Hypoglycemia, or low blood sugar, was the first complication noticed with insulin.  While testing the effectiveness of his insulin preparations in rabbits, Collip noted that insulin that was too strong caused rabbits to enter into a coma and could even induce seizures and ultimately death.  Hypoglycemia occurs in gradual forms, from a mild barely noticeable case to a severe case that results in death.

The symptoms of hypoglycemia vary by patient, and some patients may have almost no symptoms to mild hypoglycemia.  Symptoms of mild hypoglycemia typically include nervousness, perspiration, weakness, and hunger.  The more severe symptoms are drowsiness, dipolopia (double vision), mental confusion, and ataxia (loss of fine motor control).  The severe symptoms can be confused with alcohol intoxication.  Indeed, there are case reports of patients being taken to the police station on charges of public intoxication, while they are having a hypoglycemic event.[bowen, insulin hypoglycemia].

George Minot learned to recognize the symptoms of hypoglycemia and self-treat it.  Hypoglycemia is also known as an “insulin reaction”.  He would call out to his wife, “Please get me an orange or a couple of crackers, and get it quick!  I am having a reaction.” [inquisitive p 129].  He had a habit of pocketing lumps of sugar that were served with coffee in fine restaurants or hotels.  He used these whenever he needed to control his insulin reactions.

Mild cases of hypoglycemia can be temporary and hard to diagnose.  An article in the NEJM in 1933 described one such case.  A school-aged child in Minnesota with diabetes was under the care of Dr Russel Wilder, the head of diabetes research at the Mayo Clinic in Minnesota.  The patient was fastidious about following his diet and taking his insulin on a reliable schedule.  Dr Wilder noted that the child achieved excellent grades in his classes, except for one course in which he consistently had lower grades.  This pattern persisted over several months.  Upon further questioning, Dr Wilder found that the subject in which his patient did poorly was consistently taught in the late morning.  Dr Wilder then understood the problem.

The patient’s insulin from his morning shot was fully in his system before he ate lunch.  The insulin was depleting the boy’s blood glucose level, leading to a mild case of hypoglycemia.  The hypoglycemia occurred consistently each day at the same time, just as the class did.  The boy’s brain was slightly impaired for one class only, then he ate lunch.  The doctor altered the boy’s diet to have a midmorning snack light on carbohydrates.  The boy’s grades in that late morning class immediately improved.