The Most Common Cognitive Error That Physicians Make When Treating Patients with Type 1 Diabetes

Andrew Norris, MD PhDPost by
Andrew Norris, MD PhD
Director, Pediatric Endocrinology & Diabetes
University of Iowa Stead Family Children’s Hospital

it is incumbent upon the pilot/physician to keep one hand on the throttle and one on the stick by providing both glucose and insulin when someone with type 1 diabetes is unable to eat…

Managing type 1 diabetes is challenging, including for physicians. Often a physician naturally feels caught between two opposing fears.

  • Fear #1: “if too much glucose is given, the blood sugar might go too high”
  • Fear #2: “worse yet, if too much insulin is given then the blood sugar can go dangerously low”

These fears are real and represent real risks. The fear of these is especially heightened when managing diabetes in someone who is unable to eat. Unfortunately, these two fears present a false dichotomy that can lead to a cognitive error. The specific error logic is as follows:

  • Response to fear #1: “if glucose is not given, then the blood sugar can’t go high
  • Response to fear #2: “if insulin is not given, then the blood sugar can’t go low

The physician then writes orders that omit glucose (i.e. dextrose) from the IV fluids and under-dose insulin. Although this approach at first seems like a reasonable way to resolve the above conundrum, it can lead to serious issues. A useful analogy is that this is similar to flying a plane by cutting power to the engine and taking one’s hands off the stick. To better understand this, let’s first explore what happens when someone without diabetes is not given any glucose or carbs as they undergo fasting. The figure immediately below shows what happens to their plasma glucose, insulin and ketones levels.

Graph of the fasting response over time in terms of glucose, insulin, and ketones.
Normal Fasting Response: Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively.

As shown in the figure, during fasting, glucose levels drop as expected, and in response insulin levels drop . But importantly, insulin levels do not drop to zero, but rather decline to a low but basal level. As insulin levels become low, this induces a catabolic state including the production of ketones. Key to this process is the fact that a low level of insulin remains to keep ketone production in check. To use our simplistic analogy, even though we let go of the airplane controls, autopilot has kicked in, courtesy of the beta-cells that maintain a basal degree of insulin secretion.

Let’s contrast this to what happens in someone with type 1 diabetes who can not make their own insulin. In this case, if insulin is not being given, levels eventually fall to zero, as shown in the next figure.

Graph of the fasting response over time in terms of glucose, insulin, and ketones in someone who can not produce endogenous insulin.
Fasting Response When Insulin Goes to Zero: Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively. DKA stands for diabetic ketoacidosis, a life-threatening condition.

When insulin levels become abnormally low, two important things happen. Firstly, this triggers runaway gluconeogenesis, eventually leading to formation of new glucose and onset of spontaneous hyperglycemia. In other words, even though the person is not receiving glucose, their blood sugars rise because of the production of new glucose by their liver. Secondly, the abnormally low insulin levels allow runaway ketone production, eventually leading to diabetic ketoacidosis. To return to our simplistic analogy, our airplane has crashed and burned. When insulin levels reach zero, our engine can no longer burn fuel properly (i.e. insulin enables cells to properly utilize glucose), and gravity (i.e. run-away catabolism and ketone formation) ultimately wins.

Often, and typically in pediatrics, glucose is provided intravenously to patients without diabetes who can not otherwise obtain nutrition. It is informative to examine what happens to plasma insulin, glucose, and ketones in this situation, as shown in the next figure.

Fasting response while giving supplemental glucose over time in terms of glucose, insulin, and ketones.
Response to Glucose Infusion in Persons without Diabetes: Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively.

As is shown in the figure, the ongoing administration of intravenous glucose causes blood sugar to rise some, but the body responds by increasing insulin to compensate such that blood sugar remains normal. Importantly, because insulin does not reach low levels, ketone production remains suppressed and catabolism is avoided. This is a safe state for the patient. To keep a patient with diabetes safe, the physician can mimic this state by providing insulin and glucose. The insulin and glucose must be counterbalanced, and importantly insulin levels must be maintained always at a basal level, either through provision of long acting insulin or via intravenous insulin drip. Additionally , the blood sugars typically will vary. Despite this, because insulin is being continually supplied, ketone production is suppressed and the patient remains safe. The next figure illustrates this approach.

Graph of the fasting response in someone who can not make endogenous insulin while giving glucose and insulin exogenously.
Provision of glucose and insulin in a fasting person with type 1 diabetes. Plasma glucose (mmol/L), insulin (pmol/dL), and ketones (mmol/L) are shown in blue, green, and red respectively.

Although the blood sugar varies, the patient remains safe because insulin levels do not fall to zero and because glucose is administered to maintain blood sugar levels. This way run-away catabolism and ketone formation are avoided, as are hypoglycemia and severe hyperglycemia.

Returning to our airplane analogy, functioning beta-cells are our usual autopilot. Someone with normally functioning beta-cells can be fasted or fed or given IV dextrose and remain euglycemic, avoiding hypoglycemia and ketoacidosis. In type 1 diabetes this autopilot is absent and it is incumbent upon the pilot to keep one hand on the throttle and one on the stick. Just like flying a plane, with study, practice and experience, the flight can be less turbulent.

In infants, children and adolescents with type 1 diabetes, the risks are heightened. Infants and children develop ketones at a more rapid pace than adults, and adolescence induces a state of physiological insulin resistance. Likewise, during illness and medical stress, the drive towards catabolism is increased, and the risks of crashing greater. Please know that your local pediatric endocrinology team remains happy to assist, helping ensure many safe landings.

Some notes: (1) Although the above discussion is simplified in many ways and the actual involved physiology is complex, nonetheless almost without exception out-of-control ketogenesis ensues when insulin levels become extremely low. (2) In the airplane analogy, gravity represents the incessant pull towards catabolism when insulin levels are low. (3) Although we think of dextrose containing fluids as driving major hyperglycemia, it should be remembered that 100 mL of D5 contains only 5 grams of glucose, about the same as 3 skittles or 2 saltine crackers. Interestingly, hepatic glucose production during routine fasting (i.e. overnight) is roughly the same as D10 containing IV fluids running at maintenance rates. For this reason, many metabolism experts advocate D10 containing IV fluids at maintenance rates to best avoid catabolism in patients both with and without diabetes. (4) Please know that blood glucose and plasma glucose are nearly equivalent, especially conceptually for the above purpose, and are thus used interchangeably above. (5) I don’t have actual data that this is the most common severe conceptual error in managing inpatient diabetes, but rather this reflects over a decades experience. (6) On a brief personal note, I would like to thank my life partner for proofing this.

Hormone-Secreting Pituitary Tumors

When these tumors occur in children, the manifestations are often different than in adults.

Andrew Norris, MD PhDPost by
Andrew Norris, MD PhD
Director, Pediatric Endocrinology & Diabetes
University of Iowa Stead Family Children’s Hospital

A concise review of hormone-secreting pituitary tumors and their clinical syndromes appears in today’s New England Journal of Medicine. The article starts by noting that hormone secreting pituitary adenomas account for ~15% of all intercranial tumors. Although the article is informative and well written, it largely omits the characteristics of these disorders in childhood. When these tumors occur in children, the manifestations are often different than in adults. Below I have tabulated the anterior pituitary hormones that can be oversecreted by pituitary adenomas, and their common related childhood syndromes / symptoms. The table is listed in order of prevalence, from occasional to exceedingly rare (just a few case reports ever). Some of the symptoms of these conditions are common and non-specific (e.g. headache) and usually do not indicate a pituitary adenoma. Other symptoms almost always warrant an endocrine workup, especially growth failure, galactorrhea, precocious puberty, pubertal failure, gigantism, and acromegaly. On the flip side of hormone-secreting adenomas are pituitary adenomas that do not secrete hormones. Even though such adenomas do not secrete hormones, they eventually can lead to symptoms once their size impinges on local function. These manifestations can include visual field defects, headache, deficiency of pituitary hormones though prolactin can be modestly elevated due to pituitary stalk compression. Importantly, hormone secreting adenomas can also lead to these size-related effects as well.

Hormone oversecretedChildhood manifestations
Prolactin
(prevalence ~1/10,000)

Menstrual disturbance (girls)
Galactorrhea (girls)
Gynecomastia (boys)
Pubertal delay/failure (boys)
ACTH
(incidence <1/million/yr)
Weight gain
Growth failure
Striae
Hypertension
Amenorrhea (girls)
Hirsutism (girls)
Growth hormone (rare)Gigantism
Acromegaly
TSH (exceedingly rare)Hyperthyroidism
Headache
LH, FSH (exceedingly rare)Precocious puberty

Endocrine Conditions that “Break the Rules”

Andrew Norris, MD PhDPost by
Andrew Norris, MD PhD
Director, Pediatric Endocrinology & Diabetes
University of Iowa Stead Family Children’s Hospital

In pediatrics and medicine we are taught various rules that help us interrogate a person’s health . However, there are a variety of endocrine  disorders that alter normal physiology such that the usual rules no longer apply. Failure to recognize this can lead to erroneous interpretation of a person’s condition, sometimes with even fatal results


“Good urine output indicates that a child is well hydrated”

This is a stalwart rule in pediatrics. When a child is making plenty of urine, this proves that the child is well hydrated. In general this is sage advice, but there are important endocrine exceptions:.

  • Hyperglycemia / diabetes mellitus: When a child’s blood sugar is elevated, this produces an obligate osmotic diuresis. As a result, urine output remains brisk even when the child has become significantly dehydrated. To further exacerbate this, hyperglycemia leads to an osmotic fluid shift from the interstitium to the intravascular compartment, further increasing renal fluid output at the expense of worsening whole body hydration status. For these reasons, the child presenting with severe hyperglycemia is typically more dehydrated than the history and physical examination would suggest. There are cases where clinicians have been falsely reassured by a vomiting child’s brisk urine output, concluding that everything is fine when the child truly has severe hyperglycemia, with sometimes fatal consequences. Pediatricians in training are advised to become practiced and adept at asking children and families about any changes in thirst and urination, as this can be a fairly effective screening tool to assess for out-of-control undiagnosed severe diabetes.
  • Diabetes insipidus: In the child who has diabetes insipidus, urine output is not a reliable indicator of hydration status. When diabetes insipidus is not treated, brisk urine output occurs even in the face of dehydration. When diabetes insipidus is treated with vasopressin or DDAVP, urine output diminishes when the medication is active, even when hydration status is excellent.

“Children and adolescents can tolerate the physical stress of fever or vomiting.”

Typically, children can tolerate common physiological stressors such as significant febrile illness or vomiting / fasting during gastroenteritis. However, often children with underlying medical conditions do not tolerate such physiological stressors as well. Included in such underlying illnesses are several important and relatively common endocrine conditions

  • Adrenal insufficiency: An important component of the response to physiologic stress is increased secretion of adrenal hormones, especially cortisol. Children who are unable to secrete adequate amounts of cortisol can experience hypoglycemia, hyponatremia, and sometimes even cardiovascular collapse in response to physiologic stressors that ordinarily a child could tolerate without difficulty. Conditions in which cortisol secretion in response to stress can be impaired include panhypopituitarism, central adrenal insufficiency, congenital adrenal hyperplasia, Addison’s disease, iatrogenic adrenal suppression, and any form of hypoadrenalism. Children who have impaired mineralocorticoid secretion are at even greater risk for electrolyte imbalance, specifically hyponatremia and hyperkalemia, and cardiovascular collapse. common causes of mineralocorticoid deficiency include congenital adrenal hyperplasia and Addison’s disease. Fortunately stress dose hydrocortisone is an effective means to treat children with these conditions and enable them to better tolerate physiologic stressors.
  • Diabetes mellitus: Pediatric patients with diabetes require special attention to blood glucose and Insulin management during times of physiological stress. During such times, especially in patients with type 1 diabetes, there will be an increased risk of dysglycemia, ketones, dehydration, and diabetic ketoacidosis.
  • Hyperthyroidism: Patients who have active hyperthyroidism can experience significant deterioration during physiological stress and illness. In some cases, illness can precipitate thyroid storm, which can include life-threatening hyperthermia, confusion, diarrhea, tachycardia, arrhythmia, cardiovascular collapse, and coma.

“Children and adolescents tolerate exercise well”

In general children and adolescents can exercise seemingly ad infinitum. however there are a number of medical exceptions to this, including situations in which it is not entirely safe for a child to exercise vigorously. Several endocrine conditions are included among these exceptions to this common rule.

  • Hyperthyroidism: Children and adolescents with active hyperthyroidism typically experience a degree of exercise intolerance. If the hyperthyroidism is significant, some patients will even experience cardiovascular decompensation and/or hyperthermia triggered by vigorous exercise.
  • Ketonemia: children with diabetes can benefit greatly from exercise. however, when diabetes and ketones are present, exercise can exacerbate the degree of ketonemia, and in extreme cases can contribute to the development of diabetic ketoacidosis. standard advice during ketonemia in pediatric patients with diabetes is to administer supplemental insulin, optimize hydration, and delay a vigorous exercise until after the ketones have been cleared.

“Children do not experience electrolyte problems as long as renal function is normal and fluid / electrolyte intake is adequate.”

Although adequate fluid and electrolyte intake coupled with normal renal function is typically sufficient to maintain normal electrolyte balance, there are important exceptions to this rule especially in the endocrine system.

  • Diabetes insipidus: Patients with untreated diabetes insipidus generally develop hypernatremia during normal intakes of fluid and electrolytes. provision of greater than normal amounts of free water and or medical treatment of the diabetes insipidus is required to prevent hypernatremia.
  • SIADH (syndrome of inappropriate ADH secretion): Patients with SIADH have a tendency towards hyponatremia when provided normal amounts of fluid and electrolyte. Fluid restriction is commonly used to prevent hyponatremia in such patients.
  • Mineralocorticoid deficiency: Patients with untreated mineralocorticoid deficiency are prone to hyponatremia and hyperkalemia despite normal fluid and electrolyte intake. Common pediatric causes of mineralocorticoid deficiency include congenital adrenal hyperplasia and Addison’s disease.

“Failure of an infant to gain weight is a feeding issue.”

Many times, when an infant is not adequately gaining weight this can indicate various feeding issues. However, there are many medical diseases which can cause poor weight gain during infancy for reasons other than poor nutritional intake. There are several important to endocrine diseases among these conditions. Congenital adrenal hyperplasia typically causes poor weight gain and failure to thrive beginning towards the end of the first week of life. Neonatal Graves disease, when severe, presents with failure of a newborn to gain weight typically in the first week or two of life. Neonatal diabetes mellitus can present at various times in the first six months of life and can lead to poor weight gain.