Continuous subcutaneous insulin infusion (CSII) in children with type 1 diabetes

Recent studies have shown that continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, provides a treatment option that can assist in the attainment of current goals of treatment in children and adolescents with type 1 diabetes (T1DM). 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 excessive 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.     

Continuous subcutaneous insulin infusion in patients with diabetes mellitus

During the last quarter of a century continuous subcutaneous insulin infusion (CSII) with external portable insulin pumps has been increasingly used in selected type 1 diabetic subjects and also in some patients with type 2 diabetes mellitus. The treatment of diabetes mellitus with insulin pumps has become more and more popular and accepted by diabetic patients as well as by medical professionals worldwide. Published trials have shown that, in most patients, mean blood glucose concentration and glycated hemoglobin (HbA1c) percentages are either slightly lower or similar on CSII versus an optimized therapy with multiple daily insulin injections. Hypoglycemic episodes seem to be less frequent and ketoacidoses occur at a comparable rate to that during intensive injection therapy. Moreover, nocturnal glycemic control can be improved with insulin pumps, and automatic basal rate changes help to minimize a prebreakfast blood glucose increase (often called 'the dawn phenomenon'). For many patients, CSII provides greater flexibility in timing of meals with the result of better quality of life and higher treatment satisfaction. However, despite these promising data, and although many patients with diabetes mellitus with well-defined clinical problems are likely to benefit substantially from CSII, either in respect to glycemic control, acute complications or quality of life and treatment satisfaction, we are still far away from reaching'dream diabetes management', the fully automatic closed-loop system. Presently, the most difficult problem concerns not the design of an 'optimal' insulin pump, but rather the development of a system which is able to provide continuous and reliable blood glucose monitoring. Hence, because this problem has not been solved with maximum satisfaction, the development of a feedback-controlled 'artificial pancreas' is one of the main goals in diabetes management in the new millennium.     

Continuous subcutaneous insulin infusion versus intensive conventional insulin therapy in type I and type II diabetic pregnancy

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.     

Continuous subcutaneous insulin infusion allows tolerance induction and diabetes treatment in a type 1 diabetic child with insulin allergy

AimInsulin allergy is a rare but serious and challenging condition in patients with type 1 diabetes (T1D). This is a case report of an 8-year-old boy with T1D and an allergy to insulin.Case reportThree months after being diagnosed with T1D, the patient developed progressive skin reactions to insulin, characterized by small 1.5-cm pruritic wheals at injection sites that persisted for several days. Seven months after diagnosis, he experienced two episodes of generalized urticaria with systemic symptoms that were seen within a few seconds of insulin injection. Examination revealed lipoatrophy of the thighs. Intradermal skin tests were positive for protamine, glargine and lispro. The patient was started on a continuous subcutaneous insulin infusion (CSII) tolerance induction protocol, consisting of a very low basal rate that was progressively increased, with the first bolus given under medical supervision, and was well tolerated for 4 months. After this period of time, the skin wheals reappeared, localized to the infusion sites, but without urticaria or any other generalized reactions. Intradermal skin tests were repeated and were again positive. Serum insulin-specific IgE measured 30 months after the first allergic reactions were positive. After 3 years, pump therapy is ongoing and blood glucose control has remained relatively good (HbA_1c 7.6%).ConclusionIn T1D children with insulin allergy, CSII can successfully be used to both induce insulin tolerance and allow diabetes insulin therapy, although insulin desensitization cannot always be fully achieved. The induction protocol was easily manageable partly due to the “honeymoon” period that the patient was still in, but it should nonetheless be used even when the patient has higher insulin requirements.     

Continuous insulin infusion therapy and retinopathy in patients with type I diabetes

The effect of continuous subcutaneous insulin infusion (CSII) and conventional injection therapy (CIT) on retinopathy was evaluated in a 1-year crossover study (6 + 6 months) with 54 type I diabetic patients. The glycaemic control improved significantly but did not reach euglycaemic levels during CSII (P less than 0.01-0.001), whereas no change was observed during CIT. At baseline, 50% of the patients had no retinopathy, 20% had only minimal changes, 26% had moderate background retinopathy, and 2 patients had proliferative changes. During CSII, the retinopathy grade impaired in 7 patients, whereas no deterioration occurred during CIT. Improvement of retinopathy grading was observed in 2 patients during CSII and in 5 during CIT, respectively. Individual retinal lesions also progressed more and improved less during CSII (12:3) as compared with CIT (10:9). The net impairment in both retinopathy grading and individual lesions was significant during CSII as compared with CIT (P less than 0.05). There was no difference in the baseline characteristics (severity of retinopathy, age, sex, duration of diabetes, insulin dose, blood pressure, serum creatinine), in the fall of glycosylated haemoglobin or number of hypoglycaemic episodes between the patients with and without worsening of retinopathy during CSII. The present study suggests that even a moderate improvement in metabolic control induced by CSII may be associated with a risk of progression of retinopathy during the first months of therapy.     

Continuous subcutaneous insulin infusion in children

Insulin-dependent diabetes mellitus usually presents in childhood. Since it i is generally accepted that persisting metabolic derangements contribute to the development of micro- and macrovascular complications, a primary aim of the management of children with diabetes is to achieve near normalization of metabolism. In adults continuous subcutaneous insulin infusion (CSII) has been used to optimize control. Despite a reluctance amongst paediatricians to use CSII in children, several studies with pumps have been performed in adolescents. The results of these studies are contradictory with respect to acceptability and achieved metabolic control. Thus, some authors report a near normalization of blood glucose concentrations, whereas others only find a temporary improvement. Patient selection seems to account for many of these differences. This suggests that methods ought to be developed to predict success or failure of CSII in a particular adolescent patient. For diabetic toddlers with their age-specific problems CSII may be a therapy of choice. So far, good acceptability and improved metabolic control are reported in this group. More studies are needed to confirm this. It is important that the diabetic clinic as well as the patient is organized to high standard before starting CSII. Home blood glucose measurements, education, and a 24-h telephone service are essential factors for the management of diabetic children, treated conventionally or with CSII.     

Continuous subcutaneous insulin infusion: a comprehensive review of insulin pump therapy

A tremendous amount of data suggest that near-normal glycemic control prevents or delays complications of diabetes, which has led to a dramatic increase in continuous subcutaneous insulin infusion (CSII) or insulin pump use. In this article, the data supporting CSII in type 1 diabetes is reviewed, and the advantages and disadvantages of CSII are analyzed. In addition, CSII use in specific situations is examined, including during childhood and pregnancy and while exercising. The published articles suggest that CSII provides better glycemic control than does conventional therapy and comparable to or slightly better control than multiple daily injections. The use of CSII may be especially indicated during pregnancy or for preconception care and for diabetes presenting in childhood or adolescence.     

Meta-analysis of short-acting insulin analogues in adult patients with type 1 diabetes: continuous subcutaneous insulin infusion versus injection therapy

Aims/hypothesis This study aimed to compare the effect of treatment with short-acting insulin (SAI) analogues versus structurally unchanged short-acting insulin (regular insulin) on glycaemic control and on the risk of hypoglycaemic episodes in type 1 diabetic patients using different insulin treatment strategies.Methods We performed a meta-analysis of 27 randomised controlled trials that compared the effect of SAI analogues with regular insulin in patients with type 1 diabetes mellitus. The treatments were administered either via continuous subcutaneous insulin infusion (CSII) or by conventional intensified insulin therapy (IIT) with short-acting insulin injections before meals and basal insulin administered once or twice daily in most cases.Results HbA₁c levels were reported for 20 studies. For studies using CSII, the weighted mean difference between values obtained using SAI analogues and regular insulin was –0.19% (95% CI: –0.27 to –0.12), whereas the corresponding value for injection studies was –0.08% (95% CI: –0.15 to –0.02). For the analysis of overall hypoglycaemia, we used the results from nine studies that reported the mean frequency of hypoglycaemic episodes per patient per month. For studies using CSII, the standardised mean difference between SAI analogues and regular insulin was –0.07 (95% CI: –0.43 to 0.28), whereas for IIT studies the corresponding value was –0.04 (95% CI: –0.24 to 0.16).Conclusions/interpretation Taking into consideration the low quality of the trials included, we can conclude that use of a short-acting insulin analogue in CSII therapy provides a small, but statistically significant improvement in glycaemic control compared with regular insulin. An even smaller effect was obtained with the use of ITT. The rate of overall hypoglycaemic episodes was not significantly reduced with short-acting insulin analogues in either injection regimen.Conflict of interest statement: A. Siebenhofer, J. Plank, K. Horvath, T.R. Pieber performed clinical trials on short- and long-acting insulin analogues with the companies Aventis, Eli Lilly and Novo Nordisk. T.R. Pieber was or is a currently paid consultant for these companies. T.R. Pieber is on the advisory board of Novo Nordisk.     

Continuous subcutaneous insulin infusion during pregnancy

The development of battery-powered pumps for continuous subcutaneous insulin infusion added new dimensions to control of diabetes during pregnancy. In this report, we describe our experiences with 28 pregnant diabetic women offered participation in an insulin pump program. Fifteen (54%) accepted pump therapy and ten continued usage during their pregnancies. Excluding abortions, eight women continuing pump use are compared to 11 others who declined such therapy and were treated with conventional methods. Although these two groups are small and not strictly comparable, the experiences now reported provide clinical insights into the application of this new technology during pregnancy. Women who successfully used insulin pumps were typically from the private sector and in better glucose control at study entry. The degree of control during pregnancy in women using pumps was not significantly different compared to conventional glucose control methods (mean glucose 120 mg/dl and 142 mg/dl, respectively). Similarly, several indices of pregnancy outcome including length of hospitalization, costs, and perinatal morbidity associated with diabetes were analyzed and no significant differences were observed. We conclude that insulin pumps are not acceptable to all pregnant diabetic women and that such therapy may not necessarily improve pregnancy outcome.     

Continuous subcutaneous insulin infusion therapy: effects on quality of life

OBJECTIVE: To compare the diabetes-specific quality of life in subjects with type 1 diabetes treating their diabetes with multiple daily injections (MDI) to that of subjects on continuous subcutaneous insulin infusion (CSII). METHODS: Diabetes-specific quality of life was measured with the DSQOLS-Questionnaire in 81 adult subjects with type 1 diabetes on MDI and 78 subjects on CSII (cross-sectional study). In addition, 19 subjects were followed prospectively, measuring their quality of life before and after switching from MDI to CSII (longitudinal study). RESULTS: Preference-weighted treatment satisfaction score was significantly higher in subjects on CSII than in those on MDI in both the longitudinal (+63 points, 95%CI 37-89) and the cross-sectional study (+14 points, 95%CI 3 to 25). "Diet restrictions" were significantly less of a burden for CSII subjects in both the longitudinal (+6 points, 95%CI 1-10) and the cross-sectional study (+3 points, 95%CI 0 to 6). "Leisure time flexibility" (+3 points, 95%CI 0 to 7), "Physical complaints" (+4 points, 95%CI 1 to 8), "Daily hassles" (+4, 95%CI 0 to 7), and the overall quality of life (+29 points, 95%CI 3 to 54) were significantly better in CSII compared to MDI only in the longitudinal study. Despite a small overall rate of severe hypoglycaemia in both studies, subjects on CSII experienced fewer severe episodes than subjects on MDI. CONCLUSIONS: Subjects with type 1 diabetes on CSII have a better quality of life than type 1 diabetic subjects on MDI. They are more satisfied with their treatment in respect to their metabolic goals as well as psychosocial factors, physical performance and protection from long-term complications and hypoglycaemia. Furthermore, the subjects on CSII experience greater flexibility in their daily routines, leisure time and diet than the subjects on MDI.     

胰岛素泵治疗儿童1型糖尿病疗效观察

目的 观察胰岛素泵持续皮下输注短效胰岛素(CSII)对儿童1型糖尿病(T1DM)的治疗效果。方法 ①胰岛素泵持续皮下输注CSII治疗6例传统胰岛素治疗(CIT)血糖控制不满意的TDM患儿。并比较其用泵前后空腹血糖(FBG)、餐后2小时血糖(2hPBG)、糖化血红蛋白(HbAk)、胰岛素(INS)用量、胆固醇(CH)及甘油三酯(FG)的变化；②治疗组用泵后上述代谢指标与33例正常对照组比较。结果 ①治疗组用泵后FBG、2hPBG、HbAk、INS用量、TG均较用泵前显著降低；用泵后INS用量减少16％；用泵后患儿依从性增高。②治疗组用泵后FBG、CH及TG均较正常对照组无差异，2hPBG、HbAk仍显著高于正常对照，但均达到强化治疗目的。结论 ①CSII治疗儿童TDM可显著改善其代谢指标，使血糖和血脂降至正常和接近正常。②CSII治疗儿童通过改善HbAk及血脂TDM，可延缓其慢性并发症的发生。     

胰岛素泵治疗2型糖尿病疗效研究

目的观察胰岛素泵连续皮下注射胰岛素(CSII)治疗2型糖尿病、减少低血糖反应、改善生活质量的效果.方法对血糖控制不良,需要住院使用或调整胰岛素治疗的2型糖尿病26例患者,随机分为CSII组(12例)和常规多次皮下注射胰岛素(MSII)组(14例) 进行强化胰岛素治疗.结果两组均达到目标血糖值,但CSII组血糖控制时间显著少于MSII组(P＜0.05),且胰岛素用量少于MSII组,低血糖发生率较低,能较有效地控制黎明现象发生.结论胰岛素泵治疗糖尿病快速、安全、方便,是难治性2型糖尿病患者理想的强化治疗方案.