In Type 1 diabetic patients with good glycaemic control,blood glucose variability is lower during continuous subcutaneous insulin infusion than during multiple daily injections with insulin glargine

Aims The superiority of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) with glargine is uncertain. In this randomized cross‐over study, we compared CSII and MDI with glargine in patients with Type 1 diabetes well controlled with CSII. The primary end‐point was glucose variability. Methods Thirty‐nine patients [38.1 ± 9.3 years old (mean ± sd ), diabetes duration 16.6 ± 8.2 years, glycated haemoglobin (HbA_1c) 7.6 ± 0.8%], already on CSII for at least 6 months, were randomly assigned to CSII with lispro or MDI with lispro and glargine. After 4 months they were switched to the alternative treatment. During the last month of each treatment blood glucose variability was analysed using glucose standard deviation, mean amplitude of glycaemic excursions (MAGE), lability index and average daily risk range (ADRR). As secondary end‐points we analysed blood glucose profile, HbA_1c, number of episodes of hypo‐ and hyperglycaemia, lipid profile, free fatty acids (FFA), growth hormone and treatment satisfaction. Results During CSII, glucose variability was 5–12% lower than during MDI with glargine. The difference was significant only before breakfast considering glucose standard deviation (P = 0.011), significant overall using MAGE (P = 0.016) and lability index (P = 0.005) and not significant using ADRR. Although HbA_1c was similar during both treatments, during CSII blood glucose levels were significantly lower, hyperglycaemic episodes were fewer, daily insulin dose was less, FFA were lower and treatment satisfaction was greater than during MDI with glargine. The frequency of hypoglycaemic episodes was similar during both treatments. Conclusions During CSII, glucose variability is lower, glycaemic control better and treatment satisfaction higher than during MDI with glargine.     

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.     

Continuous subcutaneous insulin infusion versus multiple daily insulin injections in patients with diabetes mellitus: systematic review and meta-analysis

Aims We compared the effects of continuous subcutaneous insulin infusion (CSII) with those of multiple daily insulin (MDI) injections on glycaemic control, risk of hypoglycaemic episodes, insulin requirements and adverse events in type 1 and type 2 diabetes mellitus. Methods The electronic databases MEDLINE, EMBASE and CENTRAL were systematically searched for randomised controlled trials up to March 2007. A systematic review and meta-analysis were performed. Results Overall, 22 studies were included (17 on type 1 diabetes mellitus, two on type 2 diabetes mellitus, three on children). With regard to adults with type 1 diabetes mellitus, our meta-analysis found a between-treatment difference of −0.4% HbA_1c (six studies) in favour of CSII therapy. Available median rates of mild or overall hypoglycaemic events were comparable between the different interventions (1.9 [0.9–3.1] [CSII] vs 1.7 [1.1–3.3] [MDI] events per patient per week). Total daily insulin requirements were lower with CSII than with MDI therapy. In patients with type 2 diabetes mellitus, CSII and MDI treatment showed no statistically significant difference for HbA_1c. The incidence of mild hypoglycaemic events was comparable between the treatment groups. In adolescents with type 1 diabetes mellitus, glycated haemoglobin and insulin requirements were significantly lower in the CSII groups; no data were available on hypoglycaemic events. The only study performed in younger children did not provide enough data for conclusive inferences. No overall conclusions were possible for severe hypoglycaemia and adverse events for any of the different patient groups due to rareness of such events, different definitions and insufficient reporting. Conclusions/interpretation CSII therapy in adults and adolescents with type 1 diabetes mellitus resulted in a greater reduction of glycated haemoglobin, in adult patients without a higher rate of hypoglycaemia. No beneficial effect of CSII therapy could be detected for patients with type 2 diabetes mellitus. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Continuous subcutaneous insulin infusion is more effective than multiple daily insulin injections in preventing albumin excretion rate increase in Type 1 diabetic patients

Aims To compare the effect of continuous subcutaneous insulin infusion (CSII) and multiple daily insulin injections (MDI) on albumin excretion rate (AER) in Type 1 diabetic patients. Methods In a 3‐year multicentre retrospective observational study, 110 Type 1 diabetic patients treated with CSII were compared with 110 patients treated with MDI matched at baseline for age, sex, diabetes duration and HbA_1c. At entry, 90 patients in each group had normal AER and 20 persistent microalbuminuria. AER, estimated glomerular filtration rate (eGFR), HbA_1c, lipids and blood pressure were assessed. Results HbA_1c was lower in the CSII than in the MDI group (8.1 ± 0.9 vs. 8.4 ± 1.3%; P < 0.005 after 3 years). Blood pressure and eGFR were similar during the study. AER [median (95% confidence interval)], similar at baseline [6.0 μg/min (9, 21) in the CSII group vs. 4.4 (8, 16) in the MDI group, NS] was significantly lower in the patients treated with CSII both at year 2 and at year 3 of follow‐up [4.7 μg/min (6, 12) vs. 6.4 (13, 29), P < 0.002]. This difference was observed even when normo‐ and microalbuminuric patients were analysed separately. Nine patients progressed to microalbuminuria in the MDI group and only one in the CSII group. Nine patients regressed to normoalbuminuria in the CSII group, whereas only two regressed to normoalbuminuria in the MDI group. Conclusions Despite a small benefit in terms of improved glycaemic control, CSII therapy may be useful in decreasing the progressive increase in AER in Type 1 diabetic patients.     

The cost-effectiveness of continuous subcutaneous insulin infusion compared with multiple daily injections for the management of diabetes.

AIMS: To estimate the cost effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) for patients using insulin pumps. METHODS: We constructed a Markov model to estimate the costs and outcomes for patients with insulin-dependent diabetes (IDDM) treated with CSII using an insulin pump compared with MDI. Key parameters were obtained from the published scientific literature. The primary outcome was quality-adjusted life years (QALYs). Monte Carlo simulations were undertaken for 10 000 hypothetical patients over 8 years of monthly cycles (the expected life of a pump). RESULTS: Over an 8-year period an average patient could expect to gain 0.48 [standard deviation (sd) 0.20] QALYs using CSII compared with MDI. The additional cost over 8 years for this gain was pounds 5462 (sd pounds 897). The incremental cost per QALY was pounds 11,461 (sd pounds 3656). CSII was most cost-effective in patients who had more than two severe hypoglycaemic events per year and who required admission to hospital at least once every year. Cases where CSII might be not economically viable are cases where diabetes is well controlled with few severe hypoglycaemic events. Results were most sensitive to the number of hypoglycaemic events per patient and the utility weights used to estimate QALYs. CONCLUSION: CSII is a worthwhile investment when targeted to those who might benefit most.     

Comparison of continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI) in paediatric Type 1 diabetes: a multicentre matched‐pair cohort analysis over 3 years

Aims To conduct a multicentre, matched‐pair cohort analysis comparing glycaemic control and adverse events of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) in paediatric patients. Methods Using standardized computer‐based prospective documentation, HbA_1c, insulin dose, body mass index–standard deviation score (BMI–SDS), rate of hypoglycaemia, rate of diabetic ketoacidosis (DKA) and intensity of care were analysed in 434 matched pairs during a follow‐up period of 3 years after initiation of MDI or CSII. Results HbA_1c was significantly lower in the CSII group during the first year of new regimen (CSII 7.5 ± 0.05 vs. MDI 7.7 ± 0.06; P < 0.05), but rose to the same level as in the MDI group during year 3. Insulin requirement remained significantly lower in the CSII group. The BMI–SDS increased in both study groups, with no significant difference. The rate of severe hypoglycaemia decreased significantly after the change of regimen (CSII 17.87 ± 2.85 vs. MDI 25.14 ± 3.79; P < 0.05) and during year 3 of the regimen, particularly when compared with baseline (?21% vs. ?16%). The rate of DKA was lower at baseline in the CSII group and remained significantly lower over all 3 years. Intensity of care was the same in both subsets. Conclusions Employing a large cohort, this matched‐pair analysis has demonstrated over a 3‐year study period that CSII is a safe form of intensive insulin therapy with similar glycaemic effects, but with significantly reduced rates of hypoglycaemia and DKA and a lower insulin requirement when compared with MDI.     

Comparison of the effects of continuous subcutaneous insulin infusion (CSII) and NPH-based multiple daily insulin injections (MDI) on glycaemic control and quality of life: results of the 5-nations trial.

AIMS: The goal of the study was to determine whether continuous subcutaneous insulin infusion (CSII) differs from a multiple daily injection (MDI) regimen based on neutral protamine hagedorn (NPH) as basal insulin with respect to glycaemic control and quality of life in people with Type 1 diabetes. METHODS: The 5-Nations trial was a randomized, controlled, crossover trial conducted in 11 European centres. Two hundred and seventy-two patients were treated with CSII or MDI during a 2-month run-in period followed by a 6-month treatment period, respectively. The quality of glycaemic control was assessed by HbA(1c), blood glucose values, and the frequency of hypoglycaemic events. For the evaluation of the quality of life, three different self-report questionnaires have been assessed. RESULTS: CSII treatment resulted in lower HbA(1c) (7.45 vs. 7.67%, P < 0.001), mean blood glucose level (8.6 vs. 9.4 mmol/l, P < 0.001) and less fluctuation in blood glucose levels than MDI (+/- 3.9 vs. +/- 4.3 mmol/l, P < 0.001). There was a marked reduction in the frequency of hypoglycaemic events using CSII compared with MDI, with an incidence ratio of 1.12 [95% confidence interval (CI): 1.08-1.17] and 2.61 (95% CI: 1.59-4.29) for mild and severe hypoglycaemia, respectively. The overall score of the diabetes quality of life questionnaire was higher for CSII (P < 0.001), and an improvement in pump users' perception of mental health was detected when using the SF-12 questionnaire (P < 0.05). CONCLUSION: CSII usage offers significant benefits over NPH-based MDI for individuals with Type 1 diabetes, with improvement in all significant metabolic parameters as well as in patients' quality of life. Additional studies are needed to compare CSII with glargine- and detemir-based MDI.     

Efficacy of continuous subcutaneous insulin infusion in Type 1 diabetes: a 2-year perspective using the established criteria for funding from a National Health Service.

AIM: To determine the 2-year efficacy of continuous subcutaneous insulin infusion (CSII) following the current established criteria for funding of a National Health Service. METHODS: Longitudinal, prospective, observational unicentre study. Included in the study were 153 Type 1 diabetes (T1D) subjects, previously treated with multiple daily injections (MDI) of insulin, in whom CSII was started in accordance with the criteria for reimbursement of the Catalan National Health Service. At baseline, we recorded data on age, gender, duration of the disease, body mass index (BMI), insulin dose and indications for CSII. Glycated haemoglobin (HbA(1c)) and the frequency of hypoglycaemic events were used to assess glycaemic control. Quality of life was assessed using three different self-report questionnaires. After 24 months, these same items were remeasured in all subjects. Serious adverse events and injection-site complications were also recorded. RESULTS: In 96% of subjects, CSII indication included less than optimal glycaemic control using MDI. HbA(1c) fell from 7.9 +/- 1.3 to 7.3 +/- 1.1% (P < or = 0.001) after 24 months of CSII. Insulin requirements were significantly lower at the end of follow-up (0.55 +/- 0.21 U/kg body weight) in comparison with before use of CSII (0.70 +/- 0.20, P < or = 0.001). BMI increased from 24.0 +/- 3.1 to 24.4 +/- 3.2 kg/m(2) after 24 months (P < or = 0.025). The rate of episodes of diabetic ketoacidosis per year remained unchanged. Mild and severe hypoglycaemic episodes were significantly reduced. The scores in all subsets of the Diabetes Quality-of-Life (DQoL) questionnaire significantly improved after 24 months of CSII. CONCLUSIONS: CSII, commenced according to the criteria for a nationally funded clinical programme, improves glycaemic control and quality-of-life outcomes with fewer hypoglycaemic episodes in T1D subjects previously conventionally treated with MDI.     

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.     

Safety and efficacy of glargine compared with NPH insulin for the treatment of Type 2 diabetes: a meta‐analysis of randomized controlled trials

Aims We systematically analysed evidence from randomized controlled trials (RCTs) examining the safety and efficacy of neutral protamine Hagedorn (NPH) insulin and glargine in the management of adults with Type 2 diabetes. Methods Studies were identified by searching medline (1966–March 2007), embase (1974–2007), American Diabetes Association abstract database and the Cochrane Central Register of Controlled Trials using Medical Subject Headings (MeSH) diabetes mellitus, Type 2, insulin, insulin isophane, hypoglycaemic agents and the keywords glargine and NPH. Data on study design, participants, fasting plasma glucose (FPG), glycated haemoglobin (HbA_1c), body weight and hypoglycaemia were independently abstracted by two investigators using a standardized protocol. Results Data from a total of 4385 participants in 12 RCTs were pooled using a random‐effects model. The mean net change (95% confidence interval) for FPG, HbA_1c and body weight for patients treated with NPH insulin as compared with glargine was 0.21 mmol/l (?0.02 to 0.45), 0.08% (?0.04 to 0.21) and ?0.33 kg (?0.61 to ?0.06), respectively, with negative values favouring NPH and positive values favouring glargine. More participants experienced symptomatic and nocturnal hypoglycaemia on NPH than glargine, but there was no significant difference in confirmed or severe episodes. Conclusions We identified no difference in glucose‐lowering between insulin glargine and NPH insulin, but less patient‐reported hypoglycaemia with glargine and slightly less weight gain with NPH in adults with Type 2 diabetes.     

Prevalence and associations of psychological distress in young adults with Type 1 diabetes

Aims To determine the prevalence of psychological distress in young adults with Type 1 diabetes and to explore associated factors. Methods Ninety‐two participants with Type 1 diabetes (46 male, 46 female) attending a young adult clinic completed two psychological self‐report assessments; the Centre for Epidemiological Studies–Depression Scale (CES‐D) and Adult Self‐Report Scale (ASR). The mean age was 21.6 ± 2.8 years (sd ) and mean duration of diabetes was 9.3 ± 5.4 years. A questionnaire identified the method of insulin delivery, the frequency of blood glucose monitoring and hypoglycaemia requiring third‐party assistance. HbA_1c was measured. Results Of the participants, 35.2% reported depressive symptoms (CES‐D ≥ 16), 23.1% indicating severe depressive symptoms (CES‐D ≥ 24), and 32.2, 40.4 and 35.5% of participants reported significant distress (ASR ≥ 60) on the ASR total problem scales, ASR internalizing and ASR externalizing scores, respectively. Mean HbA_1c levels were higher in participants with depressive symptoms compared with those with normal scores (CES‐D ≥ 16, HbA_1c= 9.4% vs. CES‐D < 16, HbA_1c= 8.4%, P = 0.01). Factors associated with psychological distress included use of continuous subcutaneous insulin infusion (CSII) (P = 0.02) and increased frequency of hypoglycaemic episodes (P = 0.03). CSII users had higher CES‐D (21.3 vs. 11.9, P = 0.001) and ASR‐Total (59.7 vs. 53.0, P = 0.02) scores than non‐CSII users. Conclusions  Approximately one‐third of young adults with Type 1 diabetes experience psychological distress, which is associated with poorer glycaemic control. Psychological distress was related to frequency of hypoglycaemic episodes and method of insulin administration, with significantly greater distress being observed in those using CSII. These findings support inclusion of a psychologist in the diabetes team.     

Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness

Aims

To investigate the relationship between arterial stiffness and insulin treatment mode [continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI)] in type 1 diabetes patients.

Methods

Cross-sectional study, from 2009 to 2011, including 601 Caucasian type 1 diabetes patients, 58 and 543 treated with CSII and MDI, respectively. Arterial stiffness was measured as pulse wave velocity (PWV) (SphygmoCor, AtCor Medical). Adjustment included gender, age, diabetes duration, HbA_1c, heart rate, mean arterial pressure, P-creatinine, urinary albumin excretion rate (UAER), smoking, total daily insulin dose, antihypertensive treatment, previous cardiovascular disease (CVD), total cholesterol and statin treatment. Albuminuria was UAER ≥30 mg/24-h, and CVD included myocardial infarction, revascularization, peripheral arterial disease and stroke.

Results

CSII- versus MDI-treated patients were 48 versus 57 % men, 51 ± 11 versus 54 ± 13 years old (mean ± SD), had 33 ± 12 versus 32 ± 16 years diabetes duration and HbA_1c 7.8 ± 0.9 % (62 ± 10 mmol/mol) versus 8.0 ± 1.2 % (64 ± 13 mmol/mol) (P ≥ 0.08 for all). PWV was lower in CSII- versus MDI-treated patients (9.3 ± 2.8 vs. 10.4 ± 3.4 m/s; P = 0.016). In fully adjusted analysis, CSII treatment was significantly (P = 0.038) associated with lower PWV, whereas HbA_1c-level was not (P = 0.93).

Conclusions

In type 1 diabetes patients, CSII treatment was associated with lower arterial stiffness independent of other risk factors, while HbA_1c was not. Although glucose variability was not assessed, our results suggest that glucose variability and not HbA_1c-level affect arterial stiffness. This needs confirmation in randomised prospective studies.     

Is insulin pump therapy effective in Type 1 diabetes?

There continues to be uncertainty about the effectiveness in Type 1 diabetes of insulin pump therapy (continuous subcutaneous insulin infusion, CSII) vs. multiple daily insulin injections (MDI). This narrative review discusses the reasons for this uncertainty, summarizes the current evidence base for CSII and suggests some future research needs. There are difficulties in interpreting trials of CSII because effectiveness varies widely due to factors such as differing baseline control, suboptimal use of best CSII practices, and psychological factors, for example, high external locus of control, non‐adherence and lack of motivation. Many summary meta‐analyses are also misleading because of poor trial selection (e.g. short duration, obsolete pumps, low baseline rate of hypoglycaemia) and reliance on mean effect size for decision‐making. Both MDI and CSII can achieve strict glycaemic control without hypoglycaemia in some people with Type 1 diabetes, especially those who are motivated and have undergone structured diabetes education, and with high levels of ongoing input from healthcare professionals. CSII is particularly effective in those people with Type 1 diabetes who have not achieved target HbA_1c levels without disabling hypoglycaemia using best attempts with MDI, and here there can be valuable and substantial improvement. Insulin pumps are safe, effective and accepted when used in newly diagnosed diabetes, particularly in children, where MDI may not be practicable. Future research needs include more studies on mortality associated with insulin pumps where registry data have suggested lower rates vs. MDI; and psychological strategies to improve non‐adherence and suboptimal glycaemic outcomes on CSII.     

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.     

Reducing snacks when switching from conventional soluble to lispro insulin treatment: effects on glycaemic control and hypoglycaemia

The lack of significant improvement in HbA_1c during insulin lispro treatment in previous studies may have been due to inadequate dietary adjustments. We tested whether reduction of snacks and a compensatory increase in main meals results in improved metabolic control when switching to lispro treatment. One hundred and forty-one Type 1 diabetic patients, mean ± SD age 36 ± 9 years, diabetes duration 14 ± 10 years, had two daily NPH injections throughout the study. After a baseline visit, the patients used conventional soluble insulin preprandially thrice daily for 12 weeks. Thereafter they were switched to lispro insulin and advised to transfer ≥50 % of their snack carbohydrates to preceding main meals. Mean HbA_1c at baseline was 8.05 %. After the conventional period and the 12-week lispro period, HbA_1c was 7.81 and 7.70 % (p = 0.088), respectively. In those patients who diminished their snacks as advised (n = 67), HbA_1c decreased from 7.91 to 7.66 % (p = 0.014) during lispro, whereas no change was observed in patients not compliant with the dietary change. The number of hypoglycaemic episodes was lower during lispro period (blood glucose <2.5 mmol l⁻¹: 1.43 vs 2.19 episodes, p = 0.004; symptomatic nocturnal hypoglycaemia 1.16 vs 1.67 episodes, p<0.001). When switching from conventional soluble to lispro insulin, reduction of snack carbohydrates is safe and results in slightly improved HbA_1c in patients who are fully compliant with the dietary change. © 1998 John Wiley & Sons, Ltd.     

Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month 'proof-of-concept' study

Aim: Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated. Methods: This was a 6‐month, parallel‐group, randomized, open‐label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA_1c 7.5–9.5%) using any basal insulin underwent a 3‐month run‐in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA_1c >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2‐h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre‐meal/bedtime BG 100–120 mg/dl (5.5–6.7 mmol/l; US). Results: HbA_1c and fasting plasma glucose levels decreased during the run‐in period. In the 3 months after randomization, more participants in the basal‐plus‐bolus group reached HbA_1c <7.0% than the basal‐only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA_1c (?0.37 vs. ?0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups. Conclusions: In people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects.     

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 with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectiveness

Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or insulin aspart, may offer an advantage over regular human insulin for insulin pumps. Several open-label randomised crossover trials demonstrated that continuous subcutaneous insulin infusion (CSII) with insulin lispro provided a better control of postprandial hyperglycaemia and a slightly but significantly lower glycated haemoglobin level, with lower daily insulin requirement and similar or even less hypoglycaemic episodes. A CSII study comparing insulin lispro and insulin aspart demonstrated similar results with the two analogues, and better results than those with regular insulin. Because these analogues have a quicker onset and a shorter duration of action than regular insulin, one might expect an earlier and greater metabolic deterioration in case of CSII interruption, but a more rapid correction of metabolic abnormalities after insulin boluses when reactivating the pump. These expectations were confirmed in randomised protocols comparing the metabolic changes occurring during and after CSII interruption of various durations when the pump infused either insulin lispro or regular insulin. The extra cost resulting from the use of CSII and insulin analogues in diabetes management should be compensated for by better metabolic control and quality of life. In conclusion, CSII delivering fast-acting insulin analogues may be considered as one of the best methods to replace insulin in a physiological manner by mimicking meal and basal insulin requirements, without higher risk of hypoglycaemia or ketoacidosis in well-educated diabetic patients.     

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.     

Antibody response to insulin in children and adolescents with newly diagnosed Type 1 diabetes

Aims To compare levels of insulin antibodies in children and adolescents after initiation of insulin therapy using either insulin aspart (IAsp) or human insulin (HI) in combination with Neutral Protamine Hagedorn (NPH) insulin, and to investigate the relationships between insulin antibodies and HbA_1c and insulin dose. Methods IAsp‐specific antibodies (IAsp‐Ab) and antibodies cross‐reacting with HI and IAsp (HI‐cross‐Ab) were analysed by radioimmunoassay at diagnosis of diabetes and every 3–6 months for 30 months. Seventy‐two patients (HI = 30, IAsp = 42) with Type 1 diabetes, aged 2–17 years were included. Data on HbA_1c, insulin dose and serious adverse events (SAEs) were collected retrospectively. Results IAsp‐Ab levels remained low throughout the study. After 9 months, the level of HI‐cross‐Ab increased [mean (sd ) HI, 48.8% (21.53); IAsp, 40.2% (17.92)] and remained elevated. Repeated measurement analysis of HI‐cross‐Ab levels showed no significant difference between treatments (P = 0.16). HI‐cross‐Ab were significantly associated with total insulin dose (U/kg) (P = 0.001) and time (P < 0.0001), but not with HbA_1c (P = 0.24). Mean (± sd ) HbA_1c was similar at diagnosis (HI 9.5 ± 1.97%; IAsp 9.6 ± 1.62%); HbA_1c then decreased and stabilized to about 6.0% in both groups. Few SAEs were reported, the majority being hypoglycaemic episodes. Conclusions Treatment with IAsp and with HI was associated with an increase in HI‐cross‐Ab in insulin‐naive children, but this did not influence treatment efficacy or safety. These results support the safe use of IAsp in children and adolescents with Type 1 diabetes.