3. Glucose and Carbohydrate Metabolism (Part III) Flashcards
What is the general age of onset for T2DM?
Over 40 years old
What are the two risk factors for T2DM?
- Visceral obesity
- Heredity
- African, native American, Asian, Pacific Island, and Southern European origin
Why isn’t T2DM considered to be adult-onset diabetes anymore?
As an increase in adiposity in youth may trigger its onset as well
Why isn’t T2DM considered to be non-insulin-dependent diabetes mellitus anymore?
Because as the disease advances, even if the issue is with insulin sensitivity, a person may require exogenous insulin
What percentage of individuals with diabetes have T2DM?
90%
How many people will become diabetic by the year 2025?
300 million
How many Canadians have diabetes? How many will have diabetes by the end of the decade?
- 2 million
- 3 million
Why is diabetes underestimated?
As it is a late-onset disease
What factors are causing the increased rate of diabetes?
- Population is aging
- Obesity rates are rising
- Canadian lifestyles are increasingly more sedentary
What are the symptoms of T2DM?
- Glucosuria
- Ketonuria
- Dehydration
- Weight loss
- Increased appetite (polyphagia)
- Hyperglycemia
What is the renal threshold for glucose?
10 mM/L
What are the symptoms of diabetic ketoacidosis?
- Drowsiness
- Lethargy
- Nausea
- Vomiting
Why does dehydration particularly affect the elderly?
Since people don’t tend to listen to their thirst signals as much as they get older
Why does severe T2DM lead to weight loss?
Because glucose is not used, but spilled in the urine
What is the FIRST symptom of T2DM?
- Increased insulin
- Peripheral tissues are not sensitive to insulin
- Pancreas continually secretes insulin to get the high blood glucose into cells
When does fasting blood glucose rise in T2DM?
- AFTER the rise of insulin levels
- After awhile, the pancreas must work harder to produce enough insulin to maintain euglycemia
What are the consequences of hyperglycemia?
- Increased infections
- Decreased blood flow
- Decreased wound healing
What is administered in the ICU to decrease complications and infections?
Insulin
What becomes resistant in T2DM?
GLUT4, which is normally insulin-mediated, becomes insulin resistant
What does the hyperstimulation of B-cells in T2DM cause?
Exhausts B-cell, which may no longer sustain the high insulin production, resulting in the requirement for exogenous insulin
What metabolic effects are caused by insulin resistance?
- Binding of insulin to receptor are decreased
- Less GLUT4 synthesized and transported to the surface (decreases glucose uptake)
- Decreased anabolic response within the cell
- Blunted protein synthesis response
How is the inflammatory nature of obesity linked to insulin resistance?
- Excess fatty acids are metabolized in cells that do not have glucose, which sets up a disequilibrium in cell metabolism
- Causes ER stress
- Cell cannot cope with the lack of homeostasis
What is exacerbating the hyperinsulin state?
The high rate of gluconeogenesis, while blood glucose is already high
What are the effects of diabetes in GLUT4 peripheral tissues?
- Decreased glucose uptake
- Fat-based economy
- Accumulation of Acetyl-CoA
- Increase in muscle proteolysis
- High rate of gluconeogenesis
What are the effects of diabetes in the liver?
- Increased glucose uptake increases glycogenesis and lipogenesis
- Increased VLDL and LDL (atherosclerosis)
- Non-alcoholic fatty liver disease (NAFLD)
How is atherosclerosis increased in T2DM?
- High glucose uptake by the liver induces lipogenesis
- Synthesis of VLDL, which increases LDL and causes the invasion of artery walls
What are the effects of diabetes in non-GLUT4 peripheral tissues?
- Increased glucose uptake
- Results in damaging effects of the hyperglucose state
What effects link diabetes and cardiovascular disease?
- Increased lipogenesis
- Increased VLDL secretion
- Increased oxidation and glycation of LDL
How does higher LDL promote atherosclerosis?
- LDL is more likely to be damaged
- Uptake by the liver and LDLR receptor is lower
- Increases plaque formation and atherosclerosis
What are the functions of metformin?
- Decrease hepatic gluconeogenesis
- Increase peripheral insulin sensitivity
- Increase GLUT4-mediated glucose uptake
- Increase fatty acid oxidation
What are the four net effects of metformin?
- Decreases hepatic steatosis
- Increases liver insulin sensitivity
- Decreases plasma glucose
- Decreases plasma triglycerides
What is metformin’s mechanism of action?
- Increased phosphorylation activates AMPK
- Decreases SREBP-1 activity
- Increases hepatic fatty acid oxidation and decreases fatty acid synthesis
What is the function of sulphonylureas?
Increases insulin production and release
What is the function of Toujeo?
- Made of long-acting insulin microcrystals
- Allows insulin to act over a period of 24-hours, providing a basal insulin level
What are incretins? Give an example.
- SGLT2 inhibitors
- Farxiga
What was recommended in the 1930s for diabetes? Why did it change?
- Low-carb, high-fat diet
- They realized that excess fat synthesis is responsible for many of the symptoms observed in diabetes
What is the AMDR for protein? How much is recommended in diabetics? Are we thinking of changing the amount?
- 10 to 35%
- 15% recommendation
- As protein metabolism may also be resistant to insulin, the recommendations should be increased
What is the key to management of T2DM?
- Weight management and activity
- Decrease in 10% of an individual’s body weight over a period of 6 months is enough to increase insulin sensitivity
How may surgery influence diabetes?
- The stress reaction may exacerbate diabetes
- Increased insulin resistance (hyperglycemia and protein breakdown)
What aids in the loss of body protein?
Nutrition support
What aids in the neuroendocrine response causing insulin resistance and hyperglycemia?
Epidural (analgesia)
How does loss of body protein negatively influence the response to surgery?
- Immunosuppression (delayed wound healing)
- Muscle wasting (delayed convalescence)
