Failure of Warning in Insulin-induced Hypoglycemic Reactions

Spontaneous Leg Cramps and “Restless Legs” Due to Diabetogenic Hyperinsulinism: Observations on 131 Patients*

“…For example, a nonobese 66‐year‐old diabetic male had longstanding severe cramps and “drawing” of the lower extremities that predictably occurred about 2–3 a.m. A reduction of his tolbutamide dosage and insistence upon taking a bedtime snack effected prompt and persistent relief of these symptoms. Others (18) have commented upon the vulnerability of diabetic patients in the first category to severe hypoglycemic complications.…”

Multifactorial Origin of Hypoglycemic Symptom Unawareness in IDDM: Association With Defective Glucose Counterregulation and Better Glycemic Control

“…A pathophysiological common denominator of defective glucose counterregulation, altered glycemic thresholds during intensive therapy, and hypoglycemic symptom unawareness is a reduced sympathochromaffin response to plasma glucose decrements (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Evidence of a reduced parasympathetic response (increments in plasma levels of pancreatic polypeptide) to hypoglycemia has been demonstrated in defective glucose counterregulation (23) and might be anticipated in the other two syndromes.…”

“…It has been shown in prospective studies (5,6) to be associated with at least a 25-fold increase in the risk for severe iatrogenic hypoglycemia. Although it has not been documented by prospective studies, it is reasonably assumed that the absence of warning symptoms of developing hypoglycemia also contributes to this high frequency of iatrogenic hypoglycemia (7)(8)(9)(10)(11). Indeed, hypoglycemia unawareness segregates with defective glucose counterregulation (10), with which it shares a pathophysiological feature-a reduced epinephrine response to hypoglycemia.…”

An Inquiry Into the Pathogenesis, Rational Treatment and Prevention of Multiple Sclerosis, With Emphasis Upon the Combined Role of Diabetogenic Hyper‐insulinism and Recurrent Edema*

“…The mode of action of oxytocin in these patients may encompass one or several of the following: 1) changes in glomerular filtration (14); 2) an alteration of cell membrane permeability to sodium, potassium and water flux in central neurones and glial cells (including the hypothalamus) and in the pituitary; 3) replenishment of reduced tissue oxytocin concentrations resulting from hypothalamic or pituitary stress and metabolic injury; 4) the inherent metabolic effects of oxytocin on intermediate metabolism; 5) stabilization of liposomal membranes (which diethylstilbestrol and progesterone render more permeable), an action comparable to that of cortisone; and 6) modification of the action of insulin (or its A and B chains), growth hormone, vasopressin, antibodies with interchain disulfide bonds, or combinations thereof, on target‐cell membranes or organelles by preferential attachment to sulfhydryl or disulfide receptors. The inability of several observers (15) to detect amino acids containing disulfide bonds (notably cysteine) in encephalitogenic proteins derived from brain or spinal cord (both animal and human) is germane.…”