Frequency Of Severe Hypoglycemia Research Articles

Multicenter User Evaluation of ACCU-CHEK® Combo, an Integrated System for Continuous Subcutaneous Insulin Infusion

The aim of this study was to evaluate a newly developed system for insulin delivery incorporating a multifunctional blood glucose meter and a remotely controlled insulin pump (ACCU-CHEK® Combo system) in established pump users with type 1 diabetes. The technology was assessed both from device performance and subject usability perspectives. A multicenter, prospective, single group study was carried out in five centers in the Netherlands and four centers in the United Kingdom for more than 6 months. The study was divided into two phases: Phase 1 (4 weeks) for device validation purposes and phase 2 (22 weeks) to observe the impact of the system on metabolic control, patient satisfaction [using the Diabetes Treatment Satisfaction Questionnaire (DTSQ)] and device safety. Eighty subjects completed the planned study period. There were no unexpected device errors. Treatment satisfaction was high at baseline and further increased to study end (DTSQ change version: sum score, 10.6±7.2; scale score range, -18 to +18, p<0.0001). Hemoglobin A1c improved continuously over time, from 7.9% (±0.9%) to 7.7% (±0.8%) at month 3 (p<0.001) and 7.6% (±0.8%) at month 6 (p<0.0001). The frequency of severe hypoglycemia was 0.08 per patient years. There was no case of ketoacidosis. The new system was evaluated by experienced continuous subcutaneous insulin infusion users as safe in daily practice and associated with favorable treatment satisfaction and a modest improvement in glycemic control.

Acute consequences of hypoglycaemia in diabetic patients

Strict glycaemic control is a major concern in many people with diabetes, hypoglycaemia being the most limiting factor in the daily management of patients with diabetes. Acute consequences of hypoglycaemic attacks are not precisely evaluated. Acute cardiovascular (CV) complications as myocardial ischaemia or stroke seem to be rare, but possibly ignored mainly in older frail patients. Recent large trials in type 2 diabetic patients have not shown the anticipated mortality benefits of strict glycaemic control, and reported a higher frequency of severe hypoglycaemia in the intensive treatment arms with an excess of CV deaths. The authors of these trials persist to deny a direct link between CV deaths and hypoglycaemia. In young type 1 diabetics “dead in bed” syndrome represents a rare but devastating consequence probably due to arrhythmia and prolonged QTc interval. Driving mishaps represent another complication but with a controversial frequency. Neurologic syndromes are frequent during severe hypoglycaemia but usually reversible. Major brain damages are scarce, but cognitive defects or dementia should be underestimated in older and frail type 2 diabetics. Thus, iatrogenic hypoglycaemia due to insulin or sulphonylureas may cause recurrent morbidity in type 1 and type 2 diabetic subjects, and should be prevented by a reevaluation of glycaemic targets in some patients, patient education and the use of new antidiabetic drugs without hypoglycaemic risk.

Hypoglycaemia following gastric bypass surgery—diabetes remission in the extreme?

Postprandial hypoglycaemia is increasingly recognised as a complication of gastric bypass surgery. While post-bypass hypoglycaemia is often responsive to dietary modification, a subset of individuals develop life-threatening neuroglycopenia, with loss of consciousness, seizures and motor vehicle accidents. Such patients require complex nutritional and medical management strategies to reduce postprandial insulin secretion and stabilise glucose excursions, using medications including acarbose, octreotide and diazoxide, and frequent monitoring of glucose values. In an article in this issue of Diabetologia, nationwide registry data from Sweden were used to assess the frequency of severe hypoglycaemia and potentially related diagnoses (e.g. confusion, syncope, seizures, accidental death) following obesity surgery. Relative risk of hypoglycaemia and related diagnoses were two- to sevenfold higher in the post-gastric bypass population, but absolute risk was small. While these data underscore that hypoglycaemia is an important complication of gastric bypass, many questions regarding frequency, pathogenesis and optimal therapy remain unanswered. Given that hypoglycaemia is usually evaluated in the outpatient setting, more precise assessments of hypoglycaemia frequency will require prospective longitudinal studies in post-bypass cohorts. Until such data are available, practitioners should have a higher awareness of symptoms consistent with neuroglycopenia in patients with a history of bariatric surgery. Understanding the beneficial and challenging metabolic consequences of bariatric surgery is a key imperative for the diabetes community, as such data may yield novel insights into mechanisms by which bariatric surgery can lead to diabetes remission.

Continuous subcutaneous insulin infusion (CSII) versus multiple insulin injections for type 1 diabetes mellitus

Type 1 diabetes arises from a failure of insulin secretion, which leads to elevated blood glucose and disturbances in carbohydrate, fat and protein metabolism. There is no means of either preventing or curing type 1 diabetes. Instead, life-long insulin replacement and monitoring of blood glucose levels are required. The conventional means for taking insulin has for some time involved several injections each day, usually two, three or four. However, continuous subcutaneous insulin infusion provides an alternative. Our Cochrane review compares multiple injections with continuous subcutaneous insulin infusion (1). Continuous subcutaneous insulin infusion, or CSII, involves attachment, via a catheter, to an insulin pump. The pump is programmed to deliver insulin to match the person's needs. They can also deliver extra doses themselves to cover meals and correct blood glucose fluctuations. Before starting the review, we knew of numerous studies that had evaluated the two ways of administering insulin but many of these were of poor quality and previous reviews were either out of date or had not used rigorous methodology. This meant that there was uncertainty about which treatment is better. To overcome this, we used a carefully prespecified methodology and searched the literature up to July of 2009. We found and reviewed 23 studies, published from 1982 to 2008. These had recruited a total of 976 patients from a dozen different countries across Europe, North America and the Middle East. Most of the studies had been done in adults, but seven were performed in children. Compared to multiple injections, CSII led to a slight improvement in overall blood glucose control and reduced the frequency of severe hypoglycaemia by at least 50% in most studies. We were not able to investigate short and long term adverse effects, and late complications of diabetes or mortality, because of a lack of data in the trials. While our Cochrane review presents a rigorous and comprehensive analysis of the evidence, there are still many issues that need to be addressed in future trials. Type 1 diabetes may occur at any age and it is one of the most common chronic diseases of childhood and adolescence, so it is interesting that so few patients took part in these trials comparing CSII with multiple injections. Although there is a relatively large number of studies, 23, these tended to be fairly small. The largest recruited 275 patients, but eighteen of the studies had fewer than 50 participants. It is important to be cautious about conclusions drawn from such small trials. Evidence about adverse effects, late complications and mortality is also essential to well informed decision making and needs to be gathered in large scale methodologically rigorous trials. Information about cost effectiveness would also help in making the choice between these two types of insulin therapy.

Fear of hypoglycaemia in adults with Type 1 diabetes

The aim of this study was to examine the fear of hypoglycaemia and its association with demographic and disease-specific variables in a large and unselective population of adult patients with Type 1 diabetes. Questionnaires were sent by post to all patients with Type 1 diabetes who were identified in the local diabetes registries of two hospitals in Stockholm, Sweden (n=1387). Fear of hypoglycaemia was measured using the Swedish Hypoglycaemia Fear Survey, the Worry subscale and the Aloneness subscale. Demographic variables and disease-specific factors were collected from patients' self reports and medical records. Univariate analysis and multiple stepwise linear regression analysis were used in the statistical analyses of the data. Seven hundred and sixty-four (55%) patients participated in the study (mean age 43.3 years and mean HbA(1c) 7.0%, normal <5.0%). The Hypoglycaemia Fear Survey - Worry subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, hypoglycaemic symptoms during hyperglycaemia and hypoglycaemic unawareness. The Hypoglycaemia Fear Survey - Aloneness subscale was significantly associated with frequency of severe hypoglycaemia, number of symptoms during mild hypoglycaemia, gender, frequency of mild hypoglycaemia, HbA(1c) , hypoglycaemic unawareness and visits to the emergency room because of severe hypoglycaemia. Fear of hypoglycaemia proved to be more prevalent in females and indicated a different pattern between genders in relation to factors associated with fear of hypoglycaemia. This study identifies the frequency of severe hypoglycaemia as the most important factor associated with fear of hypoglycaemia. Moreover, for the first time, we document gender differences in fear of hypoglycaemia, suggesting that females are more affected by fear of hypoglycaemia than men.

Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes

Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes. Prospective observational follow-up study. Totally 219 patients with type 1 diabetes (41% females, age 46+/-13 years (mean+/-s.d.), duration of diabetes 21+/-12 years, and HbAlc 8.5+/-1.1%) were followed in a 1-year observational study. Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h. Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported by 82 patients (37%). At baseline, plasma EPO was 8.6 (3.1-34.3) U/l (median (range)), and serum VEGF was 52.2 (6.6-337) pg/ml. The levels of EPO and VEGF were not associated with frequency of severe and mild hypoglycaemia. The levels of EPO were not associated with age, sex, duration of diabetes, body mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex. Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes.

Determinants of Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study

There are limited published data characterizing severe hypoglycemia complicating type 2 diabetes. The objective of the study was to determine the incidence and predictors of severe hypoglycemia in community-dwelling type 2 patients. This was a longitudinal observational cohort study. This was a community-based study. There were 616 patients (mean age 67.0 yr, 52.3% males, median diabetes duration 7.7 yr) assessed in 1998 and followed up to the end of June 2006. Severe hypoglycemia defined as that requiring ambulance attendance, emergency department services, and/or hospitalization. Cox proportional hazards modeling was used to determine predictors of first episode, and Poisson, negative binomial, zero-inflated Poisson, and zero-inflated negative binomial regression models identified predictors of frequency. Fifty-two (8.4%) experienced 66 episodes during 3953 patient-years (incidence 1.7 per 100 patient-years). Those experiencing severe hypoglycemia had one to four episodes. Significant independent predictors of time to first episode were duration of insulin treatment, estimated glomerular filtration rate less than 60 ml/min per 1.73 m(2), peripheral neuropathy, education beyond primary level, and past severe hypoglycemia. The zero-inflated negative binomial provided the best model of severe hypoglycemia frequency. Lower fasting serum glucose and higher glycosylated hemoglobin were significantly associated with frequency, whereas patients at minimal risk of repeated severe hypoglycemia were unlikely to use insulin or to have short-duration insulin treatment, to have renal impairment or peripheral neuropathy, or to be educated beyond primary level. Duration of insulin treatment was confirmed as an independent risk factor for severe hypoglycemia. The novel association with educational attainment suggests knowledge-driven intensive glycemic self-management. The positive relationship between frequency and glycosylated hemoglobin may identify patients with unstable glycemic control.

Review: Does hypoglycaemia cause cardiovascular events?

Strict glycaemic control is strongly advocated in people with type 2 diabetes to prevent vascular disease. However, the outcomes of two large clinical trials have indicated the potential dangers of pursuing this policy in those at high risk of cardiovascular disease, with an excess of fatal vascular events being associated with a higher frequency of severe hypoglycaemia. Hypoglycaemia secondary to insulin and sulphonylurea therapy is often associated with serious morbidity; anecdotal evidence has long implicated hypoglycaemia as a potential cause of myocardial ischaemia or a cardiac arrhythmia. Hypoglycaemia provokes sympatho-adrenal activation and counterregulatory hormone secretion, which exert pronounced cardiovascular effects. Although well tolerated in healthy people, the superimposition of these profound physiological effects on a diseased coronary vasculature and a dysfunctional cardiac conductive system may induce serious or even fatal cardiovascular events. These risks should influence therapeutic targets and the approach to diabetes management in people with diabetes with established vascular disease in whom exposure to severe hypoglycaemia could be dangerous.

Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated Type 2 diabetes

Aims The present study sought to ascertain the prevalence of impaired awareness of hypoglycaemia (IAH) in people with insulin-treated Type 2 diabetes (T2DM) and its effect on risk of hypoglycaemia. Methods Data were obtained from 122 people with insulin-treated T2DM (63 male; mean (SD) HbA1c 8.4% (1.5); median (inter quartile range, IQR) age, 67 (58–72) years; duration of T2DM 15 (10–20) years; duration of insulin therapy, 6 (4–9) years). A questionnaire was used to evaluate hypoglycaemia awareness status and estimate the frequency of severe hypoglycaemia (SH) in the preceding year. Capillary blood glucose was monitored prospectively over a 4-week period to document biochemical hypoglycaemia. Results The prevalence of IAH was 9.8%. In the subgroup with IAH the incidence of SH in the preceding year was 17-fold higher than those with normal hypoglycaemia awareness (0.83 (1.12) vs. 0.05 (0.28) episodes per patient; p < 0.001 ( n = 122)) and had a five-fold higher incidence of biochemical hypoglycaemia (2.43 (4.39) vs. 0.46 (1.21) episodes; p < 0.001 ( n = 63)). Conclusion The prevalence of IAH in insulin-treated T2DM was associated with higher frequencies of SH and biochemical hypoglycaemia. Therefore the presence of IAH in those with insulin-treated T2DM should be evaluated at clinical review.

Role of Continuous Subcutaneous Insulin Infusion in Patients with Recalcitrant Diabetes in South India

We aimed to assess the effect of continuous subcutaneous insulin infusion (CSII) therapy in patients with "recalcitrant diabetes" whose glycemia had not been controlled adequately with multiple daily injections of insulin or insulin plus oral hypoglycemic agents. We retrospectively analyzed the medical records of patients with diabetes who were initiated on insulin pump therapy at our center in India between 2002 and 2007. Data analysis included fasting and postprandial blood glucose and glycated hemoglobin (HbA1c) values, insulin requirement, body weight, and the occurrence of hypoglycemia and diabetic ketoacidosis. We studied 33 patients with diabetes (type 1 [n = 17] and type 2 [n = 16]) who were on CSII therapy for a mean duration of 3.4 years. A statistically significant reduction in HbA1c was found after initiating CSII (prepump 10.7% vs. postpump 8.3%, P < 0.001). The reduction was greater in type 1 patients (10.6 +/- 2.1 vs. 8.0 +/- 1.6%) than in type 2 patients (11.0 +/- 2.1 vs. 8.8 +/- 1.4%). There was a reduction in frequency of severe hypoglycemia after starting the CSII pump, and there were no instances of diabetic ketoacidosis. Although HbA1c levels did not reach optimal targets, our data indicate that CSII is an effective therapy for patients with diabetes having recalcitrant diabetes who can afford this treatment and whose glycemia is poorly controlled with conventional therapies.

Use of Continuous Glucose Monitoring System in the Management of Severe Hypoglycemia

Severe hypoglycemia can have a dramatic impact on daily life for people with diabetes. Hypoglycemia is quantifiable by the HYPO-Score derived from the frequency of severe hypoglycemia over a year and a component based on 4 weeks of glucose records. The latter gives a modified HYPO-Score as a short-term measure of hypoglycemia. We used a continuous glucose monitoring system (CGMS) in patients with severe hypoglycemia to assess if we could decrease hypoglycemia as measured by the modified HYPO-Score. Sixteen type 1 diabetes subjects, 52.0 +/- 2.3 years old with a diabetes duration of 29.4 +/- 2.8 years having problematic hypoglycemia were enrolled. All used multiple daily insulin injections, and the glycosylated hemoglobin level was 8.4 +/- 0.3%. After a month of gathering hypoglycemia information for baseline modified HYPO-Score, subjects wore the CGMS for 2 months, and a modified HYPO-Score was repeated. To assess long-term benefit, CGMS was then discontinued for 3 months, and a final modified HYPO-Score was determined. The modified HYPO-Score decreased from 857 +/- 184 to 444 +/- 92 (P = 0.055) (intention-to-treat basis). Further analysis of the modified HYPO-Score when the CGMS was actually functioning showed it decreased from 857 +/- 184 to 366 +/- 86 (P = 0.023). Severe hypoglycemia episodes dropped from 16 at baseline to three when wearing the CGMS. The number of hypoglycemia episodes <3.0 mmol/L dropped from 8.6 +/- 1.5 to 4.7 +/- 0.9 (P = 0.01). Subjects expressed less fear of hypoglycemia with CGMS. In 11 who completed modified Final Month HYPO-Scores, the number of severe hypoglycemic events rose to six. At study end, 13 of 16 subjects elected to continue using the CGMS. When the CGMS was worn and functioning there was a significant decrease in the modified HYPO-Score and number of hypoglycemic values <3.0 mmol/L.

Utilização da insulina glargina em crianças menores de oito anos de idade

To evaluate prospectively the efficacy and safety of insulin glargine use for the metabolic control of type 1 diabetes mellitus (T1DM) children younger than eight years old. Nineteen boys and 11 girls with T1DM were included. Before initiating insulin glargine, all children received intensive NPH and aspart insulins for three months. Afterwards, they were assisted for 12 more months for glargine treatment. All patients performed self blood glucose monitoring before and two hours after meals and in early morning (3:00 AM). Primary endpoints: metabolic control using A1C levels; frequency of mild hypoglycemia (capillary glycemia < 60 mg/dL); and frequency of severe hypoglycemia (loss or alteration of consciousness, seizures or need for medical intervention). Mean A1C at the study entry was 8.68% and after 12 months of glargine, was 8.64% (p = 0.82). Frequency of mild hypoglycemia at 3.00 AM was 1.43/3 months during the NPH period and 0.28/3 months during the glargine period (p < 0.007). Frequency of severe hypoglycemia was 0.56/3 months during the NPH period and 0.008/3 months during the glargine period (p < 0.002). The treatment of T1DM children with insulin glargine was considered as efficacious as with NPH. However, a better safety profile, disclosed by the lower incidence of nocturnal and severe hypoglycemia episodes, was observed for insulin glargine.

Severe hypoglycaemia during pregnancy in women with Type 1 diabetes is common and planning pregnancy does not decrease the risk

The aim of this study was to identify risk factors for severe hypoglycaemia (SH) in pregnancy in Type 1 diabetes, including associations with pregnancy planning and glycaemic control. Clinical data including details of the pregnancy and its outcome, glycaemic control, frequency of SH and evidence of pregnancy planning were collected prospectively as part of a national audit of 160 pregnancies in women with Type 1 diabetes. An episode of SH was experienced by 29.4% of women at some point during the pregnancy, with the percentage of women experiencing SH decreasing from 21.9% in the first trimester to 18.1% in trimester 2 and 10.9% in trimester 3. Longer duration of diabetes was associated with increased frequency of SH during pregnancy (r = 0.191, P = 0.012). A greater fall in glycated haemoglobin (HbA(1c)) between pre-pregnancy and the first trimester was not associated with increased risk of SH in trimester 1. Planned pregnancies had better glycaemic control but higher risk of SH in trimester 1 (P = 0.047). Women with pre-pregnancy retinopathy and current smokers had an increased risk of SH in trimester 3 (P = 0.029, P = 0.033). SH is common during pregnancy and particularly in the first trimester. Planning pregnancy does not decrease the risk of SH. Improvements in glycaemic control at the start of pregnancy do not appear to increase the risk of SH. Education of women and their partners about the risks of SH and its management is essential when planning pregnancy.

Nuevas estrategias terapéuticas en diabetes mellitus tipo 1

The main determinant of the risk of complications from type 1 diabetes mellitus is the total lifetime blood glucose levels. To impact on the health and quality of life of individuals with diabetes, safe and effective methods of achieving and maintaining normoglycemia are needed. Unfortunately, intensive insulin therapy does not achieve normal levels of blood glucose, is difficult to implement for many patients, and limited by the accompanying increased frequency of severe hypoglycemia. Hence, the only way at present to restore permanently normoglycemia without hypoglycemia is to provide the patient with additional beta-cells. This can be achieved by transplanting an intact pancreas, or by transplanting islets. The shortage of functional beta-cells from available donors is one of the major limiting factors for the treatment of diabetes by islet transplantation. Therefore, methods to preserve or even promote regeneration of the beta-cell mass are dearly needed. Significant progress has been made over the last decade in stem cell biology. However, the quest for identification of stem cells has been hampered by the lack of appropriate research tools including assays that allow assess their differentiation potential in vitro and in vivo. Therefore, new techniques are necessary in order to develop new therapeutic strategies based on stem cells for the treatment of diabetes mellitus type 1.

Review: Continuous subcutaneous insulin infusion therapy and children with type 1 diabetes mellitus: the 2008 updated NICE guidelines

Approximately 25,000 children and young people live with type 1 diabetes in the UK. Their high risk of long-term complications is compounded by the problematic management of diabetes in children. CSII (continuous subcutaneous insulin infusion), or `insulin pump', therapy has the potential to improve glycaemic control, reduce the frequency of severe hypoglycaemia and improve quality of life, but is presently underused. NICE (National institute for Health and Clinical Excellence) now recommends CSII as a treatment option for adults and children aged 12 years or older with type 1 diabetes, when MDI (multiple daily injection) insulin therapy results in disabling hypoglycaemia or fails to reduce HbA 1c levels below 8.5%, and for children aged under 12 years whenever MDI therapy is impractical or inappropriate. These new recommendations are likely to increase the use of CSII across the UK. Accordingly, healthcare providers will need to integrate this modality routinely within a cohesive service for adults and children with diabetes. As CSII therapy should be initiated only by a specialist team (normally comprising a physician with a special interest in CSII, a diabetes specialist nurse and a dietician), improving access to accredited staff training is a priority.

Treatment of diabetes mellitus using an external insulin pump: the state of the art

The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetic complications while reducing the frequency of hypoglycaemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump is an intensive diabetes therapy recognized to improve metabolic control and glycaemic instability, and to reduce the frequency of severe hypoglycaemia. For years, the theoretical advantages of the insulin pump (constancy of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycaemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, insulin pump therapy is now challenged by new MDI regimens based on long-acting insulin analogues that could replace the use of CSII. As a consequence, health professionals now have to determine which patients are likely to benefit the most from CSII. Recently, several studies reported that children and adolescents, and patients whose blood glucose imbalance was initially the most pronounced with basal-bolus regimens, would particularly benefit from CSII. Other indications were also proposed in marginal clinical situations with highly selected patients in whom a significant improvement of blood glucose was demonstrated. Finally, the use of CSII in type 2 diabetic patients now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients. However, past experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Use of CSII also requires strict medical supervision by physicians and a regular programme of patient education by paramedical teams, to ensure optimal responsible use of this technique by healthcare professionals.

Use of Continuous Glucose Monitoring in Patients with Type 1 Diabetes

The prevalence of type 1 diabetes continues to increase worldwide at a rate higher than previously projected, while the number of patients achieving American Diabetes Association (ADA) glycated hemoglobin (A1c) goals remains suboptimal. There are numerous barriers to patients achieving A1c targets including increased frequency of severe hypoglycemia associated with lowering plasma glucose as measured by lower A1c values. Continuous glucose monitoring (CGM) was first approved for retrospective analysis and now has advanced to the next step in diabetes management with the approval of real-time glucose sensing. Real-time CGM, in short term studies, has been shown to decrease A1c values, improve glucose variability (GV), and minimize the time and number of hypoglycemic events in patients with type 1 diabetes. These products are approved for adjunctive use to self-monitoring of blood glucose (SMBG), but future long-term studies are needed to document their safety, efficacy, ability to replace SMBG as a tool of monitoring, and ultimately utility into closed-loop insulin delivery systems. New algorithms will need to be developed that account for rapid changes in the glucose values, so that accuracy of the sensor data can be maintained. In addition, for better clinical care and usage, algorithms also need to be developed for both patients and the providers to guide them for their ongoing diabetes care.

Improved glycemic control and lower frequency of severe hypoglycemia with insulin detemir; long-term experience in 105 children and adolescents with type 1 diabetes

To assess the effect of the insulin analog detemir on glycemic control and severe hypoglycemia in children and adolescents with type 1 diabetes. A retrospective chart analysis was performed in 105 patients with type 1 diabetes after switching to insulin detemir between 2004 and 2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn (NPH) insulin was replaced by insulin detemir if therapeutic goals were not reached and blood glucose levels were unpredictable or hardly controllable. In adolescents above 12 yr of age (n = 52), insulin detemir was started when changing to intensified insulin therapy. In children below 12 yr of age, hemoglobin A1c (HbA1c) at start was 8.3 +/- 0.8% and after 12 months of treatment with insulin detemir significantly lowered (7.6 +/- 0.6%, p < 0.001). In the age-group above 12 yr of age at the start of the study, the improvement of HbA1c after 12 months of treatment was less pronounced (8.0 +/- 1.2 vs. 7.6 +/- 1.0%) but still significant (p < 0.01). The risk for severe hypoglycemia was significantly decreased compared with patients attending the outpatient clinic between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p = 0.003). From the beginning to the end of the follow-up period, body mass index dropped significantly in children below 12 yr of age but no effect was observed in adolescents. Use of insulin detemir allows a safe nocturnal glycemic control in children and adolescents with type 1 diabetes and is associated with significantly improved HbA1c levels and fewer severe hypoglycemic events. This makes insulin detemir a most valuable new tool for the treatment of children and adolescents with type 1 diabetes.

Vascular disease and diabetes: is hypoglycaemia an aggravating factor?

Acute hypoglycaemia provokes profound physiological changes affecting the cardiovascular system and several haematological parameters, principally as a consequence of sympatho-adrenal activation and counter-regulatory hormonal secretion. Many of these responses have an important role in protecting the brain from neuroglycopenia, through altering regional blood flow and promoting metabolic changes that will restore blood glucose to normal. In healthy young adults the cardiovascular effects are transient and have no obvious detrimental consequences. However, some of the effected changes are potentially pathophysiological and in people with diabetes who have developed endothelial dysfunction, they may have an adverse impact on a vasculature that is already damaged. The acute haemodynamic and haematological changes may increase the risk of localized tissue ischaemia, and major vascular events can certainly be precipitated by acute hypoglycaemia. These include myocardial and cerebral ischaemia and occasionally infarction. Established diabetic retinopathy often deteriorates after strict glycaemic control is instituted, the latter being associated with a threefold increase in frequency of severe hypoglycaemia, and enhanced exposure to mild hypoglycaemia. The possible mechanisms underlying these hypoglycaemia-induced effects include haemorrheological changes, white cell activation, vasoconstriction, and the release of inflammatory mediators and cytokines. The concept that acute hypoglycaemia could aggravate vascular complications associated with diabetes is discussed in relation to evolving comprehension of the pathogenesis of atherosclerosis and blood vessel disease.

Effects of insulin pump vs. injection treatment on quality of life and impact of disease in children with type 1 diabetes mellitus in a randomized, prospective comparison

Effects of pump treatment vs. four times daily injections were explored in children with diabetes with regard to quality of life and impact of disease as well as adverse effects and parameters of metabolic control. An open, parallel, randomized controlled prospective comparative study lasting 14 months was completed by 38 type 1 children with diabetes (age 4-16 yr) following a 3.5-months run-in phase. Standardized quality-of-life Pediatric Quality of life Inventory (PedsQL) and impact of disease scores were obtained every 3.5 months as well as regular medical parameters. Parallel treatment group data and longitudinal within-patient data were analysed for each treatment modality. Within-patient comparisons of the two treatment modalities showed significant improvement in PedsQL and impact scores after pump treatment. Treatment group comparisons did not show significant improvement. Pump treatment resulted in decreased symptomatic hypoglycaemia and lowered haemoglobin A1c by 0.22% after run in. Within-patient comparison suggests that metabolic control, frequency of severe hypoglycaemia (a threefold decrease), quality of life and impact of disease scores are improved by pump treatment in comparison to regular treatment with four daily insulin injections.