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SECTION Type 1 Diabetes Mellitus Nikhil Goyal Adam Schlichting INTRODUCTION AND EPIDEMIOLOGY Diabetes can be classified into type 1 diabetes (T1DM), type 2 diabetes (T2DM), gestational diabetes, and other specific types of diabetes based on the etiology (Table 223-1); however, many people with diabetes do not easily fit into a single class. 1 About 5% of people with diabetes are estimated to have T1DM, which is about 1.25 million American children and adults. 2,3 PATHOPHYSIOLOGY T1DM is characterized by an autoimmune, cellular-mediated destruc tion of β cells of the pancreas. These patients usually have almost no circulating insulin. 1 It is mostly diagnosed in children and young adults, but it can also develop in adults. 4 Spontaneous ketoacidosis almost always develops in untreated cases, and insulin is required for survival. Chapter 224, “Type 2 Diabetes Mellitus, ” discusses T2DM in detail. Hyperglycemia is present in all types of diabetes mellitus and is the main factor responsible for chronic complications. Therefore, maintaining euglycemic control is the cornerstone of management. DIAGNOSIS The American Diabetes Association criteria for diagnosis are listed in Table 223-2. 1 Any one of these can be used to make the diagnosis. Patients with a fasting plasma glucose of 100 to 125 milligrams/dL (5.6 to 7.0 mmol/L), a hemoglobin A1C of 5.7% to 6.4%, or a 2-hour plasma glucose of 140 to 199 milligrams/dL (7.8 to 11.0 mmol/L) as part of an oral glucose tolerance test are classified as having prediabetes. 4 This should be viewed as an increased risk for diabetes and cardiovascular disease rather than a clinical diagnosis. Glycated hemoglobin (hemoglobin A1C) represents the average blood glucose level over a 2- to 3-month period. 1 It is an indirect measure, and age, race/ethnicity, pregnancy, hemoglobinopathies, and recent transfusions may impact interpretation. In the ED, it is common to encounter isolated elevations of blood glucose with no established relationship to a meal. If patients have classic symptoms of hyperglycemia (polydipsia, polyuria) or are in hyperglycemic crisis, they may indeed be diagnosed with diabetes. TREATMENT T1DM is characterized by an absolute insulin deficiency, so some form of insulin is required for survival. Select patients with T1DM may also be treated with additional prandial injections of pramlintide, a synthetic form of the β-cell–produced hormone amylin. 5 Patients with T1DM may also benefit from β-cell transplantation or pancreas transplantation. Other noninsulin agents are useful in T2DM and are discussed sepa rately in Chapter 224. INSULIN As of 2006, all U.S. Food and Drug Administration–approved insulin preparations are recombinant human insulin or an analog. 6 These insulins are highly pure and stable, and vials in use can be kept up to 28 days at room temperature. 7 The most common concentration of insulin is 100 units/mL (“U100”), but other concentrations including 200 units/ mL (“U200”), 300 units/mL (“U300”), and 500 units/mL (“U500”) are available, allowing a smaller volume to be injected. Although unmodi fied “regular” insulin was the first type of human-derived insulin used, many new insulin analogues have now become available ( Table 223-3, Figure 223-1).

trations including 200 units/ mL (“U200”), 300 units/mL (“U300”), and 500 units/mL (“U500”) are available, allowing a smaller volume to be injected. Although unmodi fied “regular” insulin was the first type of human-derived insulin used, many new insulin analogues have now become available ( Table 223-3, Figure 223-1). 8,9 Regardless of the insulin analog, 1 unit of insulin can be substituted for a longer- or shorter-acting analog, as long as the total daily dose is equivalent (e.g., neutral protamine Hagedorn [NPH] 20 units twice daily can be converted to glargine 40 units daily). 7 There can be considerable variability in the onset and duration of action depending on the dose (e.g., regular insulin has a longer duration of action with larger doses), site of injection, degree of exercise, and presence of circulating anti-insulin antibodies. A physiologic regimen of insulin generally starts with half of the daily requirement given as basal insulin (once-daily long-acting or twice-daily intermediate-acting insulin) and prandial doses of rapid-acting insulin administered 5 to 30 minutes before each meal ( Figure 223-2). 8 Most patients with T1DM require a total daily dose of insulin between 0.4 and 1 unit/kg/d, with approximately half given as basal insulin such as insulin glargine and half to be given in divided doses preprandially. 10,11 This can provide a rough idea when a patient says, “I have no idea how much insulin I take. ” Prandial dosing is most often based on the anticipated amount of carbohydrate about to be consumed, for example, 1 unit of insulin for each 15 grams of carbohydrate; this is known as “carb counting. ” Prandial dosing must also take into consideration the premeal measured glucose level. In this case, the patient adds an additional amount of insulin to correct for premeal hyperglycemia or reduces the prandial dose to account for premeal hypoglycemia. Some patients may be on a simpli fied, fixed amount of insulin for each meal. Insulin can be given as intermittent subcutaneous dosing, IV infusion, inhalation, or continuous subcutaneous infusion using an insulin pump. Intramuscular injection of insulin is not approved by the U.S. Food and Drug Administration. Intermittent insulin doses are given subcutane ously with a syringe or pen. The syringe method is the least expensive but requires care and precision to give the correct dose. Pens provide more accurate dosing, and many patients consider these to be more convenient. Subcutaneous injection is the most common method of insulin administration. Absorption varies due to regional circulatory differences, and frequent use of a single site may lead to fibrosis or lipodystrophy. Patients are instructed to limit injections to one region of the body but rotate sites within that region. IV administration of regular insulin results in an onset of action within 10 to 15 minutes and rapid reductions in plasma glucose, and is the recommended method of administration in hyperglycemic crises—diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state. See Chapters 225 and 227 for management of these conditions. CHAPTER Endocrine Disorders Tintinalli_Sec17_p1419-1460.indd 1419 8/2/19 12:23 PM

apid reductions in plasma glucose, and is the recommended method of administration in hyperglycemic crises—diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic state. See Chapters 225 and 227 for management of these conditions. CHAPTER Endocrine Disorders Tintinalli_Sec17_p1419-1460.indd 1419 8/2/19 12:23 PM 1420 SECTION 17: Endocrine Disorders  INHALED INSULIN In 2006, inhaled insulin was marketed in the United States but was discontinued by the manufacturer. The U.S. Food and Drug Administration approved a new formulation of inhaled regular insulin in 2014 for prandial use in adults without pulmonary disease. 12 This recombinant regular Technosphere insulin (Afrezza®) may be noninferior to injected prandial insulin combined with long-acting insulin injections, but there are minimal long-term data available. GLYCEMIC COMPLICATIONS IN INSULIN- DEPENDENT PATIENTS The major hyperglycemic emergencies, hyperosmolar hyperglycemic state and diabetic ketoacidosis, are discussed in Chapter 227, “Hyperosmolar Hyperglycemic State, ” and Chapter 225, “Diabetic Ketoacidosis, ” respectively. Here we discuss the common ED presentation of an “abnormal lab value” (i.e., patients with no acute symptoms of hyperglycemia found to have elevated plasma glucose levels).  HYPERGLYCEMIA IN PREVIOUSLY DIAGNOSED T1DM For patients with T1DM with hyperglycemia noted on multiple ED visits, refer to the primary physician for insulin dose adjustment. In the interim, ask patients to keep a daily record of every meal, every dose of insulin administered (along with type of insulin), and blood glucose levels four times a day (after rising in the morning, before lunch, before dinner, and at bedtime). If an insulin dose adjustment is made in the ED, the basic regimen should conform to a once- or twice-daily dose of long- or intermediateacting insulin, combined with prandial doses of rapid-acting insulin. The magnitude of increase in the basal insulin dose should be carefully tailored to the degree of hyperglycemia in the patient and duration of time since the last meal, but typically should change by no more than 10%. For example, if a patient has a measured glucose of 300 milligrams/ dL (16.6 mmol/L) 1 hour after consuming a meal, increasing longacting insulin may result in late hypoglycemia as the measured glucose is more attributable to recent carbohydrate ingestion; this episode of hyperglycemia may be better managed by recommending an increase in preprandial insulin dosing. A conservative supplemental dose of rapid-acting insulin may be calculated as follows: 1 unit per 50 milligrams/dL (2.8 mmol/L) above target glucose level for T1DM, and 1 unit per 30 milligrams/dL (1.7 mmol/L) above target glucose level for T2DM. For example, to achieve a goal blood glucose of 100 milligrams/dL (5.5 mmol/L) in a patient with T1DM who has a glucose level of 350 milligrams/dL (19.5 mmol/L), administer 5 units of rapid-acting insulin. Anticipated carbohydrate consumption would require addi tional insulin. If the patient is using neutral protamine Hagedorn (NPH or isophane) insulin, inspect the insulin vial; if frosting is noted on the sides of the bottle, this may indicate denaturation, which renders the insulin ineffective. Provide the patient with a new prescription, and discard the old vial. Falsely Elevated Capillary Glucose Several substances can falsely elevate point-of-care and home blood glucose monitoring accuracy, including acetaminophen, ascorbic acid, and peritoneal dialysis solu tions using icodextrin. 14-17 Falsely elevated point-of-care glucose reading and reflexive insulin administration have been responsible for several reports of severe hypoglycemia.

lsely elevate point-of-care and home blood glucose monitoring accuracy, including acetaminophen, ascorbic acid, and peritoneal dialysis solu tions using icodextrin. 14-17 Falsely elevated point-of-care glucose reading and reflexive insulin administration have been responsible for several reports of severe hypoglycemia. Point-of-care test strips for both home and hospital use are also sensitive to temperature and humidity and thus may provide inaccurate glucose levels. If the point-of-care glucose level does not fit the clinical presentation or if the patient receives perito neal dialysis, obtain a laboratory plasma glucose level for treatment decisions.  HYPOGLYCEMIA IN INSULIN-DEPENDENT PATIENTS Hypoglycemia (plasma glucose <70 milligrams/dL [<3.9 mmol/L]) is the major adverse effect of tight glycemic control. Apart from insulin administration, patients with T1DM are prone to hypoglycemia because the surge of glucagon is absent and epinephrine secretion may be blunted due to neuropathy, age, or autonomic dysfunction from prior hypoglycemic episodes. Older insulin regimens used once- or twice-daily injections of NPH, Lente insulin, or premixed combinations (70/30, 75/25, or 50/50) of basal insulin and regular insulin as the prandial dose. These sched ules mandated fixed meal times and activity schedules, so it was not unusual to develop hypoglycemia with missed meals or unusual stress. Modern physiologic regimens of insulin administration (once-daily long-acting insulin with short-acting doses immediately before meals) have significantly reduced the incidence of hypoglycemia. 11 However, many patients remain on premixed dosing due to familiarity or financial limitations. Determine the cause of hypoglycemia. Common causes include inadequate intake of food, inaccurate administration of insulin, infection, renal failure, acute coronary syndrome, and unusual physi cal or mental stress. Identify the timing and administration of insulin in relation to meals. Ask if the patient is measuring blood glucose TABLE 223-2 American Diabetes Association Criteria for the Diagnosis of Diabetes A1C ≥6.5% * The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. Fasting plasma glucose ≥126 milligrams/dL (7.0 mmol/L) * Fasting is defined as no caloric intake for at least 8 h. Casual plasma glucose ≥200 milligrams/dL (11.1 mmol/L) and symptoms of hyperglycemia or hyperglycemic crisis Classic symptoms of hyperglycemia include polyuria and polydipsia. 2-h plasma glucose ≥200 milligrams/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT) * OGTT must be performed as described by the World Health Organization. Abbreviations: A1C = glycated hemoglobin; DCCT = Diabetes Control and Complications Trial; NGSP = National Glycohemoglobin Standardization Project. *Should be confirmed by repeat testing unless unequivocal hyperglycemia is present.

ance test (OGTT) * OGTT must be performed as described by the World Health Organization. Abbreviations: A1C = glycated hemoglobin; DCCT = Diabetes Control and Complications Trial; NGSP = National Glycohemoglobin Standardization Project. *Should be confirmed by repeat testing unless unequivocal hyperglycemia is present. TABLE 223-1 Etiologic Classification of Diabetes Mellitus Type 1 diabetes (β-cell destruction, usually leading to absolute insulin deficiency) •  Immune  mediated •  Idiopathic Type 2 diabetes (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance) Other specific types, such as •  Genetic  defects of β-cell function •  Genetic  defects in insulin action •  Diseases  of the exocrine pancreas (pancreatitis, trauma, cystic fibrosis, etc.) •   Endocrinopathies (Cushing’s syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, glucagonoma, etc.) •   Drug- or chemical-induced  (interferon-α,  β-adrenergic  agonists,  diazoxide,  phenytoin,  glucocorticoids,  nicotinic  acid, pentamidine,  thiazides,  thyroid  hormone, pyrinuron,  etc.) •  Infections  (congenital rubella, cytomegalovirus, etc.) •   Uncommon forms of immune-mediated diabetes (anti-insulin receptor antibodies in conditions like lupus, etc.) •   Other genetic syndromes sometimes associated with diabetes (Down’s syndrome, Klinefelter’s syndrome, Turner’s syndrome, etc.) Gestational diabetes mellitus Tintinalli_Sec17_p1419-1460.indd 1420 8/2/19 12:23 PM

common forms of immune-mediated diabetes (anti-insulin receptor antibodies in conditions like lupus, etc.) •   Other genetic syndromes sometimes associated with diabetes (Down’s syndrome, Klinefelter’s syndrome, Turner’s syndrome, etc.) Gestational diabetes mellitus Tintinalli_Sec17_p1419-1460.indd 1420 8/2/19 12:23 PM CHAPTER 223: Type 1 Diabetes Mellitus 1421 TABLE 223-3 Commonly Used Insulin Preparations, Their Pharmacokinetics and Unique Features * Category of Insulin or Analogue Name Pharmacokinetics Unique PropertiesOnset (hours) Peak (hours) End (hours) Rapid acting Insulin lispro (Humalog®) 0.1–0.25 1.0–1.5 4 Fixed duration of action, regardless of dose Insulin aspart (NovoLog®) 0.1–0.25 1–2 4–6 More stable than other rapid-acting insulins Insulin glulisine (Apidra®) 0.1–0.25 1.0–1.5 3–4 Antiapoptotic; may counteract β-cell destruction Regular insulin Technosphere® (Afrezza®) 0.1–0.25 0.9 2.5–3 Inhaled insulin; contraindicated in chronic lung disease Short acting Regular insulin (Humulin R®, Novolin R®) 0.25–1.0 2–4 6–8 — Intermediate acting NPH (Humulin N®, Novolin N®) 2–4 6–7 10–20 Inexpensive Insulin detemir (Levemir®) 1–3 3–9 6–24 Action is relatively constant with gentle peak Long acting Insulin glargine (Lantus®, Toujeo®) 1.5 No peak 24+ Cannot be mixed with other insulins in same syringe Insulin degludec (Tresiba®) 2 No peak >42 Allows variation in time of injection from day to day Mixtures 70/30 Humulin®/Novolin® (70% NPH, 30% regular) 0.5–1.0 3–12 10–20 — 75/25 Humalog® (75% NPL, 25% lispro) 0.2–0.5 1–4 10–20 — 50/50 Humalog® (50% NPL, 50% lispro) 0.2–0.5 1–4 10–20 — 70/30 NovoLog Mix® (70% protamine aspart, 30% aspart) 0.2–0.5 1–4 10–20 — 70/30 Ryzodeg® (70% degludec, 30% aspart) 0.1–0.25 2–3 >24 — Note: All brand names are copyrighted by their respective owners. Abbreviations: NPH = neutral protamine Hagedorn (also called isophane insulin); NPL = neutral protamine lispro. *Ultralente, Lente, and 50/50 insulin formulations are no longer available in the United States. Insulin lispro (Humalog®) Insulin aspart (NovoLog®) Insulin glulisine (Apidra®) Regular insulin Technosphere® (Afrezza®) Note: All brand names are copyrighted by their respective owners. Abbreviations: NPH = neutral protamine Hagedorn (also called isophane insulin); NPL = neutral protamine lispro. *Ultralente, Lente and 50/50 insulin formulations are no longer available in the United States. NPH (Humulin N®, Novolin N®) Insulin detemir (Levemir®) Insulin glargine (Lantus®, Toujeo®) Insulin degludec (Tresiba®) 05 10 15 20 25 50 Regular insulin (Humulin R®, Novolin R®) 70/30 Humulin®/Novolin® (70% NPH, 30% regular) 75/25 Humalog® (75% NPL, 25% lispro) 50/50 Humalog® (50% NPL, 50% lispro) 70/30 NovoLog Mix® (70% protamine aspart, 30% aspart) 70/30 Ryzodeg® (70% degludec, 30% aspart) Rapid acting Intermediate acting Long actingMixtures Short acting Category of Insulin or Analogue Onset Peak End FIGURE 223-1. Insulins: onset, peak, and duration of action. NPH = neutral protamine Hagedorn; NPL = neutral protamine lispro. Tintinalli_Sec17_p1419-1460.indd 1421 8/2/19 12:23 PM

(70% degludec, 30% aspart) Rapid acting Intermediate acting Long actingMixtures Short acting Category of Insulin or Analogue Onset Peak End FIGURE 223-1. Insulins: onset, peak, and duration of action. NPH = neutral protamine Hagedorn; NPL = neutral protamine lispro. Tintinalli_Sec17_p1419-1460.indd 1421 8/2/19 12:23 PM 1422 SECTION 17: Endocrine Disorders at home; at a minimum, it should be checked daily before breakfast and recorded in a diary. There is great variation in the pattern of hypoglycemic signs and symptoms from patient to patient; however, individual patients tend to experience the same pattern from epi sode to episode. Common neuroglycopenic symptoms may include headache, irritability, drowsiness, confusion, dizziness, tiredness, inability to concentrate, and difficulty speaking. These symptoms may mimic an acute ischemic stroke. Adrenergic symptoms such as tremor, sweating, anxiety, nausea, palpitations, feelings of warmth, and shiver ing are also seen, as are other symptoms such as hunger, weakness, and blurred vision. Hypoglycemic unawareness or hypoglycemia-associated auto nomic failure occurs when diabetic patients have deficient counter regulatory hormone excretion, resulting in a lack of symptoms of hypoglycemia. 19 This results in frequent episodes of hypoglycemia and profound hypoglycemia. β-Blocker medication may also contribute to this condition by masking typical adrenergic symptoms of hypoglycemia. Treatment of Hypoglycemia Glucose is the preferred treatment, although any glucose-containing carbohydrate may be used. The initial dose is 15 to 20 grams of glucose (PO, IV , or IO), which can be repeated if hypoglycemia persists after 15 minutes. Sublingual glucose (40% dextrose gel preferred; teaspoon of sugar may suffice) may also be effective in resource-limited situations. 20-22 Pure fructose does not cross the blood–brain barrier and does not significantly improve blood glucose levels. Most sweet foods or drinks contain both glucose and fructose; they are labeled as contain ing “sugars, ” which includes glucose, fructose, or sucrose. Protein has a negligible contribution to serum glucose, so foods such as peanut butter or cheese are not recommended for hypoglycemia treatment. Once hypoglycemia has resolved, have the patient eat a meal or carbo hydrate snack. Table 223-4 lists the sugar content of commonly used oral agents. Glucagon emergency kits are available for caregivers of patients with T1DM for emergency situations. One milligram of intramuscular glucagon stimulates glycogenolysis and is effective in 10 to 15 minutes. Preliminary data show that intranasal glucagon may also be effective. Once the patient is alert enough to swallow, give oral glucose imme diately. Glucagon is not effective in glycogen-depleted patients, and glucagon may induce nausea and vomiting, which can make it difficult to consume oral glucose subsequently. Insulin Overdose Short-acting insulin may have delayed and pro longed absorption; patients with a significant accidental or inten tional overdose should be monitored for several hours. Patients with a significant overdose of a long-acting insulin should be admitted for monitoring of glucose levels. Most patients may be discharged if caregivers and family members can monitor symptoms and capillary glucose levels. INSULIN PUMPS (CONTINUOUS SC INSULIN INFUSION) The use of an insulin pump (continuous SC insulin infusion) (See Video: The Insulin Pump) is common, but prevalence of pump use varies from 14% to 70% depending on demographics and country. 24-29 An insulin pump is a small device (about the size of a pager) that delivers rapidacting insulin at a basal rate and boluses of insulin for prandial and hyperglycemia correction.

usion) (See Video: The Insulin Pump) is common, but prevalence of pump use varies from 14% to 70% depending on demographics and country. 24-29 An insulin pump is a small device (about the size of a pager) that delivers rapidacting insulin at a basal rate and boluses of insulin for prandial and hyperglycemia correction. Once programmed, the pump can automatically calculate dosing for a certain amount of carbohydrates about to be consumed and correct for premeal hyperglycemia or hypoglycemia. The insulin is pumped through a flexible tube and infused via a subcutane ous catheter. The pump is usually attached to the patient’s waistband. The patient must refill the insulin reservoir and change the catheter every 2 to 3 days. Table 223-5 lists manufacturers of insulin pumps available in the United States. Some insulin pumps do not use tubing but directly attach to the patient with adhesive. The basal rate of insulin (generally, 0.5 to 1.5 units/h) can be varied throughout the day; for example, increased to counteract an early morning cortisol surge or decreased before exercising. Continuous insulin delivery eliminates the need for long-acting insulin injection such that the pump delivers all insulin required by the patient in the form of rapid-acting insulin. Rarely, patients requiring exceptionally high doses of insulin using an insulin pump, patients who wish to be disconnected from their pump for extended periods of time, or patients at higher risk of hyperglycemia or diabetic ketoacidosis (e.g., young children) may inject an additional once- or twice-daily long-acting insulin. 31,32 The TABLE 223-4 Sugar* Content of Agents Available at Home or Over the Counter Agent Dose/Route Sugar Content Fruit juice 1 cup PO Variable depending on type of juice and manufacturer (mostly fructose) 8 oz Mott’s® apple juice: 28 grams sugar Honey 1 Tbsp PO 17 grams sugar (glucose and fructose) Sugar-containing soda 12 oz (one can) PO (Non-diet) Pepsi®: 41 grams sugar (mostly fructose) (Non-diet) Sprite®: 38 grams sugar (mostly fructose) (Non-diet) Coca-Cola (Coke)® Original: 39 grams sugar (mostly fructose) Glucose tablets 4 tablets PO 16 grams glucose Glucose gel 1 tube PO/SL 15 grams glucose *”Sugar” may include glucose, fructose, galactose, sucrose, lactose, or maltose. 6:00 25Insulin (mU/I) 9:00 12:00 3:00 6:00 Time (hours) Breakfast Lunch Dinner 9:00 12:00 3:00 6:00 Endogenous insulin secretion Ideal basal insulin Ideal prandial insulin FIGURE 223-2. Representation of basal and prandial insulin dosing. Tintinalli_Sec17_p1419-1460.indd 1422 8/2/19 12:23 PM

crose, lactose, or maltose. 6:00 25Insulin (mU/I) 9:00 12:00 3:00 6:00 Time (hours) Breakfast Lunch Dinner 9:00 12:00 3:00 6:00 Endogenous insulin secretion Ideal basal insulin Ideal prandial insulin FIGURE 223-2. Representation of basal and prandial insulin dosing. Tintinalli_Sec17_p1419-1460.indd 1422 8/2/19 12:23 PM CHAPTER 223: Type 1 Diabetes Mellitus 1423 pump can be manually activated to deliver a bolus for hyperglycemia and for prandial dosing. Insulin pumps are most appropriate for moti vated patients who are mechanically adept, well educated about diabetes and carbohydrate counting, and able to monitor their capillary glucose four to six times a day. Benefits of insulin pump therapy over multiple daily injections include average reduction in hemoglobin A1C of 0.5% and reduction in hypoglycemic episodes (See Video: The Insulin Pump). 24,33  INSULIN PUMP COMPLICATIONS Insulin pump delivery can fail for a variety of reasons (disconnection, empty reservoir, kinked catheter, priming errors), although modern pumps have built-in alarms to detect these conditions. 34 Because pumps use only rapid-acting insulin, onset of ketoacidosis can be very rapid after pump failure—an hour or less. If the pump is defective or needs to be removed for a procedure such as MRI , give the patient either a dose of rapid-acting insulin or long-acting insulin, especially if the insulin pump is to be interrupted for over an hour. If a patient on an insulin pump needs to be nothing by mouth (NPO), the insulin pump should not be removed and glucose levels should be checked every 30 to 60 minutes. If the patient has hypoglycemic episodes, the pump basal rate can be reduced; consultation with an endocrinologist is recommended. Patients being switched from multiple daily injections of insulin to insulin pumps are typically handled as outpatients and will require special attention if presenting to the ED during this transition period. Specific considerations for patients on insulin pumps presenting with hyperglycemia or hypoglycemia are discussed elsewhere in this chapter. Other important complications of insulin pump therapy include cellulitis at the infusion site or lipodystrophy. If patients using insulin pumps are incidentally found to have hyperglycemia or hypoglycemia, they should be allowed to treat themselves either by administering an insulin bolus through their insulin pump or by consuming carbohy drates, respectively. 19,28,35 Their endocrinologist should have provided them instructions on how to address this.  CONTINUOUS INTERSTITIAL GLUCOSE MONITORING VERSUS POINT-OF-CARE (CAPILLARY) OR SERUM GLUCOSE MONITORING Continuous glucose monitoring devices measure interstitial glucose concentrations with a subcutaneous sensor and then transmit glucose values to an insulin pump or other display device. Intersti tial glucose values are adjuncts to capillary glucose monitoring and typically require manipulation of the insulin pump to administer insulin. An even newer technology, the hybrid closed-loop system, was approved by the U.S. Food and Drug Administration in 2016. The hybrid closed-loop system adjusts insulin dosing based on continuous glucose monitoring data. The system can maintain the target glucose for a longer period, reduce episodes of hyper- or hypoglycemia, and reduce hemoglobin A1C levels. 36,37 Despite the substantial benefits of monitoring continuous interstitial glucose levels, it must be noted that interstitial glucose is a proxy, but not identical to, the more traditionally measured and validated serum glucose levels. There is about a 10-minute time lag for change between serum glucose and interstitial glucose levels. 38 Several common medications may result in inaccurate continuous interstitial glucose sensor readings, notably including acetaminophen.

identical to, the more traditionally measured and validated serum glucose levels. There is about a 10-minute time lag for change between serum glucose and interstitial glucose levels. 38 Several common medications may result in inaccurate continuous interstitial glucose sensor readings, notably including acetaminophen. 39 Measure capillary or serum glucose levels in the ED, and do not use interstitial glucose values (i.e., those displayed on the patient’s continuous glucose monitor) for diagnostic purposes.  HYPERGLYCEMIA IN PATIENTS USING INSULIN PUMPS There are no widely accepted published guidelines for the ED management of patients with insulin pumps who present to the ED with hyperglycemia. Extrapolating from inpatient recommendations, we recommend that patients using insulin pumps who present to the ED with either hyperglycemia or hypoglycemia should be treated the same as patients who are on multiple daily doses of insulin, and the insulin pump should not be disabled. 19,28 Once the patient has been stabilized, ask about dietary indiscretions and search for infections. Ask specific questions about the insulin pump: When was the insulin reservoir filled? When was the infusion set last changed? Is the insertion site of the infusion set periodically changed? When was the insulin reservoir last changed? Has the pump been sub merged in water? Have any device alarms been sounding? 40 Examine the device thoroughly to ensure the pump is on, the reservoir is not empty, no alarms are indicated, the tubing is not kinked, and the infusion site is well attached to the skin. The patient or caregiver may provide useful information on pump operation, diagnostics, and how to disconnect it if necessary. All pumps have a telephone number for 24-hour technical support from the manufacturer (Table 223-5). If there is suspicion for pump malfunction, consult endocrinology for consideration of replacement of the insulin pump with long-acting basal insulin.  DIABETIC KETOACIDOSIS IN PATIENTS USING INSULIN PUMPS In the case of diabetic ketoacidosis in a patient using an insulin pump, assume a problem with the pump, disconnect the pump, and start an IV insulin infusion following protocols for management of diabetic ketoacidosis. We recommend against bolus IV insulin prior to initiation of an insulin drip because this provides no clinical benefit. 41 Consider SC administration of long-acting insulin at the initiation of an insulin drip, particularly if re-initiation of insulin pump therapy is not expected after resolution of the diabetic ketoacidosis. 42 If the patient remains in the ED and their ketoacidosis resolves, ensure that a dose of long-acting insulin is administered at least 1 hour before stopping the insulin drip unless the insulin pump is to be re-initiated—in that case, restart pump therapy approximately 1 hour before stopping the IV insulin drip. To re-initiate pump therapy, make sure that the pump is working appro priately by running diagnostics on the device, checking that the insulin reservoir is filled with fresh insulin, and placing a new SC insulin infu sion catheter. Check serum glucose levels every 30 to 60 minutes. See Chapter 225 for further discussion of transition of insulin dosing in diabetic ketoacidosis.  HYPOGLYCEMIA IN PATIENTS USING INSULIN PUMPS Treat hypoglycemia just as in other patients. Do not discontinue the pump, as diabetic ketoacidosis can rapidly develop. If recurrent hypoglycemia develops after initial treatment, pump malfunction may be the cause. Please see the earlier section “Hyperglycemia in Patients Using Insulin Pumps. ” SPECIAL CONSIDERATIONS  UNDIAGNOSED DIABETIC A long asymptomatic period is common for T2DM, but T1DM typically has a short period before the disease becomes overt.

cemia develops after initial treatment, pump malfunction may be the cause. Please see the earlier section “Hyperglycemia in Patients Using Insulin Pumps. ” SPECIAL CONSIDERATIONS  UNDIAGNOSED DIABETIC A long asymptomatic period is common for T2DM, but T1DM typically has a short period before the disease becomes overt. If the patient is newly identified with severe and symptomatic hyperglycemia (>250 to 300  milligrams/dL [13.8 to 16.7 mmol/L]), insulin should be TABLE 223-5 Manufacturers of Insulin Pumps Available in the United States with Their 24-Hour Phone Numbers Manufacturer Website Telephone Number Animas* http://www.animas.com (877) 937-7867 Insulet OmniPod http://www.myomnipod.com (800) 591-3455 Medtronic MiniMed http://www.medtronicdiabetes.com (800) 646-4633 Roche Accu-Chek https://www.accu-chek.com/support/ insulin-pumps (800) 688-4578 Sooil DANA http://www.sooil.com (866) 747-6645 ext. Tandem Diabetes https://www.tandemdiabetes.com (877) 801-6901 *Animas insulin pump is no longer manufactured but is still in use. Telephone number is still active. Tintinalli_Sec17_p1419-1460.indd 1423 8/2/19 12:23 PM