Flexible Insulin Research Articles

Minimizing hypoglycemia while maintaining glycemic control in diabetes.

In an accompanying Perspectives article, Cryer (1) identifies a number of different areas where therapeutic interventions have the potential to reduce hypoglycemia without compromising glycemic control. Some approaches provide well-defined clinical benefits, a few offer dramatic reductions in hypoglycemia but remain out of reach for most people, and others, although promising, have yet to be properly evaluated (Table 1). In this Perspectives article, I examine the evidence that underpins these interventions. It is beyond the scope of this article to review the data for each potential intervention in detail, but the reader is directed to the source where appropriate. The focus of this article is treatment of type 1 diabetes, as most of the specific potential therapies have been evaluated in this group, although included are comments in relation to recent trials of intensive therapy in type 2 diabetes. ### Education and skills training in self-management. Long before the benefits of tight glucose control had been established (2), the belief that insulin therapy should be designed to replace insulin “physiologically” had been advocated by a small number of enthusiastic clinicians. The advent of blood glucose monitoring in the late 1970s had a major impact, since background and meal-related insulin could be given separately and adjusted according to self-monitored blood glucose measurements. Participants were encouraged to eat freely, calculating their insulin dose according to their chosen amount of carbohydrate. Integrating these components was a complex task, probably beyond that of many physicians, let alone patients. If this was to be undertaken every day, then patients needed to acquire the skill of flexible insulin self-management and apply it successfully. The therapeutic education approach was pioneered by Assal et al. (3), and Berger and Muhlhauser (4) went on to develop a residential training course (Insulin Treatment and Training program [ITTP]) evaluating the intervention in a series of studies, including …

Treatment of diabetes mellitus using an external insulin pump in clinical practice

Before the initiation of insulin pump therapy, patients must be aware of the different aspects of this form of intensive insulin therapy. Most healthcare professionals recommend a sequential approach to inform patients about CSII. Factors that need to be considered in choosing an insulin pump include its safety features, durability of the device, tolerability and comfort of the catheter, user-friendliness, technical features and appearance. The initial insulin requirements need to be individualized for the given patient, using different methods to determine the appropriate dosages for the basal rate and prandial boluses. Glycaemic targets and algorithms for insulin dose adaptation need to be learned by the patients to enable them to avoid and/or correct hypo- and hyperglycaemia/ketosis episodes. Patients are also advised on how to carry out frequent self-monitoring of blood glucose—and of ketone bodies, if necessary. Insulin pumps are now able to deliver a range of basal rates and boluses that increase the flexibility of CSII. One specific issue is the approach to meal-planning, based on carbohydrate-counting or the equivalent: this method of so-called ‘flexible insulin therapy’can improve metabolic control (for instance, by diminishing postprandial excursions) as well as the quality of life of patients. Evaluation of the knowledge and practices of the patient can be made through a continuous educational programme carried out by experienced nurses and physicians at the start of therapy and during follow-up. In addition, it may be necessary to identify the reasons for lack of improvement in metabolic control after several months of therapy, which include pump malfunction, cannula problems, miscalculated insulin dosages and insufficient metabolic control in specific clinical situations with a high risk of metabolic deterioration (illness, exercise, concomitant drugs). Annual assessment of the patient using an itemized checklist is required to verify the continued efficacy and safety of insulin pump therapy, two main factors of success with CSII treatment.

Flexible eating and flexible insulin dosing in patients with diabetes: Results of an intensive self-management course

Aims To evaluate the outcomes of an established programme to teach patients to match their insulin dose to their carbohydrate intake. Research design and methods A prospective observational study in Australia (Newcastle, NSW) of 137 consecutive patients with type 1 ( n = 82) or type 2 diabetes ( n = 55) over two successive years. Four educational principles were used to teach intensive insulin management and diabetes self-care skills including: carbohydrate counting and insulin dose adjustment, exercise, appropriate treatment of hypoglycaemia and hyperglycaemia, managing sickness, problem solving, communication with health professionals, goal setting, and the importance of support. Outcomes included changes at 4 and 12 months in HbA1c, self-efficacy measured by a diabetes empowerment scale (DES), diabetes specific quality of life (ADDQoL), and problem solving. Both intention to treat and efficacy analyses were performed. Results Diabetes-related quality of life and diabetes problem solving skills improved significantly. Excluding 16 people who failed to adopt intensive insulin management and 24 who started with an HbA1c less than 7%, intention to treat analysis showed the average HbA1c fell from 8.7% initially to 8.1% at 12 months and the number of people with an HbA1c of less than 8% rose from 67 (48.9%) before the program to 86 (62.8%) afterwards. Conclusions An intensive diabetes self-management program led to improvements in HbA1c, empowerment, and quality of life that were largely sustained at 1 year. This is all the more remarkable given that the intervention was once only, entailed no long-term follow-up, and took place in normal clinical operations.

Insulin Analog Preparations and Their Use in Children and Adolescents with Type 1 Diabetes Mellitus

Standard or 'traditional' human insulin preparations such as regular soluble insulin and neutral protamine Hagedorn (NPH) insulin have shortcomings in terms of their pharmacokinetic and pharmacodynamic properties that limit their clinical efficacy. Structurally modified insulin molecules or insulin 'analogs' have been developed with the aim of delivering insulin replacement therapy in a more physiological manner. In the last 10 years, five insulin analog preparations have become commercially available for clinical use in patients with type 1 diabetes mellitus: three 'rapid' or fast-acting analogs (insulin lispro, aspart, and glulisine) and two long-acting analogs (insulin glargine and detemir). This review highlights the specific pharmacokinetic properties of these new insulin analog preparations and focuses on their potential clinical advantages and disadvantages when used in children and adolescents with type 1 diabetes mellitus. The fast-acting analogs specifically facilitate more flexible insulin injection timing with regard to meals and activities, whereas the long-acting analogs have a more predictable profile of action and lack a peak effect. To date, clinical trials in children and adolescents have been few in number, but the evidence available from these and from other studies carried out in adults with type 1 diabetes suggest that they offer significant benefits in terms of reduced frequency of nocturnal hypoglycemia, better postprandial blood glucose control, and improved quality of life when compared with traditional insulins. In addition, insulin detemir therapy is unique in that patients may benefit from reduced risk of excessive weight, particularly during adolescence. Evidence for sustained long-term improvements in glycosylated hemoglobin, on the other hand, is modest. Furthermore, alterations to insulin/insulin-like growth factor I receptor binding characteristics have also raised theoretical concerns that insulin analogs may have an increased mitogenic potential and risk of tumor development, although evidence from both in vitro and in vivo animal studies do not support this assertion. Long-term surveillance has been recommended and further carefully designed prospective studies are needed to evaluate the overall benefits and clinical efficacy of insulin analog therapy in children and adolescents with type 1 diabetes.

New Strategies for Glucose Control in Patients With Type 1 and Type 2 Diabetes Mellitus in Pregnancy

Over the past 5 decades, perinatal outcome in pregnancies complicated by diabetes mellitus has improved dramatically due in large part to better maternal glycemic control. Self-blood glucose monitoring in combination with flexible or intensive insulin treatment including the use of newer insulin analogs and insulin pump therapy has dramatically improved glucose control in most pregnancies complicated by diabetes. In developing an insulin regimen, careful attention must be paid to both basal and prandial insulin needs. Every effort must be made to avoid hypoglycemia and prevent ketoacidosis. A team approach including the patient, diabetes nurse educator, nutritionist, and social worker is ideal.

Flexible Intensive Versus Conventional Insulin Therapy in Insulin-Naive Adults With Type 2 Diabetes

Improving metabolic control can reduce complications in type 2 diabetes (1–4). Conventional insulin therapy (CIT) and flexible intensive insulin therapy (FIT) are treatment options in insulin-dependent type 2 diabetic patients. In CIT, participants inject premixed human insulin (30% regular insulin, 70% NPH insulin) before breakfast and dinner and follow individually adjusted diet plans with fixed amounts of carbohydrates (5). In FIT, human regular insulin is adjusted before main meals according to current blood glucose readings and desired carbohydrate intake. When necessary, NPH insulin is added at bedtime. CIT can be easy to handle and requires less active diabetes self-management. In FIT, patients benefit from dietary freedom and improvement in quality of life (6). In pilot studies, FIT has shown good metabolic control and low risk of hypoglycemia (7). FIT may have additional advantages due to better postprandial blood glucose control (8). We tested the hypothesis that FIT and CIT in insulin-naive adults with type 2 diabetes are equally effective in regard to metabolic outcomes. We hypothesized that younger participants, in employment, would prefer FIT. The trial was designed as a clinical, prospective, randomized, open-label, single-center, crossover study. The primary end point was glycosylated hemoglobin A1c (GHb); secondary end points were mild and severe hypoglycemia, insulin dosage, blood pressure, BMI, and therapy preference. Participants started insulin therapy either with CIT (group A) or FIT (group B), randomly. Individual insulin dosage and carbohydrate intake were determined …

Continuous Subcutaneous Insulin Infusion Attenuated Glycemic Instability in Preschool Children with Type 1 Diabetes Mellitus

Continuous subcutaneous insulin infusion (CSII) is believed to decrease glycemic instability and hypoglycemia while increasing quality of life compared to insulin injection regimens. To evaluate indices of glycemic control and impact on quality of life, we studied a group of preschool children with type 1 diabetes mellitus (DM) on CSII. Fourteen patients (eight girls and six boys) 3.9 +/- 0.8 years old with DM duration of 2.0 +/- 0.8 years were transitioned from flexible multiple daily insulin (FMDI) (pre-meal aspart and bedtime glargine) to CSII. Patients were evaluated with hemoglobin A(1c) (HbA(1c)) and continuous glucose monitoring quarterly for 1 year. Mean blood glucose (MBG), mean amplitude of glycemic excursion (MAGE), and hypoglycemic events (blood glucose <60 mg/dL) were determined. Patients' parents completed quality of life [TNO-AZL Preschool Children Quality of Life (TAPQoL)] questionnaires for their children at baseline and 1.0 year. The total daily insulin and the bolus:basal ratio did not change during CSII (0.72 +/- 0.21 vs. 0.74 +/- 0.16 U/kg/day and 2.1 +/- 0.61 vs. 2.40 +/- 0.58 U/kg/day, respectively). There was no change in HbA(1c) (8.0 +/- 0.50% vs. 7.8 +/- 0.40%) or frequency of hypoglycemia (moderate, 92.3 vs. 73.1 events/100 patient-years; severe, 22.5 vs. 17.5 events/100 patient-years). The MBG (213 +/- 94 vs. 185 +/- 79 mg/dL) and frequency (1.9 +/- 1.6 vs. 2.1 +/- 2.2) and duration (nocturnal, 135 +/- 141 vs. 120 +/- 103 min; total, 267 +/- 222 vs. 189 +/- 148 min) of hypoglycemic events did not decrease, whereas MAGE was reduced on CSII (210 +/- 31 vs. 168 +/- 22 mg/dL, P < 0.005). The quality of life subscales on the TAPQoL questionnaire did not change on CSII. CSII improved glycemic instability without reducing HbA(1c) or frequency and duration of hypoglycemic events and altering the parent's perception of his or her child's quality of life. CSII improves glycemic instability and is an effective alternative to FMDI therapy in young children with type 1 DM.

Flexible Intensive Insulin Therapy in Adults With Type 1 Diabetes and High Risk for Severe Hypoglycemia and Diabetic Ketoacidosis

The recent subgroup analysis by Samann et al. (1) examined the effectiveness of diabetes treatment and teaching programs (DTTPs) and advocated intensive insulin therapy combined with increased dietary freedom in individuals with type 1 diabetes who were at increased risk of hypoglycemia. There were significant reductions in hypoglycemic episodes, from 6.1 to 1.4 hypoglycemic events per patient per year, after participation. Samann et al. concluded that DTTPs may reduce the occurrence of hypoglycemic episodes for those at risk, but, for several reasons, this …

Flexible Intensive Insulin Therapy in Adults With Type 1 Diabetes and High Risk for Severe Hypoglycemia and Diabetic Ketoacidosis

As we previously discussed, regression to the mean was an important bias of our study, since it was not controlled (1,2). A subgroup analysis may or may not contribute to this bias. Pennant et al. (3) performed statistical simulations of baseline results and found that a reduction from 6.1 to 4.7 (95% CI ±0.2) hypoglycemic events per patient per year may be due to regression to the mean. However, there would still remain a reduction from 4.7 to 1.4 hypoglycemic events per patient per year, which was of clinical importance in this high-risk population. The Diabetes Treatment and Teaching Program (DTTP) for type 1 diabetes has been extensively studied in …

Flexible Intensive Insulin Therapy in Adults With Type 1 Diabetes and High Risk for Severe Hypoglycemia and Diabetic Ketoacidosis

Diabetes treatment and teaching programs (DTTPs) for type 1 diabetes, which teach flexible intensive insulin therapy to enable dietary freedom, have proven to be safe and effective in routine care. This study evaluates DTTP outcomes in patients at high risk for severe hypoglycemia and severe ketoacidosis. There were 96 diabetes centers that participated between 1992 and 2004. A total of 9,583 routine-care patients with type 1 diabetes were examined before and 1 year after a DTTP. History of repeated severe hypoglycemia/severe ketoacidosis was an indication for DTTP participation. Before-after analyses were performed for subgroups of patients with three or more episodes of severe hypoglycemia or two or more episodes of severe ketoacidosis during the year before a DTTP. Main outcome measures were GHb, severe hypoglycemia, severe ketoacidosis, and hospitalization. A total of 341 participants had three or more episodes of severe hypoglycemia the year before a DTTP. Mean baseline GHb was 7.4 vs. 7.2% after the DTTP, incidence of severe hypoglycemia was 6.1 vs. 1.4 events x patient(-1) x year(-1), and hospitalization was 8.6 vs. 3.9 days x patient(-1) x year(-1). In mixed-effects models taking effects of centers and diabetes duration into account, mean difference was -0.3% (95% CI -0.5 to -0.1%; P = 0.0006) for GHb and -4.7 events x patient(-1) x year(-1) (-5.4 to -4; P < 0.0001) for severe hypoglycemia. A total of 95 patients had two or more episodes of severe ketoacidosis. GHb was 9.4% at baseline versus 8.7% after DTTP; incidence of severe ketoacidosis was 3.3 vs. 0.6 events x patient(-1) x year(-1), and hospitalization was 19.4 vs. 10.2 days x patient(-1) x year(-1). In linear models with diabetes duration as the fixed effect, the adjusted mean difference was -2.7 events x patient(-1) x year(-1) (95% CI -3.3 to -2.1; P < 0.0001) for severe ketoacidosis and -8.1 days (-12.9 to -3.2; P = 0.0014) for hospitalization. Patients at high risk for severe hypoglycemia or severe ketoacidosis may benefit from participation in a standard DTTP for intensive insulin therapy and dietary freedom.

Premeal Insulin Treatment During Basal-Bolus Regimen in Young Children With Type 1 Diabetes

The introduction of insulin analogs in clinical practice suggests updating therapeutic schemes in subjects with type 1 diabetes. We read with interest the recent article by Alemzadeh et al. (1), which was designed to determine the feasibility of a flexible multiple daily insulin regimen in preschool children. Rapid-acting insulin analogs offer unquestionable advantages due to their pharmacokinetics and pharmacodynamic properties. However, when used in a basal-bolus regimen, they also need great accuracy in determining the carbohydrate content of the meal. A small mistake could generate a significant problem, including hyperglycemia or hypoglycemia. The meal carbohydrate count system seems to be effective and safe in controlling postmeal hyperglycemia in children treated with continuous subcutaneous insulin infusion (2), but when rapid-acting analogs are associated with glargine at bedtime, they could leave a “window” of low plasma insulin levels during the first portion of the night. Indeed, glargine-insulin plasma levels could not yet be consistently stable (3). Moreover, when using rapid-acting insulin analogs, children need an additional insulin shot to control the carbohydrate intake of their afternoon snack, which is a common practice among children living in the Mediterranean area. The object of the present study was to evaluate fasting and postmeal metabolic effects in prepuberal children treated with glargine and regular or rapid-acting insulin using the carbohydrate counting system. We recruited 30 prepuberal children aged 8.1 ± 1.8 years (means ± SD) with type 1 diabetes, having basal C-peptide <0.1 nmol/l, diabetes duration 5.2 ± …

2P103 Characterization of flexible insulin fibrils induced by reducing agent(31. Protein folding and misfolding (II),Poster Session,Abstract,Meeting Program of EABS &amp; BSJ 2006)

2P103 Characterization of flexible insulin fibrils induced by reducing agent(31. Protein folding and misfolding (II),Poster Session,Abstract,Meeting Program of EABS &amp; BSJ 2006)

Type 1 diabetes: treatment without tears?

The tight relationship between intensified insulin therapy for type 1 diabetes and increased risk of severe hypoglycaemia is axiomatic. This assumption is repeated in paper after paper, usually quoting the DCCT, in which patients allocated randomly to the intensive therapy arm of the study showed a three-fold increase in severe hypoglycaemia [1]. But the DCCT, which demonstrated beyond doubt that improved glycaemic control reduced the risk of microvascular complications [2], reported its findings in 1993. It would be a sad reflection on the art and science of diabetes care if we had not moved forwards since then. In this month’s Diabetologia, Samann and colleagues report on the German experience with a programme of structured diabetes education for those with type 1 diabetes, a programme that has consistently reported improved glycaemic control in conjunction with a reduced risk of severe hypoglycaemia [3]. The report is the latest in a series dating back to 1983, all reporting the same outcome [4]. Why does the German programme succeed where the DCCT and other early programmes of intensive insulin therapy fail? And how much more evidence will be needed before all people with type 1 diabetes are offered a similar experience? The German Diabetes Training and Treatment Programme was started in Dusseldorf by the late Michael Berger and his colleagues. It was – and is – a 5-day programme with a carefully constructed curriculum that aims to teach people with diabetes exactly how insulin works, using well-documented physiological and pharmacological data [5]. It was designed to transfer skills of insulin manipulation and dose adjustment to the patient, using recognised principles of adult learning. It provides the tools for self-assessment and, at least initially, a safe environment in which to experiment, to test the principles being taught, and to define what works best for each individual. From the outset, the programme was designed with a quality control system that has allowed it to spread without dilution from one [6] to 96 diabetes centres in Germany and that, as this report testifies, continues to succeed [3]. The DTTP teaches flexible insulin usage around a flexible lifestyle. In other words, it fits insulin around the life the patient wants to lead. This was anathema to many diabetes physicians, who believed that lifestyle therapies and prescriptive dietary recommendations were the sine qua non of good diabetes control. Berger argued otherwise. Without denying the importance of healthy living as a protection against cardiovascular disease, he recognised that the rationale for dietary restriction was the inadequacy of conventional insulin regimens [7]. ‘Type 1 diabetes’, he said, ‘is an insulin deficiency disease.’ It follows that, if we could learn to use insulin optimally, we could restore choice to the person with type 1 diabetes. He and his colleagues set out to achieve just this. You don’t have to be German to achieve success with this regimen. A DTTP programme was successfully implemented in Austria some years ago [8] and the UK has finally caught up, publishing its successful pilot Dose AdMichael Berger

Flexible multiple daily insulin (FMDI) treatment with insulin glargine is beneficial in preschool aged children

Flexible multiple daily insulin (FMDI) treatment with insulin glargine is beneficial in preschool aged children

Flexible Insulin Therapy With Glargine Insulin Improved Glycemic Control and Reduced Severe Hypoglycemia Among Preschool-Aged Children With Type 1 Diabetes Mellitus

Insulin replacement regimens now stress the importance of administering throughout the day insulin doses that are based on flexible food choices and focusing on improved metabolic control. A flexible multiple daily insulin (FMDI) regimen (premeal lispro plus bedtime glargine) results in lower hemoglobin A1c (HbA1c) levels and fewer hypoglycemic episodes than does a multiple daily insulin (MDI) regimen among school-aged children and adolescents with type 1 diabetes mellitus (DM). The purpose of this study was to determine the feasibility of FMDI therapy for a group of preschool-aged children with type 1 DM who were transitioned from MDI therapy (premeal lispro plus ultralente insulin twice per day), by comparing BMI, total daily insulin requirements, HbA1c levels, and episodes of severe hypoglycemia. Data were collected over a 2-year period, during quarterly DM clinic visits, from 35 patients (17 female patients and 18 male patients, 4.8 +/- 1.0 years of age) who had received MDI insulin therapy for > or =1 year before being transitioned to a FMDI regimen. Although there was no significant change in BMI with FMDI therapy (17.1 +/- 1.8 kg/m2 vs 17.0 +/- 1.7 kg/m2), 43% of patients (6 female subjects and 9 male subjects) were overweight (BMI of >85th percentile for age) both before and after treatment. The total daily insulin requirement (0.67 +/- 0.13 U/kg per day vs 0.78 +/- 0.14 U/kg per day) and bolus/basal insulin ratio (1.1 +/- 0.4 vs 1.9 +/- 0.6) were significantly increased and overall glycemic control was improved after transition to FMDI therapy (HbA1c levels: 8.8 +/- 0.9% vs 8.3 +/- 0.8%). However, HbA1c levels improved only among normal-weight subjects (9.0 +/- 1.0% vs 8.3 +/- 1.0%) and not among overweight subjects (8.7 +/- 0.7% vs 8.4 +/- 0.6%) after FMDI therapy. The overall rate of severe hypoglycemia was significantly decreased with the FMDI regimen (25.5 events per 100 patient-years vs 10.6 events per 100 patient-years) but again only for normal-weight children (29.7 events per 100 patient-years vs 7.4 events per 100 patient-years). The use of FMDI therapy with glargine among preschool-aged children with type 1 DM was associated with improved overall glycemic control and decreased frequency of severe hypoglycemia. Although our study did not have a control group, these findings suggest that FMDI regimens may be a feasible therapeutic alternative to MDI treatment for preschool-aged children with type 1 DM. However, excess body weight status appeared to preclude a desirable therapeutic response in this group of patients.

Hypoglycemia, Hypoglycemia Unawareness and Counterregulation in Children and Adolescents with Type 1 Diabetes Mellitus

Three clinical phenomena have been defined in the last decade in patients with diabetes mellitus as a dangerous iatrogenic sequel of hypoglycemia. These are hypoglycemia unawareness, defective glucose counterregulation and a lowered hypoglycemic threshold for hypoglycemic symptoms. Former mild hypoglycemia episodes cause a decrease and a delay in the protective hormonal counterregulatory response and warning symptoms in subsequent episodes, and in the absence of these, risk of severe hypoglycemia increases considerably. It has been demonstrated that when protection is provided against hypoglycemia with strict monitoring programs designed to avoid even mild hypoglycemia episodes, blunted autonomic symptoms and counterregulatory hormonal responses are rectified. Therefore, the best course of action in the treatment of pediatric diabetes mellitus is frequent blood sugar measurements, flexible multiple dose insulin regimens facilitating insulin dose adjustments as required, and a diet. In order to implement this, it is essential to organize an intensive training program with the patient and family, and to provide psychological support and close coordination with the diabetes treatment team.

Will Long Acting Insulin Analogs Influence the Use of Insulin Pump Therapy in Type 1 Diabetes?

Insulin pump therapy enjoys a steadily growing number of users and is associated with an approximately 0.5% lower A1c as compared to flexible insulin injection therapy in type 1 diabetes patients. An important question is whether superiority of insulin pump therapy persists in the era of rapid acting analogs and will persist in the era of long acting analogs. Pooled data of three randomized clinical trials using rapid acting analogs in both arms shows a 0.35% lower A1c when on the pump. Treatment effect was shown to be larger in those with higher baseline A1c's. Results of three trials comparing insulin pump therapy with regimens consisting of both rapid acting and long acting analogs are inconsistent, probably indicating the advantage of pump therapy at group level is likely to have become relatively small. Therefore, the challenge for the treatment team is to identify those patients who benefit most from insulin pump treatment. Poor glycemic control merits a trial of insulin pump therapy in the motivated patient. Other indications for insulin pump therapy include the need for several basal rates, a life style characterized by unpredictable physical activity and patient preference.

Diabetes care in children is complex

The care of children with type 1 diabetes mellitus (T1DM) has changed dramatically in the past 20 years. This change has been fuelled, in part, by the publication of the results of the Diabetes Complications and Control Trial (DCCT) in 1993 (1). The DCCT included the evaluation of intensive diabetes management in adolescents. The DCCT taught us that glycemic control is directly related to microvascular complications. It also demonstrated the need for a dedicated, skilled, full-time diabetes education team to be co-located with physicians. This has been successfully translated into paediatric practice in the post-DCCT era. Sophisticated, full-time, paediatric diabetes teams with 24 h emergency telephone access have been established in every tertiary children’s hospital in Canada, as well as in many secondary centres with consultant paediatricians. The majority of children with T1DM at diagnosis are now managed on an ambulatory basis by such teams. Key ingredients of these modern diabetes teams are coordinated and flexible integration of care, education, support with case management, empowerment of parents and information systems for quality outcome assessment. Other remarkable developments that have catalyzed the revolution in T1DM diabetes care in children include faster and smaller blood glucose monitors, new ‘designer’ insulins and new technologies for insulin delivery. The rigid exchange system of starch, fruit and milk choices was abandoned as we recognized that all carbohydrates in the diet are similar in T1DM diabetes care and can be given in a usual eating pattern with appropriate flexible insulin doses. We have gained new insight into the psychology of diabetes in children, recognized that the most common cause of diabetic ketoacidosis is insulin omission and learned to use the hemoglobin A1c for identification of youth at risk for diabetic ketoacidosis. Insulin omission to promote weight loss is now a recognized form of an eating disorder in the Diagnostic and Statistical Manual of Mental Disorders, 4th revision (2) psychiatry diagnosis code. The globalization of information has provided parents and adolescents with endless sources of information to keep themselves well-informed. Paediatric diabetes care became even more complicated with the recognition of type 2 diabetes mellitus (T2DM) in youth in the 1980s. In most tertiary paediatric diabetes clinics in Canada, children with T2DM now account for 5% to 30% of the population followed in the clinic. Once diagnosed, T2DM is difficult to treat. It differs fundamentally from T1DM because it is a multisystem disorder, now known as the metabolic syndrome. The approach and treatment of an adolescent with T2DM must include the evaluation of the other components of the syndrome. Our understanding of the etiology, treatment and natural history of this new disease in children is evolving. It is imperative that we continue to expand our knowledge with well-designed treatment trials in this population. The extrapolation of adult data to the paediatric population is fraught with potential pitfalls. To add another wrinkle, it is now believed that 5% of children with diabetes have a monogenic form of inherited diabetes which is neither T1DM nor T2DM and which may respond to selective oral agents or insulin. We must be vigilant in asking a detailed family history of diabetes. The provision of care, education and support for children and adolescents with all forms of diabetes in children is complex. This complexity is reflected in the papers included in this special issue of Paediatrics & Child Health. All children and youth with diabetes in Canada need to have access to a coordinated and integrated diabetes care team to optimize their survival and minimize their morbidity. Diabetes is not a disease that can be managed well in isolation. We must work together to ensure that all our children and youth have access to care that truly makes a difference. The optimum system for delivery of care in our large country requires unique, flexible and creative solutions. Dedicated paediatric regional diabetes education teams are the cornerstone of this system and the creation of dedicated teams to meet the needs of vulnerable young adults with diabetes is the next logical step.

Beneficial Effects of Continuous Subcutaneous Insulin Infusion and Flexible Multiple Daily Insulin Regimen Using Insulin Glargine in Type 1 Diabetes

The aim of this study was to evaluate the metabolic effects of continuous subcutaneous insulin infusion (CSII) with flexible multiple daily insulin (FMDI; premeal lispro + bedtime glargine) therapy as determined by glycosylated hemoglobin (HbA1c), body mass index (BMI), and hypoglycemic episodes in a group of patients who made the transition from multiple daily insulin (premeal lispro + bid ultralente) to either CSII or FMDI therapy. Data from 40 (27 female and 13 male) patients (10.1-17.8 years of age) who were on CSII and 40 age- and gender-matched (27 female and 13 male) patients (10.3-17.3 years of age) who were on FMDI were collected during regularly scheduled visits at a similar frequency over a 1-year period. The total daily insulin dose did not change in CSII (0.97 +/- 0.24 vs 0.91 +/- 0.22 U/kg) and FMDI (0.98 +/- 0.21 vs 0.97 +/- 0.21 U/kg) patients, whereas the bolus:basal insulin ratio was significantly increased in both CSII (1.01 +/- 0.43 vs 1.32 +/- 0.52) and FMDI (1.07 +/- 0.0.41 vs 1.29 +/- 0.47) patients. The total cohort of CSII patients showed a decrease in HbA1c from 8.4 +/- 1.0% to 7.8 +/- 0.8%, whereas the FMDI cohort did not show a significant change in HbA1c (8.5 +/- 1.1% to 8.2 +/- 0.9%). However, 40% of the CSII group and 22.5% of the FMDI group showed > or =1.0% improvement in HbA1c. Also, a similar number of patients in CSII (52.5%; 8.0 +/- 1.1 to 7.2 +/- 0.5%) and FMDI (47.5%; 8.0 +/- 0.5% to 7.5 +/- 0.4%) maintained or achieved target HbA1c values <8.0%. The BMI increased significantly in the CSII group (21.6 +/- 3.2 vs 23.0 +/- 3.0 kg/m2) but did not change in the FMDI group (21.9 +/- 3.9 vs 22.6 +/- 3.8 kg/m2). There was a significant reduction in the rate of severe hypoglycemia (events/100 patient-years) in both cohorts: 20.6 to 8.2 in the CSII and 18.8 to 7.5 in the FMDI. Similarly, the rate of moderate hypoglycemia decreased in both CSII (68.3-35.4) and FMDI (56.3-30.4). CSII therapy resulted in a significant improvement in HbA 1c in the entire group, whereas FMDI therapy improved HbA1c in only a subgroup of patients. However, almost half of the patients in each of the treatment groups maintained or achieved target glycemic control. Both CSII and FMDI treatment groups demonstrated a decreased rate of hypoglycemia without an abnormal increase in BMI. Although the design of this study does not allow direct comparison of the metabolic effects of CSII and FMDI therapies, both regimens seem to be superior to basal ultralente and lispro multiple daily insulin regimen and offer desirable therapeutic alternatives in pediatric diabetes care.

Cost-effectiveness of flexible intensive insulin management to enable dietary freedom in people with Type 1 diabetes in the UK.

To determine the cost-effectiveness of a structured treatment and teaching programme (STTP) combining dietary freedom with insulin adjustment for Type 1 diabetes. Incremental cost-effectiveness analysis based on effectiveness data from three RCTs in Germany, Austria, and Dose Adjustment for Normal Eating (DAFNE) in the UK, to model the long-term microvascular complications of Type 1 diabetes. The STTP approach yields effectiveness gains at a lower cost compared with current standard practice for treatment of Type 1 diabetes. STTPs are likely to save 0.05 life years, yield 0.12 EuroQol 5 dimensions (EQ-5D) and 0.09 visual analogue scale (VAS) incremental quality-adjusted life years, and save approximately pound 2200 per patient treated discounted over 10 years. Introducing STTPs as standard treatment for people with Type 1 diabetes in the UK may help to achieve the primary goal of the National Service Framework (NSF) for Diabetes by enabling individuals to manage their own lifestyle and condition. In doing so it could save valuable resources for the NHS and yield important morbidity and mortality gains.