Relationship between Clinical Features of Diabetic Retinopathy and Systemic Factors in Patients with Newly Diagnosed Type II Diabetes Mellitus

Background@#We investigated the relationship between clinical features of diabetic retinopathy (DR) and systemic factors in patients with newly diagnosed type II diabetes mellitus (T2DM). @*Methods@#Retrospective review of newly diagnosed T2DM-patients who underwent complete ophthalmic examinations at the time of T2DM diagnosis were conducted. We reviewed DM related systemic factor data and investigated systemic factors related to the presence of DR at T2DM diagnosis. In DR patients, the relationship between DR severity and systemic factors was analyzed. @*Results@#Of 380 patients, forty (10.53%) patients had DR at the initial ophthalmologic examination. Glycated hemoglobin (HbA1C), fasting plasma glucose (FPG), urine albumin to creatinine ratio (UACR), and urine microalbumin level were significantly higher in DR patients than in patients without DR. In the multivariate logistic regression analysis, high HbA1C was a significant risk factor for the presence of DR at new T2DM diagnosis (odds ratio, 2.372; P < 0.001). HbA1C, FPG, UACR, and urine microalbumin level showed significantly positive correlations with DR severity. @*Conclusion@#In patients with newly diagnosed T2DM, 10.53% have DR at initial ophthalmologic examination and high HbA1C, FPG, UACR and urine microalbumin levels. These factors are significantly positively correlated with DR severity. Therefore, more careful fundus examination is needed for newly diagnosed T2DM patients with high HbA1C, FPG, UACR, and urine microalbumin levels.

Associations between the HaeIII Single Nucleotide Polymorphism in the SLC2A1 Gene and Diabetic Nephropathy in Korean Patients with Type 2 Diabetes Mellitus

BACKGROUND: Diabetic nephropathy (DN) is the most serious microvascular complication of diabetes mellitus and is one of the leading causes of end stage renal failure. In previous studies, the contribution of genetic susceptibility to DN showed inconsistent results. In this study, we investigated the association between the solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism and DN in Korean patients with type 2 diabetes mellitus (T2DM) according to disease duration. METHODS: A total of 846 patients with T2DM (mean age, 61.3 ± 12.3 years; mean duration of T2DM, 10.3 ± 7.9 years; 55.3% men) who visited the Chungbuk National University Hospital were investigated. The HaeIII polymorphism of the SLC2A1 gene was determined by the real time polymerase chain reaction method. Genotyping results were presented as GG, AG, or AA. A subgroup analysis was performed according to duration of T2DM (≤ 10 years, < 10 years). RESULTS: The AG + AA genotype showed a significantly higher risk of DN compared with the GG genotype in patients with a type 2 DM duration less than 10 years (12.4% vs. 4.2%; P < 0.001). No significant differences were observed in terms of other diabetic complications, including retinopathy, peripheral neuropathy, cardiovascular disease, cerebrovascular disease or peripheral artery disease, according to the genotypes of the SLC2A1 HaeIII polymorphism. CONCLUSION: The SLC2A1 HaeIII polymorphism was associated with DN in Korean patients with T2DM, particularly in the group with a relatively short disease duration.

Association of Adiponectin 45T/G Polymorphism with Diabetic Cardiovascular Complications in Korean Type 2 Diabetes

BACKGROUND: Adiponectin is an adipokine that regulates lipid and glucose metabolism and has been shown to have anti-inflammatory and anti-atherogenic effects. It also plays an important role in the development of cardiovascular disease (CVD). METHODS: This study evaluated the association between adiponectin 45T/G polymorphism and cardiovascular complication in type 2 diabetes in Koreans. RESULTS: The present study included 758 patients with type 2 diabetes. The distribution of the adiponectin 45T/G polymorphism was 3.56% (n = 27) for GG, 42.35% (n = 321) for TG, and 54.09% (n = 410) for TT in patients with type 2 diabetes. The prevalence of CVD was significantly higher in subjects with the GG + TG genotype compared to those with the TT genotype (17.5% vs. 9.8%, P = 0.002). The G allele was associated with a higher risk of CVD (P = 0.002). CONCLUSION: Our findings suggest that the adiponectin 45T/G polymorphism is associated with diabetic cardiovascular complication in type 2 diabetes.

A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. MATERIALS AND METHODS: Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. RESULTS: Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). CONCLUSION: We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.

Impact of Hyperglycemia on Survival and Infection-Related Adverse Events in Patients with Metastatic Colorectal Cancer Who Were Receiving Palliative Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. MATERIALS AND METHODS: We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. RESULTS: The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 ( 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). CONCLUSION: Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.

Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 microIU/mL, free T4 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH.

Safety and Efficacy of Modern Insulin Analogues

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

A Case of Lingual Thyroid Treated by 131I Ablation

A lingual thyroid is a rare developmental anomaly caused by the failure of the descent of the thyroid gland anlage early in the course of embryogenesis. The incidence of lingual thyroid has been reported to be 1/100,000. Lingual thyroid is often asymptomatic but may cause dysphagia, dysphonia, upper airway obstruction and hemorrhage. In this report, we described the case of a 50-year-old women experiencing lingual thyroid who had subclinical hypothyroidism. She underwent successful 131I ablation and has done well on thyroid hormone replacement therapy.

CellprepPlus(R) Liquid-based Smear in Sono-guided Thyroid Fine Needle Aspiration: A Comparison of Conventional Method and CellprepPlus(R) Liquid-based Cytology

BACKGROUND: Fine needle aspiration (FNA) of the thyroid is a useful tool for the evaluation of benign or malignant thyroid nodules. The improvements in the quality of cytological preparations using the liquid-based cytology (LBC) method have been well-documented. The principal objective of this study was designed to evaluate the diagnostic adequacy, sensitivity, and specificity of the thyroid FNA comparing a conventional smear with the LBC adapted with the filtration method described herein. METHODS: One hundred ninety eight cases of FNA samples obtained from May 2009 to September 2009 were included in this study. All patients were subjected to ultrasound-guided aspiration twice at a target lesion by a radiologist and two types of slides were prepared using conventional smear and LBC. RESULTS: When compared with conventional method, the cellularity was reduced in LBC. However, the malignant tumor cells evidenced the larger and more vesicular nuclei, prominent nucleoli, and distinct nuclear membranes in LBC. Thirty two cases (16.16%) of conventional smear were inadequate, but 96 cases (48.49%) of LBC were inadequate. CONCLUSIONS: Most of the slides using CellprepPlus(R) LBC evidenced lower cellularity and clearer background. However, the conventional smears were found to generate much more applicable samples than CellprepPlus(R) LBC.

Comparison of Vildagliptin-Metformin and Glimepiride-Metformin Treatments in Type 2 Diabetic Patients

BACKGROUND: The present study investigated the efficacy and safety of vildagliptin-metformin treatment compared to those of glimepiride-metformin treatment for type 2 diabetes. METHODS: In a randomized, open-label, comparative study, 106 patients with type 2 diabetes were enrolled. The primary endpoint was a reduction in HbA1c from baseline and secondary endpoints included fasting plasma glucose (FPG) or 2-hour postprandial glucose (2h-PPG) reduction from baseline, as well as HbA1c responder rate and HbA1c reduction according to baseline HbA1c category. RESULTS: Comparable HbA1c reduction was observed with a mean+/-standard deviation change from baseline to the 32-week endpoint of -0.94+/-1.15% in the vildagliptin group and -1.00+/-1.32% in the glimepiride group. A similar reduction in 2h-PPG (vildagliptin group 3.53+/-4.11 mmol/L vs. the glimepiride group 3.72+/-4.17 mmol/L) was demonstrated, and the decrements in FPG (vildagliptin group 1.54+/-2.41 mmol/L vs. glimepiride group 2.16+/-2.51 mmol/L) were not different between groups. The proportion of patients who achieved an HbA1c less than 7% at week 32 was 50.1% in the vildagliptin group and 56.0% in the glimepiride group. An average body weight gain of 2.53+/-1.21 kg in the glimepiride group was observed in contrast with the 0.23+/-0.69 kg weight gain noted in the vildagliptin group. A 10-fold lower incidence of hypoglycemia was demonstrated in the vildagliptin group, in addition to an absence of severe hypoglycemia. CONCLUSION: Vildagliptin-metformin treatment provided blood glucose control efficacy comparable to that of glimepiride-metformin treatment and resulted in better adverse event profiles with lower risks of hypoglycemia and weight gain.

Delivery of Factor VIII Gene into Skeletal Muscle Cells Using Lentiviral Vector

PURPOSE: This study was designed to investigate whether transduction of lentiviral vectors (LV) carrying human coagulation factor VIII (hFVIII) cDNA into skeletal muscle could increase circulating hFVIII concentrations. MATERIALS AND METHODS: A LV containing bacterial LacZ gene as a control or human FVIII gene was intramuscularly administered into the thigh muscle of 5 weeks old Sparague-Dawley rats. The plasma human FVIII concentration and neutralizing anti-FVIII antibodies were measured for up to 12 weeks in these experimental animals. RESULTS: The plasma human FVIII levels in the rats injected with LV carrying FVIII cDNA peaked at post-injection 1st week (5.19 +/- 0.14 ng/mL vs. 0.21 +/- 0.05 ng/mL in control rats , p < 0.05). Elevated hFVIII concentrations were maintained for 4 weeks (2.52 +/- 0.83 ng/mL vs. 0.17 +/- 0.08 ng/mL in control rats, p < 0.05) after a single intramuscular injection. In the Bethesda assay, neutralizing antibodies for FVIII protein were detected only in FVIII-LV injected rats by the 10th week, but not in control rats. CONCLUSION: This study suggested that a single administration of an advanced generation LV carrying the human FVIII cDNA resulted in elevation of FVIII level in immune competent rats, and that this gene transfer approach to the skeletal muscle could be an effective tool in treatment of hemophilia A.

Association Study of the Peroxisome Proliferators-Activated Receptor gamma2 Pro12Ala Polymorphism with Diabetic Nephropathy / 당뇨병

BACKGROUND: Peroxisome proliferators-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors and known to play a role in regulating the expression of numerous genes involved in lipid metabolism, metabolic syndrome, inflammation, and atherosclerosis. The PPARgamma2 Pro12Ala polymorphism has recently been shown to be associated with diabetic nephropathy. In this study, we evaluated the relationship between PPARgamma2 Pro12Ala polymorphism and type 2 diabetic nephropathy whose duration of diabetes was over 10 years. METHODS: We conducted a case-control study, which enrolled 367 patients with type 2 diabetes. Genotyping of PPARgamma2 Pro12Ala polymorphism was performed using polymerase chain reaction followed by digestion with Hae III restriction enzyme. RESULTS: The genotype or allele frequencies of PPARgamma2 Pro12Ala polymorphism were not significantly different in diabetic patients with or without diabetic nephropathy. The genotype frequencies in terms of diabetic retinopathy and macrovascular complications such as coronary artery disease or stroke were not different either. Interestingly, nephropathy patients with Ala/Pro genotype showed lower C-peptide levels than those of Pro/Pro genotype. CONCLUSION: Our results suggest that PPARgamma2 Pro12Ala polymorphism is not associated with diabetic nephropathy in type 2 diabetic patients.

The association of chemokine receptor 5 gene 59029A/G polymorphisms with diabetic nephropathy in type 2 diabetic patients / 대한내과학회지

BACKGROUND/AIMS: Chemokine receptor 5 (CCR5) is a receptor for several chemokines, including regulated upon activation, normal T-cell-expressed and -secreted (RANTES; also known as CCL5) and macrophage inflammatory protein 1 (MIP-1), and mediates the recruitment of monocytes and their differentiation to macrophages during the inflammatory process. As such, CCR5 plays an important role in the development and progression of atherosclerosis, which has an underlying inflammation component and contributes to the development or progression of diabetic complications. Several studies have reported that a genetic variation of the CCR5 gene with A/G at basepair 59029 (59029 A/G) was associated with diabetic complications, although conflicting data exist. We evaluated the association of the CCR5 59029 A/G polymorphism with diabetic complications in type 2 diabetes patients. METHODS: We conducted a case-control study, enrolling 325 patients with type 2 diabetes. We examined the association of CCR5 genotypic variations with diabetic nephropathy, retinopathy, and macrovascular complications such as coronary heart disease and stroke. Genotyping was performed using the polymerase chain reaction and restriction fragment length polymorphism technology with Bsp1286I restriction enzyme. RESULTS: We determined no allelic association of CCR5 59029 A/G with diabetic nephropathy (p=0.500) in the male or female patients. Diabetic retinopathy and macrovascular complications such as coronary heart disease and stroke were not associated with the 59029 A/G polymorphism. Among those patients with diabetic nephropathies, those with the GG genotype showed a tendency toward higher serum levels of LDL-cholesterol. CONCLUSIONS: These results suggest that that the 59029 A/G polymorphism of the CCR5 gene is not associated with diabetic complications in type 2 diabetes patients. Further studies are required to understand the role of CCR5 polymorphisms in the development of diabetic complications.

Vitamin D Receptor Genotype is Associated with Secondary Hyperparathyroidism in Hemodialysis Patients / 대한신장학회지

PURPOSE: It is known that secondary hyperparathyroidism in end stage renal disease (ESRD) patients is associated with vitamin D receptor (VDR) gene polymorphism, but there is no consensus on its genotype. There is lack of data in Ca, P, calcitriol and VDR polymorphism. METHODS: We measured serum Ca, P, alkaline phosphatase, parathyroid hormone (PTH), and 1,25 (OH)2D3 of the 53 hemodialysis patients. The genotypes of VDR were classified BB, Bb, bb according to restriction patterns in PCR of the patients' DNA using Bsm I restriction enzyme. RESULTS: The patients with BB, Bb, bb type were 0 (0%), 15 (28.3%), 38 (71.7%) respectively. Serum PTH levels were 70.0+/-63.3 pg/mL and 146.9+/-184.9 pg/mL in Bb, bb type respectively, and showed significant statistical difference (p<0.05). Serum 1,25 (OH)2D3 levels were 7.68+/-3.41 pg/mL and 6.59+/-2.67 pg/mL in Bb and bb genotype respectively without statistical significance. And there was no significant statistical differences among the serum levels of calcium, phosphorus, alkaline phosphatase. CONCLUSION: Vitamin D receptor gene polymorphism is associated with secondary hyperparathyroidism in hemodialysis patients, and the b allelle is suggestive of poorer bone mineral metabolism.

Increased Anti-tumor Effect by a Combination of HSV Thymidine Kinase Suicide Gene Therapy and Interferon-gamma/GM-CSF Cytokine Gene Therapy in CT26 Tumor Model

The potential therapeutic benefit of introducing IFN-gamma and GM-CSF genes in combination with the HSVtk suicide gene into subcutaneously implanted CT26 tumor cells was compared with that from each treatment alone. Cells, unmodified or retrovirally transduced with HSVtk or IFN-gamma/GM-CSF genes, were inoculated subcutaneously into syngeneic BALB/c mice in various combinations. HSVtk gene, with intraperitoneal ganciclovir treatment, reduced tumor volume by 81% at locally inoculated tumor sites (p<0.01) and by 25% at distantly inoculated tumor sites (p=0.052). IFN-gamma/GM-CSF genes showed a 56% tumor volume reduction at local tumor sites (p<0.01) and 15% volume reduction at remote tumor sites, although this was not statistically significant. The combination of HSVtk (with GCV) and IFN-gamma/GM-CSF genes showed an 81% volume reduction at local tumor sites (p<0.01) and a 43% volume reduction at remote tumor sites (p<0.01). Thus, the combination of HSVtk and IFN-gamma/GM-CSF gene therapy produced greater therapeutic efficacy than either treatment alone.

A Case of Langerhans Cell Histiocytosis Presented with Central Diabetes Insipidus / 대한내분비학회지

Langerhans cell histiocytosis can cause central diabetes insipidus. Here, a case of Langerhans cell histiocytosis invading the pituitary stalk was experienced. The patient was 15 years old boy, with complaint of polydipsia and polyuria. A water deprivation test was carried out, and the urine osmolarity was increased from 165 to 469 mosm/kg following an injection of AVP to confirm the diagnosis of central diabetes insipidus. A pituitary function stimulation test gave a normal response. A sellar MRI was performed, which showed a thickened pituitary stalk mass (about 5.7mm), with an increased size, 6.9 mm, on a second MRI 2 month later. A tissue biopsy was performed, which showed aggregates of histiocytes and inflammatory cells, with prominent eosinophils (H&E), and also revealed strong reactivity to anti-CD1a antibody on the immunohistochemistry. After confirmative tissue diagnosis, the patient received radiotherapy (900 cGy). The thickened mass of the pituitary stalk disappeared on the MRI following the radiotherapy. The patient was managed with DDAVP nasal spray, after which the polyuric symptoms were completely relieved.