Complications

This topic is presented by dividing it into two categories: acute and long-term complications. The complications identified as acute are hypoglycemia, hyperglycemia (including Hyperosmolar Hyperglycemic State, or HHS), and diabetic ketoacidosis (DKA). Because development of any one of these can be relatively rapid, prevention must be practiced on a day-to-day or sometimes moment-to-moment basis. The causes of these problems are easily understood. As a result, successful prevention is likely.

Those complications designated as long-term are not as well understood in terms of cause and effect, and take longer to develop. These problems affect the kidneys, heart, brain, and nerves (most notably the retinas), and are believed to be due fundamentally to vascular changes which occur in diabetes: microangiopathies and macroangiopathies, diseases of the small and large vessels.

It has long been believed that the complications due to vascular changes are a consequence of high blood glucose levels over long periods of time. The findings of the Diabetes Control and Complications Trial (DCCT) (Reichard, Nilsson, & Rosenqvist, 1993) as well as those of the United Kingdom Prospective Diabetes Study Group (UKPDS) (1998) support this assertion.

It is also possible that the vascular changes are a part of the disease itself. Or, it may be that complications are due to antibodies which build up in response to exogenous insulin. There are many theories which are being studied.

Acute Complications


Hypoglycemia (Insulin Shock or Low Blood Sugar)

The most frequently encountered emergency is that of hypoglycemia. Other terms for this are insulin reaction, insulin shock, and low blood glucose. It can occur rapidly and, though most diabetics become very sensitive to early signs of a drop in blood glucose, it can occur without obvious symptoms or signs (hypoglycemia unawareness). The causes are due to any one or a combination of the following:

1. Taking too much insulin or oral hypoglycemic agent. This can happen accidentally as in the diabetic with poor eyesight, or can be done purposely in an effort to prepare for over-eating. It is, however, very difficult in the latter case to know just how much is enough, and too much may be taken.

2. Vomiting after taking the normal amount of insulin.

3. Eating less than what is prescribed while taking the same dose of insulin or oral agent.

4. Delaying a meal.

5. Exercising excessively.

The end result is hypoglycemia and the onset is rapid: within minutes or hours. The brain cannot function properly when blood glucose gets too low. Mental functions and coordination become disrupted. Headache, blurred vision, tachycardia and diaphoresis may occur. Most noticeable to an on-looker are the reduced motor control, shakiness, and mental confusion. It may be possible to detect hypoglycemia of the sleeping patient by assessing his/her skin for diaphoresis, but a negative assessment is not 100% reliable.

The cure is immediate ingestion of a highly concentrated source of glucose. If the individual is not able to swallow or unconscious, sublingual (under the tongue or inside the cheek) application of concentrated sugar (with the individual in the side-lying position), injection of glucagon, or 50% dextrose IV are the emergency treatments. Well educated diabetics will have glucose products nearby - in a purse, pants pocket, glove compartment, etc.

Commercially available glucose products are a more concentrated source of glucose than most foods, so may work more rapidly and with more predictable results. Look for Glutose (Paddock Labs), Glucose Tablets (Becton-Dickenson), or other over-the-counter products. Such products are available at most drug stores, and people with diabetes who take medications that could cause hypoglycemia should be strongly urged to never be further than an arm's length away from such products!

Fifteen grams of carbohydrate will raise the blood glucose approximately 40 mg/dL in some people – more, or less, in others. The exact effect varies individually. People with diabetes should be encouraged to find their own response with blood glucose testing after ingesting fifteen grams of carbohydrate. Relief of symptoms should occur in 10-15 minutes. Retreatment should be delayed until this time to avoid over-treating the hypoglycemia and thereby creating hyperglycemia.

Chocolate or other foods high in fat should not be ingested to treat hypoglycemia due to the delayed absorption of glucose caused by the fat, unless nothing else is readily available.

Critical to know: When in doubt about the cause of a known diabetic's unconsciousness, administer highly concentrated glucose (sugar) as quickly as possible. If the cause is hypoglycemia, this could prevent brain damage and save a life. If it is due to hyperglycemia and/or ketoacidosis, the additional glucose will cause relatively little harm.

Injectable glucagon - a hormone made by the alpha cells of the pancreas - is available by prescription. As recommended by the American Diabetes Association (2018), "Glucagon should be prescribed for all individuals at increased risk of clinically significant hypoglycemia, defined as blood glucose < 54 mg/dL (3.0 mmol/L), so it is available should it be needed. Caregivers, school personnel, or family members of these individuals should know where it is and when and how to administer it. Glucagon administration is not limited to health care professionals” (p. S61).

Anyone who takes insulin, takes a medication that stimulates the production of insulin, is declining cognitively, or who has hypoglycemia unawareness (a condition in which the blood glucose drops but the individual is not aware that it is dropping or is low) is at "significant risk of severe hypoglycemia." Considering these issues, the American Diabetes Association advises asking patients at every medical visit about their experiences with hypoglycemia, and conducting regular assessments of cognitive functioning of those patients who are at such risk (2014, p. S33).

Glucagon stimulates the release of glucose stored in the liver. It should be used if the individual is unconscious and his or her blood glucose level is unknown or is under 60 mg/dL, or if the conscious person is hypoglycemic, but unwilling or unable to ingest food. A Glucagon Emergency Kit should be stored according to the manufacturer's instructions, and replaced by the expiration date. Significant others of the diabetic must be taught how to prepare and administer this drug.

(Tip: Advise patients to conduct, among family members, a trial run of their response to an episode of unconsciousness on the part of the patient. Family members should practice verifying the patient is truly unresponsive and is not just taking a nap, and should draw up the glucagon and explain how it would be administered. Information about how to contact emergency medical personnel should be readily available. This would be far better than simply throwing the unused glucagon in the trash!)

It is important to teach the diabetic individual to take action at the earliest sign of hypoglycemia, but even more important is prevention:

All diabetics who take insulin or oral hypoglycemic agents should wear or carry identification so that their condition is known and emergency measures can be taken in the event of being found unconscious or unable to communicate. Convulsions, brain damage, and death can occur rapidly without appropriate intervention. Medic Alert is an organization established to speak for one's hidden medical problems. A member wears an emblem which carries basic information as well as a collect phone number to call for specific information in an emergency. Medical personnel are taught to look for such things. The address for more information is:

Medic Alert Foundation
2323 Colorado Avenue
Turlock, CA 95382
www.medicalert.org
1-888-633-4298

Many pharmacies carry generic identification necklaces and bracelets as well.

Hypersmolar Hyperglycemic State (HHS)

Hyperglycemia results when intake exceeds that permitted in proportion to the amount of exogenous insulin or oral hypoglycemic agent taken. Most cases of simple hyperglycemia resolve slowly when normal food intake is resumed.

Supplemental fast-acting insulin will reduce the blood glucose most efficiently but there are inherent problems with this form of intervention. It is very difficult to accurately determine how much insulin to take in such circumstances, and the chance of over doing it is great. The resultant hypoglycemia is simply trading one problem for another.

Another concern is with regard to the anabolic effect insulin has on the body: repeated supplementation with insulin will result in weight gain. If hyperglycemia is a persistent problem and over-eating is not the obvious cause, an adjustment in the daily insulin dosage, oral hypoglycemic agent, eating patterns or food intake (or both), and/or exercise might be in order.

Increased exercise when the blood glucose is elevated will usually hasten resolution of the problem. Exercise when blood glucose is over 300 mg/dL, however, is not recommended, due to insufficient insulin to ensure glucose uptake by muscles. When severe, the condition is called Hyperosmolar Hyperglycemic State (HHS) and hospitalization is necessary.

HHS is a condition characterized by blood glucose in the range of > 600 mg/dL and serum osmolality > 330 mOsm/L (i.e. significant dehydration) with little or no ketone production in the blood or urine (Kitabchi et al., 2001). It can be the result of excessive overeating, the effects of a profound emotional or physical crisis in which glucocorticoids stream into the blood thereby elevating the glucose level, or due to an infusion of highly concentrated glucose solutions. Treatment requires immediate hospitalization to restore fluid volume and reduce the blood glucose.

HHS can affect persons with DMT1 or DMT2, though it is more common among those with DMT2 and/or those with DMT2 who have a concomitant illness such as an infection. Older patients with DMT2 are more often the victims of HHS than are younger patients, and among this group, HHS carries a higher mortality than does diabetic ketoacidosis (Hemphill, 2012). The fundamental problem in HHS is extremely high blood glucose, and the fact that it is non-ketotic indicates that it is not a result of the aberrant pathway taken when insulin is not available. One should be suspicious of HHS in the emergency setting when an elderly patient who has DMT2 presents with altered mentation or dehydration or both.

Until recently, the condition, HHS was called Hyperglycemic Hyperosmolar Nonketotic coma or HHNK. The issue of the presence or absence of ketones warranted a change in the name of the condition because it was found that, on occasion, ketones were present. The fundamental issue focuses on the pathology associated with severe hyperglycemia.

The Somogyi Effect

The Somogyi effect is not a complication, but an important concept to understand. The Somogyi effect is often misdiagnosed as evidence of the need for more insulin when, in fact, the need is for less. Typically, a surprisingly high blood glucose level occurs after a period in which no food has been eaten (such as through the night). It should be suspected when a normal bedtime blood glucose level is followed by a high morning level. The initial impression is that the individual is receiving too little insulin. However, what has happened is that the blood glucose has dropped to levels low enough to stimulate a profound episode of hypoglycemia. The body resorts to processes designed to raise the blood sugar: the release of epinephrine and glucagon. It is important to recognize the precipitating factor of hypoglycemia in this case and to reduce the insulin accordingly.

The Somogyi effect would be demonstrated by the following scenario: An individual routinely checks his blood glucose at about 9 pm every night and typically obtains a value within normal limits. He has a small snack of 15 grams of carbohydrate and 1 oz of protein, takes his prescribed dose of Lente at that time, and goes to sleep. Every morning, his fasting blood glucose is over 250 mg/dL so he thinks he should increase his bedtime Lente dose. If the Somogyi effect is working here, this could have very dangerous effects.

Before making such a change, this patient should set an alarm and check his blood glucose around 4 a.m. – when the activity of the Lente insulin typically peaks. A low blood glucose at this time would confirm that the Somogyi effect is occurring. What the patient should actually do is take less Lente insulin at bedtime, but he should do this under the guidance of his health care provider.

Since insulin glargine has no peak of insulin activity, the Somogyi effect is not associated with this type of insulin. However, it would be wise to recommend that any patient taking insulin of any kind occasionally obtain a blood glucose in the middle of the night just to get a sense of how well covered she/he is during this time.

Diabetic Ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is a complication which usually develops over a relatively longer period of time than the acute complications. However, DKA can begin to develop within hours of pump failure in the individual whose insulin needs are met by an insulin pump since the pump uses only rapid, short-acting insulin.

The pathophysiology of uncontrolled/undiagnosed diabetes explains this phenomenon. A diabetic in ketoacidosis may be an undiagnosed diabetic, or might be one that is known, but is not under control. Accidental or willful omission of insulin is a common cause in the diagnosed diabetic, as is mistakenly taking too little insulin. Diabetics who are very poor and/or uneducated may simply stop taking their usual dose of insulin in an effort to cut costs.

Overwhelming infections, surgery, pregnancy, trauma, and puberty which increase the metabolic needs of the body result in an increased need for insulin. Last, insulin resistance due to antibody development leads to the need for higher doses of insulin. If these needs are not met, ketoacidosis can result. Severe hyperglycemia along with glycosuria, ketonemia, ketonuria, dehydration and a low blood pH are part of the laboratory picture in DKA. Though most common in DMT1, ketoacidosis can occur in the individual with DMT2 who is under extreme stress (physical or emotional) which could increase metabolic needs beyond that with which her/his body could deal.

Treatment of DKA requires hospitalization for carefully monitored fluid and electrolyte replacement and insulin administration. The fluid and electrolyte imbalances can be life-threatening.