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Hypoglycemia-associated autonomic failure in advanced type 2 diabetes
Scott A Segel1, Deanna S Paramore, Philip E Cryer
1Division of Endocrinology, Diabetes and Metabolism, and the General Clinical Research Center and the Diabetes Research and Training Center, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Diabetes
|March 2, 2002
Summary
Patients with advanced type 2 diabetes have a reduced glucagon response to hypoglycemia. Recent hypoglycemia further lowers glucose thresholds for autonomic and symptomatic responses, increasing the risk of recurrent hypoglycemia.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Diabetes Mellitus Research
Background:
- The glucagon response to hypoglycemia is a critical counter-regulatory mechanism.
- In type 2 diabetes, particularly as it progresses to insulin deficiency, this response may be impaired.
- Understanding these responses is vital for managing hypoglycemia in diabetic patients.
Purpose of the Study:
- To investigate if the glucagon response to hypoglycemia is diminished in type 2 diabetes patients nearing insulin deficiency.
- To determine if prior hypoglycemia alters autonomic and symptomatic responses to subsequent low glucose levels in type 2 diabetes.
- To compare these responses between patients on oral hypoglycemic agents and those on insulin therapy, and with non-diabetic controls.
Main Methods:
- Hyperinsulinemic stepped hypoglycemic clamps were used to induce controlled hypoglycemia.
- The study involved 13 patients with type 2 diabetes (7 on OHA, 6 on insulin) and 15 non-diabetic controls.
- Measurements were taken over two consecutive days, including a prolonged hypoglycemia period on day 1.
Main Results:
- The glucagon response to hypoglycemia was virtually absent in insulin-deficient type 2 diabetic patients.
- Both glucagon and epinephrine responses, along with autonomic and symptomatic responses to hypoglycemia, were reduced on day 2 following antecedent hypoglycemia.
- These responses, while not eliminated, occurred at lower plasma glucose concentrations in type 2 diabetic patients.
- Baseline glycemic thresholds for these responses were higher in patients on oral hypoglycemic agents with poorer glycemic control.
Conclusions:
- Patients with advanced, insulin-deficient type 2 diabetes exhibit an absent glucagon response to hypoglycemia.
- Recurrent hypoglycemia can lead to hypoglycemia-associated autonomic failure in type 2 diabetes, similar to type 1 diabetes.
- This impaired counter-regulation increases the risk of a vicious cycle of recurrent iatrogenic hypoglycemia in advanced type 2 diabetes.