Symptoms of Acute Insulin-Induced Hypoglycemia in Humans With and Without IDDM: Factor-Analysis Approach

Abstract

Objective This study allocated the symptoms identified during acute hypoglycemia objectively to the autonomic or neuroglycopenic groups of symptoms by the use of factor analysis. Research Design and Methods Twenty-five nondiabetic subjects, 14 newly diagnosed insulin-dependent diabetic patients, and 16 insulin-dependent diabetic patients with diabetes > 4 yr duration were studied. Acute hypoglycemia was induced with insulin (2.5 mU·kg−1 body wt·min−1 i.v.), and symptoms of hypoglycemia were recorded with a seven-point scale at regular time points throughout the studies. Factor analysis of the symptom scores at the time of the acute autonomic reaction with principal component analysis followed by Varimax rotation was used to separate those symptoms that might belong to neuroglycopenic and autonomic groups. Results Hypoglycemia was induced to a mean ± SE plasma glucose nadir of 1.3 ± 0.1 mM in nondiabetic subjects, to 2.0 ± 0.3 mM in newly diagnosed diabetic patients, and 1.4 ± 0.2 mM in patients with diabetes of > 4 yr duration. The most frequently reported autonomic symptoms were sweating, trembling, and warmness, and the most frequently reported neuroglycopenic symptoms were inability to concentrate, weakness, and drowsiness. Neuroglycopenic symptoms were reported more commonly at the onset of hypoglycemia, which was identified by the development of symptoms. Factor analysis grouped trembling, anxiety, sweating, warmness, and nausea together, and this grouping was labeled an autonomic factor. A second factor was identified that included dizziness, confusion, tiredness, difficulty in speaking, shivering, drowsiness, and inability to concentrate, which was labeled a neuroglycopenic factor. Conclusions This study demonstrated the high frequency with which neuroglycopenic symptoms occur at the onset of hypoglycemia and the symptoms that could be used by an individual patient as a warning of the development of acute hypoglycemia, although the rapid reduction of plasma glucose is faster than experienced by the ambulant diabetic patient. Factor analysis assisted with the allocation of symptoms to either the autonomic or neuroglycopenic groupings, but the allocation of some symptoms remained undefined, and care must be taken when assessing symptoms such as hunger, weakness, blurred vision, and drowsiness when comparing the frequency of autonomic versus neuroglycopenic symptoms. To reduce the confusion resulting from the use of different symptom questionnaires in studies of hypoglycemia, a sample questionnaire is presented, the development of which was assisted by our analysis.