Purpose: To investigate hypoglycemic and hyperglycemic symptoms, accuracy of estimating blood glucose, and their relation to glycemic control and counterregulatory hormone levels in insulin-dependent diabetes mellitus.
Patients and methods: During randomly ordered stepped hypoglycemic and hyperglycemic insulin clamps on two separate days, 42 patients with insulin-dependent diabetes mellitus rated the intensity of 40 moods and symptoms when glucose was 8.9, 5.6 and 2.2 mmol/L, and 8.9, 14.4 and 21.1 mmol/L. The subjects were blinded to their actual glucose levels and asked to estimate them at each step. Epinephrine, norepinephrine, cortisol, growth hormone, and glucagon were measured at each glucose plateau.
Results: Cluster analysis yielded five symptom groups during hypoglycemia: autonomic symptoms, negative moods, positive moods, feeling weak/dizzy, and feeling relaxed. At 2.2 mmol/L, mean scores for all five symptom groups and 11 of 17 unclustered symptoms differed from those reported at the baseline glucose of 8.9 mmol/L (P < or = 0.05), but 34% of patients reported no awareness of autonomic symptoms. The intensity of autonomic symptoms correlated positively with HbA1 (r = .43, P < 0.01), epinephrine (r = .59, P < 0.001), norepinephrine (r = .45, P < 0.01) and cortisol (r = .62, P < 0.001), and negatively with glucose estimation error (r = -.45, P = 0.01). Six patients (15%) were unaware of both autonomic and neuroglycopenic symptoms during hypoglycemia. At 21.1 mmol/L, only 5 of 40 symptoms differed (P < 0.05) from baseline. Seventeen percent of subjects made potentially serious errors when estimating glucose at 2.2 mmol/L, and 66% at 21.1 mmol/L. Many patients experienced symptoms different from those they reported as their usual manifestations of changing glucose levels.
Conclusions: Since the majority of patients made clinically serious errors in glucose estimation, and many used symptoms that did not discriminate hyperglycemia and hypoglycemia, individualized training to increase awareness of glucose-related symptoms and glucose levels may help patients reduce the frequency or severity of hyperglycemic and hypoglycemic events.