Diabetes Mellitus Diagnosis- Knudson

Question 1

How does glucose entry into beta cells control insulin release?

Answer 1

1. Glucose allows the mitochondria to make ATP.
2. The ATP is used to power the ATP-sensitive potassium channel
3. Pumping potassium out of the cell depolarizes it
4. Calcium enters into the cell to repolarize it
5. Calcium wave causes release of insulin granules

Question 2

How do acetylcholine and CCK cause insulin release from the beta cells?

How do glucagon and GLP-1 cause insulin release from the beta cells?

Answer 2

Acetylcholine and CCK activate PLC to release calcium stores.

Glucagon and GLP-1 activate adenylyl cyclase to release calcium stores.

Question 3

What is the pathology behind diabetes mellitus?

What tests can be done to diagnose it?

Answer 3

Diabetes is caused by hyperglycemia secondary to insulin function or secretion.

1. HbA1c >6.5%
2. Fasting Glucose > 125mg/dL
3. post-challenge 2 hour glucose >200mg/dL
4. Random glucose >200mg/dL

Question 4

What test results can indicate pre-diabetes?

Answer 4

1. Fasting Glucose 100-125 mg/dL
2. 2 hour post-challange glucose 140-199 mg/dL
3. HgA1c 5.7-6.4%

Question 5

What are some consequences of diabetes mellitus?

Answer 5

SHORT TERM

• electrolyte abnormalities
• fatigue
• poor wound healing
• impaired immunity
• ketoacidosis

LONG TERM

• Microvascular
  
  • retinopathy
  • nephropathy
  • neuropathy
• Macrovascular
  
  • Coronary artery disease
  • Peripheral artery disease

Question 6

What biochemically causes the pathogenesis of diabetes mellitis?

Answer 6

• Accumulation of glycosylation end products
• Accumulation of sorbitol
• Disruption of hexamine pathway
• Disruption of PKC pathway
• Activation of Poly (ADP-ribose) polymerase
• Increased oxidative stress

Question 7

What are the two stages of diabetic retinopathy?

Answer 7

Initially, non-proliferative retinopathy occurs due to damage to the blood vessels. Microaneurysms and distention take place.

Eventually, the eye lacks sufficient oxygen and must begin growing new vessels. This is proliferative retinopathy. It causes bleeding, glaucoma, and retinal detachment due to fibrous build-up.

Question 8

What is the cause of Type 1 diabetes?

What is the cause of Type 2 diabetes?

What is the cause of gestational diabetes?

(answer is not ‘gestation’)

Answer 8

• Autoimmune destruction of the beta cells with lack of insulin
• Insulin resistance leads to a relative insulin deficiency
• Mother becomes both resistant to insulin and does not release enough insulin

Question 9

How does macrophage cytology change in obesity/diabetes?

How does the immune system profile change?

Answer 9

In lean adults, M2 (encourage tissue repair and decrease inflammation) macrophages predominate. This leads to an abundance of Th2 CD4+, T reg, and Eosinophils.

In obese adults, M1 (encourage inflammation) macrophages predominate. This leads to an abundance of mast cells, B lymphocytes, CD8+, and Th1/Th17 cells.

Question 10

How does type 2 diabets present clinically?

Answer 10

• Frequent urination
• Polydipsia
• Insidious onset
• Dylipidemia
• Truncal obesity
• Hypertension