Somatostatin reduces posthypoglycemic insulin resistance in insulin-dependent diabetes mellitus.

In order to study whether somatostatin reduces posthypoglycemic insulin resistance, hypoglycemia was induced between 7.00 and 8.00 h by an iv infusion of insulin with and without somatostatin (250 micrograms/h) in 6 male patients with insulin-dependent diabetes mellitus (IDDM). Exogenous glucagon was infused to substitute for the suppression of its endogenous release (1.0-1.5 ng.kg-1.min-1). Insulin resistance was assessed by a somatostatin-insulin-infusion test (SIGIT) between 11.00 and 15.00 h. In the study without hypoglycemia, blood glucose was kept close to 6 mmol/l from 8.00 h until start of the SIGIT. In both hypoglycemic studies similar nadir blood glucose levels were achieved and hypoglycemia evoked the same increase of plasma epinephrine and cortisol, whereas plasma glucagon remained at its basal level. The growth hormone response to hypoglycemia was suppressed by somatostatin. At the onset of the SIGIT, the plasma levels of the counterregulatory hormones had returned to basal, and blood glucose and plasma free insulin concentrations were almost identical. During the SIGIT there were no differences in plasma free insulin or counterregulatory hormone levels. Insulin resistance, as seen following hypoglycemia, was not demonstrable in the study with somatostatin. It is concluded that somatostatin reduces insulin resistance following hypoglycemia in patients with IDDM. It is therefore suggested that an analogue with a specific GH release inhibiting property may be useful in reducing glycemic instability when given as adjunct therapy to insulin in patients with labile glycemic control.