NIHMS: DKA Flashcards
what does HHS stand for?
hyperglycemic hyperosmolar state
what does DKA stand for?
diabetic ketoacidosis
in what kind of patients does HHS and DKA occur in?
both DKA and HHS can occur in patients type I and II diabetes
DKA is more common in young people with T1D
HHS is more common in adult & elderly patients with T2D
is DKA or HHS more common?
DKA frequency has increased 30% in the last decade with more than 140,000 hospital admissions
HHS accounts for <1% of all diabetes-related admissions
what are both DKA and HHS characterized by?
insulinopenia and severe hyperglycemia
what is the general treatment for both DKA and HHS?
- agressive rehydration
- insulin therapy
- electrolyte replacement
- discovery/treatment of underlying precipitating events
what’s a hallmark of diabetic comas?
Kussmaul rapid breathing
what are the two types of diabetic coma?
- Kaussmaul breathing and positive ketones
- unusal, in older well-nourished individuals - severe hyperglycemia and glycosuria but without Kaussmaul breathing, fruity breath odor or positive urine acetone test
what are the typical symptoms of diabetic coma?
- polydipsia (thirst)
- polyuria (lots of dilute urine)
- glucose in urine
- declined mental status
- high acetoacetic acid and BHB acid in urine
- preceding deep and frequent respiration and severe dyspnea = Kussmaul breathing
when was the first diabetic coma reported?
1828
august W. von stosch
when was Kaussmaul breathing discovered?
1874
when was insulin discovered?
1921
what was the DKA mortality rate before insulin?
90%
which individuals are at higher risk for DKA?
- high HbA1C
- longer diabetes duration
- adolescents (18-25 years)
- girls
- T1D
- ethnic minorities
does HHS or DKA have a higher mortality rate?
HHS (5-16% which is 10x DKA %)
HHS occurs most commonly in older patients with T2D with an intercurrent illness like infection, surgery or ischemic events
what is usually the cause of mortality in DKA and HHS patients?
usually not from metabolic complication of hyperglycemia or metabolic acidosis
usually due to severe dehydration and advanced age
what is the leading cause of death for children and young adults with T1D?
DKA
accounts for 50% of all deaths in diabetic patients <24 yrs
what is the DKA mortality rate?
<1% in the US
it’s higher with elderly patients with life-threatening illnesses
> 10% in countries with limited acute care resources
what increases DKA mortality?
recurrent DKA admissions vs. 1 DKA admission
23.4% vs 5.2%
what does the outcome of patients HHS depend on?
severity of dehydration, presence of co-morbidities and advanced age
hospitalization and multiple HHS episodes increase mortality risk
how much is spend on treatment of hyperglycemic crises?
$2.4 billion
it’s a severe economic burden
what are the most common precipitating causes of DKA in USA?
41-60% poor adherence to treatment = #1 cause! aka discontinuing insulin
17-24% newly diagnosed diabetes mellitus (insulin deficiency or resistance) - people find out they have diabetes because they go into DKA
14-16% infection
10-18% other (malfunctioning insulin pump)
3-4% unknown
*in other countries, infection is usually the highest cause
what is a psychological risk factor in DKA?
depression and eating disorders
reported in up to 20% of recurrent episodes of DKA in young patients
what are common causes of HHS?
- UTIs
- pneumonia
- acute cardiovascular events
any illness that causes dehydration or reduced insulin activity can lead to HHS
poor aberrance to medical treatment and new diabetes onset are less common causes of HHS than DKA
which medications can cause DKA and HHS to develop?
SGLT2 inhibitors
- glucocorticoids
- B-blockers
- thiazide diuretics
- certain chemotherapeutic agents
- atypical antipsychotics (olanzapine and resperidone)
SGLT2 inhibitors cause DKA and ketosis in T1D and T2D (mostly T1D)
what is euglycemic DKA?
only mild to moderate elevations in blood glucose
an atypical presentation of DKA that can lead to delayed recognition and treatment
what are potential mechanisms that would cause SGLT2 inhibitors to lead to ketosis and DKA?
SGLT2 inhibitors lower plasma glucose by inhibiting proximal tubular reabsorption of glucose in the kidney
- higher glucagon levels
- reduction of daily insulin requirement = decreased suppression of lipolysis and ketogenesis
- decreased urinary excretion of ketone
what are the two most pathophysiological mechanisms for DKA and HHS?
- significant insulin deficiency
- increased concentration of counter-regulatory hormones like glucagon, catecholamines, cortisol and growth hormone
these lead to increased hepatic glucose production due to increased hepatic gluconeogenesis and glycogenolysis as well as reduced glucose utilization in tissues
low insulin leads to activation of hormone-sensitive lipase which accelerates triglyceride breakdown to FFA - in the liver, FFA are oxidized to ketone bodies due to increased glucagon/insulin ratio
what does the increased glucagon/insulin ratio in DKA and HHS cause?
lowers the activity of malonyl CoA which modulates movement of FFA into hepatic mitochondria where FA oxidation takes place
what leads to metabolic acidosis in DKA?
increased production of ketone bodies (acetoacetate and BHB which are strong acids) leads to reduction of bicarbonate and metabolic acidosis
do HHS patients have high ketone bodies? why?
no
due to:
- higher levels of insulin (most important)
- lower levels of counter-regulatory hormones and FFA
- inhibition of lipolysis by the hyperosmolar state
hyperglycemia and ketoacidosis result in what immune response?
- an inflammatory state characterized by an elevation of pro-inflammatory cytokines
- increased oxidative stress markers
increased inflammatory response, oxidative stress, and ROS production can lead to capillary perturbation and cellular damage of lipids, membranes, proteins and DNA
what are some pro-inflammatory cytokines? when are they produced? what do they do?
during hyperglycemia
macrophages produce pro-inflammatory cytokines:
- tumor necrosis factor-alpha (TNFα)
- interleukin (IL)-6
- IL-1β
- C-reactive protein
lead to impaired insulin secretion and reduced insulin sensitivity
what do increased FFA levels cause?
increases insulin resistance
impaired NO production
what are the signs and symptoms of DKA?
- fatigue
- GI complaints: nausea, vomiting, ab pain
- Kussmaul respiration
- fruity breath (acetone)
- hyperglycemia symptoms: polyuria, polydipsia, weight loss
- dehydration: dry mucous membranes, poor skin turgor, tachycardia, hypotension
what’s the triad of things that happens with DKA?
hyperglycemia
ketonemia
metabolic acidosis
DKA classifies by degree of acidosis, decrease in bicarbonate and altered sensorium
what are the characteristics of mild DKA?
> 250 blood glucose
bicarbonate between 10-18
pH < 7.3
high ketones in urine or blood
increased anion gap metabolic acidosis >12
in what patients does euglycemic DKA happen?
it’s DKA but blood sugar is <250
- pregnancy
- prolonged starvation
- alcohol intake
- SGLT2 inhibitor use
what test is used to diagnose DKA?
high anion gap metabolic acidosis >12
nitroprusside test in urine or serum which estimates acetoacetate and acetone levels - can underestimate severity of ketoacidosis because it doesn’t recognize BHB
what are the symptoms of HHS?
plasma glucose > 600 mg/dl
efective osmolality > 320 mOsm/kg
absence of ketoacidosis
pH > 7.3
bicarbonate > 18
increased anion gap metabolic acidosis as the result of concomitant ketoacidosis and/or increase in serum lactate levels or renal failure
what are the leukocyte counts for a patient in DKA?
significant leukocytosis = WBC count in 10-15,000 range
attributed to stress, dehydration
what are sodium serum levels for a DKA patient?
low serum Na because of the osmotic flux of water from the intracellular to extracellular space in the presence of hyperglycemic
increase in serum Na in the presence of severe hypoglycemia indicates a profound degree of dehydration and water loss
what are potassium serum levels for a DKA patient?
serum K+ levels are usually elevated in DKA and HHS
happens because of a shift of K from the intracellular to the extracellular space due to insulin deficiency and hypertonicity and academia in DKA
during insulin treatment and fluid administration, K+ levels decrease due to a shift back to intracellular space which can result in hypokalemia
what are serum phosphate levels in DKA patients?
elevated serum levels
phosphate shifts from intracellular to extracellular space due to insulin deficiency, hypertonicity and catabolic state
dehydration can also increase total serum protein, albumin, amylase and creatinine phosphokinase concentrations
what is starvation ketosis?
patients rarely have serum bicarbonate concentration less than 18 because of the slow onset of ketosis that allows increased ketone clearance and enhanced kidney ability to excrete ammonia to compensate for the increased acid production
how do you treat hyperglycemic crisis?
fix:
- dehydration
- hyperglycemia
- hyperosmolality
- electrolyte imbalance
- increased ketonemia
monitor fluid administration, insulin dosage, urine output, lab measurement of glucose/electrolytes/venous pH/bicarbonate/anion gap every 2-4 hours
where in the hospital do DKA patients get treated?
ED or step-down units
ICU not necessary
where in the hospital do HHS patients get treated?
ICU
because they have altered mental status and significant higher mortality rates than DKA
how does fluid therapy help with hyperglycemic emergencies?
IV fluids:
- expand intravascular volume
- restore renal perfusion
- reduce insulin resistance by decreasing circulation counter-regulatory hormone levels
isotonic saline @ 500-1000 mL/hour initially
200 mL/hour after volume depletion is corrected
once glucose is 200, fluids should contain dextrose to allow continued insulin administration until ketonemia is correctected while avoiding hypoglycemia
how does potassium therapy help with hyperglycemic emergencies?
metabolic acidosis and insulin deficiency lead to extracellular movement of potassium = total body depleted of K+ even if serum K levels are normal or elevated in DKA
insulin therapy lowers serum K levels by promoting movement back into intracellular compartment
insulin administration in patients with admission hypokalemia & with really low K levels could result in severe hypokalemia so you need to replace K at a lower rate and insulin administration needs to be delayed till K levels get higher
acute or chronic renal failure patients need lower doses of K
how does bicarbonate therapy help with hyperglycemic emergencies?
only recommended in patients with life threatening acidosis (pH<6.9)
bicarbonate therapy can increase the risk of hypokalemia and cerebral edema
what is the main treatment for DKA?
continuous IV insulin administration:
- it lowers serum glucose by inhibiting endogenous glucose production and increasing peripheral utilization
-it also inhibits lipolysis, ketogenesis and glucagon secretion = decreases production of ketoacidosis
subcutaneous and intramuscular injections of insulin can also be used if needed but not recommended for patients with hypotension, severe DKA or with HHS
under what conditions is DKA considered resolved?
<250 mg/dl
venous pH >7.3
normal anion gap
serum bicarbonate > 18 mEq/L
under what conditions is HHS resolution considered resolved?
serum osmolality < 310 mOsm/kg
glucose < 250 mg/dL
recovered mental alertness and mental status
what are some types of subcutaneous basal insulin? when should they be used?
NPH, (insulin analogs: glargine, deter, degludec)
should be given at least 2 hours before discontinuing IV insulin because abruptly stoping IV insulin could result in hyperglycemia, ketogenesis and metabolic acidosis rebound because the half-life of insulin is only 10 minutes
what’s the preferred insulin regimen for patients with T1D and DKA? (and for most HHS patients)
multi-dose insulin regimens with basal insulin and prandial rapid-acting insulin analogs
what’s the most common complication of DKA?
hypoglycemia
lack of frequent monitoring, failure to reduce insulin infusion rate, or to use detrox-containing solutions when blood glucose levels hit 200 can cause hypoglycemia during insulin treatment
most hypoglycemic patients don’t exhibit adrenergic manifestations (sweaty, nervous) so you have to monitor glucose levels every 1-2 hours
what are side effects of hypoglycemia?
seizures, arrhythmias, cardiovascular events
what is the second most common complication during DKA and HHS treatment?
hypokalemia
even though admission serum K is usually elevated, during insulin treatment plasma K will decrease due to increased cellular K uptake in peripheral tissues
to prevent hypokalemia, replacement with IV K+ when concentration <5.2 is needed
what is the third complication with DKA?
cerebral edema (rare)
not really understood but we think it has to do with disruption of the blood-brain barrier
degree of edema formation during DKA correlates with degree of dehydration and hyperventilation at presentation but it doesn’t correlate with initial osmolality, osmotic changes during treatment or rate of fluid/Na+ administration
what are signs of cerebral edema?
4-12 hours after treatment has started but as late as 24-48 hours after treatment
altered consciousness, abnormal motor or verbal response to pai, cranial nerve palsy, abnormal respiratory pattern
what’s the treatment for cerebral edema?
administer mannitol
or hypertonic saline if there’s no response to mannitol
then get a CT scan to rule out other causes of neurological deterioration like thrombosis and cerebral infarction, hemorrhage, or dural sinus thrombosis
corticosteroids and diuretic therapy don’t help
what is the fourth complication of DKA?
rhabdomyolysis
in DKA patients but more commonly HHS patients
results in increased risk of acute kidney failure
symptoms: myalgia, weakness, dark urine
need to monitor creatine kinase levels
how do you prevent hyperglycemic emergencies?
medication-noncompliance is leading cause of DKA due to inability to afford medication or get transportation to pharmacy
can reduce hospitalization rate by developing assistance programs to provide insulin to patients and reduce lapses in treatment
also providing diabetes educators in close contact with and easily accessible to patients reduces number of hospitalizations related to hyperglycemic emergencies
why are DKA and HHS patients dehydrated?
High blood sugar causes further dehydration as your kidneys attempt to unload glucose and ketones by producing large amounts of urine
Increased dehydration causes higher blood sugars, which in turn cause further dehydration
