Kim C. Donaghue

Assessment and monitoring of glycemic control in children and adolescents with diabetes

Marian J Rewersa, Kuben Pillayb, Carine de Beaufortc, Maria E Craigd, Ragnar Hanase, Carlo L Acerinif and David M Maahsa aBarbara Davis Center, University of Colorado Denver, Aurora, CO, USA; bWestville Hospital, Durban, South Africa; cDECCP, Clinique Pediatrique/CHL, Luxembourg, Luxembourg; dInstitute of Endocrinology and Diabetes, Westmead, Australia; eDepartment of Pediatrics, Uddevalla Hospital, Uddevalla, Sweden and fDepartment of Pediatrics, University of Cambridge, Cambridge, UK

Definition, epidemiology and classification of diabetes in children and adolescents

Diabetes mellitus is a group of metabolic diseases characterised by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The abnormalities in carbohydrate, fat, and protein metabolism that are found in diabetes are due to deficient action of insulin on target tissues. If ketones are present in blood or urine, treatment is urgent, because ketoacidosis can evolve rapidly.

The diagnosis and management of monogenic diabetes in children and adolescents

Oscar Rubio-Cabezasa, Andrew T Hattersleyb, Pal R Njolstadc,d, Wojciech Mlynarskie, Sian Ellardb, Neil Whitef, Dung Vu Chig and Maria E Craigh,i aDepartment of Paediatric Endocrinology, Hospital Infantil Universitario Nino Jesus, Madrid, Spain; bInstitute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK; cDepartment of Clinical Science, University of Bergen, Bergen, Norway; dDepartment of Pediatrics, Haukeland University Hospital, Bergen, Norway; eDepartment of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, Lodz, Poland; fDivision of Pediatric Endocrinology and Metabolism, Department of Pediatrics, Washington University School of Medicine, St Louis Children’s Hospital, St. Louis, MO, USA; gDepartment of Pediatric Endocrinology, National Hospital for Pediatrics, Hanoi, Vietnam; hThe Children’s Hospital at Westmead and Discipline of Pediatrics and Child Health, University of Sydney, Sydney, Australia and iSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia

Microvascular and macrovascular complications associated with diabetes in children and adolescents

Department of Pediatrics, Ulleval University˚Hospital, and Faculty of Medicine, University of Oslo, NorwayCorresponding author:Assoc. Prof. Kim DonaghueThe Children’s Hospital at Westmead, Locked Bag 4001,Westmead, NSW 2145, Australia.Tel: C61 2 9845 3172;fax: C61 2 9845 3170;e-mail: kimd@chw.edu.auAcknowledgments: Esko Wiltshire, Gisela Dahlquist, KennethLee Jones, Edna Roche, Amina Balafrej and Riccardo Bonfanti.Conflicts of interest: The authors have declared no conflictsof interest.Editors of the ISPAD Clinical Practice Consensus Guide-lines 2009 Compendium: Ragnar Hanas, Kim Donaghue,Georgeanna Klingensmith, and Peter Swift.This article is a chapter in the

Quantitative Assessment of Early Diabetic Retinopathy Using Fractal Analysis

OBJECTIVE—Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS—We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12–20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. RESULTS—In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023–1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02–7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21–1.56]). This association remained after additional adjustment for retinal vascular caliber. CONCLUSIONS—Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

Microvascular and macrovascular complications

Clinically evident diabetes-related vascular complications should be rare in childhood and adolescence. However, early functional and structural abnormalities may be present a few years after the onset of the disease. There has been a declining incidence of complications reported in many areas with specialized clinics (1–3). This has occurred over a period of time during which there have been major changes in diabetes management, identification of putative risk factors, and the advent of regular screening for complications. There is no evidence that this is a worldwide occurrence: in areas where health care is not optimal, a greater risk of complications will remain. Interventional studies of intensive glycemic control

ISPAD Clinical Practice Consensus Guidelines 2006-2007 The diagnosis and management of monogenic diabetes in children

Authors: Andrew Hattersley, Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, UK Jan Bruining, Sophia Children’s Hospital, Rotterdam, the Netherlands Julian Shield, Department of Child Health, University of Bristol, Bristol, UK Pal Njolstad, Department of Child Health, University of Bergen, Bergen, Norway Kim Donaghue, The Children’s Hospital at Westmead, University of Sydney, NSW, Australia e-mail KimD@chw.edu.au Editors: Kim Donaghue, Ragnar Hanas, Georgeanna Klingensmith, Peter Swift

The Effect of Prepubertal Diabetes Duration on Diabetes: Microvascular Complications in Early and Late Adolescence

OBJECTIVE To define the significance of prepubertal diabetes duration in the development of diabetic microvascular complications in adolescents. RESEARCH DESIGN AND METHODS Study A compares complications in 38 prepubertal (PreP) and 140 pubertal (Pub) subjects of the same age (10-14 years) and diabetes duration (3–12 years) to determine if the absence of puberty itself confers a lower risk of complications. Study B examines the importance of prepubertal and pubertal diabetes duration in 193 older adolescents (ages 15–22 years) with prepubertal onset of diabetes. Retinopathy status was assessed using stereoscopic fundus photography of seven fields per eye. Albumin excretion rate (AER) was assessed by three consecutive overnight urine collections, using a polyclonal radioimmunoassay. RESULTS In study A, there were no significant differences between the PreP and Pub groups for retinopathy (27 vs. 29%, P = 0.8) or differences in elevated AER (17 vs. 31%, P = 0.1). In study B, longer prepubertal diabetes duration improved the prediction for retinopathy over postpubertal duration alone (P < 0.0005). No relationship with duration was found for elevated AER (> 7.5, > 15, and > 30 micrograms/min). CONCLUSIONS Prepubertal subjects with diabetes did not have less retinopathy or elevated albumin excretion compared with pubertal subjects of the same age. Prepubertal diabetes duration is significantly related to the presence of retinopathy in adolescents.

Definition, epidemiology, and classification of diabetes in children and adolescents: Definition, epidemiology, and classification of diabetes

Maria E Craiga,b, Craig Jefferiesc, Dana Dabelead, Naby Baldee, Anju Sethf and Kim C Donaghuea aInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead and University of Sydney, Sydney, Australia; bSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; cPaediatric Endocrinology, Starship Children’s Hospital, Auckland, New Zealand; dDepartment of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA; eDepartment of Endocrinology, University Hospital, Conakry, Guinea and fLady Hardinge Medical College, New Delhi, India

Retinal arteriolar dilation predicts retinopathy in adolescents with type 1 diabetes.

OBJECTIVE—Alterations in retinal vascular caliber may reflect early subclinical microvascular dysfunction. In this study, we examined the association of retinal vascular caliber to incident retinopathy in young patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—This was a prospective cohort study of 645 initially retinopathy-free type 1 diabetic patients, aged 12–20 years. Participants had seven-field stereoscopic retinal photographs taken of both eyes at baseline and follow-up. Retinal vascular caliber was measured from baseline photographs using a computer-based program following a standardized protocol. Incident retinopathy was graded according to the modified Airlie House classification from follow-up photographs. RESULTS—Over a median follow-up of 2.5 years, 274 participants developed retinopathy (14.8 per 100 person-years). After adjustments for age, sex, diabetes duration, glycemia, mean arterial blood pressure, BMI, and cholesterol levels, larger retinal arteriolar caliber (fourth versus first quartile) was associated with a more than threefold higher risk of retinopathy (hazard rate ratio 3.44 [95% CI 2.08–5.66]). Each SD increase in retinal arteriolar caliber was associated with a 46% increase in retinopathy risk (1.46 [1.22–1.74]). This association was stronger in female than in male participants. After similar adjustments, retinal venular caliber was not consistently associated with incident retinopathy. CONCLUSIONS—Retinal arteriolar dilatation predicts retinopathy development in young patients with type 1 diabetes. Our data suggest that arteriolar dysfunction may play a critical role in the pathogenesis of early diabetic retinopathy and that computer-based retinal vascular caliber measurements may provide additional prognostic information regarding risk of diabetes microvascular complications.