Insulin Injection Regimen and Metabolic Control

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.

Relationship between Insulin Injection Regimen and Metabolic Control over Three Years

As the optimal insulin regimen for paediatric patients with type 1 diabetes remains controversial, this issue was investigated in a separate paper, Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: results from the Hvidøre Study Group.4 Of the 2,873 children and adolescents in the international survey in 1995,1 872 adolescents (433 boys, 439 girls, mean age in 1995 11.3 ± 2.2 years) were restudied in 1998, relating insulin regimens to HbA1C in order to investigate whether differences in insulin management were associated with outcome differences across centres.

The changes in HbA1C, injection frequency, insulin dose, and BMI were evaluated by using a repeated measurements model for the 1995 and 1998 data in order to account for the effect of covariates and the fact that patients each contributed two measurements. Sex, centre, age, and diabetes duration were included in order to adjust for these factors and the effect of the increase in age and diabetes duration during the three-year period.

Over three years, the use of multiple-injection regimens increased from 42% to 71%: 251 children (group 1) remained on twice-daily insulin, 365 (group 2) remained on multiple injections, and 256 (group 3) 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 regardless of insulin injection regimen. The increase in BMI was greatest in patients switching from twice-daily to multiple injections, and greater in girls than in boys.

Thus the HbA1C levels deteriorated irrespective of the insulin injection regimen prescribed, even in children who shifted from a conventional regimen with two daily injections to a more intensified regimen with multiple injections. This finding is in contrast to the adolescent subgroup in the DCCT, where a distinct and stable difference was observed between the conventionally treated group (one- or two-injection regimen) and the group on intensified insulin therapy (multiple-injection regimen or pumps).6,7 The DCCT was a prospective, highly intensive intervention study, comparing multiple-injection to standard ketosis-preventiontype insulin treatment. The present study was observational at two time points three years apart. No information was available on the insulin therapy during the three years or on other interventions to improve metabolic control, such as patient re-education, hospitalisation, camps etc. Each treatment centre was entirely free in its choice of insulin therapy, and no information was collected on the reasons for individual patients continuing or changing their insulin regimen.

Reports in the literature, based on retrospective or cross-sectional observations, on the relationship between insulin treatment regimen and metabolic control are conflicting. While some studies report a significant improvement in metabolic control in adolescents with increasing injection frequency,17,20,21 others are in agreement with our data and do not confirm such a relationship.9,13,22 The number of insulin injections per day is only one aspect of treatment intensity in diabetes. Frequent self-monitoring of blood glucose, patient education, dietary counselling, and effective self-management represent equally important areas.

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 over three years, not even in patients switching from twice-daily to multiple injections, while the increase in BMI was most pronounced in this group. This indicates that other factors, such as attitudes of the treatment team, selfcare behaviour, educational models, and patient satisfaction, may be more directly related to the outcome than insulin regimens.


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.

4. Holl RW, Swift PG, Mortensen HB et al. Insulin injection regimens and metabolic control in an international survey of adolescents with type 1 diabetes over 3 years: results from the Hvidøre Study Group. Eur J Pediatr 2003; 162(1): 22-9.

6. Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. J Pediatr 1994; 125(2): 177-88.

7. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977-86.

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.

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.

22. Wysocki T, Hough BS, Ward KM et al. Diabetes mellitus in the transition to adulthood: adjustment, selfcare, and health status. J Dev Behav Pediatr 1992; 13(3): 194-201.