Birthe S. Olsen

The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes

OBJECTIVE A Danish nationwide prospective cohort of children and adolescents with type 1 diabetes was followed for 8 years to study the effect of the prepubertal duration of diabetes on early retinopathy and elevated albumin excretion rate (AER) (>20 microg/min). RESEARCH DESIGN AND METHODS In 1989, blood glucose control (HbA(1c)) and AER was investigated in approximately 80% of all Danish children and adolescents with type 1 diabetes. A cohort of 339 young patients were restudied in 1995 including physical examination, demographic data, HbA(1c), AER, and fundus photography with central reading. Among the patients, a number of 304 had a prepubertal onset of diabetes defined as an onset age less than 11.7 years in girls and 12.9 years in boys. Microalbuminuria was defined as an AER of 20-150 microg min(-1) and macroalbuminuria as AER >150 microg min(-1) in two out of three timed overnight urine samples. RESULTS At the follow-up in 1995-1996, no patients were younger than 12 years of age. The prevalence of any level of retinopathy was 17.7% in the age group 12-15 years, 45.4% from 16 to 20 years, and increased to 67.6% in patients more than 20 years of age. Diabetic retinopathy was significantly associated to poor long-term metabolic control (HbA(1c)) (P<.0001) and to diabetes duration both in patients with a prepubertal onset of disease as well as patients with a pubertal (P<.001) onset of disease. However, the pubertal diabetes duration contributed two times more than the prepubertal diabetes duration. Mean postpubertal diabetes duration to any retinopathy was significantly shorter (9.4 years) in patients with prepubertal onset of the disease compared to patients with postpubertal onset (11.8 years) (P=.0004). In total, the prevalence of elevated AER (>20 microg/min) increased from 4% in 1989 to 13% in 1995. None of the patients younger than 15 years of age had elevated AER, while the prevalence of elevated AER was about 14% from 15 years of age and onwards. Elevated AER in 1995 was significantly related to long-term metabolic control (P<.001) and elevated AER in the preceding years (P<.001) but was not correlated to diabetes duration neither before nor after the age of 12 years. CONCLUSION The prepubertal diabetes duration is significantly associated with the development of diabetic retinopathy. The period, however, contributes less compared to the years after puberty. In concert with other studies, we found no association between raised AER and diabetes duration. This may be explained by the fact that other factors are more significant and dilute the significance of diabetes duration. Nonetheless, it seems prudent to optimise blood glucose control irrespective of age.

Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes

Abstract The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6–12 years) and nine adolescents (aged 13–17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (Cmax ins), 881 ± 321 (SD) pmol/l versus 422 ± 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin tmax ins, 40.0 min (interquartile range: 40–50 min) versus 75.0 min (interquartile range: 60–120 min) for human insulin, (P < 0.001). An age-related effect on Cmax ins and area under the curve (AUC0–5h ins) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted ΔCmax glu being lower for insulin aspart compared with human insulin (increase of 7.6 ± 5.1 versus 9.4 ± 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types. Conclusion The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes.

Novopen Echo® for the delivery of insulin: a comparison of usability, functionality and preference among pediatric subjects, their parents, and health care professionals.

Background: Despite advances in insulin pen design and functionality, the selection of pens available for children with diabetes is limited. This study assessed the usability, functionality and attitudes towards NovoPen Echo®, a new durable insulin pen designed for pediatric patients that combines a simple memory function with half-increment dosing, versus NovoPen® Junior and HumaPen® Luxura® HD in pediatric subjects, their parents, and health care professionals (HCPs). Methods: Pens were evaluated in random order during 1:1 interviews in the three target groups (pediatric subjects, parents, and HCPs) in Germany, France, and Canada. Study participants were asked to prepare each pen, perform injections into foam cushions, and provide feedback via a standardized questionnaire. Results: In total, 205 participants were included in the study. On a scale of 1–6 (1 = most favorable; 6 = least favorable regarding overall appearance, shape, colors, thickness and length), NovoPen Echo received the most favorable rating for design and overall appearance (mean ± standard deviation = 1.71 ± 0.79) compared with NovoPen Junior (2.02 ± 0.93) and HumaPen Luxura HD (2.36 ± 1.01). Furthermore, 89% of pediatric subjects and 94% of parents rated the memory function of NovoPen Echo as very easy/easy to use. When asked to rate the pens overall, 80% of participants preferred NovoPen Echo to the other pens (p < 0.0001). Conclusions: The results demonstrate a high overall level of satisfaction with NovoPen Echo among pediatric subjects, parents, and HCPs. The novel design aspects of NovoPen Echo, namely t1468-he simple memory function, half-increment units and, ease of use and design, may contribute towards promoting treatment adherence, which is essential in the pediatric setting.

Sick day management in children and adolescents with diabetes

Departmentof Pediatrics, Uddevalla Hospital, Uddevalla, SwedenCorresponding author:Ragnar Hanas, MD, PhDDepartment of Pediatrics, Uddevalla HospitalS-451 80 UddevallaSweden.Tel: 146 522 92000;fax: 146 522 93149;e-mail: ragnar.hanas@vgregion.seEditors of the ISPAD Clinical Practice Consensus Guidelines2006–2007: Ragnar Hanas, Kim Donaghue, GeorgeannaKlingensmith, and Peter Swift.

Retinal Vessel Calibers Predict Long-term Microvascular Complications in Type 1 Diabetes: The Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5–1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.

Insulin pump treatment; increasing prevalence, and predictors for better metabolic outcome in Danish children and adolescents with type 1 diabetes.

Few studies have looked at nationwide data for insulin pump treatment. Since 1996 the Danish Childhood Diabetes Registry (DanDiabKids) has collected data on all Danish diabetic patients aged 0–15 yr. The purpose of this study is to evaluate the prevalence of continuous subcutaneous insulin infusion (CSII) use among Danish children with diabetes and to compare metabolic control in CSII‐treated children and adolescents to those treated with MDI.

Comparison between Early Treatment Diabetic Retinopathy Study 7-field retinal photos and non-mydriatic, mydriatic and mydriatic steered widefield scanning laser ophthalmoscopy for assessment of diabetic retinopathy

AIMS To compare non-mydriatic, mydriatic and steered mydriatic widefield retinal images with mydriatic 7-field Early Treatment Diabetic Retinopathy Study (ETDRS)-standards in grading diabetic retinopathy (DR). METHODS We examined 95 patients (190 eyes) with type 1 diabetes. A non-mydriatic, a mydriatic and four steered mydriatic 200° widefield retinal images were captured (Optos 200Tx, Optos plc, Dunfermline, Scotland) and compared to mydriatic 7-field 45° ETDRS images (Topcon 3D OCT-2000, Topcon, Tokyo, Japan). Images were graded for DR according to ETDRS-protocol by a trained and certified grader masked to the results of the corresponding grading. For agreement kappa-statistics were used. RESULTS Exact level agreement with 7-field images was found in 76.3%, 76.1% and 70.7% for non-mydriatic, mydriatic and steered mydriatic widefield images, respectively. Corresponding values for one-level agreement were 99.0%, 98.9% and 99.5%, respectively. Non-mydriatic matched mydriatic widefield images almost fully with exact and one-level agreement of 96.8% and 100.0%, respectively. Mydriatic steered images resulted in higher grading in 24 eyes. CONCLUSIONS Widefield images matched 7-field images favorably. Widefield images can be captured without pupil-dilation and only one image is needed. However, because of overlapping eyelashes and distortion some lesion might be missed. Mydriatic steered images in selected cases may solve some of these problems.

Improving the outcome for children and adolescents with type 1 diabetes: results of a changing service in Copenhagen

In 1995, an international study of HbA1c levels in 22 centres showed that our centre in Glostrup, Copenhagen, recorded a mean HbA1c significantly above the average. As a consequence, we instituted a series of changes in the structure and process of our service. During the period from 1995 to 1998 we have closely monitored and evaluated the human and financial resources to optimise outpatient care. We reorganised the work of the medical and paramedical staff to concentrate more on outpatient than on inpatient management, established a 24 hour dedicated telephone hotline and defined clear standards of care and criteria for evaluation. In 1993, new rules for the referral system in the Copenhagen area were agreed, resulting in more children being seen at our centre. Consequently, a single, large, centralised childrens clinic for Copenhagen was founded at Glostrup. Despite the increased number of children being seen, the changes made have resulted in a reduction in hospital admissions and a fall in mean HbA1c of approximately 1% across all age groups. This process was facilitated by use of a quality-focused computer program allowing easy data access and surveillance. Copyright

Prevalence and predictors of severe hypoglycemia in Danish children and adolescents with diabetes

To investigate the prevalence of severe hypoglycemia in Danish children and adolescents with type 1 diabetes and to pinpoint predictors of this acute complication in children on modern treatment modalities.

Thiamine-responsive megaloblastic anaemia: a cause of syndromic diabetes in childhood.

Abstract:  Thiamine‐responsive megaloblastic anaemia (TRMA) is a rare autosomal recessive condition, characterized by megaloblastic anaemia, non‐autoimmune diabetes mellitus, and sensorineural hearing loss. We describe three infants with TRMA from two consanguineous Pakistani families, who were not known to be related but originated from the same area in Pakistan. All children were homozygous, and the parents were heterozygous for a c.196G>T mutation in the SLC19A2 gene on chromosome 1q23.3, which encodes a high‐affinity thiamine transporter. The result is an abnormal thiamine transportation and vitamin deficiency in the cells. Thiamine in high doses (100–200 mg/d) reversed the anaemia in all our patients. Two patients discontinued insulin treatment successfully after a short period, while the third patient had to continue with insulin. The hearing loss persisted in all three children. The diagnosis of TRMA should be suspected in patients with syndromic diabetes including hearing loss and anaemia, even if the latter is only very mild and, particularly, in the case of consanguinity.