Physiological Responses to Relative Hypoglycemia in Uncontrolled Type 2 Diabetes Mellitus: A Pilot Study

Abstract To evaluate the hormonal, cardiac, and neuronal responses during relative hypoglycemia in uncontrolled type 2 diabetes mellitus patients. Fifteen uncontrolled type 2 diabetes mellitus patients underwent insulin infusion at 0.05 U/kg/h, titrated at 1 U/h every 10 minutes, until they developed symptoms of hypoglycemia with a glucose level >3.9 mmol/L. Blood samples for glucose, cortisol, glucagon, and epinephrine, as well as electrocardiogram and electroencephalogram readings, were taken before insulin infusion and repeated once hypoglycemic symptoms developed. Data were analyzed using paired t-tests and Wilcoxon signed-rank tests. The p-value of <0.05 was considered significant. The median glucose level during relative hypoglycemia was 6.7 (4.3–7.3) mmol/L, and 86.7% of patients experienced autonomic symptoms. The mean glucagon level was significantly higher at baseline than during relative hypoglycemia (4,842.93 vs. 4,300.13 pg/mL, p = 0.041). During relative hypoglycemia, 66.7 and 60% of patients had declined glucagon and cortisol levels, respectively. Meanwhile, 53.3% of patients experienced an increase in epinephrine levels. There was no significant change in cortisol and epinephrine levels during relative hypoglycemia compared to baseline. The electroencephalogram showed generalized background attenuation in eight patients, and none had electrocardiogram changes. This study demonstrates that relative hypoglycemia, in uncontrolled type 2 diabetes mellitus, only leads to autonomic symptoms without significant counterregulatory hormonal, cardiovascular, and neurological changes. Clinically, recognizing relative hypoglycemia is crucial to avoid misinterpreting it as true hypoglycemia and to highlight its potential role in causing impaired patient awareness of subsequent true hypoglycemic episodes. The small sample size and potential confounding factors warrant cautious interpretation, and larger studies are needed to confirm these findings and to develop strategies for monitoring and managing relative hypoglycemia in clinical practice.