Insulin resistance in Type 1 (insulin-dependent) diabetes following hypoglycaemia - evidence for the importance of β-adrenergic stimulation

Abstract

The insulin effect, evaluated with the euglycaemic clamp technique, was studied before and after hypoglycaemia in 7 patients with Type 1 (insulin-dependent) diabetes. Following an initial 2 h clamp (clamp I) hypoglycaemia was induced and 2 h later a second clamp (clamp II), identical to the former, was performed. Each subject was studied twice; during infusion with saline (placebo) or propranolol. Glucose production and disposal were studied with the 3(3H)glucose technique. During placebo infusion, hypoglycaemia elicited an insulin resistance leading to approx. 50% reduction in the steady state glucose infusion rate during clamp II as compared to clamp I (clamp I 2.58±0.32, clamp II 1.26±0.08 mg·kg-1·min-1, p<0.02). The insulin resistance was prevented by infusing propranolol (clamp I 2.29±0.29, clamp II 2.85±0.56 mg·kg-1·min-1). The posthypoglycaemic insulin resistance was due to a less pronounced insulin effect on both glucose production (clamp I 0.29±0.21, clamp II 0.86±0.19 mg·kg-1·min-1, p<0.05) and glucose utilisation (clamp I 2.84±0.26, clamp II 2.13±0.23 mg·kg-1·min-1, p<0.05). The insulin resistance on both glucose production and utilisation was prevented by propranolol. Thus, the present study demonstrates that hypoglycaemia elicits a prolonged insulin resistance which is due to a less pronounced effect of insulin to both inhibit splanchnic glucose production and to stimulate peripheral glucose utilisation. The insulin resistance is due to β-adrenergic stimulation and can be prevented by propranolol. © 1987 Springer-Verlag.