Insulin-Resistant Diabetes Associated With Increased Endogenous Plasma Insulin Followed by Complete Remission

Abstract

Insulin unresponsiveness may be associated with a multitude of conditions and reflect diverse etiologies (1). In most cases of chronic insulin resistance it has been possible to demonstrate insulin antagonists in the plasma which have many of the characteristics of antibodies (2-4). The resistance to insulin has usually been attributed to these antibodies, but several cases of insulin resistance associated with increased amounts of insulin in the plasma have been reported (5-8). In these cases tissue unresponsiveness was postulated as the cause for the resistance. In all of these cases circulating insulin could be demonstrated only at a time when the patients were receiving large doses of exogenous insulin, and therefore the insulin in the plasma probably represented injected insulin. We recently have had occasion to study a patient with severe insulin resistance whose plasma contained large amounts of insulin 3 months after her last known injection. Over the ensuing 18 months she had a gradual but complete remission of both diabetes and insulin unresponsiveness. The purpose of this paper is to report studies on this case which indicate that the insulin-like activity in her plasma did, in fact, represent endogenous insulin and that the cause for her insulin resistance was probably due to decreased tissue responsiveness to the hormone. The explanation for her remission is unknown, although there are occasional reports in the literature of spontaneous remission in severe diabetics (9). As far as we know this is the first reported case of insulin-resistant diabetes associated with greatly increased levels of endogenous insulin. METHODSThe rat hemidiaphragm. studies were done as follows.Fed rats weighing between 120 and 170 g were killed by a blow on the head; the diaphragms were removed as rapidly and with as little trauma as possible. Each hemidiaphragm was trimmed, blotted, weighed on a torsion balance and then put into a flask holding 2 ml of incubation medium which contained 0.5 ml of 1,000 mg per 100 ml glucose in Krebs-Ringer bicarbonate buffer (pH 7.4), variable amounts up to 1 ml of dialyzed plasma to be tested, and enough Krebs-Ringer bicarbonate buffer to make the final volume 2 ml.

Comparative Effects of Insulin on Adipose Tissue Segments and Isolated Fat Cells of Rat and Man*

“…Previous reports describe an insulin effect on glucose metabolism by human adipose tissue only with pharmacological doses of either 100 mU/ml (25,26,(4)(5)(6) or 10 mU/ml of insulin (7). Since completion of our work, Owen et al (27) …”

A case of insulin resistant diabetes with possible antibodies to insulin receptors.

“…The mechanism of spontaneous remission of insulin resistance also remains to be clarified though this peculiar phenomenon has been described previously (Field, et al, 1961;Bruce et al, 1970;Barnes et al, 1974;Kahn et al, 1976).…”

Effects of Autoantibodies to the Insulin Receptor on Isolated Adipocytes

“…In an elegant study of one of the first patients with insulin resistance and acanthosis nigricans (it is difficult to decide if this patient was more like our Type A or Type B patients), Field and co-workers demonstrated a marked increase in the insulin-like activity of serum by bioassay (29). On fractionation of the serum by starchblock electrophoresis, this bioactivity appeared in the zone between y-and , 8- (11).…”