Korean women with a history of gestational diabetes mellitus (GDM) have a 3.5 times greater risk of developing postpartum diabetes than the general population. The incidence of type 2 diabetes mellitus in early postpartum is reported as 10-15% in Korean women. A prospective follow-up study on Korean women with GDM showed that approximately 40% of women with previous GDM were expected to develop diabetes within 5 years postpartum. Independent risk factors for the development of diabetes in Korean women with previous GDM are pre-pregnancy body weight, gestational age at diagnosis, antepartum hyperglycemia on oral glucose tolerance test, low insulin response to oral glucose load, and family history of diabetes. Women with postpartum diabetes have greater body mass indexes, body weight, and waist circumferences than women with normal glucose tolerance. Multiple logistic regression analysis has revealed that waist circumference is the strongest obesity index along with systolic blood pressure and that triglyceride levels are a major independent risk factor for developing diabetes. These results in Korean women with previous GDM underline the importance of postpartum testing in Korean women diagnosed with GDM, and demonstrate that impaired B-cell function, obesity, and especially visceral obesity, are associated with the development of diabetes.
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Diabetic vascular complications are among the leading causes of morbidity and mortality in diabetic patients. In the past, many studies have focused on the mechanisms of hyperglycemia-induced chronic vascular complications via the formation of toxic metabolites such as oxidative stress, advanced glycosylated end products, persistent activation of protein kinase C, and increased sorbitol concentrations. However, vascular complications result from imbalances caused by increases in systemic toxic metabolites, such as those that occur under conditions of hyperglycemia and dyslipidemia, and by reductions in endogenous protective factors such as insulin, vascular endothelial growth factor, and platelet derived growth factor. This review outlines some of the evidence supporting the importance of enhancing endogenous regenerative factors.
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Type 2 diabetes mellitus (T2DM) is caused by complex interplay between multiple genetic and environmental factors. The three major approaches used to identify the genetic susceptibility include candidate gene approach, familial linkage analysis and genome- wide association analysis. Recent advance in genome-wide association studies have greatly improved our understanding of the pathophysiology of T2DM. As of the end of 2010, there are more than 40 confirmed T2DM-associated genetic loci. Most of the T2DM susceptibility genes were implicated in decreased β-cell function. However, these genetic variations have a modest effect and their combination only explains less than 10% of the T2DM heritability. With the advent of the next-generation sequencing technology, we will soon identify rare variants of larger effect as well as causal variants. These advances in understanding the genetics of T2DM will lead to the development of new therapeutic and preventive strategies and individualized medicine.
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Although many anti-diabetic drugs have been used to control hyperglycemia for decades, the efficacy of commonly-used oral glucose-lowering agents in Korean type 2 diabetic patients has yet to be clearly demonstrated.
We evaluated the efficacy of glimepiride, metformin, and rosiglitazone as initial treatment for drug-naïve type 2 diabetes mellitus patients in a 48-week, double-blind, randomized controlled study that included 349 Korean patients. Our primary goal was to determine the change in HbA1c levels from baseline to end point. Our secondary goal was to evaluate changes in fasting plasma glucose (FPG) levels, body weight, frequency of adverse events, and the proportion of participants achieving target HbA1c levels.
HbA1c levels decreased from 7.8% to 6.9% in the glimepiride group (
The efficacy of glimepiride, metformin, and rosiglitazone as antidiabetic monotherapies in drug-naïve Korean type 2 diabetic patients was similar in the three groups, with no statistical difference. This study is the first randomized controlled trial to evaluate the efficacy of commonly-used oral hypoglycemic agents in Korean type 2 diabetic patients. An additional subgroup analysis is recommended to obtain more detailed information.
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The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD).
A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT).
Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years,
In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.
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Recent studies have revealed that C-peptide induces smooth muscle cell proliferation and causes human atherosclerotic lesions in diabetic patients. The present study was designed to examine whether the basal C-peptide levels correlate with cardiovascular risk in type 2 diabetes mellitus (T2DM) patients.
Data was obtained from 467 patients with T2DM from two institutions who were followed for four years. The medical findings of all patients were reviewed, and patients with creatinine >1.4 mg/dL, any inflammation or infection, hepatitis, or type 1 DM were excluded. The relationships between basal C-peptide and other clinical values were statistically analyzed.
A simple correlation was found between basal C-peptide and components of metabolic syndrome (MS). Statistically basal C-peptide levels were significantly higher than the three different MS criteria used in the present study, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program's (NCEP's), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria (NCEP-ATP III,
Basal C-peptide is related to cardiovascular predictors (IMT) of T2DM, suggesting that basal C-peptide does provide a further indication of cardiovascular disease.
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Advanced information technology can be used when developing diagnostic and treatment strategies to provide better care for diabetic patients. However, the levels of need and demand for the use of technological advances have not been investigated in diabetic patients. We proposed and developed an individualized, ubiquitous (U)-healthcare service using advanced information technology for more effective glucose control. Prior to our service initiation, we surveyed patient needs and other pertinent information.
During August 2009, we conducted a 34-item questionnaire survey among patients with diabetes who were older than 40 years in two certain hospitals in Korea.
The mean age of the 228 participants was 61.2±9 years, and males made up 49.1% of the sample. Seventy-one percent replied that they wanted individualized healthcare service, and they also wanted their health information to be delivered through mobile devices such as a cellular phone or a personal digital assistant (40.4%). Most patients had never heard of U-healthcare services (81.1%); however, after explaining the concept, 71.1% of participants responded that they would use the service if it was provided. Despite their willingness, participants were concerned about technical difficulty in using the service (26.3%) as well as the cost of the service (29.8%).
The current study suggests that more than 70% of diabetic patients are interested in using U-healthcare services. To encourage widespread use, the application program or device of U-healthcare services should be simple, easy to use and affordable while also including a policy for the protection of private information.
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We examined the change in the levels of incretin hormone and effects of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) on insulin secretion in women with previous gestational diabetes (pGDM).
A 75-g oral glucose tolerance test (OGTT) was conducted on 34 women with pGDM. In addition, 11 women with normal glucose tolerance, matched for age, height and weight, were also tested. The insulin, GIP, GLP-1, and glucagon concentrations were measured, and their anthropometric and biochemical markers were also measured.
Among 34 women with pGDM, 18 had normal glucose tolerance, 13 had impaired glucose tolerance (IGT) and 1 had diabetes. No significant differences were found in GLP-1 concentration between the pGDM and control group. However, a significantly high level of glucagon was present in the pGDM group at 30 minutes into the OGTT. The GIP concentration was elevated at 30 minutes and 60 minutes in the pGDM group. With the exception of the 30-minute timepoint, women with IGT had significantly high blood glucose from 0 to 120 minutes. However, there was no significant difference in insulin or GLP-1 concentration. The GIP level was significantly high from 0 to 90 minutes in patients diagnosed with IGT.
GLP-1 secretion does not differ between pGDM patients and normal women. GIP was elevated, but that does not seem to induce in increase in insulin secretion. Therefore, we conclude that other factors such as heredity and environment play important roles in the development of type 2 diabetes.
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Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood.
INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours.
The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine.
Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress.
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Previously, we reported that neonatal porcine pancreatic cells transfected with hepatocyte growth factor (HGF) gene in an Epstein-Barr virus (EBV)-based plasmid (pEBVHGF) showed improved proliferation and differentiation compared to those of the control. In this study, we examined if pancreatic cells transfected repeatedly with pEBVHGF can be successfully grafted to control blood glucose in a diabetes mouse model.
Neonatal porcine pancreatic cells were cultured as a monolayer and were transfected with pEBVHGF every other day for a total of three transfections. The transfected pancreatic cells were re-aggregated and transplanted into kidney capsules of diabetic nude mice or normal nude mice. Blood glucose level and body weight were measured every other day after transplantation. The engraftment of the transplanted cells and differentiation into beta cells were assessed using immunohistochemistry.
Re-aggregation of the pancreatic cells before transplantation improved engraftment of the cells and facilitated neovascularization of the graft. Right before transplantation, pancreatic cells that were transfected with pEBVHGF and then re-aggregated showed ductal cell marker expression. However, ductal cells disappeared and the cells underwent fibrosis in a diabetes mouse model two to five weeks after transplantation; these mice also did not show controlled blood glucose levels. Furthermore, pancreatic cells transplanted into nude mice with normal blood glucose showed poor graft survival regardless of the type of transfected plasmid (pCEP4, pHGF, or pEBVHGF).
For clinical application of transfected neonatal porcine pancreatic cells, further studies are required to develop methods of overcoming the damage for the cells caused by repeated transfection and to re-aggregate them into islet-like structures.
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Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans.
To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patient's dialyzed serum before and after immunosuppressive therapy.
In the patient's pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%.
We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patient's insulin receptor antibodies by measuring the inhibition of insulin binding.
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