胰岛素短程皮下持续输注后换用分次皮下注射的用量探讨

观察了197例2型糖尿病患者从持续皮下胰岛素输注换用皮下分次注射预混人胰岛素过程中胰岛素用量之间的相关关系，发现两个用量呈正相关（r=0．60，P〈0．05），其直线回归方程为y=11．12＋0．49x，此方程可作为临床应用的胰岛素用量参考。     

Continuous infusion of insulin vs repeated S.C. injections in the treatment of diabetic ketoacidosis in children

Summary Thirty-two episodes of diabetic ketoacidosis in 30 children treated with conventional repeated s.c. injections of insulin every 4 h are compared with 18 episodes in 14 children treated with continuous i.v. insulin infusion. Fluid therapy, bicarbonate and potassium supplementation were essentially the same for both groups. Recovery as reflected in serum glucose, bicarbonate and the rate of rehydration, was smoother and more rapid in the children receiving continuous i.v. insulin, though the difference just failed to attain statistical significance in this small series of cases. There was, however, a marked difference in insulin administered (0.58 U/kg ± 0.05 SEM in the children treated with continuous i.v. insulin infusionvs 2.54 ± 0.27 SEM in the children treated with repeated s.c. injections). Hypoglycemia was noted in 11 and hypokalemia in 10 children on conventional insulin therapy given every 4 h s.c. In contrast, there was no hypoglycemia and only one case of hypokalemia with the i.v. insulin infusion. Supported in part by P.H.S. General Research Support Grant No. RR 5360.     

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.     

Low subcutaneous degradation and slow absorption of insulin in insulin-dependent diabetic patients during continuous subcutaneous insulin infusion at basal rate

Summary As information on the absorption kinetics and local degradation of infused insulin is relevant to programming strategies for continuous subcutaneous insulin infusion, we examined the time relationship of systemic insulin appearance and quantitated subcutaneous degradation during a near-basal rate of continuous subcutaneous insulin infusion in five insulin-dependent diabetic patients. Plasma free insulin was monitored for 8 h during and 3 h after a subcutaneous (abdominal wall) infusion of neutral insulin at 2.4 U/h. An identical intravenous infusion (2–4 h) was given on a separate occasion. Plateau levels of free insulin were not significantly different during the subcutaneous (37±8 mU/l) and intravenous (40±7 mU/l) infusions. Fitting of the free insulin data to our two-pool model of the subcutaneous space gave a mean estimate of 9.2 units insulin (= 3.8 h infusion) for the subcutaneous depot after 8 h. Model estimates of systemic insulin appearance, as a percentage of subcutaneous infusion rate, were 59% and 93% after 4 and 8 h respectively, and 76% 2 h after cessation of infusion. In insulin-dependent diabetic patients subcutaneous degradation of infused insulin is negligible but local accumulation in the subcutaneous space is considerable. The delay in absorption has important clinical implications for interruption and resumption of continuous subcutaneous insulin infusion and also for programming of variable basal rates.     

Validation of I.V. small-dose insulin infusion therapy in diabetic ketoacidosis of depancreatized dogs

Summary A validation of small-dose insulin infusion therapy was studied by the constant i.v. infusion of various doses of insulin into ketoacidotic depancreatized dogs. Constant insulin infusion of 5 × B, 10 × B, 30 × B and 50 × B (B=225 μU/kg/min) was performed for 3 h by mechanical pump. The following results were obtained: (1) plasma concentrations of immunoreactive insulin (IRI) increased proportionally to the dose of infused insulin, but the higher IRI did not result in a greater fall in plasma glucose concentration, correspondingly; the mean rate of fall in plasma glucose concentration of 5 × B was not significantly lower than that of 50 × B; β-hydroxybutyrate and arterial pH improvements were observed in each group during the 3-h insulin infusion. These data suggested that for the improvement of diabetic ketoacidosis, the insulin infusion rate of more than 30 × B, which raised the plasma IRI levels above the physiological range, was not essential; (2) the necessity of potassium supplementation during the small-dose insulin infusion was suggested if the pre-treatment level of serum potassium was low. These results confirmed that in the absence of infection or severe acidosis small-dose insulin infusion therapy is as effective as the conventional large-dose insulin therapy.     

Lack of influence of arginine preloading on the insulin response to I.V. glucagon in children and adolescents

Summary Nine normal children (6 males and 3 females) aged from 7 1/2 to 14 1/2 years underwent a 30-min arginine infusion (0.5 g/kg) followed at 90 min by one bolus i.v. glucagon injection (0.03 mg/kg). On a separate occasion the same children underwent an i.v. glucagononly test. No significant difference was found when the glucose and insulin responses in the two glucagon tests were compared, in contrast to previous findings that preloading with glucose resulted in a significantly increased response of insulin to glucagon. Established Investigator of the Chief Scientist’s Bureau Ministry of Health.     

Remission from insulin dependence induced by continuous subcutaneous insulin infusion (CSII) in type I,newly diagnosed diabetics: Role of some hormonal and immunologic factors

Summary Optimal and early control of recent onset, type I diabetes by intensive insulin therapy has been reported to allow insulin withdrawal in about two thirds of subjects treated. We used continuous s.c. insulin infusion (CSII) in the attempt to induce a temporary remission of insulin dependence in 18 newly diagnosed young adult diabetics. After 10 days of optimized glycometabolic control, insulin infusion was stopped and patients were switched to glibenclamide (15 mg/die) plus metformin (1 g/die). Diabetics were considered in remission of insulin dependence when their metabolic control fulfilled the following criteria for at least 3 months: absence of glycosuria, pre- and post-prandial blood glucose ≤ 120 and 180 mg/dl, respectively, HbA_lc ≤ 7%. Insulin therapy could be discontinued for periods of over three months in 11 subjects (61%) and for as long as 18 months in one case. Insulin requirement during CSII was slightly higher in non-remitters (NR) than in remitters (R): 0.36–0.64vs 0.26–0.41 U/kg/die. After 24 months from CSII, R still showed lower insulin requirement (0.35–0.42 U/kg/die) than NR (0.55–0.75 U/kg/die). Further, the role of some hormonal and immunologic factors was investigated. Plasma C-peptide and glucagon were measured, fasting and 2h after each meal, both on admission and immediately after CSII, when patients were switched to oral therapy. No difference in hormone levels could be detected on admission, whereas, after CSII, mean post-prandial increase of C-peptide over basal was significantly higher in R than in NR (1.18 ± 0.37vs 0.22 ± 0.16 ng/ml, p<0.001). Finally, blood distribution of T, B, T4 and T8 lymphocyte subsets was measured in all patients, both before and after CSII. The T4/T8 ratio was found to be significantly increased in NR group patients (3.19 ± 0.45vs 2.41 ± 0.23, p<0.005). The immunologic pattern did not show any significant modification after ten days of optimized control by CSII. In conclusion, immunologic background and residual B-cell function may be associated with a different susceptibility to remission from insulin therapy in newly diagnosed young adult diabetics.     

2型糖尿病患者预混胰岛素类似物治疗与持续胰岛素输注治疗剂量的相关性研究

分析经短期持续皮下胰岛素输注(CSII)强化治疗后换为预混胰岛素类似物治疗的2型糖尿病患者,发现CSII治疗末日胰岛素使用量小于45 U/d宜选择每日2次预混胰岛素类似物治疗,大于45 U/d 宜选择每日3次预混胰岛素类似物治疗.其治疗剂量可根据以下方程:每日2次预混胰岛素类似物治疗剂量=13.093+0.395×CSII治疗总量,每日3次预混胰岛素类似物治疗剂量=23.114+0.405×CSII治疗总量.     

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.     

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.     

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.     

Influence of glucoregulation with continuous subcutaneous insulin infusion on nerve conduction velocity and beat to beat variation in diabetics

Limited and contrasting data are available on the relationship between metabolic control and diabetic neuropathy. In eight type I diabetics peripheral and autonomic neuropathy were studied, first in conditions of poor metabolic control and then after one and three months during which an improved control of glycemic levels had been obtained by continuous subcutaneous insulin infusion. Autonomic neuropathy was investigated by evaluating beat to beat variation during deep breathing; peripheral neuropathy by measuring maximum motor conduction velocity of peroneal and median nerves and sensory conduction velocity of median nerve. Our data showed significant improvement of motor conduction velocity in both nerves studied, whilst sensory conduction velocity did not show any significant variation. The changes observed in beat to beat variation in five subjects with initially abnormal scores might reflect an improvement in autonomic nervous function, even if long-term studies are needed.     

短期胰岛素泵强化治疗对新诊断2型糖尿病患者胰岛素分泌和敏感性的影响

目的 探讨短期胰岛素泵强化治疗对新诊断2型糖尿病患者胰岛素敏感性和胰岛素分泌功能的影响.方法 选取2006年6月至2007年2月在本院就诊的新诊断2型糖尿病患者10例进行为期2周的胰岛素泵强化治疗,在治疗前和停泵24 h后分别进行两次静脉葡萄糖耐量试验(IVGTT)和高胰岛素-正葡萄糖钳夹试验.结果 (1)在治疗前所有糖尿病患者均缺乏急性胰岛素分泌(AIR),经2周强化治疗使血糖正常后,所有患者AIR均有了不同程度地恢复[(7.63±4.73 vs 0.83±1.96)mU/L,P＜0.01)].AIR恢复较好的患者略为年轻和肥胖.(2)糖耐量正常志愿者平均葡萄糖输注率(GIR)为(8.26±2.48)mg·kg-1·min-1,而初发2型糖尿病患者在胰岛素泵强化治疗前GIR为(2.30±0.81)mg·kg-1·min-1(与正常者比,P＜0.01),胰岛素泵强化治疗后GIR升高到(5.33±1.43)mg·kg-1·min-1(P＜0.01).GIR升高显著的患者腰围和体重指数低、治疗前的平均血糖高.结论 短期胰岛素泵强化治疗使血糖"正常化",同时可改善胰岛细胞功能,提高胰岛素敏感性.     

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.     

甘精胰岛素联合那格列奈与胰岛素泵对2型糖尿病骨折患者围手术期的疗效观察

分析甘精胰岛素联合那格列奈和胰岛素泵治疗2型糖尿病骨折患者围手术期的资料,发现两种治疗均能使血糖达标[空腹血糖(6.89±1.96)对(6.75±2.33)mmol/L],达标时间无显著差异[(3.6±1.6)对(2.9±1.2)d,均P0.05],但胰岛素泵组的平均血糖值更低.     

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).

Insulin and glucose profiles during continuous subcutaneous insulin infusion compared with injection of a long-acting insulin in Type 2 diabetes1

Aims To compare insulin and glucose profiles during basal continuous subcutaneous infusion of a rapid-acting insulin analogue and once daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes. Methods Twenty-one patients with Type 2 diabetes treated with oral glucose-lowering agents were randomized in this two-period crossover study to an equivalent 24-h dose of continuous subcutaneous infusion of insulin aspart and subsequently once-daily bedtime subcutaneous injection of insulin glargine, or vice versa, for eight consecutive days. Plasma profiles of insulin and glucose were recorded. Results On the last day of each treatment period, the area under the curve (AUC) for glucose was 10% lower on the continuous subcutaneous infusion regimen compared with the insulin injection regimen (P = 0.002). This was accomplished by a flat exogenous insulin infusion profile compared with a peaking profile with injected insulin (AUC was 74% higher after injection compared with pre-injection levels (P = 0.001)). During the last 6 days in each treatment period, the intra-subject variability of exogenous fasting insulin levels in the mornings was 41% lower during insulin infusion compared with insulin injection (P = 0.012). The corresponding intra-subject variability for fasting glucose only showed a tendency to be lower during infusion as compared to the injection regimen (28%; P = 0.104). Thirteen symptomatic-only or minor hypoglycaemic episodes were recorded during the entire infusion period compared with three episodes during the injection period. Conclusions Basal continuous subcutaneous infusion of a rapid-acting insulin analogue improved plasma insulin (more flat insulin profile with a lower variability) and glucose (lower AUC) profiles compared with once-daily subcutaneous injection of a long-acting insulin analogue in Type 2 diabetes.     

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.     

An alteration in internodal myelin membrane structure in large sciatic nerve fibres in rats with acute streptozotocin diabetes and impaired nerve conduction velocity

Summary Replicas of the freeze-fracture surfaces of the internodal myelin membranes of large sciatic nerve fibres from normal and diabetic rats were compared by quantitative electron microscopy. The internodal myelin of the diabetics was examined 14 days after streptozotocin (70 mg/kg IV) induced persistent hyperglycaemia, conditions under which sciatic motor nerve conduction velocity (MNCV) is consistently decreased by 20%. The number of intramembranous particles per unit area of both the P-face and the E-face of the internodal myelin membrane was significantly decreased in the diabetics. This alteration in the structure of the internodal myelin membrane was not found in large sciatic nerve fibres from diabetic rats treated with insulin from day 3 through 14, or from diabetic rats fed a diet containing 1% myoinositol; these are conditions under which the development of decreased sciatic MNCV is prevented or ameliorated. An alteration in internodal myelin structure occurs in acute streptozotocin diabetes which may explain the associated decreased sciatic MNCV.The authors wish to thank Mrs. Sarah Aquino and Marthe Sidler, Misses Irina Barinov and Isabelle Bernard, and Mr. Patrice Fruleux for their expert assistance.     

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.