Eero A. Kaprio

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.

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.

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.

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 <11 yr with type 1 diabetes mellitus.

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.

Targets and teamwork: Understanding differences in pediatric diabetes centers treatment outcomes

The reason for center differences in metabolic control of childhood diabetes is still unknown. We sought to determine to what extent the targets, expectations, and goals that diabetes care professionals have for their patients is a determinant of center differences in metabolic outcomes.

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

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

Metabolic outcomes in young children with type 1 diabetes differ between treatment centers

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