Hilary Hoey

Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: Results from the Hvidore study group

Abstract. The optimal insulin regimen for paediatric patients with type 1 diabetes remains controversial. Therefore this multicentre study was performed in adolescents over a 3-year period to assess metabolic control, severe hypoglycaemia, and weight gain in relation to insulin injection regimens. Out of 2873 children and adolescents in an international survey in 1995, 872 adolescents (433 boys, 439 girls, mean age in 1995 11.3±2.2 years) were restudied in 1998, relating insulin regimens to HbA1c measured in a central laboratory. In addition, the daily dose of insulin, changes in body mass index (BMI), and events of severe hypoglycaemia were evaluated. Over 3 years, the use of multiple injection regimens increased from 42% to 71%: 251 patients remained on twice daily insulin, 365 remained on multiple injections and 256 shifted from twice daily insulin to multiple injections. In all three subgroups an increase in insulin dose, a deterioration of metabolic control, and an increase in BMI were observed. Metabolic control deteriorated less than expected over 3 years during adolescence (HbA1c 1995: 8.7±1.6%; 1998 observed: 8.9±1.6%, HbA1c expected for 1998: 9.0%). BMI increased more than expected, the increase was greatest in patients switching from twice daily to multiple injections, and higher in females compared to males. Conclusion: in this international study, metabolic control was unsatisfactory in many adolescents with type 1 diabetes irrespective of the insulin regimen. No improvement in metabolic control was observed in this cross-sectional survey, over 3 years in any of the subgroups. Even the group switching from twice to multiple injections did not improve blood glucose control and the increase in body mass index was most pronounced in this group. Conclusive evidence, however, should be based on prospectively planned, randomised therapeutic trials in paediatric patients.

New definition for the partial remission period in children and adolescents with type 1 diabetes

OBJECTIVE To find a simple definition of partial remission in type 1 diabetes that reflects both residual β-cell function and efficacy of insulin treatment. RESEARCH DESIGN AND METHODS A total of 275 patients aged <16 years were followed from onset of type 1 diabetes. After 1, 6, and 12 months, stimulated C-peptide during a challenge was used as a measure of residual β-cell function. RESULTS By multiple regression analysis, a negative association between stimulated C-peptide and A1C (regression coefficient −0.21, P < 0.001) and insulin dose (−0.94, P < 0.001) was shown. These results suggested the definition of an insulin dose–adjusted A1C (IDAA1C) as A1C (percent) + [4 × insulin dose (units per kilogram per 24 h)]. A calculated IDAA1C ≤9 corresponding to a predicted stimulated C-peptide >300 pmol/l was used to define partial remission. The IDAA1C ≤9 had a significantly higher agreement (P < 0.001) with residual β-cell function than use of a definition of A1C ≤7.5%. Between 6 and 12 months after diagnosis, for IDAA1C ≤9 only 1 patient entered partial remission and 61 patients ended partial remission, for A1C ≤7.5% 15 patients entered partial remission and 53 ended, for a definition of insulin dose ≤0.5 units · kg−1 · 24 h−1 5 patients entered partial remission and 66 ended, and for stimulated C-peptide (>300 pmol/l) 9 patients entered partial remission and 49 ended. IDAA1C at 6 months has good predictive power for stimulated C-peptide concentrations after both 6 and 12 months. CONCLUSIONS A new definition of partial remission is proposed, including both glycemic control and insulin dose. It reflects residual β-cell function and has better stability compared with the conventional definitions.

Clinical presentation of type 1 diabetes

Abstract:u2002 Objective:u2002 To identify the presenting features of type 1 diabetes in a national incident cohort aged under 15u2003yr, the duration of symptoms, the occurrence of diabetic ketoacidosis (DKA) at presentation, and the frequency of a family history of diabetes.

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers: the Hvidoere Study in Young Children 2009

To investigate whether center differences in glycemic control are present in prepubertal children <11u2009yr with type 1 diabetes mellitus.

Lessons from the Hvidoere International Study Group on childhood diabetes: be dogmatic about outcome and flexible in approach.

Type 1 diabetes is one of the most commonchronic diseases of childhood. nBetween 1989 and 2003, the incidence of type 1 diabetes in youth increased nat approximately 3.9% per year with a projected doubling of cases in nchildren aged <5 yr between 2005 and 2015 (1). This has substantial nimpact on those affected, their families, on pediatric diabetes care, and non national health care budgets. Much has changed over the last decade nin terms of management strategies in type 1 diabetes, however, as Edwin nGale editorialized in 2005 that the challenges of diabetes remain much the nsame (2). In short, there are more cases resulting in increasing disease years ncharacterized by greater medical and psychosocial complexity. The Hvidoere International Study Group on Childhood Diabetes nevolved in 1994 during a meeting that was held in the immediate post nDiabetes Control and Complication Trial (DCCT, 3) era to discuss nstrategies that could improve the quality of pediatric diabetes care nand thereby improve subsequent adult outcomes. The objectives and nmission statement of the Hvidoere group can be found on its website nhttp://www.hvidoeregroup.org/. In short, this unique collaboration of 26 npediatric diabetes centers from 23 countries (Europe, North America, nJapan, and Australia) has undertaken a series of research projects ninvestigating critical determinants for long-term outcome of type 1 ndiabetes care discriminating in terms of outcomes and which aspects of ncare are universally effective. In all the Hvidoere studies, HbA1c was nanalyzed centrally at the Steno Diabetes Center, Denmark. In the period nfrom 1997 to December 2002 HbA1c was analyzed using an automated nhigh pressure liquid chromatographic method (Bio-Rad Variant, Bio-Rad nLaboratories, Hercules, CA, USA) using the same calibrator lots as nthe DCCT laboratory. From 2003 till now, HbA1c was analyzed by nthe DCCT aligned TOSOH Automated Glycohemoglobin Analyzer nHLC-723G7, Tosoh Corporation, Tokyo, Japan. Five major studies have been undertaken, both crosssectional nand longitudinal, serving this goal. The nfindings detailed below show that these studies have led nto an internationally recognized remission parameter n(4) and have validated well-being and quality-of-life n(QOL) questionnaires (with relevant translation, (5). nThe key thematic and practical findings of this body nof work (published in 28 peer reviewed medical and nscientific journals) are summarized in this review.

Prevalence of renal malformation in Turner syndrome.

Abstract. The presence of renal malformation was evaluated in 43 patients with Turner syndrome (TS) and compared with the karyotype in each case; 28 patients (65%) had a mosaic karyotype and the other 15 (35%) had only 45,X metaphases. Renal malformations characteristic of TS were found in 24% of the complete sample group. Of the 15 cases of pure 45,X karyotype, 8 (53%) had abnormal renal findings, while these were found in only 2 of the 28 mosaic cases (7.1%). The probability of this distribution having occurred by chance is P <0.05. More than 50% of girls with TS are said to have a renal anomaly. In this study renal malformations were found in 25% of the sample group. A significantly greater association of renal malformation was found with monosomy 45,X than with mosaicism. As mosaicism occurs in up to 60% of all girls with TS, the lower figure reported here represents a truer prevalence than that quoted in older series, where the figures quoted applied only to the 45,X syndrome.

Management of obesity in children differs from that of adults

Obesity in childhood is a very common disorder with an increasing prevalence. It is one of the most serious public health challenges. The objectives of the present paper are to increase the awareness of the problem of obesity in childhood, its serious complications and the need for prevention. Overweight and obese children are likely to remain obese into adulthood and more likely to develop serious complications including health problems such as diabetes and CVD, as well as psychological and social challenges. Overweight and obesity are largely preventable. In adults it is difficult to reduce excessive weight gain once it has become established, thus children should be considered the priority population for intervention strategies and prevention. Nutrition, exercise, weight gain in infancy, genetic and environmental factors, all contribute to the aetiology. Prevention and treatment of obesity in childhood requires education and empowerment of families relating to diet and exercise, along with the regulation and control of food marketing and clear nutritional labelling. The eating and physical activity behaviour of a child is strongly influenced by environmental and social factors. Therefore treatment will have only limited success in an environment where adequate physical activity is inhibited and the consumption of high-energy food is stimulated. Government investment in a health promotion programme addressing the issue of obesity in the population as a whole, with particular emphasis on the prevention and management of obesity in childhood is vital. The family doctor and multidisciplinary team play an important role. Regular visits to the family doctor, including growth assessment, will help motivate the family to restrict energy intake and to increase exercise. Therefore the prevention of childhood obesity needs high priority.

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study.

BACKGROUNDnShort children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies.nnnMETHODSnIn the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67u200aμg/kg per day) to three different regimens: high dose (67u200aμg/kg per day), low dose (35u200aμg/kg per day) or IGF1 titration.nnnRESULTSnThe average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38u200aμg/kg per day, s.d. 0.019) and the low-dose group (35u200aμg/kg per day, s.d. 0.002; P=0.46), but there was a wide variation in the IGF1 titration group (range 10-80u200aμg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS, s.d. 0.18) during the second year of the randomised trial compared with the high-dose group (0.46 SDS, s.d. 0.25), but not significantly lower than the low-dose group (0.23 SDS, s.d. 0.15; P=0.17). The IGF1 titration group had lower IGF1 levels after 2 years of the trial (mean 1.16, s.d. 1.24) compared with both the low-dose (mean 1.76, s.d. 1.48) and the high-dose (mean 2.97, s.d. 1.63) groups.nnnCONCLUSIONnIGF1 titration of GH dose in SGA children proved less effective than current dosing strategies. IGF1 titration resulted in physiological IGF1 levels with a wide range of GH dose and a poorer growth response, which indicates the role of IGF1 resistance and highlights the heterogeneity of short SGA children.

Head Circumference Standards for Irish Children

Abstract. A cross‐sectional study measuring head circumference was performed on 3344 Irish Children aged from 5 to 19 years. Comparison with other countries showed a slightly larger head circumference than the 1965 British standards produced by Tanner, but significantly smaller than the Ounsted data from Oxford. There Was no significant difference between the urban and rural children, but the children of non‐manual workers had a significantly larger head than those of manual workers.

Is the incidence of type 1 diabetes in children and adolescents stabilising? The first 6 years of a National Register.

AbstractThe Irish Childhood Diabetes National Register (ICDNR) was established in 2008 to define accurately the incidence and monitor the epidemiology of type 1 diabetes (T1D) in the Irish population. Here, we report data from the first 6xa0years of the National Register and compare with previous national data. Prospective national incident data regarding T1D in those under 15xa0years resident in Ireland were collected from 2008 to 2013 and national incidence rates (IRs) calculated. Ascertainment completeness was assessed using capture-recapture methodology. The period identified 1566 new cases of T1D, ascertainment reached 96.8xa0% in 2013. The standardised incidence rate was 27.5 in 2008 stabilising at 28.7 and 28.8 cases /100,000/year in 2012 and 2013. There was no evidence that the incidence changed significantly in the 6-year period either overall or for each age group and gender. There was evidence of a difference in the incidence of T1D across the age groups with the overall incidence highest in the 10–14xa0year age category. A strong seasonal association was demonstrated.n Conclusions: This study confirms Ireland as a high-incidence country for type 1 diabetes whilst demonstrating that the previous marked increase in IR from 16.3 cases/100,000/year in 1997 has not continued. Ongoing monitoring through the robust mechanism of the ICDNR is required to clarify whether this is a fluctuation or if the incidence of T1D diabetes has stopped rising in our population. Alternatively, this apparent stabilisation may reflect a shift to a later age at diagnosis.“What is known:”• The incidence of Type 1 diabetes (T1D) is increasing in most populations worldwide although in certain high-incidence populations, it may be stabilising• There was a marked increase in T1D in Ireland between 1997 and 2008• T1D incidence increases with affluence“What is New:”• The high incidence of T1D in Ireland has been confirmed at 28.8 cases/100,000/year in 2013 and has been effectively stable in the period 2008–2013• Incidence is highest in Irish 10–14xa0year olds• Changes in incidence possibly reflecting life style and economic climate• Marked seasonality of diagnosis confirmed