Tintinallis Emergency Medicine A Comprehensive Study Guide 9e

Chapter 223 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 andother specific types of diabetes based on the etiology (Table 223-1) however many people with diabetes do

not easily fit into a single class1 About 5 of people with diabetes are estimated to have T1DM which is

about 125 million American children and adults23

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 (Cushingrsquos 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 (Downrsquos syndrome Klinefelterrsquos syndrome

Turnerrsquos syndrome etc)

Gestational diabetes mellitus

PATHOPHYSIOLOGY

T1DM is characterized by an autoimmune cellular-mediated destruction of β cells of the pancreas These

patients usually have almost no circulating insulin1 It is mostly diagnosed in children and young adults but

it can also develop in adults4 Spontaneous ketoacidosis almost always develops in untreated cases andinsulin is required for survival

Chapter 224 ldquoType 2 Diabetes Mellitusrdquo discusses T2DM in detail Hyperglycemia is present in all types ofdiabetes mellitus and is the main factor responsible for chronic complications Therefore maintainingeuglycemic control is the cornerstone of management

DIAGNOSIS

The American Diabetes Association criteria for diagnosis are listed in Table 223-21 Any one of these can beused to make the diagnosis Patients with a fasting plasma glucose of 100 to 125 milligramsdL (56 to 70mmolL) a hemoglobin A1C of 57 to 64 or a 2-hour plasma glucose of 140 to 199 milligramsdL (78 to

110 mmolL) as part of an oral glucose tolerance test are classified as having prediabetes4 This should beviewed as an increased risk for diabetes and cardiovascular disease rather than a clinical diagnosis

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 223-2

American Diabetes Association Criteria for the Diagnosis of Diabetes

A1C ge65 The test should be performed in a laboratory using a

method that is NGSP certified and standardized to the

DCCT assay

Or

Fasting plasma glucose ge126 milligramsdL (70

mmolL)

Fasting is defined as no caloric intake for at least 8 h

Or

Casual plasma glucose ge200 milligramsdL (111

mmolL) and symptoms of hyperglycemia or

hyperglycemic crisis

Classic symptoms of hyperglycemia include polyuria

and polydipsia

Or

2-h plasma glucose ge200 milligramsdL (111

mmolL) during an oral glucose tolerance test

(OGTT)

OGTT must be performed as described by the World

Health Organization

Glycated hemoglobin (hemoglobin A1C) represents the average blood glucose level over a 2- to 3-month

period1 It is an indirect measure and age raceethnicity pregnancy hemoglobinopathies and recent

transfusions may impact interpretation4

In the ED it is common to encounter isolated elevations of blood glucose with no established relationship toa meal If patients have classic symptoms of hyperglycemia (polydipsia polyuria) or are in hyperglycemiccrisis they may indeed be diagnosed with diabetes

TREATMENT

T1DM is characterized by an absolute insulin deficiency so some form of insulin is required for survivalSelect patients with T1DM may also be treated with additional prandial injections of pramlintide a synthetic

form of the β-cellndashproduced hormone amylin5 Patients with T1DM may also benefit from β-celltransplantation or pancreas transplantation Other noninsulin agents are useful in T2DM and are discussedseparately in Chapter 224

INSULIN

As of 2006 all US Food and Drug Administrationndashapproved insulin preparations are recombinant human

insulin or an analog6 These insulins are highly pure and stable and vials in use can be kept up to 28 days at

room temperature7 The most common concentration of insulin is 100 unitsmL (ldquoU100rdquo) but otherconcentrations including 200 unitsmL (ldquoU200rdquo) 300 unitsmL (ldquoU300rdquo) and 500 unitsmL (ldquoU500rdquo) areavailable allowing a smaller volume to be injected Although unmodified ldquoregularrdquo insulin was the first typeof human-derived insulin used many new insulin analogues have now become available (Table 223-3 Figure

223-1)89 Regardless of the insulin analog 1 unit of insulin can be substituted for a longer- or shorter-actinganalog as long as the total daily dose is equivalent (eg 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 andduration of action depending on the dose (eg regular insulin has a longer duration of action with largerdoses) site of injection degree of exercise and presence of circulating anti-insulin antibodies

FIGURE 223-1

Insulins onset peak and duration of action NPH = neutral protamine Hagedorn NPL = neutral protaminelispro

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 (Humalogreg) 01ndash

025

10ndash15 4 Fixed duration of

action regardless of

dose

Insulin aspart (NovoLogreg) 01ndash

025

1ndash2 4ndash6 More stable than other

rapid-acting insulins

Insulin glulisine (Apidrareg) 01ndash

025

10ndash15 3ndash4 Antiapoptotic may

counteract β-cell

destruction

Regular insulin

Technospherereg (Afrezzareg)

01ndash

025

09 25ndash3 Inhaled insulin

contraindicated in

chronic lung disease

Short acting Regular insulin (Humulin Rreg

Novolin Rreg)

025ndash

10

2ndash4 6ndash8 mdash

Intermediate

acting

NPH (Humulin Nreg Novolin

Nreg)

2ndash4 6ndash7 10ndash20 Inexpensive

Insulin detemir (Levemirreg) 1ndash3 3ndash9 6ndash24 Action is relatively

constant with gentle

peak

Long acting Insulin glargine (Lantusreg

Toujeoreg)

15 No

peak

24+ Cannot be mixed with

other insulins in same

syringe

Insulin degludec (Tresibareg) 2 No

peak

gt42 Allows variation in time

of injection from day to

day

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 5050 insulin formulations are no longer available in the United States

Category of

Insulin or

Analogue

Name

Pharmacokinetics

Unique PropertiesOnset

(hours)

Peak

(hours)

End

(hours)

Mixtures 7030 HumulinregNovolinreg

(70 NPH 30 regular)

05ndash10 3ndash12 10ndash20 mdash

7525 Humalogreg (75 NPL

25 lispro)

02ndash05 1ndash4 10ndash20 mdash

5050 Humalogreg (50 NPL

50 lispro)

02ndash05 1ndash4 10ndash20 mdash

7030 NovoLog Mixreg (70

protamine aspart 30

aspart)

02ndash05 1ndash4 10ndash20 mdash

7030 Ryzodegreg (70

degludec 30 aspart)

01ndash

025

2ndash3 gt24 mdash

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 dailydose of insulin between 04 and 1 unitkgd with approximately half given as basal insulin such as insulin

glargine and half to be given in divided doses preprandially1011 This can provide a rough idea when apatient says ldquoI have no idea how much insulin I takerdquo

FIGURE 223-2

Representation of basal and prandial insulin dosing

Prandial dosing is most oen based on the anticipated amount of carbohydrate about to be consumed forexample 1 unit of insulin for each 15 grams of carbohydrate this is known as ldquocarb countingrdquo Prandialdosing must also take into consideration the premeal measured glucose level In this case the patient addsan additional amount of insulin to correct for premeal hyperglycemia or reduces the prandial dose toaccount for premeal hypoglycemia Some patients may be on a simplified fixed amount of insulin for eachmeal

Insulin can be given as intermittent subcutaneous dosing IV infusion inhalation or continuoussubcutaneous infusion using an insulin pump Intramuscular injection of insulin is not approved by the USFood and Drug Administration Intermittent insulin doses are given subcutaneously with a syringe or penThe syringe method is the least expensive but requires care and precision to give the correct dose Pensprovide more accurate dosing and many patients consider these to be more convenient Subcutaneousinjection is the most common method of insulin administration Absorption varies due to regional circulatorydierences and frequent use of a single site may lead to fibrosis or lipodystrophy Patients are instructed tolimit injections to one region of the body but rotate sites within that region IV administration of regularinsulin results in an onset of action within 10 to 15 minutes and rapid reductions in plasma glucose and isthe recommended method of administration in hyperglycemic crisesmdashdiabetic ketoacidosis andhyperglycemic hyperosmolar nonketotic state See Chapters 225 and 227 for management of theseconditions

INHALED INSULIN

In 2006 inhaled insulin was marketed in the United States but was discontinued by the manufacturer TheUS Food and Drug Administration approved a new formulation of inhaled regular insulin in 2014 for prandial

use in adults without pulmonary disease12 This recombinant regular Technosphere insulin (Afrezzareg) may benoninferior to injected prandial insulin combined with long-acting insulin injections but there are minimal

long-term data available13

GLYCEMIC COMPLICATIONS IN INSULIN-DEPENDENT PATIENTS

The major hyperglycemic emergencies hyperosmolar hyperglycemic state and diabetic ketoacidosis arediscussed in Chapter 227 ldquoHyperosmolar Hyperglycemic Staterdquo and Chapter 225 ldquoDiabetic Ketoacidosisrdquorespectively Here we discuss the common ED presentation of an ldquoabnormal lab valuerdquo (ie patients with noacute 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 forinsulin dose adjustment In the interim ask patients to keep a daily record of every meal every dose ofinsulin administered (along with type of insulin) and blood glucose levels four times a day (aer rising in themorning 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-dailydose of long- or intermediate-acting insulin combined with prandial doses of rapid-acting insulin Themagnitude of increase in the basal insulin dose should be carefully tailored to the degree of hyperglycemia inthe patient and duration of time since the last meal but typically should change by no more than 10 Forexample if a patient has a measured glucose of 300 milligramsdL (166 mmolL) 1 hour aer consuming ameal increasing long-acting insulin may result in late hypoglycemia as the measured glucose is moreattributable to recent carbohydrate ingestion this episode of hyperglycemia may be better managed byrecommending an increase in preprandial insulin dosing

A conservative supplemental dose of rapid-acting insulin may be calculated as follows 1 unit per 50milligramsdL (28 mmolL) above target glucose level for T1DM and 1 unit per 30 milligramsdL (17 mmolL)

above target glucose level for T2DM11

For example to achieve a goal blood glucose of 100 milligramsdL(55 mmolL) in a patient with T1DM whohas a glucose level of 350 milligramsdL (195 mmolL) administer 5 units of rapid-acting insulin Anticipatedcarbohydrate consumption would require additional insulin

If the patient is using neutral protamine Hagedorn (NPH or isophane) insulin inspect the insulin vial iffrosting is noted on the sides of the bottle this may indicate denaturation which renders the insulinineective 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 solutions using icodextrin14-17 Falsely elevated point-of-care glucose reading and reflexive insulin administration have been responsible for several reports ofsevere hypoglycemia Point-of-care test strips for both home and hospital use are also sensitive totemperature 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 peritoneal dialysis obtain a laboratory plasmaglucose level for treatment decisions

HYPOGLYCEMIA IN INSULIN-DEPENDENT PATIENTS

Hypoglycemia (plasma glucose lt70 milligramsdL [lt39 mmolL]) is the major adverse eect of tight glycemiccontrol Apart from insulin administration patients with T1DM are prone to hypoglycemia because the surgeof glucagon is absent and epinephrine secretion may be blunted due to neuropathy age or autonomicdysfunction from prior hypoglycemic episodes

Older insulin regimens used once- or twice-daily injections of NPH Lente insulin or premixed combinations(7030 7525 or 5050) of basal insulin and regular insulin as the prandial dose These schedules mandatedfixed meal times and activity schedules so it was not unusual to develop hypoglycemia with missed meals orunusual 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 hypoglycemia11

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 inaccurateadministration of insulin infection renal failure acute coronary syndrome and unusual physical or mentalstress Identify the timing and administration of insulin in relation to meals Ask if the patient is measuringblood glucose at home at a minimum it should be checked daily before breakfast and recorded in a diaryThere is great variation in the pattern of hypoglycemic signs and symptoms from patient to patient howeverindividual patients tend to experience the same pattern from episode to episode Common neuroglycopenicsymptoms may include headache irritability drowsiness confusion dizziness tiredness inability toconcentrate and diiculty speaking These symptoms may mimic an acute ischemic stroke Adrenergicsymptoms such as tremor sweating anxiety nausea palpitations feelings of warmth and shivering are also

seen as are other symptoms such as hunger weakness and blurred vision18

Hypoglycemic unawareness or hypoglycemia-associated autonomic failure occurs when diabetic patients

have deficient counterregulatory hormone excretion resulting in a lack of symptoms of hypoglycemia19 Thisresults in frequent episodes of hypoglycemia and profound hypoglycemia β-Blocker medication may alsocontribute 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 initialdose is 15 to 20 grams of glucose (PO IV or IO) which can be repeated if hypoglycemia persists aer 15minutes Sublingual glucose (40 dextrose gel preferred teaspoon of sugar may suice) may also be

eective in resource-limited situations20-22

Pure fructose does not cross the bloodndashbrain barrier and does not significantly improve blood glucose levelsMost sweet foods or drinks contain both glucose and fructose they are labeled as containing ldquosugarsrdquo which

rdquoSugarrdquo may include glucose fructose galactose sucrose lactose or maltose

includes glucose fructose or sucrose Protein has a negligible contribution to serum glucose so foods suchas peanut butter or cheese are not recommended for hypoglycemia treatment Once hypoglycemia hasresolved have the patient eat a meal or carbohydrate snack Table 223-4 lists the sugar content of commonlyused oral agents

TABLE 223-4

Sugar Content of Agents Available at Home or Over the Counter

Agent DoseRoute Sugar Content

Fruit juice 1 cup PO Variable depending on type of juice and manufacturer (mostly

fructose)

8 oz Mottrsquosreg 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) Pepsireg 41 grams sugar (mostly fructose)

(Non-diet) Spritereg 38 grams sugar (mostly fructose)

(Non-diet) Coca-Cola (Coke)reg Original 39 grams sugar (mostly

fructose)

Glucose tablets 4 tablets PO 16 grams glucose

Glucose gel 1 tube POSL 15 grams glucose

Glucagon emergency kits are available for caregivers of patients with T1DM for emergency situations Onemilligram of intramuscular glucagon stimulates glycogenolysis and is eective in 10 to 15 minutes

Preliminary data show that intranasal glucagon may also be eective23 Once the patient is alert enough toswallow give oral glucose immediately Glucagon is not eective in glycogen-depleted patients andglucagon may induce nausea and vomiting which can make it diicult to consume oral glucosesubsequently

Insulin Overdose

Short-acting insulin may have delayed and prolonged absorption patients with a significant accidental orintentional 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 ifcaregivers 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 country24-29 An insulinpump is a small device (about the size of a pager) that delivers rapid-acting insulin at a basal rate andboluses of insulin for prandial and hyperglycemia correction Once programmed the pump canautomatically calculate dosing for a certain amount of carbohydrates about to be consumed and correct forpremeal hyperglycemia or hypoglycemia The insulin is pumped through a flexible tube and infused via asubcutaneous catheter The pump is usually attached to the patientrsquos waistband The patient must refill theinsulin reservoir and change the catheter every 2 to 3 days Table 223-5 lists manufacturers of insulin pumpsavailable in the United States Some insulin pumps do not use tubing but directly attach to the patient with

adhesive30

Video 223-1 Insulin Pump

Used with permission from Camille Izlar

Play Video

Animas insulin pump is no longer manufactured but is still in use Telephone number is still active

TABLE 223-5

Manufacturers of Insulin Pumps Available in the United States with Their 24-Hour Phone Numbers

Manufacturer Website Telephone Number

Animas httpwwwanimascom (877) 937-7867

Insulet OmniPod httpwwwmyomnipodcom (800) 591-3455

Medtronic MiniMed httpwwwmedtronicdiabetescom (800) 646-4633

Roche Accu-Chek httpswwwaccu-chekcomsupportinsulin-pumps (800) 688-4578

Sooil DANA httpwwwsooilcom (866) 747-6645 ext 102

Tandem Diabetes httpswwwtandemdiabetescom (877) 801-6901

The basal rate of insulin (generally 05 to 15 unitsh) can be varied throughout the day for exampleincreased to counteract an early morning cortisol surge or decreased before exercising Continuous insulindelivery eliminates the need for long-acting insulin injection such that the pump delivers all insulin requiredby the patient in the form of rapid-acting insulin Rarely patients requiring exceptionally high doses of insulinusing an insulin pump patients who wish to be disconnected from their pump for extended periods of timeor patients at higher risk of hyperglycemia or diabetic ketoacidosis (eg young children) may inject an

additional once- or twice-daily long-acting insulin3132 The pump can be manually activated to deliver abolus for hyperglycemia and for prandial dosing Insulin pumps are most appropriate for motivated patientswho are mechanically adept well educated about diabetes and carbohydrate counting and able to monitortheir capillary glucose four to six times a day Benefits of insulin pump therapy over multiple daily injectionsinclude average reduction in hemoglobin A1C of 05 and reduction in hypoglycemic episodes (See Video

The Insulin Pump)2433

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 conditions34 Because pumpsuse only rapid-acting insulin onset of ketoacidosis can be very rapid aer pump failuremdashan hour or less Ifthe pump is defective or needs to be removed for a procedure such as MRI give the patient either a dose ofrapid-acting insulin or long-acting insulin especially if the insulin pump is to be interrupted for over an hourIf 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 hypoglycemicepisodes 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 asoutpatients and will require special attention if presenting to the ED during this transition period Specificconsiderations for patients on insulin pumps presenting with hyperglycemia or hypoglycemia are discussedelsewhere in this chapter

Other important complications of insulin pump therapy include cellulitis at the infusion site or lipodystrophyIf patients using insulin pumps are incidentally found to have hyperglycemia or hypoglycemia they shouldbe allowed to treat themselves either by administering an insulin bolus through their insulin pump or by

consuming carbohydrates respectively192835 Their endocrinologist should have provided theminstructions on how to address this

CONTINUOUS INTERSTITIAL GLUCOSE MONITORING VERSUS POINT-OF-CARE (CAPILLARY) ORSERUM GLUCOSE MONITORING

Continuous glucose monitoring devices measure interstitial glucose concentrations with a subcutaneoussensor and then transmit glucose values to an insulin pump or other display device Interstitial glucosevalues are adjuncts to capillary glucose monitoring and typically require manipulation of the insulin pump toadminister insulin An even newer technology the hybrid closed-loop system was approved by the US Foodand Drug Administration in 2016 The hybrid closed-loop system adjusts insulin dosing based on continuousglucose monitoring data The system can maintain the target glucose for a longer period reduce episodes of

hyper- or hypoglycemia and reduce hemoglobin A1C levels3637

Despite the substantial benefits of monitoring continuous interstitial glucose levels it must be noted thatinterstitial glucose is a proxy but not identical to the more traditionally measured and validated serumglucose levels There is about a 10-minute time lag for change between serum glucose and interstitial

glucose levels38 Several common medications may result in inaccurate continuous interstitial glucose

sensor readings notably including acetaminophen39 Measure capillary or serum glucose levels in the EDand do not use interstitial glucose values (ie those displayed on the patientrsquos 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 pumpswho present to the ED with hyperglycemia Extrapolating from inpatient recommendations we recommendthat patients using insulin pumps who present to the ED with either hyperglycemia or hypoglycemia shouldbe treated the same as patients who are on multiple daily doses of insulin and the insulin pump should not

be disabled1928

Once the patient has been stabilized ask about dietary indiscretions and search for infections Ask specificquestions about the insulin pump When was the insulin reservoir filled When was the infusion set lastchanged Is the insertion site of the infusion set periodically changed When was the insulin reservoir last

changed Has the pump been submerged in water Have any device alarms been sounding40 Examine thedevice thoroughly to ensure the pump is on the reservoir is not empty no alarms are indicated the tubing isnot kinked and the infusion site is well attached to the skin The patient or caregiver may provide usefulinformation on pump operation diagnostics and how to disconnect it if necessary All pumps have atelephone number for 24-hour technical support from the manufacturer (Table 223-5) If there is suspicion forpump 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 pumpdisconnect the pump and start an IV insulin infusion following protocols for management of diabeticketoacidosis We recommend against bolus IV insulin prior to initiation of an insulin drip because this

provides no clinical benefit41 Consider SC administration of long-acting insulin at the initiation of an insulindrip particularly if re-initiation of insulin pump therapy is not expected aer resolution of the diabetic

ketoacidosis42 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 bere-initiatedmdashin that case restart pump therapy approximately 1 hour before stopping the IV insulin drip Tore-initiate pump therapy make sure that the pump is working appropriately by running diagnostics on thedevice checking that the insulin reservoir is filled with fresh insulin and placing a new SC insulin infusioncatheter Check serum glucose levels every 30 to 60 minutes See Chapter 225 for further discussion oftransition 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 canrapidly develop If recurrent hypoglycemia develops aer initial treatment pump malfunction may be thecause Please see the earlier section ldquoHyperglycemia in Patients Using Insulin Pumpsrdquo

SPECIAL CONSIDERATIONS

UNDIAGNOSED DIABETIC

A long asymptomatic period is common for T2DM but T1DM typically has a short period before the diseasebecomes overt If the patient is newly identified with severe and symptomatic hyperglycemia (gt250 to 300milligramsdL [138 to 167 mmolL]) insulin should be administered in the ED Insulin can be given even if itis not known at the time whether the patient has T1DM or T2DM Patients with severe or symptomatic

hyperglycemia should be admitted or placed in an observation unit for further glucose control andeducation

For patients with hyperglycemia but without ketoacidosis a low dose of regular or rapid-acting insulin (1 unitsubcutaneously for every 30 to 50 milligramsdL above glucose of 250 to 300 milligramsdL) may be given toreduce hyperglycemia and a long-acting insulin (eg 01 to 02 unitskg of insulin glargine) should be givenin the ED to prevent diabetic ketoacidosis

For patients without severe and symptomatic hyperglycemia regular or rapid-acting insulin can be given toreduce the glucose to about 250 milligramsdL Then most patients may be discharged with a prescription

for metformin and referral to their physician or clinic within 24 hours for further evaluation and care1943 Forfurther discussion of T2DM care and noninsulin antidiabetic agents such as metformin see Chapter 224

GLUCOCORTICOID THERAPY

Patients with T1DM who are started on glucocorticoids before discharge from the ED will likely develophyperglycemia They should be informed about warning signs of hyperglycemia and advised to seek closefollow-up with their primary physician with frequent monitoring of blood glucose at home and additionalbolus doses of insulin Routine increase in long-acting basal insulin dosage is not advised as both theduration of action of the insulin as well as the steroid must be carefully considered

Although previously undiagnosed patients with diabetes may develop hyperglycemia while onglucocorticoid therapy the hyperglycemia will oen resolve spontaneously once the glucocorticoid course iscompleted If hyperglycemia is persistent or symptomatic medication may be required aer failure of dietarymodification and exercise

PRAMLINTIDE

Patients with T1DM who are unable to achieve optimal glucose control may also be treated with injections ofprandial pramlintide in addition to prandial or continuous SC insulin Pramlintide a synthetic form of thehormone amylin is produced by β-cells Amylin promotes satiety slows gastric emptying aids in suppressing

postprandial glucagon secretion and reduces hemoglobin A1C levels54445 Despite these benefits thenecessity for injection of a second prandial medication incidence of nausea and severe hypoglycemiaespecially during dose titration prevent the great majority of patients with T1DM from using this

medication4647

TRANSPLANTATION

There are three methods of pancreas transplantation simultaneous pancreas and kidney (75 of

transplants) pancreas aer kidney (18) and pancreas transplant alone (7)48 In 2016 215 pancreas

transplants and 798 combined kidneypancreas transplants were performed in the United States49 Life-longimmunosuppression is required One-year gra survival with insulin independence approaches 86

1

2

3

4

5

6

7

8

(simultaneous pancreas and kidney) 80 (pancreas aer kidney) and 78 (pancreas transplant alone) 10-year gra survival is 68 (simultaneous pancreas and kidney) 46 (pancreas aer kidney) and 39

(pancreas transplant alone)4850

Another promising modality is islet cell transplantation The Edmonton protocol has led to insulin

independence in T1DM51 Insulin independence is short lived however 2 years aer transplantation 76 ofpatients again required the use of exogenous insulin Some longitudinal studies have demonstrated insulin

independence 12 years aer Edmonton protocol islet cell transplant52

REFERENCES

American Diabetes Association Diagnosis and classification of diabetes mellitus Diabetes Care 37(suppl1) S81 2014 [PubMed 24357215]

httpwwwdiabetesorgdiabetes-basicsstatistics (American Diabetes Association Statistics aboutdiabetes) Accessed on August 27 2017

httpswwwcdcgovdiabetespdfsdatastatisticsnational-diabetes-statistics-reportpdf (Centers forDisease Control and Prevention National Diabetes Statistics Report 2017) Accessed on December 4 2017

American Diabetes Association Classification and diagnosis of diabetes Diabetes Care 40(suppl 1) S112017 [PubMed 27979889]

Edelman S Maier H Wilhelm K Pramlintide in the treatment of diabetes mellitus BioDrugs 22 375 2008[PubMed 18998755]

httpswwwfdagovdrugsresourcesforyouconsumersquestionsanswersucm173909htm (US Foodand Drug Administration Questions and answers on importing beef or pork insulin for personal use)Accessed on August 31 2017

httpswwwfdagovDrugsEmergencyPreparednessucm085213htm (US Food and Drug AdministrationInformation regarding insulin storage and switching between products in an emergency) Accessed July 242017

Hahr AJ Molitch ME Optimizing insulin therapy in patients with type 1 and type 2 diabetes mellitusoptimal dosing and timing in the outpatient setting Am J Ther 15 543 2008 [PubMed 19127139]

9

10

11

12

13

14

15

16

17

18

Mooradian AD Bernbaum M Albert SG Narrative review a rational approach to starting insulin therapyAnn Intern Med 145 125 2006 [PubMed 16847295]

American Diabetes Association Pharmacologic approaches to glycemic treatment Diabetes Care40(suppl 1) S64 2017 [PubMed 27979895]

DeWitt DE Hirsch IB Outpatient insulin therapy in type 1 and type 2 diabetes mellitus scientific reviewJAMA 289 2254 2003 [PubMed 12734137]

httpsdailymednlmnihgovdailymeddrugInfocfmsetid=29f4637b-e204-425b-b89c-7238008d8c10(National Institutes of Health AFREZZA - insulin human powder metered) Accessed August 31 2017

Bode BW McGill JB Lorber DL et al Inhaled technosphere insulin compared with injected prandialinsulin in type 1 diabetes a randomized 24-week trial Diabetes Care 38 2266 2015 [PubMed 26180109]

Frias JP Lim CG Ellison JM Montandon CM Review of adverse events associated with false glucosereadings measured by GDH-PQQ-based glucose test strips in the presence of interfering sugars DiabetesCare 33 728 2010 [PubMed 20351227]

Sartor Z Kesey J Dissanaike S The eects of intravenous vitamin C on point-of-care glucosemonitoring J Burn Care Res 36 50 2015 [PubMed 25127026]

Ginsberg BH Factors aecting blood glucose monitoring sources of errors in measurement J DiabetesSci Technol 3 903 2009 [PubMed 20144340]

Klono DC Point-of-care blood glucose meter accuracy in the hospital setting Diabetes Spectr 27 1742014 [PubMed 26246776]

Deary IJ Hepburn DA MacLeod KM Frier BM Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis Diabetologia 36 771 1993 [PubMed 8405746]

19

20

21

22

23

24

25

26

27

28

Marathe PH Gao HX Close KL American Diabetes Association standards of medical care in diabetes2017 J Diabetes 9 320 2017 [PubMed 28070960]

Graz B Dicko M Willcox ML et al Sublingual sugar for hypoglycaemia in children with severe malaria apilot clinical study Malar J 7 242 2008 [PubMed 19025610]

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