Intensive insulin therapy with insulin lispro: a randomized trial of continuous subcutaneous insulin infusion versus multiple daily insulin injection. In Type 1 diabetic patients with good glycaemic control, blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine. A randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Incremental value of continuous glucose monitoring when starting pump therapy in patients with poorly controlled type 1 diabetes: the RealTrend study. Continuous subcutaneous insulin infusion (Mill-Hill Infuser) versus multiple injections (Medi-Jector) in the treatment of insulin-dependent diabetes mellitus and the effect of metabolic control on microangiopathy. A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8). Patient-reported outcomes for an integrated real-time continuous glucose monitoring/insulin pump system. Improved treatment satisfaction but no difference in metabolic control when using continuous subcutaneous insulin infusion vs. multiple daily injections in children at onset of type 1 diabetes mellitus. 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. Continuous glucose monitoring-guided insulin adjustment in children and adolescents on near-physiological insulin regimens: a randomized controlled trial. Continuous subcutaneous insulin infusion (CSII) of insulin aspart versus multiple daily injection of insulin aspart/insulin glargine in type 1 diabetic patients previously treated with CSII. Glycemic patterns detected by continuous subcutaneous glucose sensing in children and adolescents with type 1 diabetes mellitus treated by multiple daily injections vs continuous subcutaneous insulin infusion. Glycaemic impact of patient-led use of sensor-guided pump therapy in type 1 diabetes: a randomised controlled trial. A crossover comparison of continuous subcutaneous insulin infusion (CSII) against multiple insulin injections in insulin-dependent diabetic subjects: improved control with CSII. Comparison of continuous subcutaneous insulin infusion with multiple insulin injections using the NovoPen. 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. Special management of insulin lispro in continuous subcutaneous insulin infusion in young diabetic children: a randomized cross-over study. Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy. Improving glycaemic control of patients with Type 2 diabetes in a primary care setting: a French application of the Staged Diabetes Management programme. A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients. Effects of aggressive versus moderate glycemic control on clinical outcomes in diabetic coronary artery bypass graft patients.
To evaluate glycemic control, hypoglycemic events, and quality of life in patients treated with continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injection (MDI), with insulin lispro as the principal insulin.
                This clinical trial enrolled 27 patients with type 1 diabetes. They were randomly assigned to CSII (n = 13) or MDI (n = 14) treatment regimens. Glycemic control (HbA(1c) level) was the primary outcome and was measured monthly for 9 months. Secondary outcomes were patient reports of hypoglycemic events (recorded monthly for 9 months) and quality of life assessed at 9 months using the Diabetes Quality of Life (DQOL) questionnaire.
                A significant decrease in HbA(1c) from baseline was shown for both groups. However, the overall treatment effect (CSII - MDI) for HbA(1c) was +0.08% (95% CI -0.23 to +0.39, P > 0.10). This was significantly less than the a priori limit of +/-0.5% (P = 0.004). The relative treatment effect ([CSII - MDI]/MDI) for the overall number of hypoglycemic events was +9% (95% CI -37 to +87, P > 0.10). There were no statistically significant differences between treatment groups for any of the DQOL subscales.
                No statistically significant differences in glycemic control, reported hypoglycemic events, or quality of life were found in this study. Furthermore, a clinically significant difference of more than +/-0.5% HbA(1c) between the two regimens can be confidently ruled out. We conclude that the choice of intensive insulin therapy should be a matter of patient preference, consistent with lifestyle. The superiority of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) with glargine is uncertain. In this randomized cross-over study, we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII. The primary end-point was glucose variability.
                Thirty-nine patients [38.1 +/- 9.3 years old (mean +/- sd), diabetes duration 16.6 +/- 8.2 years, glycated haemoglobin (HbA(1c)) 7.6 +/- 0.8%], already on CSII for at least 6 months, were randomly assigned to CSII with lispro or MDI with lispro and glargine. After 4 months they were switched to the alternative treatment. During the last month of each treatment blood glucose variability was analysed using glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). As secondary end-points we analysed blood glucose profile, HbA(1c), number of episodes of hypo- and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction.
                During CSII, glucose variability was 5-12% lower than during MDI with glargine. The difference was significant only before breakfast considering glucose standard deviation (P = 0.011), significant overall using MAGE (P = 0.016) and lability index (P = 0.005) and not significant using ADRR. Although HbA(1c) was similar during both treatments, during CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was less, FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments.
                During CSII, glucose variability is lower, glycaemic control better and treatment satisfaction higher than during MDI with glargine. The efficacy of the insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in type 1 diabetes has not yet been established in pediatric patients. Our principal aim in this short-term study was to compare the efficacy of CSII to MDI with glargine in lowering HbA(1c) levels in children and adolescents with type 1 diabetes.
                Thirty-two youth with type 1 diabetes (age 8-21 years) were randomly assigned to receive either MDI treatment with once-daily glargine and premeal/snack insulin aspart or CSII with insulin aspart. Dose titration in both groups was based on home self-monitored blood glucose measurements and monthly HbA(1c). HbA(1c), total daily insulin dose (TDD), self-monitored blood glucose readings, and adverse events were compared after 16 weeks of therapy.
                While there was no significant change in the glargine group (HbA(1c) 8.2% at baseline vs. 8.1% at 16 weeks), youth randomized to CSII had a sharp reduction in HbA(1c) levels, from 8.1 to 7.2% after 16 weeks of therapy (P < 0.02 vs. baseline and <0.05 vs. glargine group). TDD was unchanged in the glargine group, but significantly dropped with CSII (1.4 units/kg at baseline vs. 0.9 units/kg at 16 weeks, P < 0.01). Both groups had similar basal doses and insulin-to-carbohydrate ratios. Fasting self-monitored blood glucose was similar in both groups, but lunch, dinner, and bedtime readings were significantly lower in the CSII group (P < 0.01).
                Lower HbA(1c) and premeal glucose levels were more achievable in this short-term study with CSII than with glargine-based MDI treatment. CSII is an efficacious treatment to improve metabolic control in youth with type 1 diabetes. To compare the improvements in glycemic control associated with transitioning to insulin pump therapy in patients using continuous glucose monitoring versus standard blood glucose self-monitoring.
                The RealTrend study was a 6-month, randomized, parallel-group, two-arm, open-label study of 132 adults and children with uncontrolled type 1 diabetes (A1C >or=8%) being treated with multiple daily injections. One group was fitted with the Medtronic MiniMed Paradigm REAL-Time system (PRT group), an insulin pump with integrated continuous subcutaneous glucose monitoring (CGM) capability, with instructions to wear CGM sensors at least 70% of the time. Conventional insulin pump therapy was initiated in the other group (continuous subcutaneous insulin infusion [CSII] group). Outcome measures included A1C and glycemic variability.
                A total of 115 patients completed the study. Between baseline and trial end, A1C improved significantly in both groups (PRT group -0.81 +/- 1.09%, P < 0.001; CSII group -0.57 +/- 0.94%, P < 0.001), with no significant difference between groups. When the 91 patients who were fully protocol-compliant (including CGM sensor wear >or=70% of the time) were considered, A1C improvement was significantly greater in the PRT group (P = 0.004) (PRT group -0.96 +/- 0.93%, P < 0.001; CSII group -0.55 +/- 0.93%, P < 0.001). Hyperglycemia parameters decreased in line with improvements in A1C with no impact on hypoglycemia.
                CGM-enabled insulin pump therapy improves glycemia more than conventional pump therapy during the first 6 months of pump use in patients who wear CGM sensors at least 70% of the time. The present study was designed to compare continuous subcutaneous insulin infusion (CSII) using the Mill-Hill Infuser (Muirhead Medical Products Ltd., London, England) with multiple injections (MI) using the Medi-Jector (Derata Corporation, Minneapolis, Minnesota) in the treatment of insulin-dependent diabetes mellitus (IDDM), and to assess the effect of glucose control on diabetes complications. Twelve diabetic subjects were treated 3 mo with CSII and 3 mo with MI (bedtime ultralente and premeal boluses of regular insulin) in a randomized fashion. Prestudy preprandial/postprandial glucose levels were 147-215 mg/dl and improved to 108-138 mg/dl during CSII, and to 115-139 mg/dl during MI with glycosylated hemoglobin of 12.9%, 9.1%, and 8.7%, respectively. This improved glucose control with either CSII or MI was associated with an increase in sural nerve conductivity from 42.9 to 45 m/s and a decrease in proteinuria from 1.9 to 0.5 g/24 h. The 24-h insulin dose consisted of 45 U before the study, 44 U during CSII, and 56 U during MI. After the study, seven patients opted to continue with the Mill-Hill Infuser, and five with the Medi-Jector. We conclude the following: (1) treatment with both the Mill-Hill Infuser and the Medi-Jector was well accepted by the patients and resulted in similar improvement in measured blood glucose and glycosylated hemoglobin; (2) this improved metabolic control was associated with an increased nerve conductivity and a decreased protein excretion; and (3) MI required 20% more insulin than CSII to achieve similar glycemic control. In a pilot study, the metabolic effects of continuous subcutaneous insulin infusion (CSII) versus intensive subcutaneous insulin therapy (ISIT) started at diagnosis in patients with Type 1 diabetes and continued for a 2-year period were evaluated and compared. Twenty-three patients (between 12 and 35 years old, mean +/- SD 18.4 +/- 9 years) were randomized into two treatment groups (CSII vs. ISIT), and both received supplemental nicotinamide (NA), 25 mg/kg of body weight. CSII was started immediately after admission to the hospital. Parameters of metabolic control [insulin dose, hemoglobin A1c (HbA1c), and C-peptide] were evaluated for a 2-year follow-up period. Data are presented for a total of 19 patients who remained in the study for its duration. Two years after diagnosis, mean +/- SD HbA1c was 6.3 +/- 0.5% and 6.2 +/- 0.3% for the CSII and ISIT groups, respectively (p=not significant). Compared with baseline values, an increase of baseline C-peptide of 38% for the CSII group and 27% for the ISIT group was observed; however, the difference between the groups was not significant. The insulin requirement for the entire duration of the study, but not at entry and 3 months, was significantly higher in CSII compared with ISIT patients (0.62 +/- 0.4 IU/kg/day vs. 0.3 +/- 0.4 IU/kg/day, respectively; p<0.01). After trial completion patients on CSII continued with this mode of therapy. Implementation of CSII as well as ISIT at diagnosis of Type 1 diabetes and continuation for 2 years thereafter achieved similar and optimal metabolic control, but more insulin was required with the CSII group. Both types of intensive insulin therapy combined with NA are able to preserve C-peptide secretion or even increase baseline levels for up to 2 years after diagnosis. A 16-week, two-site study evaluated outcomes for a new device (the Paradigm 722 System, Medtronic MiniMed, Northridge, CA) that combines a "smart" continuous subcutaneous insulin infusion (CSII) pump with real-time (RT) continuous glucose monitoring (CGM) and CareLinktrade mark data management software (DMS).
                CSII-naive adults with type 1 diabetes in suboptimal control (mean glycosylated hemoglobin [A1C] = 8.6%) were randomized to the control arm, consisting of multiple daily injections (MDI) and self-monitoring of blood glucose (SMBG), or the study arm (CSII with RT-CGM as an adjunct to SMBG). Participants (n = 28) completed the validated Insulin Delivery System Rating Questionnaire (IDSRQ) and the parallel Blood Glucose (BG) Monitoring System Rating Questionnaire (BGMSRQ) at study start and end. Participants in the study arm (n = 14) also completed newly developed User Acceptance Questionnaires (UAQs) for CSII, RT-CGM, and DMS at study end.
                A1C reduction from study start to end was significant (P < 0.05) in both arms (-1.7% for study arm;-1.0% for control arm); there was no significant change in weight in either arm. The IDSRQ showed significantly (P < 0.05) greater benefit for the study arm in convenience, acceptability of BG monitoring requirements, BG control efficacy, diabetes worries, and interpersonal hassles, as well as higher overall satisfaction/preference. The BGMSRQ showed significantly (P < 0.05) greater benefit for the study arm in the BG monitoring system's ability to help manage glycemic control and less interest in changing to another BG monitoring system. The Study Arm UAQs showed positive ratings of system features.
                Several patient-reported outcomes were significantly more positive in the study arm than the control arm; none was significantly more positive in the control arm. The features of the integrated RT-CGM/CSII system were frequently used and highly rated by participants, with high user satisfaction. The aim of this study was to compare safety, metabolic control, and treatment satisfaction in children/adolescents at onset of type 1 diabetes mellitus who were treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).
                Seventy-two children/adolescents (7-17 yr of age) were enrolled in this open, randomized, parallel, multicenter study. Approximately half of the patients were treated with MDI (natural protamine hagedorn [NPH] insulin twice daily and rapid-acting insulin three to -four times daily, n = 38) by pen, and the other half received CSII (n = 34). The patients were followed for 24 months with clinical visits at the entry of the study and after 1, 6, 12, and 24 months. During these visits, hemoglobin A1c, insulin doses, weight, and height were registered. Severe episodes of hypoglycemia and ketoacidosis as well as technical problems were recorded. In addition, the patients/parents answered the Diabetes Treatment Satisfaction Questionnaire.
                There was no significant difference in metabolic control between the treatment groups. Treatment satisfaction was significantly higher in the group treated with CSII compared with the MDI group (p <or= 0.01 at all screening visits). There were no episodes of ketoacidosis and there was no significant difference regarding severe hypoglycemia between the treatment groups.
                CSII treatment proved to be a safe therapy in children/adolescents followed for 24 months after onset of their diabetes. Treatment satisfaction was higher in the CSII group, although there was no difference in metabolic control compared with the MDI group. 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. This randomized controlled trial assesses the effect on glycemic control of continuous glucose monitoring system (CGMS)-guided insulin therapy adjustment in young people with type 1 diabetes on intensive diabetes treatment regimens with continuous subcutaneous insulin infusion (CSII) or glargine.
                Pediatric subjects were recruited if they had an HbA(1c) (A1C) <10% and had been on CSII or glargine for at least 3 months. Thirty-six subjects were randomized to insulin adjustment on the basis of 72 h of CGMS every 3 weeks or intermittent self-monitoring of blood glucose (SMBG) for 3 months. A1C and fructosamine were measured at baseline and 6 and 12 weeks. Follow-up A1C was measured at 6 months. Mean baseline A1C was 8.2% (n = 19) in the CGMS group and 7.9% (n = 17) in the control group.
                There was a significant improvement in A1C from baseline values in both groups, but there was no difference in the degree of improvement in A1C at 12 weeks between the CGMS (-0.4% [95% CI -0.7 to -0.1]) and the control group (-0.4% [-0.8 to 0.2]). In the CGMS group, improved A1C was at the cost of increased duration of hypoglycemia.
                CGMS is no more useful than intermittent fingerstick SMBG and frequent review in improving diabetes control in reasonably well-controlled patients on near-physiological insulin regimens when used in an outpatient clinic setting. Multiple daily injection (MDI) therapy of bolus insulin aspart and basal insulin glargine was compared with continuous subcutaneous insulin infusion (CSII) with aspart in type 1 diabetic patients previously treated with CSII.
                One hundred patients were enrolled in a randomized, multicenter, open-label, crossover study. After a 1-week run-in period with aspart by CSII, 50 subjects were randomly assigned to MDI therapy (aspart immediately before each meal and glargine at bedtime) and 50 subjects continued CSII. After 5 weeks of the first treatment, subjects crossed over to the alternate treatment for 5 weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system for 48-72 h.
                Mean serum fructosamine levels were significantly lower after CSII therapy than after MDI therapy (343 +/- 47 vs. 355 +/- 50 micromol/l, respectively; P = 0.0001). Continuous glucose monitoring profiles over a 24-h time period showed that glucose exposure was 24 and 40% lower for CSII than MDI as measured by area under the curve (AUC) glucose >/=80 mg/dl (1,270 +/- 742 vs. 1,664 +/- 1,039 mg . h . dl(-1); P < 0.001) and AUC glucose >/=140 mg/dl (464 +/- 452 vs. 777 +/- 746 mg . h . dl(-1), CSII vs. MDI, respectively; P < 0.001). Similar percentages of subjects reported hypoglycemic episodes (CSII: 92%, MDI: 94%) and nocturnal (12:00 a.m. to 8:00 a.m.) hypoglycemic episodes (CSII: 73%, MDI: 72%). Major hypoglycemia was infrequent (CSII: two episodes, MDI: five episodes).
                In a trial of short duration, CSII therapy with insulin aspart resulted in lower glycemic exposure without increased risk of hypoglycemia, as compared with MDI with insulin aspart and glargine. To compare glycemic patterns by mode of therapy in children with type 1 diabetes mellitus using the Continuous Glucose Monitoring System (CGMS).
                Open randomized crossover comparing 3(1/2) months of multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII).
                Tertiary care, university-affiliated medical center. Patients Twenty-three children and adolescents with type 1 diabetes mellitus.
                The CGMS was applied for 72 hours after 1 month and at the end of each study arm.
                Hemoglobin A(1c) levels and glucose level profiles were compared between the 2 study arms and the 2 sensor applications for each arm.
                The arms were similar for mean (SD) hemoglobin A(1c) levels (CSII, 8.0% [0.8%]; and MDI, 8.2% [0.8%]) and glucose levels. Areas under the curve were significantly larger during MDI for nocturnal and 24-hour hypoglycemia (P =.01 and.04, respectively) and for postprandial hypoglycemia and hyperglycemia (P =.03 and.05, respectively). The rate of hyperglycemia increased during CSII (P =.03), but 24-hour duration and area under the curve for hyperglycemia were similar. Compared with the first CGMS reading in each arm, the second had a longer mean duration of postprandial within-target glucose levels (P =.04), tendency for lower rate of diurnal hypoglycemic events (P =.1), shorter duration of nocturnal hypoglycemia (P =.05), and smaller 24-hour area under the curve for hypoglycemia (P =.04).
                Intensive treatment with CSII seemed to be associated with slightly better prebreakfast, postprandial, and within-target glucose profiles than MDI, as well as a smaller area under the curve for hypoglycemia. Lower hypoglycemia-related variables in the second sensor reading in each arm indicate that the CGMS may serve as an educational tool to decrease the rate and magnitude of hypoglycemia. The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy.
                An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA(1c) level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA(1c), time in hypoglycaemic (< or =3.9 mmol/l) and hyperglycaemic (> or =10.1 mmol/l) ranges and glycaemic variability.
                Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA(1c) was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p = 0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI -5.37 to 8.81), hypoglycaemic (0.54; 95% CI -3.48 to 4.55) or hyperglycaemic (-2.18; 95% CI -10.0 to 5.69) range or in glycaemic variability (-0.29; 95% CI -0.34 to 0.28). Within the intervention group, HbA(1c) was 0.51% lower in participants with sensor use > or =70% compared with participants with sensor use <70% (95% CI -0.98 to -0.04, p = 0.04). Five episodes of device malfunction occurred.
                Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, frequent use of this technology (> or =70%) was not universally acceptable.
                ACTRN12606000049572 Ten insulin-dependent C-peptide-negative diabetic subjects, whose control had been optimized on twice-daily injection therapy, were treated for periods of 10 wk in a crossover study, with either a thrice-daily subcutaneous insulin injection regimen (Actrapid + Ultratard) or by continuous subcutaneous insulin infusion (CSII). On CSII insulin dose stabilized at 51 +/- 5 U/day, compared with 80 +/- 9 U/day (P = 0.004) on the thrice-daily injection regimen, having been 60 +/- 6 U/day on twice-daily therapy. After 10 wk glycosylated hemoglobin was 11.7 +/- 0.6% on injection therapy and 10.0 +/- 0.7% (P = 0.026) on CSII. Mean blood glucose concentration and urinary glucose excretion were lower at most points during the study on CSII than on injection therapy. Patients on pumps gained weight compared with the thrice-daily injection regimen (P = 0.023 at 10 wk) and the previous twice-daily regimen, despite the reduction in insulin dose. Considering individual patients, four markedly improved on CSII compared with the previous twice-daily regimen and five compared with Actrapid + Ultratard. No patient showed impaired control on CSII compared with either injection regimen. The benefits of portable insulin infusion pumps over injection therapy are thus clearly demonstrable under outpatient conditions even with equal and intensive medical attention. Twenty-one patients with insulin-dependent diabetes mellitus (IDDM) participated in a 20-week randomized cross-over comparison of continuous subcutaneous insulin infusion (CSII) with intensified conventional treatment (ICT) using the NovoPen. The Medix or the Auto-Syringe pumps were used for CSII and, during ICT with NovoPen, conventional plastic syringes were used for injections of intermediate-acting insulin at bedtime. At entry HbA1c, was 8.7 +/- 0.4% (mean +/- SE) in CSII patients and 8.8 +/- 0.5% in the ICF group. HbA1c declined significantly in both groups (ICT 7.6 +/- 0.2%; CSII 7.6 +/- 0.2%) though there was no significant difference between the responses. Overall mean blood glucose was slightly but significantly lower during CSII than during ICT (CSII: 7.6 +/- 0.2 mmol/l; ICT: 8.7 +/- 0.4 mmol/l, p less than 0.05). The number of hypoglycaemic episodes did not differ significantly between patients treated with NovoPen and CSII. At the end of the study, a questionnaire revealed that all but one patient preferred ICT with NovoPen to conventional therapy. Given the choice for future treatment, 6 patients chose CSII, 12 patients preferred ICT with NovoPen and 1 was unsure. 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.
                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.
                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).
                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. To compare the safety, efficacy and management of insulin lispro (LP) with regular human insulin (RH) in young diabetic children treated with continuous subcutaneous insulin infusion (CSII).
                27 very young diabetic children (age 4.6 +/- 2.2 years) treated with CSII participated in an open-label, randomized cross-over multicenter study comparing 2 periods of 16 weeks of CSII with LP or RH.
                Mean daily basal rate was significantly higher during the LP period (p = 0.04). No differences were seen in changes in HbA1c levels, number of hypoglycemic events, cutaneous infections and catheter occlusions. There was no significant difference between the two treatments for preprandial and postprandial glucose values, although prandial glucose excursions tended to be lower with LP (significant at dinner, p = 0.01). Mean blood glucose levels were significantly higher at 0.00 and 3.00 a.m. during LP therapy (p < 0.05). No episode of ketoacidosis occurred during LP treatment. More parents indicated that LP made their own and the child's daily life easier (p = 0.02) and preferred LP (p = 0.01).
                LP in CSII therapy in children is safe, as effective as RH, improved postprandial excursions, met the needs of young children in their daily life well, and gained their parents' satisfaction and preference. However, a shorter duration of LP resulted in hyperglycemia during the first part of the night, which must be compensated for by increasing nocturnal basal rates during this time. Two groups of pregnant diabetic women, fifteen with type I and fourteen with type II diabetes, were randomly assigned either to CSII or to ICT and the subgroups compared with respect to glycaemic control, insulin requirement and perinatal out-come. Ten non-diabetic pregnant women served as controls for the variations in the metabolic parameters considered (24-hour mean blood glucose and glycosylated hemoglobin). Strict glycaemic control was achieved and maintained by both regimens before week 13 in all patients with type I and in 57.1% of patients with type II diabetes. The mean insulin requirements in the type I group increased up to week 34-36 and then stabilized to term in patients receiving CSII and rose progressively to term in those receiving ICT. In the type II group insulin requirements rose up to week 36 in patients receiving CSII and up to week 32 in those receiving ICT, stabilizing thereafter on both regimens. No significant differences in mean insulin requirement at the different stages of gestation were found between the patients receiving CSII and those receiving ICT of either group. Perinatal outcome was satisfactory in both groups, although control of foetal growth was better with ICT than with CSII. CSII is a practical, safe and effective method of maintaining maternal normoglycemia in pregnancy but for the present we cannot consider it superior to ICT in the treatment of pregnant diabetic women. To assess the impact of a French adaptation of the Staged Diabetes Management (SDM) programme on glycaemic control of people with Type 2 diabetes in primary care. Secondary endpoints were blood pressure, blood lipids, healthcare costs and quality of life.
                Prospective, randomized controlled study, of 1 years' duration. General practitioners (GPs) were recruited in four separate districts of a French region. They enrolled consecutive patients with Type 2 diabetes. GPs in the intervention group were educated in the SDM programme. GPs in the control group were asked to provide usual care. Healthcare costs were collected by medical departments of the Health Insurance systems. Quality of life was assessed with the Duke Health Profile.
                Three hundred and forty patients enrolled by 57 GPs completed the study, 192 in the intervention group and 148 in the control group. Patients in the intervention group were managed more adequately in accordance with the guidelines (P < 0.05 for nine out of 10 items). HbA(1c) decreased by 0.31% in the intervention group and increased by 0.56% in the control group, resulting in a difference of 0.87% by the end of the study (P = 0.001). Blood pressure and blood lipids did not differ between groups. Occurrence of major complications was low and identical in both groups. Incremental costs during the study in the intervention group were 35 euros per patient per month, and this was not significantly different in comparison with the control group. Quality of life was not affected by the intervention.
                Educating GPs in the French adaptation of the SDM programme improves glycaemic control in a primary care setting, without significantly increasing healthcare costs. 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. This study sought to determine whether aggressive glycemic control (90-120 mg/dL) would result in more optimal clinical outcomes and less morbidity than moderate glycemic control (120-180 mg/dL) in diabetic patients undergoing coronary artery bypass graft (CABG) surgery.
                Maintaining serum glucose levels between 120 and 180 mg/dL with continuous insulin infusions decreases morbidity in diabetic patients undergoing CABG surgery. Studies in surgical patients requiring prolonged ventilation suggest that aggressive glycemic control (<120 mg/dL) may improve survival; however, its effect in diabetic CABG patients is unknown.
                Eighty-two diabetic patients undergoing CABG were prospectively randomized to aggressive glycemic control (90-120 mg/dL) or moderate glycemic control (120-180 mg/dL) using continuous intravenous insulin solutions (100 units regular insulin in 100 mL: normal saline) beginning at the induction of anesthesia and continuing for 18 hours after CABG. Primary end points were the incidence of major adverse events (major adverse events = 30-day mortality, myocardial infarction, neurologic events, deep sternal infections, and atrial fibrillation), the level of serum glucose, and the incidence of hypoglycemic events.
                There were no differences in the incidence of major adverse events between the groups (17 moderate vs 15 aggressive; P = 0.91). Patients with aggressive control had a lower mean glucose at the end of 18 hours of insulin infusion (135 ± 12 mg/dL moderate vs 103 ± 17 mg/dL aggressive; P < 0.0001). Patients with aggressive control had a higher incidence of hypoglycemic events (4 vs 30; P < 0.0001).
                In diabetic patients undergoing CABG surgery, aggressive glycemic control increases the incidence of hypoglycemic events and does not result in any significant improvement in clinical outcomes that can be achieved with moderate control. Clinical Trials.gov (ID #NCT00460499).
There is some evidence to suggest that CSII may be better than MI for glycaemic control in people with type 1 diabetes. Non-severe hypoglycaemic events do not appear to be reduced with CSII. There is insufficient evidence regarding adverse events, mortality, morbidity and costs.