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 in type 1 diabetic during pregnancy: case report and literature review

The type 1 diabetic patient pregnancy is subjected to various attempts to obtain good glycemic control, since the pre-conception period throughout the gestation. Continuous subcutaneous insulin infusion (CSII) is a therapeutic tool to achieve the glycemic targets. Here it is presented the case of a Type 1 diabetic woman, who was not under multiple insulin daily injections therapy, and whose insulin therapy started on CSII during the second trimester of gestation, obtaining successful therapeutic outcome.     

Continuous subcutaneous insulin infusion therapy decreases insulin resistance in type 1 diabetes

The influence of continuous sc insulin infusion therapy for 6 weeks on sensitivity to insulin (euglycemic clamp technique) and hepatic glucose production (3-[3H]glucose technique) was measured in 10 type 1 diabetic patients whose mean duration of diabetes was 8 yr. Mean diurnal blood glucose fell from 8.5 +/- 0.8 (SEM) mmol/liter to 6.0 +/- 0.6 mmol/liter (P less than 0.05) and glycosylated hemoglobin from 10.5 +/- 0.4% to 8.7 +/- 0.3%. Insulin requirements declined by 23% from 47 +/- 4 U/day prepump to 36 +/- 2 U/day after 6 weeks of pump therapy (P less than 0.01). During the insulin clamp, plasma insulin was maintained at approximately 90 mU/liter and plasma glucose at approximately 5.0 mmol/liter in all studies. The rate of glucose metabolism in diabetic patients during conventional therapy (4.65 +/- 0.41 mg/kg X min) was 35% lower than in normal subjects (7.20 +/- 0.42 mg/kg X min, n = 14, P less than 0.001). After 6 weeks of pump therapy, total glucose uptake increased by 27% to 5.90 +/- 0.60 mg/kg X min, P less than 0.05 vs. prepump). This was still 18% lower than in the normal subjects (P less than 0.05). Basal hepatic glucose production in the diabetic patients during conventional therapy (3.07 +/- 0.14 mg/kg X min) was 70% higher than in the normal subjects (1.79 +/- 0.07 mg/kg X min, n = 7, P less than 0.001). After 6 weeks of pump therapy, hepatic glucose production fell to 2.48 +/- 0.19 mg/kg X min (P less than 0.05), which was still 40% higher than in the normal subjects (P less than 0.01). Basal hepatic glucose production was directly related to the fasting plasma glucose level (r = 0.67, P less than 0.001) and inversely proportional to fasting insulin concentration (r = -0.48, P less than 0.05) in the diabetic patients. Specific tracer insulin binding to erythrocytes in the diabetic patients (19.4 +/- 1.5%) was comparable to that in the normal subjects (19.6 +/- 1.2%) and remained unchanged during pump therapy. Thus the improved metabolic control resulting from pump therapy is associated with enhancement in sensitivity to insulin, and reduction in basal hepatic glucose production.     

Continuous subcutaneous insulin infusion versus injection therapy: a randomized cross-over trial under usual diabetic clinic conditions

Twelve C-peptide negative insulin-dependent diabetic patients participated in a randomized cross-over study of 6 months treatment with twice or thrice daily insulin injection therapy and continuous subcutaneous insulin infusion (CSII). Standard, non-intensified management conditions were maintained throughout. Glycosylated haemoglobin levels were similar on both regimens (9.2 +/- 0.5% versus 9.0 +/- 0.4%; CSII vs injection therapy; (mean +/- SEM). Capillary blood glucose concentrations before breakfast (5.2 +/- 0.4 mmol/l vs 9.1 +/- 0.8 mmol/l), after lunch (6.5 mmol/l +/- 0.8 vs 7.9 +/- 1.0 mmol/l) and before the evening meal (5.0 +/- 0.7 mmol/l vs 7.7 +/- 0.7 mmol/l) were lower on CSII, as were 24-hour urine glucose excretion and total insulin dose (39.3 +/- 2.2 vs 49.8 +/- 4.0 U/day). There was a significant positive correlation between fasting blood glucose values and glycosylated haemoglobin on injection but not pump treatment. Thus although blood glucose control at some individual daytime points appeared lower on CSII, overall diabetic control was similar on the two regimens.     

Continuous subcutaneous insulin infusion (CSII) versus conventional injection therapy in newly diagnosed diabetic children: two-year follow-up of a randomized, prospective trial

The effect of continuous subcutaneous insulin infusion (CSII), begun at diagnosis, on blood glucose control and endogenous insulin production was studied in a group of consecutively referred newly diagnosed diabetic children. In a random order, 15 children started CSII (age 9.5 +/- 4.2 (+/- SD) years) and 15 conventional injection therapy (age 7.0 +/- 3.6 years). For 2 years HbA1 and urinary C-peptide were measured monthly, C-peptide responses to glucagon 6-monthly, and insulin antibodies every 3 months. None of the patients requested change of therapy during the study period, but at 28 months 1 adolescent girl changed to injection therapy from CSII. Severe hypoglycaemia was observed once in each group, but ketoacidosis only once, in the injection therapy group. From 2 months after diagnosis onwards the CSII group had significantly lower HbA1 levels. Urinary and plasma C-peptide levels did not differ between the two groups and similar insulin doses were used throughout the study. At the end of the 2 years of therapy, the CSII group had significantly lower insulin antibody levels. The observations suggest that CSII is well accepted in newly diagnosed children and improves metabolic control, but does not prolong endogenous insulin production.     

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.     

Behavior of fatty acid patterns in serum lipids in type I diabetic patients in intensive conventional insulin therapy

The relationship between an improvement of the carbohydrate metabolism due to a four-week intensified conventional insulin treatment and changes in fatty acid patterns of serum lipids was investigated in 12 insulin-dependent diabetic patients. At the commencement of the study the diabetic patients were characterized by higher relative linolic acid contents in the serum cholesterolesters and phospholipids in comparison with control subjects. The intensified insulin treatment was associated with a significant improvement of the glycaemic control, whereas the fatty acid patterns of the serum lipids remained unchanged. The results demonstrate that short-time improvement of the carbohydrate metabolism is not associated with qualitative changes of serum lipids in insulin-dependent diabetic patients. Remains to be established the long-term effect of improved metabolic control on fatty acid metabolism.     

Blood glucose control on Sunday in IDDM patients: intensified conventional insulin therapy versus continuous subcutaneous insulin infusion

We have assessed the capacity of continuous subcutaneous insulin infusion (CSII) to maintain good blood glucose metabolic control on Sundays, when waking is delayed, with reference to intensified conventional insulin therapy by multiple daily injections (MDI). The study lasted 3 weeks, including 3 week-ends. A total of 20 IDDM patients were selected for metabolic control: ten were treated by CSII and ten by MDI. Blood glucose was determined at least three times a day (fasting on waking, pre-lunch and pre-dinner). The times of blood glucose determinations and their values were recorded in a memory reflectance meter. Waking, the first blood glucose measurement and the first insulin injection (MDI) or bolus (CSII) were about 1 h later on Sundays than on a weekday (44±4 min in MDI group, P<0.04; and 59±7 min in CSII group, P<0.02). The times of the pre-lunch and pre-dinner blood glucose determinations were not significantly different. The mean waking and pre-lunch blood glucose values of the MDI group were higher on Sundays (11.5±3.8 and 9.7±4.5 mmol/l) than on weekdays (8.7±2.3 and 7.1±2.5 mmol/l)(P<0.01). The pre-prandial blood glucose levels of the CSII group on Sundays and weekdays were not statistically different at any time. Changes in the waking time and the subsequent delay in the first insulin bolus on Sunday may alter blood glucose control in patients on MDI, but CSII allows such changes without any glycemic side effects.     

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 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.     

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.     

住院2型糖尿病患者胰岛素泵的合理应用

目的 探讨短期胰岛素泵强化治疗对2型糖尿病住院患者的应用方法,分析影响疗效及胰岛素用量的相关因素.方法 对1 276例2型糖尿病患者行胰岛素泵强化治疗,观察总体胰岛素泵应用情况,在初诊、老年伴肥胖或感染等特殊情况下胰岛素泵应用上的差别.结果 胰岛素强化治疗后总体血糖在(5.7±2.6)d达标,达标时单位胰岛素用量为(0.69±0.31)U·kg-1·d-1;初诊组达标较快,达标后胰岛素减量更早,幅度更大,达到临床缓解的比例更高;老年组夜间基础率较低,且夜间低血糖发生的风险较大;伴肥胖组餐前胰岛素用量较大,但低血糖风险较低;伴感染组胰岛素用量较大,主要是基础率明显增加;血糖达标天数和胰岛素用量主要与感染、基础血糖及肥胖显著相关.结论 对不同人群的连续皮下胰岛素输注应用方法存在着差别,患者的感染、基础血糖和肥胖指标有助于确定初始胰岛素用量.     

Sexual activity in diabetic patients treated by continuous subcutaneous insulin infusion therapy

Background and aimsAs concerns over interference with sexual activity may be an obstacle to initiating pump therapy in diabetic patients, the aim of the study was to assess the impact of continuous subcutaneous insulin infusion (CSII) therapy on sexual activity.Patients and methodsPatients filled out a questionnaire on their demographic data, diabetes history, pump-treatment history, metabolic control, inconvenience/convenience of the pump and catheter, and information on sexual activity.ResultsA total of 271 diabetic patients (aged 44 ± 17 years, 51% women, 22% single), treated with CSII for 4.2 ± 5.9 years and with a diabetes duration of 19 ± 11 years, filled out the questionnaire. Their HbA_1c was 7.7 ± 1.1%, with 2.4 ± 2.1 mild hypoglycaemic episodes over the past week, and their frequency of sexual activity was: never 29.9%; < 1/month 12.3%; > 1/month and < 1/week 18.2%; and > 1/week 39.6%. Age and cohabitation were independently correlated with frequency of sexual activity (P < 0.0001 and P < 0.0003, respectively), but not diabetes duration or complications. To the question “Does the pump have an influence on your sexual activity?”, The answer was “no” in 90% and “yes” in 10%. However, intercourse frequency was significantly decreased in the latter (P = 0.04). On multivariate analyses, this negative influence of CSII was correlated with HbA_1c (P < 0.05), discomfort with the pump (P < 0.05) and the number of mild hypoglycaemic episodes (P < 0.01).ConclusionFrequency of sexual activity appears to be unaffected by pump therapy or diabetes, but is decreased by the expected characteristics–namely, age and being single. Also, only 10% of patients believe that CSII is an obstacle during sexual activity and, in particular, because of the catheter.     

Outcome of pregnancy in women with type 1 diabetes intensively treated with continuous subcutaneous insulin infusion or conventional therapy. A case-control study

The aim was to evaluate and compare the outcome of pregnancies of women with type 1 diabetes (T1D) intensively treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Twenty-nine women with T1D receiving CSII during pregnancy as intensive insulin therapy (27 started CSII during pregnancy planning while 2 started CSII during the 1st month of gestation) were matched for age, duration of T1D, White's classification, BMI before gestation, parity and HbA1c before pregnancy with 29 women treated with MDI. Metabolic control and acute complications were registered including ketoacidosis and severe hypoglycaemic episodes, and the development of hypertension induced by pregnancy and pre-eclampsia. Perinatal mortality, stillbirth, minor and major congenital malformations, macrosomia, weeks at delivery, caesarean section and perinatal complications were also recorded. As expected, there were no differences between the two groups in terms of age, duration of the disease, White's classification, BMI before gestation, parity and HbA1c before pregnancy. The proportion of subjects who received preconceptional guidance and planned pregnancy did not differ between groups. No differences were observed in HbA1c, insulin dose and BMI throughout gestation in either group of patients. Maternal, foetal and perinatal outcome were similar in women treated with CSII or MDI. The use of CSII in pregestational T1D women is associated with similar results in metabolic control, maternal, foetal and perinatal outcome during pregnancy to those obtained using MDI.     

A 2-year pilot trial of continuous subcutaneous insulin infusion versus intensive insulin therapy in patients with newly diagnosed type 1 diabetes (IMDIAB 8)

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.     

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.