hyperglycemic crises in pa

8/12/2019 Hyperglycemic Crises in Pa

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Hyperglycemic Crises in Patients

With Diabetes Mellitus

dr. Tjatur Winarsanto SpPD


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Introduction

Ketoacidosisand hyperosmolar hyperglycemiaare the

two most serious acute metabolic complications ofdiabetes, even if managed properly.

They can occur in both type 1 and type 2 diabetes.

Mortality ratein DKA is


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PATHOGENESIS(1)

Pathogenesis of DKA is better understood than that of HHS,

the basic underlying mechanism for both disorders is areduction in net effective action of circulating insulincoupled

with a concomitant elevation of counterregulatory hormones,

such as glucagon, catecholamines, cortisol, and growth

hormone. These hormonal alterations in DKA and HHS lead to

increased hepatic and renal glucose productionand impaired

glucose utilization inperipheral tissues, which result in

hyperglycemiaand parallel changes in osmolality of theextracellular space.


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PATHOGENESIS(2)

The combination of insulin deficiency and increased

counterregulatory hormones in DKAalso leads to releaseof free fatty acidsinto the circulation from adipose tissue(lipolysis) and to unrestrained hepatic fatty acid oxidationto ketone bodies(-hydroxybutyrate [-OHB] andacetoacetate), with resulting ketonemiaand metabolicacidosis.

HHS may be due to plasma insulin concentrationinadequate to facilitate glucose utilization by insulin-

sensitive tissues but adequate (as determined by residual peptide) toprevent lipolysis and subsequent ketogenesis,although the evidence for this is weak.


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PATHOGENESIS(3)

Both DKA and HHS are associated with

glycosuria, leading to osmotic diuresiswith loss

of water, sodium, potassium, and other

electrolytes.

The laboratory and clinical characteristics ofDKA and HHS are summarized in Tables 1 and 2.

As can be seen, DKA and HHS differ in

magnitude of dehydrationand degree of ketosis

(and acidosis).


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PRECIPITATING FACTORS (1)

The most common in development of DKA or HHS isinfection. Others include CVA, alcohol abuse,

pancreatitis, MI, trauma, and drugs.

Newly onset type 1 diabetes or discontinuation orinadequate insulin in established type 1 diabetescommonly leads to DKA.

Elderly individualswith newly onset diabetes(particularly residents of chronic care facilities) orindividuals with known diabetes who become

hyperglycemic and are unaware of it or are unable to tafluidswhen necessary are at risk forHHS.


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PRECIPITATING FACTORS (2)

Drugs that affect carbohydrate metabolism, such as

corticosteroids, thiazides, and sympathomimetic agents(e.g., dobutamine and terbutaline), may precipitate thedevelopment of HHS or DKA.

In young type 1 diabetes,psychologicalproblems

complicated by eating disordersmay be a contributingfactor in 20%of recurrent ketoacidosis.

Factors that may lead to insulin omissionin youngerpts include fear of weight gain with improved

metabolic control, fear of hypoglycemia, rebellion fromauthority, and stress of chronic disease.


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DIAGNOSIS-History and physical examination (1)

The process of HHS usually evolves over several days

to weeks, whereas the evolution of acute DKA

episode in type 1 diabetes or even in type 2 diabetes

tends to be much shorter.

Although the symptoms of poorly controlled diabetesmay be present for several days, the metabolic

alterations typical of ketoacidosisusually evolve

within a short time frame (typically


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Occasionally, the entire symptomatic presentation may

evolve or develop more acutely, and the pt maypresent in DKA with no prior clues or symptoms.

For both DKA and HHS, the classical clinical picture

includes polyuria, polydipsia, polyphagia, weight loss,

vomiting, abdominal pain (only in DKA), dehydration,

weakness, clouding of sensoria, and finally coma.


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Physical findingsmay include poor skin turgor, Kussma

respirations (in DKA), tachycardia, hypotension,alteration in mental status, shock, and ultimately coma

(more frequent in HHS).

Up to 25%of DKA haveemesis, which may be coffee-

ground in appearance and guaiac positive. Endoscopy h

related this finding to presence of hemorrhagic gastritis

Mental statuscan vary from full alertness to profound

lethargy or coma, with the latter more frequent in HHS.


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Althoughinfectionis a common precipitating factor for

both DKA and HHS, pts can be normothermic or even

hypothermic primarily because ofperipheral vasodilation

Hypothermia is a poor prognostic sign.

Caution when abdominal painon presentation, could be

either a result or a cause (particularly in younger) of DKAFurther evaluation is necessary if this complaint does not

resolve with resolution of dehydration and metabolic

acidosis.


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DIAGNOSIS-Laboratory findings (1)

Initial laboratory evaluation of suspected DKA or HHS

should include determination of plasma glucose, BUN/Crserum ketones, electrolytes (with calculated anion gap),

osmolality, urinalysis, urine ketones by dipstick, as well a

initial ABG, CBC/DC, and ECG.

Bacterial culturesof urine, blood, and throat, etc., should

obtained and appropriate antibiotics given if infection is

suspected.


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HbA1cmay be useful in determining whether this acute

episode is the culmination of an evolutionary process

in previously undiagnosed or poorly controlled

diabetes or a truly acute episode in an otherwise well-

controlled p

t. CXRshould also be obtained if indicated. Tables 1 and

2depict typical laboratory findings in DKA or HHS.


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The majority of hyperglycemic emergencies present with

leukocytosisproportional toblood ketone bodyconcentration.

Serum sodiumis usually decreasedbecause of the osmotiflux of water from intracellular to extracellular space in th

presence of hyperglycemia, and less commonly, serumsodium may be falsely lowered by severehypertriglyceridemia.

Serumpotassiummay be elevatedbecause of an

extracellular shift of potassium caused by insulindeficiency, hypertonicity, and acidemia.


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Pts with low-normal or low serum potassium onadmission have severe total-body potassium deficiency anrequire very careful cardiac monitoring and more vigorou

potassium replacement, because treatment lowerspotassium further and can provoke cardiac dysrhythmia.

The occurrence of stupor or coma in diabetic p

ts in theabsence of definitive elevation of effective osmolality(>320 mOsm/kg) demands immediate consideration ofother causes of mental status change.

Effective osmolalitymay be calculated by the followingformula: 2[measured Na (mEq/l)]glucose (mg/dl)/18.


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Amylaselevels are elevated in the majority of DKA,

but this may be due to nonpancreatic sources, such astheparotid gland.

Serum lipase determination may be beneficial in the

D/D of pancreatitis. However, lipase could also beelevated in DKA.

Abdominal pain and elevation of serum amylase and

liver enzymes are noted more commonly in DKA than

in HHS.

Diff i l di i (1)


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Differential diagnosis (1)

Not all pts with ketoacidosis have DKA.

Starvation ketosis and alcoholic ketoacidosis (AKA)aredistinguished by clinical history and by plasma glucose thatrange from mildly elevated (rarely >250 mg/dl) tohypoglycemia. Although AKA can result in profound acidosis,the serum bicarbonate in starvation ketosis is usually not lower

than 18 mEq/l. DKA must also be distinguished from other causes of high AG

metabolic acidosis, including lactic acidosis, ingestion of drugssuch as salicylate, methanol, ethylene glycol, and paraldehyde,and CRF (which is more typically hyperchloremic acidosisrather than high AG acidosis).


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Differential diagnosis (2)

Clinical historyof previous drug intoxications or metformin

use should be sought. Measurement of blood lactate, serumsalicylate, and blood methanol level can be helpful in thesesituations.

Ethylene glycol (antifreeze)is suggested by presence ofcalcium oxalate and hippurate crystals in the urine.

Paraldehyde ingestionis indicated by its characteristic strongodor on the breath.

Because these intoxicants are low molecular weight organiccompounds, they can produce an osmolar gap in addition to

AG acidosis


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TREATMENT

Successful treatment of DKA and HHS requirescorrection of dehydration, hyperglycemia, and

electrolyte imbalances; identification of comorbid

precipitating events; and above all, frequent pt

monitoring. Guidelines for management of pts with DKA and

HHS follow and are summarized in Figs. 1, 2, and 3.

Table 3includes a summary of major recommendationsand evidence gradings.


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Fluid therapy- Adult patients (1)

Initial fluid therapy is directed toward expansion of theintravascular and extravascular volume and restoration o

renal perfusion.

In the absence of cardiac compromise, isotonic saline

(0.9% NaCl)is infused at a rate of 1520ml/kgw/h orgreater during 1st hour (~11.5 liters in average adult).

Subsequent choice for fluid replacement depends on sta

of hydration, serum electrolyte levels, and urinary outpu


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Fluid therapy- Adult patients (2)

In general, 0.45% NaClinfused at 414 ml/kg/h isappropriate if the corrected serum sodium is normal or

elevated.

0.9% NaClat a similar rate is appropriate if corrected

serum sodium is low. Once renal function is assured, the infusion should

include 2030mEq/l potassium (2/3 KCl and 1/3

KPO4) until pt is stable and can tolerate oral

supplementation.


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Fluid therapy- Adult patients (3) Successful progress with fluid replacement is judged by

hemodynamic monitoring (improvement in BP),measurement of fluid input/output, and clinical

examination.

Fluid replacement should correct estimated deficits

within first 24 h. The induced change in serumosmolality should not exceed 3 mOsm/kg/H2O/h.

In pts with renal or cardiac compromise, monitoring

of serum osmolality and frequent assessment of cardiacrenal, and mental status must be performed during fluid

resuscitation to avoid iatrogenic fluid overload.

Fluid therapy- Pediatric patients (


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Fluid therapy Pediatric patients (


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Insulin therapy (1)

Unless the episode of DKA is mild (Table 1), RI by

continuous intravenous infusion is treatment of choice. Once hypokalemia (K+


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Insulin therapy (2)

If plasma glucose does not fall by 50 mg/dlfrom initiavalue in 1st hour, check hydration status; if acceptable

insulin infusion may be doubled every hour until asteady glucose decline between 50 and 75mg/h.

When plasma glucose reaches 250 mg/dl in DKAor300 mg/dl in HHS, it may be possible to decrease

insulin infusion rate to 0.050.1U/kg/h (36 U/h), anddextrose (510%)may be added to IV fluids.

Thereafter, insulin administration rate or concentrationof dextrose may need to be adjusted to maintain theabove glucose values until acidosis in DKA or mentalobtundation and hyperosmolarity in HHS are resolved.

Insulin therapy (3)


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Insulin therapy (3)

Ketonemiatypically takes longer to clear thanhyperglycemia.

The nitroprusside methodonly measures acetoaceticacid and acetone. However, -OHB, the strongest andmost prevalent acid in DKA, is not measured by thenitroprusside method.

During therapy, -OHB is converted to acetoacetic acidwhich may lead the clinician to believe that ketosis hasworsened. Therefore, assessments of urinary or serumketone levels by nitroprusside method should notbeused as an indicator of response to therapy.

Insulin therapy (4)


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Insulin therapy (4)

During therapy for DKA or HHS, blood should be

drawn every 24 hfor determination of serum

electrolytes, glucose, BUN, Cr, osmolality, and

venous pH(for DKA).

Generally, repeat ABGs are unnecessary; venous pH(which is usually 0.03 Ulower than arterial pH) and

anion gap can be followed to monitor resolution of

acidosis.

Insulin therapy (5)


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Insulin therapy (5)

With mild DKA, RI given subcutaneously or

intramuscularly every hour is as effective asintravenous administration in lowering bloodglucose and ketone bodies.

Mild DKA should first receive a "priming" dose of

RI of 0.40.6 U/kgw, half as an intravenous bolusand half as a subcutaneous or intramuscularinjection.

Thereafter, 0.1U/kg/h of RI should be given

subcutaneously or intramuscularly.

Insulin therapy (6)


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Insulin therapy (6)

After resolution of DKA (glucose 18 mEq/l, venous pH >7.3, anion gap


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Potassium (1)

Despite total-body potassium depletion, mild to

moderate hyperkalemiais not uncommon in pts withhyperglycemic crises. Insulin therapy, correction of

acidosis, and volume expansion decrease serum

potassium concentration.

To prevent hypokalemia, potassium replacement is

initiated after serum levels fall below 5.5 mEq/l,

assuming the presence of adequate urine output.

Potassium (2)


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( )

Generally, 2030 mEqpotassium (2/3 KCl and 1/3

KPO4) in each liter of infusion fluid is sufficient to

maintain a serum potassium concentration within the

normal range of 45 mEq/l.

Rarely, DKA pts may present with significant

hypokalemia. In such cases, potassium replacementshould begin with fluid therapy, and insulin treatment

should be delayed until potassium concentration is

restored to >3.3 mEq/lto avoid arrhythmias or cardiac

arrest and respiratory muscle weakness.

Bicarbonate (1)


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( ) Bicarbonate use in DKA remains controversial. At a

pH >7.0, reestablishing insulin activity blocks

lipolysis and resolves ketoacidosis without any addedbicarbonate. Prospective randomized studies have

failed to show either beneficial or deleterious changes

in morbidity or mortality with bicarbonate therapy in

DKA with pH between 6.9 and 7.1.

No prospective randomized studies concerning the use

of bicarbonate in DKA with pH values


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Bicarbonate (2)

Given that severe acidosis may lead to a myriad of

adverse vascular effects, it seems prudent that for adultpts with apH 7.0.

Bicarbonate (3)


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Bicarbonate (3)

In the pediatric pt, there are no randomized studies in

pts with pH 7.0.

Bicarbonate (4)


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( )

Insulin, as well as bicarbonate therapy, lowers serum

potassium; therefore, potassium supplementation shouldbe maintained in intravenous fluid as described above a

carefully monitored. (See Fig. 1for guidelines.)

Thereafter, venous pHshould be assessed every 2 h unt

the pH rises to 7.0, and treatment should be repeatedevery 2 h if necessary. (See Kitabchi et al. for a comple

description of studies done to date on the use of

bicarbonate in DKA.)

Phosphate (1)


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p ( )

Despite whole-body phosphate deficits in DKA that

average ~1.0 mmol/kgw, serum phosphate is oftennormal or increased at presentation.

Phosphate concentration decreases with insulin therapy

Prospective randomized studies have failed to show

any beneficial effect of phosphate replacement on theclinical outcome in DKA, and overzealous phosphate

therapycan cause severe hypocalcemiawith no

evidence of tetany

Phosphate (2)


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p ( )

To avoid cardiac and skeletal muscle weakness and

respiratory depression due to hypophosphatemia, carefuphosphate replacement may sometimes be indicated incardiac dysfunction, anemia, or respiratory depressionand those serum phosphate


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Hypoglycemia and hypokalemia

Hyperglycemia

Hyperchloremic metabolic acidosis

Cerebral edema

Adult respiratory distress syndrome

COMPLICATIONS (1)


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The most common complications of DKA and HHS

include hypoglycemiadue to overzealous treatmentwith insulin, hypokalemia due to insulin

administration and treatment of acidosis with

bicarbonate, and hyperglycemiasecondary to

interruption/discontinuance of intravenous insulintherapy after recovery without subsequent coverage

with subcutaneous insulin.

COMPLICATIONS (2)


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( )

Commonly, pts recovering from DKA develop

hyperchloremiacaused by the use of excessive saline ffluid and electrolyte replacement and transient non

Anion gap metabolic acidosisas chloride from

intravenous fluids replaces ketoanions lost as sodium

and potassium salts during osmotic diuresis. These biochemical abnormalities are transient and are

not clinically significant except in cases of acute renal

failure or extreme oliguria.

COMPLICATIONS (3)


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( )

Cerebral edemais a rare but frequently fatal complication

of DKA, occurring in 0.71.0%of children with DKA. Itmost common in children with newly diagnosed diabetes

but has been reported in children with known diabetes an

in young people in their twenties.

Fatal cases of cerebral edema have also been reported witHHS. Clinically, cerebral edema is characterized by a

deterioration in the level of consciousness, with lethargy,

decrease in arousal, and headache.

COMPLICATIONS (4)


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( )

Neurological deterioration may be rapid, with seizures,

incontinence, pupillary changes, bradycardia, andrespiratory arrest.

These symptoms progress asbrain stem herniation

occurs, may be so rapid that papilledema is not found.

Once clinical symptoms other than lethargy and

behavioral changes occur, mortality is high (>70%),

with only 714%pts recovering without permanent

morbidity.

COMPLICATIONS (5)


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Although mechanism of cerebral edema is not known, it

likely results from osmotically driven movement of waterinto CNS when plasma osmolality declines too rapidly w

treatment of DKA or HHS.

Lack of information on morbidity associated with cerebra

edema in adult pts; therefore, any recommendations for

adult pts are clinical judgments, rather than scientific

evidence.

COMPLICATIONS (6)


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Prevention measures that might decrease risk of cerebral

edema in high-risk pts are gradual replacement of

sodium and water deficits in pts who are hyperosmolar(maximal reduction in osmolality3mOsm/kg/H2O/h) and

the addition of dextrose to hydrating solution once blood

glucose reaches 250 mg/dl.

In HHS, a glucose level of 250300mg/dl should be

maintained until hyperosmolarity and mental status

improves and pt becomes clinically stable.

COMPLICATIONS (7)


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Hypoxemiaand, rarely, noncardiogenic pulmonary edem

may complicate the treatment of DKA. Hypoxemia is

attributed to a reduction in colloid osmotic pressure that

results in increased lung water content and decreased lung

compliance.

DKAwho have a widenedalveolo-arteriolar oxygengradient noted on initial blood gas measurement or with

pulmonaryraleson physical examination appear to be at

higher risk for the development ofpulmonary edema.

Clues To Complications In DKA (1)


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ComplicationAcute gastric dilatation or

erosive gastritis

Cerebral edema

Hyperkalemia

Hypoglycemia

Hypokalemia

Infection

CluesVomiting of blood or coffee-grou

material

Obtundation or coma with or witho

neurologic signs, especially if

occurring after initial improvemen

Cardiac arrest

Adrenergic or neurologic signs;

rebound ketosis

Cardiac arrhythmias

Fever

SOURCE: Adapted from DW Foster, in Current Therapy in Endocrinology and Metabolism 1985

1986, DT Krieger, CW Bardin (eds), Toronto/Philadelphia, Decker, 1985.

Clues To Complications In DKA (2)


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Insulin resistance

Myocardial infarction

Mucormycosis

Respiratory distress syndrome

Vascular thrombosis

Unremitting acidosis after 46 h of

adequate therapy

Chest pain, appearance of heartfailure; appearance of hypotension

despite adequate fluids

Facial pain, bloody nasal discharge,

blackened nasal turbinates, blurred

vision, proptosis

Hypoxemia in the absence of

pneumonia, chronic pulmonary

disease, or heart failure

Strokelike picture or signs of

ischemia in nonnervous tissue

PREVENTION(1)


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Many DKA and HHS can be prevented by better

access to medical care, proper education, and

effective communication with a health care provider

during an intercurrent illness.

The observation that stopping insulinfor economic

reasons is a common precipitant of DKA in urbanAfrican-Americans is disturbing and underscores the

need for our health care delivery systems to address

this problem, which is costly and clinically serious.

PREVENTION(2)


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Sick-day managementshould be reviewed periodically

with all pts, include specific information on(1)when to contact the health care provider.

(2)blood glucose goals and use of supplemental short-

acting insulin during illness.(3)means to suppress fever and treat infection.

(4)initiation of an easily digestible liquid diet containing

carbohydrates and salt.

PREVENTION(3)


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Most importantly, pt should be advised never to

discontinue insulin and to seek professional adviceearly in the course of illness. Successful sick-daymanagement depends on involvement by pt and/orfamily member.

The p

t/family member must be able to accuratelymeasure and record blood glucose, urine ketonedetermination when blood glucose is >300 mg/dl,insulin administered, BT, RR , PR, and BW and must

be able to communicate this to a health careprofessional.

PREVENTION(4)


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Adequate supervision and helpfrom staff or family may

prevent many admissions for HHS due to dehydration

among elderly individuals who are unable to recognize or

treat this evolving condition.

Better educationof care givers as well as pts regarding

signs and symptoms of new-onset diabetes; conditions,procedures, and medications that worsen diabetes control

and use of glucose monitoring could potentially decrease

incidence and severity of HHS.

PREVENTION(5)


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Annual incidence rate for DKA from population-based studies

ranges from 4.6 to 8 episodesper 1,000 pts with diabetes, with

trend toward an increased hospitalization rate in the past twodecades. Incidence of HHS accounts for


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Because repeated admissions for DKAare estimated todrain approximately one out of every two health caredollars spent on adult type 1 diabetes, resources need to bredirected toward prevention by funding better access tocare and educational programs tailored to individual needincluding ethnic and personal health care beliefs.

In addition, resources should be directed toward educatioof primary care providers and school personnel to identifysigns and symptomsof uncontrolled diabetes and newlyonset diabetes can be diagnosed early. This has been showto decrease incidence of DKA at the onset of diabetes.

hyperglycemic crises in pa

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