Predictors of glycaemic control and hypoglycaemia in children and adolescents with type 1 diabetes from NSW and the ACT

Type 1 diabetes is the most common chronic disease of childhood, with about 300 new cases diagnosed each year in New South Wales (NSW) and the Australian Capital Territory (ACT).1 The assessment of glycaemic control in children and adolescents with diabetes, as for adults, is based on measurement of glycosylated haemoglobin (HbA1c). The Diabetes Control and Complications Trial (DCCT), a multicentre study of 1441 patients (195 of whom were adolescents), showed a positive benefit of improved glycaemic control, with a reduction in long-term risk of microvascular complications.2 However, this was associated with a twofold to threefold increase in the rate of severe hypoglycaemia and weight gain. The applicability of the DCCT findings to managing diabetes in children is not known. Surveys of glycaemic control have shown that many children with type 1 diabetes are not achieving optimal diabetes control (HbA1c level, < 8%), and yet rates of hypoglycaemia are unacceptably high.3,4 The risk of severe hypoglycaemia, particularly in preschool children, and fear of weight gain in adolescents may be potential impediments to achieving targets for glycaemic control.

The predictors of glycaemic control are likely to be multifactorial in young people with diabetes. In NSW and ACT children with type 1 diabetes, we have previously reported that variation in public versus private care, socioeconomic background and urban versus rural location were not predictors of glycaemic control.5 In contrast, a recent survey of young people from Scotland proposed strategies of medical care and clinic organisation as factors contributing to between-centre variation in HbA1c level,6 and an audit from France found better glycaemic control in university-affiliated hospitals and centres following more than 50 patients.4 The aim of our study was to further explore the relationship between glycaemic control, hypoglycaemia and body mass index (BMI) in a large population-based cohort of children with type 1 diabetes in NSW and the ACT.

The NSW/ACT type 1 diabetes incidence register1,7 and clinic data were used to compare study participants and non-participants.

Date of diagnosis (defined as date of first insulin injection), number of injections per day, number of units of insulin per day, number of severe episodes of hypoglycaemia (defined by unconsciousness or seizures) over the previous three months, sex, height, weight and residential postcode were recorded on the day of HbA1c estimation. Standard deviation scores (z scores) for height, weight and BMI were derived from published standards,8 with a score of zero being the mean for the population.

Of a total target group of 1765, 1190 children and adolescents (67.4%) participated in the study. There were more females (649) than males (541), reflecting the higher incidence of type 1 diabetes in females in this population.1 Median age was 11 years (range, 1.2–15.8 years) and median diabetes duration was three years (range, 0.2–14.2 years). Comparing the 1190 participants with the 571 non-participants, the former were younger (11 years [IQR, 8.1–13.2] v 12.7 years [IQR, 9.1–14.4]; P < 0.0001) and had shorter diabetes duration (3 years [IQR, 1.3–5.5] v 4.5 years [IQR, 2.9–6.9]; P < 0.0001), but did not differ in sex distribution or urban versus rural location.

The outlook for preventing long-term complications remains a challenge in children and adolescents with type 1 diabetes. In our audit of 1190 children, longer diabetes duration was a predictor of higher HbA1c level, and an elevated HbA1c level (> 8%) is a known risk factor for microvascular complications.2 Our participants' median HbA1c level of 8.2%, with a median duration of diabetes of three years, is comparable to that found in the multicentre Hvidore Study3 (DCCT equivalent, 8.3%) and in a Brisbane clinic-based study11 (mean HbA1c level, 8.6%, determined by several assay methods). However, six years after diagnosis of type 1 diabetes in childhood, early microvascular complications were found in 34% of an incident cohort from NSW, whose median HbA1c level was 8.7%.12

Our response rate of 67.4% compares favourably with other surveys. However, we cannot exclude the possibility of selection bias. The children identified from the diabetes register who did not participate in the study were older and had longer diabetes duration. Adolescents are at greatest risk of non-compliance and worse glycaemic control, so our participants may represent the better-controlled two-thirds of the population.

The relationship between higher insulin dose and higher HbA1c level was initially surprising. There was no difference in insulin dose per kg between the conventionally and intensively treated cohorts in the DCCT,13 but the same positive relationship between suboptimal glycaemic control and higher insulin dose has been reported in several studies.4,5 The cross-sectional design of these studies clearly limits the conclusions that can be drawn from these data and further investigation of these findings is required. It may be that the insulin dose had recently been increased in children with worse glycaemic control in an attempt to improve control. Also, higher HbA1c levels may have resulted from non-compliance with prescribed doses in our cohort. Adolescent girls with diabetes are at increased risk of eating disorders,14 are worried about the risk of weight gain,15 and have been found to manipulate or omit insulin therapy as a means of weight control.16,17

Children in the highest quartile of BMI standard deviation score, who were all overweight (BMI, > 85th percentile) had higher levels of HbA1c, were younger and had shorter diabetes duration. Parental fear of hypoglycaemia has been shown to be an impediment to improved glycaemic control,15 particularly in young children. Parents may respond by overfeeding their young children, but obesity itself is a growing problem in Australian children.18 Therefore, the heaviest children may have a combination of type 1 and type 2 diabetes or insulin resistance.19

It is of concern that, while children in our study had a relatively high rate of severe hypoglycaemia, there was no association with glycaemic control. The incidence of severe hypoglycaemia (36 per 100 patient-years) is higher than that in the Hvidore study (22 per 100 patient-years)3 and the DCCT intensively treated adolescent cohort (26.7 per 100 patient-years),13 but lower than that in the French study (42 per 100 patient-years).4 A regimen of four injections per day was also a significant risk factor for hypoglycaemia in the Poisson regression model. Subjects in the intensively treated DCCT cohort, who were on a regimen of at least three daily insulin injections, had a higher rate of hypoglycaemia, but lower HbA1c level, than those receiving conventional therapy. An increase in severe hypoglycaemia was associated with improved glycaemic control in a Western Australian study, although all children aged less than 17 years in that cohort were treated with two injections per day.20

In conclusion, children with longer duration of diabetes and those receiving higher doses of insulin provide a challenge for healthcare providers to determine how best to improve glycaemic control and prevent severe hypoglycaemia. Younger children are at particular risk of hypoglycaemia and being overweight. Investigation into the quality of life, fears and coping skills of children and their parents is needed to better understand the barriers to improving glycaemic control.