Diabetes B&B

Question 1

what are the 2 classic symptoms of diabetes mellitus

Answer 1

often presents asymptotically, but classic symptoms are polyuria (glucose is osmotic diuretic) and polydipsia (to replace fluids)

[recall these are the same symptoms of diabetes insipidus, though by completely different mechanisms]

Question 2

What measurements of fasting plasma glucose are considered normal, pre-diabetic, and diabetic?

Answer 2

normal <100mg/dl
pre-diabetic 100-125mg/dl
diabetic >126mg/dl

Question 3

how does hemoglobin A1C develop in diabetes? what level of hemoglobin A1C is indicative of diabetes?

Answer 3

non-enzymatic glycation of hemoglobin - within the beta chains, terminal valines have NH2 group, which glucose can hydrogen bond to

diabetes: >6.5% HgbA1C

Question 4

what type of hypersensitivity reaction is Type 1 diabetes?

Answer 4

Type IV - T cell mediated destruction of beta cells —> loss of insulin

associated with HLA-DR3/4

Question 5

why does it makes sense that diabetic ketoacidosis is more common in Type 1 diabetes?

Answer 5

common initial presentation of Type I, often precipitated by infection/trauma (or skipping insulin therapy)

development of DKA requires low insulin - more common in Type I when there is low insulin due to beta cell destruction (Type IV hypersensitivity)

Question 6

why type of breathing presents with DKA (diabetic ketoacidosis) and why?

Answer 6

Kussmaul breathing: deep, labored hyperventilation - the body is trying to blow off CO2 and raise the pH

Question 7

describe why ketoacidosis occurs in type I diabetes

Answer 7

DKA occurs following injury/trauma - this causes increase in epinephrine

in type I diabetes, insulin is low because of beta cell autoimmune destruction - this stalls the TCA cycle

low insulin + high epinephrine = high fatty acid utilization, producing acetyl-CoA

acetyl-CoA is diverted away from TCA and into ketone synthesis

Question 8

patient with DKA is showing signs of respiratory failure - what should you do?

Answer 8

check the phosphorus level!! [classic board question]

acidosis in DKA causes phosphate to leave cells, and is then lost via osmotic diuresis (mediated by high blood glucose) —> loss of ATP, leading to muscle weakness presenting as respiratory failure / heart failure

Question 9

what type of infection is a classic complication of DKA (diabetic ketoacidosis)?

Answer 9

mucormycosis - fungal infection caused by Rhizopus or Mucor species, which thrive in high glucose/ketoacidosis environment

presents as patient recovering from DKA with new onset fever/headache/eye pain (infection starts in sinuses)

Question 10

blood levels of what 2 substances need to be closely monitored when administering insulin for DKA (diabetic ketoacidosis)?

Answer 10

1. potassium - despite hyperkalemia during acidosis, total body K+ is low due to diuresis… insulin will cause K+ to shift into cells, leading to hypokalemia
2. glucose - insulin therapy must be continued until acidosis resolves (this is what causes symptoms of DKA), but this can cause hypoglycemia

K+ and glucose are usually administered concurrently

Question 11

which poses a higher risk for Type 2 diabetes, visceral (intra-abdominal) or subcutaneous fat? why?

Answer 11

visceral fat, because its breakdown is less inhibited by insulin

more lipolysis (due to insulin resistance) produces more free fatty acids - this may contribute to diabetes because FA is used for fuel instead of glucose (therefore there is less glucose transport into cells)

Question 12

which is a greater risk factor for type 2 diabetes, “apple” or “pear” shape? why?

Answer 12

apple shape is worse because it is due to increased visceral adipose tissue, while pear shape is due to increased subcutaneous adipose tissue (which is more responsive to insulin)

Question 13

what is the classic histological finding of pancreatic islets in type 2 diabetes?

Answer 13

amyloid in pancreatic islets

amylin normally made by beta cells and packaged with insulin

amylin accumulates and gives appearance of amyloid

Question 14

what is hyperglycemic hyperosmolar syndrome (HHS) and is it more common in Type 1 or Type 2 diabetes?

Answer 14

life-threatening complication of diabetes, VERY high glucose (>1000) causes extreme diuresis and dehydration

very high serum osmolarity causes CNS dysfunction

more common in Type 2

Question 15

acanthosis nigricans

Answer 15

hyperpigmented plaques within skin folds (neck, axillae) associated with insulin resistance (type 2 diabetes)

Question 16

what are the 2 mechanisms underlying most of the complications of diabetes (cardiac disease, renal failure, neuropathy, etc)

Answer 16

1. non-enzymatic glycation - causes cross-linked proteins (“advanced glycosylation end products,” AGEs)
2. sorbitol accumulation (Polyol pathway)

Question 17

what is the cause of diabetic macroangiopathy? how can this present?

Answer 17

AGEs (advanced glycosylation end products, due to non-enzymatic glycation) trap LDL in large vessels —> atherosclerosis

—> coronary artery disease (angina, MI)
—> stroke/TIA
—> peripheral vascular disease (claudication, arterial ulcers, poor wound healing, gangrene)

Question 18

what is the cause of diabetic microangiopathy?

Answer 18

AGEs (advanced glycosylation end products, due to non-enzymatic glycation) cause damage to glomerulus and arterioles —> end stage kidney disease

Question 19

renal efferent arteriosclerosis is rarely seen except in…

Answer 19

diabetes - causes hyaline arteriosclerosis

can occur in afferent arterioles (—> ischemia) or efferent arterioles (—> hyperfiltration)

can treat efferent arteriosclerosis with ACE inhibitor (causes dilation)

Question 20

what 2 forms of glomerulosclerosis are associated with diabetes? how do they differ?

Answer 20

1. diffuse glomerulosclerosis: collagen IV deposits on basement membrane of capillary loops, can cause nephrotic syndrome if severe
2. nodular glomerulosclerosis: specific to diabetes, Kimmelstiel-Wilson nodules form in mesangium

Question 21

nodular glomerulosclerosis is rare except in…

Answer 21

diabetes (pathognomonic of diabetic kidney disease)

nodular glomerulosclerosis: Kimmelstiel-Wilson nodules form in mesangium of glomerulus

can lead to fibrosis/scarring of entering kidney

Question 22

fill in the blanks regarding the polyol pathway:
1. glucose is converted to sorbitol via [enzyme], which requires [cofactor]
2. sorbitol is converted to [sugar] via sorbitol dehydrogenase, producing [cofactor]

Answer 22

1. glucose is converted to sorbitol via ALDOSE REDUCTASE, which requires NADPH
2. sorbitol is converted to FRUCTOSE via sorbitol dehydrogenase, producing NADH

Question 23

what is the cause of diabetic neuropathy, and how does this present?

Answer 23

sorbitol accumulates in Schwann cells (myelinating cells), causing osmotic damage

presents as “stocking-glove” sensory loss - longest axons most affected (those going to feet/legs), sensation gets worse moving distally

autonomic neuropathy can also occur —> postural hypotension, delayed gastric emptying

Question 24

how could you distinguish diabetic neuropathy from B12 deficiency?

Answer 24

both can cause loss of sensation in lower extremities; however, diabetic neuropathy causes “stocking-glove” sensory loss - gets worse distally / better proximally

B12 deficiency causes even loss of sensation in legs

Question 25

how does sorbitol contribute to the development of diabetic retinopathy?

Answer 25

sorbitol accumulates in pericytes, which wrap around capillaries —> microaneurysms develop and rupture, causing hemorrhage

Question 26

explain the link between elevated free fatty acids and insulin resistance in patients with obesity?

Answer 26

increased release of fatty acids due to high volume of adipocytes (esp. from visceral adipocytes)

elevated plasma FFA inhibit insulin-stimulated glucose uptake —> insulin resistance

Question 27

what is the role of incretins on postprandial insulin secretion?

Answer 27

incretins: gastrointestinal hormones that cause “anticipatory” rise in insulin after eating, before blood glucose becomes elevated

secreted by enteroendocrine cells of small intestine

ex: GLP-1 (glucagon-like peptide 1), GIP (glucose dependent insulinotropic polypeptide)

Question 28

how do hyperglycemia and hypertriglyceridemia develop, respectively, in type I diabetes?

Answer 28

hyperglycemia caused by increased liver gluconeogenesis combined with reduced glucose uptake by muscle/adipose (GLUT4 is insulin dependent)

hypertriglyceridemia caused by decreased expression of lipoprotein lipase due to low insulin levels