Hilary Hoey

Insulin management and metabolic control of Type 1 diabetes mellitus in childhood and adolescence in 18 countries

Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross‐sectional, non‐population‐based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4–6.3 %, mean 5.4 %). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 ± 1.3 % (mean ± SD) compared with 8.9 ± 1.8 % in those aged 12–18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg−124 h−1) in children aged 2–9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37 % (n = 1071) used three or more. Of those on two or three injections daily, 37 % used pre‐mixed insulins, either alone or in combination with short‐ and intermediate‐acting insulin. Pre‐adolescent children on pre‐mixed insulin showed similar HbA1c levels to those on a combination of short‐ and long‐acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long‐acting insulin. Among adolescent boys, lower HbA1c was related to use of more short‐acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.

Continuing Stability of Center Differences in Pediatric Diabetes Care: do advances in diabetes treatment improve outcome? The Hvidoere Study Group on Childhood Diabetes

OBJECTIVE—To reevaluate the persistence and stability of previously observed differences between pediatric diabetes centers and to investigate the influence of demography, language communication problems, and changes in insulin regimens on metabolic outcome, hypoglycemia, and ketoacidosis. RESEARCH DESIGN AND METHODS—This was an observational cross-sectional international study in 21 centers, with clinical data obtained from all participants and A1C levels assayed in one central laboratory. All individuals with diabetes aged 11–18 years (49.4% female), with duration of diabetes of at least 1 year, were invited to participate. Fourteen of the centers participated in previous Hvidoere Studies, allowing direct comparison of glycemic control across centers between 1998 and 2005. RESULTS—Mean A1C was 8.2 ± 1.4%, with substantial variation between centers (mean A1C range 7.4–9.2%; P < 0.001). There were no significant differences between centers in rates of severe hypoglycemia or diabetic ketoacidosis. Language difficulties had a significant negative impact on metabolic outcome (A1C 8.5 ± 2.0% vs. 8.2 ± 1.4% for those with language difficulties vs. those without, respectively; P < 0.05). After adjustement for significant confounders of age, sex, duration of diabetes, insulin regimen, insulin dose, BMI, and language difficulties, the center differences persisted, and the effect size for center was not reduced. Relative center ranking since 1998 has remained stable, with no significant change in A1C. CONCLUSIONS—Despite many changes in diabetes management, major differences in metabolic outcome between 21 international pediatric diabetes centers persist. Different application between centers in the implementation of insulin treatment appears to be of more importance and needs further exploration.

Are family factors universally related to metabolic outcomes in adolescents with Type 1 diabetes

Aims  To assess the importance of family factors in determining metabolic outcomes in adolescents with Type 1 diabetes in 19 countries.

Target setting in intensive insulin management is associated with metabolic control: The Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005

Swift PGF, Skinner TC, de Beaufort CE, Cameron FJ, Åman J, Aanstoot H‐J, Castaño L, Chiarelli F, Daneman D, Danne T, Dorchy H, Hoey H, Kaprio EA, Kaufman F, Kocova M, Mortensen HB, Njølstad PR, Phillip M, Robertson KJ, Schoenle EJ, Urakami T, Vanelli M, Ackermann RW, Skovlund SE for the Hvidoere Study Group on Childhood Diabetes. Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005.

Psychosocial factors are associated with metabolic control in adolescents: research from the Hvidoere Study Group on Childhood Diabetes.

Despite major advances in diabetes management tools, metabolic control in children with diabetes is suboptimal. For example, data show that only one third of children achieve the International Society for Pediatric and Adolescent Diabetes (ISPAD) target of HbA1c < 7.5% (1, 2). These data come from research by the Hvidoere Study Group on Childhood Diabetes, an organization that unites 21 consultant pediatric endocrinologists in 19 countries across Europe, Japan, North America, and Australia. The Hvidoere Study Group is committed to stimulating and performing high-quality collaborative multicenter research in children and adolescents to provide an evidence base for improving diabetes care, and to enhance the impact of and raise awareness of the need for scientific research in this area.

VALIDATION OF CONTINUOUS GLUCOSE MONITORING IN CHILDREN AND ADOLESCENTS WITH CYSTIC FIBROSIS - A PROSPECTIVE COHORT STUDY

OBJECTIVE To validate continuous glucose monitoring (CGM) in children and adolescents with cystic fibrosis. RESEARCH DESIGN AND METHODS Paired oral glucose tolerance tests (OGTTs) and CGM monitoring was undertaken in 102 children and adolescents with cystic fibrosis (age 9.5–19.0 years) at baseline (CGM1) and after 12 months (CGM2). CGM validity was assessed by reliability, reproducibility, and repeatability. RESULTS CGM was reliable with a Bland-Altman agreement between CGM and OGTT of 0.81 mmol/l (95% CI for bias ± 2.90 mmol/l) and good correlation between the two (r = 0.74–0.9; P < 0.01). CGM was reproducible with no significant differences in the coefficient of variation of the CGM assessment between visits and repeatable with a mean difference between CGM1 and CGM2 of 0.09 mmol/l (95% CI for difference ± 0.46 mmol/l) and a discriminant ratio of 13.0 and 15.1, respectively. CONCLUSIONS In this cohort of children and adolescents with cystic fibrosis, CGM performed on two occasions over a 12-month period was reliable, reproducible, and repeatable.

Continuing stability of center differences in pediatric diabetes care: do advances in diabetes treatment improve outcome?

OBJECTIVE—To reevaluate the persistence and stability of previously observed differences between pediatric diabetes centers and to investigate the influence of demography, language communication problems, and changes in insulin regimens on metabolic outcome, hypoglycemia, and ketoacidosis. RESEARCH DESIGN AND METHODS—This was an observational cross-sectional international study in 21 centers, with clinical data obtained from all participants and A1C levels assayed in one central laboratory. All individuals with diabetes aged 11–18 years (49.4% female), with duration of diabetes of at least 1 year, were invited to participate. Fourteen of the centers participated in previous Hvidoere Studies, allowing direct comparison of glycemic control across centers between 1998 and 2005. RESULTS—Mean A1C was 8.2 ± 1.4%, with substantial variation between centers (mean A1C range 7.4–9.2%; P < 0.001). There were no significant differences between centers in rates of severe hypoglycemia or diabetic ketoacidosis. Language difficulties had a significant negative impact on metabolic outcome (A1C 8.5 ± 2.0% vs. 8.2 ± 1.4% for those with language difficulties vs. those without, respectively; P < 0.05). After adjustement for significant confounders of age, sex, duration of diabetes, insulin regimen, insulin dose, BMI, and language difficulties, the center differences persisted, and the effect size for center was not reduced. Relative center ranking since 1998 has remained stable, with no significant change in A1C. CONCLUSIONS—Despite many changes in diabetes management, major differences in metabolic outcome between 21 international pediatric diabetes centers persist. Different application between centers in the implementation of insulin treatment appears to be of more importance and needs further exploration.

Social, communicational, and behavioral deficits associated with ring X Turner syndrome

We describe the cognitive and behavioral characteristics of five individuals with a ring X chromosome. All subjects had a small active (early replicating) ring X chromosome. The X inactive specific transcript (XIST) locus was confirmed by fluorescent in situ hybridisation (FISH) to be present in all ring X chromosomes. Mental retardation was present in four individuals. All patients with or without mental retardation had a characteristic profile of aggression toward self and others, episodes of screaming, attentional problems, and impulsiveness. Autistic-like features were also present in all individuals and included limited communication, obsessive compulsive behavior, and social difficulties. In some cases the obsessive behavior was extreme and incapacitating. This characteristic behavioral profile may aid the diagnosis and future understanding of ring X.

Differences between males and females in the seasonality of birth and month of clinical onset of disease in children with type 1 diabetes mellitus in Ireland.

The aim was to study the monthly rhythm of birth and clinical onset in 303 children with type 1 diabetes mellitus (DM1) aged 0-15 years (156 males, 147 females) born between 1980 and 1996 in Ireland and compare to 951,717 infants born in the general population during the same period. Analysis was performed using the cosine fit for rhythm and t-test between the seasons of the year. Whereas the males showed a rhythmic pattern of month of birth, peaking in the summer (p < 0.05), similar to that in the general population, the females showed no seasonal differences in either month of birth or month of onset. A mirror image pattern, nadir in spring and summer (p < 0.01), was observed in month of clinical onset, also only in males. If we assume a viral infectious etiology of DMI, females seem to be less susceptible than males to the environmental infectious influences.

Varicella Zoster Virus Associated Acute Aseptic Meningitis Without Exanthem In An Immunocompetent 14-year-old Boy

Neurologic complications can occur with varicella-zoster virus (VZV) infection, usually after vesicular exanthem. We report the case of a previously healthy 14-year-old boy with aseptic meningitis as a result of reactivated-VZV infection without exanthem. Diagnosis was made by detection of VZV-DNA in cerebrospinal fluid. VZV should be considered in cases of aseptic meningitis, even without a history of exanthem or immune compromise.