T2DM Pathophysiology Flashcards Preview

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Flashcards in T2DM Pathophysiology Deck (23):

What are the consequences of an absolute or relative lack of insulin on the liver

• Glycogenolysis: release glucose
• Takes up amino acids released from skeletal muscle to produce new glucose (gluconeogenesis)
• Takes up free FA released from adipose tissue during lipolysis and produces ketones (ketogenesis)
• Takes up glycerol released from adipose tissue during lipolysis to produce glucose (gluconeogenesis)


What are the consequences of an absolute or relative lack of insulin on the muscle

• Protein breakdown and decreased aa uptake by muscle
• Liver uses the aa for gluconeogenesis
• Net loss of protein in patients with uncontrolled DM. Can lead to decreased muscle mass until DM is controlled.


What are the consequences of an absolute or relative lack of insulin on the adipose tissue

• Lipolysis → release of free FA and glycerol
• Lipoprotein lipase in adipose tissue is very sensitive to insulin. Without insulin, enzyme doesn’t work well → increased lipolysis and more FFA and glycerol leaving adipocytes
• FFA are converted to ketones by the liver (cause of DKA in severe cases)
• Decreased TG synthesis by the liver
• Net result: increased lipolysis and decreased lipogenesis → weight loss and decreased fat stores


Define diabetes

- DM is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion or insulin action, or both.
- The chronic hyperglycemia of DM is associated with long term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels


Define Type 1 DM

• D/t beta cell destruction, usually leading to absolute insulin deficiency
• May be immune-related or idiopathic
• About 2-5% of all DM


Define type 2 DM

• Ranges from predominantly insulin resistance with relative insulin deficiency to predominantly secretory defect with insulin resistance.
• About 95-98% of DM


ID risk factors for a person for pre-DM or DM (13)

- >45 yo
- BMI ≥ 25 (BMI ≥ 23 in Asians)
- Physically inactive
- First-degree relative with DM (mother, father, brother, sister)
- High-risk ethnic group (AA, Hispanic, Native American, Asian, Pacific Islander)
- Hx or Dx of gestational DM
- Women with PCOS
- Hx of CVD
- HTN (≥140/90) or treated for HTN
- HDL cholesterol <35 mg/dL and/or TG >250 mg/dL
- Previous impaired glucose tolerance test or impaired fasting glucose test
- A1C ≥ 5.7% previously
- Other clinical conditions associated with insulin resistance (severe obesity, Acanthosis nigracans)


What chances occur in the liver in T2DM

• Insulin resistance → glucose overproduction during basal state despite fasting hyperinsulinemia (even though have a ton of glucose and insulin, none of it is getting in the cells so the body keeps releasing/making more glucose)
• Impaired suppression of hepatic glucose production by insulin


What chances occur in the muscle in T2DM

Insulin resistance → impaired glucose uptake after CHO ingestion, resulting in postprandial hyperglycemia


What chances occur in the beta cells in T2DM

- Insulin resistance → beta cells augment insulin secretion
• As long as able to augment sufficiently to offset resistance, glucose tolerance remains normal
• Over time beta cells start to fail, initially postprandial plasma glucose levels rise (insulin can’t keep up), then fasting plasma glucose levels rise (insulin really can’t keep up)
- Progressive beta cell failure determines the rate of disease progression


Use one word to describe the progression from normal blood glucose to pre-DM to DM



Describe insulin resistance

- There is a cellular resistance to insulin’s action in promoting glucose uptake by adipose and muscle cells
- Beta cells of pancrease respond by increasing insulin which may maintain blood sugar levels for a long time
- Eventually beta cells can't keep up and blood sugar begins to rise higher than normal, esp. after eating


Describe blood glucose, insulin production, insulin resistance in pre-DM

• Blood glucose remains fairly normal
• Insulin production is increased
• Insulin resistance increases


Describe blood glucose, insulin production, insulin resistance in T2DM

• Blood glucose continues to elevate
• Insulin production declines to below normal levels
• Insulin resistance increases past pre-diabetes levels


What happens to hepatic glucose production as insulin resistance increases?

insulin secretion defects increase, lead to increased hepatic glucose production


Describe the first and second phase of insulin release in early T2DM

• First phase response is very minimal
• Second phase is initially lower than normal but continues at an elevated rate past where a normal level would drop


What are the effects of the changes to first and second phase insulin release in early T2DM

• When early phase is inhibited, portal vein insulin levels are low → hepatic glucose production is not suppressed (more glucose into the blood)
• Excessive hyperglycemia due to nonsuppressed release of glucose from the liver and incoming endogenous glucose intake from GI tract
• Hyperglycemia leads to increased secretion of insulin during the hours after glucose ingestion (has to play catch-up)
• Plasma glucose will return to normal but at the expense of late hyperinsulinemia


Describe the first and second phase of insulin release in late T2DM

• First phase is gone
• Second phase is very slight, very little insulin response to glucose


What are the effects of the changes to first and second phase insulin release in late T2DM

• Beta cell dysfunction leads to reduced insulin production
• Beta cells no longer able to compensate for insulin resistance → hyperglycemia
• If present with sx of hyperglycemia, severe beta dysfunction is present, hepatic glucose is elevated, and insulin resistance is present.


What are the sx of hyperglycemia (12)

- Polydipsia
- Polyphagia
- Polyuria
- Nocturia
- Unintended weight loss
- Repeated vaginal yeast infections (2-3+ / 6 months)
- Repeated fungal/yeast infections elsewhere in body (otitis externa, body folds)
- Repeated UTI
- Fatigue
- Sores that don’t heal
- Erectile dysfunction in men
- Blurred vision


Pathophysiology of repeated yeast/fungal/bacterial infections

due to disruption of normal GU flora.

Not sure about yeast/fungal infections in ear and body folds…


Pathophysiology of sores that won't heal

- microvascular damage reduces blood flow to damaged tissues.
- Injuries can occur due to neuropathy that prevents perception of injuries.


There are other pathophysiology question in the LO that are also covered in the NC for T1DM

So I didn't put them here also, you are welcome