初诊与非初诊2型糖尿病患者胰岛素泵的应用

目的探讨短期持续皮下胰岛素输注（CSⅡ）对明显高血糖的初诊和非初诊2型糖尿病（T2DM）患者的应用方法。方法T2DM患者1276例,其中初诊组479例,非初诊组797例,观察两组血糖达标时间、胰岛素用量、低血糖的发生率及其相关因素。结果CSⅡ治疗使初诊和非初诊糖尿病患者血糖达标时间分别为4．76±2．56天和5．87±2．69天,初诊组达标较快（P〈0．05）,两组胰岛素用量相似,平均每天0．69±0．31U／kg,基础用量占全天用量的61％,但初诊组达标后胰岛素减量较早,降幅较大（P〈0．05）;两组低血糖的发生率相差不多（P〉0．05）。结论CSII治疗于高糖急性期的初诊和非初诊患者都能迅速减轻胰岛素抵抗,改善B细胞功能。     

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.     

Short-term subcutaneous insulin infusion in diabetic children. Comparison with three daily insulin injections

Summary Sixteen insulin-dependent diabetic children and adolescents were studied on intenisifed insulin treatment (3II) and during continuous subcutaneous insulin infusion (CSII). Mean blood glucose, M-value and 24-h glycosuria were similar in both types of treatment. Symptomatic hypoglycemia occurred more often in patients on 3II than CSII. With 3II we observed blood glucose peaks early in the morning confirming that better overnight control can be achieved by CSII. Supported byConsiglio Nazionale delle Ricerche, Grant No. 80.00410.     

A nationwide study of continuous subcutaneous insulin infusion (CSII) in Denmark.

AIMS: To record the number of patients treated with continuous subcutaneous insulin infusion (CSII), the attitude to CSII treatment among diabetes care providers and the characteristics of pump users in Denmark. METHODS: A questionnaire was mailed to all departments of endocrinology, internal medicine and paediatrics in Denmark (n = 73) to determine the number of diabetic patients treated with CSII and the attitudes of chief consultants to it. All patients using CSII were identified and data from their records collected. RESULTS: Primarily Type 1 diabetic patients (n = 142) were treated with CSII, approx. 0.5% of patients in Denmark. The explanations given for this low frequency varied for non-CSII and CSII-using diabetologists. Both found lack of funding important. In addition, the non-CSII-using group had a perception that CSII was dangerous. The CSII-using diabetologists found that no more patients were interested and that it did not significantly improve metabolic control. The mean age of pump users was 48.1 +/- 10.5 years and the mean time wearing a pump 14.1 +/- 6.3 years. Mean HbA1c was 7.9 +/- 1.2% during CSII, with a significant difference among the 15 centres (P < 0.05) and a tendency to be lower in females (P = 0.07). CONCLUSIONS: CSII is infrequently used in Denmark despite pump users showing reasonably good metabolic control. The most common explanations for these low figures are lack of expertise and funding for CSII. If more patients in Denmark were to be offered pumps, education of healthcare providers would be needed and the funding would have to be clarified.     

Diurnal variation of carbohydrate insulin ratio in adult type 1 diabetic patients treated with continuous subcutaneous insulin infusion

To estimate the carbohydrate‐to‐insulin ratio (CIR), a formula dividing a constant, usually 300–500, by the total daily dose (TDD) of insulin, is widely utilized. An appropriate CIR varies for each meal of the day, however. Here, we investigate diurnal variation of CIR in hospitalized Japanese type 1 diabetic patients treated with continuous subcutaneous insulin infusion. After optimization of the insulin dose, TDD and total basal insulin dose (TBD) were 34.9 ± 10.2 and 9.3 ± 2.8 units, respectively, with a percentage of TBD to TDD of 27.3 ± 6.0%. The products of CIR and TDD at breakfast, lunch and dinner were 311 ± 63, 530 ± 161, and 396 ± 63, respectively, suggesting that in the formula estimating CIR using TDD, the constant should vary for each meal of the day, and that 300, 500, and 400 are appropriate for breakfast, lunch, and dinner, respectively.     

Improvement of cardiovascular risk factors in patients with type 2 diabetes after long-term continuous subcutaneous insulin infusion

BACKGROUND: The effects of long-term continuous subcutaneous insulin infusion (CSII) on cardiovascular risk factors such as hyperglycaemia, dyslipidaemia, and proinflammatory cytokine levels have not been assessed so far in type 2 diabetes. METHODS: We analysed the levels of HbA(1c), serum lipids, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) at 0, 2, and 30 weeks after CSII in 15 patients with type 2 diabetes (mean age, 53.3+/-10.1 years; disease duration, 9.4+/-5.3 years) without previous history of major cardiovascular events. RESULTS: At week 30, CSII significantly lowered HbA(1c) by 5.0+/-0.9% compared to baseline (7.9+/-1.9%, p<0.001) and improved high-density lipoprotein cholesterol (HDLc; 1.09+/-0.16 at baseline vs 1.25+/-0.15 mmol/L at week 30; p<0.05) and low-density lipoprotein cholesterol (LDLc)/HDLc ratios (2.8+/-1.4 at baseline vs 2.2+/-0.9 at week 30; p<0.05). CSII also decreased the proportion of patients with dyslipidaemia at week 30. At baseline, TNF-alpha and IL-6 levels were up-regulated (2.65+/-4.04 and 2.82+/-1.81 pg/mL, respectively) compared to the normal control (p<0.01 and p<0.05, respectively); however, cytokine levels decreased significantly at week 30 (1.44+/-2.25 and 1.99+/-1.05 pg/mL, respectively; p=NS vs control). CONCLUSIONS: Long-term CSII alone decreased cardiovascular risk factors in poorly controlled type 2 diabetes, suggesting that the synchronization of sufficient insulin peaks with meal ingestion and continuous pulsatile infusion of basal insulin corrects metabolic derangements.     

Effect of carbohydrate counting using bolus calculators on glycemic control in type 1 diabetes patients during continuous subcutaneous insulin infusion

The present study examined the long‐term efficacy of insulin pump therapy for type 1 diabetes patients when carried out using carbohydrate counting with bolus calculators for 1 year. A total of 22 type 1 diabetes patients who had just started continuous subcutaneous insulin infusion were examined and divided into two groups: one that was educated about carbohydrate counting using bolus calculators (n = 14); and another that did not use bolus calculators (n = 8). After 1 year, the hemoglobin A1c levels of the patient group that used bolus calculators decreased persistently and significantly (P = 0.0297), whereas those of the other group did not. The bodyweight, total daily dose of insulin and bolus percentage of both groups did not change. Carbohydrate counting using bolus calculators is necessary to achieve optimal and persistent glycemic control in patients undergoing continuous subcutaneous insulin infusion.     

Metabolic control and complications in Italian people with diabetes treated with continuous subcutaneous insulin infusion

Background and aim

The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII).

Continuous subcutaneous insulin infusion (CSII) 30 years later: still the best option for insulin therapy

Thirty years after its introduction, the use of continuous subcutaneous insulin infusion (CSII) keeps increasing, especially among children and adolescents. The technique, when used properly, is safe and effective. Compared with traditional NPH‐based multiple daily injections (MDI), CSII provides a small but clinically important reduction of HbA_1c levels, diminishes blood glucose variability, decreases severe hypoglycaemic episodes and offers a better way to cope with the dawn phenomenon. Insulin analogues have improved the treatment of diabetes, eroding part of the place previously occupied by CSII, but CSII still remains the first option for patients experiencing severe hypoglycaemic episodes, high HbA_1c values or marked glucose variability while being treated with optimized MDI. Furthermore CSII is better than MDI considering the effects on quality of life and the possibility to adjust insulin administration according to physical activity or food intake. CSII may be limited by cost. Present estimates suggest that CSII may be cost‐effective just for patients experiencing a marked improvement in HbA_1c or a decrease in severe hypoglycaemic episodes, but the effects on quality of life are difficult to measure. CSII does not merely imply wearing an external device; it requires a multidisciplinary team, intensive patient education and continuous follow up. Copyright © 2009 John Wiley & Sons, Ltd.     

An observational study comparing continuous subcutaneous insulin infusion (CSII) and insulin glargine in children with type 1 diabetes

OBJECTIVE: The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. RESEARCH DESIGN AND METHODS: We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. RESULTS: At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 +/- 1.8 to 7.4 +/- 1.1% and to 7.6 +/- 1.2%, respectively. The insulin requirement significantly decreased from 0.93 +/- 0.2 IU/kg to 0.73 +/- 0.2 IU/kg of body weight and to 0.74 +/- 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 +/- 1.7 to 8.3 +/- 0.9% (not significant) in the first 6 months of treatment and to 8.2 +/- 0.9% after 12 months. CONCLUSION: The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control.     

Altered recognition of hypoglycaemic symptoms in type I diabetes during intensified control with continuous subcutaneous insulin infusion

The effect of intensified metabolic control obtained with continuous subcutaneous insulin infusion (CSII) on the frequency and symptoms of hypoglycaemia was studied in type I diabetic patients. The reproducibility of the questionnaire used to evaluate the hypoglycaemic symptoms was verified in a control group receiving unchanged conventional insulin therapy for 2 months. Metabolic control was significantly improved during CSII (HbA1c 6.8 +/- 0.4% versus 8.7 +/- 0.7%, normal range up to 5.4%) in all patients while no change was seen in the control group. The results of frequent self glucose monitoring showed that the incidence of low glucose levels (below 3.5 mmol/l) increased about threefold in the CSII group. Awareness of hypoglycaemia was clearly changed during CSII with less pronounced adrenergic symptoms while no alterations were found in the group with unchanged metabolic control. These results emphasize the importance of regular self glucose monitoring during CSII and of informing the patients that their hypoglycaemic symptoms may change during intensified control.     

Continuous subcutaneous insulin infusion (CSII) in the Veneto region: efficacy,acceptability and quality of life

Aim To study the effect of continuous subcutaneous insulin infusion (CSII) on metabolic control and well‐being in patients with Type 1 diabetes. Methods Efficacy, safety and interference with everyday life associated with CSII were studied retrospectively in 138 diabetic patients from the Veneto region treated for 7.4 ± 0.4 years. Results Glycosylated haemoglobin decreased during the first year of CSII from 9.3 ± 0.2% to 7.9 ± 0.1% (P < 0.0001), and then remained unchanged. Serious hypoglycaemia decreased from 0.31 ± 0.07/year to 0.09 ± 0.02/year (P < 0.003), as did ketoacidosis (from 0.41 ± 0.12/year to 0.11 ± 0.03/year, P < 0.013). During the first year of therapy daily insulin requirement decreased from 49 ± 1 to 42 ± 2 U/day (P < 0.0001) and did not change thereafter. The number of out‐patient consultations and hospital admissions per year also decreased significantly. CSII was associated with a progressive increase of body weight (P < 0.05) and with 0.2 ± 0.04 infections/patient per year at the infusion site. Infection was rated as mild in 72%, moderate in 18%, severe in 10%. Patients reported that CSII improved metabolic control (71%), sense of well‐being (41%), and allowed more freedom (40%). Quality of life, assessed using the DQOL, after 7 years of CSII was rated as good by patients (score of 73.0 ± 1.8 on a scale from 0 to 100). Conclusions This retrospective analysis suggests that CSII improves metabolic control in Type 1 diabetic patients, reduces hypoglycaemic and ketoacidotic events, is well accepted, allows a good quality of life and decreases out‐patient consultations and hospital admissions.     

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.     

甘精胰岛素与双相门冬胰岛素用于初诊2型糖尿病患者胰岛素泵治疗后的疗效比较

目的比较甘精胰岛素（来得时）和双相门冬胰岛素（诺和锐30）皮下注射应用于初诊T2DM短期持续皮下胰岛素输注（CSII）治疗后的疗效。方法60例初诊T2DM患者应用CSII治疗后,随机分为以诺和锐30治疗的BIAsp30组和以来得时治疗的Lantus组。比较两组7个时点血糖、HbA1c、低血糖事件及其他不良事件的差异。结果与BIAsp30组相比,Lantus组20周后三餐后血糖水平明显降低,低血糖事件发生次数低（P均〈0．05）;两组FPG、HbA1c及不良事件差异无统计学意义（P均〉0．05）。结论初诊T2DM患者CSII治疗所用Ins剂量相同且血糖达标后,采用来得时睡前1次注射,比早、晚餐前诺和锐30皮下注射治疗者全天血糖控制满意,且低血糖事件发生率低。     

A 6-hour nocturnal interruption of a continuous subcutaneous insulin infusion: 1. Metabolic and hormonal consequences and scheme for a prompt return to adequate control

Summary Interruption of a continuous subcutaneous insulin infusion, most often due to technical problems occurring during the night, is a not uncommon event whose metabolic consequences have received relatively little attention until now. We have therefore investigated the changes in blood glucose, plasma non-esterified fatty acids, 3-hydroxybutyrate, glucagon and free insulin in eight C-peptide negative Type 1 diabetic patients whose pumps were deliberately stopped between 23.00 h and 05.00 h. A control test with the pump functioning normally was carried out in each patient and the studies were randomized. Considering the values at 23.00 h as reference, interruption of the insulin infusion resulted in (1) a rapid decrease in plasma free insulin significant after 1 h and reaching a nadir of 6±2 mU/l after 6 h; (2) a rise in blood glucose which was significant at hour 3 and reached 17.4±1.9 mmol/l at hour 6; (3) a moderate increase in plasma non-esterified fatty acids which remained in the range of 700–800 mol/l; (4) an early and linear rise in plasma 3-hydroxybutyrate, significant after 1 h and averaging 1290±140 mol/l after 6 h; (5) a late increase (hour 5) in plasma glucagon. The second aim of our study was to provide for the patient a precise scheme of insulin supplements administered via the pump and based on blood glucose monitoring (Dextrostix — Glucometer) and semi-quantitative evaluation of ketonuria (Acetest). Resetting the pump at its basal rate at 05.00h and giving insulin supplements (2–8 U) at 06.45 h (with the usual breakfast dose) and again at 10.00 h have proved efficacious in restoring satisfactory metabolic control by noon the day after starting the experiment. These results form practical recommendations to patients undergoing this type of accident.     

Serum levels of insulin-like growth factor (IGF) I, II and IGF binding protein in diabetic adolescents treated with continuous subcutaneous insulin infusion

IGF-I and IGF-II as well as the low molecular type of IGF binding protein (IGFPB) were determined in serum from 11 adolescents with insulin-dependent diabetes mellitus (IDDM) during a cross-over study with conventional and continuous subcutaneous insulin infusion (CIT and CSII) therapy. At the onset of the study the mean IGF-I level, 127 +/- 15 ng ml-1, was significantly decreased (P less than 0.001) in comparison with age-matched controls, whereas the mean IGF-II level, 1024 +/- 48 ng ml-1, was increased. A significant correlation (r = 0.70, P less than 0.05) was found between IGF-II and HbA1c levels. The mean morning level of IGFBP, 75 +/- 17 ng ml-1, at the onset of the study, was increased threefold above that in age-matched controls (P less than 0.01). There was a significant correlation between IGFBP and blood glucose values (r = 0.66, P less than 0.05). During CSII therapy a significant decrease (P less than 0.05) of the IGFBP levels was seen in subjects with a decrease in glucose levels, whereas no change was observed in IGF levels. The findings of elevated IGF-II and IGFBP levels and correlations between IGFBP and blood glucose concentration as well as IGF-II and HbA1c levels in adolescents with IDDM indicate that both IGF-II and IGFBP reflect a deranged metabolism caused by inadequate insulin administration.     

Optimization of basal insulin delivery in Type 1 diabetes: a retrospective study on the use of continuous subcutaneous insulin infusion and insulin glargine.

AIMS: To compare the effects on glycaemic control after using continuous subcutaneous insulin infusion (CSII) or insulin glargine. METHODS: Data were obtained from 17 diabetes outpatient clinics in Sweden, employing the same diabetes data management system. Type 1 diabetic patients using multiple dose injections were included prior to starting on either CSII (n = 563) or glargine (n = 513). The median duration of therapy was 25 months for CSII and 6 months for glargine. The comparison between the treatment modalities was carried out by multiple regression analysis and logistic regression analysis in an attempt at reducing the influence of confounding factors. RESULTS: The mean HbA1c decrease was 0.59 +/- 1.19% for CSII and 0.20 +/- 1.07% for glargine (P < 0.001, when assessed by logistic regression). An additional 0.1% lower HbA1c would be expected if glargine had been optimized with basal insulin 40-60% of the daily dose. The more pronounced effect of CSII was achieved with a lower daily dosage of insulin. In a multiple regression analysis with a change of HbA1c as the dependent variable, the following variables were significant: choice of treatment (P < 0.001), HbA1c prior to treatment (P < 0.001) and BMI prior to treatment (P < 0.01). CONCLUSION: Both regimes improved metabolic control, but CSII resulted in significantly higher reduction in HbA1c than after insulin glargine treatment, particularly in those individuals who had higher levels of HbA1c at baseline.     

Absence of exercise-induced hypoglycaemia in Type I (insulin-dependent) diabetic patients during maintenance of normoglycaemia by short-term,open-loop insulin infusion

Summary To assess the risk and possible mechanisms of hypoglycaemia during moderate exercise in Type I (insulin-dependent) diabetic patients receiving constant insulin infusion, five insulin-dependent male diabetic patients were exercised 18 h after their last meal and 30 h after their last injection of intermediate acting insulin. Intravenous insulin was initially delivered via a closed-loop infusion system programmed to lower mean blood glucose from 11.3 ± 1.8 to 4.8 ± 0.4 mmol/l over approximately 3.5 h. Blood glucose was then maintained at this level for 4 h. At this time, the closed-loop infusion was discontinued and replaced by an open-loop system. The average amount of insulin infused per min during the 4 h normoglycaemic closed-loop period was calculated and this amount was infused at a constant rate during both a 30 min period of exercise on a bicycle ergometer (approximately 65% maximum oxygen uptake) and a 30 min rest period which followed. Five nondiabetic males served as control subjects. Despite significantly higher free insulin concentrations (p < 0.05) and identical preexercise blood glucose concentrations, blood glucose rose during exercise only in the diabetic group (0.5 ± 0.2 mmol/l; p < 0.01). Changes in the serum concentrations of lactate, glycerol, glucagon, cortisol, non-esterified fatty acids and growth hormone were similar in the two groups and did not account for the increment of blood glucose in the diabetic patients. Beta-hydroxybutyrate concentrations were, however, higher in the diabetic patients at the onset of exercise (p < 0.01) and decreased significantly more than the control subjects during exercise. We conclude that exercise under these conditions in diabetic patients is not attended by hypoglycaemia.     

The effect of six months continuous subcutaneous insulin infusion on kidney function and size in insulin-dependent diabetics

Glomerular filtration rate (GFR), renal plasma flow (RPF), kidney volume, and urinary albumin excretion rate were measured in 24 insulin-dependent diabetics, aged 29 +/- 7 years (mean +/- S.D.) of 8 +/- 4 years duration, randomly allocated to either continuous subcutaneous insulin infusion (CSII) (n = 12) or unchanged conventional insulin treatment (CIT) (n = 12). Glomerular filtration rate, renal plasma flow, and kidney volume were identical in the two groups at the start of the study, although significantly increased above normal values. During the 6 months CSII treatment a reduction of the GFR from 145 +/- 21 to 132 +/- 14 ml/min (2p = 2.4%) was seen, no change was observed in the CIT group while in both groups RPF and kidney volume remained unchanged. Urinary albumin excretion rate was normal or near normal in both groups and remained unchanged. Thus improved glycaemic control in insulin-dependent diabetics studied before the onset of microalbuminuria is associated with improved (reduced) GFR. Nephromegaly does not improve with 6 months CSII treatment. Whether it would improve with more prolonged treatment is uncertain.