Topic 3 - part 2 Flashcards
How can you diagnose type 1 diabetes?
Glucosuria/ Ketonuria
- urine sample
Fasting plasma glucose concentration
> 7mmol/L
Oral glucose tolerance test
> 11 mmol/L
Glycated hemoglobin
> 6,5% (normal range 3,5-5,5%)
What are some direct consequences of acute high blood glucose?
- Hyperglycemia
- Ketoacidosis
- Hyperosmolar coma - dehydration (diabetic coma)
- happens in untreated diabetes
What is the problem in type 1 diabetes?
Cell-mediated destruction of B-cells producing insulin in pancrease
=> No production of insulin
What is a long term consequence of glucose not being able to enter the cell?
Inapropriatly high rate of amino acid oxidation
Acetyl - CoA accumulation=> ketones in breath, blood, urine
What is SGLT2?
transporter in cell membrane from lumen of renal tubule
What is farxiga? how does it act, what consequences?
Inhibits SGLT2 => so inhibits reabsorption of glucose in the renal tubule. This leads to even more glucose spilled in urine. Could lead to severe dehydration, because glucose excretion pulls a lot of water. Also, could potentially loose weight because glucose (calories) excreted…
What are chronic consequences of diabetes?
Microvascular problems => disease of small blood vessels
RETINOPATHY - Retina damaged => blindness (retina has fine blood vessels that could be damaged by high blood glucose)
NEPHROPATHY - Kidney damage due to long term exposure to high blood glucose => can become leaky. Watch for blood pressure…
NEUROPATHY - nerve damage- peripheral nerves damaged by high blood glucose
Macrovascular:
ATHEROSCLEROSIS
- more dominant in T2DM.. but still
What is management solution for type 1 diabetes?
- Insulin injection ( intra muscular = the most popular, pump, nasal, islet transplant)
- Activity
- Balanced intake
Insulin producing cells = ?
Glucagon producing cells =
Beta cells = insulin
Alpha cells = glucagon
What are the steps in insulin synthesis?
- translation and translocation => preinsulin
- Folding, oxidation and SIGNAL PEPTIDE CLEAVAGE=> proinsulin
- ER export, Golgi transport, vesicle packaging
- Protease cleavage liberates C -peptide
- Carboxypeptidase E produces insulin => insulin
*** take home message => progressively more cleavage, what looked like 2-3 polypeptide chain is actually one
Explain how insulin is excreted.
- High influx of glucose inside Beta-cell using GLUT2
- Increase ATP production will close K+ channels, cause depolarization
- Depolarization will cause opening of Ca 2+ channels
- Calcium will change gene expression through CREBP (calcium responsive element binding protein)
- Increase gene expression to increase insulin production, and also increase insulin mobilization from stores because we don’t want to wait.
What are the 4 anabolic effect of insulin?
- Glycogen synthesis
- Fat synthesis
- Protein synthesis
- Growth and gene expression
Prevalence of T2DM has _____ since 2000
tripled
What are some causes why number of people having T2DM is increasing? (prevalence…)
- Population aging
- Obesity rates are rising
- Canadian lifestyles are increasingly sedentary
- (indigenous people are 3-5 times more likely to develop T2DM than the general population…)
2 risks factors for T2DM?
- Heredity
- Obesity
What are some symptoms of T2DM?
- Glucosuria
- Blood glucose > 10mmol/L (hyperglycemia)
- Frequent urination, excessive thirst
- Ketonuria
- DEhydration => HHNKS
- Weight loss
- Increased appetite
What does HHNKS stand for?
Hyperglycemic Hyperosmolar Nonketotic Syndrom
- Dehydration of cell due to high blood glucose…
What is the first symptom in T2DM?
increased INSULIN! not increased blood glucose! because insensitivity to insulin…
How is there insulin insensitivity?
GLUT 4 cells are insulin resistant
- Non GLUT 4 cells exposed to high concentration of glucose
- High insulin followed by Beta cell exhaustion
- Then requirement for exogenous insulin
What is the effect of insulin insensitivity on GLUT 4 peripheral tissues?
- FAt based economy
- Low glycogen
- Increased muscle proteolysis to provide gluconeogenic a.a.
- Cori cycle
What is the effect of lack of insulin sensitivity on liver?
- Gluconeogenesis (even if glucose levels are high!)
- Lipogenesis (increased VLDL)
- NAFLD (non-alcoholic fatty liver disease)
What substrate is primarily going to be metabolized in GLUT 4 tissues?
fat! Since no glucose in cells, using fat for energy
- but other cells are going to be metabolizing CHO…
What is one widely used drug used to treat T2DM, and how does it act?
Metformin
- Decreases hepatic gluconeogenesis
- Increased peripheral insulin sensitivity
- Increases GLUT 4 medicated glucose uptake
- Increases fatty acid oxidation (hepatic oxidation)
What is really key in recommendations fo managing T2DM?
- Weight management
- Activity
