DM Pathophysiology Flashcards
1
Q
Diabetes
A
- Chronic, metabolic disorder of fat, carb, and protein metabolism
- Hyperglycemia arising from defects in insulin secretion, action, or both
2
Q
Type I DM
A
- B-cell destruction
- Absolute insulin deficiency
- 5-10% of DM cases
3
Q
Type II DM
A
- Insulin resistance _ relative insulin deficiency
- 90-95% of all DM cases
4
Q
DM I Pathophysiology
A
Autoimmune cells
destruction of B-cells
Four Features of Disease Progression:
- Pre-clinical period: presence of immune markers
- Hyperglycemia after 80-90% of B-cells are destroyed due to deficiency of insulin and amylin
- Honeymoon phase - transient remission
- Established disease
5
Q
T1DM Autoimmune Markers
A
- Type I diabetes: immune mediated in >95% of cases
- Idiopathic in less than 5%
- GAD65 (70-90%), IAA, ICA512, ZnT8
6
Q
Insulin Cleavage
A
- Synthesized as preproinsulin
- Cleaved to proinsulin
- Proinsulin split into insulin and C peptide
7
Q
T2DM Pathophysiologu
A
- Progressive, heterogeneous disorder with ongoing B-cell failure
- Relative insulin deficiency
- Range from severe insulin resistance, minimal insulin secretory defects, primary defect in insulin secretion
- Majority of patients have glycemic control that deteriorates with time
- Metabolic disorder
8
Q
T2DM Development
A
- Healthy individuals: insulin secretion by pancreatic islet allows for normal glucose disposal into insulin-sensitive tissues
- Prediabetes: genetic predisposition, over-nutrition, and physical inactivity reduce the response to insulin-stimulated glucose uptake that is compensated for by increasing insulin production
- Type 2 DM: insulin secretion no longer compensates for increased peripheral insulin demand
9
Q
T2DM Progression
A
- Insulin Resistance
- Increased insulin production
- Death/burnout of beta cells
- Reduced or absent insulin
10
Q
T2DM: Insulin Resistance
A
- Body cells become less responsive to the insulin we make
- Usually takes a long time to develop (years to decades)
11
Q
T2DM Beta Cell Burnout
A
- By the time of T2DM diagnosis, more than 80% of B-cells may be gone
- Progression doesn’t always occur
12
Q
Hyperglycemia - Ominous Octet
A
- Decreased insulin secretion
- Increased glucagon secretion
- Increased HGP
- Neurotransmitter dysfunction
- Decreased glucose uptake
- Increased glucose reabsorption
- Increased lipolysis
- Decreased incretin effect
13
Q
Egregious Eleven: B-Cell destruction Effects
A
- Pancreatic B-Cells
- Incretin Effect
- Alpha-cell defect
4-6. Adipose, Muscle, Liver - Brain
- Colon/Biome
- Immune Dysregulation/inflammation
- Stomach/Small Intestine
- Kidneys: SGLT2
14
Q
Pancreatic B-Cells Dysfunction
A
- Insulin resistant organs: liver, muscle, adipose tissue (increased lipid exposure can lead to B-cell dysfunction)
- Other organs: brain, colon, immune system
15
Q
Incretin Effect
A
- Resistance to the action of glucose-dependent insulinotrophic polypeptide also called gastric inhibitory polypeptide (GIP)
- B-cell resistance to the stimulatory effect of GIP on insulin secretion
- Deficiency of GLP-1: resistance to stimulatory effect of GLP-1 on insulin secretion
16
Q
Alpha-cell Defect
A
-Increased glucagon
17
Q
Adipose, Muscle Liver
A
- Insulin promotes fuel storage (anabolism) in these tissues
- Also prevents the breakdown of release of fuel that have already been stored (catabolism)
- Insulin resistance and inflammation lead to production/release of FFAs and insulin resistance-provoking proinflammatory cytokines in the adipose cells
18
Q
Brain Effects
A
- May experience insulin resistance like other organs
- Increased appetite due to decreased GLP-1/GIP
- Decreased morning dopamine surge
- Increased sympathetic tone
19
Q
Colon/Biome
A
- Gut microbiome role in digestion: strengthens immune system, prevents infection
- Antibiotic use may increase risk of T2DM: kill “good” bacteria allowing for “bad” bacteria to dominate GI tract, alters nutrient absorption/metabolism
- Associated insulin resistance
20
Q
Stomach/Small Intestine
A
- Amylin production decreased as a result of B-cell dysfunction: amylin co-secreted with insulin from B-cell
- Effects of decreased amylin: accelerated gastric emptying, increased glucose absorption in small intestine, corresponding increases in postprandial glucose levels
21
Q
Kidneys Effects
A
- As blood glucose increases, the kidney begins to reabsorb the glucose so it will not go into urine
- Up-regulates SGLT-2 protein in kidney to further hyperglycemia
22
Q
Complexities of Diabetes
A
- Increased insulin resistance
- Increased hepatic glucose production
- B-cell failure or destruction
- Abnormalities in incretin action
- Enhanced renal SGLT2 activity
- Abnormalities of glucagon physiology
