Diabetes

Question 1

Where is insulin made?

Answer 1

Insulin is made by the beta cells in the pancreatic islets.

Question 2

Where is glucagon made?

Answer 2

Glucagon is made by the alpha cells in the pancreatic islets.

Question 3

What does insulin do?

Answer 3

Insulin allows glucose to be transported into cells.

Question 4

What does glucagon do?

Answer 4

Glucagon stimulates the break down of glycogen.

Question 5

What are the features of pre-diabetes?

Answer 5

1) impaired fasting glucose (IFG) 6.1-6.9 mmol/L
2) HbA1C of 6-6.4% (normal is under 6)
3) impaired glucose tolerance test (IGT) 7.8-11 mmol/L (normally BG will return to ~5.5 mmol/L after 2 hrs of ingesting glucose)

Question 6

Which type of diabetes has an absolute insulin deficiency?

Answer 6

Type 1 diabetes mellitus.

Question 7

Why is metabolic syndrome important?

Answer 7

It may or may not precede diabetes. It predisposes you to type 2 diabetes and cardiovascular disease.

Question 8

What are some features of metabolic syndrome?

Answer 8

• IFG
• IGT
• insulin resistance (insulin is unable to bring about a hypoglycemic response in a hyperglycemic state)
• hypertension
• abdominal obesity/diabesity (in women, waist circumference of over 88 cm, in men over 102 cm)
• hyperlipidemia

Question 9

What are three acute complications of diabetes mellitus?

Answer 9

1) hypoglycemia
2) diabetic ketoacidosis
3) hyperosmolar hyperglycemic state (HHS)

Question 10

What can cause hypoglycemia?

Answer 10

• missed meal
• insulin overdose
• overexertion

Question 11

What do we worry about with hypoglycemia?

Answer 11

If glucose is too low, the brain is deprived of glucose. As a result the patient will usually lose consciousness, enter hypoglycemic coma.

Question 12

How is hypoglycemia treated?

Answer 12

• if mild - give 15 g of carbs PO
• if severe (under 2.8 mmol/L) - give 20 g of carbs PO
• if pt unconscious - give 1 mg glucagon subcut or IM (this will break down glycogen stores)

Question 13

Diabetic ketoacidosis develops when these two circumstances are in place.

Answer 13

1) very low insulin levels

2) high levels of glucagon

Question 14

What 3 derangements are seen when diabetic ketoacidosis develops?

Answer 14

1) hyperglycemia
2) ketosis (formation of ketones from lipid breakdown)
3) ketoacidosis (depresses the CNS and can lead to coma)

Question 15

Why does hyperosmolar hyperglycemic state normally occur in type 2 diabetes?

Answer 15

Because the cells are not completely deprived of glucose (insulin deficiency is not absolute) and there is no breakdown of lipids.

Question 16

What two problems are caused by hyperosmolar hyperglycemic state?

Answer 16

1) hyperglycemia

2) hyperosmolarity

Question 17

What causes hyperosmolar hyperglycemic state?

Answer 17

• excessive carb intake

- increased insulin resistance

Question 18

Explain what happens in hyperosmolar hyperglycemic state.

Answer 18

• severe hyperglycemia leads to hyperosmolarity (an increase in the glucose concentration in blood)
• this leads to cellular fluid efflux
• the kidneys try to correct and excrete glucose = glycosuria
• water follows
• result is dehydration

Question 19

What are 5 chronic complications of diabetes mellitus?

Answer 19

1) vascular damage (that can lead to atherosclerosis, MI, CVA)
2) retinopathy
3) nephropathy
4) neuropathy
5) infections

Question 20

What are the different types of diabetes mellitus?

Answer 20

• type 1 (type 1a is more prevalent, is immune-based, type 1b is rare and idiopathic)
• type 2
• gestational

Question 21

What is the etiology of both type 1 and type 2 diabetes?

Answer 21

complex trait (polygenic AND an environmental factor)

Question 22

What genes have been found to be affected in people with type 1 diabetes?

Answer 22

• 10% have a defect of the insulin gene on chromosome 11 (this gene codes for a protein that regulates division and function of beta cells)
• 40% have a problem with the MHC genes on chromosome 6, they code for self markers on beta cells (this problem causes autoimmunity)

Question 23

What gene is often affected in young people who develop type 2 diabetes?

Answer 23

• 50% from a problem with glucokinase gene on chromosome 7 (codes for an enzyme that helps lock glucose in the cell by adding a phosphate group)

Question 24

If a member of your family has type 1 diabetes, does your risk for developing it increase? By how much?

Answer 24

yes, your risk inreases x10

Question 25

What happens at the cellular level to cause type 1 diabetes? What is the result?

Answer 25

In most cases beta cells in the pancreas are destroyed due to autoimmunity. The cells are destroyed by insulin and islet cell auto-antibodies, as well as T cells. This causes an absolute insulin deficiency.

Question 26

What is insulitis?

Answer 26

inflammation within the islets of Langherhans, can be caused by autoimmune destruction of beta cells preceding type 1 diabetes

Question 27

What happens in type 2 diabetes?

Answer 27

The beta cells in the pancreas are mostly intact but there is a relative insulin deficiency. There can be hyalinization occurring in the islets though, from the deposition of amyloid protein. This can be from: - a delay in insulin secretion - defective target cell response - insulin resistance (can't bring about hypoglycemic response to hyperglycemic state)

Question 28

Describe the pathology of diabetes.

Answer 28

- insulin deficiency - impaired utilization of glucose causes cells to signal that there is no glucose - causes increased glucogenesis in liver, making more glucose - this adds to hyperglycemia (11 to 67 mmol/L) - renal threshold for glucose (10 mmol/L) is exceeded, glucose above this threshold is excreted in urine = glycosuria - all the glucose in the filtrate in Bowman's capsule increases the osmotic pressure and causes fluid to follow - results in polyuria - eventually leads to dehydration - causes polydypsia (excessive thirst & excessive intake) also at the cellular level: - impaired glucose utilization by cells - increased mobilization and use of proteins and lipids for energy - causes increase in protein and lipid metabolizes (ketone) in blood - when renal threshold exceeded ketones also excreted in urine = ketoneuria (also enhances polyuria) - ketone accumulation = metabolic acidosis = ketoacidosis - can lead to coma and death

Question 29

What are the major manifestations of diabetes?

Answer 29

- polyuria (increased volume and frequency) - polydypsia (excessive thirst and excessive fluid intake) - polyphagia (increased food intake) - weight loss (calories lost in urine and energy stores used)

Question 30

Why is vascular damage a chronic complication of diabetes? What other problems can this cause?

Answer 30

- increase/accumulation of metabolites in blood damages blood vessels - glucose attaches to proteins = glycosylated proteins and causes them to function abnormally (ex. Hb, albumin, collagen) - glycosylated proteins deposit on endothelium and impair transcapillary exchange, cause platelet aggregation and impede blood flow - this can cause atherosclerosis, MI, CVA - inadequate blood flow can impair healing and can allow anaerobic bacteria to grow

Question 31

Why is retinopathy a chronic complication of diabetes? What problems can this cause?

Answer 31

- capillaries in the retina are damaged | - can cause visual impairment, ex. cataracts and glaucoma

Question 32

Why is nephropathy a chronic complication of diabetes? What major problem can this cause?

Answer 32

- glomerulus can be damaged, this decreases renal function and can lead to renal failure

Question 33

Why is neuropathy a chronic complication of diabetes? What problem can this cause?

Answer 33

- decreased blood flow to neurons = neural ischemia - causes some demyelination, which causes poor conduction - results in neural deficit - this can cause problems ex. foot ulcers d/t lack of sensation

Question 34

Why are infections a chronic complication in diabetes?

Answer 34

- decreased blood flow impairs healing, can allow anaerobic bacteria to grow - neuropathies can mean infections not caught early - UTIs - glucose in urine facilitates bacterial growth

Question 35

How is diabetes diagnosed?

Answer 35

``` - history (3 Ps, unexplained weight loss) and - random glucose over 11 mmol/L on ongoing basis or - IFG equal or over 7 mmol/L or - IGT over 11 mmol/L or HbA1C equal or over 6.5 % ```

Question 36

How is diabetes treated?

Answer 36

- lifestyle modification - glycemic control through: - --- oral hypoglycemics for type 2 (give metformin if HbA1C is still over 7% after 2-3 months of lifestyle mod; give metformin and insulin if HbA1C is over or equal to 9%) - --- insulin for type 1

Question 37

What are the different types of oral hypoglycemics?

Answer 37

- thiazolidinediones: increases tissue response to insulin - insulin secretogogues: stimulate beta cells - biguanides: decrease hepatic glucogenesis