Treatment of Diabetic Retinopathy With Estrogens

Afternoon Glucose Tolerance Testing: A Key to the Pathogenesis, Early Diagnosis and Prognosis of Diabetogenic Hyperinsulinism

“…Although the writer has earnestly attempted to treat “early” cases of diabetes in adults with tolbutamide or phenformin—chiefly because of the purported beneficial effect of these drugs during this crucial period (77, 78)—the intensification of hypoglycemic symptoms and their clinical exacerbations have caused him to withhold the “prophylactic” use of these drugs. This policy is consistent with our observations on the unequivocal aggravating effect of hypoglycemia on diabetic neuropathy and retinopathy (30, 79) and the conviction that recurrent hypoglycemic stress with its various endocrine and metabolic sequelae probably plays a crucial role in the genesis of diabetes mellitus and its complications. The latter concept has received added support by Roth and co‐workers’(75) demonstration that hypoglycemia is the most potent stimulus in man for the elaboration of diabetogenic growth hormone.…”

“…On the twenty‐third day of somatotropin treatment, the injection of tolbutamide produced a hyperglycemic instead of a hypoglycemic response.” Although these investigators stated that the oral administration of tolbutamide concomitantly with daily intramuscular injections of growth hormone decreases or inhibits the diabetogenic effect, the relatively short periods of tolbutamide administration and the subsequent return of hyperglycemia with continued growth‐hormone administration do not justify the application of such observations to the management of clinical diabetes. Moreover, instances are now on record of severe protracted tolbutamide‐induced hypoglycemia in both diabetics and nondiabetics—even with total decompensation in a diabetic, as manifested by failure to respond to intravenous administration of tolbutamide (81).…”

Estrogenic Control of Corticosteroid‐induced Bruising, With a Commentary on Estrogen‐corticosteroid Interrelationships

“…However, the writer's observations on the control of corticosteroid‐induced cutaneous bleeding by administration of relatively small amounts of estrogenic substances are the result of several long‐term studies on the value of estrogens for the management of bleeding in other pressing medical disturbances for which specific therapy currently is lacking. Such situations have included bleeding as a complication of long‐term anticoagulant therapy (4), retinal bleeding associated with diabetic retinopathy (17), massive upper gastrointestinal hemorrhage (both variceal and nonvariceal) (16, 18), and bleeding due to hemorrhagic telangiectasia (19). Reports by others also have appeared regarding the control of bleeding by oral and intravenous administration of estrogens in hemorrhagic telangiectasia (20, 21), delayed post‐traumatic hemorrhage, functional uterine bleeding, traumatic hyphema (22), and bleeding (including fibrinolysis) following tonsillectomy, prostatectomy and ophthalmic surgery (23–28).…”

“…There is reason to believe that the enhanced resorption of hemorrhagic residues following administration of estrogens—particularly in cases of acute intraocular bleeding—is explainable in part by an effect upon some spreading factor (17, 41). Other mechanisms proposed to explain the hemostatic action of estrogen therapy include serotonin‐like activity, and the neutralization of a vascular toxin comparable to “menotoxin” (51).…”

Obesity Due to the Syndrome of Narcolepsy and Diabetogenic Hyperinsulinism: Clinical and Therapeutic Observations on 252 Patients*

“…In the writer's experience, however, the purported "prophylactic" use of sulfonylurea drugs in patients with decreased glucose tolerance (22) was attended by intensification of hypoglycemia. Accordingly, this approach has been either avoided, or limited to the administration of phenformin-a policy consistent with the following observations and convictions: (a) the likehood that "secondary tolbutamide failure" represents iatrogenic highoutput failure of insulinogenesis in patients who are "on the brink" of insulinogenic decompensation (11); (b) the aggravation of diabetic retinopathy (23) and diabetic neuropathy (24) by hypoglycemic attacks; (c) the demonstration that hypoglycemia is a potent stimulus for the elaboration of diabetogenic growth hormone (12a); (d) the reduction by phenformin of excessive insulin (25) and insulin-like activity (26) levels after glucose loading in obese and diabetic patients; and (e) the demonstration of improved or normal glucose tolerance during phenformin therapy in patients with "early chemical diabetes," i.e., patients repeatedly showing decreased glucose tolerance only by afternoon testing (27). For example, the following values (mg per 100 ml) were obtained in the blood of a 26-year-old obese white male with recurrent hypoglycemia, symptomatic epileptiform seizures (four years), narcolepsy, and a cafe-au-Iait spot:…”