icodextrin and Insulin-Resistance

Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial.. This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days.. Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195).. The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.

Topics: Adult; Case-Control Studies; Dialysis Solutions; Female; Glucans; Glucose; Humans; Icodextrin; Insulin Resistance; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Risk Factors

A postprandial increase in blood glucose in peritoneal dialysis (PD) patients with diabetes was observed in our previous study using continuous blood glucose monitoring. The response was observed in diabetic but not in nondiabetic PD patients. In addition, the response was reduced when patients used icodextrin; glucose absorbed from the peritoneum was responsible for the postprandial increase in blood glucose. Because our PD patients often change their PD fluid before meals, the present study aimed to determine the blood glucose and insulin responses to PD fluid. The 26 patients who agreed to participate in the study protocol [16 with diabetes (12 men, 4 women; 11 receiving insulin; 5 being controlled with oral antidiabetic drugs; average duration from diagnosis with diabetes: 16.4 ± 11 years); 10 without diabetes (4 men, 6 women)] had an average age of 60.5 ± 13.0 years. Average PD vintage was 578.7 ± 352.9 days. Blood samples were taken during a peritoneal equilibration test (PET) with 2.5% glucose solution at baseline and at 0.5, 2, and 4 hours. Levels of blood glucose and insulin were analyzed. A rapid increase in blood glucose (peak at 0.5 hours, 23.5 ± 22.2 mg/dL increase from baseline) was observed in nondiabetic patients. A delayed but higher peak response was observed in diabetic patients (peak at 1 hour, 54.9 ± 38.3 mg/dL increase from baseline). Peak response of insulin occurred at 0.5 hours in nondiabetic patients; in diabetic patients it occurred at 2 hours. No differences in the average insulin level during the PET were observed in the two groups (nondiabetic: 35.3 ± 15.6 μU/mL; diabetic: 38.9 ± 7.6 μU/mL). The study results suggest that a delayed insulin response after a PD fluid exchange could participate in the exaggerated postprandial increase in blood glucose in diabetic PD patients, particularly when the PD fluid exchange is performed before food intake.

Topics: Adult; Aged; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes Complications; Dialysis Solutions; Female; Glucans; Glucose; Humans; Hypoglycemic Agents; Icodextrin; Insulin; Insulin Resistance; Male; Middle Aged; Peritoneal Dialysis; Peritoneum; Renal Insufficiency

Icodextrin peritoneal dialysis solution reportedly benefits patients suffering from metabolic derangement due to glucose load from dialysate. However, the effects of icodextrin on insulin resistance and adipocytokine profile remain unclear. Subjects comprised 14 stable patients on peritoneal dialysis for >6 months. Their mean age was 57 +/- 11 years and the mean duration of peritoneal dialysis was 49 +/- 30 months. Patients were classified into groups according to the index of insulin resistance (index of homeostasis model assessment: HOMA-IR): Group A, HOMA-IR < 2.0 (n = 7); and Group B, HOMA-IR >or= 2.0 (n = 7). Glucose peritoneal dialysis solution was subsequently switched to icodextrin once daily during the night. Changes in HOMA-IR and adipocytokine profiles were examined after three months. The glucose absorption dose tended to decrease in both groups after icodextrin introduction, with significant reductions in Group B. No changes were seen in body mass index, fluid status, peritoneal dialysis dose, residual renal function or fasting plasma glucose levels in either group. Plasma insulin levels were unchanged in Group A, but decreased significantly in Group B. The index of insulin resistance was thus unchanged in Group A (from 1.4 +/- 0.4 to 1.5 +/- 0.8) and significantly decreased in Group B (from 5.9 +/- 2.2 to 3.2 +/- 0.6; P < 0.01). Regarding plasma adipocytokine profiles, no changes were found in plasma leptin, tissue necrosis factor-alpha or total plasminogen activator inhibitor-1 levels in either group. Plasma adiponectin levels were unchanged in Group A, but significantly increased in Group B. Icodextrin solution could ameliorate insulin resistance by decreasing insulin levels due to a reduction in the glucose load and an increase in plasma adiponectin levels.

Topics: Adipokines; Adiponectin; Adult; Aged; Aged, 80 and over; Dialysis Solutions; Female; Glucans; Glucose; Homeostasis; Humans; Icodextrin; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Plasminogen Activator Inhibitor 1

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

Topics: Adult; Biomarkers; Blood Glucose; Cardiovascular Diseases; Dialysis Solutions; Fasting; Female; Glucans; Glucose; Homeostasis; Humans; Icodextrin; Insulin; Insulin Resistance; Kidney Failure, Chronic; Male; Metabolic Diseases; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Treatment Outcome

Peritoneal dialysis patients have particular risks with respect to their lipid status and hyperinsulinemia. The aim of this study was to investigate the relation between insulin resistance and the type of the peritoneal dialysis solution.. 41 randomly selected non-diabetic patient cohort who were already under treatment with continuous ambulatory peritoneal dialysis (CAPD) and 10 healthy controls participated in the study. 24 of the 41 patients were using 3 standard 1.36% glucose solutions during the day and 1 hypertonic solution with 2.27% glucose dwell during the night (glucose group: mean age 45.54 +/- 16.67 years and median CAPD duration 16.5 months). The remaining 17 patients were using 3 standard 1.36% glucose solutions during the day and 1 icodextrin dwell during the night for 8-10 hours (icodextrin group: mean age 47.47 +/- 13.15 years, median duration of icodextrin use 6 months (range 2-20 months), and median CAPD duration 30 months). Insulin resistance (IR) was calculated according to the homeostasis model assesment (HOMA) formula: HOMA-IR = fasting glucose (mmol/l) x fasting insulin (microU/1/22.5. The HOMA cutoff point for diagnosis of insulin resistance was established with receiver-operating characteristic (ROC) curves. The patients were called HOMA-IR(+) if their HOMA scores were higher than cutoff value.. There were no significant differences between age, BMI, triglyceride, total and high-density lipoprotein (HDL) cholesterol, iron and ferritin, alanine aminotransferase, fibrinogen, intact parathyroid hormone, magnesium, hemoglobin and hematocrit levels of the 2 groups. The mean glucose levels of the groups were not different but fasting insulin levels and HOMA scores of the icodextrin group were significantly lower than the glucose group (10.15 +/- 6.87 vs. 18.11 +/- 13.15, p = 0.028, and 2.28 +/- 1.67 vs. 4.26 +/- 3.27, p = 0.027, respectively). The ratio of patients with low HOMA scores (cutoff = 2.511) were significantly higher in the icodextrin group than in the glucose group (71% vs 38%, p = 0.037). Other than fasting insulin and glucose levels, significantly positive correlation was found between HOMA score and BMI in both groups. With regression analysis, we found that the main parameters effecting HOMA score were BMI (p = 0.008) and triglyceride (p = 0.029) in the glucose group, but no parameters were found to affect HOMA score in icodextrin group.. These results suggest that insulin resistance is reduced in peritoneal dialysis patients using icodextrin-based dialysis fluid instead of glucose-based dialysis fluid.

Topics: Adult; Blood Glucose; Dialysis Solutions; Glucans; Glucose; Humans; Icodextrin; Insulin; Insulin Resistance; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

Glucose absorption from peritoneal dialysis solutions causes a chronic stimulation of insulin secretion, which leads to hyperinsulinism. The use of solutions without glucose should correct this metabolic derangement together with the associated cardiovascular risk. To verify this hypothesis, we studied the entire non diabetic continuous ambulatory peritoneal dialysis (CAPD) population of our center: 27 patients with a mean age of 62 +/- 15 years, and a median 17 months on treatment. Morning fasting serum insulin was 32.8 +/- 9.3 microU/mL; glucose, 104.4 +/- 21.8 mg/dL; triglycerides, 162.4 +/- 125.7 mg/dL; cholesterol, 221.9 +/- 54.7 mg/dL; intact parathyroid hormone (iPTH), 212 +/- 189 pg/mL; fibrinogen, 519 +/- 112 mg/dL; body mass index, 24.1 +/- 4.1; and daily erythropoietin subcutaneous therapy dose, 17 +/- 6 U/kg. Insulin sensitivity, measured as ISI-HOMA (insulin sensitivity index, derived from the homeostasis model assessment) was 2.4 +/- 0.7. Daily glucose load, calculated from dialytic schedules, was 135 +/- 38 g. Of the 27 patients, 12 were treated with standard glucose solutions during the day and with one icodextrin dwell during the night for a median of 9 months (range: 1-28). The remaining 15 patients were treated with standard glucose solutions. The icodextrin group showed significantly lower serum insulin levels (28.6 +/- 6.0 microU/mL vs 36.1 +/- 10.2 microU/mL, p = 0.021) and significantly higher ISI-HOMA values (2.7 +/- 0.5 vs 2.2 +/- 0.7, p = 0.041) than the control group. The two groups showed no significant differences for glucose, triglycerides, cholesterol, iPTH, fibrinogen, body mass index, or erythropoietin therapy dose. Daily glucose load was lower in the icodextrin group, but without reaching statistical significance (128 +/- 31 g vs 142 +/- 43 g). This study shows, in a preliminary way, that the chronic use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.

Topics: Blood Glucose; Cardiovascular Diseases; Cross-Sectional Studies; Dialysis Solutions; Glucans; Glucose; Humans; Hyperinsulinism; Icodextrin; Insulin; Insulin Resistance; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Risk Factors