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Plasma catecholamine responses to hypoglycemia in children and adolescents with IDDM
R P Hoffman1, C Singer-Granick, A L Drash
1Department of Pediatrics, University of Pittsburgh, Pennsylvania.
Insights
Children and adolescents with insulin-dependent diabetes mellitus (IDDM) show reduced catecholamine responses to hypoglycemia. Intensive insulin therapy further diminishes this response, suggesting hyperinsulinism plays a role.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Pediatric Research
Background:
- Insulin-dependent diabetes mellitus (IDDM) affects children and adolescents.
- Adults with IDDM exhibit blunted catecholamine responses to hypoglycemia.
- The underlying mechanisms in pediatric populations are not fully understood.
Purpose of the Study:
- To determine if children and adolescents with IDDM have reduced catecholamine responses to hypoglycemia.
- To investigate the role of autonomic neuropathy and hyperinsulinism in this response.
- To assess the impact of intensive insulin therapy on catecholamine responses.
Main Methods:
- A before-and-after trial involving 60 subjects with IDDM and 5 controls.
- Hypoglycemia induced via intravenous insulin bolus.
- Assessment of autonomic neuropathy through R-R variation and pancreatic polypeptide response.
Main Results:
- Diabetic subjects had lower basal catecholamine levels post-intensive therapy compared to controls.
- Significantly decreased peak and incremental catecholamine responses in IDDM subjects post-therapy.
- Diminished epinephrine response was the primary contributor to the reduced response.
Conclusions:
- Children and adolescents with IDDM exhibit diminished catecholamine response to hypoglycemia.
- Short-term intensive insulin therapy further suppresses this response.
- Hyperinsulinism is implicated in suppressing the catecholamine response; autonomic neuropathy is not a significant factor.
Objective:
The goal of this study was to assess whether children and adolescents with insulin-dependent diabetes mellitus (IDDM) have decreased catecholamine responses to insulin-induced hypoglycemia as has been reported in adults and to explore the pathogenesis of the decreased response in terms of possible relationships to autonomic neuropathy or hyperinsulinism.
Research Design And Methods:
A before-and-after trial on the effects of 3 days of intensive insulin therapy was conducted on 60 subjects with IDDM (age 15.4 +/- 2.6 yr, duration of diabetes 7.8 +/- 3.5 yr). The control group consisted of 5 children with non-growth hormone-deficient short stature (age 14.8 +/- 3.2 yr). Hypoglycemia was induced with an intravenous insulin bolus (0.15-0.75 U/kg) after insulin withdrawal and 3 days of intensive insulin therapy in diabetic subjects on an inpatient basis to assess the role of hyperinsulinism in suppressing the catecholamine response to hypoglycemia. Control subjects were studied once and received an insulin bolus of 0.1 microU/kg. Autonomic neuropathy was assessed by computerized assessment of the basal R-R variation during inspiration and expiration and the pancreatic polypeptide response to hypoglycemia.
Results:
Basal plasma catecholamine levels were lower in diabetic subjects after intensive insulin therapy than in control subjects (P = 0.008). The peak and incremental catecholamine responses after insulin withdrawal and intensive insulin therapy in IDDM subjects were significantly decreased compared with control subjects (P less than 0.001). Peak catecholamine responses to hypoglycemia in IDDM were decreased after intensive insulin therapy (P = 0.002). This was particularly true in those with plasma glucose nadir levels of less than 2.2 mmol (P less than 0.001). The diminished catecholamine responses were primarily due to decreased peak epinephrine responses after intensive insulin therapy compared with insulin withdrawal (P = 0.011). There were no significant correlations between the catecholamine response to hypoglycemia and age, duration of diabetes, pancreatic polypeptide, or R-R interval.
Conclusions:
These results suggest that children and adolescents with IDDM after insulin withdrawal have diminished catecholamine response to hypoglycemia compared with control subjects and indicate that short-term intensive insulin therapy diminishes this response further. Thus, hyperinsulinism may play a role in suppressing the catecholamine response to hypoglycemia. There is no evidence for a clinical or subclinical role of autonomic neuropathy to explain the altered catecholamine responses.