Top Causes of Unexplained Hyperglycemia

Health Professional

As you know, many of my postings are based on clinical experience (as well as from my spies on this site). This past week a mother of one of my patients asked if I could blog about unexplained hyperglycemia.

We are not talking about forays into fast food restaurants with "neon" signs (as one expert diabetes educator used to quip) but rather despite perfect carbohydrate counting, proven insulin/carbohydrate ratios and insulin sensitivity factors, blood sugars still spike without obvious explanation.

One must always keep in mind when trying to analyze the reasons for highs (and lows), that at best, we are trying to approximate the magical workings of the pancreas (particularly the beta cells). Understanding pancreatic infrastructure in relation to the interaction of the beta cells and alpha cells, as well as other types of cells, also may be a piece of the puzzle related to glycemic control. Any attempt to mimic pancreatic function is still evolving in sophistication, at best.

What would be the most common causes of "unexplained" hyperglycemia? I would divide these causes into four major categories:

  1. Food related (explainable....but less obvious at the surface)
  2. Mechanical difficulties
  3. Physiological Counter-regulatory hormone response
  4. No idea
  1. Food related: Hyperglycemia may occur at a different time that one might expect due to the company of other nutrients associated with carbohydrates. Examples include hyperglycemia that occurs hours after the pasta/pizza/high fat/protein concentrated meal. These meals do not have to consist of fast food with hidden carbohydrates.

Hyperglycemia occurs due to the slower absorption of carbs secondary to the presence of fat and protein. Strategies are available to counteract this process including employment of the extended bolus/dual wave bolus functions on insulin pumps. Other strategies available with MDI regimes are to combine rapid acting insulin analogs (humalog, novolog, or apidra) with fast acting regular insulin.

  1. Mechanical difficulties include:
  • Hypertrophy of injection sites that prevent or delay insulin absorption (that is why we suggest rotation of all injection sites)
  • Leaking of insulin from the syringe or insulin
  • User error (miscalculation of insulin units)
  • Expiration of insulin in the pen or vial (Our diabetes team at Children's National Medical Center recommends tossing all vials of analog insulin (lantus, levemir, humalg, novolog, and apidra) after 28 days of use. We also suggest tossing any used vial/pen after a month if left at room temperature.
  • Kinked pump tubing/ walled off pump catheter sites (typically less than 3 days)
  • Malfunctioning pump hardware
  • Insulin or pump left out in extreme weather (hot/cold) thereby causing the insulin to be denatured
  1. Physiologic Counter-regulatory response. Any situation that is viewed in an emotional context (happy or sad) may provoke the release of epinephrine/norepinephrine or cortisol, endogenous glucagon, or growth hormone. Other hormones such as testosterone and those related to puberty also can wreak havoc and cause hyperglycemia (and sometimes even hypoglycemia-depending on the time of a woman's menstrual cycle).
  • Stress, such as examinations, meeting new teachers/friends, celebrations, death in family, deployment, new sibling, divorce, new marriage, fight with family members/significant others, sporting event, college or job interview, etc.
  • Illness--stress hormones are released in effort to fight the offending organism or repair the body after surgery.
  • Growth--blood sugars are often elevated overnight due to the release of growth hormone (dawn phenomenon).
  • Puberty--those pesky pubertal hormones often cause high blood sugars due to insulin resistance.
  • Chronic stress due to occupational worries, school difficulties, family stress, etc.
  • Anticipatory stress--boarding an airplane, dread, diffuse anxiety, depression, etc.
  • Medication induced--steroids for treatment of asthma, rheumatologic conditions, inflammation, or injuries. Other medications may include over the counter decongestants, liquid medications that may be reconstituted with a glucose containing syrup, or diluents.
  • Chemotherapeutic agents used to treat oncologic disease or to prevent rejection of an organ (kidney, pancreas, heart, etc.)
  • Hospitalization in which dextrose is automatically added to intravenous fluids unnecessarily in people with diabetes (this happens).
  1. No idea. In these situations, there is often an unknown stimulus that is provoking hyperglycemia. The difficulty lies in the detective work. In most cases, the situation is short- lived without discovering the reason, which is very frustrating for the person with diabetes, the caregiver, and diabetes team. The key is to look for patterns and to determine if this recurring hyperglycemia.

One often must become a diabetes detective to uncover the offending hyperglycemic stimulus.