ICL 5.5: Acute Complications of DM and Hypoglycemia Flashcards
what does HHS stand for?
hyperosmolar hyperglycemic state
what is the difference between DKA and HHS?
DKA = hyperglycemia + ketoacidosis
HHS = more severe hyperglycemia with no ketoacidosis
what is the epidemiology of DKA?
- Characteristically associated with type 1
- may occur in type 2 under extreme stress → ketosis-prone diabetes
- more common in young patients (<65 years)
what is the epidemiology of HHS?
- more common in older than 65 years
- mortality rate 10-20%
10x higher than DKA; related to underlying precipitating illness
which GLUT transporter is on the B cells?
GLUT2
what do incretins do?
- increase release insulin!
- decrease glucagon release
- slows gastric emptying
- increased satiety
GLP1 and GIP
what are the 2 pathways that the insulin receptor activates?
autophosphoyrlation of tyrosine residues on insulin receptor after insulin binds results in activation of:
- MAPK singnaling responsible for cell growth and gene expression
- PI3K signaling pathway responsible for synthesis of lipids, proteins and glycogen and GLUT4 translocation to membrane
what are the effects of insulin on adipose?
- increased glucose uptake and lipogenesis
2. decreased lipolysis
what are the effects of insulin on muscle?
- increased protein synthesis
- increased glycogen synthesis
- increased glucose uptake
what are the effects of insulin on the liver?
- increased glycogen synthesis
- increased lipogenesis
- decreased glyconeogeneis s
what is the triad associated with DKA?
- elevated glucose
- acidosis
- ketosis
what is the pathophysiology of DKA?
it all stems from absent insulin which is why this is more common in type I DM
if the muscle doesn’t have insulin to take up glucose it needs other energy sources so it breaks down AA via gluvoneogenesis to make energy
adipose tissue also doesn’t have insulin so it starts to break down TGs into glycerol and FA – glycerol goes to the liver used in gluconeogeneisis while FA get turned into ketones, eventually resulting in ketoacidosis
low insulin also results in elevated glucagon so that also results in increased glucose levels and gluconeogenesis
- acute insulin deficiency: rapid mobilization of energy from stores in muscle and fat depots increased AA to the liver for conversion to glucose and for FA for conversion to ketones (acetoacetate, acetone, β OH-butyrate)
- direct effect of low insulin-glucagon ratio on the liver: that promotes increased production of ketones as well as of glucose
- increased level of antagonistic hormones: (corticosteroid, catechol amines, glucagon, and GH) due to acute insulin deficiency and the metabolic stress of ketosis)
- reduced peripheral utilization of glucose and ketones due to absence of insulin
what is the pathophysiology of HHS?
relative insulin deficiency rather than no insulin at all
so because there’s some insulin then there isn’t a lot of ketogenesis because there’s still glucose uptake allowing to glycolysis so that ketones don’t build up from the lack of oxaloacetate
however, there is hyperosmolarity since glucose isn’t being taken up that well which can result in really bad CNS symptoms unlike DKA
what are the common causes of DKA?
- infection
- noncompliance
- inappropriate adjustment
- cessation of insulin
- cessation of insulin
- new onset DM
- myocardial ischemia
- SGLT2 inhibitors
- cocaine and lithium
- hyperthyroidism, acromegaly, steroids and Cushing’s
what are the signs and symptoms of DKA?
DKA usually evolves more rapidly while HSS develops more insidiously but they have the same symptoms for the most part except DKA has abdominal pain, N/V while HSS doesn’t usually have that since they don’t have ketoacidosis – however, HSS has more neurologic symptoms than DKA due to the extremely elevated glucose levels
- feeling very thirsty
- urinating often
- high blood glucose levels
- high ketone levels
- feeling weak or sleepy
- dry/flushed skin
- N/V
- difficulty breathing due to compensatory respiration from metabolic acidosis to try and remove CO2 (Kausmaul breathing)
- fruity smelling breath from ketones
how do you diagnose DKA?
triad = hyperglycemia, + ketonemia + anion gap metabolic acidosis
- BG > 250
- metabolic acidosis: arterial pH <7.3 and/or serum HCO3 <18
- elevated ketones in urine and blood
- AG = Na - (Cl - HCO3)
normal AG = 12
how do you calculate a corrected sodium AG during DKA?
hyperglycemia with DKA and HSS can cause pseudohyponatremia
for every 100 mg over 100 mg glucose, you add 2 to the sodium
ex. if glucose is 300, then add 2+2=4 to the plasma Na level to get corrected Na level
this will guide you on which fluids to use when treating the patient for DKA which is why it’s important to calculate it
what is the labroty diagnosis of DKA?
- BG > 250
- low arterial pH in absence of coexistent respiratory disease (metabolic acidosis)
- high anion gap (>10mEq/L) [Na+ – (Cl- + HCO3)]
- impaired electrolyte level (hyperK due to acidosis shift K from IC to EC spaces)
even though there’s a total body K deficit but there’s acidosis which shifts K from intracellular to extracellular space causing hyperkalemia– once you give insulin you drive K into the cells
- elevated urea and creatinine due to dehydration
- elevated Ketones and B-hydroxybutyrate
- elevated WBCs even in absence of infection because of hypercortisolemia and increased catecholamine secretion due to the stressful state of DKA
how do you diagnose HSS?
- marked hyperglycemia: glucose > 1000 mg/dl
- Posm > 320, may reach > 380 mosm/kg (neurologic abnormalities are frequent)
- little or no ketoacid accumulation
- minimal acidosis
- pH > 7.3, serum HCO3 > 20 mg mEq/L, glucose > 600 mg/dl
how do you classify the severity of DKA?
based on the pH
mild: 7.25-7.3
moderate: 7-7.24
severe: <7
what are the goals of treating DKA/HSS?
- correct fluid and electrolyte abnormalities
- restore plasma volumen and tissue perfusion
- reduce glucose and plasma osmolality
- give insulin
- correct acidosis
- identify precipitating factors and treat
- replenish K even if they’re in DKA because they have a total body K depletion even though they’re hyperkalemic (below 3.3 K give K! if it’s in the normal range just add it to your fluids and give insulin; if K is over 3.5 then don’t give any K and just keep an eye on nit)
when do you give insulin if K is low?
you hold off and correct K first if it’s below 3.3
this is because insulin will lower K levels even more and hypokalemia can result in cardiac arrhythmias and respiratory muscle weakness
once you stabilize someone in DKA, what do you do?
The American Diabetes Association (ADA) recommends switching to subcutaneous insulin rather than IV insulin when BG < 200mg/dLand at least two of the following goals are met :
- serum anion gap <12mEq/L(or at the upper limit of normal for the local laboratory)
- serum bicarbonate ≥15mEq/L
- venous pH >7.30
why do you need to overlap your subcutaneous insulin with your IV insulin when resolving DKA?
onset of action of long acting insulin takes 2 hrs for it to kick in so if you stop the drop and then give a long acting insulin then it’s gonna take 2 hrs to kick in and so you can have rebound hyperglycemia if you quickly stop IV insulin
so you need to overlap them for little to make sure that doesn’t happen!
glucose = 961
Na = 143
Cl = 106
HCO3 = 18
K = 5.3
what does she have? how would you treat?
AG = 143 - (106+18) = 10 so she has a normal anion gap!
also her serum glucose is hella high so she has HSS and not DKA
give IV fluids and insulin; don’t need to give K since her K is high
A 52-year-old woman is brought to the ER by her husband because of weakness, abdominal pain, and a productive cough for 4 days. She also reports increased urination for the past 2 days. This morning she had nausea and five episodes of vomiting. She has type 1 diabetes mellitus and hypertension. Current medications include insulin and lisinopril. She admits to having forgotten to take her medication in the last few days.
Her temperature is 38.4° C (101.1°F), pulse is 134/min, respirations 31/min, and blood pressure is 95/61 mm Hg. Examination shows dry mucous membranes and decreased skin turgor. Abdominal examination shows diffuse tenderness with no guarding or rebound. Bowel sounds are normal.
Na+ = 139 mEq/L K+ = 5.3 mEq/L Cl- =106 mEq/L Glucose = 420 mg/dL pH = 7.12 HCO3 = 12
diagnosis and treatment?
AG = 139 - (106 + 12) = 21 =- metabolic acidosis
elevated glucose + metabolic acidosis + ketones = DKA
treat with insulin, fluids and no K since her K is fine
her sodium level is also fine but if it was on the higher end then maybe you would use 1/2 saline so it doesn’t get too high
also if the patient’s glucose is dropping below 200 in DKA or 250 in HSS but they still haven’t met other parameters like a bad anion gap or pH is still low then you need to add dextrose to fluids so you can keep the insulin drop going without making them hypoglycemic
A 52-year-old woman is brought to the ER by her husband because of weakness, abdominal pain, and a productive cough for 4 days. She also reports increased urination for the past 2 days. This morning she had nausea and five episodes of vomiting. She has type 1 diabetes mellitus and hypertension. Current medications include insulin and lisinopril. She admits to having forgotten to take her medication in the last few days.
Her temperature is 38.4° C (101.1°F), pulse is 134/min, respirations 31/min, and blood pressure is 95/61 mm Hg. Examination shows dry mucous membranes and decreased skin turgor. Abdominal examination shows diffuse tenderness with no guarding or rebound. Bowel sounds are normal.
Na+ = 139 mEq/L K+ = 5.3 mEq/L Cl- =106 mEq/L Glucose = 420 mg/dL pH = 7.12 HCO3 = 12
Which of the following is the most likely underlying cause of this patient’s normal to increased potassium level?
A. Increased renal potassium absorption
B. Intracellular potassium shift
C. Decreased renal potassium excretion
D. Muscle cell breakdown
E. Extracellular potassium shift
E. Extracellular potassium shift
the elevated glucose causes increased plasma osmolarity of the blood which leads to a shift of blood from the intracellular to extracellular space and this then causes the K to shift down the gradient out of the cell but there’s still a total body K deficiet
what are the classifications of hypoglycemia?
- diabetic
2. non-diabetic
what are the causes of hypoglycemia?
- drugs
ex. insulin or insulin secretagogues, gatlifloxacin, pentamidine, quinine, indomethacin, etc. - critical illness
ex. hepatic, renal or cardiac failure, sepsis - hormone deficiency
ex. cortisol, glucagon, epinephrine - non-islet cell tumor
- endogenous hyperinsulinism
ex. insulinoma, - functional B-cell disorders
ex. NIPHS, post-gastric bypass hypoglycemia - insulin autoimmun hypoglycemia
what are non-islet cell tumors?
rare but serious complication of tumors that causes hypoglycemia
this is because the tumor produces insulin-like growth factor 2
with increased tumor burden and high metabolic needs and reduced glycogen stores, it causes hypoglycemia
what are the symptoms of hypoglycemia?
- palpitations
- anxiety
- tremor
- diaphoresis
- hunger
- paresthesias
- headache
- double or blurred vision
- weakness or fatigue
- feeling warm
- inability to concentrate
- confusion
- seizures/coma/transient focal neurologic deficits
how do you diagnose hypoglycemia?
whipple’s triad:
1. symptoms of hypoglycemia
- hypoglycemia under 70 for diabetics and under 55 for non-diabetics
- reversal of symptoms with glucose
once they meet these criteria you work them up to determine the cause of hypoglycemia
what are the workups to determine the cause of hypoglycemia?
- fasting evaluation
- postprandial evaluation
3 .72 hr fast
how does insulin effect ketogeneisis?
it inhibits it so B-hydroxybutyrate levels will be low
that’s why in DKA when you have no insulin you get ketoacidosis
what are the concerns to keep in mind with hypoglycemia?
hypoglycemia associated autonomic failure that’s triggered by recurrent hypoglycemic events in patients with an inadequate glucagon response
due to an attenuated epinephrine response
this causes defective glucose counter-regulation and leads to a loss of behavioral response (i.e., loss of symptoms) coined “hypoglycemic unawareness”
you treat this by scrupulous avoidance of hypoglycemia for 2-3 weeks
how you treat acute hypoglycemia?
- glucagon
- IV dextrose
these are for when people are unconscious and they can’t eat something
how do you manage an insulinoma?
- localization study
- selective arterial calcium stimulation test
treat underlying malignancy and maybe give steroids too to help with hypoglycemia
how do you medically treat an insulinoma?
- diazoxide
opens ATP-dependent K+ channels on pancreatic β-cells → hyperpolarization of the cell, inhibition of insulin release
- octreotide (analog of somatostatin)
inhibits insulin secretion
- verapamil
direct inhibition of voltage gated Ca2+channels - acarbose (alpha-glucosidase inhibitor)
decreases absorption of glucose
