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Centre Differences

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.

Differences between Centres

Many potential explanations for the between-centre differences have been discussed in the study group, but real evidence for any of these explanations has not been found. The feedback from the first study and the discussions of the centre differences have caused each study group member to consider whether anything could be changed at their centre in order to improve metabolic control. Three years after the first crosssectional study, a second study was carried out to restudy the between-centre differences after this feedback. The third paper, Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group,3 investigated the reproducibility of the between-centre differences and analysed factors potentially influencing the variations in glycaemic control between centres, including number of injections, insulin dose, and rate of severe hypoglycaemia. Twenty-one international paediatric diabetes centres from 17 countries participated.

Figure 7
Adjusted means ± 1 SE (adjustment for sex, age, and diabetes duration) of the HbA1C at the participating centres at the baseline evaluation (1995, top panel) sorted according to their HbA1C levels. The bottom panel shows the change in the adjusted mean after three years.
Figure 7

Reproduced from Danne et al. Diabetes Care 2001; 24(8): 1342-7.

Striking differences in average HbA1C were found between centres; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. Three centres had improved significantly, and four centres had deteriorated significantly in their overall adjusted HbA1C, while glycaemic control did not change in 14 centres (Figure 7). During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, in the adjusted number of injections by 0.23 injections per day, and in the adjusted BMI by 0.95 kg/m2.

To examine whether the betweencentre differences were particularly pronounced early or later in the course of diabetes, the mean HbA1C was calculated for each centre separately for children with duration = 3 years and > 3 years. The differences were apparent even in patients with short diabetes duration and remained stable three years later (mean adjusted HbA1C 8.62 ± 0.03 [1995] versus 8.67 ± 0.04 [1998]) (Figure 8). An alternative explanation for the good correlation between the average control in patients with short diabetes duration and those with a long-term course of the disease could be differences in the diabetes education and management from the onset of the disease. Thus differing attitudes of the diabetes teams and/or differing degrees of patient empowerment may represent a major factor underlying these differences between centres.

Figure 8
Relationship between the average control of short-term patients (during the first three years of diabetes) and of patients with diabetes duration > 3 years at the 21 individual centres. Results show a stable correlation between the two timepoints. (Rs: 0.77, p < 0.001).  

Figure 8

Reproduced from Danne et al. Diabetes Care 2001; 24(8): 1342-7.  

Parameters of insulin therapy showed no clear-cut association with glycaemic control or hypoglycaemia rates, either in the original sample1 or in the reassessment of the between-centre differences. As a consequence of the unsatisfactory level of glycaemic control in the first survey, it is possible that most centres had increased the number of injections and the insulin dose before reinvestigation at the second sampling. These changes were not associated with an improvement in glycaemic control. Furthermore, this strategy resulted in an unfavourable increase in BMI in many centres, particularly in girls.19 

Similar to the experience with hypoglycaemia in the DCCT, there was no clear-cut association between average control at an individual centre and the rate of severe hypoglycaemia. At both sampling periods, a higher rate of severe hypoglycaemia was associated with lower age and better glycaemic control. However, some centres are more successful than others in preventing hypoglycaemia, independent of the prevailing average HbA1C levels (Figure 9).

Figure 9
Incidence of severe hypoglycaemic episodes per 100 patient-years in centres above, below, and not significantly different from the mean level of HbA1C. To show the estimated rates of events, a standard person from the 1998 group is considered (male, aged 13, diabetes duration of five years). The predicted rate of events is shown in the figure as a function of centre class (dotted line centre significantly below the mean) and individual HbA1C using a Poisson log-linear regression model.

Figure 9

Reproduced from Danne et al. Diabetes Care 2001; 24(8): 1342-7.

This important finding may relate to other features of management, such as psychological support and more successful education in centres with a low incidence of hypoglycaemia.

Conclusion:
This study revealed significant outcome differences across large international paediatric diabetes centres. Feedback and comparison of HbA1C levels led to an intensification of insulin therapy in most centres, but improved glycaemic control in only a few. Centres with HbA1C values below the average had fewer severe hypoglycaemic events, possibly as a result of better education programmes.

Reference

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.

3. Danne T, Mortensen HB, Hougaard P et al. Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group. Diabetes Care 2001; 24(8): 1342-7.

19. Diabetes Control and Complications Trial Research Group. Weight gain associated with intensive therapy in the Diabetes Control and Complications Trial. Diabetes Care 1988; 11(7): 567-73.