Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion

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.     

Continuous intraperitoneal insulin infusion partly restores the glucagon response to hypoglycaemia in type 1 diabetic patients

The glycaemic and hormonal responses to a hypoglycaemic event induced by an i.v. bolus of insulin was studied in seven type 1 diabetic patients treated first with continuous subcutaneous insulin infusion (CSII) and subsequently with continuous intraperitoneal insulin infusion (CIPII). Arterialised blood glucose and venous hormonal responses were analyzed. HbA1c was improved by CIPII. Although a regimen of a higher basal insulin infusion rate was applied during CIPII the basal peripheral venous insulin levels were lower. The i.v. bolus of insulin resulted in hypoglycaemia in both tests but was more pronounced during the CSII test expressed as a smaller area under the curve (AUC) for the first hour (13.0 +/- 2.3 vs. 13.7 +/- 1.2 mmol l(-1) h(-1), p=0.016, CSII vs. CIPII). The hypoglycaemia resulted in a significant and similar increase in the plasma levels of adrenaline, cortisol and growth hormone in both experiments. A significant increase in the glucagon level was only observed during CIPII. The incremental glucagon response was also significantly more pronounced in the CIPII test expressed as maximal responses (7.5 +/- 3.0 vs. 17.0 +/- 3.1 pg ml(-1), p =0.048, CSII vs. CIPII) as well as incremental AUC (5.1 +/- 12.0 vs. 44.4 +/- 13.2 pg ml(-1) h(-1), p =0.027, CSII vs. CIPII). It seems that CIPII in type 1 diabetic patients could improve the glucagon release to hypoglycaemia. This observation may contribute in explaining why CIPII is associated with a lower incidence of hypoglycaemia in spite of an improvement in metabolic control.     

Determinants of glycaemic control in type 1 diabetes during intensified therapy with multiple daily insulin injections or continuous subcutaneous insulin infusion: importance of blood glucose variability

BACKGROUND AND METHODS: We investigated the factors that determine the best glycaemic control on multiple daily insulin (MDI) injections and continuous subcutaneous insulin infusion (CSII), and the hypothesis that blood glucose variability is a major determinant of control and that the resultant HbA(1c) on MDI correlates with the improvement achieved by CSII. We studied 30 type 1 diabetic subjects already receiving MDI. Renewed attempts to improve control on MDI were made for a median of five months, and then the subjects were switched to CSII. The variability of within-day and between-day blood glucose concentrations was calculated from blood glucose self-monitoring data. RESULTS: HbA(1c) during MDI varied from 5.7 to 11.7% (mean +/- SD, 8.5 +/- 1.4%). Within- and between-day blood glucose variability correlated with HbA(1c) on MDI (r = 0.59, p < 0.001; r = 0.48, p < 0.03). Within-day variability remained an independent predictor of HbA(1c) on MDI. Mean HbA(1c) improved with CSII (to 7.3 +/- 0.9%, p < 0.001), but reduction in HbA(1c) was variable and was related to the HbA(1c) on MDI (r = 0.79, p < 0.001) and within-day variability (r = 0.56, p < 0.01). Similar results were observed for subjects treated only with glargine-based MDI. CONCLUSIONS: The best glycaemic control achievable on MDI is related to blood glucose variability-those with the largest swings in blood glucose retaining the highest HbA(1c). The improvement in control achieved by CSII is related to HbA(1c) and blood glucose variability on MDI. Pump therapy is most effective in those worst controlled on MDI.     

Chronic continuous intraperitoneal insulin infusion (CIPII) in type I diabetic patients non-satisfactorily responsive to continuous subcutaneous insulin infusion (CSII)

Summary Six unstable C-peptide negative type I diabetic patients who had been previously treated with continuous subcutaneous insulin infusion (CSII) for at least one year without achieving satisfactory metabolic control, were admitted to this study and switched to continuous intraperitoneal insulin infusion (CIPII). The results obtained with the two treatments have been compared from the metabolic and clinical points of view. CIPII produced a decrease in HbA_1c (p<0.05), in MAGE value (p<0.005), in the percentage of blood glucose determinations above 14 mmol/l (p<0.05) and below 3.9 mmol/l (p<0.05); an increase in serum cholesterol, and a decrease in HDL-cholesterol (p<0.05) due to a reduction of the HDL₂ fraction (p<0.01). A mean body weight reduction of 3 kg was observed during CIPII (p<0.01), not related to dietary changes or to a reduction of the daily insulin dose. Twenty-four hour metabolic profiles during CIPII showed lower mean plasma glucose (p<0.001), serum free insulin (p<0.001), blood β-OH-butyrate (p<0.001), and higher serum glycerol (p<0.001) as compared to CSII. It is concluded that CIPII may be of clinical value in the out-patient management of unstable type I diabetic patients, and that metabolic modifications induced by CIPII are not limited to changes in glucose utilization and production, but include changes in triglyceride, cholesterol and lipid metabolism which may have clinical relevance. Supported by the National Research Council (CNR), Target Project ‘Preventive Medicine and Rehabilitation’, Subproject ‘4’ and by the Juvenile Diabetes Foundation, U.S.A., file No. 184066.     

Continuous intraperitoneal insulin infusion in the management of severely brittle diabetes--a metabolic and clinical comparison with intravenous infusion

We report a comparison of continuous intraperitoneal insulin infusion (CIPII) and continuous intravenous insulin infusion (CIVII) in 6 diabetic patients in whom severe hyperglycaemia and ketoacidosis could not be prevented with subcutaneous or intramuscular insulin. In the short term both methods were equally effective in maintaining glycaemic control. Blood glucose, glycerol, and 3-hydroxybutyrate levels were normal but lactate and pyruvate levels remained elevated with both treatments. Insulin requirements were significantly lower on CIPII than CIVII (70 vs 113 U/day, p less than 0.01). Intraperitoneal insulin delivery was associated with near physiological peripheral plasma insulin profiles in 3 patients. In the longer term CIVII was associated with frequent septicaemia and thrombosis, and was successful in preventing hospitalization for 6 months or more in only one patient. Despite technical problems with CIPII complications were less serious and hospital admission due to metabolic decompensation was prevented for 6 months or more in 3 patients. When subcutaneous insulin delivery is unsuccessful in the management of brittle diabetes, CIPII should be considered rather than CIVII because it is more likely to be successful and less likely to cause serious complications.     

Insulin Kinetics in Type I Diabetic Patients Treated by Continuous Intraperitoneal Insulin Infusion: Influence of Anti-insulin Antibodies

Continuous intraperitoneal insulin infusion (CIPII) is a promising therapy of patients with Type 1 (insulin-dependent) diabetes mellitus (IDDM), since it improves metabolic control and decreases frequency of severe hypoglycaemia. This could be due to more appropriate insulin kinetics. Our aim, therefore, was to compare plasma free insulin levels achieved in patients with Type 1 diabetes chronically treated with CSII or CIPII. Furthermore, as anti-insulin antibodies increase with this treatment, we wanted to assess their influence upon insulin kinetics. Plasma free insulin profiles were obtained during the night and then after the bolus for breakfast and the bolus for lunch in 11 patients with Type 1 diabetes treated successively by CSII and CIPII. In another group of 16 patients with long-term Type 1 diabetes, treated by CIPII, we examined the influence of anti-insulin antibody level on insulin kinetics after a bolus. During the night, plasma free insulin levels were lower with CIPII than with CSII (12:00 am: 10.1 ± 1.7 vs 18.5 ± 2.6 mU l⁻¹; 4:00 am: 9.1 ± 2 vs 15 ± 3 mU l⁻¹), p < 0.01. After the bolus, CIPII lead to an earlier (1h vs 3h) and higher (25.8 ± 3.3 vs 18 ± 2.7, p < 0.05) plasma free insulin peak than CSII. With CIPII, the return to baseline level was observed within 3 h. Conversely, during CSII, insulin levels did not return to baseline until the next meal. After the bolus, high insulin-antibody levels were associated with a reduced maximal value of plasma free insulin peak. Taken together, these findings suggest that CIPII provides plasma free insulin profiles which are much closer to physiology than CSII. This could explain the lower rate of severe hypoglycaemia observed with this type of treatment. But in long-term CIPII treated patients with high anti-insulin antibody level, insulin profile could be moderately modified. This emphasizes the need for a less immunogenic insulin preparation.     

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.     

胰岛素泵治疗老年2型糖尿病的疗效观察

目的对比应用胰岛素泵(CSII)与多次皮下注射胰岛素(MSII)对血糖控制不佳的老年2型糖尿病(T2DM)患者的治疗效果及安全性。方法将58例老年T2DM患者随机分为CSII组(30例)和MSII组(28例),进行胰岛素治疗。分别检测2组治疗前后的三餐前后及睡前血糖、血糖控制时间、每日胰岛素用量、低血糖发生的次数以及治疗后的糖化血红蛋白(HbA1c)水平并进行统计分析。结果2组均能达到目标血糖值,但CSII组血糖控制达标时间、胰岛素用量及低血糖发生率均明显少于MSII组(P<0.01),CSII治疗后HbA1c水平显著低于MSII组(P<0.01)。结论CSII有效模拟人体生理胰岛素分泌,用于老年T2DM患者能更快、更有效地控制高血糖,减少低血糖的发生率,并且效果能持续较长时间。     

Long-term benefits of continuous subcutaneous insulin infusion in children with Type 1 diabetes: a 4-year follow-up.

AIM: To determine the safety and effectiveness of continuous subcutaneous insulin infusion (CSII) in attaining long-term glycaemic control in paediatric patients with Type 1 diabetes and to compare the results with those previously recorded in the same patients taking multiple daily injections (MDI) (four injections a day). METHODS: Forty-two patients (mean age 12.2 +/- 3.4 years; range 4.5-17 years; 24 males; mean duration of Type 1 diabetes 5.1 +/- 3.0 years) were studied. The following parameters were assessed in the year before starting CSII treatment (during MDI treatment) and during the 4 years of insulin pump treatment: annual mean HbA1c, insulin requirements (U/kg per day), annual mean of body mass index (BMI) z scores, and adverse events (severe hypoglycaemia and diabetic ketoacidosis/patient per year). Two patients discontinued pump therapy (after 1-year and 2-year follow-up, respectively) because of non-compliance with CSII therapy. RESULTS: Compared with the annual mean HbA1c observed prior to CSII therapy (8.9 +/- 1.0%), the mean HbA1c levels were lower during the first (8.2 +/- 0.9%; P = 0.00), second (8.6 +/- 1.0%; P = 0.05), third (8.4 +/- 0.9%; P = 0.01) and fourth (8.2 +/- 1%; P = 0.00) year of CSII therapy. The insulin requirements (U/kg per day) decreased during CSII treatment compared with MDI treatment. Compared with the annual mean of BMI z scores prior to CSII therapy, BMI z scores were significantly lower during the third and fourth years of CSII therapy. Through the first, second, third and fourth years of follow-up the number of episodes of severe hypoglycaemia (20.0, 20.0, 20.0 and 0 episodes/1000 patient-years, respectively) and diabetic ketoacidosis (0.05, 0.00, 0.03 and 0.00 episodes/patient per year, respectively), events were similar to that in the year preceding CSII therapy (20.0 and 0.03, respectively). CONCLUSION: In this population of selected patients in our clinic, CSII appears to be a safe and effective therapeutic alternative to MDI treatment. This therapy may ensure a stable improvement in long-term glycaemic control in paediatric patients, with no increase in diabetic ketoacidosis and severe hypoglycaemic events and, on the other hand, with a trend of reduction in BMI z scores.     

Cost-effectiveness of sensor-augmented pump therapy in two different patient populations with type 1 diabetes in Italy

Background and aims

Sensor-augmented pump therapy (SAP) combines real time continuous glucose monitoring (CGM) with Continuous Subcutaneous Insulin Infusion (CSII) and provides additional benefits beyond those provided by CSII alone. SAP with automated insulin suspension provides early warning of the onset of hyperglycemia and hypoglycemia and has the functionality to suspend insulin delivery if sensor glucose levels are predicted to fall below a predefined threshold. Aim of this study was to assess the cost-effectiveness of SAP with automated insulin suspension versus CSII alone in type 1 diabetes.

HYPOGLYCEMIC EPISODES DURING CONTINUOUS SUBCUTANEOUS INSULIN INFUSION: DECREASED FREQUENCY BUT INCREASED SUSCEPTIBILITY

There has been concern regarding the susceptibility of patients on continuous subcutaneous insulin infusion (CSII) to hypoglycemic episodes. This study has examined glycemic control, the frequency of hypoglycemic reactions and the counterregulatory response to an IV insulin infusion of 2.4 units per hour in five brittle insulin-dependent diabetics before and during CSII. CSll was associated with a significant reduction in glycosylated hemoglobin, standard deviation of blood glucose estimations and daily insulin dosage. The frequency of symptomatic hypoglycemic reactions was reduced (mean 14/4 weeks pre CSII, 5/4 weeks post CSII, p<0.05). However, after CSll the IV insulin infusion caused a more rapid fall in blood glucose from the physiological to the hypoglycemic range while growth hormone and cortisol responses were both reduced (p<0.05) and the deficient glucagon response was not improved. Thus, although the frequency of reported hypoglycemic reactions was reduced by CSII, susceptibility to hypoglycemia due to excess insulin delivery was enhanced, owing to increased insulin sensitivity and/or additional impairment of the counterregulatory response.     

Aktuelle Aspekte der Insulinpumpentherapie bei Erwachsenen

In type 1 diabetes achieving a close to normal HbA1c level is a key target to avoid micro- and macro-vascular complications. However, close to normal HbA1c levels increase the risk of hypoglycemia and severe hypoglycemia considerably. With continuous subcutaneous insulin infusion (CSII) compared to the intensified conventional therapy (ICT) even lower HbA1c levels are achievable with an additional decreased blood glucose variability, e.g. less hypo- und hyperglycemic events. In addition to the improvement in glycemic control and variability, other typical indications include an increased rate of (nocturnal) hypoglycemia, hypoglycemia unawareness, the“dawn-phenomenon”, (planned) pregnancy, work-related reasons like shift work, high insulin sensitivity and various diabetes-related organ complications. At our center more than one third of patients with type 1 diabetes seen as in- or outpatients are currently on CSII. Across centers, different“recipes” exist to tailor an ideal CSII therapy for the individual patient; nevertheless, typical features for adult patients are discussed in this review. Special focus is put on the basal rate, bolus options, patient selection, education/training, technical capabilities of the currently available pumps and catheters and the choice of insulin.     

Less severe hypoglycaemia, better metabolic control, and improved quality of life in Type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII) therapy; an observational study of 100 consecutive patients followed for a mean of 2 years.

AIMS: To compare glycaemic control, occurrence of acute complications, and diabetes-specific quality of life in Type 1 diabetic patients (on intensified conventional insulin treatment (ICT)) before and after initiation of CSII. METHODS: One hundred and three patients (58 women) started CSII between October 1995 and April 1999 in our department. The indication for CSII was optimization of metabolic control and improvement of flexibility of life style (OF group) in 60 patients (58%), and prevention of severe hypoglycaemia (HY group) in 43 patients. Mean age at initiation of CSII was 33 +/- 11 years (OF 33 +/- 10, HY 33 +/- 11 (mean +/- sd)), diabetes duration 18 +/- 9 years (OF 16 +/- 9, HY 20 +/- 9). Three patients stopped CSII, mean duration of CSII of the remaining 100 patients was 1.8 +/- 1.2 years. The occurrence of hypoglycaemia, ketoacidosis and skin abscesses was assessed retrospectively for the 12 months before starting CSII, and recorded continuously during CSII. Quality of life was assessed with a validated, diabetes-specific questionnaire before and after CSII in 50 patients. RESULTS: The incidence of serious hypoglycaemia (any external help) was reduced from 1.23 (OF 0.0; HY 2.93) during ICT to 0.29 cases/patient per year (OF 0.09; HY 0.55) during CSII. The incidence of severe hypoglycaemia (SH) (treated with i.v. glucose or glucagon injection) fell from 0.70 (OF 0.0; SH 1.67) during ICT to 0.06 cases/patient per year (OF 0.02; HY 0.12) during CSII. HbA1c improved from 7.7 +/- 1.1% to 7.2 +/- 1.0% (P < 0.001) (OF 7.8% vs. 7.2%; HY 7.6% vs. 7.2%). During CSII the incidence of abscesses was 0.11 and of ketoacidosis 0.01 cases/patient per year. Quality of life assessments showed significant improvement in all parameters during CSII. CONCLUSIONS: In our cohort of Type 1 diabetic patients, we observed a substantial decrease of hypoglycaemia along with a significant fall of HbA1c. Quality of life on CSII was improved when compared with ICT.     

A randomized pilot study in Type 1 diabetes complicated by severe hypoglycaemia, comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or education alone.

AIM: To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-standing Type 1 diabetes (T1DM). METHODS: Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE; lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII; lispro); or re-education with relaxation of blood glucose targets on existing conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose. RESULTS: Further severe hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06). Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7 (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/- 0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no episodes of diabetic ketoacidosis or any other adverse events in any group. CONCLUSIONS: In this pilot randomized trial comparing optimized ANALOGUE, CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups.     

Continuous intraperitoneal insulin infusion in patients with 'brittle' diabetes: favourable effects on glycaemic control and hospital stay.

AIMS: To evaluate the effects of continuous intraperitoneal insulin infusion (CIPII) using implantable pumps on glycaemic control and duration of hospital stay in poorly controlled 'brittle' Dutch diabetes patients, and to assess their current quality of life. METHODS: Thirty-three patients were included. Glycaemic control was retrospectively assessed with HbA(1c) levels acquired before implantation, 1 year later and at long-term follow up of 58 months. Duration of hospital stay the year before and the year following first implantation was extracted from hospital records. Determinants of long-term glycaemic response were sought. Self-report questionnaires were administered at 58 months follow-up only, to assess current psychopathology and quality of life. RESULTS: Mean HbA(1c) decreased from 10.0 +/- 2.3% to 9.0 +/- 1.8% (P = 0.039) 1 year after implantation and stabilized at 9.0 +/- 1.6% (P = 0.023) during long-term follow-up. Median number of hospital days in the 20 patients suffering from hospital admission before implantation decreased from 45 the year before implantation to 13 the year after (P = 0.005). Patients with a higher baseline HbA(1c) showed a larger long-term response (P < 0.001). Relatively low levels for quality of life were found, as well as a higher than expected number of patients with psychiatric symptoms. CONCLUSIONS: CIPII proved effective in complex patients with a history of poor control and hospital admission. Despite a substantial long-term improvement in glycaemic control and diminished hospital stay, normal levels of glycaemic control and quality of life were not attained.     

The Evidence Base for Diabetes Technology: Appropriate and Inappropriate Meta-Analysis

When we are interested in making decisions about best use, comparative therapeutic efficacy, or cost-effectiveness of diabetes technologies such as insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] or continuous glucose monitoring, meta-analysis for the purpose of literature summary is inappropriate and may be misleading. Instead, “decision-making meta-analysis” is more appropriate and should involve either preselection of trials based on intended use [e.g., elevated baseline hemoglobin A1c or hypoglycemia rate for trials of multiple daily injections (MDI) versus CSII] or metaregression of summary effect sizes in different trials against potential effect-modifying covariates such as baseline risk, or models of the covariates that determine effect size using individual patient data. Appropriate meta-analysis should also only include trials that are of sufficient duration to accurately measure outcomes such as severe hypoglycemia, and they should not use obsolete technology that is of proven inferiority to current technology. The use of appropriate decision-making meta-analysis is illustrated by the change in the rate ratio for severe hypoglycemia in randomized controlled trials of MDI versus CSII in type 1 diabetes from 1.56 (95% confidence interval 0.96–2.55; p = .074) for literature-summary meta-analysis to 2.0 (1.08–3.69; p = .027) for decision-making meta-analysis of all patients and 3.91 (1.35–11.36; p = .01) for trials in children.     

Indications for insulin pump therapy in different age groups: an analysis of 1,567 children and adolescents.

AIMS: The German working group for pump therapy in paediatric patients has defined seven indications for continuous subcutaneous insulin infusion (CSII): dawn phenomenon, reduction of severe hypoglycaemia, improvement of hyperglycaemia, more flexibility, motivation, failure of injection therapy and pregnancy. In this study we analysed age-specific differences for starting CSII in four age groups (group A: 0-4 years; group B: 5-9 years; group C: 10-14 years; group D: 15-19 years). We also investigated whether glycaemic goals could be reached. METHODS: A total of 1567 children and adolescents (mean age 12.4 years, mean diabetes duration 5.2 years) with documented indications for CSII from the DPV-database (December 2005) were included. RESULTS: Dawn phenomenon (27.4%), reduction of hypoglycaemia (20%) and improvement of hyperglycaemia (18.1%) were the commonest indications for starting CSII. Indications differed by age group (P < 0.0001). In infants and toddlers (group A, n = 138) reduction of hypoglycaemia (42.5%) was the commonest indication. For adolescents (group C, n = 789/group D, n = 408) dawn phenomenon (32.1/21.7%) and flexibility (21.7/25.8%) were the main indications. The rate of severe hypoglycaemia with coma in patients commencing CSII in order to reduce hypoglycaemia fell (12.1/100 patient years before CSII vs. 5.8 after 1 year, 4.49 at study end). Glycated haemoglobin (HbA(1c)) in patients with the treatment goal 'improvement of hyperglycaemia' was lowered significantly in the first year of CSII (HbA(1c) start: 8.8%; after 1 year: 8.5%, P < 0.01) and was stable thereafter (8.8% after 36 months). CONCLUSIONS: CSII in children and adolescents is safe and can reduce the rate of severe hypoglycaemia without deterioration in glycaemic control. In patients with poor glucose control, a significant reduction in HbA(1c) can be achieved in the first year.     

Variation of insulin absorption during subcutaneous and peritoneal infusion in insulin-dependent diabetic patients with unsatisfactory long-term glycaemic response to continuous subcutaneous insulin infusion.

The aim of present study was to analyse the reproducibility of plasma-free insulin profiles of subcutaneously (CSII) and intraperitoneally (CIPII) administered insulin in 6 C-peptide-negative, type 1, diabetic patients. The patients were selected for CIPII because of unsatisfactory, long-term, metabolic response to CSII. Plasma-free insulin was measured repeatedly, twice during subcutaneous infusion and twice during intraperitoneal infusion, for 4 hours, following a standard breakfast. In the CSII experiment, insulin was given as a meal-dose of 0.1 U per kg body weight, and in the CIPII experiment the meal-dose was 0.05 U per kg body weight. The dose-induced peak occurred earlier after the CIPII than with the CSII (60.0 +/- 8.0 vs 133.6 +/- 16.3 min). In conclusion, the intra-patient coefficient of variation (C.V.) of plasma-free-insulin profiles at 0-60 min and 0.240 min, as well as the peak time, were markedly lower for CIPII insulin than for CSII, indicating a more reproducible way of insulin administration with CIPII in this selected group of patients.     

The renaissance of insulin pump treatment in childhood type 1 diabetes

Current goals for the treatment of children and adolescents with type 1 diabetes mellitus include achieving near-normal blood sugar levels, minimizing the risk of hypoglycemia, optimizing quality of life, and preventing or delaying long-term microvascular and macrovascular complications. Continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of all of these goals in all ages of children. In pediatric patients, CSII has been demonstrated to reduce both glycosylated hemoglobin levels and frequency of severe hypoglycemia, without sacrifices in safety, quality of life, or weight gain, particularly in conjunction with the use of new insulin analogs and improvements in pump technology. Clinical studies of safety and efficacy of CSII in children are reviewed, as well as criteria for patient selection and practical considerations using pump therapy in youth with T1DM. Supported by grants from the National Institute of Health (K12 DK063709, T32 DK063703 and RR 00125), the Juvenile Diabetes Research Foundation, and the Stephen I. Morse Pediatric Diabetes Research Fund.     

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2-year perspective using the established criteria for funding from a National Health Service.

AIM: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. METHODS: Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. RESULTS: In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CONCLUSIONS: CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.