The Augmented Insulin Tolerance Test for Detecting Insulin Resistance

Abstract

SUMMARY 1. An augmented insulin tolerance test and its normal response is described; after a standard preparation, 11·1 u. of soluble insulin/m.2 of body surface is injected intravenously, and the level of blood sugar followed for 2 hr. 2. The degree of insulin resistance, in such states as acromegaly, can be indexed by the sum of the blood sugar values, as mg./100 ml., at 60, 90 and 120 min. after insulin. In normal subjects the mean 'insulin resistance index' was 92 (range 62–142). The test is valid only if the fasting blood sugar is normal. 3. Results are reported in: (a) twelve 'untreated' acromegalics in all of whom the test showed an abnormal insulin resistance index (mean 173 and range 144–228); (b) fourteen treated acromegalics (after gold-198 or yttrium-90 implants), in eight of whom the insulin resistance index was normal, although only five were judged to be in full clinical remission; (c) twelve subjects with gross but 'simple' obesity in whom the test results were nearly as abnormal as those of the 'untreated' acromegalics (mean insulin resistance index 159 and range 119–221). 4. The test can be used to assess the 'activity' of acromegaly and its response to treatment, provided the subject is not also grossly obese.

The plasma sugar, free fatty acid, cortisol, and growth hormone response to insulin, and the comparison of this procedure with other tests of pituitary and adrenal function. II. In patients with hypothalamic or pituitary dysfunction or anorexia nervosa.

“…Thus patients with acromegaly have been shown to be resistant to the hypoglycemic action of insulin (17); the four patients with untreated acromegaly in the present study required 0.30 U of insulin per kg to produce a response similar to that found in control subjects given half this amount. The increased insulin sensitivity found in hypopituitarism (18) or hypothalamic dysfunction (19) would appear to be of less diagnostic value, since some patients in the present study, who had definite endocrine hypofunction, showed a normal plasma sugar response to insulin.…”

“…Thus Patients 5, 6,12,13,14,17,19,21,22, and 24 were receiving 0.2 or 0.3 mg of L-thyroxine daily, Patients 5,6,12,14,19,21, and 22 were receiving 20 or 30 mg of cortisol daily, and Patient 27 was receiving 15 mg daily of methyl testosterone.…”

Human Placental Lactogen: Studies of Its Acute Metabolic Effects and Disposition in Normal Man*

“…Pregnancy is associated with an antagonism to the hypoglycemic action of insulin (3,4) which is comparable to that observed in acromegaly (5,6) and to that which follows the administration of growth hormone (7,8). Experimental studies have indicated that HPL, like growth hormone, induces impaired glucose tolerance in cortisol-treated hypophysectomized rats (9), stimulates glucose oxidation to CO2 and incorporation into fat in the rat epididymal fat pad (10), and promotes lipolysis in isolated fat cells ( 11 ).…”

The plasma sugar, free fatty acid, cortisol, and growth hormone response to insulin. I. In control subjects.

“…There is evidence that glucocorticoids and growth hormone play an important role as hormonal insulin antagonists. Thus both Addison's disease and hypopituitarism are known to be associated with increased insulin sensitivity, whereas patients with Cushing's syndrome or acromegaly are resistant to its hypoglycemic action (2,3). The observation that the intravenous injection of insulin into control subjects results in rapid elevations of plasma cortisol (4,5) and growth hormone (6)(7)(8)(9) also supports the possible physiologic importance of these hormones as insulin antagonists.…”