BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine. RESULTS: Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment. CONCLUSION: This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.
Diabetes Mellitus, Type 2* ; Fasting ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Humans ; Hypoglycemia ; Insulin Glargine ; Insulin Lispro* ; Insulin* ; Korea ; Meals ; Metformin ; Obesity ; Prevalence ; Weight Gain

Eprex used to treat anemia and improves quality of life, assessment and exercise capacity in predialysis patients. There are two groups of predialysis patients with Hemoglobin <100 g/dl, follow up 5 months in our study: group A (n=17; Eprex- treated predialysis patients) for the treatment by Eprex with 2000 UI x 2 time/week x 2 months, and continuous 2000 UI/week x 3 months; group B non anemia treatment (n=11 non Eprex - treated predialysis patients). The results after 5 months follow up: group A receiving Eprex had higher RBC, Hb and Ht levels than those non receiving Eprex (group B) with P<0.001. The Eprex - treated predialysis patients in group A for a duration of 5 months and observed no accelerated decline in renal function compared with non - Eprex treated predialysis patients, treatment of anemia might improved energy level and physical function.
Kidney Failure, Chronic ; Epoetin Alfa

BACKGROUND: The initial insulin dose is often determined by clinical experience or with a formula using the body weight. However, it may be difficult to determine the initial insulin dose because various factors such as insulin sensitivity and the glycemic status can influence the insulin requirement. The purpose of this study was to assess the factors that influence the initial insulin requirement in insulin naive patients with type 2 diabetes mellitus. METHODS: A total 128 patients who were admitted for glycemic control were investigated. The patients were managed with long-acting insulin glargine and rapid-acting insulin lispro. RESULTS: The basal insulin requirement was positively correlated with waist circumference, body mass index (BMI), the HbA1C, AST, ALT, fasting plasma glucose and 2-hour postprandial glucose levels and the homeostasis model assessment of insulin resistance (HOMA-IR), but it was negatively correlated with age and the stimulated C-peptide level. The daily insulin requirement was positively correlated with waist circumference, BMI, the HbA1C, AST, ALT, triglyceride, fasting plasma glucose and 2-hour postprandial glucose level and HOMA-IR, but it was negatively correlated with age. On the multiple linear regression analysis, the basal insulin requirement was independently associated with BMI (beta = 0.507, p < 0.001), the 2-hour postprandial glucose level (beta = 0.307, p < 0.001), the ALT level (beta = 0.214, P = 0.015) and the meal-stimulated C-peptide level (beta = -0.209, P = 0.010). The daily insulin requirement was independently associated with BMI (beta = 0.508, p < 0.001) and the 2-hour postprandial glucose level (beta = 0.404, p < 0.001). CONCLUSION: Our results show that the BMI and 2-hour postprandial glucose level are useful predictors of the initial insulin requirement in insulin naive type 2 diabetic patients. It may be prudent to consider the other various factors that influence the insulin requirement together when insulin therapy is required.
Body Mass Index ; Body Weight ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Lispro ; Insulin Resistance ; Insulin, Long-Acting ; Insulin, Short-Acting ; Linear Models ; Plasma ; Waist Circumference ; Insulin Glargine

PURPOSE: This study was undertaken to examine whether differences exist in the hemoglobin variability according to the types of erythropoiesis stimulating agent (ESA) in hemodialysis (HD) patients. METHODS: Clinical data were retrospectively analyzed from 72 patients on maintenance hemodialysis who were using darbepoetin alfa (n=27), epoetin beta (n=27), and epoetin alpha (n=18). As parameters of hemoglobin variability, hemoglobin cycling, the variance of hemoglobin and the SD/mean of hemoglobin were analyzed. Hemoglobin cycling was defined as the presence of cycles with an amplitude >1.5 g/dL and lasting more than 2 months. RESULTS: Hemoglobin cycling was present in 53 (73.6%) out of 72 HD patients. Hemoglobin cycling in patients receiving darbepoetin alfa had greater frequency (1.63+/-0.93 vs. 1.00+/-0.88 times/year, p<0.05), amplitude (2.88+/-1.48 vs. 1.88+/-1.60 g/dL, p<0.05), and velocity (1.21+/-0.74 vs. 0.73+/-0.66 g/dL/month, p<0.05) than that in patients receiving epoetin beta. The variance of hemoglobin in patients receiving epoetin beta (0.79+/-0.53 g/dL) was smaller than that in patients receiving darbepoetin alfa (1.29+/-0.70 g/dL, p<0.05) and epoetin alfa (1.08+/-0.52 g/dL, p<0.05). Also, the ratio of SD/mean of hemoglobin in patients receiving epoetin beta (8.20+/-2.59%) was lower than that in patients receiving darbepoetin alfa (10.81+/-2.10%, p<0.05) and epoetin alfa (10.30+/-2.10%, p<0.05). CONCLUSION: Hemoglobin variability is differential according to various ESAs, and it may be less with epoetin beta compared with darbepoetin alpha and epoetin alpha.
Anemia ; Erythropoiesis ; Erythropoietin ; Hematinics ; Hemoglobins ; Humans ; Recombinant Proteins ; Renal Dialysis ; Retrospective Studies ; Darbepoetin alfa ; Epoetin Alfa

PURPOSE: We aim to compare the erythropoietic effects of epoetin-alpha (EA, 4000 IU SC thrice a week) with those of darbepoetin-alpha (DA, 60ug IV weekly, conversion rate to EA=200:1). METHODS: Forty one stable hemodialysis patients were enrolled in this randomized crossover study. After a washout period of erythropoietin stimulating agents (ESA), the patients with hemoglobin (Hb) level of < or =11.0 g/dL were randomly assigned to DA or EA and we measured Hb and reticulocyte levels. When Hb reached >11.0 g/dL, we stopped ESA. When Hb level decreased to < or =11.0 g/dL again, we switched to alternative ESA and repeated the rest of the steps. RESULTS: Thirty six patients (M:F=20:16, age 62+/-11 years, Kt/V 1.65, nPCR 1.13 g/kg/day) completed the study. No significant differences were observed in baseline parameters between DA and EA during the period of the clinical trial. The rate of Hb level increase (EA 0.29 g/dL/week, DA 0.30 g/dL/week, p=0.76) and decrease (EA 0.45 g/dL/week, DA 0.38 g/dL/week, p=0.14) were not different between two periods. After ESA stopped, the duration of decreased Hb level of < or =11.0 g/dL was not significantly different (4 weeks in EA vs. 3.9 weeks in DA, p=0.86). Erythropoietin resistance index was 10.59 in the EA period. It was not significantly different from 10.97 in DA period (p=0.49). Nine patients (25%) showed a >30% change in EA efficiency relative to DA efficiency. CONCLUSION: There was no significant difference in erythropoietic parameters for both EA and DA.
Anemia ; Cross-Over Studies ; Erythropoietin ; Hemoglobins ; Humans ; Recombinant Proteins ; Renal Dialysis ; Reticulocytes ; Darbepoetin alfa ; Epoetin Alfa

STUDY DESIGN: Prospective randomized clinical trial. OBJECTIVES: To determine the minimal effective pretreatment dosage of recombinant human erythropoietin for preoperative autologous donation in lumbar stenosis surgery. SUMMARY OF LITERATURE REVIEW: Preoperative autologous donation is one of the most widely used methods of autotransfusion. However securing predetermined amount may be difficult due to falling hematocrit with repeated donation especially in patients with low basal hematocrit. In this situation recombinant human erythropoietin(Epoetin alfa) may be used. MATERIALS AND METHODS: Forty five lumbar stenosis patients requiring posterior wide decompression and posterolateral fusion with instrumentation, who had basal hematocrit less than 40% were selected and alloted randomly into 3 groups. Group I(n=15) had pretreatment with Epoetin alfa 50 unit/kg. Group II(n=15) was pretreated with 25 unit/kg. Group III(n=15) had no pretreament. Patients were excluded from donation when their hematocrit values were less than 33%. RESULTS: The mean number of units collected per patient(mean+/-SD) was 3 for group I(P<0.05), 2.84 for group II and 2.67 for the control group. The red cell volumes in pretreated groups(347 ml, 325 ml) were greater than in group III(255 ml, P<0.05). The differences between hematocrits of the first and the third preoperative donations were significantly less in group I(1.50) and group II(1.51) than that of control group(3.73). Two patients in group II and 3 patients in group III required additional homologous transfusion postoperatively. And there were no significant differences in the pattern of postoperative changes of hemoglobin among the groups. There were no significant differences in amount of intraoperative saved blood, postoperative reinfused blood, and postoperative drainage. CONCLUSION: Fifty units/kg of Epoetin alfa seems to be more effective than twenty-five units/kg for preoperative autologous donation in patients requiring posterior wide decompression, posterolateral fusion with instrumentation.
Blood Transfusion, Autologous ; Cell Size ; Constriction, Pathologic* ; Decompression ; Drainage ; Erythropoietin* ; Hematocrit ; Humans* ; Prospective Studies ; Epoetin Alfa

PURPOSE: Compared with the practice of administrating subcutaneous erythropoietin injection two or three times a week in end-stage renal failure, a weekly administration reduces the frequency of injection and the workload in renal units. We investigated whether subcutaneous epoetin alfa administered weekly was as effective as the same weekly dosage given in two or three divided doses. METHODS: Eighty-three patients were randomized to treatment with subcutaneous epoetin alfa either once a week (n=44), or to their original dosage two or three times a week (control, n=39) for 12 weeks. If hemoglobin was out of range (9.0-12.0 g/dL), the dosage was changed. RESULTS: Mean hemoglobin levels at randomization and after 4, 8 and 12 weeks were 10.7, 11.1, 11.3 and 11.0 g/dL, respectively, in the once weekly group compared with 10.5, 11.3, 11.5 and 11.3 g/dL, respectively, in the control group. The mean weekly epoetin alfa dosage at randomization and after 4, 8 and 12 weeks were 142.8, 123.0, 116.7 and 112.3 IU/kg, respectively, in the once-a-week group compared with 128.4, 119.3, 103.5 and 101.2 IU/kg, respectively, in the control group. No statistically significant differences between the groups were apparent in changes in hemoglobin levels or epoetin alfa dosages at week 12. There was no significant difference between the groups in number of patients who maintained stable hemoglobin levels without epoetin alfa dose increases. CONCLUSION: This study demonstrates that a weekly subcutaneous administration of epoetin alfa is as effective and safe as injecting it two or three times a week administration in maintaining hemoglobin levels in stable hemodialysis patients.
Anemia ; Erythropoietin ; Humans ; Kidney Failure, Chronic ; Random Allocation ; Renal Dialysis ; Epoetin Alfa

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an established treatment for renal anemia. We aimed to determine that high dose subcutaneous epoetin alfa is as efficient and safe as usual dose for treating anemia in peritoneal dialysis patient. METHODS: Twenty four patients on CAPD were randomly assigned to either 10, 000 IU (high dose group, n=12) or 4, 000 IU (usual dose group, n=12) epoetin alfa regimen with variable interval for 24 weeks. If hematocrit was out of range (30-39%), the interval was changed within 50% of previous interval. RESULTS: Mean hemoglobin levels at randomization and after 12 weeks and 24 weeks were 11.4+/-1.3, 11.3+/-1.1, and 11.6+/-1.2 g/dL in high dose group compared with 10.8+/-0.8, 11.5+/-1.1, and 10.9+/-1.2 g/dL in usual dose group (p<0.05). The mean weekly epoetin alfa dosages at randomization and after 12 and 24 weeks were 93.2+/-45.3, 95.5+/-33.6, and 102.5+/-43.6 IU/kg in high dose group compared with 78.8+/-29.4, 75.9+/-20.6 and 75.5+/-39.7 IU/kg in usual dose group (p<0.05). But, interval in high dose group was two times as longer as usual dose group. Adverse events were generally mild and transient CONCLUSION: This study demonstrates that epoetin alfa 10, 000 IU is as efficient and safe as 4, 000 IU with similar weekly dose in CAPD patients. epoetin alfa 10, 000 IU administration reduces frequency of injections about one half.
Anemia ; Erythropoietin ; Hematocrit ; Humans ; Peritoneal Dialysis ; Peritoneal Dialysis, Continuous Ambulatory* ; Random Allocation ; Epoetin Alfa

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is an essential and well-established treatment for renal anemia. Rcently, clinicians have moved toward administration of high dose rHuEPO to reduce the inconvenience and time efficient.We aimed to determine whether high dose subcutaneous (SC) epoetin alfa is as efficient and safe as the usual dose for treating anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Twenty-four patients on CAPD were randomly assigned to a high-usual dose group (n=12) and an usual-high dose group (n=12) with a variable interval for 48 weeks. Patients received 10 times treatments by scheduled visiting during Period I lasting 24 weeks and received 4 times treatments by scheduled visiting in Period II lasting 24 weeks by cross-over. The high dose was 10,000 IU and the usual dose was 4,000 IU epoetin alfa regimen. If hematocrit was out of the targeted range, 30~39%, the interval of epoetin alfa was changed within 50% of the previous interval. RESULTS: Fifteen patients, out of 24, completed the study (8 patients in the high-usual dose group; 7 patients in the usual-high dose group). Mean hemoglobin levels at randomization and after 12, 24, 36 and 48 weeks were 10.8+/-1.1, 11.5+/-0.9, 11.5+/-1.5, 11.4+/-1.5, 11.5+/-0.8 g/dL, respectively, in high-usual dose group compared with 11.2+/-0.8, 11.4+/-1.2, 11.2+/-0.9, 11.2+/-1.4, 11.4+/-0.9 g/dL, respectively, in usual-high dose group. The mean weekly epoetin alfa dosages at randomization and after 12, 24, 36 and 48 weeks were 83.6+/-38.1, 87.1+/-35.8, 89.4+/-34.2, 60.1+/-25.1, 62.8+/-30.7 IU/kg/week, respectively, in high-usual dose group compared with 69.8+/-31.6, 64.9+/-12.2, 69.9+/-46.1, 78.8+/-29.3, 75.9+/-16.4 IU/kg/week, respectively, in usual-high dose group. No statistically significant differences between the two groups were apparent for hemoglobin levels or mean weekly epoetin alfa dosages. Treatment interval at Period I and Period II were 13.3+/-5.3, 8.2+/-4.3 days in high-usual dose group compared with 7.0+/-2.5, 13.4+/-4.0 days in usual-high dose group with statistically significant differences. Treatment interval in high dose was about two times as longer as usual dose. Adverse events were generally mild and transient, and pain on injection site following subcutaneous administration was rarely reported. CONCLUSIONS: This study demonstrates that epoetin alfa 10,000 IU is as efficient and safe as 4,000 IU with a similar weekly dose in CAPD patients. Epoetin alfa 10,000 IU administration can reduce frequency of injections by about one half.
Anemia ; Cross-Over Studies* ; Erythropoietin ; Hematocrit ; Humans ; Peritoneal Dialysis, Continuous Ambulatory* ; Random Allocation ; Epoetin Alfa

A large body of evidence demonstrates that dendritic cells (DC) play a pivotal role in the control of immunity by priming and tolerizing T cells. In multiple sclerosis (MS), autoreactive T cells are proposed to play a pathogenic role by secreting pro-inflammatory cytokines, but comparison studies on the effects of immature and mature dendritic cells on the cytokines profile of antigen-specific T cell lines are lacking. To evaluate the actions of dendritic cell maturation on T cell polarization, the effects of immature and mature dendritic cells derived from MS patients on in vitro proliferative responses, and cytokine production by glatiramer acetate (GA)- specific T cell lines (TCL) derived from MS patients were analyzed. The results demonstrated that it is easy to derive GA-specific TCL from MS patients with high specificity; lipopolysaccharide can efficiently induce DC maturation within 24 hours at a concentration of 5 micro g/ml; mature DC showed higher co-stimulatory capacity of GA-specific TCLs than immature DC. GA-specific TCLs produce dominantly IL-2, IL-4, IFN-gamma and IL-10, but low levels of IL-6. In contrast to immature DC, mature DC enhanced capacity to induce IL-6 and IL-10 secretion, but down-regulate IL-2, IL-4 and IFN-gamma production by GA- specific TCLs. It is concluded that DC maturation status modulating proliferation of TCL and production of cytokines may represent another focus for the study on both immuno-pathogenesis and immunotherapeutic interventions in MS.
Adult ; Cell Line ; Cytokines ; biosynthesis ; Dendritic Cells ; physiology ; Female ; Glatiramer Acetate ; Humans ; Lymphocyte Activation ; Male ; Middle Aged ; Multiple Sclerosis ; immunology ; Peptides ; immunology ; T-Lymphocytes ; immunology