DKA) in Korea over the last two decades.

Antioxidant treatment may protect pancreatic beta cells through the attenuation of islet fibrosis in an animal model of type 2 diabetes

Islet fibrosis could be important in the progression of pancreatic beta cell failure in type 2 diabetes. It is known that oxidative stress is involved in the pancreatic fibrosis through the activation of pancreatic stellate cells. However, no study has investigated the in vivo effects of antioxidants on islet fibrogenesis in type 2 diabetes. In this study, antioxidants (taurine or tempol) were administered in drinking water to Otsuka Long-Evans Tokushima Fatty rats, an animal model of type 2 diabetes, for 16 weeks. An intraperitoneal glucose tolerance test revealed that the blood glucose levels after the glucose injection were decreased by the antioxidants. The insulin secretion after the glucose injection, which was markedly reduced in the rats, was also restored by the antioxidants. Beta cell mass and pancreatic insulin content were greater in the rats treated with the antioxidants than in the untreated rats. Beta cell apoptosis was attenuated in the rats by the antioxidants. Finally, islet fibrosis and the activation of pancreatic stellate cells were markedly diminished in the rats by the antioxidants. Our data suggest that antioxidants may protect beta cells through the attenuation of both islet fibrosis and beta cell apoptosis in type 2 diabetes.

Inducible nitric oxide synthase-nitric oxide plays an important role in acute and severe hypoxic injury to pancreatic beta cells.

Background. Islet transplantation is a potential strategy to cure type 1 diabetes mellitus. However, a substantial part of the islet graft becomes nonfunctional due to several factors including hypoxia. However, the precise mechanism of cell damage is largely unknown in hypoxic exposure to pancreatic beta cells. The aim of the present study was to investigate whether acute and severe hypoxic injury could involve inducible nitric oxide synthase (iNOS)-nitric oxide (NO) signaling in beta cells. Methods. The rat beta cell line (INS-1) and primary rat islets were incubated in an anoxic chamber. Cell viability was determined by propium iodide staining or cell counting kit. The expression of iNOS mRNA and protein was examined using reverse-transcription polymerase chain reaction and Western blot analysis. NO production was measured as nitrite accumulation by Griess reagent method. Results. After hypoxic exposure, marked cell death occurred in INS-1 cells and rat islets, accompanied by increase in activated caspase-3 expression. NO production was increased in the culture medium in a time-dependent manner. Increase in expression of iNOS mRNA and protein was found. Pretreatment with a selective iNOS inhibitor, 1400W, significantly prevented cell death during hypoxia. In addition, hypoxia activated c-Jun N-terminal kinase (JNK) significantly, but the addition of 1400W inhibited hypoxia-induced JNK phosphorylation. Conclusions. Our data suggest that iNOS-NO plays an important role in acute and severe hypoxic injury to pancreatic beta cells. Therefore, iNOS-NO might be a potential therapeutic target for preserving beta cell survival in islet transplantation through prevention of hypoxia-mediated cell death.

Normal weight obesity in Korean adults

A better way to define obesity is in terms of the percentage of body fat (BF). Subjects with normal weight, but excess BF are vulnerable to cardiovascular diseases.

Loss of beta-cells with fibrotic islet destruction in type 2 diabetes mellitus.

Recent morphologic analyses of human pancreases strongly suggest that a decreased beta-cell mass is observed from the early stages of diabetes and is caused by accelerated apoptosis of the beta-cells. In this article, we propose that fibrotic islet destruction might be one of the important pathogenic mechanisms of the limited capacity of beta-cell proliferation and accelerated apoptosis in diabetic patients. We have found that pancreatic stellate cells (PSCs) are involved in the progression of islet fibrosis in type 2 diabetes. High concentrations of glucose and insulin in islets contribute to PSC activation and proliferation through angiotensin II type 2 (ATII) signaling pathway, although the exact mechanisms remain to be confirmed. Angiotensin-converting enzyme inhibitors attenuate fibrotic islet destructions and that these have some beneficial effects on glucose tolerance. We suggest that PSCs might play a major role for the fibrotic islet destruction in patients with type 2 diabetes, and suppression of PSCs activation and proliferation might be one of the reasonable target to prevent and delay the progression of the type 2 diabetes mellitus.

The effect of rosiglitazone on serum lipoprotein(a) levels in korean patients with type 2 diabetes mellitus

The aim of the study was to determine if rosiglitazone increases serum levels of lipoprotein(a) [Lp(a)] in Korean patients with type 2 diabetes mellitus. A total of 118 patients were divided into 2 groups: those with rosiglitazone (rosiglitazone group, n = 49) and those without rosiglitazone (control group, n = 69). The rosiglitazone group was given rosiglitazone (4 mg/d) with previous treatment, insulin, or sulfonylurea, for 12 weeks, whereas the control group continued previous treatment with some dose modification for glycemic control. The patients had their blood glucose, lipid levels, as well as Lp(a) levels assessed to obtain a baseline, which were remeasured 12 weeks later. The fasting blood glucose and glycosylated hemoglobin (HbA(1c)) levels decreased significantly in both groups as compared with the baseline. The fasting glucose and HbA(1c) levels in both groups were similar at 12 weeks. The total cholesterol levels increased significantly in the rosiglitazone group (190.6 +/- 32.4 to 212.2 +/- 47.2 mg/dL, P =.002), while they were unchanged in the control group (185.4 +/- 36.8 to 188.0 +/- 35.8 mg/dL, P =.615). The triglyceride levels did not change in either group. Significant increases in high-density lipoprotein (HDL) cholesterol levels were observed in the rosiglitazone group as compared with the baseline (41.7 +/- 10.6 to 45.9 +/- 11.4 mg/dL, P =.004). The low-density lipoprotein (LDL) cholesterol levels increased significantly in the rosiglitazone group (120.5 +/- 29.9 to 136.3 +/- 40.0 mg/dL, P =.012), while they did not change in the control group (113.0 +/- 29.1 to 118.3 +/- 31.7 mg/dL, P =.234). Significant increases in Lp(a) levels were observed in the rosiglitazone group as compared with the baseline (22.4 +/- 17.4 to 25.7 +/- 20.5 mg/dL, P =.015), approximately a 15% increase in average values. In contrast, there was no change in Lp(a) levels in the control group. There was no correlation between the changes in Lp(a) and changes in fasting blood glucose or HbA(1c) levels in all study subjects. In summary, rosiglitazone increased serum total cholesterol, LDL cholesterol, as well as Lp(a) levels in patients with type 2 diabetes mellitus. Considering that patients with type 2 diabetes mellitus have increased risks for cardiovascular disease, caution should be taken when prescribing rosiglitazone to patients who already have other risk factors, such as hypertension and smoking.