ICL 5.5: Acute Complications of DM and Hypoglycemia

Question 1

what does HHS stand for?

Answer 1

hyperosmolar hyperglycemic state

Question 2

what is the difference between DKA and HHS?

Answer 2

DKA = hyperglycemia + ketoacidosis

HHS = more severe hyperglycemia with no ketoacidosis

Question 3

what is the epidemiology of DKA?

Answer 3

1. Characteristically associated with type 1
2. may occur in type 2 under extreme stress → ketosis-prone diabetes
3. more common in young patients (<65 years)

Question 4

what is the epidemiology of HHS?

Answer 4

1. more common in older than 65 years
2. mortality rate 10-20%

10x higher than DKA; related to underlying precipitating illness

Question 5

which GLUT transporter is on the B cells?

Answer 5

GLUT2

Question 6

what do incretins do?

Answer 6

1. increase release insulin!
2. decrease glucagon release
3. slows gastric emptying
4. increased satiety

GLP1 and GIP

Question 7

what are the 2 pathways that the insulin receptor activates?

Answer 7

autophosphoyrlation of tyrosine residues on insulin receptor after insulin binds results in activation of:

1. MAPK singnaling responsible for cell growth and gene expression
2. PI3K signaling pathway responsible for synthesis of lipids, proteins and glycogen and GLUT4 translocation to membrane

Question 8

what are the effects of insulin on adipose?

Answer 8

1. increased glucose uptake and lipogenesis

2. decreased lipolysis

Question 9

what are the effects of insulin on muscle?

Answer 9

1. increased protein synthesis
2. increased glycogen synthesis
3. increased glucose uptake

Question 10

what are the effects of insulin on the liver?

Answer 10

1. increased glycogen synthesis
2. increased lipogenesis
3. decreased glyconeogeneis s

Question 11

what is the triad associated with DKA?

Answer 11

1. elevated glucose
2. acidosis
3. ketosis

Question 12

what is the pathophysiology of DKA?

Answer 12

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

1. 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)
2. direct effect of low insulin-glucagon ratio on the liver: that promotes increased production of ketones as well as of glucose
3. increased level of antagonistic hormones: (corticosteroid, catechol amines, glucagon, and GH) due to acute insulin deficiency and the metabolic stress of ketosis)
4. reduced peripheral utilization of glucose and ketones due to absence of insulin

Question 13

what is the pathophysiology of HHS?

Answer 13

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

Question 14

what are the common causes of DKA?

Answer 14

1. infection
2. noncompliance
3. inappropriate adjustment
4. cessation of insulin
5. cessation of insulin
6. new onset DM
7. myocardial ischemia
8. SGLT2 inhibitors
9. cocaine and lithium
10. hyperthyroidism, acromegaly, steroids and Cushing’s

Question 15

what are the signs and symptoms of DKA?

Answer 15

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

1. feeling very thirsty
2. urinating often
3. high blood glucose levels
4. high ketone levels
5. feeling weak or sleepy
6. dry/flushed skin
7. N/V
8. difficulty breathing due to compensatory respiration from metabolic acidosis to try and remove CO2 (Kausmaul breathing)
9. fruity smelling breath from ketones

Question 16

how do you diagnose DKA?

Answer 16

triad = hyperglycemia, + ketonemia + anion gap metabolic acidosis

1. BG > 250
2. metabolic acidosis: arterial pH <7.3 and/or serum HCO3 <18
3. elevated ketones in urine and blood
4. AG = Na - (Cl - HCO3)

normal AG = 12

Question 17

how do you calculate a corrected sodium AG during DKA?

Answer 17

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

Question 18

what is the labroty diagnosis of DKA?

Answer 18

1. BG > 250
2. low arterial pH in absence of coexistent respiratory disease (metabolic acidosis)
3. high anion gap (>10mEq/L) [Na+ – (Cl- + HCO3)]
4. 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

5. elevated urea and creatinine due to dehydration
6. elevated Ketones and B-hydroxybutyrate
7. elevated WBCs even in absence of infection because of hypercortisolemia and increased catecholamine secretion due to the stressful state of DKA

Question 19

how do you diagnose HSS?

Answer 19

1. marked hyperglycemia: glucose > 1000 mg/dl
2. Posm > 320, may reach > 380 mosm/kg (neurologic abnormalities are frequent)
3. little or no ketoacid accumulation
4. minimal acidosis
5. pH > 7.3, serum HCO3 > 20 mg mEq/L, glucose > 600 mg/dl

Question 20

how do you classify the severity of DKA?

Answer 20

based on the pH

mild: 7.25-7.3
moderate: 7-7.24
severe: <7

Question 21

what are the goals of treating DKA/HSS?

Answer 21

1. correct fluid and electrolyte abnormalities
2. restore plasma volumen and tissue perfusion
3. reduce glucose and plasma osmolality
4. give insulin
5. correct acidosis
6. identify precipitating factors and treat
7. 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)

Question 22

when do you give insulin if K is low?

Answer 22

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

Question 23

once you stabilize someone in DKA, what do you do?

Answer 23

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 :

1. serum anion gap <12mEq/L(or at the upper limit of normal for the local laboratory)
2. serum bicarbonate ≥15mEq/L
3. venous pH >7.30

Question 24

why do you need to overlap your subcutaneous insulin with your IV insulin when resolving DKA?

Answer 24

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!

Question 25

glucose = 961

Na = 143

Cl = 106

HCO3 = 18

K = 5.3

what does she have? how would you treat?

Answer 25

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

Question 26

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?

Answer 26

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

Question 27

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

Answer 27

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

Question 28

what are the classifications of hypoglycemia?

Answer 28

1. diabetic

2. non-diabetic

Question 29

what are the causes of hypoglycemia?

Answer 29

1. drugs
   ex. insulin or insulin secretagogues, gatlifloxacin, pentamidine, quinine, indomethacin, etc.
2. critical illness
   ex. hepatic, renal or cardiac failure, sepsis
3. hormone deficiency
   ex. cortisol, glucagon, epinephrine
4. non-islet cell tumor
5. endogenous hyperinsulinism
   ex. insulinoma,
6. functional B-cell disorders
   ex. NIPHS, post-gastric bypass hypoglycemia
7. insulin autoimmun hypoglycemia

Question 30

what are non-islet cell tumors?

Answer 30

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

Question 31

what are the symptoms of hypoglycemia?

Answer 31

1. palpitations
2. anxiety
3. tremor
4. diaphoresis
5. hunger
6. paresthesias
7. headache
8. double or blurred vision
9. weakness or fatigue
10. feeling warm
11. inability to concentrate
12. confusion
13. seizures/coma/transient focal neurologic deficits

Question 32

how do you diagnose hypoglycemia?

Answer 32

whipple’s triad:
1. symptoms of hypoglycemia

2. hypoglycemia under 70 for diabetics and under 55 for non-diabetics
3. reversal of symptoms with glucose

once they meet these criteria you work them up to determine the cause of hypoglycemia

Question 33

what are the workups to determine the cause of hypoglycemia?

Answer 33

1. fasting evaluation
2. postprandial evaluation

3 .72 hr fast

Question 34

how does insulin effect ketogeneisis?

Answer 34

it inhibits it so B-hydroxybutyrate levels will be low

that’s why in DKA when you have no insulin you get ketoacidosis

Question 35

what are the concerns to keep in mind with hypoglycemia?

Answer 35

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

Question 36

how you treat acute hypoglycemia?

Answer 36

1. glucagon
2. IV dextrose

these are for when people are unconscious and they can’t eat something

Question 37

how do you manage an insulinoma?

Answer 37

1. localization study
2. selective arterial calcium stimulation test

treat underlying malignancy and maybe give steroids too to help with hypoglycemia

Question 38

how do you medically treat an insulinoma?

Answer 38

1. diazoxide

opens ATP-dependent K+ channels on pancreatic β-cells → hyperpolarization of the cell, inhibition of insulin release

2. octreotide (analog of somatostatin)

inhibits insulin secretion

3. verapamil
   direct inhibition of voltage gated Ca2+channels
4. acarbose (alpha-glucosidase inhibitor)

decreases absorption of glucose