Insulin Resistance and Hyperinsulinemia
Is hyperinsulinemia the cart or the horse?
1) Mice transfected with extra copies of the insulin gene produce basal and stimulated insulin levels that are two to four times elevated. The mice are of normal weight but show insulin resistance, hyperglycemia, and hypertriglyceridemia.
2) Somogyi described patients with unusually high doses of insulin and hyperglycemia. Episodes of hypoglycemia with release of glucose-raising hormones, postulated as the culprits in early studies, have largely been excluded by studies including continuous glucose monitoring.
3) Rats and humans treated with escalating doses of insulin show both hyperinsulinemia and insulin resistance.
4) The pulsatile administration of insulin (rather than continuous) results in reduced requirements for insulin.
5) Many patients with insulinoma who have elevated basal levels of insulin have reduced (but not absent) responsiveness to administered insulin.
In summary, hyperinsulinemia is often both a result and a driver of insulin resistance.