Absence of sexual dimorphism in the symptomatic responses to hypoglycemia in adults with and without type 1 diabetes.

I nsulin-induced hypoglycemia provokes counterregulatory hormonal responses, the magnitude of which is lower in women with and without type 1 diabetes than in their male counterparts (1–5), although the glycemic thresholds at which these responses are triggered are similar in both sexes (6,7). In nondiabetic adults and people with type 1 diabetes, antecedent hypoglycemia and exercise had less effect on the magnitude of the counterregulatory hormonal responses in women than in men (8,9). It has therefore been suggested that exposure to recurrent episodes of hypoglycemia could abolish the difference in counterregulatory responses between the sexes, explaining the absence of a difference in the overall frequency of severe hypoglycemia observed in the Diabetes Control and Complications Trial (10). Detection of the symptoms of hypoglycemia alerts the person with diabetes to the decline in blood glucose, prompting corrective action to be taken before the effects of neuroglycopenia become disabling. Symptoms of hypoglycemia are generated as part of the established hierarchy of responses (11,12) and are idiosyncratic and age specific (13). Sex differences have not been reported, but in small studies with few subjects, a putative difference may not be discernible (1,14). The most common hypoglycemia symptoms have been classified into subgroups in physiological studies (15,16) and by statistical methodology (17–20) using factor analysis. The subgroups include autonomic symptoms, such as hunger, pounding heart, sweating, or shaking, arising from central autonomic neural activation via hypothalamic centers (21), predominantly of the sympathetic division; neuroglycopenic symptoms, such as drowsiness, confusion, odd behavior, speech difficultly, or incoordination, caused by the direct effect of glucose deprivation on the brain; and nonspecific symptoms, including headache and malaise. The symptoms of hypoglycemia can be measured using the Edinburgh Hypoglycemia Score (17–19). The symptoms of hypoglycemia are generated independently of the counterregulatory hormonal responses, although falling blood glucose triggers both. To ascertain whether sexual dimorphism occurs in the hypoglycemia symptomatic response, symptom scores were analyzed in 160 subjects in whom controlled hypoglycemia had been induced.