Exam #4: Pathophysiology of DM Flashcards
What are the distinguishing features between Type I and Type II DM related to B-cell function?
Type I= absolute beta cell destruction leading to beta cell destruction
- Decrease in beta-cell mass
Type II= insulin resistance followed by an insulin secretory defect
- Increase in beta-cell mass
*Note that there are 2x subtypes of DM-I, a & b. A= autoimmune, B= idiopathic–diagnosis is based on NOT finding autoantibodies
What are the distinguishing features between Type I and Type II DM related to insulin sensitivity?
- In type-II DM the body is NOT responding to insulin i.e. a decrease in insulin sensitivity, which initially results in an INCREASE in insulin secretion–a compensatory mechanism
- Type I, the body simply is NOT producing insulin
What are the distinguishing features between Type I and Type II DM related to blood glucose levels?
Generally, normal fasting blood glucose level is ~95 mg/dL
DM= higher fasting glucose, higher peak glucose, and longer time to return to normal
*Note that this is assuming some insulin activity i.e. DM-II, in DM-I, glucose levels simply continue to rise following glucose challenge.
What are the distinguishing features between Type I and Type II DM related to ketone production?
Type I is more commonly associated with ketogenesis and the development of DKA
Describe the significance of obesity, genetics, environment, and the immune system in the development of Type I DM.
Type 1= insulin-dependent DM
- genetic predisposition
- typically immune mediated i.e. autoantibodies to B-cells that are detectable PRIOR to the onset of symptoms
- environmental trigger via a virus or toxin–antigenic exposure may play a role as well
*****Note that key genes associated with DM-I are located on the MHC the locus. Also, despite the presence of autoantibodies in DM-I, these do NOT destroy the pancreas; rather, INFILTRATION OF T-LYMPOCYTES causes destruction of B-cells
Describe the significance of obesity, genetics, environment, and the immune system in the development of Type II DM.
- There is a strong correlation between visceral adiposity and DM-II
- However, there is also a genetic correlation related to B-cell function & turnover (e.g. twin studies–one twin has DM-II, the other has 90% chance of having it as well, which is HIGER than the same study in DM-I)
- Environmental= low physical activity and high caloric/fat intake are major contributing environmental factors to the development of DM-II
What are the signs and symptoms of Type I DM?
- Osmotic diuresis leads to POLYURIA
- POLYDIPSIA (thirst) due to a hyperosmolar state
- Blurred vision due to hyperosmolar state
- Weight loss
- Weakness/ Dizziness
- Paresthesias
- Depressed level of consciousness that is more severe with rapid insulin deficiency
What are the signs and symptoms of Type II DM?
1) Asymptomatic initially
2) Infections become more frequent b/c of the energy (glucose) source for microorganisms
3) Neuropathy
4) Classic severe insulin deficiency signs occurs late in the progression of symptoms
5) Obesity & metabolic syndrome
*****#4, note that type II DM becomes apparent when the Beta-cells are no longer able to compensate for increased resistance to insulin
What are the metabolic changes that occur in patients in Type I DM?
- Cells think that they’re starving b/c they don’t have glucose in the cell; thus, they try to mobilize energy, leading to…
- Gluconeogenesis
- Glycogenolysis
- Ketogenesis
What are the metabolic changes that occur in Type II DM patients?
Metabolic Syndrome:
1) Hyperinsulinemia
2) Dyslipidemia
3) HTN
What are the therapeutic strategies employed & rationale for these strategies in treating Type I DM?
1) Diet i.e. balanced carbs, fat, and protein
2) Patient education on:
- Carb counting
- Insulin action
- Blood glucose targets
3) Insulin ABSOLUTELY required it must be non-PO route b/c insulin is a peptide that will be degraded in the GI tract
What are the therapeutic strategies employed & rationale for these strategies in treating Type II DM?
First, remember that potential therapies for the DM may have a negative impact on the overall Metabolic Syndrome in DM-II, which presents a challenge to treating DM-II
1) Diet
2) Patient education
3) Pharmacologic strategies
*Insulin is used ONLY when other agents DO NOT allow for achievement of therapeutic goals
What are the acute complications potentially experienced by DM patients? How are these addressed?
Hypoglycemia (e.g. insulin overdose)
- Glucose
- Glucagon
DKA
- Restore plasma volume
- Reduce blood glucose
- Correct acidosis
- Replenish electrolytes
Outline the different pharmacological strategies that are used to treat DM-II.
1) Increase insulin secretion
2) Increase insulin action
3) Inhibit gluconeogenesis
4) Inhibit glucose digestion & absorption from the GI tract
5) Suppress glucagon secretion
How can you pharmacologically increase insulin secretion in DM-II?
- GLP1 analogs are used to activate GLP1 receptors to promote insulin secretion
- DPP4 (enzymes that breaks down GLP1) inhibitors, which indirectly promote insulin secretion
- Inhibition of ATP-sensitive K+ channels on B-cells to eventually cause insulin release
