Long-term benefits of continuous subcutaneous insulin infusion in children with Type 1 diabetes: a 4-year follow-up.

AIM: To determine the safety and effectiveness of continuous subcutaneous insulin infusion (CSII) in attaining long-term glycaemic control in paediatric patients with Type 1 diabetes and to compare the results with those previously recorded in the same patients taking multiple daily injections (MDI) (four injections a day). METHODS: Forty-two patients (mean age 12.2 +/- 3.4 years; range 4.5-17 years; 24 males; mean duration of Type 1 diabetes 5.1 +/- 3.0 years) were studied. The following parameters were assessed in the year before starting CSII treatment (during MDI treatment) and during the 4 years of insulin pump treatment: annual mean HbA1c, insulin requirements (U/kg per day), annual mean of body mass index (BMI) z scores, and adverse events (severe hypoglycaemia and diabetic ketoacidosis/patient per year). Two patients discontinued pump therapy (after 1-year and 2-year follow-up, respectively) because of non-compliance with CSII therapy. RESULTS: Compared with the annual mean HbA1c observed prior to CSII therapy (8.9 +/- 1.0%), the mean HbA1c levels were lower during the first (8.2 +/- 0.9%; P = 0.00), second (8.6 +/- 1.0%; P = 0.05), third (8.4 +/- 0.9%; P = 0.01) and fourth (8.2 +/- 1%; P = 0.00) year of CSII therapy. The insulin requirements (U/kg per day) decreased during CSII treatment compared with MDI treatment. Compared with the annual mean of BMI z scores prior to CSII therapy, BMI z scores were significantly lower during the third and fourth years of CSII therapy. Through the first, second, third and fourth years of follow-up the number of episodes of severe hypoglycaemia (20.0, 20.0, 20.0 and 0 episodes/1000 patient-years, respectively) and diabetic ketoacidosis (0.05, 0.00, 0.03 and 0.00 episodes/patient per year, respectively), events were similar to that in the year preceding CSII therapy (20.0 and 0.03, respectively). CONCLUSION: In this population of selected patients in our clinic, CSII appears to be a safe and effective therapeutic alternative to MDI treatment. This therapy may ensure a stable improvement in long-term glycaemic control in paediatric patients, with no increase in diabetic ketoacidosis and severe hypoglycaemic events and, on the other hand, with a trend of reduction in BMI z scores.     

Insulin-pump use in everyday practice: data from an exhaustive regional registry in France

AIM: The aim of this study is to evaluate the effectiveness and safety of continuous subcutaneous insulin infusion (CSII) under real-life conditions among all patients treated with CSII in the south of Paris. METHODS: The 42 diabetologists practising in the region enrolled all patients treated with CSII or admitted for CSII initiation. During the study visit, the data for pump use and clinical results were recorded. RESULTS: Data were obtained for 424 patients, mean age 44.2+/-15.6 years, disease duration 18.7+/-10.6 years, including 339 treated with CSII for longer than three months (mean duration: 3.5+/-3.5 years; range: 3-258 months). Most of the patients (N=285, 84.8%) had type 1 diabetes; 44 (13.1%) had type 2 diabetes. In patients treated for more than three months, HbA1c decreased significantly between CSII initiation (9.1+/-1.9%) and the study visit (7.8+/-1.4%; P<0.0001). Patients with HbA1c >9%, using the pump, experienced a significant 0.9% improvement in their HbA1c levels with CSII versus multiple daily injections (P=0.001). The number of episodes of moderate hypoglycaemia was 2.7+/-2.5 per patient per week; of severe hypoglycaemia, 0.34 per patient per year and of ketoacidosis, 0.11 per patient per year. Factors significantly associated with HbA1c levels included amount of physical activity, pregnancy, HbA1c at CSII initiation and number of glucose self-determinations. Those associated with the number of moderate hypoglycaemia episodes were basal rate number, female gender and HbA1c level. HbA1c was negatively correlated with moderate hypoglycaemia (P<0.001), but not with severe hypoglycaemia. CONCLUSION: This 'pump' registry establishes the effectiveness of CSII in everyday practice, yet underscores the risks of severe hypoglycaemia and ketosis episodes. It could help diabetologists to improve patient training programmes and follow-up.     

Better long-term glycaemic control with the basal insulin glargine as compared with NPH in patients with Type 1 diabetes mellitus given meal-time lispro insulin.

BACKGROUND: Glargine is a long-acting insulin analogue potentially more suitable than NPH insulin in intensive treatment of Type 1 diabetes mellitus (T1 DM), but no study has proven superiority. The aim of this study was to test superiority of glargine on long-term blood glucose (BG) as well as on responses to hypoglycaemia vs. NPH. METHODS: One hundred and twenty-one patients with T1 DM on intensive therapy on four times/day NPH and lispro insulin at each meal, were randomized to either continuation of NPH four times/day (n = 60), or once daily glargine at dinner-time (n = 61) for 1 year. Lispro insulin at meal-time was continued in both groups. In 11 patients from each group, responses to stepped hyperinsulinaemic-hypoglycaemia were measured before and after 1 year's treatment. RESULTS: Mean daily BG was lower with glargine [7.6 +/- 0.11 mmol/l (137 +/- 2 mg/dl)] vs. NPH [8.1 +/- 0.22 mmol/l (146 +/- 4 mg/dl)] (P < 0.05). HbA(1c) at 4 months did not change with NPH, but decreased with glargine (from 7.1 +/- 0.1 to 6.7 +/- 0.1%), and remained lower than NPH at 12 months (6.6 +/- 0.1%, P < 0.05 vs. NPH). Frequency of mild hypoglycaemia [self-assisted episodes, blood glucose < or = 4.0 mmol/l (72 mg/dl)] was lower with glargine vs. NPH (7.2 +/- 0.5 and 13.2 +/- 0.6 episodes/patient-month, P < 0.05). After 1 year, NPH treatment resulted in no change of responses to hypoglycaemia, whereas with glargine plasma glucose, thresholds and maximal responses of plasma adrenaline and symptoms to hypoglycaemia improved (P < 0.05). CONCLUSIONS: The simpler glargine regimen decreases the percentage of HbA(1c) and frequency of hypoglycaemia and improves responses to hypoglycaemia more than NPH. Thus, glargine appears more suitable than NPH as basal insulin for intensive treatment of T1 DM.     

Ethnicity and social deprivation independently influence metabolic control in children with type 1 diabetes

AIMS/HYPOTHESIS: This study was performed to evaluate the influence of ethnicity and socioeconomic status (SES) on metabolic control in a population-based cohort of children with type 1 diabetes mellitus, and to evaluate whether any relationship between ethnicity and HbA(1c) is mediated by SES. METHODS: We performed a retrospective review of all patients under age 16 years with type 1 diabetes (n = 555) from 1995 to 2005 in the greater Auckland region, New Zealand. Diabetes care variables and HbA(1c) values were collected prospectively, during clinic visits. RESULTS: The mean population HbA(1c) was 8.3 +/- 1.3%. Maori and Pacific patients had poorer metabolic control than their European counterparts (9.1% and 9.3% vs 8.1%, p < 0.001) and higher rates of moderate to severe hypoglycaemia (31.1 and 24.8 vs 14.9 events/100 patient-years, p = 0.03). In multiple linear regression analysis, both ethnicity and SES were independently associated with HbA(1c) (p < 0.001). Other factors associated with higher HbA(1c) level were longer duration of diabetes, higher insulin dose, lower BMI z score and less frequent blood glucose monitoring (p < 0.001). CONCLUSIONS/INTERPRETATION: Both ethnicity and SES independently influenced metabolic control in a large, unselected population of children with type 1 diabetes. Irrespective of SES, Maori and Pacific youth with type 1 diabetes were at greater risk of both moderate to severe hypoglycaemia and long-term complications associated with poor metabolic control.     

The effect of an education programme (HyPOS) to treat hypoglycaemia problems in patients with type 1 diabetes

BACKGROUND: In a randomized, prospective multi-centre trial, the effect of a specific training programme (HyPOS) for patients with hypoglycaemia problems was compared with a control group (CG), receiving a standardized education programme aiming at avoidance of hypoglycaemia by optimization of insulin therapy. METHODS: A total of 164 type 1 diabetes patients (age 46.0 +/- 12.5 yrs, HbA(1c) 7.3 +/- 1.0%, 50% male) were randomized. Hypoglycaemia awareness was measured by the hypoglycaemia awareness questionnaire (HAQ) and by a visual analogue scale (VAS). There were no baseline differences. RESULTS: After a 6-month follow-up, hypoglycaemia awareness significantly improved in HyPOS compared to that in the CG (Delta HAQ 0.7 [95% CL 0.1-1.2], p = 0.024, Delta VAS 0.8 [95% CL 0.2 - 1.2], p = 0.015). In HyPOS, the threshold for detection of low blood glucose (Delta 0.2 mmol/L [95% CL 0.03 - 0.04], p = 0.02) and the treatment of low blood glucose (Delta 4.6 g [95% CL 1.6 - 7.6], p = 0.03) increased significantly. The number of undetected hypogylcaemic episodes (Delta - 1.4 episodes per week [95% CL 0.4-2.5], p = 0.01) and the rate of mild hypoglycaemia dropped significantly in HyPOS (Delta 2.1% [95% CL 0.5-5.3], p = 0.015). The numbers of severe (Delta 0.3 events per patient per year [95% CL - 0.04-1.0], p = 0.037) and very severe hypoglycaemic episodes (Delta 0.3 events per patient per year [95% CL - 0.1-0.7], p = 0.09) were lower in HyPOS, but these differences were not significant. CONCLUSION: Compared to the CG, HyPOS demonstrates additional benefits in terms of improving impaired hypoglycaemia awareness, reducing mild hypoglycaemia, detecting low blood glucose, and treating low blood glucose.     

Evaluation of a holistic treatment and teaching programme for patients with Type 1 diabetes who failed to achieve their therapeutic goals under intensified insulin therapy.

AIMS: To evaluate a treatment and teaching programme including psychosocial modules for patients with Type 1 diabetes mellitus on intensified insulin therapy who failed to achieve their treatment goals despite participation in standard programmes. METHODS: The 5-day inpatient programme comprises small groups of 4-6 patients, focusing on individual needs and problems. Beyond the teaching lessons (most topics are deliberately chosen by the patients), the programme provides intensive group discussions and offers individual counselling concerning motivational aspects, psychosocial problems and coping strategies. Of the first consecutive 83 participants, 76 were re-examined after 17.5 +/- 5.5 months (range 9-31 months). RESULTS: At follow-up, HbA1c was not improved compared to baseline (8.0 +/- 1.3% vs. 8.1 +/- 1.5%). However, the incidence of severe hypoglycaemia per patient/year (glucose i.v., glucagon injection) was substantially decreased: 0.62 +/- 1.5 episodes at baseline compared to 0.16 +/- 0.9 at follow-up (P < 0.001). Twenty-six per cent of the patients at baseline, and 4% at re-examination had experienced at least one episode of severe hypoglycaemia during the preceding year (P < 0.001). Sick leave days per patient/year decreased from 17.0 +/- 38.5-7.7 +/- 13.6 days (P < 0.05). Patients improved their perceptions of self-efficacy, their relationship to doctors and felt less externally controlled (P < 0.001). The majority of patients perceived an improved competence regarding diet (80.6%) and adaptation of insulin dosage (82.4%), an improved knowledge (82.2%), and a renewed motivation for the treatment (84.5%). Treatment success was significantly associated with baseline HbA1c, stability of motivation, frequency of blood glucose self-monitoring, control beliefs and change in subsequent outpatient care. CONCLUSIONS: The programme improved glycaemic control mainly as a result of a substantial reduction in the incidence of severe hypoglycaemia. Patients with persistent poor glycaemic control may benefit from structured follow-up care focusing on motivational aspects of self-management and psychosocial support.     

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.     

Glargine is superior to neutral protamine Hagedorn for improving glycated haemoglobin and fasting blood glucose levels during intensive insulin therapy

AIM: To compare glycaemic control and symptomatic hypoglycaemia rates with glargine versus neutral protamine Hagedorn (NPH) in poorly controlled type 1 diabetes patients. METHODS: Patients (n = 125) received preprandial insulin lispro and either glargine (n = 62) or NPH (n = 63) at bedtime for 30 weeks in a multicentre, randomized, single-blind (a blinded investigator made titration decisions) study. Basal insulin dosage was titrated to achieve fasting blood glucose (FBG) values < 5.5 mmol/L. RESULTS: Baseline characteristics were similar for the two groups (mean diabetes duration 17.5 +/- 10.1 years) except mean glycated haemoglobin (HbA(1c)), which was lower in the glargine versus NPH group (9.2 +/- 1.1% vs 9.7 +/- 1.3%; P < 0.02). At end-point, mean HbA(1c) was 8.3 versus 9.1% for the glargine versus NPH groups. Adjusted least-squares mean (LSM) change from baseline was -1.04 versus -0.51%, a significant treatment benefit of 0.53% for HbA(1c) in favour of glargine (P < 0.01). Mean baseline FBG were similar for the glargine and NPH groups (11.2 vs 11.4 mmol/L). The means for end-point FBG were 7.9 versus 9.0 mmol/L. Adjusted LSM change from baseline was -3.46 versus -2.34 mmol/L, with a significant difference of 1.12 mmol/L in favour of glargine (P < 0.05). There were similar total numbers of daytime mild, moderate or severe hypoglycaemia episodes in the two treatment arms. However, significantly fewer moderate or severe nocturnal hypoglycaemic episodes were observed in the glargine group (P = 0.04 and P = 0.02). CONCLUSION: Glargine is superior to NPH for improving HbA(1c) and FBG levels during intensive insulin therapy in patients with type 1 diabetes, and is associated with less severe nocturnal hypoglycaemia.     

Therapy with insulin glargine (Lantus) in toddlers, children and adolescents with type 1 diabetes

OBJECTIVE: To determine the efficacy and safety of insulin glargine (IG) in children and adolescents with type 1 diabetes. In a prospective, 6-month study, 80 patients, aged 2-19 years, received IG once daily plus insulin regular or rapid analogue before meals. The data of body mass index, frequency of severe hypoglycaemia, daily mean blood glucose, fasting blood glucose, haemoglobin A1c and total daily insulin dosage before and after institution of glargine therapy were collected. RESULTS: After 6 months, the average HbA1c level in the entire cohort dropped from 7.63+/-0.81 to 7.14+/-0.70% (p<0.001). Fasting blood glucose decreased from 161+/-37 to 150+/-35 mg/dl (p<0.05) in the total group. Severe hypoglycaemic episodes were reduced from 0.18 events per patient in the 6 months before IG therapy to 0.11 events per patient in the 6 months after IG therapy. The total daily insulin dose was reduced in the entire group from 0.90+/-0.32 to 0.83+/-0.29 u/kg/day (p<0.05). Body mass index (BMI) remained unchanged. In the 14 preschooler children, the HbA1c dropped from 7.54+/-0.60 to 6.96+/-0.57% (p<0.05). CONCLUSIONS: Insulin glargine is an efficacious treatment to improve metabolic control in children and adolescents with type 1 diabetes. It also improved the metabolic control in preschool-age children, without increasing the number of hypoglycaemic events.     

A randomized pilot study in Type 1 diabetes complicated by severe hypoglycaemia, comparing rigorous hypoglycaemia avoidance with insulin analogue therapy, CSII or education alone.

AIM: To determine potential for amelioration of recurrent severe hypoglycaemia without worsening in overall control in individuals with long-standing Type 1 diabetes (T1DM). METHODS: Twenty-one people with T1DM characterized by altered hypoglycaemia awareness and debilitating severe hypoglycaemia were randomized in a pilot 24-week prospective study to optimized analogue therapy (ANALOGUE; lispro/glargine); continuous subcutaneous insulin infusion therapy (CSII; lispro); or re-education with relaxation of blood glucose targets on existing conventional insulin regimen (EDUCATION). Glycaemic profiles and duration of biochemical hypoglycaemia were measured by continuous subcutaneous glucose monitoring and self-monitored blood glucose. RESULTS: Further severe hypoglycaemia was prevented in five participants (71%) in each group (P = 0.06). Incidence of severe hypoglycaemia was: 0.6 (ANALOGUE), 0.9 (CSII), and 3.7 (EDUCATION) episodes per patient year. Restoration of hypoglycaemia awareness was confirmed by validated questionnaire in three (43%) ANALOGUE, four (57%) CSII and five (71%) EDUCATION patients. Glycated haemoglobin (HbA1c) was significantly improved in the ANALOGUE group between weeks 0 and 24 (8.6 +/- 1.1 vs. 7.6 +/- 0.8%; P = 0.04 for change). Non-significant improvement was seen in the CSII group (8.5 +/- 1.9 vs. 7.4 +/- 1.0%; P = 0.06). No change in HbA1c was seen in the EDUCATION group (8.5 +/- 1.1 vs. 8.3 +/- 1.0%; P = 0.54). There were no episodes of diabetic ketoacidosis or any other adverse events in any group. CONCLUSIONS: In this pilot randomized trial comparing optimized ANALOGUE, CSII or EDUCATION alone in unselected individuals with recurrent severe hypoglycaemia, we show potential for restoring hypoglycaemia awareness and preventing further severe hypoglycaemia with concomitant improvement in glycaemic control in ANALOGUE and CSII groups.     

Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes

AIM: This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin. METHODS: In this multinational, open-labelled, parallel group, 16-week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA(1c) at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored. RESULTS: In the total population (HbA(1c) 7.5-13.0% at screening), end-of-trial HbA(1c) levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (+/-s.e.m), 0.39 +/- 0.15%, p = 0.007]. In a subpopulation (HbA(1c) > or = 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA(1c) levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 +/- 0.21%, p = 0.027). Mean body weight (+/-s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 +/- 13.3 kg vs. 88.9 +/- 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms-only hypoglycaemia were low and similar between treatment groups (0.03-0.04 events/patient/week). CONCLUSION: BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA(1c) > or = 9%.     

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.     

Comparison of lunch and bedtime NPH insulin plus mealtime insulin Lispro therapy with premeal regular insulin plus bedtime NPH insulin therapy in type 2 diabetes

AIM: Nonfasting plasma glucose is claimed to be a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. In this study we compared the efficacy and safety profile of two different intensive insulin treatment strategies in patients with uncontrolled type 2 diabetes despite using a twice-daily insulin regimen. METHODS: We studied 60 insulin-treated patients who had uncontrolled type 2 diabetes. The study was a 6-month, open-label, randomised, parallel clinical trial conducted in two diabetes centres. The main end-points for analysis were weekly self-monitored blood glucose readings, HbA1c levels, total daily insulin dose, weight gain and the number of hypoglycaemic episodes. RESULTS: The breakfast 2-h, lunch 2-h and dinner 2-h postprandial glucose values and pre-dinner glucose values were significantly lower in the Lispro group than the regular insulin group. The HbA1c value at the end of the study was significantly lower in the Lispro group (7.3 +/- 0.7%) compared with the regular insulin group (7.7 +/- 0.7%; P<0.05). Mean insulin doses were similar in the treatment groups initially and at the end. There was a statistically significant increase in insulin dose in both groups from baseline to the end of the study (P<0.05). Overall hypoglycaemia rates were comparably low and similar in both groups during the study. CONCLUSIONS: We have shown that mealtime insulin Lispro plus additional lunch and bedtime NPH insulin is superior to premeal regular insulin plus bedtime NPH insulin for overall glycaemic regulation with similar weight gain and comparable rates of hypoglycaemia.     

The effect of subclinical hypothyroidism on metabolic control in children and adolescents with Type 1 diabetes mellitus.

AIMS: Associated autoimmune phenomena might influence metabolic control in children and adolescents with Type 1 diabetes mellitus. A retrospective case control study was performed in order to explore the effect of subclinical hypothyroidism on metabolic control in Type 1 diabetes mellitus. PATIENTS AND METHODS: For this purpose each patient with Type 1 diabetes and subclinical hypothyroidism (cases) was matched for age, duration of disease and, if possible, for sex, with two to three diabetic patients without hypothyroidism (controls). Parameters of metabolic control such as HbA1c, total insulin requirement and frequency of symptomatic hypoglycaemia were retrieved for 12, 6 and 3 months before and after diagnosis of hypothyroidism. RESULTS: Thirteen patients (two male/11 female) patients were diagnosed with subclinical hypothyroidism and were matched with 31 controls (nine male/22 female). There was no difference (mean and range) in terms of age (11.9 years (4.4-18.1) vs. 11.7 years (3.5-18.1), P = 0.9) and duration of disease (5.1 years (1.2-10.5) vs. 4.38 years (0.9-10.8), P = 0.6) between the two groups. There was no difference in HbA1c and total insulin requirement between the two groups at any time point of assessment (anova P = 0.8 and P = 0.1, respectively). Patients with hypothyroidism had significantly more symptomatic hypoglycaemic episodes during the 12 months before diagnosis (anova P = 0.05), increasing progressively during this time period and reaching a peak at time 0 (5.5+/-0.4 vs. 1.6+/-0.1 episodes/month, P = 0.01). No difference could be detected within 6 months of starting substitution therapy (2.4+/-0.2 vs. 1.6+/-0.1 episodes/week, P = 0.8). CONCLUSIONS: These data suggest that subclinical hypothyroidism is associated with an increased risk of symptomatic hypoglycaemia. The prompt introduction of substitution therapy is recommended as it reduces its frequency.     

Management of diabetes mellitus: is the pump mightier than the pen?

Continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) reduces HbA1c levels and hypoglycaemia in patients with type 1 diabetes mellitus (T1DM) compared with multiple daily insulin injections (MDI). The greatest reduction in HbA(1c) levels with CSII occurs in patients with the worst glycaemic control; therefore, the most appropriate and cost-effective use of CSII in adults with T1DM is in those who have continued, elevated HbA(1c) levels or disabling hypoglycaemic episodes with MDI (including the use of long-acting insulin analogues and structured patient education). The disadvantages of CSII include higher costs than MDI and the risk of ketosis in the event of pump failure. In children with T1DM, CSII may be used when MDI is considered impractical or inappropriate. Pumps are not generally recommended for patients with type 2 diabetes mellitus but may improve control in some subgroups. A new generation of smaller insulin infusion pumps with an integrated cannula, called patch pumps, could improve uptake of CSII in general. The important clinical question is not whether CSII is more efficacious than MDI in general adult T1DM, but whether CSII further improves glycaemic control when this control continues to be poor with MDI, and evidence exists that in most cases it does.     

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.     

Improvement of blood glucose control in Type 1 diabetic patients treated with lispro and multiple NPH injections.

AIMS: To evaluate a multiple daily injections (MDI) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally. METHODS: Twenty-five C-peptide negative Type 1 patients already trained to MDI were randomized to lispro (lispro + NPH 5 min before breakfast and lunch, lispro before dinner, NPH at bedtime) or soluble insulin (20-30 min before each meal and NPH at bed-time) for 3 months before crossing over to the other regimen for another 3 months. The mean initial HbA1c level was 8.32+/-1.5%. RESULTS: The variability of capillary blood glucose values was significantly lower with lispro (MAGE 0.75+/-0.36 g/l vs. 0.99+/-0.50, P<0.01; MODD 0.64+/-0.26 g/l vs. 0.80+/-0.40, P<0.05). There was a nonsignificant reduction in HbA1c with lispro: -0.40+/-0.86 vs. -0.08+/-0.71. Mean daily blood glucose levels were significantly lower with lispro (1.53+/-0.48 g/l vs. 1.82+/-0.57 g/l, P<0.05). The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro, P = 0.048. At the end of the study, 75% of the patients chose the lispro associated with multiple NPH regimen for their own treatment. The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro (53% vs. 34%). CONCLUSIONS: An MDI regimen using lispro combined with multiple NPH compared to a standard MDI regimen using soluble insulin reduced day-to-day blood glucose fluctuations, was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control.     

Long-term efficacy and safety of biphasic insulin aspart in patients with type 2 diabetes

BACKGROUND: In this study, we sought to compare the long-term safety and efficacy of biphasic insulin aspart 30 (BIAsp30) with that of biphasic human insulin 30 (BHI30) over a period of 24 months in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes (n=125) were assigned to twice-daily BIAsp30 or BHI30 and participated in both a 3-month initial period and a 21-month extension of a randomized, controlled, multinational trial. RESULTS: No significant difference was found in mean HbA(1c) after 24 months [BIAsp30, 8.35+/-0.20%; BHI30 8.13+/-0.16%; adjusted mean difference (BIAsp30-BHI30) 0.03 (90% CI -0.29 to 0.34)%, P=0.89]. The proportion of patients experiencing major hypoglycaemia was also similar during the first year (BIAsp30, 5%; BHI30, 8%; P=0.72), but it was significantly lower with BIAsp30 than with BHI30 during the second year (BIAsp30, 0%; BHI30, 10%; P=0.04). The proportion experiencing minor hypoglycaemia was not significantly different. No significant difference was recorded in changes in nonspecific insulin antibody levels after 24 months (BIAsp30, 4.87+/-1.92%; BHI30; 1.00+/-1.66%; P=0.13). Body weight change was 0.05+/-0.81 kg in the BIAsp30 group and 2.00+/-0.69 kg in the BHI30 group (P=0.07). CONCLUSIONS: Reduced major hypoglycaemia compared with BHI30 during the second year of treatment and comparable HbA(1c) levels after 24 months appear to support the hypothesis that the improved pharmacokinetic profile of BIAsp30 may favourably affect the balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes.     

Mobile diabetes education and care: intervention for children and young people with Type 1 diabetes in rural areas of northern Germany.

AIMS: To improve the quality of care in children with Type 1 diabetes who have limited access to specialized diabetes care in rural areas, by providing a mobile diabetes education and care team, affiliated with a University hospital paediatric diabetes centre. METHODS: A cohort of 107 children and their families from eight rural hospitals was followed between July 2000 and July 2002. Parameters on quality of metabolic control (HbA(1c), hospitalization rate and number of episodes of severe hypoglycaemia), diabetes knowledge and quality of life at baseline (t(0)), 6 weeks (t(1)) and 6 months (t(2)) after the interventions were measured. RESULTS: Mean HbA(1c) was 7.9 +/- 1.4% at t(0). The proportion of HbA(1c) values < 6.8% increased significantly (P < 0.05) and of values > 8.0% decreased significantly (P < 0.01) at t(1) and t(2). The rate of hospitalization fell significantly by 9.4%, from 16.2% at baseline to 6.8% at t(2) (P < 0.05). The children reported significantly better diabetes-specific quality of life (P < 0.05) and higher self-esteem (P < 0.01) after the intervention. Theoretical diabetes knowledge was increased both in the short and long term (P < 0.05). CONCLUSIONS: The intervention improved metabolic control, diabetes knowledge and diabetes-specific quality of life. We conclude that high-quality diabetes care in a rural area can be provided by a mobile diabetes education and care team.     

Less severe hypoglycaemia, better metabolic control, and improved quality of life in Type 1 diabetes mellitus with continuous subcutaneous insulin infusion (CSII) therapy; an observational study of 100 consecutive patients followed for a mean of 2 years.

AIMS: To compare glycaemic control, occurrence of acute complications, and diabetes-specific quality of life in Type 1 diabetic patients (on intensified conventional insulin treatment (ICT)) before and after initiation of CSII. METHODS: One hundred and three patients (58 women) started CSII between October 1995 and April 1999 in our department. The indication for CSII was optimization of metabolic control and improvement of flexibility of life style (OF group) in 60 patients (58%), and prevention of severe hypoglycaemia (HY group) in 43 patients. Mean age at initiation of CSII was 33 +/- 11 years (OF 33 +/- 10, HY 33 +/- 11 (mean +/- sd)), diabetes duration 18 +/- 9 years (OF 16 +/- 9, HY 20 +/- 9). Three patients stopped CSII, mean duration of CSII of the remaining 100 patients was 1.8 +/- 1.2 years. The occurrence of hypoglycaemia, ketoacidosis and skin abscesses was assessed retrospectively for the 12 months before starting CSII, and recorded continuously during CSII. Quality of life was assessed with a validated, diabetes-specific questionnaire before and after CSII in 50 patients. RESULTS: The incidence of serious hypoglycaemia (any external help) was reduced from 1.23 (OF 0.0; HY 2.93) during ICT to 0.29 cases/patient per year (OF 0.09; HY 0.55) during CSII. The incidence of severe hypoglycaemia (SH) (treated with i.v. glucose or glucagon injection) fell from 0.70 (OF 0.0; SH 1.67) during ICT to 0.06 cases/patient per year (OF 0.02; HY 0.12) during CSII. HbA1c improved from 7.7 +/- 1.1% to 7.2 +/- 1.0% (P < 0.001) (OF 7.8% vs. 7.2%; HY 7.6% vs. 7.2%). During CSII the incidence of abscesses was 0.11 and of ketoacidosis 0.01 cases/patient per year. Quality of life assessments showed significant improvement in all parameters during CSII. CONCLUSIONS: In our cohort of Type 1 diabetic patients, we observed a substantial decrease of hypoglycaemia along with a significant fall of HbA1c. Quality of life on CSII was improved when compared with ICT.