L22 - Blood Glucose control III

Why is there a greater insulin response when eating glucose vs injection?

L cells in small intestine secrete GLP1 into bloodstream → stimulates beta cells to release insulin, missing GLP1 stimulus only gives a 50% insulin reaction

How is GLP1 broken down?

Enzyme called DDP4, GLP1 lasts about 7 mins in body

What proportion of insulin released is due to blood vs GLP1?

50/50

What percentage of DM patients are DM1?

10%

Why do blood glucose levels rise in DM2?

Without translocation and insertion of GLUT4, glucose cannot be taken up

If 50% of IRs work…

50% of IRS phosphorylated → 50% of GLUT4 translocated → 50% of glucose transported

What is lipotoxicity in DM2?

Fat cells make TNFα, based on BMI, inhibits step one of insulin transduction signalling pathway

How can DM2 patients reduce TNFα?

Losing weight and exercise

Comparison DM1 vs DM2: age at onset

<20 yrs vs >40 yrs

Comparison DM1 vs DM2: speed of symptom development

Rapid vs slow

Comparison DM1 vs DM2: percentage of DM population

~5% vs ~95%

Comparison DM1 vs DM2: development of ketoacidosis

Common vs rare

Comparison DM1 vs DM2: association with obesity

Rare vs common

Comparison DM1 vs DM2: beta cells of islets (at onset)

Destroyed vs not destroyed

Comparison DM1 vs DM2: insulin secretion

Decreased vs normal/increased

Comparison DM1 vs DM2: autoantibodies to islet cells

Present vs absent

Comparison DM1 vs DM2: associated with particular MHC antigens

Yes vs unclear

Comparison DM1 vs DM2: treatment

Insulin injection vs diet/exercise

Significance of cross bridge cycle in DM2

By exercising Ca2+ channels can activate GLUT4 translocation

What is glycogenolysis?

Glucagon releases phosphorylase to break down glycogen to glucose

Why does LGO increase in DM2?

Too little insulin binding to muscles, blood glucose raises from liver, insulin resistant in skeletal muscles, insulin resistant in liver

Glipizide

Oral hypoglycemic drug → targets beta cells to produce more insulin

Metformin

First drug choice, oral hypoglycemic drug, stops gluconeogeneis, reduces LGO

GLP1 analog (exenatide)

Oral hypoglycemic drug, targets beta cells for more insulin secretion, looks like GLP1

DDP4 antagonist (liptin)

Oral hypoglycemic drug, blocks DDP4 enzyme from breaking down GLP1, insulin lasts longer in body

Test for diabetes: blood glucose level

Normal is 70-100 mg/dL, fasting before test

Test for diabetes: oral glucose tolerance test (OGTT)

3 hrs for 75g of carbohydrates to be absorbed in cells, after 2 hrs, blood glucose should be 140 mg/dL.

OGTT results

>200 mg/dL → DM, 140-200 mg/dL → pre DM

Test for diabetes: Hemoglobin A1C test

No fasting, high levels of glucose → glucose will bind to beta chain, higher glucose level, higher HbA1c, marks 100 days of glucose levels, normal is 5% HbA1c, over 7% → DM

Glucagon emergency kit for insulin shock

Inject subcutaneous, glucagon targets liver to phosphorylase 1-4 bonds, releases glucose into blood

When does insulin resistance begin in gestational DM?

~24 weeks

Weight gain in GDM

Gain 40+ lbs (25 lbs normal)

Macrosomia

Large baby 12+ lbs, fetuses make own insulin, large fat deposits in fetus, baby too big for vaginal birth, baby becoming hypoglycemic after birth

GDM treatment

Special diet, reducing glucose intake, exercise → activating GLUT4, daily glucose monitoring (after each meal), insulin injections