L46 Diabetes Flashcards
Type 1 DM, three major metabolic changes and why
caused by AI destruction of Panc B cells
-10-20% cases, at any age
60-80% genetic factors and 20-40% environmental
onset market by
polyuria
-hyperglycemia exceeds renal threshold for glucose reabsorbtion
polydipsia
-renal water loss triggers osmotic diuresis
polypagia
-catabolism of proteins and fats produces negative energy balance, increased appetite
UNCONTROLLED: low IG ratio
- hyperglycemia
- increased production: liver glycogenolysis (early) gluconeogenesis (using muscle protein)
- decreased clearance: GLUT4 in MUSCLE…also adipo, and glycogen storage in muscle - hypertriacylglyceridemia
- increased production: extreme lipolysis from HSL activation, fatty acyl CoA repackaged into VLDL
- decreased Clearance: lipoprotein lipase (lower activity??) - ketoacidosis (diabetic ka- DKA)
elevated epinephrine and extremely low IG ratio generate very active HSL and excesive lipolysis
-increased hepatic Box
-increased acCoA from Mito (sub for Box)
-large amounts of ketone bodies (by liver)
—dehydration (from hyperglycemia) combined with extreme ketosis is ketoacidosis
T1 diabetic ketoacidosis
low insulin, illness, stress most often trigger DKA
signs: urinary ketones, sweet fruity breath, difficulty breathing, shock, coma, death
hyperglycemia, decreased pH, ketones present
Treat: IV insulin and IV fluids
- promote glucose uptake and inhibit lipolysis
- relive dehydration
- continual monitoring **
T1 hypoglycemia in response to insulin injection
triggered by skipping meals, eating at wrong time, strenuous exercise, medication
after insulin injection
glucagon levels typically fall during the course of the disease (not known why)
signs: shakey, nervous, tired, sweaty, hungry, confused, irritable, impatient,
treat: eat something with HIGH glycemic index, know how to inject glucagon or arrange for IV glucose
T2 DM and two major things that need to happen for it to be T2DM
non immune
80-90% typically after 35. 90-100% genetic factors, stronger than type I
- insulin resistance-decreased peripheral tissues to respond to insulin, especially muscle and adipose tissue
-primarily muscle and adipo
-obesity is the most common cause
-DOES NOT ALONE LEAD TO T2 DM
-muscle and adipose become VERY insulin resisten, liver/kidney/ovaries have less I resistance
THEORIES FOR OBESITY AND INSULIN R
-lipid overload: adipo cannot store any more fat, inappropriately stores in muscles, DAGs activates protein kinase C
-InflammationL ad tissue is endocrine releasing adipokines, increased fat storage messes up release of adipokines (cascade of fuck) - Pancreatic beta cell dysfunction
time course for type II diabetic
phase I: prediabetic
-high insulin
IR
phase II: diabetic -insulin decreasing -high insulin -IR and B cell exhaustion -BETA CELL DYSFUNCTION reflects the inability of bcells to continue to produce enough insulin. hyperinsulinemic stat cen happen for some time, some people can maintain it, some cannot, those who cannot progress to T2 DM
phase III -insulin decreased even more -low insulin -IR and B cell exhaustion FUTHER DECREASE IN INSULIN
T2DM metabolic changes
low insulin glucagon ration
hyperglycemia
- increased production: glycogenolysis in liver early days, and gluconeogenesis, using muscle protein.
- decreased clearance: glut 4 in muscle/adipo
hypertriacylglyceridemia
- increased production via high lipolysis from HSL. Fatty aculCoA repacked into VLDLs,
- less sever Hypertriacylglyceridemia than T1
- decreased clearance: lipoprotein lipase
hyperosmolar syndrome (T2DM emergency)
stress, alcohol con, illness, infection
signsL sweet smell to breath, extreme thurst, frequent urin, dehyd, fatigue, blurred vision, vomit, weak, rapid breath
BG level so high that can lead to cerebal edema (10fold) during fluid replacement
administer IV for dehydration
IV insulin for hyperglycemia
Diagnostic tests (TWO)
FPG (fasting plasma glucose)
blood glucose level after fasting for 8 hours.
-normal 99 or below
-impared fasting glucose (pre diabetics) 100-125
diagnostic test >126 on two tests
Oral Glucose tolerance test: OGTT
- high carb diet for three days prior
- glucose load following an overnight fast
- BG concentrations measured for next three hours
- usually used for gestational DM
- plasma glucose levels 200 at TWO time points in DM
TYPE ONE DIAG BY ONE CASE OF DKA, confirmed by FPG or Hb1ac
TYPE TWO DIAG BY either FPG or HbA1c
- HB1Ac test: maillard reaction: non enz chem reaction between amino acid and sugar
- 1% glucose contains a reactive aldehyde group
- glycationL non specific non enzymatic binding of glucose to NH2 groups
- Hb1Ac is glycated form of HbA (bound to N terminal valine of HbA Bchain)
- Hb1Ac is greater than 6.5%, and confirmed by another one, or FPG then you have DM
- Advantages: sample stability, easier for patient
- measures for past 6-8 wks
Chronic long term effects of DM
hyperglycemia
- vascular system damage (50% of deaths)
- advanced glycation end products (AGE’s)- non enzymatic reaction between glucose and exposed NH2 of any protein . All protiens can be potentially damaged by AGE formation.
- bind to target receptors, in vac undo, and promote vasc inflammation and CV risk
- vasc function also affected by AGE’s leading to hypertension
- disordered lipid metabolism : atherosclerosis
arm and leg pain, but also more central vessels, for heart attacks
- musculoskeletal: CT protiens (collagen) damaged by AGEs. reduced flex, limited joint mobility. (advanced glycation end products)
- AGE impare function of the immuse system, which increases rick of infections, and amputation - eyes, kidneys, nerves
- retinopathy of blood vessel s in eye, nuropathy and nephropathy
- most cells can reduce glucose tranport into the cell during hyperglycemia but eye kidney and nerve cannot…especially ses to hyperglycemia,
