Diabetes Complications

Question 1

hyperglycemic emergencies - overview

Answer 1

*occur when there is either too little insulin, or too much glucagon/cortisol/epinephrine/NE
*includes: 1) DKA; 2) hyperosmolar hyperglycemic state (HHS)

Question 2

diabetic ketoacidosis (DKA) - pathophysiology

Answer 2

*an effect of insulinopenia or relative insulinopenia (too little insulin)
*not enough insulin to suppress fatty acids from being released from fat and sent to liver (lipolysis)
*liver mitochondria cannot handle all the fatty acids, and the excess become ketones
*glucose rises, as does serum ketones: beta-hydroxybutyrate > acetoacetate
*the serum ketones cause an anion gap metabolic acidosis

Question 3

diabetic ketoacidosis (DKA) - presentation

Answer 3

*typically occurs in T1DM, but can occur in extreme cases of T2DM
*presenting signs/symptoms:
-hyperglycemia
-polyuria/polydipsia
-Kussmaul respirations (rapid deep breathing, respiratory compensation for metabolic acidosis)
-GI sx: abdominal pain, N/V (due to acidemia)
-fruity breath odor (due to exhaled acetone, a breakdown product of acetoacetate)

Question 4

hyperosmolar hyperglycemic state (HHS)

Answer 4

*there is enough insulin to suppress fatty acid release from adipose tissue, but not enough insulin to drive the glucose into the cells
*therefore: glucose increases, but no ketones are produced
*takes longer to present with sx compared to DKA
*has a higher mortality than DKA, likely due to high osmolality leading to coma

Question 5

4 key problems in hyperglycemic emergencies

Answer 5

1. dehydration: due to osmotic diuresis from hyperglycemia; can be severe and life threatening
2. hyperosmolality: more of an issue in HHS; causes osmotic fluid shift (intracellular → extracellular); occurs in brain as well
3. acidosis: in DKA; mental obtundation, coma, cardiac dysfunction, etc
4. electrolyte abnormalities: HYPOKALEMIA (potassium shifts out of cells into extracellular space due to acidemia and insulin deficiency; then K+ is lost in urine)

Question 6

dilutional hyponatremia

Answer 6

*sodium level is a concentration, influenced by intravascular fluid status
*in severe hyperglycemia, water is drawn into intravascular space, which will decrease the sodium concentration (i.e. dilutional hyponatremia)
*must calculate a corrected sodium based on how high the blood sugar is

Question 7

treatment of DKA

Answer 7

1. IV fluids
2. potassium
3. insulin
4. assess need for bicarbonate

note - do not correct too rapidly d/t risk of cerebral edema

Question 8

treatment of HHS

Answer 8

1. IV fluids
2. insulin
3. potassium

note - do not correct too rapidly d/t risk of cerebral edema

Question 9

prevention of hypoglycemia in a normal (non-diabetic) state

Answer 9

1. as blood sugar approaches 70 mg/dl (low end of normal), insulin secretion from beta cells ceases
2. at glucose < 70 mg/dL, alpha cells secrete glucagon
3. as glucose continues to fall, epinephrine and cortisol are secreted to help increase sugar

Question 10

hypoglycemia in diabetes

Answer 10

*this is iatrogenic due to insulin (you are giving insulin) or insulin secretagogues (sulfonylureas)
*only failsafe against hypoglycemia is epinephrine/cortisol
*the more hypoglycemia you have, the less of an adrenergic response you have → hypoglycemic unawareness

Question 11

symptoms of hypoglycemia - general

Answer 11

1. adrenergic symptoms: tremors, sweating, anxiety, hunger
2. neuroglycopenic symptoms: AMS, seizures, CNS toxicity

Question 12

adrenergic symptoms of hypoglycemia

Answer 12

*due to epinephrine (released in attempt to increase blood glucose)
1. tremulousness
2. diaphoresis
3. anxiety
4. hunger

Question 13

neuroglycopenic symptoms of hypoglycemia

Answer 13

*lack of glucose to brain, usually glucose < 50
1. altered mental status
2. seizures
3. CNS toxicity (mimics anoxic brain injury)
4. cardiac arrest

Question 14

treatment of hypoglycemia

Answer 14

*mild to moderate (pt is still alert and oriented) = consume 15g of sugar and recheck in 15 mins
*severe hypoglycemia (pt requiring assistance, can’t consume carbs) = give glucagon injection; if pt is hospitalized, give IV dextrose

Question 15

macrovascular complications of diabetes: atherosclerotic coronary vascular disease (ASCVD)

Answer 15

*coronary artery disease, cerebral vascular disease, peripheral artery disease
*pts with DM are 2-4x more likely to develop ASCVD
*pathogenesis is complex and not fully understood, but advanced glycation end products (AGEs) play a role

Question 16

advanced glycation end products (AGEs)

Answer 16

*form when glucose reacts with proteins and lipids in the endothelial wall, leading to direct & indirect damage
*leads to inflammation and a cascade of events in the endothelial wall

Question 17

microvascular complications of diabetes - overview

Answer 17

*small blood vessels/capillaries are particularly susceptible to advanced glycation end products (AGEs)
*most commonly affected vessels include:
-retinal vessels
-vessels supplying small nerve fibers
-arterioles of nephrons

Question 18

diabetic retinopathy - epidemiology

Answer 18

*leading cause of blindness in developed countries
*up to 90% of patients with T1DM will develop some degree of diabetic retinopathy
*in T2DM, 50-60% will develop diabetic retinopathy
*2 types: non-proliferative and proliferative
*classic findings = exudates and cotton wool spots

Question 19

non-proliferative diabetic retinopathy

Answer 19

*starts with microaneurysms, which then bleed
*vessel walls become more permeable, and fluid/lipids leak into retina, causing macular edema, hard exudates

Question 20

proliferative diabetic retinopathy

Answer 20

*vessel damage/occlusion can lead to hypoxia → neovascularization
*new blood vessels are weak/fragile and have a tendency to bleed

Question 21

diabetic nephropathy

Answer 21

*most common cause of ESRD in the US
*50% of T1DM pts will develop CKD, 30% of T2DM pts
*earliest sign = small amounts of albumin lost in urine (albuminuria)
*histology: GBM thickening, nodular glomerulosclerosis, Kimmelstein-Wilson nodules
*treatment = ACE inhibitors/ARBs

Question 22

diabetic neuropathy - overview

Answer 22

*damage to small nerve fibers, most commonly sensory nerves
*symmetric and length-dependent: longer nerves are affected first (i.e. sx typically start in FEET and eventually have a stocking-glove distribution)
*some pts experience painful neuropathy, some simply lose sensation
*main contributing factor to diabetic foot wounds/amputations
*can also cause autonomic neuropathy - cardiac issues & orthostatic hypotension

Question 23

diabetic neuropathy - screening & treatment

Answer 23

*screening: monofilament test, annual foot exams
*treatment: gabapentin, SNRIs

Question 24

other complications of diabetes

Answer 24

*heart failure
*gastroparesis
*diabetic foot wounds/amputations
*periodontal disease
*infections
*sexual dysfunction
*skin manifestations
*metabolic dysfunction-associated steatotic liver disease (MASLD)
*diabetic myonecrosis (muscle infarction)