in the clinic in the clinic Diabetic Ketoacidosis Prevention page ITC1-2 Diagnosis page ITC1-5 Treatment page ITC1-9 Practice Improvement page ITC1-14 CME Questions page ITC1-16 Section Editors Christine Laine, MD, MPH Barbara J. Turner, MD, MSED Sankey Williams, MD Science Writer Jennifer F. Wilson The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including PIER (Physicians’ Information and Education Resource) and MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic from these primary sources in collaboration with the ACP’s Medical Education and Publishing Division and with the assistance of science writers and physician writers. Editorial consultants from PIER and MKSAP provide expert review of the content. Readers who are interested in these primary resources for more detail can consult http://pier.acponline.org and other resources referenced in each issue of In the Clinic. CME Objective: To provide information about the prevention, diagnosis, and management of diabetic ketoacidosis. The information contained herein should never be used as a substitute for clinical judgment. © 2010 American College of Physicians

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Page 1: 27247997 Diabetic Ketoacidosis


clinicin the clinic

Diabetic KetoacidosisPrevention page ITC1-2

Diagnosis page ITC1-5

Treatment page ITC1-9

Practice Improvement page ITC1-14

CME Questions page ITC1-16

Section EditorsChristine Laine, MD, MPHBarbara J. Turner, MD, MSEDSankey Williams, MD

Science WriterJennifer F. Wilson

The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), includingPIER (Physicians’ Information and Education Resource) and MKSAP (MedicalKnowledge and Self-Assessment Program). Annals of Internal Medicineeditors develop In the Clinic from these primary sources in collaboration withthe ACP’s Medical Education and Publishing Division and with the assistance of science writers and physician writers. Editorial consultants from PIER andMKSAP provide expert review of the content. Readers who are interested inthese primary resources for more detail can consult http://pier.acponline.org andother resources referenced in each issue of In the Clinic.

CME Objective: To provide information about the prevention, diagnosis, andmanagement of diabetic ketoacidosis.

The information contained herein should never be used as a substitute for clinical judgment.

© 2010 American College of Physicians

Page 2: 27247997 Diabetic Ketoacidosis

Who is at risk for DKA?Although most patients with DKAhave type 1 diabetes, 10% to 30%have type 2 diabetes (3, 6). There-fore, all patients with diabetes needto be provided with educationalmaterials and the tools to self-monitor glucose and urine ketonelevels or blood 3-β-hydroxybutyratelevels (7). Physicians and other cli-nicians who manage the care ofpersons with diabetes need to edu-cate their patients about the manyconditions that can precipitateDKA, including infections (for ex-ample, pneumonia or urinary tractinfection); alcohol misuse; psycho-logical stress; pregnancy; cardiovas-cular events; trauma; and medica-tions, such as corticosteroids (8)(Box). The most prevalent con-tributing factor to DKA is poor adherence to diabetes treatmentprogram (9–10). Patients may dis-continue diabetes medications ormonitoring for many reasons, suchas cost, poor understanding of thedisease, or weight control. In ado-lescents, psychological disorders,such as depression and eating dis-orders, are frequently underlyingepisodes of DKA. In addition to

medication nonadherence, patientsmay not monitor their blood sugarlevels and may, therefore, be un-aware of increasingly poor control.

Patient education and remindersthat promote adherence to pre-scribed diabetes monitoring, diet,and medication are importantmeans to prevent DKA. BecauseDKA is often the initial presenta-tion of diabetes in minority com-munities (11), community-basededucation about the warning signsof diabetes is particularly impor-tant. The same patients can present

© 2010 American College of Physicians ITC1-2 In the Clinic Annals of Internal Medicine 1 January 2010

1. Neu A, Hofer SE,Karges B, et al; DPVInitiative and the Ger-man BMBF Compe-tency Network for Di-abetes Mellitus.Ketoacidosis at dia-betes onset is still fre-quent in children andadolescents: a multi-center analysis of14,664 patients from106 institutions. Dia-betes Care.2009;32:1647-8.[PMID: 19549730]

2. Wild S, Roglic G,Green A, et al. Globalprevalence of dia-betes: estimates forthe year 2000 andprojections for 2030.Diabetes Care.2004;27:1047-53.[PMID: 15111519]

3. Henriksen OM, RøderME, Prahl JB, et al. Di-abetic ketoacidosis inDenmark Incidenceand mortality esti-mated from publichealth registries. Dia-betes Res Clin Pract.2007;76:51-6.[PMID: 16959363]

4. Freire AX, UmpierrezGE, Afessa B, et al.Predictors of inten-sive care unit andhospital length ofstay in diabetic ke-toacidosis. J Crit Care.2002;17:207-11.[PMID: 12501147]

5. Lin SF, Lin JD, HuangYY. Diabetic ketoaci-dosis: comparisons ofpatient characteris-tics, clinical presenta-tions and outcomestoday and 20 yearsago. Chang GungMed J. 2005;28:24-30.[PMID: 15804145]

Diabetic ketoacidosis (DKA), the complication of diabetes mellitusthat causes the greatest risk for death, is characterized by hyper-glycemia and metabolic acidosis due to the accumulation of ketones

from the breakdown of free fatty acids. Treatment requires hospitalization tocorrect hyperglycemia as well as serious volume depletion and electrolyte ab-normalities. DKA occurs primarily in patients with type 1 diabetes mellitusbut can also occur in those with type 2 diabetes. In a multicenter study ofnearly 15 000 children and adolescents, DKA was the initial presentation oftype 1 diabetes for 21.1%, and this proportion did not change substantiallyfrom 1997 to 2007 (1). The number of persons with diabetes is increasingrapidly, but the number of hospitalizations for DKA has increased at a slowerpace (2). This relative reduction in the incidence of DKA is probably due toimprovements in diabetes management. The risk for death with DKA hastypically been about 4% (3, 4), but some studies report lower mortality ratesin recent years (5). Deaths are concentrated primarily in elderly persons (3).Patient education and self-monitoring tools can prevent DKA. When it doesoccur, management that follows evidence-based treatment principles, whichinclude hydration, insulin therapy, potassium repletion, and correction of theprecipitating factor, can prevent DKA-related morbidity and mortality.


Factors That Can Precipitate DKA• Infection (for example, pneumonia,

urinary tract infection, sepsis)• Alcohol misuse• Psychological stress• Pregnancy• Cardiovascular events• Trauma• Medications (such as corticosteroids)• Cushing disease• Acute gastrointestinal disease

(for example, pancreatitis, obstruc-tion, mesenteric thrombosis)

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© 2010 American College of PhysiciansITC1-3In the ClinicAnnals of Internal Medicine1 January 2010

repeatedly with DKA until the underlying contributory factors areidentified and addressed. These pa-tients need to understand that theyare at risk for repeated episodes andneed a program of self-monitoringand changes in medication, diet,and hydration well-defined forthem (Box). Social support may beneeded for patients with psycholog-ical or social issues that make ad-herence difficult. The patient must understand whom and when to callif symptoms and signs (blood glu-cose and urine or blood ketones)

suggest impending DKA (Box).Both primary and secondary pre-vention of DKA are critical to re-duce morbidity and mortality.

Can patients with type 2 diabetesdevelop DKA?In an analysis of admissions to alarge academic center for moderate-to-severe DKA, 21.7% were for pa-tients with type 2 diabetes whowere also significantly more likelyto be Latino or African American(12). Most persons with ketosis-prone type 2 diabetes are also morelikely to be middle aged and obeseand to have newly diagnosed dia-betes (13). In contrast to the pre-dominance of girls and womenwith type 1 diabetes who developDKA, men are more likely to havetype 2 diabetes complicated byDKA (Box).

Patients with newly diagnosed ketosis-prone type 2 diabetes oftenhave classic symptoms of poorlycontrolled diabetes, includingpolyuria, polydipsia, and weight lossfor at least 1 month. These personsoften have multiple risk factors fordiabetes, including family history ofdiabetes. The hemoglobin A1c levelat presentation is usually greaterthan 13%. Improved access to med-ical care and monitoring of the de-velopment of these symptoms inpatients at risk for diabetes may re-duce the prevalence of DKA.

According to systematic review of ketosis-prone type 2 diabetes, features that are as-sociated with near-euglycemic remissionafter an episode of DKA include minority

6. Wang ZH, Kihl-Sel-stam E, Eriksson JW.Ketoacidosis occursin both type 1 andtype 2 diabetes—apopulation-basedstudy from NorthernSweden. Diabet Med.2008;25:867-70.[PMID: 18644074]

7. Laffel LM, Wentzell K,Loughlin C, et al. Sickday management us-ing blood 3-hydroxy-butyrate (3-OHB)compared with urineketone monitoringreduces hospital visitsin young people withT1DM: a randomizedclinical trial. DiabetMed. 2006;23:278-84.[PMID: 16492211]

8. Kitabchi AE, Umpier-rez GE, Murphy MB,et al. Management ofhyperglycemic crisesin patients with dia-betes. Diabetes Care.2001;24:131-53.[PMID: 11194218]

9. Ko SH, Lee WY, LeeJH, et al. Clinical char-acteristics of diabeticketoacidosis in Koreaover the past twodecades. Diabet Med.2005;22:466-9.[PMID: 15787674]

10. Morris AD, Boyle DI,McMahon AD, et al.Adherence to insulintreatment, gly-caemic control, andketoacidosis in in-sulin-dependent di-abetes mellitus. TheDARTS/MEMO Col-laboration. DiabetesAudit and Researchin Tayside Scotland.Medicines Monitor-ing Unit. Lancet.1997;350:1505-10.[PMID: 9388398]

11. Nyenwe E, Lo-ganathan R, Blum S,et al. Admissions fordiabetic ketoacidosisin ethnic minoritygroups in a city hos-pital. Metabolism.2007;56:172-8.[PMID: 17224329]

12. Umpierrez GE, Smi-ley D, Kitabchi AE.Narrative review: ke-tosis-prone type 2diabetes mellitus.Ann Intern Med.2006;144:350-7.[PMID: 16520476]

13. Newton CA, RaskinP. Diabetic ketoaci-dosis in type 1 andtype 2 diabetes mel-litus: clinical and bio-chemical differences.Arch Intern Med.2004;164:1925-31.[PMID: 15451769]

Sick-Day Protocol*

Examples of sick days• Feeling sick or have had a fever for a

couple of days and not getting better• Vomiting or having diarrhea for more

than 6 hours

Management• Check blood sugars at least every

4 hours, but, when changing quickly,check more often

• Check urine or blood ketones• Modify usual insulin regimen accord-

ing to a plan developed by the dia-betes physician or team

• Maintain adequate food and fluid in-take. If poor appetite: aim for 50 g ofcarbohydrate every 3–4 hours. If youare nauseated, consume high-carbo-hydrate liquids, such as regular (notdiet) soft drinks, juice, frozen juicebars, sherbet, pudding, creamedsoups, and fruit-flavored yogurt.Broth is also a good alternative.

Examples of when to call physician ordiabetes team:• If glucose levels are >13.3 mmol/L

(>240 mg/dL) despite taking extra in-sulin according to a sick-day plan

• If you take diabetes pills and bloodsugar is still >13.3 mmol/L (>240 mg/dL) before meals and re-mains there for more than 24 hours

• If symptoms develop that might sig-nal DKA or dehydration, such as dizzi-ness, trouble breathing, fruity breath,or dry and cracked lips or tongue

* From American Diabetes Association.Living with diabetes. Accessed atwww.diabetes.org/living-with-diabetes/treatment-and-care/my-healthcare-team/when-youre-sick.html on 16 November 2009.

Clinical Characteristics of PersonsWith Type 2 Diabetes and DKA• African American or Latino• Male• Middle aged• Overweight or obese (body mass in-

dex, 27 to 28 kg/m2)• Family history of diabetes• With newly diagnosed diabetes

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14. Reichel A, RietzschH, Köhler HJ, et al.Cessation of insulininfusion at night-time during CSII-therapy: comparisonof regular human in-sulin and insulinlispro. Exp Clin En-docrinol Diabetes.1998;106:168-72.[PMID: 9710355]

15. Kitabchi AE, Umpier-rez GE, Miles JM, etal. Hyperglycemiccrises in adult pa-tients with diabetes.Diabetes Care.2009;32 1335-43.[PMID: 19564476]

© 2010 American College of Physicians ITC1-4 In the Clinic Annals of Internal Medicine 1 January 2010

race, obesity, family history of diabetes,newly diagnosed diabetes, and negativeautoantibodies (islet cells or glutamic aciddecarboxylase). C-peptide levels also helpdistinguish these patients. The fasting C-peptide level is greater than 0.33 nmol/Lwithin 1 week after resolution of DKA andgreater than 0.5 nmol/L on follow-up after6 to 8 weeks. The glucagon-stimulated C-peptide level is greater than 0.5 nmol/L atpresentation with DKA and greater than0.75 nmol/L on follow-up after 6 to 8weeks. Glucagon-stimulated C-peptidetest is administered after a 10-hourovernight fast with blood samples taken atbaseline and at 3 or 6 minutes after injec-tion of glucagon (1 mg) to measure levelsof glucose and C-peptide (12).

What advice should be given topatients with diabetes regardingmanagement of sick days?Because DKA is often precipitat-ed by concurrent acute infection,it is important that patients knowhow to monitor and manage dia-betes when they develop symp-toms of an infection. Specifically,adherence to self-monitoring ofblood glucose levels with a planfor treatments in specific rangesoffers an important defenseagainst DKA. Sick-day instruc-tions should include informationon how often to check glucoseand urinary ketone levels, how totreat glucose levels in specificranges, diet to maintain adequatenutrition, hydration with fluidsthat will not worsen the hyper-glycemia, and the avoidance of ex-ercise if ketosis is present (Box).When illness or other stressorsoccur, patient education shouldemphasize increasing the frequen-cy of monitoring to at least every4 hours. An infection or other ill-ness should be expected to in-crease insulin requirements. In-structions should clearly indicatewhen to consult the physician orother clinician managing diabetescare. The self-management planneeds to include maintenance ofadequate nutrition and hydrationwith appropriate fluids that willnot worsen the hyperglycemia.

The sick-day program is demand-ing and requires advance prepara-tion with clear, low-literacy edu-cational materials for patients andtheir caregivers.

However, patients should becounseled that persons with type1 diabetes mellitus need to takeinsulin even during periods ofstarvation because of the effectsof counter-regulatory hormonesthat produce hyperglycemia, suchas glucagon, cortisol, growth hor-mone, and catecholamines. Theseeffects can be worsened by nauseaand vomiting or when the patienthas a poor appetite because offeeling poorly. The sick day pro-tocol gives instructions about useof supplemental short-acting in-sulin in addition to usual insulinand management of infections.Patients who use an insulin-infusion pump should change to insulin injections until theyconfirm that the pump is func-tioning properly.

Some groups recommend thatphysicians also have patientscheck serum ketone levels inthose with type 1 diabetes. Ele-vation of urine or serum ketonesor β-hydroxybutyrate level shouldprompt the patient to contact theprovider or go to an emergencydepartment. Similarly, the patientshould seek care when unable totolerate food or liquid or if theyhave changes in mental status.The severity of the precipitatingillness influences morbidity andmortality from DKA. Specialprecautions are necessary duringpregnancy. Patients who are preg-nant should check ketones forany glucose readings greater than11.1 mmol/L (200 mg/dL). Theyshould contact their physician af-ter several high glucose readingswith positive ketones, severalhigh readings without the abilityto keep fluids down, or continuedhigh glucose readings despitenegative ketones.

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16. Delaney MF, ZismanA, Kettyle WM. Dia-betic ketoacidosisand hyperglycemichyperosmolar non-ketotic syndrome.Endocrinol MetabClin North Am.2000;29:683-705, V.[PMID: 11149157]

17. Lebovitz HE. Diabet-ic ketoacidosis.Lancet. 1995;345:767-72. [PMID:7891491]

© 2010 American College of PhysiciansITC1-5In the ClinicAnnals of Internal Medicine1 January 2010

Who should be evaluated forpotential DKA?All patients with positive ketones,constitutional symptoms, or suspi-cion of DKA and significantly ele-vated blood glucose levels (>13.9mmol/L [>250 mg/dL]) shouldhave electrolytes and blood gaseschecked to look for an anion gapmetabolic acidosis. Especially intype 1 diabetes, DKA can developwithin hours if insulin injectionsare stopped or an insulin pumpmalfunctions (14). The new Ameri-can Diabetes Association (ADA)definition of DKA includes a bloodglucose level of 13.9 mmol/L (250mg/dL) (15) and reflects manystudies that have shown that DKAis infrequent at lower levels exceptin situations with poor oral intakeor pregnancy (16). It is also impor-tant to consider DKA in the differ-ential diagnoses for a patient whohas an anion gap metabolic acido-sis. The calculation of the aniongap is Na+ − (Cl− + HCO3

−) (Table1). The serum glucose should bechecked even when the patient hasno history of diabetes. DKA mustbe considered if the serum glucose

is greater than 13.9 mmol/L (250mg/dL), but an elevated glucoselevel alone is insufficient to diag-nose DKA.

DKA should be considered in pa-tients with diabetes who have aconcurrent infection, stroke, my-ocardial infarction, or other seriousillness. These intercurrent illnessesshould be sought and treated ag-gressively. Similarly, it is importantto consider DKA when patientswith diabetes experience nauseaand vomiting, even if the bloodglucose level is less than 13.9mmol/L (250 mg/dL). EuglycemicDKA occurs more often in patientswho have not eaten but who con-tinue to take insulin. A blood glu-cose level less than 13.9 mmol/L(250 mg/dL) occurs in 1% to 7% ofreported DKA cases (17) andseems to be more common in pa-tients with hepatic dysfunction orin those who are hospitalized.

Several drugs, such as glucocorti-coids or thiazides, are well-knowncauses of hyperglycemia that maylead to DKA. Clinicians should

Prevention... DKA occurs in both type 1 and 2 diabetes. Patients at risk for DKAwith type 2 diabetes are more likely to be men, middle-aged, obese, and with afamily history of diabetes and newly diagnosed diabetes. DKA can result from in-fections or other stressors, such as cardiovascular disease, but is most commonlydue to nonadherence to the diabetes-care program, including treatment and self-monitoring. DKA can also be the first presentation of diabetes. A sick-day man-agement plan should be established for all patients with diabetes but especiallythose with a history of DKA to avoid repeated episodes.


Table 1. Serum Chemistry Calculations Relevant to Diabetic KetoacidosisSerum Chemistry Value Calculation Normal Range

Anion gap Na+ − (Cl− + HCO3−) 7–13 mmol/L

Δ Anion gap (Patient gap – 12) <10 mmol/L*Total serum osmolality 2 × (serum Na+) + (glucose / 18) 290 ± 5 mOsm/kg H2O

+ (blood urea nitrogen / 2.8)†

* Varies by institution.† Serum Na+ measured in mmol/L, glucose and blood urea nitrogen measured in mg/dL.


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18. Wilson DR, D’SouzaL, Sarkar N, et al.New-onset diabetesand ketoacidosiswith atypical an-tipsychotics. Schizo-phr Res. 2003;59:1-6.[PMID: 12413635]

19. Ananth J, VenkateshR, Burgoyne K, et al.Atypical antipsy-chotic drug use anddiabetes. PsychotherPsychosom.2002;71:244-54.[PMID: 12207104]

20. Vanelli M, Chiari G,Capuano C, et al. Thedirect measurementof 3-beta-hydroxybutyrate enhancesthe management ofdiabetic ketoacidosisin children and re-duces time andcosts of treatment.Diabetes Nutr Metab2003;16:312-6

© 2010 American College of Physicians ITC1-6 In the Clinic Annals of Internal Medicine 1 January 2010

also consider DKA in patients tak-ing atypical antipsychotic drugswho present with hyperglycemia.Atypical antipsychotic drugs havebeen linked to increased frequencyof diabetes, glucose intolerance, andDKA (18, 19). The anion gap andketone levels should be measured insuch patients. Another type of an-tipsychotic drug must be chosen tohelp resolve this complication.

What are key elements of thehistory and physical examinationin DKA?The presentation of a patient withDKA varies substantially depend-ing on the severity of the episode.Mild or moderately ill patientsmay describe vague symptoms offatigue, lethargy, poor appetite, orheadache. In type 1 diabetes, thehistory of polyuria and polydipsiamay be relatively recent, but intype 2 diabetes, these symptomsmay have been building for weeksto months. Nausea, vomiting, andabdominal pain are commonlyseen in DKA and may be relatedto the combined effects of dehy-dration, hypokalemia, ketonemia,and delayed gastric emptying.

Signs of dehydration, includingpoor skin turgor, decreased axillarysweat, or postural hypotension, maybe present on physical examination.Kussmaul respirations (a pattern ofdeep breathing and hyperventila-tion in response to metabolic aci-dosis) may be present. Patients’breath may smell fruity due to in-creased acetone from ketonemia,but the absence of this finding doesnot rule out DKA. One aspect ofthe examination that can be con-fusing is abdominal tenderness,which may resolve as the DKA istreated or may reflect a more acuteabdominal process that precipitatedDKA. Abdominal pain correlateswith the level of acidosis. Thephysical examination should focuson identifying potential precipitat-ing factors, such as infections orcardiovascular events. Patients may

have mental status changes rangingfrom mild lethargy to delirium orcoma. The most-severe cases arecharacterized by hypotension,tachycardia, and coma.

Is measurement of capillary blood ketones helpful in thediagnosis of DKA?Capillary blood ketone measure-ment is a relatively new quantitativeand enzymatic test that determineslevels of 3-β-hydroxybutyrate, 1 ofthe 3 ketone bodies. The equip-ment is similar to that used by pa-tients for home blood glucose de-termination, but it requires specificstrips. In 1 small study, the levels of3-β-hydroxybutyrate were moreclosely related to the bicarbonatelevel than to the serum ketones(20). However, checking capillaryblood ketones is much more expen-sive than checking urine ketones,and further clinical studies areneeded to define the most appro-priate role for β-hydroxybutyratemonitoring.

A prospective study of the utility of point-of-care blood ketone testing in patients with di-abetes presenting to the emergency depart-ment found that a rapid, bedside capillaryblood ketone test for β-hydroxybutyratemeasures this blood ketone better thanurine ketones. The sensitivity and specifici-ty of urine ketone dipstick testing and cap-illary blood ketone testing in determiningDKA were 66% and 78% and 72% and 82%,respectively; and in determining hyperke-tonemia were 82% and 54% and 91% and56%, respectively (21).

Are low levels of ketones in bloodor urine diagnostic of DKA?If clinical suspicion of DKA ishigh, a negative urine dipstick forketones does not exclude DKA.Clinicians should be aware thaturine test sticks do not measure β-hydroxybutyrate, which is thepredominant ketone. Acetoacetatemeasured on the dipstick may notbe elevated until later in the courseof the illness (22).

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© 2010 American College of PhysiciansITC1-7In the ClinicAnnals of Internal Medicine1 January 2010

21. Bektas F, Eray O, SariR, et al. Point of careblood ketone testingof diabetic patientsin the emergencydepartment. EndocrRes. 2004;30:395-402. [PMID:15554356]

22. Koul PB. Diabetic ke-toacidosis: a currentappraisal of patho-physiology andmanagement. ClinPediatr 2009; 48:135-44.

23. Ma OJ, Rush MD,Godfrey MM, et al.Arterial blood gasresults rarely influ-ence emergencyphysician manage-ment of patientswith suspected dia-betic ketoacidosis.Acad Emerg Med.2003;10:836-41.[PMID: 12896883]

What laboratory tests are used toevaluate for DKA?Table 2 shows recommended labo-ratory and other studies for DKA.DKA is diagnosed when the bloodglucose level is greater than 13.9mmol/L (250 mg/dL), arterial pHis less than 7.3, serum bicarbonateis less than 15 mmol/L, and amoderate degree of ketonemia orketonuria is present. A total bodydeficit of potassium frequentlycomplicates DKA, so initial meas-urement and frequent monitoringof potassium is required to deter-mine replacement need. Because ofthe metabolic acidosis, hyper-kalemia may initially be present.

Are arterial blood gases requiredto make the diagnosis of DKA?Arterial blood gas (ABG) assess-ment is generally considered to bethe most reliable method to evalu-ate the degree of acidosis in DKA,but a venous pH may be a morepractical alternative. The normalanion gap is 7 to 9 mmol/L, but isapproximately 25 mmol/L inDKA. Rarely, patients with DKAhave a mixed acidosis and alkalo-sis with a pH that is close to nor-mal. However, treatment of DKA

should not be affected by this un-expected laboratory result. Deter-mination of the ABG may be lessessential than originally thought.

A prospective, observational study exam-ined emergency physicians’ decision mak-ing for 200 consecutive patients with sus-pected DKA. Venous pH, chemistry panel,and ABGs were obtained for all patients,but the physicians based their decisionsonly on the venous pH or the ABG. The ad-ditional information obtained from theABG changed: diagnosis for only 1%;management for 3.5%; and disposition for1%. The venous pH was closely correlatedwith the arterial pH (r = 0.951), so the au-thors concluded that it could serve as asubstitute (23).

How does DKA differ fromhyperosmolar hyperglycemicstate?Patients with type 1 diabetes areat greater risk for DKA than pa-tients with type 2 diabetes, butpatients with type 2 diabetes areat greater risk for hyperosmolarhyperglycemic state (HHS), whichhas a similar presentation toDKA. In DKA, the serum glucoselevel is generally less than 33.3mmol/L (600 mg/dL), whereas inthe ADA definition of HHS, the

Table 2. Laboratory and Other Studies for Diabetic Ketoacidosis Test Notes

Plasma glucose Usually >13.9 mmol/L (>250 mg/dL)Arterial blood gas pH is usually <7.3Serum ketones Usually 7–10 mmol/L in DKA or >1:2 dilutionAnion gap (electrolytes) Usually >15 in DKASerum sodium Usually lowSerum potassium May be high, normal, or low. Potassium level will guide managementSerum phosphate May be normal or high initially but usually decreases with insulin therapySerum amylase/lipase May be high in DKA, unrelated to pancreatitis. Diagnosis of pancreatitis in DKA

should be based on clinical judgment and imagingBlood urea, creatinine levels Usually elevated due to dehydration and decreased renal perfusionCBC count and differential Leukocytosis is common and may not represent infection.

Levels >25 × 109 cells/L should warrant diligent search for infectionUrine and blood cultures If suspicion of infection is presentChest radiography If suspicion of pneumonia or pulmonary disorderECG Should be done in all patients to assess effect of potassium status and rule out

ischemia or myocardial infarction

CBC = complete blood cell; DKA = diabetic ketoacidosis; ECG = electrocardiography.

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© 2010 American College of Physicians ITC1-8 In the Clinic Annals of Internal Medicine 1 January 2010

glucose level is greater than 33.3mmol/L (600 mg/dL) and oftengreater than 55.5 mmol/L (1000mg/dL) but with minimal ketoneaccumulation and only mild reduc-tion in the arterial pH (Table 3)(15). As the main metabolite ofketones, β-hydroxybutyrate levelsare elevated in DKA but are usu-ally normal in HHS. The in-creased serum osmolality in HHSreflects serious dehydration andoften produces mental statuschanges, including coma in 25%to 50% of cases. However, DKAand HHS can overlap and havemany similarities. Like DKA,

HHS usually results from a precipitating factor, such as an infection or poor adherence to diabetes medications.

What conditions should beconsidered in the differentialdiagnosis of DKA?If the blood glucose level is less than13.9 mmol/L (250 mg/dL), anothercause of the metabolic acidosis needsto be considered (Table 4). Otherconditions, such as starvation, canincrease ketones, but this elevation isusually mild. DKA can co-occurwith other causes of metabolic aci-dosis, including lactic acidosis.

Diagnosis... Patients with DKA may present with a wide variety of nonspecificsymptoms; therefore, it is important to have a high index of suspicion. The physi-cal examination can yield clues to the diagnosis, such as a fruity-smelling breathfrom ketonemia, or to the severity of the episode, such as signs of significant de-hydration. Laboratory assessment typically shows a blood glucose level greaterthan 13.9 mmol/L (250 mg/dL), arterial pH less than 7.3, serum bicarbonate lessthan 15 mmol/L, and a moderate degree of ketonemia or ketonuria. Patients withtype 2 diabetes are at greater risk for HHS, in which glucose level is often greaterthan 55.5 mmol/L (1000 mg/dL) but the ketones are minimally elevated and thepH is only mildly depressed. The venous pH may offer an alternative to the arteri-al pH in the emergency department.


Table 3. Diabetic Ketoacidosis Versus Hyperosmolar Hyperglycemic State*Value Mild DKA Moderate DKA Severe DKA HHS

Plasma glucosemmol/L >13.9 >13.9 >13.9 33.3mg/dL >250 >250 >250 >600

Arterial pH 7.25 to 7.30 7.00 to <7.24 <7.00 >7.30Serum bicarbonate, mmol/L 15 to 18 10 to <15 <10 18Urine ketones Positive Positive Positive SmallSerum ketones (β-hydroxybutyrate) High High High Normal or

elevatedEffective serum osmolality, mOsm/kg† Variable Variable Variable >320Anion gap‡ >10 >12 >12 VariableAlteration in sensoria or mental obtundation Alert Alert/drowsy Stupor/coma Stupor/coma

DKA = diabetic ketoacidosis; HHS = hyperosmolar hyperglycemic state.

* Adapted from Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;321335-43. [PMID: 19564476]† Effective serum osmolality = 2 × (measured Na [mmol/L]) + (glucose [mg/dL] ÷ 18).‡ Anion gap = Na+ − (Cl− + HCO3

− [mmol/L]).

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© 2010 American College of PhysiciansITC1-9In the ClinicAnnals of Internal Medicine1 January 2010

Do all patients with DKA requirehospitalization?In some cases, patients with un-complicated mild-to-moderateDKA can be treated and dis-charged from the emergency de-partment if they are stable, able toadhere to treatment, and have goodsupport at home. Rapid-acting insulin analogs, such as lispro,glulisine, and aspart, can be usedsubcutaneously in these patients.Although patients may respond totherapy quickly, they can relapse ifthey do not monitor themselves oruse sufficient doses of insulin.

Patients with moderate-to-severeDKA should be hospitalized, oftenin the intensive care unit or in anintermediate care unit. Following ofpractice guidelines, frequent moni-toring, and continuous insulin infu-sion are associated with mortalityrates of less than 1%. Patients withan arterial pH level less than 7.25,

a bicarbonate level less than 15, ora significant precipitating illnessshould be treated in care units thatare experienced with DKA man-agement and associated diseases.Some, patients may require special-ized therapy, such as treatment fora myocardial infarction at a coro-nary care unit.

What is the role of hydration inthe management of DKA?Rehydration alone will replace thefluid deficit, lower the glucose level,and improve insulin sensitivity andrenal function. It should be startedimmediately after the diagnosis ofDKA. Serum sodium should becorrected for hyperglycemia (foreach 5.55 mmol/L [100 mg/dL] ofglucose more than 5.55 mmol/L[100 mg/dL], add 1.6 mmol tosodium value for corrected serumsodium value). Begin with normalsaline (0.9% sodium chloride), andreassess fluid-replacement hourly

Table 4. Differential Diagnosis of Diabetic Ketoacidosis Disease Characteristics Notes

Starvation ketosis Patients may have intercurrent Blood glucose can be normal, low or somewhat illness and quite ill, usually a clear elevated. Starvation ketosis does not lead to history of not eating, and possibly acidosis; bicarbonate levels usually >18 mmol/L.nausea or vomiting.

Alcoholic ketoacidosis History of excessive alcohol intake Blood glucose is key: if normal or low with in patients with long-term ketonemia and metabolic acidosis, alcoholic alcohol abuse. ketoacidosis is likely. An osmolar gap occur (differ-

ence between measured and calculated osmolality).Lactic acidosis Serum lactate is usually about Can co-occur with diabetic ketoacidosis. Measure

5 mmol/L lactate if lactic acidosis suspected or history ofmetformin use.

Salicylate intoxication Anion gap metabolic acidosis, Blood glucose level is usually not elevated and may but often with primary respiratory be low. Measure the salicylate level.alkalosis.

Methanol intoxication Ketones not significantly elevated, Blood glucose level is normal to elevated. Measure symptoms include blurry vision methanol level.and abdominal pain.

Ethylene glycol Ketones not usually increased, but Blood glucose level is variable. Calcium oxalate and intoxication anion gap and osmolar gap are hippurate crystals can be seen in the urine. Measure

typically high. ethylene glycol.Chronic renal failure Mild acidosis with slight increase History of increased serum creatinine.

in anion gap, but ketones not elevated.

Pseudoketosis Paraldehyde or isopropyl Normal pH and normal anion gap.alcohol ingestion.

Rhabdomyolysis Creatine kinase is usually very pH low, glucose level normal, ketones normal with high. Causes of rhabdomyolysis, anion gap and myoglobinuria.such as statins, trauma, or heat stroke, may be present.


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24. Kitabchi AE, MurphyMB, Spencer J, et al.Is a priming dose ofinsulin necessary ina low-dose insulinprotocol for thetreatment of diabet-ic ketoacidosis? Dia-betes Care.2008;31:2081-5.[PMID: 18694978]

25. Umpierrez GE, Cuer-vo R, Karabell A, etal. Treatment of dia-betic ketoacidosiswith subcutaneousinsulin aspart. Dia-betes Care.2004;27:1873-8.[PMID: 15277410]

© 2010 American College of Physicians ITC1-10 In the Clinic Annals of Internal Medicine 1 January 2010

(Figure). Switch to 0.45% sodiumchloride after an initial bolus if theserum sodium is high or normal.The initial rate should be 15 to 20mL/kg per hour depending on thefluid deficit. Switch to dextrose-containing fluids once the bloodsugar level is approximately 11.1mmol/L (200 mg/dL). Patientswith severe hypovolemia or shockrequire more aggressive hydration,hemodynamic monitoring, andpossibly vasopressor therapy. Assesspatients for such underlying med-ical conditions before initiating flu-id resuscitation. Renal insufficiencyand congestive heart failure put

patients at risk for complicationsfrom fluid overload. Use extra cau-tion when hydrating children, whohave higher incidence of cerebraledema associated with DKA thera-py. Children are also at risk for pul-monary edema.

How should clinicians administerinsulin and potassium during thetreatment of DKA?The approach to managing DKAwith insulin and potassium re-placement is the same regardlessof the type of diabetes. Insulin isrequired to treat the hyper-glycemia and ketosis, but can

Figure. Fluid Therapy Guidelines from the American Diabetes Association.** Adapted from Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patientswith diabetes. Diabetes Care. 2009;32 1335-43. [PMID: 19564476]† Baseline electrolytes, glucose level, pH, and blood urea nitrogen creatinine.‡ Adjust fluids if cardiac compromise.

Low serum Na

Severe Hypovolemia

High serum Na

0.45% NaCl7‡

(250–500 mL/h) dependingon hydration status

0.9% NaCl‡(250–500 mL/h) depending

on hydration status

When serum glucose level 200 mg/dL: 5% dextrose with 0.45% NaCl, 150–250 mL/h

Cardiogenic shock

0.9% NaCl (1.0 L/h) Evaluate correctedserum Na+


Start IV fluids: 1.0 L of 0.9% NaCl per hour (15–20 mL/kg per h)†

Assess hydration status

Mild dehydration

Normal serum Na

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26. Umpierrez GE, LatifK, Stoever J, et al. Ef-ficacy of subcuta-neous insulin lisproversus continuousintravenous regularinsulin for the treat-ment of patientswith diabetic ke-toacidosis. Am JMed. 2004;117(5):291-6.

© 2010 American College of PhysiciansITC1-11In the ClinicAnnals of Internal Medicine1 January 2010

result in profound hypokalemiathat can produce serious cardiacarrhythmias. Both metabolic aci-dosis and insulin deficiency causepotassium to shift from the intra-cellular to the extracellular space.Insulin therapy reverses thisprocess and moves potassium backinto the intracellular space but canseriously deplete extracellularpotassium levels. Many patientswith DKA have a total bodydeficit of potassium despite nor-mal or elevated potassium levels atbaseline. The Box explains how tomanage potassium while treatingDKA. Clinicians should checkserum electrolytes before adminis-tering insulin and should measureserum potassium at baseline, at 1hour, then every 2 hours duringinitial therapy. Insulin is not giveninitially when the potassium levelis less than 3.3 mmol/L becauseof the risk for life-threatening ar-rhythmias (Box).

After treatment with intravenousfluids has been started and thepotassium level is greater than3.3 mmol/L, an initial bolus ofregular insulin is usually given in-travenously or as a subcutaneousor intramuscular injection (Table5). As an alternative, start regularinsulin infusion at a rate of 0.14U/kg per hour without initial bo-lus (about 10 U/h in a 70-kg pa-tient) (24). Then the infusion

rate is adjusted until the glucoselevel decreases by 10% or by 2.8 to 4.2 mmol/L (50 to 75 mg/dL). When the blood glucose is less than 11.1 mmol/L(200 mg/dL), the insulin dosemay then be reduced to 0.02 to0.05 U/kg per hour. Therapyshould be monitored on the basisof changes in the anion gap andserum ketones. The insulin doseor the dextrose concentrationshould be adjusted to keep theglucose between 8.3 to 11.1mmol/L (150 to 200 mg/dL).

As an alternative to an intra-venous infusion of regular in-sulin, adults with uncomplicatedmild-to-moderate DKA can betreated with subcutaneous rapid-acting insulin analogs (for exam-ple, lispro or aspart) (25). In asmall randomized, controlled tri-al, subcutaneous insulin lisproadministered on the floor result-ed in similar outcomes but lowercosts than intravenous insulin ad-ministered in the intensive careunit (26). In DKA, correction ofhyperglycemia is faster than ke-toacidosis. It is ill-advised to re-duce intravenous insulin therapytoo quickly after normalization ofblood glucose level, because thiscan prolong the duration ofDKA. When DKA resolves, amultiple-dose insulin regimenshould be initiated.

Guidelines for Initial PotassiumReplacement from the AmericanDiabetes Association*• Serum K+ <3.3 mmol/L: No in-

sulin; give 20–30 mmol K+ per h• Serum K+ >3.3 to <5.2 mmol/L:

Give 20–30 mmol/L to keep K+

between 4–5 mmol/L• Serum K+ >5.2 mmol/L: Check K+

q 2 h but do not give K+

replacement* Adapted from Kitabchi AE,

Umpierrez GE, Miles JM, et al.Hyperglycemic crises in adult pa-tients with diabetes. DiabetesCare. 2009;32 1335-43. [PMID:19564476]

Table 5. American Diabetes Association Guidelines for Insulin Replacement*Condition IV Administration

Initial bolus Regular at 0.1 U/kg as IV bolusInfusion 0.1 U/kg per h as continuous IV infusionIf glucose level does not 0.14 U/kg as IV bolus, then continue previous IV infusion

decrease by at least 10% in first hour

Serum glucose level Reduce insulin to 0.02–0.05 U/kg per h; or give rapid-acting reaches 11.1 mmol/L insulin, 0.1 U/kg SC every 2 h, to keep glucose between (<200 mg/dL) 8.3–11.1 mmol/L (150−200 mg/dL) until metabolic control


IV = intravenous; SC = subcutaneous.

* Adapted from Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients withdiabetes. Diabetes Care. 2009;32 1335-43. [PMID: 19564476]

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27. Viallon A, Zeni F, La-fond P, et al. Does bi-carbonate therapyimprove the man-agement of severediabetic ketoacido-sis? Crit Care Med.1999;27:2690-3.[PMID: 10628611]

28. Green SM, RothrockSG, Ho JD, et al. Fail-ure of adjunctive bi-carbonate to im-prove outcome insevere pediatric dia-betic ketoacidosis.Ann Emerg Med.1998;31:41-8.[PMID: 9437340]

29. Levetan CS, PassaroMD, Jablonski KA, etal. Effect of physicianspecialty on out-comes in diabeticketoacidosis. Dia-betes Care.1999;22:1790-5.[PMID: 10546009]

30. Polonsky WH, An-derson BJ, Lohrer PA,et al. Insulin omis-sion in women withIDDM. Diabetes Care.1994;17:1178-85.[PMID: 7821139]

© 2010 American College of Physicians ITC1-12 In the Clinic Annals of Internal Medicine 1 January 2010

What are the indications forphosphate therapy andbicarbonate therapy in thetreatment of DKA?Phosphate replacement is not typi-cally needed when treating DKA,because low phosphate levels usual-ly correct when the patient resumeseating. However, for patients withcardiac disease, anemia, respiratorydepression, or profound hypophos-phatemia (<0.0555 mmol/L [<1.0 mg/dL]), 20 to 30 mmol/Lof potassium phosphate may bewarranted, with close monitoringfor hypocalcemia.

Bicarbonate therapy is more con-troversial because of potential risks,including worsening hypokalemiaand intracellular acidosis. Manystudies have failed to show im-proved clinical outcomes with bi-carbonate therapy in patients withDKA (27, 28). The ADA recom-mends bicarbonate therapy if pH isless than 6.9 (15). Administer 100mmol NaHCO3 in 400 mL of wa-ter with 20 mmol KCL at 200mL/h. Repeat every 2 hours untilthe pH is 7.0 or greater and checkserum K+ every 2 hours.

Do all cases of DKA requireconsultation with a diabetesspecialist?A diabetes specialist consultationis warranted if the DKA is severe,recurrent, or unresponsive totreatment. Outcomes of DKA aresimilar whether internists, emer-gency physicians, or specialistsmanage DKA, but the time todischarge can be shortened whena diabetologist is involved (29).Other specialists may need to beinvolved; for example, a timelynephrologist consultation is neces-sary for severe renal impairmentthat may require dialysis.

How should clinicians handlepatients with recurrent episodesof DKA?Recurrent DKA is a red flag thatputs patients at high risk for future

recurrence. Repeated admissions forDKA consume an estimated onequarter of all health care dollarsspent on adults with type 1 diabetes(8). Patients must be closely moni-tored by an experienced diabetescare team to ensure that the patientis treated with an optimal insulinregimen. Recurrent DKA is oftenassociated with nonadherence to in-sulin (30); therefore, adherence bar-riers need to be addressed, such asensuring that the medications arecovered and affordable. Patientsshould use reminders to promoteadherence to checking blood glucoseand may use multiple insulin doses.

A randomized, controlled trial of an educa-tional manual was conducted in 119 pa-tients from a multidisciplinary diabetesclinic. All the participants had a hemoglo-bin A1c level of 8.0 or greater, and 35% hadtype 1 diabetes. The manual aimed to im-prove patient understanding of how toperform and use blood glucose monitor-ing results. Over 6 months of follow-up,blood glucose monitoring increased in theintervention group (1.9 [SD, 1.3] to 2.8 [SD,1.5] times daily; P < 0.001) and hemoglo-bin A1c level decreased (−0.13 [SD, 1.28] vs.standard care (0.04 [SD, 1.10]). The inter-vention group also showed better knowl-edge about hemoglobin A1c (P = 0.04). Theauthors concluded that an educationalmanual similar to the one they developedcould serve as a useful adjunct to standarddiabetes education and support to opti-mize blood glucose monitoring andglycemic control (31).

Psychosocial and other barriers toadherence must also be addressed.For example, urine drug screeningmay be warranted, because cocaineuse is an independent risk factor forrecurrent DKA (32). The manage-ment plan must be well establishedfor when the patient begins to de-velop signs and symptoms of DKA.Health insurance and access to dia-betes care is a basic requisite for themanagement of diabetes and avoid-ance of DKA.

In nearly 400 children with recently diag-nosed type 1 diabetes, the uninsured chil-dren were 6 times more likely to presentwith DKA (odds ratio, 6.19 [95% CI, 3.04 to

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© 2010 American College of PhysiciansITC1-13In the ClinicAnnals of Internal Medicine1 January 2010

31. Moreland EC,Volkening LK, LawlorMT, et al. Use of ablood glucose moni-toring manual to en-hance monitoringadherence in adultswith diabetes: a ran-domized controlledtrial. Arch InternMed. 2006;166:689-95. [PMID: 16567610]

32. Nyenwe EA, Lo-ganathan RS, Blum S,et al. Active use ofcocaine: an inde-pendent risk factorfor recurrent diabet-ic ketoacidosis in acity hospital. EndocrPract. 2007;13:22-9.[PMID: 17360297]

33. Maniatis AK, GoehrigSH, Gao D, et al. In-creased incidenceand severity of dia-betic ketoacidosisamong uninsuredchildren with newlydiagnosed type 1 di-abetes mellitus. Pe-diatr Diabetes. 2005;6: 79-83.[PMID: 15963034]

12.60]) than were those with insurance.The uninsured children also had a 6-foldincrease in the odds of presenting withsevere DKA (pH <7.10) (odds ratio, 6.09[CI, 3.21 to 11.56]) compared with insuredchildren (33).

When can treatment withsubcutaneous insulin therapyresume?When patients can eat adequatecarbohydrates, they should resumerapid-acting insulin at meals andintermediate- or long-acting in-sulin. Intravenous insulin shouldcontinue for several hours after re-sumption of subcutaneous insulinto avoid recurrent hyperglycemiaand a possible return to ketosis.Resolution of DKA is marked by a glucose level less than 11.1mmol/L (200 mg/dL) and 2 of thefollowing: serum bicarbonate levelgreater than 15 mmol/L, venouspH greater than 7.3, and anion gapless than 12. The typical durationof DKA therapy is about 48 hours.Obese patients with type 2 dia-betes, especially minority patients,may be transitioned from insulin tooral medications after a period ofimproved diabetes control.

Patients with known diabetes canusually restart with the dose theywere using before the onset of DKA.In patients with newly diagnosed di-abetes, clinicians need to calculatethe insulin regimen. For these pa-tients, an initial insulin dose of 0.5 to0.8 U/kg per day is usually adequate

to achieve metabolic control. Themainstay regimen is human insulin(NPH and regular) usually given in2 or 3 doses per day. Frequently rec-ommended alternatives are insulinanalogs of basal (glargine or detemir)and preprandial rapid insulin analogs(aspart, lispro, glulisine). Patientswith type 2 diabetes who have anepisode of DKA do not automatical-ly require long-term insulin therapy.

When should patients who haverecovered from DKA receivefollow-up care after dischargefrom hospital?Patients, their families, and theircaregivers should receive educationabout diabetes, the early signs ofDKA, and sick-day managementwhile still in the hospital. This canprevent recurrence of DKA. Referralto a diabetes center for intensive ed-ucation may be appropriate. Afterdischarge, patients require close fol-low-up with their physician. Patientswith newly diagnosed diabetesshould visit with their physician 7 to10 days after discharge. This visit al-lows for a follow-up history andphysical examination and for assess-ment of whether dosing adjustmentsor prescription changes are neces-sary. It also allows for further patienteducation and gives patients the opportunity to address any concernswith their doctor. Subsequent moni-toring needs to be tailored to thepatient’s needs and ability to addressthe factors that precipitated theepisode of DKA.

Treatment... The therapeutic goals of treating an episode of DKA involve hydra-tion, correcting electrolyte imbalances, reducing the serum glucose level, elimi-nating ketones (both serum and urine), identifying the underlying precipitatingfactor, and managing or treating that factor. Treatment requires close monitoringin a setting in which laboratory testing can be assessed every few hours, includ-ing electrolytes, venous or arterial pH, and glucose determination. Patients mayalso need to have their phosphate levels checked periodically. Protocols can helpensure that patients have their significant metabolic and electrolyte abnormali-ties corrected at a safe, sustainable rate. Postdischarge management must focuson addressing the factors that precipitated the episode of DKA. Patient educationand adherence supports are critical to preventing further episodes.


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c linicTool Kit

in the clinic

Diabetic Ketoacidosis

PIER Modulepier.acponline.orgAccess the PIER model on diabetic ketoacidosis. PIER modules provide evidence-based, updatedinformation on current diagnosis and treatment an electronic format designed for rapid access atthe point of care.

Physician Resourceshttp://professional.diabetes.org/News_Display.aspx?TYP=9&CID=74814Abstract of new study on the use of insulin analogues and human insulin for DKAwww.ncbi.nlm.nih.gov/pubmed/17079764?dopt=AbstractPlusCitation of a clinical practice article from the New England Journal of Medicine on hyper-glycemia in the hospital setting.www.aafp.org/afp/20050501/1705.htmlFull text of a narrative review in American Family Medicine on DKA managementwww.annals.org/content/144/5/350.fullAbstract of narrative review from the Annals of Internal Medicine on ketosis-prone type 2 diabetes.http://care.diabetesjournals.org/content/27/suppl_1/s94.fullSummary of the contrasting laboratory and clinical characteristics of DKA and HHS from theAmerican Diabetes Association.

Patient Education Resourceswww.annals.org/intheclinic/toolkit-dka.htmlAccess the patient information located on the above link to download and distribute to your patients.www.diabetes.org/living-with-diabetes/complications/ketoacidosis-dka.htmlPatient information on DKA from the American Diabetes Association.

1 January 2010Annals of Internal MedicineIn the ClinicITC1-14© 2010 American College of Physicians

Practice Improvement The ADA recommends 2 options

for low-dose regular insulin in DKA.One is to give an insulin bolus doseof 0.1 U/kg, then a continuous infu-sion of 0.1 U/kg per hour. Based ona recent randomized trial (24), thesecond option is to give a continuousintravenous insulin infusion of 0.14U/kg per hour without an initial bo-lus. If serum glucose does not de-crease by at least 10% in the firsthour, give an insulin bolus of 0.14U/kg, then continue the previous in-sulin infusion until the glucosereaches 200 mg/dL. Then the regu-lar insulin infusion is reduced to 0.02to 0.05 U/kg per hour or 0.1 U/kgrapid-acting insulin given subcuta-neously every 2 hours, aiming for aglucose of 8.3 to 11.1 mmol/L (150to 200 mg/dL) until DKA resolves.

What measures do U.S.stakeholders use to evaluate thequality of DKA management?The 2010 Physician Quality Re-porting Initiative (PQRI) includes179 measures, none of which arespecifically related to the care ofpatients with DKA. However, mostpatients with DKA have a hemo-globin A1c level >9% which is ad-dressed in 1 quality measure.

What do professional organizationsrecommend regarding themanagement of DKA?In 2009, the ADA updated theirconsensus statement on DKA, whichaddresses prevention, diagnosis, andtreatment (15). The ADA definesDKA as blood glucose level >13.9mmol/L (>250 mg/dL), arterial pH<7.3, bicarbonate <15 mmol/L, andmoderate ketonuria or ketonemia.Criteria for resolution of DKA are aglucose level <11.1 mmol/L (<200mg/dL), serum bicarbonate ≥18mmol/L, and a venous pH of >7.3.

The ADA recommends fluid re-placement as the first step in DKAtreatment (Figure) (15). Frequentmonitoring of fluid input/output andclinical examination are needed, withthe goal of correcting estimated fluiddeficits within the first 24 hours. Ifthe K+ is <3.3mmol/L, give K+ at 20to 30 mmol/h but no insulin untilthe K+ is >3.3 mmol/L. If K+ is 3.3to 5.2 mmol/L, give 20 to 30 mmolK+ in each liter of fluid to maintaina normal K+. If K+ >5.2 mmol/L, noK+ supplement is given, but the levelshould be checked every 2 hours. Bi-carbonate therapy is limited to pa-tients with a pH <6.9 who shouldreceive 100 mmol of bicarbonate in400 mL water with 20 mmol KClover 2 hours until pH >7.

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In the ClinicAnnals of Internal Medicine







What is diabetic ketoacidosis?• Insulin helps the sugar in your bloodstream go into

cells, where it is used for energy.

• Diabetic ketoacidosis (DKA) happens when your bloodsugar (glucose) goes up too high because you are lowon insulin. A high blood sugar can make you pass a lotof urine, which leads to dehydration.

• In DKA, the body burns fat, which increases a toxicacid (called ketones) in the blood.

• DKA happens mostly in children or adults with type 1 di-abetes, but people (mostly adults) with type 2 diabetes orwith diabetes during pregnancy can also get DKA.

• DKA is usually brought on by an illness, such as pneu-monia, or by missing doses of diabetes medication.

• DKA is sometimes the first sign of having diabetes butcan be prevented if you can recognize the signs ofgetting diabetes or DKA.

How does a person know that theymight have DKA?• The clues to getting DKA are feeling thirsty all the

time, urinating a lot, and feeling very tired or sleepy.

• Blood sugars over 250 mg/dL can be a sign of DKA aswell as finding an acid (ketones) on a home blood orurine test.

How is DKA treated?• DKA is successfully treated more than 95% of the

time, but if untreated, can lead to coma and evendeath. People with DKA are usually hospitalized.

• Treatment is giving you fluids by vein, giving medica-tion to lower your blood sugar, and correcting prob-lems with the salt and potassium in your body.

Is DKA preventable?• Your doctor should make a plan for when you are sick

(called a Sick Day Plan) to help keep you from getting DKA.

• On sick days, you make frequent blood sugar checksand take extra insulin depending on the sugar level aswell as do home tests of urine or blood ketones. Youdrink extra fluid and eat specific foods.

• Call your doctor if your blood sugar stays over 240mg/dL even though you have been following your sickday plan.

For More Information

Web Sites With Good Information About DKAwww.diabetes.org/type-1-diabetes/ketoacidosis.jspAmerican Diabetes Association

http://diabetes.niddk.nih.gov/dm/pubs/type1and2/specialtimes.htm#sickNational Diabetes Information Clearinghouse

www.aafp.org/afp/20050501/1721ph.htmlAmerican Academy of Family Physicians

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A 43-year-old alcoholic man with type 1diabetes mellitus for 21 years is admittedfrom the emergency department forvomiting and diabetic ketoacidosis ap-parently caused by missing 2 days of insulin treatment. His initial metabolicvalues included a pH of 7.02, a bloodcarbon dioxide level of 8 mmol/L, aserum potassium level of 5.6 mmol/L,large ketones, and a plasma glucose levelof 22.9 mmol/L (412 mg/dL). After sever-al hours of treatment with intravenousfluids, insulin, and potassium, the glu-cose level decreases to 7.2 mmol/L (130mg/dL). Intravenous therapy is changedto a subcutaneous twice-daily intermedi-ate-acting insulin plus a sliding-scaleshort-acting insulin regimen. After 8hours, the patient is again vomiting. Hismetabolic values are a pH of 7.09, largeketones, a blood carbon dioxide level of12 mmol/L, a serum potassium level of5.2 mmol/L, and a serum glucose level of9/7 mmol/L (175 mg/dL).

Which of the following is not a reasonfor the persistent acidosis?

A. Alcohol withdrawal syndromeB. Volume expansion acidosisC. Premature discontinuation of

intravenous insulin administrationD. Failure to administer sodium

bicarbonateE. Lack of absorption of

subcutaneous insulin

A 26-year-old woman with type 1 dia-betes mellitus presents to the emergencydepartment because of abdominal painfor the past 24 hours. Her temperature is38°C (101°F).

Laboratory studies: blood urea nitrogen,7.14 mmol/L (20 mg/dL); serum creati-nine, 106.1 µmol/L (1.2 mg/dL); serumsodium, 133 mmol/L; serum potassium,3.9 mmol/L; serum chloride, 97 mmol/L;serum bicarbonate, 10 mmol/L; serum

glucose, 25.0 mmol/L (450 mg/dL); arte-rial blood gases: pH, 7.2, PCO2, 23 mmHg; blood cultures were negative; whole-blood lactate, 0.6 mmol/L.

What condition best explains the pa-tient’s acid–base status?

A. Diabetic ketoacidosis aloneB. Diabetic ketoacidosis complicated

by a proximal renal tubularacidosis

C. Diabetic ketoacidosis complicatedby sepsis

D. Diabetic ketoacidosis complicatedby respiratory acidosis

An 89-year-old woman is evaluated in anursing home. She has had diabetes formore than 15 years; she was treatedwith a sulfonylurea for 1 year, but sub-sequently required insulin therapy. Shehas recently been experiencing labilecontrol, with blood glucose levels fluc-tuating widely between 2.78 mmol/L (50 mg/dL) and more than 16.65 mmol/L(300 mg/dL). She takes 70/30 NPH/regu-lar insulin, 22 U in the morning and 18U at night. During a recent episode ofgastroenteritis, her morning insulin waswithheld because of concern that shewould consume few calories that day. At4 p.m. that day, her glucose level was28.47 mmol/L (513 mg/dL). Her medicalhistory is notable for stroke, coronaryartery disease, and colon cancer. Exami-nation shows a thin woman (BMI, 21mg/kg of body weight) who looks herstated age. Dipstick urinalysis showsglucose and ketones.

Which of the following is the appropriatecategorization of this patient’s diabetes?

A. Type 1 diabetes mellitusB. Type 2 diabetes mellitusC. Secondary diabetes D. Latent autoimmune diabetes of


A 20-year-old man with history of type 1diabetes treated with human insulin70/30 twice a day before meals presentsto the emergency department with nau-sea, vomiting, and a few episodes of wa-tery diarrhea of about 6 hours duration.He stopped his insulin injection becausehe could not tolerate any food. Heseemed conscious, alert, and afebrile butwas tachypneic. Initial laboratory studiesshowed serum glucose level, 33.3 mmol/L(600 mg/dL); creatinine level, 106.08μmol/L (1.2 mg/dL); sodium, 130 mmol/L;potassium, 3.1 mmol/L; chloride, 95mmol/L; bicarbonate, 12; anion gap, 28;and pH, 7.01.

Which of the following is the best initialtreatment?

A. Immediate volume repletion withintravenous normal saline

B. Correction of hyperglycemia andketosis with low-dose infusion ofregular insulin

C. Concurrent administration ofinsulin and normal saline infusion

D. Administration of normal salinewith 40 mmol/L of potassiumadded to the infusion

E. Concurrent infusion of both low-dose insulin and potassium




Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP). Go to www.annals.org/intheclinic/ to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.

CME Questions

1 January 2010Annals of Internal MedicineIn the ClinicITC1-16© 2010 American College of Physicians