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. Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy. Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo 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 randomized, prospective trial comparing the efficacy of continuous subcutaneous insulin infusion with multiple daily injections using insulin glargine. Oscillatory potentials, macular recovery time, and diabetic retinopathy through 3 years of intensified insulin treatment. Effect of pump versus pen treatment on glycaemic control and kidney function in long-term uncomplicated insulin-dependent diabetes mellitus (IDDM). 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. Human insulin analogue [LYS(B28), PRO(B29)]: the ideal pump insulin? Comparison of continuous subcutaneous insulin infusion with multiple insulin injections using the NovoPen. Intensive insulin therapy with insulin lispro: a randomized trial of continuous subcutaneous insulin infusion versus multiple daily insulin injection.
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. 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. Forty five insulin dependent diabetics were randomised to treatment with continuous subcutaneous insulin infusion (CSII), multiple insulin injections (five or six daily), or conventional twice daily insulin injections. Near normoglycaemia was obtained with CSII and multiple injections but not with conventional treatment (p less than 0.01). Hypoglycaemic coma was observed less frequently with CSII than with multiple injections and conventional treatment (p less than 0.001), but blood glucose concentrations below 2.5 mmol/l (45 mg/100 ml) were more common. After two years fewer retinal microaneurysms and haemorrhages had developed in the patients given CSII and multiple injections compared with those given conventional treatment, in whom the number had increased significantly (p less than 0.01). Motor nerve conduction velocity deteriorated in the patients given conventional treatment; in those given CSII it was unchanged during the first year but had improved after two years (p less than 0.01). Glomerular hyperfiltration was reduced with CSII, but no change occurred in urine albumin excretion rates. Long term near normoglycaemia may prevent the progression of early stages of late diabetic complications. 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. 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. Forty-five diabetic patients, 18 to 45 years of age, with mild or no retinopathy, were randomly assigned to continuous subcutaneous insulin infusion (CSII), multiple injections (Mls), and conventional insulin treatment (CIT). The effects of near-normoglycemia (CSII and MI) on oscillatory potentials (electroretinography [ERG]) and macular recovery time (nyctometry) were studied prospectively for 41 months. Before randomization, the amplitudes of oscillatory potentials were negatively correlated to age (P = 0.002) and positively correlated to the diameter of retinal veins (P less than 0.05). Men had shorter macular recovery time than women (P = 0.03). Nyctometry and oscillatory potentials were not related to mean blood glucose values, glycosylated hemoglobin (HbA1), retinopathy, blood pressure levels, or duration of diabetes. Changes in metabolic control (MI and CSII; P less than 0.01) and in microaneurysms and hemorrhages (CSII and CIT) during the study did not affect oscillatory potentials or nyctometry. Soft exudates (15 patients) and proliferative retinopathy (1 patient) transiently developed with MI and CSII regimens. No changes in oscillatory potentials or nyctometry were observed and no pretreatment characteristics of these parameters predicted the occurrence of these ischemic lesions. At the stage of proliferation, however, lowered amplitudes of oscillatory potentials and lengthened macular recovery time were observed. Glycaemic control on pump versus pen treatment was evaluated and the effects of optimised metabolic control on kidney function was studied in very long-term uncomplicated insulin-dependent diabetes mellitus (IDDM). Ten otherwise healthy patients participated, age: 36.5 yr +/- 7.9, diabetes duration: 23.7 yr +/- 2.9, urinary albumin excretion (UAE): 5.8 micrograms/min x/ divided by 2.2, se-creatinine and blood pressure were normal and only background retinopathy was present. A 2 x 6 months randomised cross-over study was performed using continuous subcutaneous insulin infusion (CSII) and multiple injection technique (MIT). Glycaemic control was evaluated by a six point profile every two weeks and by measuring HbA1c monthly. At 0, 6 and 12 months, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique, and UAE by radioimmunoassay. Glycaemic control was significantly better on CSII as compared to MIT (p = 0.01) or pre-study conventional treatment (CT), p = 0.03, whereas there was no difference between MIT and CT. There was no change in kidney function during either treatment. Thus, in these very long-term uncomplicated patients, glycaemic control was significantly improved during CSII. In spite of this, no change was found in GFR, which might suggest that in long-standing diabetes, kidney function is unaltered by changes in metabolic control. 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. The short-acting insulin analogue lispro ([LYS(B28), PRO(B29)] is absorbed from the subcutis more rapidly than soluble insulin (S). To compare the clinical effectiveness of lispro vs S, 11 Type 1 patients using continuous subcutaneous insulin infusion (CSII) therapy (6 F, 5 M, age 30 +/- 2.5 years, diabetes duration 14 +/- 1.0 years, BMI 24.0 +/- 0.8 kg m(-2), HbA1c 6.5 +/- 0.2%) were studied in an open, randomized, crossover study for 6 months (3 months lispro and 3 months S or vice versa). During lispro treatment mean fasting and 2 h postprandial blood glucose were lower compared to the S phase (fasting 6.5 +/- 0.4 vs 7.5 +/- 0.4 mmol l(-1) (NS), postprandial 6.8 +/- 0.3 vs 8.3 +/- 0.3 mmol l(-1), p = 0.03). In patients treated first with lispro HbA1c levels improved from 6.3 +/- 0.2% to 5.7 +/- 0.3%; On reversion to S HbA1c increased to 6.2 +/- 0.2%. In the group treated first with S, HbA1c fell (6.7 +/- 0.4% vs 6.5 +/- 0.3%) and then improved further to 6.3 +/- 0.3% with lispro. None of these changes were significant. There was no significant difference with respect to hypoglycaemic or other adverse events. It can be concluded that lispro in CSII therapy is safe and may improve postprandial glucose excursions. 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 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.
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.