Diabetes Intro Flashcards
What characterizes Type 1 DM?
Insulin-dependent (IDDM) → autoimmune/idiopathic destruction of pancreatic B-cells which results in absolute deficiency of insulin production
Juvenile or growth onset
Ketosis prone
What characterizes Type 2 DM?
Non-insulin dependent (mostly) → insulin resistance of cells, causing hyperglycemia/hyperinsulinemia (pancreas compensates with insulin production → may lead to damage)
Maturity onset (mostly) → also now in younger people because of high prevalence of obesity
Not prone to ketosis
What treatment is proposed for Type 2 diabetics that are ketosis prone?
Insulin
What treatment options are proposed for T2D patients who are ketosis resistant?
Diet, Oral meds and Insulin for both Obese and normal weight patients
Which provinces have the highest prevalence of diabetes?
Newfoundland (6.5%), Nova Scotia (6.1%), and Ontario (6.0%)
What are general causes of T1DM?
Environmental factors, genetic predisposition that results in the production of islet cell autoantibodies (ICA) that results in B cell injury → decreased or no insulin production. B cell injury can also be caused by other random factors.
What are the symptoms of diabetes?
- Initial Observations:
Increased thirst(polydipsia)
increased urination(polyuria)
increased hunger(polyphagia)
weight loss (T1DM) or obesity (T2DM) - What do clinical laboratory tests reveal?
Glycosuria, hyperglycemia, and an abnormal glucose tolerance (GTT)
What are insulin’s actions?
Increased glucose uptake and storage, lipogenesis, and protein synthesis
Decreased glycogenolysis, gluconeogenesis (= decreased endogenous glucose prod.), lipolysis and proteolysis.
Describe the pathophysiology of diabetes and insulin deficiency?
Insulin deficiency causes hyperglycemia in T1DM patients. This is directly due to an increase in hepatic glucose output, a decrease in glucose uptake by cells and increased gluconeogenesis (with amino acids coming from an increase in protein degradation).
As for fats, insulin deficiency causes a decrease in TG synthesis and increased lipolysis, therefore increasing blood F.A.s, which is an alternative energy source for cells. This process is called ketosis, which can lead to metabolic acidosis, increased ventilation and a diabetic coma → DEATH :)
Describe the fuel flux in diabetics in fasted state.
The liver produces endogenous glucose from gluconeogenesis using amino acids from muscle protein. Fatty acids from adipose tissue (hydrolyzed TGs) also contribute to metabolic fuel and are converted to ketones.
Describe the fuel flux in diabetics in fed state.
In fed state, there will be extra input from dietary sources in addition to contributions of amino acids from muscles and fatty acids to gluconeogenesis in the liver. There will still be muscle wasting occuring due to decreased protein synthesis as a result of insulin deficiency
Why is the fed state worse than the fasting state in diabetics from a metabolic point of view?
Because there is no insulin to stimulate protein synthesis, the ingested amino acids contribute to gluconeogenesis in the liver as well as the ones provided from muscle. This means that even if a person is ingesting protein, he/she’s muscles are still wasting to contribute to glucose production.
Describe the overall causes/pathophysiology of T2DM
In general, excessive food intake, a lack of exercise and to an extent, genetic predisposition contributes to a state of obesity. As a result of obesity, there is inflammation which along with genetic predisposition results in insulin resistance. Insulin resistance leads to hyperglycemia which leads to B-cell decompensation which is what characterizes T2DM. Hyperglycemia also results in compensatory hyperinsulinemia which further contributes to obesity. There is also lipotoxicity inflammation from excess free FA that can lead to damaging cells in the pancreas further reducing B-cell function. (for diagram reference slide 27 Lecture 18)
Define insulin resistance
A lower sensitivity of insulin’s action which will decrease the cells ability to suppress hepatic glucose production and increase glucose uptake, caused by defective insulin signaling within cells
Receptors may be defected leading to decreased number and affinity of binding
Most common cause of insulin resistance is due to post-receptor second messenger signaling
in the body, insulin resistance will increase gluconeogenesis in the liver, increase lipolysis in adipocytes and decrease glucose uptake, GLUT4 expression, glucose oxidation and glycogenesis in the muscle which ultimately will increase blood glucose levels and FFA in circulation
How does insulin-induced glucose uptake work?
Insulin release from the pancreas is stimulated by a rise in blood glucose. Insulin stimulates a membrane-bound receptor, which signals glucose transporters (GLUT4) to move from the cytoplasm to the cell membrane. These GLUT4 enable glucose to move from the extracellular space into the cytoplasm.
Insulin signaling thus increases glucose transport (GLUT4) in muscle and adipose cells, increases glycogen synthesis in muscle and liver cells, increases lipogenesis in liver and adipose cells, decreases gluconeogenesis in liver cells and decreases lipolysis in adipose cells.
What are risk factors for type 2 diabetes?
Age, obesity, sedentary lifestyle, ethnicity (aboriginal, african, south asian, hispanic), prediabetes (impaired fasting glucose or impaired glucose tolerance), family Hx, Hx of GDM, child of a woman with poorly controlled diabetes during pregnancy, low birth weight (< 2.5kg) and high birth weight (> 4kg), PCOS.
What are some other conditions related to insulin resistance?
- Obstructive sleep apnea
- Infection
- Steroid-induced
- cushing’s syndrome - rare condition that is the result of too much of the hormone cortisol in the body (most common in women over men age 20-40)
- Hemochromatosis (iron build up)
