The Impact of a Decade of Changing Treatment on Rates of Severe Hypoglycemia in a Population-Based Cohort of Children With Type 1 Diabetes

Abstract

OBJECTIVE -To determine the impact of changes to treatment on the incidence of severe hypoglycemia and its risk factors in a large population-based cohort of children with type 1 diabetes.RESEARCH DESIGN AND METHODS -The cohort consisted of 1,335 children (age at entry 9.5 Ϯ 4.3 years [mean Ϯ SD], range 0 -18), yielding 6,928 patient-years of data. The mean follow-up period was 4.7 Ϯ 3.1 years (range 0 -10.7). Prospective assessment of severe hypoglycemia (an event leading to loss of consciousness or seizure) and associated clinical factors and outcomes was made between 1992 and 2002. Patients were reviewed every 3 months. Data were analyzed using the negative binomial regression model. RESULTS -A total of 944 severe events were recorded. The incidence of severe hypoglycemia increased significantly by 29% per year for the first 5 years but appeared to plateau over the last 5 years. The overall average HbA 1c significantly decreased (by 0.2% per year) over the whole follow-up period. An increased risk of severe hypoglycemia was associated with lower HbA 1c , younger age, higher insulin dose, male sex, and lower parental socioeconomic status. Of insulin therapies, only pump treatment was associated with reduced rates of severe hypoglycemia.CONCLUSIONS -Severe hypoglycemia remains a major problem for children and adolescents with type 1 diabetes. Recent approaches to therapy may be allowing a degree of improved control without the expected increased risk of severe hypoglycemia but further monitoring will be important. Diabetes Care 27:2293-2298, 2004I nsulin-induced hypoglycemia remains a central problem in the management of type 1 diabetes. This is especially the case in children and adolescents in whom the ever-present dilemma between tight glycemic control and the risk of hypoglycemia adds to the considerable burden of the disease.The last decade has seen improved understanding of the pathophysiological mechanisms leading to hypoglycemia in type 1 diabetes. Along with this, treatment approaches have also changed dramatically. The Diabetes Control and Complication Trial (DCCT) led to a fundamental shift in the goals of management (1,2). This, along with new insulins, increased use of multiple injection regimens, pump therapy, more targeted behavioral and educational methods, and new glucose-monitoring technologies have potentially altered the epidemiology of severe hypoglycemia in young patients.It has been long recognized that it is important to survey type 1 diabetic patients to determine the risk factors for severe hypoglycemia and monitor therapeutic outcomes (3,4). Earlier reports were difficult to interpret because of methodological problems, variations in definitions of hypoglycemic episodes, and retrospective approaches. More recent reports have used a prospective study design, an approach stimulated by the DCCT experience and protocols (1). This approach, combined with careful definition of hypoglycemic events and well-described subject populations, has removed some of the limitations of crosssectional s...

The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes

“…Of the 585 patients, 186 experienced a total of 477 severe episodes with a total follow-up time of approximately 3,500 patientyears. The overall incidence rate of 14.0 per 100 patientyears is similar to the rate we have reported previously [2,22] and comparable with other studies [1,29,30]. A Swedish study reported an overall incidence rate of 17.0 per 100 patient-years [20], which is slightly higher than our study, and a median age of 12.8 years compared with 10 years in our study.…”

“…An important limiting factor to achieving good metabolic control of type 1 diabetes in children and adolescents is the increased risk and fear of hypoglycaemic episodes and in rare circumstances death [1][2][3][4]. Recurrent episodes of hypoglycaemia may result in hypoglycaemia unawareness [5].…”

“…Recurrent episodes of hypoglycaemia may result in hypoglycaemia unawareness [5]. Large population-based studies have shown that despite efforts to improve treatment of type 1 diabetes, hypoglycaemia remains a problem [2,5] and there is need for strategies that will minimise episodes of severe hypoglycaemia. On the other hand, a majority of patients never experience a hypoglycaemic coma or convulsion [2].…”

“…Large population-based studies have shown that despite efforts to improve treatment of type 1 diabetes, hypoglycaemia remains a problem [2,5] and there is need for strategies that will minimise episodes of severe hypoglycaemia. On the other hand, a majority of patients never experience a hypoglycaemic coma or convulsion [2]. It has been shown that the incidence of severe hypoglycaemia within a cohort is highly skewed [6] with variable inter-individual susceptibility.…”

“…Our aim in this study was to determine the relationship between this genetic polymorphism and susceptibility to severe hypoglycaemia in a large population-based sample of individuals with type 1 diabetes mellitus, in whom hypoglycaemic events had been closely characterised prospectively from diagnosis [2].…”