Pathophysiology of Diabetes

Question 1

In cells that uptake glucose without insulin, hyperglycemia activates the PKC. What are the downstream affects of PKC activation?

Answer 1

Increased VEGF, endothelin, plasminogen activator inhibitor, and pro-inflammatory cytokines.

Decreased nitric oxide

Question 2

What are the end effects of activation of the hexosamine pathway due to hyperglycemia?

Answer 2

Oxidative stress and damage, microvascular damage

Question 3

This is the most common acute metabolic complication among all diabetic patients.

Answer 3

Hypoglycemia

Question 4

Type 1 diabetes occurs due to destruction of beta islet cells. What cells are responsible for the asymptomatic chronic inflammatory phase of type 1 diabetes?

Answer 4

T lymphocytes and macrophages - this stage is termed insulitis

Question 5

What stage of diabetic retinopathy is shown in the accompanying image?

Answer 5

Non-proliferative diabetic retinopathy (microaneurysms, hard exudates, no hemorrhage)

Question 6

What electrolyte abnormality may present in patients in diabetic ketoacidosis? Why?

Answer 6

Hyperkalemia - low insulin enables K+ to shift out of cells into the plasma.

Remember, insulin forces K+ into cells by stimulating the Na/K ATPase

Question 7

True/False. Type 1 diabetes has greater genetic predisposition than Type 2 diabetes.

Answer 7

False - Type 2 diabetes is more genetically based

Question 8

This diabetic complication is characterized by severe hyperglycemia and insulin resistance without significant ketosis.

Answer 8

Hyperglycemia hyperosmolar State (HHS) - high risk of mortality

Question 9

What is the main mechanism for diabetic neuropathy?

Answer 9

Polyol pathway - neurons do not need insulin for glucose uptake

Question 10

What stage of diabetic retinopathy is shown in the accompanying image?

Answer 10

Proliferative diabetic retinopathy (neovascularization, hemorrhages, retinal detachment)

Question 11

A 20yo patient presents with polyuria and polydipsia. Testing reveals hyperglycemia, even after fasting, but no autoimmune antibodies. What is a potential diagnosis?

Answer 11

Maturity Onset Diabetes of the Young (MODY) - autosomal dominant gene mutation that disrupts islet cell development

Question 12

True/False. Type 2 diabetes is characterized by a gradual decrease in insulin secretion over time.

Answer 12

False - Type 2 is characterized by peripheral insulin resistance that leads to increased insulin secretion. Over time, beta cells fail and insulin secretion decreases

Question 13

FFAs are potent inhibitors of insulin signaling. Why does physical activity improve insuling resistance?

Answer 13

Physical activity increases transport of the GLUT-4 receptor to skeletal muscle cell membranes for glucose uptake

Question 14

Chronic hyperglycemia impairs beta cell function in patients with type 2 diabetes. What factor is responsible for progressive worsening of beta cell functioning?

Answer 14

Lipotoxicity due to increases FFAs

Question 15

Uncontrolled gestational diabetes is associated with what newborn complications?

Answer 15

Macrosomia (large fetal size), respiratory distress syndrome, neonatal hypoglycemia

Question 16

How do glaucoma and cataracts differ?

Answer 16

Glaucoma is due to elevated intraocular pressure the compresses the optic nerve.

Cataracts are opacification of the lens due to the accumulation of sorbitol.

Question 17

These are all microvascular complications of diaebetes.

Answer 17

Retinopathy, neuropathy, nephropathy

Question 18

Normal fasting glucose is less than 100mg/dL. What is a normal random plasma glucose?

Answer 18

Less than 140mg/dL

Question 19

True/False. Pregnant women with gestational diabetes are at higher risk of developing Type 2 diabetes later in life.

Answer 19

True

Question 20

What pathophysiologic mechanism is responsible for fasting hyperglycemia in patients with type 2 diabetes?

Answer 20

Excess liver gluconeogenesis

Question 21

What is the main cause of death in diabetic patients?

Answer 21

Macrovascular complications

Question 22

What triad characterizes the acute presentation of type 1 diabetes?

Answer 22

Polyuria, polydipsia, polyphagia

Question 23

This is the leading cause of end-stage renal disease.

Answer 23

Diabetic nephropathy

Question 24

Coronary artery disease, MI, and stroke are (microvascular/macrovascular) complications of diabetes?

Answer 24

Macrovascular. Microvascular complications include retinopathy, neuropathy, nephropathy

Question 25

What is the Somogyi effect?

Answer 25

Rebound hyperglycemia after a hypoglycemic episode due to overcorrection by counter-regulatory hormones

Question 26

True/False. Low birth weight and low weight at 12mo are associated with development of type 2 diabetes later in life.

Answer 26

True - this may indicate abnormal development of beta cells

Question 27

What pathophysiologic mechanism is responsible for post-prandial hyperglycemia in patients with type 2 diabetes?

Answer 27

Impaired glucose uptake due to insulin resistance

Question 28

What halotypes are most associated with type 1 diabetes?

Answer 28

HLA-DR3 & DR4

Question 29

What is the most common presentation of diabetic neuropathy?

Answer 29

Symmetric distal peripheral polyneuropathy - symmetric sensory loss in the hands and feet (glove and stocking distribution)

Question 30

Formation of advanced glycation end products is accelerated by hyperglycemia. What are the pathologic implications of increased AGE?

Answer 30

Altered gene expression, inflammation, vascular dysfunction, ROS, procoagulant activity

Question 31

Accumulation of this molecule is responsible for cataract formation in patients with uncontrolled diabetes.

Answer 31

Sorbitol

Question 32

True/False. In type 2 diabetes, all tissues fail to take up glucose due to insulin resistance.

Answer 32

False - some cells uptake glucose without insulin (nerves, lenses, kidneys, vessels). These cells experience high intracellular glucose that is metabolized to sorbitol via the polyol pathway. Eventually, ROS accumulate and cause cellular damage.