Counterregulatory Hormone Responses to Hypoglycemia in the Elderly Patient with Diabetes

Abstract

In patients with non-insulin-dependent diabetes mellitus (NIDDM), the risk of severe or fatal hypoglycemia associated with the use of oral agents or insulin increases exponentially with age. We conducted this study with the hypothesis that this increased susceptibility to hypoglycemia is caused by alterations in release of counterregulatory hormones and psychomotor performance during hypoglycemia. Ten healthy nonobese elderly subjects (74 ± 1 years of age; body mass index, 24.5 ± 0.6 kg/m²) and 10 nonobese elderly NIDDM subjects (72 ± 1 years of age; body mass index, 25.6 ± 0.9 kg/m²) underwent two hyperinsulinemic glucose clamp studies (insulin infusion, 60 mU·m^₋2 · min^₋1). In the control study, glucose was maintained at 5 mM for 5 h; in the hypoglycemic study, glucose was kept at 5 mM for 1 h and then lowered in a stepwise fashion to 4.4, 3.8, 3.3, and 2.8 mM in each subsequent hour. At regular intervals in each study, neuropsychological tests were performed, counterregulatory hormones were measured, and a hypoglycemic symptom questionnaire was administered. At a glucose level of 2.8 mM, NIDDM patients had reduced incremental glucagon (normal subjects, 114 ± 18 ng/l; NIDDM subjects, 63 ± 9 ng/l; P < 0.05) and growth hormone responses (normal subjects, 13.8 ± 1.0 micrograms/l; NIDDM subjects, 7.0 ± 2.0 micrograms/l; P < 0.01) and increased epinephrine (normal subjects, 925 ± 198 pM; NIDDM subjects, 4175 ± 824 pM; P < 0.001) and cortisol responses (normal subjects, 291 ± 49 nM; NIDDM subjects, 524 ± 92 mM; P < 0.05). Symptom scores were similar in both groups at all levels of glycemia. at all levels of glycemia. At a glucose level of 2.8 mM, NIDDM patients had a greater impairment on the simple (normal subjects, ₋ 10 ± 24 ms; NIDDM subjects, 108 ± 18 ms; P < 0.001) and choice (normal subjects, 20 ± 18 ms; NIDDM subjects, 111 ± 18 ms; P < 0.01) reaction time tests. We conclude that the elderly NIDDM patients have altered release of counterregulatory hormones and altered psychomotor performance during hypoglycemia.