Diabetes Flashcards
Where is insulin made?
Insulin is made by the beta cells in the pancreatic islets.
Where is glucagon made?
Glucagon is made by the alpha cells in the pancreatic islets.
What does insulin do?
Insulin allows glucose to be transported into cells.
What does glucagon do?
Glucagon stimulates the break down of glycogen.
What are the features of pre-diabetes?
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)
Which type of diabetes has an absolute insulin deficiency?
Type 1 diabetes mellitus.
Why is metabolic syndrome important?
It may or may not precede diabetes. It predisposes you to type 2 diabetes and cardiovascular disease.
What are some features of metabolic syndrome?
- 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
What are three acute complications of diabetes mellitus?
1) hypoglycemia
2) diabetic ketoacidosis
3) hyperosmolar hyperglycemic state (HHS)
What can cause hypoglycemia?
- missed meal
- insulin overdose
- overexertion
What do we worry about with hypoglycemia?
If glucose is too low, the brain is deprived of glucose. As a result the patient will usually lose consciousness, enter hypoglycemic coma.
How is hypoglycemia treated?
- 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)
Diabetic ketoacidosis develops when these two circumstances are in place.
1) very low insulin levels
2) high levels of glucagon
What 3 derangements are seen when diabetic ketoacidosis develops?
1) hyperglycemia
2) ketosis (formation of ketones from lipid breakdown)
3) ketoacidosis (depresses the CNS and can lead to coma)
Why does hyperosmolar hyperglycemic state normally occur in type 2 diabetes?
Because the cells are not completely deprived of glucose (insulin deficiency is not absolute) and there is no breakdown of lipids.
What two problems are caused by hyperosmolar hyperglycemic state?
1) hyperglycemia
2) hyperosmolarity
What causes hyperosmolar hyperglycemic state?
- excessive carb intake
- increased insulin resistance
Explain what happens in hyperosmolar hyperglycemic state.
- 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
What are 5 chronic complications of diabetes mellitus?
1) vascular damage (that can lead to atherosclerosis, MI, CVA)
2) retinopathy
3) nephropathy
4) neuropathy
5) infections
What are the different types of diabetes mellitus?
- type 1 (type 1a is more prevalent, is immune-based, type 1b is rare and idiopathic)
- type 2
- gestational
What is the etiology of both type 1 and type 2 diabetes?
complex trait (polygenic AND an environmental factor)
What genes have been found to be affected in people with type 1 diabetes?
- 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)
What gene is often affected in young people who develop type 2 diabetes?
- 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)
If a member of your family has type 1 diabetes, does your risk for developing it increase? By how much?
yes, your risk inreases x10
What happens at the cellular level to cause type 1 diabetes? What is the result?
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.
What is insulitis?
inflammation within the islets of Langherhans, can be caused by autoimmune destruction of beta cells preceding type 1 diabetes
What happens in type 2 diabetes?
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)
Describe the pathology of diabetes.
- 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
What are the major manifestations of diabetes?
- 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)
Why is vascular damage a chronic complication of diabetes? What other problems can this cause?
- 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
Why is retinopathy a chronic complication of diabetes? What problems can this cause?
- capillaries in the retina are damaged
- can cause visual impairment, ex. cataracts and glaucoma
Why is nephropathy a chronic complication of diabetes? What major problem can this cause?
- glomerulus can be damaged, this decreases renal function and can lead to renal failure
Why is neuropathy a chronic complication of diabetes? What problem can this cause?
- 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
Why are infections a chronic complication in diabetes?
- 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
How is diabetes diagnosed?
- 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 %
How is diabetes treated?
- 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
What are the different types of oral hypoglycemics?
- thiazolidinediones: increases tissue response to insulin
- insulin secretogogues: stimulate beta cells
- biguanides: decrease hepatic glucogenesis
