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。     

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.     

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.     

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.     

Comparison of continuous subcutaneous insulin infusion with multiple insulin injections using the NovoPen

Twenty-one patients with insulin-dependent diabetes mellitus (IDDM) participated in a 20-week randomized cross-over comparison of continuous subcutaneous insulin infusion (CSII) with intensified conventional treatment (ICT) using the NovoPen. The Medix or the Auto-Syringe pumps were used for CSII and, during ICT with NovoPen, conventional plastic syringes were used for injections of intermediate-acting insulin at bedtime. At entry HbA1c, was 8.7 +/- 0.4% (mean +/- SE) in CSII patients and 8.8 +/- 0.5% in the ICF group. HbA1c declined significantly in both groups (ICT 7.6 +/- 0.2%; CSII 7.6 +/- 0.2%) though there was no significant difference between the responses. Overall mean blood glucose was slightly but significantly lower during CSII than during ICT (CSII: 7.6 +/- 0.2 mmol/l; ICT: 8.7 +/- 0.4 mmol/l, p less than 0.05). The number of hypoglycaemic episodes did not differ significantly between patients treated with NovoPen and CSII. At the end of the study, a questionnaire revealed that all but one patient preferred ICT with NovoPen to conventional therapy. Given the choice for future treatment, 6 patients chose CSII, 12 patients preferred ICT with NovoPen and 1 was unsure.     

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.     

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.     

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.     

Severe hypoglycaemia and glycaemic control in Type 1 diabetes: meta‐analysis of multiple daily insulin injections compared with continuous subcutaneous insulin infusion

Aims Continuous subcutaneous insulin infusion (CSII) is a recommended treatment for reducing severe hypoglycaemia in Type 1 diabetes, but the change in hypoglycaemia compared with multiple daily insulin injections (MDI) is unclear. We therefore conducted a meta‐analysis comparing severe hypoglycaemia and glycaemic control during CSII and MDI. Methods Databases and literature (1996–2006) were searched for randomized controlled trials (RCTs) and before/after studies of ≥ 6 months’ duration CSII and with severe hypoglycaemia frequency > 10 episodes/100 patient years on MDI. Results In 22 studies (21 reports), severe hypoglycaemia during MDI was related to diabetes duration (P = 0.038) and was greater in adults than children (100 vs. 36 events/100 patient years, P = 0.036). Severe hypoglycaemia was reduced during CSII compared with MDI, with a rate ratio of 2.89 (95% CI 1.45 to 5.76) for RCTs and 4.34 (2.87 to 6.56) for before/after studies [rate ratio 4.19 (2.86 to 6.13) for all studies]. The reduction was greatest in those with the highest initial severe hypoglycaemia rates on MDI (P < 0.001). The mean difference in glycated haemoglobin (HbA_1c) between treatments was less for RCTs [0.21% (0.13–0.30%)] than in before/after studies [0.72% (0.55–0.90%)] but strongly related to the initial HbA_1c on MDI (P < 0.001). Conclusions The severe hypoglycaemia rate in Type 1 diabetes was markedly less during CSII than MDI, with the greatest reduction in those with most severe hypoglycaemia on MDI and those with the longest duration of diabetes. The biggest improvement in HbA_1c was in those with the highest HbA_1c on MDI.     

Quality of life and treatment satisfaction in adults with Type 1 diabetes: a comparison between continuous subcutaneous insulin infusion and multiple daily injections

Aims The aim of this case–control study was to compare quality of life (QoL) and treatment satisfaction in adults with Type 1 diabetes (T1DM) treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). Methods Consecutive patients aged between 18 and 55 years, and attending diabetes clinics for a routine visit, completed the Diabetes‐Specific Quality‐of‐Life Scale (DSQOLS), the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the SF‐36 Health Survey (SF‐36). Case (CSII) and control subjects (MDI) were recruited in a 1 : 2 ratio. Results Overall, 1341 individuals were enrolled by 62 diabetes clinics; 481 were cases and 860 control subjects. Cases had a longer diabetes duration and were more likely to have eye and renal complications. Age, school education, occupation and HbA_1c were similar. Of control subjects, 90% followed glargine‐based MDI regimens and 10% used NPH‐based MDI regimens. On multivariate analysis, after adjusting for socioeconomic and clinical characteristics, scores in the following areas of the DSQOLS were higher in cases than control subjects: diet restrictions (β = 5.96; P < 0.0001), daily hassles (β = 3.57; P = 0.01) and fears about hypoglycaemia (β = 3.88; P = 0.006). Treatment with CSII was also associated with a markedly higher DTSQ score (β = 4.13; P < 0.0001) compared with MDI. Results were similar when CSII was compared separately with glargine‐ or NPH‐based MDI regimens. Conclusions This large, non‐randomized, case–control study suggests quality of life gains deriving from greater lifestyle flexibility, less fear of hypoglycaemia, and higher treatment satisfaction, when CSII is compared with either glargine‐based or NPH‐based MDI regimens.     

Health-economic comparison of continuous subcutaneous insulin infusion with multiple daily injection for the treatment of Type 1 diabetes in the UK.

OBJECTIVES: The aim of this study was to project the long-term costs and outcomes of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in patients with Type 1 diabetes in the UK. METHODS: The CORE Diabetes Model is a peer-reviewed, validated model which employs standard Markov/Monte Carlo simulation techniques to describe the long-term incidence and progression of diabetes-related complications. It was used to simulate disease progression in a cohort of patients with baseline characteristics taken from published UK studies (mean age 26 years, duration of diabetes 12 years, mean HbA1c 8.68%). Direct costs for 2003 were calculated from a third-party payer perspective. Discount rates of 3.0% per annum were applied to costs and clinical outcomes. RESULTS: Treatment with CSII was associated with an improvement in mean quality adjusted life expectancy (QALE) of 0.76 +/- 0.19 years compared with MDI (12.03 +/- 0.15 vs. 11.27 +/- 0.14 years). Mean direct lifetime costs were pounds 19,407 +/- 1727 higher with CSII treatment compared with MDI (pounds 80,511 +/- 1257 vs. pounds 61,104 +/- 1249). This produced an incremental cost-effectiveness ratio (ICER) of pounds 25,648 per quality-adjusted life year (QALY) gained with CSII vs. MDI. The results were most sensitive to variation in hypoglycaemia rates and altering improvements in HbA1c associated with CSII therapy compared with MDI. CONCLUSIONS: Improvements in glycaemic control associated with CSII over MDI led to improved QALE owing to reduced incidence of diabetes-related complications. CSII was associated with an ICER of pounds 25,648 per QALY gained vs. MDI, representing good value for money by current standards in the UK.     

The relationship between the frequency of self‐monitoring of blood glucose and glycemic control in patients with type 1 diabetes mellitus on continuous subcutaneous insulin infusion or on multiple daily injections

Aims/Introduction

We investigated the relationship between the frequency of self-monitoring of blood glucose (SMBG) and glycemic control in type 1 diabetes mellitus patients on continuous subcutaneous insulin infusion (CSII) or on multiple daily injections (MDI) using data management software.

Materials and Methods

We recruited 148 adult type 1 diabetes mellitus patients (CSII n = 42, MDI n = 106) and downloaded their SMBG records to the MEQNET™ SMBG Viewer software (Arkray Inc., Kyoto, Japan). The association between the SMBG frequency and the patients'' hemoglobin A1c (HbA1c) levels was analyzed using the χ²-test and linear regression analysis was carried out to clarify their relationship.

Results

The odds ratio of achieving a target HbA1c level of <8% (63.9 mmol/mol) was significantly higher in subjects with SMBG frequencies of ≥3.5 times/day compared with those with SMBG frequencies of <3.5 times/day in the CSII group (odds ratio 7.00, 95% confidence interval 1.72–28.54), but not in the MDI group (odds ratio 1.35, 95% CI 0.62–2.93). A significant correlation between SMBG frequency and the HbA1c level was detected in the CSII group (HbA1c [%] = –0.24 × SMBG frequency [times/day] + 8.60 [HbA1c {mmol/L} = –2.61 × SMBG frequency {times/day} + 70.5], [r = –0.384, P = 0.012]), but not in the MDI group.

Conclusions

A SMBG frequency of <3.5 times per day appeared to be a risk factor for poor glycemic control (HbA1c ≥8%) in type 1 diabetes mellitus patients on CSII.     

Sandostatin,a new analogue of somatostatin,reduces the metabolic changes induced by the nocturnal interruption of continuous subcutaneous insulin infusion in Type 1 (insulin-dependent) diabetic patients

Summary With the aim of assessing a new somatostatin analogue to prevent the metabolic changes induced by a 6-h nocturnal arrest of an insulin pump, nine C-peptide negative Type 1 (insulin-dependent) diabetic patients were submitted blindly to two interruptions (from 23.00 to 05.00 hours) of their continuous s.c. insulin infusion, once after a single s.c. injection at 23.00 hours of 50 g SMS 201-995 (Sandostatin, Sandoz) and once after 0.9% NaCl. Plasma SMS 201-995 levels peaked at 24.00 hours and then declined with an elimination half-life averaging 144±15 min. Plasma glucagon and growth hormone levels were significantly reduced after SMS 201-995 whereas the progressive fall in plasma-free insulin levels from 23.00 to 05.00 hours was unaffected. In the control test, blood glucose levels tended to decrease slightly from 23.00 to 02.00 hours and then increased markedly from 02.00 to 05.00 hours (+5.3±1.5mmol/l) while after SMS 201-995 they decreased significantly from 23.00 to 02.00 hours (–2.6±0.5 mmol/l), resulting in values below 3 mmol/l in seven subjects, but showed a secondary increase until 05.00 hours (+3.5±1.5 mmol vs 23.00h; p<0.05 vs 0.9% NaCl). While the rises in plasma non-esterified fatty acid and glycerol levels were not reduced by SMS 201-995, the increase in plasma 3-hydroxybutyrate levels, although similar from 23.00 to 02.00 hours, was significantly reduced from 02.00 to 05.00 hours (+77±20 vs+124±31 mol·l^–1·h^–1 p<0.005). Thus, SMS 201-995 significantly reduced the metabolic alterations due to a 6-h nocturnal interruption of a continuous s.c. insulin infusion but at the cost of a rather high risk of early hypoglycaemia.     

Efficacy and safety of basal insulin glargine 12 and 24 weeks after initiation in persons with type 2 diabetes: A pooled analysis of data from treatment arms of 15 treat-to-target randomised controlled trials

AimEvaluate early (0–12 weeks) and later (12–24 weeks) treatment outcomes in subjects with type 2 diabetes not achieving glycaemic control with oral antidiabetes drugs (OADs).MethodsSelected data were pooled from 15 randomised, controlled treat-to-target (fasting plasma glucose < 100 mg/dL [<5.6 mmol/L]) trials adding insulin glargine to metformin, a sulphonylurea, or both. Glycaemic and hypoglycaemia parameters, insulin dose, and body weight at weeks 12 and 24 were assessed using individualised subject-level data.ResultsData from 2837 subjects were analysed. HbA1c decreased from 8.8% (73 mmol/mol) at baseline by 1.4% (15 mmol/mol) at Week 12, and a further 0.2% (2 mmol/mol) at Week 24 in the pooled population. Similar reductions were observed across the different treatment groups. HbA1c < 7.0% (<53 mmol/mol) was reached by 34.8% of participants at Week 12 and an additional 24.3% by Week 24. Hypoglycaemia incidence and rates were similar during the early and continued treatment periods across all treatment combinations, but were markedly lower for insulin glargine plus metformin versus the other 2 regimens.ConclusionsEarly and sustained glycaemic benefits with a low-risk of hypoglycaemia are observed after initiation of insulin glargine in a pooled type 2 diabetes cohort previously uncontrolled on OADs.     

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).     

Prevalence and clinical features of celiac disease in 950 children with type 1 diabetes in France

The prevalence of celiac disease is higher in children with type 1 diabetes mellitus (DM) than in the general pediatric population, but may vary widely across countries. Sensitive and specific antibody tests are available for detecting celiac disease.

Aims

To evaluate the prevalence in France of histologically documented celiac disease in a vast cohort of children with type 1 DM, and to describe the features of celiac disease and treatment response.

Methods

Retrospective cohort study of 950 children with type 1 diabetes seen between 1994 and 2001. Antibodies to gliadin, reticulin, endomysium and transglutaminase were looked for one to seven times in each patient.

Results

Fifteen patients (1.6%) had biopsy-confirmed celiac disease. Symptoms led to the diagnosis in six patients (mean age, 7 years) and screening tests in nine patients (mean age, 11 years). Anti-endomysium antibodies were consistently positive. Tests for HLA-DQB1 0201 and/or 0302 were positive. Anti-endomysium antibody seroconversion was seen in two patients, 2 and 6 years, respectively, after the diagnosis of diabetes. In another patient, the biopsy became abnormal 6 years after the first positive anti-endomysium antibody test (latent form). After a mean of 3 years on a gluten-free diet, significant increases were noted in body weight (P = 0.04) and insulin dose (P = 0.05); clinical symptoms completely resolved in five of the six symptomatic patients.

Conclusions

The prevalence of celiac disease is higher in children with type 1 DM than in the general pediatric population. Serological screening is useful for diagnosing asymptomatic celiac disease, detecting seroconversion and monitoring latent forms of disease.