Diabetes Flashcards
The 3 main types of diabetes:
- T1: insulin dependent; autoimmune against β-cells.
- T2: insulin resistance.
- Gestational: during pregnancy only.
What types of glucose channels are located on the pancreas?
GLUT2 (do not respond to insulin).
Steps in insulin release from pancreatic beta cells:
- glucose enters beta cells via GLUT2.
- glucose undergoes glycolysis and TCA cycle to produce ATP.
- increased ATP activates ATP-sensitive K+ channels; depolarization.
- depolarization activates calcium channels.
- increased intracellular calcium activates cAMP.
- cAMP triggers insulin secretion.
What molecules cause insulin secretion through direct activation of cAMP in pancreatic beta cells?
incretins binding incretin receptors.
The three incretins and their overall function:
- CCK, GLP1, GIP.
- increase insulin secretion and inhibit glucagon secretion.
Common types of organ damage due to diabetes:
- microvascular
- retinopathy
- nephropathy
- neuropathy
- macrovascualr
- stroke
- cardiovascular disease
The two causes of organ damage in diabetes:
- non-enzymatic glycosylation of proteins (alters activity).
- stimulation of polyol pathway (sorbitol accumulation).
What is HbA1C?
- glycosylated hemoglobin due to hyperglycemia.
- indicator of blood glucose status for past 120 days.
Steps in cellular damage due to sorbitol accumulation in hyperglycemia?
- glucose accumulates in tissues with insulin-independent glucose transporters.
- glucose converted to sorbitol via aldose reductase.
- sorbitol accumulaiton leads to the influx of water.
- cellular swelling causes damage.
Primary distinguishing features of T1 diabetes:
- young, sudden onset insulin deficiency and symptoms.
- ketoacidosis.
Cause of T1 diabetes:
- Autoimmune attack against pancreatic β-cells.
- insulin deficiency/absence.
Symptoms of T1 diabetes:
- abrupt onset of 3 “P”s:
- polyphagia (excessive hunger)
- polydipsia (excessive thirst)
- polyuria (frequent urination)
What leads to hypertriglyceridemia (chylomicrons, VLDL, and TAGs) in T1 diabetics?
- Lipoprotein lipase synthesis low due to insulin absence/deficiency.
- HPL activity increased due to glucagon and epinephrine.
What leads to hyperglycemia in T1 diabetics?
- increased gluconeogenesis (glucagon).
- decreased uptake of glucose by peripheral tissues (GLUT2; needs insulin) and liver (glucokinase inactive; needs insulin).
What leads to ketoacidosis in T1 diabetes?
- mobilization of FA from adipose tissue.
- increased hepatic β-oxidation and synthesis of ketone bodies.
Treatment for T1 diabetes:
- insulin therapy to normalize blood glucose and prevent ketoacidosis.
Why is ketoacidosis more common in T1 than T2 diabetes?
- T1 has complete absence of insulin.
- lipolysis is uninhibited; increased beta-oxidation.
- liver forms ketone bodies (hydroxybutyrate) from excess acetyl CoA.
Why is intensive insulin therapy contraindicted in children and elderly?
- increased risk of hypoglycemia.
- children: brain damage due to hypoglycemia.
- elderly: stroke and MI due to hypoglycemia.
HbA1C target level during standard insulin therapy:
8-9% (1-2 insulin shots a day).
HbA1C target level during intensive insulin therapy:
7% (3-4 insulin shots a day).
Symptoms of T2 diabetes:
- gradual onset of hyperglycemia and hypertriglyceridemia.
- NO KETOACIDOSIS.
Primary cause of T2 diabetes:
insulin resistance.
Which requires larger amounts of insulin to regulate glucose levels: obese or normal weight individuals?
obese
Progression of T2 diabetes:
- insulin resistance leads to increased insulin secretion.
- blood glucose continues to rise; hyperinsulinemia.
- beta-cell dysfunction; insulin secretions fall.
- hyperglycemia worsens.
