Central Analysis of HbA1C
In all the studies, HbA1C was centrally analysed at the Steno Diabetes Center using the same calibrator lots as the Diabetes Control and Complications Trial (DCCT) laboratory. By direct sample exchange, the Steno Diabetes Center HbA1C results were found to be 0.3% higher than the DCCT levels.
In the second paper, Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries,2 we examined the insulin regimens that were used in the first Hvidøre study population and the various factors that may have influenced these. There was no significant difference in insulin dosage between boys and girls until adolescence (11–18 years), when the insulin dosage in girls was considerably higher than in boys (Figure 4).
Age-specific mean values for insulin (U/kg/24h) in 1,443 boys and 1,430 girls with type 1 diabetes. The error bars represent 1 SEM value (* p < 0.05, ** p < 0.01, *** p < 0.001 in comparison of boys and girls separately in each age group).
Adapted from Mortensen et al. Diabet Med 1998; 15(9): 752-9.
The average insulin dosages seen in these adolescents were comparable to those used in the adolescent group of the DCCT. The increase in insulin requirement during puberty has also been shown by Dorchy et al9 and Kerouz,10 with girls again needing higher doses than boys. The difference in insulin requirement between girls and boys may be due, in part, to the earlier age of onset of puberty in girls, but also to the differential effects of sex hormones on glucose homeostasis.11,12
Increasing insulin resistance during puberty leads to increased insulin requirements,13 which may be at least partly responsible for the increase in age-related body mass index (BMI) seen in boys and girls with type 1 diabetes during both the prepubertal and the pubertal periods when compared with healthy control children (Figure 5).14 BMI, especially in girls with diabetes, continues to increase during adolescence. This finding is in agreement with the results of a recent nationwide Danish investigation.15 Controversy remains as to whether multiple injection therapy per se is associated with weight gain. Some studies have shown a possible association,1,5,13,15 while others dispute this.16–18 Multiple daily injections allow more flexibility, and the attitude of teenagers towards their diet may become more relaxed on such intensive insulin therapy, leading to weight gain.
Age-specific median values for body mass index (BMI) in 1,443 boys and 1,430 girls with type 1 diabetes, with a group of healthy British children serving as controls.
Adapted from Mortensen et al. Diabet Med 1998; 15(9): 752-9.
Age-related frequency distribution of number of daily insulin injections in 2,857 children and adolescents with insulin-dependent diabetes mellitus.
Reproduced from Mortensen et al. Diabet Med 1998; 15(9): 752-9.
Most children aged under 9 years were on two (78%) or three (13%) insulin injections daily. Only a few children (7%) received one insulin injection daily, and most of these had a very short duration of diabetes. In the adolescent group, the use of three and four insulin injections increased at the expense of two insulin injections per day (Figure 6). Of those on two or three injections daily, 37% received premixed insulin, given either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on premixed insulin had 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 shortacting insulin. This association was not found in girls, casting some doubt on its clinical significance.
Numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards multiple insulin injections, particularly in older adolescents. Nevertheless, the goal of near-normoglycaemia is achieved in only a few patients.
1. Mortensen HB, Hougaard P. Comparison of metabolic control in a cross-sectional study of 2,873 children and adolescents with IDDM from 18 countries. The Hvidøre Study Group on Childhood Diabetes. Diabetes Care 1997; 20(5): 714-20.
2. Mortenson HB, Robertson KJ, Aanstoot HJ et al. Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvidøre Study Group on Childhood Diabetes. Diabet Med 1998; 15(9): 752-9.
5. Hoey H, Aanstoot HJ, Chiarelli F et al. Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes. Diabetes Care 2001; 24(11): 1923-8.
9. Dorchy H, Roggemans MP, Willems D. Glycated hemoglobin and related factors in diabetic children and adolescents under 18 years of age: a Belgian experience. Diabetes Care 1997; 20(1): 2-6.
10. Kerouz N, el-Hayek R, Langhough R et al. Insulin doses in children using conventional therapy for insulin dependent diabetes. Diabetes Res Clin Pract 1995; 29(2): 113-20.
11. Arslanian SA, Heil BV, Becker DJ et al. Sexual dimorphism in insulin sensitivity in adolescents with insulindependent diabetes mellitus. J Clin Endocrinol Metab 1991; 72(4): 920-6.
12. Widom B, Diamond MP, Simonson DC. Alterations in glucose metabolism during menstrual cycle in women with IDDM. Diabetes Care 1992; 15(2): 213-20.
13. Mortensen HB, Villumsen J, Vølund A et al. Relationship between insulin injection regimen and metabolic control in young Danish Type 1 diabetic patients. The Danish Study Group of Diabetes in Childhood. Diabet Med 1992; 9(9): 834-9.
14. Cole TJ, Freeman JV, Preece MA. Body mass index reference curves for the UK, 1990. Arch Dis Child 1995; 73(1): 25-9.
15. Mortensen HB, Hougaard P. Microvascular complications in childhood. In: Shield JPH, Baum JD (Eds). Bailliere's Clinical Paediatrics. Volume 4. London: Bailliére Tindall, 1996: 641-61.
16. Danne T, Kordonouri O, Enders I et al. Factors influencing height and weight development in children with diabetes. Results of the Berlin Retinopathy study. Diabetes Care 1997; 20(3): 281-5.
18. Holl RW, Grabert M, Heinze E et al. Why do children with type 1 diabetes develop overweight? J Ped Endocrinol Metab 1997; 10(Suppl 2): A39 (366) (Abstract).