>> Understand the significant effect diabetes mellitus has on the population and EMS.
>> Learn the physiology and pathophysiology concepts underlying diabetes mellitus.
>> Recognize the acute complications associated with diabetes mellitus.
>> Identify the prehospital management of acute diabetic complications.
>> Know the basic function of the major classes of diabetic medications.
Diabetic Ketoacidosis (DKA): A condition produced by insulin deficiency, characterized by starvation-state metabolism despite hyperglycemia, resulting in acidosis, dehydration and ketone production; most common in type 1 diabetics.
Glucagon: A hormone produced by the pancreas; its primary purpose is counter-regulation of glucose levels, leading to elevation of blood glucose.
Hyperglycemic hyperosmolar nonketotic coma (HHNC): A condition produced by absolute and/or relative insulin deficiency, resulting in hyperglycemia, dehydration and hyperosmolarity without significant ketone production or acidosis; most common in type 2 diabetics.
Type 1 diabetes: A hyperglycemic condition caused by failure of pancreatic insulin production, requiring insulin administration and most frequently presenting in young patients.
Type 2 diabetes: A hyperglycemic condition caused primarily by insulin resistance, treated with oral medications and/or insulin and more often presenting in older patients.
Diabetes mellitus (DM) affects many of the patients in the prehospital setting. It’s a group of diseases that share the characteristics of elevated blood glucose and altered carbohydrate and lipid metabolism, which results from absolute and/or relative insulin deficiency. DM is estimated to affect 8.3% of Americans (26.9% of those older than 65); although 27% of those affected remain undiagnosed. It’s the seventh leading cause of death in the U.S. and the leading cause of kidney failure, non-traumatic lower limb amputations and new cases of blindness among adults. It’s also a major contributor to heart disease and stroke.
Significant Healthcare Impact
Diabetic patients are admitted to the hospital four times as often, incur twice the medical costs and have twice the risk of death as that of similar-age, non-diabetic patients.1 In addition to the many long-term medical issues tied to DM, three life-threatening emergencies are frequently encountered by prehospital providers: hypoglycemia, diabetic ketoacidosis (DKA) and a hyperglycemic hyperosmolar nonketotic coma. This article discusses the etiology, presentation and management of each entity. We’ll also provide a basic overview of DM and the standard medications used in its daily treatment.
Glucose is an important metabolic fuel throughout the body and is by far the predominant fuel for the central nervous system, which lacks the ability to produce glucose or store adequate supplies. Without appropriate blood glucose supplies, neural death rapidly begins. As such, complex regulatory mechanisms exist in the body to maintain blood concentrations within a narrow window of approximately 60–150 mg/dL.
The pancreas is central to this regulatory machine, producing and releasing insulin from beta cells—primarily in response to glucose levels. However, some amino acids and certain medicines can also act as insulin release triggers. The insulin, which survives only minutes once released into the circulation, enhances glucose uptake by the liver for storage purposes and other tissues for storage and as a fuel source. It also inhibits the liver’s production and release of glucose.
Counterbalancing the effects of insulin are several other hormones, including glucagon, epinephrine, norepinephrine, growth hormone and cortisol. The latter two are slower acting agents with more relevance to long-term regulation. Glucagon is released by pancreatic alpha cells in response to numerous metabolic stressors, including a perceived fasting state. That perception may be due to actual hypoglycemia from low glucose intake or poor tissue uptake of glucose in the absence of adequate insulin. It acts to increase the production and release of glucose from the liver.2,3
Type 1 diabetes is sometimes referred to as insulin-dependent DM or juvenile-onset DM. Type 2 diabetes has been referred to as non-insulin-dependent DM or adult-onset DM. These other monikers are now discouraged because they’re inaccurate. Although all type 1 patients must use insulin, many type 2 patients are also dependent on insulin injections for their health. Similarly, although type 1 patients are usually diagnosed in childhood or early adulthood, the diagnosis of type 2 DM is being made at younger and younger ages.
Many less common forms of DM exist. One less common form is gestational DM, which occurs during pregnancy only. It’s believed to have a pathophysiology similar to type 2 DM and to affect 18% of pregnancies.4–6 Rare forms can also be caused by other pancreatic diseases, surgeries, infections and medications. Some patients are referred to as “pre-diabetic” or having impaired glucose tolerance when their glucose levels are abnormal but don’t quite qualify for a full diagnosis.
Type 1 DM represents 5% of all cases.7 It’s defined by the all-out failure of insulin production by the pancreas. For this reason, all type 1 patients require insulin therapy. In 85–90% of these patients, this state was produced by the body’s immune system destroying pancreatic beta cells.8,9 Type 2 DM accounts for at least 90% of diagnosed cases.10 It’s produced, at least initially, by insulin resistance, in which cells have an impaired ability to detect and/or appropriately react to insulin. This causes a compensatory increase in insulin production, which eventually leads to pancreatic burnout and decreased levels of insulin.
Treatment of type 2 patients may include diet and exercise, oral medications and insulin or any combination of those treatments. Factors associated with the development of type 2 DM include genetics, age, obesity, sedentary lifestyle, diet and race. There’s a significantly higher rate of disease among minorities.1
Four separate criteria can be used to diagnose DM. The three traditional tests are a fasting blood glucose concentration of greater than or equal to 126 mg/dL, a random blood glucose concentration of greater than or equal to 200 mg/dL or a two-hour oral glucose tolerance test with a concentration greater than or equal to 200 mg/dL. More recently, a test showing a glycosylated hemoglobin (HbA1c) level greater than or equal to 6.5% has been approved for many patients. This test is based on the fact that glucose in the blood binds to hemoglobin in a manner proportionate to glucose concentration. Therefore, it represents average blood glucose levels over the preceding two to three months.
Fifty-eight percent of diabetics use only oral medication; 12% use insulin only, and 14% use a combination of the two and 16% don’t use medication.1
Insulin: Only human-type insulin, produced by recombinant DNA processes, is sold in the U.S. (Bovine and porcine insulin is only available with special FDA approval.)3 Home-use insulin is concentrated such that 1 mL contains 100 units and is usually administered subcutaneously (SC) by syringe, preloaded pen or pump. Through protein modification, numerous formulations of insulin are produced with variable pharmacokinetics, primarily shorter or longer times to onset and peak effect.
Actual timing of insulin effect varies based on numerous patient factors, including site of injection, circulation and physical activity.3 Regular insulin begins acting within 15–60 minutes and continues to have an effect for six to eight hours. The names and timing of onset, peak and duration of action are the most common forms of insulin (see Table 1, p. 38).
Combination formulations also exist, consisting of mixtures of the insulin forms in Table 1. They’re usually designated with a number, such as “70/30,” indicating 70% intermediate acting insulin and 30% rapid or short-acting insulin. Anaphylactic reactions to insulin occur and should be treated as any anaphylactic reaction.
Insulin pumps: These pumps are about the size of a cellular phone or pager and can be worn in a pocket or on a belt. These devices deliver a continuous supply of SC insulin from a reservoir via a catheter and can also be used to give bolus mealtime doses. Reservoirs must be refilled and catheters changed every few days. Malfunction can lead to hyperglycemia or hypoglycemia. In the case of hyperglycemia, the patient should be treated as with other patients.
The EMS provider shouldn’t attempt to use the pump to administer treatment. In the case of hypoglycemia, the simplest and surest way to deactivate the pump is to remove the catheter from the patient’s skin. Tape the catheter to the pump to prevent damage.
Sulfonylureas: These oral medications (e.g., glipzide and glyburide) increase the pancreas’ secretion of insulin. They can produce hypoglycemia in overdose, renal insufficiency or decreased oral intake.
Metformin: This oral medication increases peripheral uptake and decreases hepatic output of glucose. It shouldn’t lead to hypoglycemia when taken alone.
Thiazolidinediones: These oral medications (e.g., pioglitazone and rosiglitazone) decrease peripheral insulin resistance. They’ve been associated with hepatotoxicity.
Alpha-glucosidase inhibitors: These oral medications (e.g., acarbose and miglitol) decrease the absorption of sugars from the gastrointestinal tract. They tend to increase flatus.
Repaglinide (Prandin): This oral medication is similar to sulfonylureas but with a slightly smaller risk of hypoglycemia.
Exanatide (Byetta) (SC) and sitagliptin (Januvia) (oral): These medications augment the glucose-dependent pancreatic response to food intake by two different mechanisms. They carry a small risk of hypoglycemia.
Pramlintide (Symlin): This SC medication decreases glucagon levels, slows gastric emptying and speeds satiety. Alone, it doesn’t cause hypoglycemia; however, it’s frequently combined with other agents, including insulin, which can increase the risk of hypoglycemic events.
Hypoglycemia: This complication is arguably the most concerning acute complication experienced by diabetics. In severe cases, with blood glucose levels below 40–50 mg/dL, altered mental status (AMS) may ensue, and the disease process can progress to seizures, coma and death from central nervous system cell injury.2 It can occur in any patient using insulin or certain oral DM medications. Although necessary, artificially supplementing the body’s drive to lower blood glucose levels with such therapies hinders the body’s counter-regulatory mechanisms described above.
Myriad ways exist for a diabetic patient to become hypoglycemic. Most commonly, the patient fails to consume an adequate meal after administration of their insulin, or they make a dosage miscalculation. However, dozens of other triggers have been implicated, including stressors, increased exercise, alcohol, liver or kidney impairment, insulin-pump malfunction, infection and such medications as propranolol, salicylates (aspirin and Pepto-Bismol) and some antimalarials and antibiotics.2
The most important sign of hypoglycemia is AMS. It may be preceded by signs of sympathetic response: diaphoresis, anxiety and tachycardia. However, the degree to which individuals express these findings is highly variable, and patients can rapidly progress to seizure and coma.
Patients may also demonstrate signs that mimic stroke or intoxication. It’s for precisely these reasons that all patients suffering from AMS, seizure or suspected stroke must have their blood glucose level checked emergently. In the absence of a glucose level, (e.g., in the case of equipment failure), it’s reasonable to initiate glucose therapy based on clinical suspicion (i.e., history consistent with hypoglycemia), because the benefit to a severely hypoglycemic patient far outweighs the potential harm to others.
Treatment is dependent on the patient’s mental status. With awake patients capable of oral intake, administering glucose in the form of tables, gels, candy, food or sugar-containing beverages (e.g., orange juice or soda) is usually adequate. It’s also important to encourage consumption of foods with complex carbohydrates and protein to assist in preventing rebound hypoglycemia.
If oral treatment isn’t safe, IV administration of dextrose containing sterile water (D50W) should be given at a dose of one to three ampules. Each 50 mL ampule of D50W contains 25 g of dextrose, approximately equal to two tablespoons of cake icing or seven ounces of soda.3 The precise effect this will have on a patient’s blood glucose level is unpredictable. D50W can be diluted with normal saline (NS) or sterile water to facilitate use in small IVs as needed.
Dextrose can be given intraosseously if necessary, but it should be preceded by lidocaine infusion when possible to limit pain. Due to the electrolyte imbalances that may accompany altered glucose levels, patients should be monitored for dysrhythmia.
The treatment regimen must be altered for pediatric patients, because D50W has the potential to damage immature veins. D25W, which can be produced by diluting D50W one to one with sterile water or NS, is preferred for patients younger than 8 years.
For infants, D10W is recommended and can be prepared by diluting D50W one to four with sterile water or NS. Pediatric doses are 0.5–1 g/kg of glucose.2 Volume of administration for children can be more easily remembered by the rule of “50.” The dosage in mL/kg multiplied by the dextrose concentration should always equal 50 (e.g, for D25W, 2 x 25 = 50, so the dosage is 2 mL/kg).
When IV access can’t be obtained quickly, intramuscular or SC glucagon may be used at a dosage of 1–2 mg for adults or 0.025–0.1 mg/kg in children. It typically begins to work after 10–20 minutes and has its peak effect at 30–60 minutes.2
Some DM patients or families are able to administer glucagon at home; history of this should be identified. The EMS provider should continue attempts to provide glucose to the patient after glucagon administration. Also be aware that because of its mechanism of action, glucagon has a limited effect on some forms of hypoglycemia, particularly alcohol-induced hypoglycemia and in children because of limited sugar stores in the liver. Finally, glucose gels or honey can actually be effectively administered rectally.3
Hypoglycemia involving the use of long-acting insulins or oral hypoglycemics, such as sulfonylureas (e.g., glyburide and glipizide) and chlorpropamide, present a significantly greater risk of rebound hypoglycemia. So these patients must have a longer period of hospital observation. There’s some evidence that other patients, in certain circumstances, can be safely definitively treated in the prehospital setting.
Several physician-based EMS agencies in Europe have had significant success with treating hypoglycemic patients who return to a normal mental status and tolerate oral intake after treatment without transport.4,5 Similar results were found in a Milwaukee study comparing transported patients to those who refused transport.6
A British study demonstrated good patient satisfaction and success with patient follow-up arranged after non-transport hypoglycemia runs.7 Many EMS agencies are now incorporating such practices into their protocols.
DKA: In the absence of insulin, the body’s cells are unable to take up adequate glucose from the blood to run necessary metabolic processes. Unable to uptake glucose, cells shift to a starvation state in which proteins are broken down to amino acids and lipids are broken down to free fatty acids and oxidized to ketones, an alternative source of energy for the brain and heart. Buildup of these substances leads to a state of acidosis, which when extreme contributes to significant metabolic derangements, collectively referred to as DKA.
Additionally, when blood glucose levels exceed the kidneys’ threshold, glucose overflows into the urine, taking with it large volumes of body water and electrolytes. Hyperosmolarity of the blood resulting from dehydration and hyperglycemia substantially contributes to AMS, as well as acidosis and ketosis.2 The multifaceted pathology leads to poor oral intake and vomiting, further exacerbating the derangements of DKA. Although DKA is possible in type 2 patients, it’s far more common in type 1 DM.
Patients may exhibit a variety of symptoms, including polyuria, polydipsia, abdominal pain (particularly common in children), weakness, visual changes, nausea and vomiting. They may demonstrate variable signs, including hyperventilation (as the body tries to clear the acidosis), tachycardia, hypotension, dry appearance, acetone breath odor and AMS. As many as 25% of DKA episodes occur in patients without previously diagnosed DM.
Although blood glucose levels will usually be above 350 mg/dL, up to 18% of DKA patients will have levels less than 300 mg/dL.2 It’s important to note that the clinical appearance of a DKA patient may be extremely similar to that of a severely hypoglycemic patient.
Additionally, alcoholic ketoacidosis can be clinically indistinguishable, but these patients often have normal or even low blood glucose levels. As such, insulin should never be given to a patient without accurate measurement of glucose level.
Emergent treatment of the DKA patient is highly dependent on the state of the patient. Unresponsive patients, especially those with vomiting and aspiration risk, require intubation. As discussed above, the DKA patient often attempts to compensate for their acidosis with hyperventilation. This hyperventilation should be maintained when the provider takes control of the airway with intubation.
Due to the electrolyte imbalances that frequently accompany hyperglycemia, patients should be monitored for dysrhythmia. Some consideration should be given to the instigating factor. It could be as simple as the patient running out of insulin or a small cellulitis, or it could be life threatening, such as sepsis, a GI bleed or myocardial infarction (MI). Management of each possible trigger of DKA is beyond the scope of this article, but it’s vital not to miss another primary disease process because the patient has been labeled a DKA patient.
An adult patient can have a water deficit of greater than 5 L.2 Evidence of shock should be treated as in any other patient in the prehospital setting, with fluids, ideally NS. Fluid boluses (20 mL/kg each for children) should be infused until a systolic blood pressure of at least 80–90 mmHg is maintained. In the dehydrated patient without shock, NS should be used more judiciously, typically 1 L (20 mL/kg in children) over the first hour, with careful monitoring for signs of pulmonary edema or worsened mental status.
Appropriate use of fluids alone can produce a substantial improvement in hyperglycemia and acidosis. Overly aggressive fluid administration should be avoided because of the risk of cerebral edema, particularly in children. Bicarbonate shouldn’t be administered in the prehospital setting unless indicated for another disease process.
Hyperglycemic hyperosmolar nonketotic coma (HHNC): Insulin deficiency, either actual or relative due to insulin resistance, leads to hyperglycemia, hyperosmolarity and dehydration in much the same manner as DKA. Unlike DKA, however, ketosis and acidosis are usually absent. The reason for this is uncertain but may be due to the blockade of ketone production by the small amount of insulin secretion maintained by these patients.
HHNC is more commonly seen in type 2 DM. Some consider HHNC and DKA to be ends of a single spectrum of disease. Clinical features are similar to those of DKA but usually have a more prolonged onset, sometimes even building over months. Blood glucose levels are typically higher (usually greater than 600 mg/dL), and fluid deficit is usually greater in HHNC patients, averaging 9 L in adults.2,3 Prehospital management and complications of HHNC are essentially the same as those for DKA.
It’s important to be mindful of the potential effects diabetes can have on the presentation of other diseases. Diabetic patients are at a significantly increased risk of cardiac, cerebrovascular and thromboembolic disease. Additionally, the disparity in age at onset of cardiac disease between males and females seems to be overcome by DM, with diabetic females suffering coronary events earlier than their non-diabetic counterparts.3
Unfortunately, DM can mask the presentation of acute coronary syndrome. Sometimes referred to as the “silent MI,” the diabetic presentation of cardiac ischemia often lacks the characteristic crushing substernal pain common in other patients and can be much less specific with fatigue, sweating, shortness of breath or worsened glucose control.8,9
Because of their impaired immune function, infectious pathology is significantly more concerning in DM patients; a cellulitis that might be treated with outpatient antibiotics in other patients often warrants hospitalization in diabetics.
Threatened by the combination of impaired sensation, impaired blood flow and poor immune response, diabetic patients’ feet are prone to limb amputation and even life-threatening ulcers that frequently progress to amputation. Underlying occult bone infection is also common. Such ulcers require early medical intervention.
DM is a complex and widespread disease. It affects nearly every aspect of a patient’s life. The prehospital provider must keep this in mind when evaluating a diabetic patient with a seemingly non-diabetic complaint. When managing specific diabetic emergencies, providers must remember the fundamental concepts: The brain and heart need glucose, and disordered glucose metabolism frequently leads to significant dehydration.
Providing glucose to a hyperglycemic patient will do little or no harm, while failing to do so for a hypoglycemic patient can be detrimental. When you are presented with a patient with AMS, always consider hypoglycemia. JEMS
1. Centers for Disease Control and Prevention. (Sept. 19, 2011). 2011 National Diabetes Factsheet. In Centers for Disease Control and Prevention. Retrieved from www.cdc.gov/diabetes/pubs/factsheet11.htm.
2. Marx J, Hockberger R & Walls R. Rosen’s Emergency Medicine: Concepts & Clinical Practice, 7th Edition. Elsevier: St. Louis. 2009.
3. Tintinalli J, Stapczynski J, John Ma O, et al. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th Edition. McGraw-Hill. 2010.
4. Holstein A, Plaschke A, Vogel MY, et al. Prehospital management of diabetic emergencies—a population-based intervention study. Acta Anaesthesiol Scand. 2003;47(5):610–615.
5. Anderson S, Hogskilde PD, Wetterslev J, et al. Appropriateness of leaving emergency medical service treated hypoglycemic patients at home: A retrospective study. Acta Anaesthesiol Scand. 2002;46(4):464–468.
6. Socransky SJ, Pirrallo RG, Rubin JM. Out-of-hospital treatment of hypoglycemia: Refusal of transport and patient outcome. Acad Emerg Med. 1998;5(11):1080–1085.
7. Walker A, James C, Bannister M, et al. Evaluation of a diabetes referral pathway for the management of hypoglycemia following emergency contact with the ambulance service to a diabetes specialist nurse team. Emerg Med J. 2006;23(6):449–451.
8. Canto JG, Shlipak MG, Rogers WJ, et al. Prevalence, clinical characteristics, and mortality among patients with myocardial infarction presenting without chest pain. JAMA. 2000;283(24):3223–3229.
9. American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20(7):1183–1197.
10. Tarascon. Tarascon Pocket Pharmacopoeia, 22nd Edition. Jones and Bartlett. 2008.
This article originally appeared in November 2011 JEMS as “Distinguishing Diabetes: Differentiate between type 1 & type 2 DM.”