Hypoglycemia Unawareness in Older Compared With Middle-Aged Patients With Type 2 Diabetes

OBJECTIVE

Older patients with type 2 diabetes are at a particularly high risk for severe hypoglycemic episodes, and experimental studies in healthy subjects hint at a reduced awareness of hypoglycemia in aged humans. However, subjective responses to hypoglycemia have rarely been assessed in older type 2 diabetic patients.

RESEARCH DESIGN AND METHODS

We tested hormonal, subjective, and cognitive responses (reaction time) to 30-min steady-state hypoglycemia at a level of 2.8 mmol/l in 13 older (≥65 years) and 13 middle-aged (39–64 years) type 2 diabetic patients.

RESULTS

Hormonal counterregulatory responses to hypoglycemia did not differ between older and middle-aged patients. In contrast, middle-aged patients showed a pronounced increase in autonomic and neuroglycopenic symptom scores at the end of the hypoglycemic plateau that was not observed in older patients (both P < 0.01). Also, seven middle-aged patients, but only one older participant, correctly estimated their blood glucose concentration to be <3.3 mmol/l during hypoglycemia (P = 0.011). A profound prolongation of reaction times induced by hypoglycemia in both groups persisted even after 30 min of subsequent euglycemia.

CONCLUSIONS

Our data indicate marked subjective unawareness of hypoglycemia in older type 2 diabetic patients that does not depend on altered neuroendocrine counterregulation and may contribute to the increased probability of severe hypoglycemia frequently reported in these patients. The joint occurrence of hypoglycemia unawareness and deteriorated cognitive function is a critical factor to be carefully considered in the treatment of older patients.Hypoglycemia is the limiting factor in the glycemic management of diabetes (1). For a long time hypoglycemia was assumed a major problem only in patients suffering from type 1 diabetes (2); however, there is increasing evidence that hypoglycemic episodes are a critical factor also in type 2 diabetes (3,4). Older subjects aged >65 years, who represent the majority of type 2 diabetic patients, appear at a particularly high risk of experiencing severe hypoglycemia (3,4). Previous studies (5–7) have shown weakened perception of hypoglycemia-related symptoms in healthy older (i.e., nondiabetic older subjects, aged 65–80 years) as compared with younger subjects (aged 24–49 years). Of note, in aged humans, the perception of hypoglycemic symptoms was found to simultaneously occur with the impairment of cognitive functions during a stepwise reduction of blood glucose levels (7), contrasting the well-known hierarchical succession of central nervous responses to hypoglycemia in younger healthy adults who normally perceive hypoglycemic symptoms at higher glucose levels than cognitive dysfunction (4). The concurrence of glycemic thresholds for the onset of symptoms and of cognitive dysfunction may be expected to increase the risk for severe hypoglycemic episodes since it likely prevents behavioral counteractions (e.g., the intake of carbohydrates) (3).To date only one study (8) has assessed subjective responses to standardized hypoglycemia in older type 2 diabetic patients (aged 72 ± 1 years), revealing an impairment in the perception of hypoglycemic symptoms that was comparable to that of age-matched healthy control subjects. Although this finding points to a decrease in hypoglycemia awareness that develops in the course of aging also in type 2 diabetic patients, this assumption has not yet been experimentally elucidated. Moreover, in the previous studies in healthy subjects (5–7), the age gap between experimental groups was rather large, raising the question as to the perception of hypoglycemia in middle-aged subjects. On this background, we examined whether older (aged ≥65 years) as compared with middle-aged (aged 39–64 years) type 2 diabetic patients differ in their subjective response to hypoglycemia and how hypoglycemia awareness in these age-groups relates to hormonal and cognitive effects of hypoglycemia.