Use of insulin lispro in continuous subcutaneous insulin infusion treatment. Results of a multicenter trial. German Humalog-CSII Study Group.
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OBJECTIVE: Insulin lispro is an analog of human insulin with a faster onset and a shorter duration of action than regular human insulin. Efficacy and tolerability of insulin lispro in continuous subcutaneous insulin infusion (CSII) treatment were assessed in an open randomized crossover trial comparing insulin lispro and regular human insulin, both applied with insulin pumps. RESEARCH DESIGN AND METHODS: A total of 113 type 1 patients (60 male, 53 female, age [mean +/- SD] 37 +/- 12 years, duration of diabetes 19 +/- 9 years) participated in this open, randomized crossover study. Both insulins were applied for 4 months each with the appropriate intervals between the prandial insulin bolus and the meal (human insulin: 30 min; lispro: 0 min). Observation parameters were HbA1c, daily and postprandial blood glucose profiles, adverse events, rate of hypoglycemic and hyperglycemic events, number of catheter obstructions, and treatment satisfaction as assessed with an international validated questionnaire. RESULTS: The patients were well controlled with a mean HBA1c of 7.24 +/- 1.0% at baseline. HbA1c decreased in both treatment periods, but it was better during insulin lispro treatment (insulin lispro: 6.8 +/- 0.9%, regular human insulin: 6.9 +/- 1.0%, Friedman's rank-sum test: P < 0.02). In addition, the 1-h and 2-h postprandial rises in blood glucose were significantly lower (P < 0.001 for each meal) with insulin lispro, resulting in smoother daily glucose profiles as compared with regular human insulin. No significant differences were reported for the rate of hypoglycemia (mean +/- SD [median]: insulin lispro 12.4 +/- 13.9 [8], regular human insulin 11.0 +/- 11.2 [8]), for the rate of catheter obstructions (42 events in each treatment arm), and for the number and type of adverse events. No severe case of ketoacidosis was seen during insulin lispro treatment, whereas one case was reported during therapy with regular human insulin. Treatment satisfaction was better when patients were treated with insulin lispro. CONCLUSIONS: Insulin lispro is a suitable and very convenient pump insulin that may result in an improvement of long-term glucose control during CSII treatment. Its safety profile does not differ from that of regular human insulin. (+info)
A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients.
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Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels. We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type 2 diabetic patients. To avoid the confounding effect of improved glycemic control on insulin action and secretion, patients were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion (CSII) before randomization to CSII plus troglitazone (n = 10) or CSII plus metformin (n = 10); euglycemia was maintained for another 6-7 weeks. Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1) at baseline, 2) after 4 weeks of CSII, and 3) after CSII plus either troglitazone or metformin. The 24-h glucose, insulin, and C-peptide profiles were performed on the day before the second and third glucose clamps. Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent (mean 24-h glucose: troglitazone, 6.2+/-0.6 mmol/l; metformin, 6.2 +/-0.3 mmol/l). Insulin requirements decreased 53% with troglitazone compared with CSII alone (48+/-4 vs. 102+/-13 U/day, P < 0.001), but only 31% with metformin (76+/-13 vs. 110+/-18 U/day, P < 0.005). The 24-h C-peptide profiles were similar. Normal fasting hepatic glucose output was maintained with both agents despite lower insulin levels than on CSII alone. Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin, but improved 29% with CSII plus troglitazone (P < 0.005 vs. CSII alone) and was then 45% higher than in the CSII plus metformin patients (P < 0.005). In conclusion, metformin has no effect on insulin-stimulated glucose disposal independent of glycemic control in type 2 diabetes. Troglitazone (600 mg/day) has greater insulin-sparing effects than metformin (1,700 mg/day) in CSII-treated euglycemic patients. This is probably explained by the peripheral tissue insulin-sensitizing effects of troglitazone. (+info)
Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion.
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This study was performed to determine whether metabolic and hormonal responses during moderate exercise differ between continuous intraperitoneal insulin infusion (CIPII) and continuous subcutaneous insulin infusion (CSII). In seven Type 1 diabetic patients, treatment was changed from CSII to CIPII. Prior to the change, these patients performed an ergometer exercise at 60% of VO2max for 40 min followed by a 200-min rest. About one year later, when the procedure was repeated during CIPII, HbA1c had improved from 8.5 to 7.1%. Arterial blood glucose, venous lactate and hormonal responses were analysed. Although a regimen with a higher basal insulin infusion rate was applied during the exercise test on CIPII, corresponding venous insulin levels were lower (28.0 +/- 2.2 vs. 48.1 +/- 7.9 pmol L-1, p = 0.04). Exercise caused a more marked decline in blood glucose during CIPII, with nadir blood glucose at the end of exercise (3.6 +/- 0.4 vs. 5.1 +/- 0.4 mmol L-1, p = 0.005). Both exercise tests yielded significant and similar increases in plasma levels of adrenaline, noradrenaline, cortisol and growth hormone. A significant rise in plasma glucagon (15.1 +/- 4.5 pg mL-1, p = 0.01) was observed during CIPII, but not during CSII (7.4 +/- 3.5, pg mL-1, n.s.). It is concluded that patients on CIPII should reduce their insulin infusion rate during exercise. CIPII appears to have favourable effects on counterregulatory capacity; in particular, a more prominent glucagon response to exercise may prove important. (+info)
Use of insulin pump therapy at nighttime only for children 7-10 years of age with type 1 diabetes.
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OBJECTIVE: Because of age-related developmental and cognitive issues, children <10 years of age may not be able to wear an insulin pump safely when they are not under direct parental supervision. The purpose of this study was to determine if insulin pump therapy at nighttime only, when children are at home, could improve fasting and nighttime blood glucose levels without adverse effects. RESEARCH DESIGN AND METHODS: The study cohort consisted of 10 children aged 7-10 years. A randomized crossover design was used to compare nighttime-only pump usage from dinner and throughout the night, combined with a prebreakfast injection of intermediate-acting NPH and rapid-acting lispro insulin, with 3 insulin injections per day. Comparisons were made among mean blood glucose values and percentage of blood glucose levels within the target range (70-150 mg/dl) before meals, at bedtime, and at 3:00 A.M.; serum fructosamine levels; and scores on measures of adherence and fear of hypoglycemia. RESULTS: Compared with baseline levels, the use of the pump resulted in a significant decrease in the mean average (P < 0.001), breakfast (P < 0.0001), and 3:00 A.M. (P < 0.003) blood glucose levels. There was a decrease in the percentage of blood glucose values less than the target range (P < 0.01) and in fructosamine (P < 0.01) values and an increase in the percentage of blood glucose levels within the target range (P < 0.03). CONCLUSIONS: Nighttime-only insulin pump therapy may be a viable alternative that young children can use to improve glycemia when they are not capable of independently managing an insulin pump. (+info)
Effects of nicotinamide and intravenous insulin therapy in newly diagnosed type 1 diabetes.
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OBJECTIVE: To investigate the effect of intravenous insulin therapy combined with nicotinamide in the metabolic control and beta-cell function of newly diagnosed type 1 diabetic subjects in comparison with intensive insulin therapy and nicotinamide alone. RESEARCH DESIGN AND METHODS: A total of 34 newly diagnosed type 1 diabetic patients were included. After the correction of initial metabolic disturbances, subjects were randomly assigned to the following three groups within 72 h after admission: 1) intensive insulin therapy + placebo (C) (n = 12); 2) intensive insulin therapy + nicotinamide, 700 mg three times a day (NIC) (n = 11); and 3) 72-h intravenous insulin followed by intensive insulin therapy + nicotinamide, 700 mg three times a day (NIV) (n = 11). The subjects were monitored for 12 months. GAD, tyrosine phosphatase antibodies, and insulin autoantibodies were measured. C-peptide was measured basally and after 2, 4, 6, 8, and 10 min of 1 mg intravenous glucagon. HbA1c, glucagon, and antibody measurements were determined initially and at 1, 3, 6, 9, and 12 months. RESULTS: HbA1c values declined to normal after treatment was initiated in all groups and remained not significantly different during the follow-up period. We did not find differences between experimental (NIC and NIV) and placebo (C) groups in terms of beta-cell function, considering basal or glucagon-stimulated C-peptide (maximal stimulated C-peptide and area under the curve [AUC] of C-peptide) values during the follow-up period. After pooling data from the NIC and NIV groups (both including nicotinamide) and comparing it with data from the C group, the results remained unchanged. At diagnosis, GAD positivity was observed in 10 of 12, 8 of 11, and 10 of 11 subjects (NS) in the C, NIC, and NIV groups, respectively, and IA2 positivity was observed in 3 of 12, 4 of 11, and 4 of 11 subjects (NS) in the C, NIC, and NIV groups, respectively. Antibody titers displayed a similar behavior in all groups during the follow-up period. CONCLUSIONS: Our pilot study failed to demonstrate that the addition of 72-h intravenous insulin and nicotinamide to conventional intensive insulin therapy produces any beneficial effect in newly diagnosed type 1 diabetic subjects in terms of beta-cell function and metabolic control. (+info)
Improved blood glucose variability, HbA1c insuman Infusat and less insulin requirement in IDDM patients using insulin lispro in CSII. The Swedish Multicenter Lispro Insulin Study.
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The aim of the study was to compare lispro (LP) and Insuman(R) (I) insulin in continuous subcutaneous insulin infusion (CSII) therapy with respect to blood glucose control as expressed by the standard deviation of blood glucose (SD(BG) ) and HbA(1c) and to monitor the well-being (WBQ) and treatment satisfaction (DTSQ) parameters during such treatment. Forty-one IDDM patients who had used CSII for at least 6 months participated in an open-label, randomized, cross-over, multicenter study for 4 months (2 months LP and 2 months I or vice versa). Boluses with LP were given 5 min before each meal and with I 30 min before each meal. During LP administration compared with I, the SD(BG) of all blood glucose values (3.6 mmol/l vs. 3.9 mmol/l, p=0.012), as well as the SD(BG) of the postprandial, blood glucose values (3.6 mmol/l vs. 4.0 mmol/l, p=0.006), were significantly reduced. The HbA(1c) was significantly lower during LP administration (7.4% vs. 7.6%, p=0.047). The incidence of hypoglycemic events per 30 days (capillary blood glucose<3.0 mmol/l and/or symptoms) did not significantly differ between LP and I (9.7 vs. 8.0 per month, p=0.23). The total amount of daily insulin was slightly but significantly lower with LP, compared to I (38.0 IU vs. 40.3 IU, p=0.004). There was no treatment effects of LP compared to I concerning WBQ and DTSQ. It is concluded that in CSII therapy LP is superior to I with respect to the stability of blood glucose control, a lower HbA(1c), a less insulin requirement without increasing the frequency of hypoglycemia. (+info)
Glucose profiles in a type 1 diabetic patient successively treated with CSII using regular insulin, lispro and an implantable insulin pump.
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The delayed subcutaneous insulin absorption makes stable blood glucose difficult to achieve in patients with type 1 diabetes, and there is a high risk for severe hypoglycemia. The human insulin analogs demonstrated to circumvent this major limitation of rapid-acting insulin particularly in the context of a continuous subcutaneous insulin infusion (CSII). As insulin profiles generated by implantable insulin pump (IP) are similar to lispro, we studied glucose profiles and the risk for severe hypoglycemia assessed by the low blood glucose index (LBGI) in a patient successively moved from CSII using regular-acting insulin to CSII using lispro and finally to an IP. Insulin delivery with the IP, and to a lesser extent CSII using lispro tend to reduce the average glycemia in comparison with CSII using regular-acting insulin (114.2+/-53.0, 131. 6+/-56.8 and 140.7+/-81.5 mg/dl, respectively). Reduction of glycemic fluctuations assessed by area under the curves was more pronounced during IP therapy in comparison with lispro and with rapid-acting insulin in CSII (789.5, 798.2 and 891.5 h.mg.dl-1, respectively). LBGI remained in the moderate range with IP and CSII using lispro (4.3+/-6.8 and 4.0+/-5.7 respectively), while LBGI was in the high range with rapid-acting insulin (5.5+/-10.2). In conclusion our case report suggests that IP tends to reduce the average glycemia and affect the amplitude of glycemic fluctuations in comparison with CSII using lispro, with an equivalent risk for severe hypoglycemia. A prospective randomized study is needed to compare these two modes of insulin replacement. (+info)
Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in type 1 diabetic patients on intensified treatment: a randomized study. The Study Group for the Development of Pump Therapy in Diabetes.
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OBJECTIVE: To compare the efficacy of 2 intensified insulin regimens, continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), by using the short-acting insulin analog lispro in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 41 C-peptide-negative type 1 diabetic patients (age 43.5+/-10.3 years; 21 men and 20 women, BMI 24.0+/-2.4 kg/m2, diabetes duration 20.0+/-11.3 years) on intensified insulin therapy (MDI with regular insulin or lispro, n = 9, CSII with regular insulin, n = 32) were included in an open-label randomized crossover study comparing two 4-month periods of intensified insulin therapy with lispro: one period by MDI and the other by CSII. Blood glucose (BG) was monitored before and after each of the 3 meals each day. RESULTS: The basal insulin regimen had to be optimized in 75% of the patients during the MDI period (mean number of NPH injections per day = 2.65). HbA1c values were lower when lispro was used in CSII than in MDI (7.89+/-0.77 vs. 8.24+/-0.77%, P<0.001). BG levels were lower with CSII (165+/-27 vs. 175+/-33 mg/dl, P<0.05). The SD of all the BG values (73+/-15 vs. 82+/-18 mg/dl, P<0.01) was lower with CSII. The frequency of hypoglycemic events, defined as BG levels <60 mg/dl, did not differ significantly between the 2 modalities (CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days). Mean insulin doses were significantly lower with CSII than with MDI (38.5+/-9.8 vs. 47.3+/-14.9 U/day. respectively, P< 0.0001). CONCLUSIONS: When used with external pumps versus MDI, lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes. (+info)