Lecture 26 - 2018/2017 Flashcards
When does glucose appear in urine?
When the blood glucose is >10mmol.
What is insulin resistance?
When cells in the body (muscle and fat) do not respond properly to insulin so there are high levels of glucose in the blood. There are high insulin levels and high glucose levels as well - basically a receptor problem.
What is insulin resistance associated with?
- Obesity.
- Type 2 Diabetes.
- Endocrine disorders e.g. Cushings, Acromegaly.
- Metabolic syndrome.
What can you see in someone who is insulin resistance?
- Metabolic syndrome cluster.
- Acanthosis nigricans.
- Polycystic Ovarian Syndrome.
What do you see in metabolic syndrome?
Central obesity (waist >94cm men and >80cm women)
[Plus two of]:
1. Hypertension.
2. Elevated triglycerides (>1.7).
3. Low HDL (<1.1 women and <0.9 men).
4. Abnormal glucose (IGT, IFG - reduced glucose uptake so reduced gluconeogenesis in muscle).
What do you see in acanthosis nigricans?
Black rash around the back of the neck, armpits and knuckles - due to growth factor of insulin.
What are the causes of insulin resistance?
Environmental factors:
- Intrauterine environment.
- Central obesity
How does central obesity cause insulin resistance?
- increased visceral fat (esp. intra-abdominal) therefore increased stored triglyceride leading to large adipocytes.
- large adipocytes are resistant to the ability of insulin to suppress lipolysis.
- uncontrolled lipolysis leads to an increase in non-esterified fatty acids (NEFA) and an increase in glycerol (do not present with DKA because there is enough insulin around to prevent major ketogenesis).
- increased glycerol turns into glucose, so patient produces more insulin to counteract, which creates viscous cycle with an increase in insulin (trying to keep blood sugar normal).
- NEFA, glycerol and inflammatory cytokines are released by visceral adipose tissue aggravate insulin resistance in muscle and liver.
- NEFA and glycerol also accumulate in beta cells of pancreas, which may cause lipotoxicity (fat prevent beta cells from functioning properly).
How does insulin resistance occur?
It occurs inside the cell, but the mechanisms are uncertain:
- Inflammation - obesity is a pro-inflammatory state, produces a lot of cytokines that will cause inflammation which can lead to development of a fatty liver.
- Fatty liver - fatty liver can cause chronic liver disease, which can lead to the liver itself being insulin resistant. The fatty liver will also produce cytokines and add to increased adipocyte size.
- Increased adipocyte size - increased adipocyte size leads to reduced adiponectin and increased resistin, also increased free fatty acids. The increasing free fatty acids then lead to beta cell toxicity, and adds to the fatty liver.
What are the consequences of insulin resistance?
Diabetes Mellitus (Type 2).
What is lean normal?
Where the person produces enough insulin with glucose load and respond accordingly to insulin.
What is obese normal (insulin resistant)?
Produce a lot more insulin with glucose load, but able to produce enough to keep glucose in normal range.
What is lean type 2 (insulin deficit)?
Can’t produce enough insulin with glucose load.
What is obese type 2 (insulin deficit and resistant)?
Can’t produce enough insulin with glucose load. But because they’re insulin resistant they are actually producing more insulin than lean normal without diabetes (still not sufficient to maintain glucose level).
What is the normal fasting range for blood glucose?
<6mmol/mol.
