6: Diabetes mellitus Flashcards
DM- class
Type 1 Type 2 Gestational Genetic defects of beta cells, insulin (Maturity onset diabetes of young- MODY) Certain drugs Defects of exocrine pancreas Endocrinal disease
DM- definition
Metabolic condition characterized by hyperglycemia involving multiple systems caused by absolute or relative deficiency of insulin
Gestational DM
During 3rd trimester- maternal diabetes -> after birth, it goes back to normal
It increase the chance of getting diabetes for the rest of her life**(36%)
-weight loss and physical activity can reduce the chance of getting DM for those female
Type1- info
Immunological component- cellular and humeral
-Ab are seen but after the disease happens- only dx values- Ab vanish after the beta cells are killed off (Honeymoon phase: till >80% of the cells are destroyed)
-cellular component (T cells) damage the beta cells*
-asso w/ auto-immune thyroid disease
Genetic component- 50% concordance rate in twins (HLA-DR3, DR4, DQ)
Environmental component- Coxsackie, Rubella, cow milk to baby, Nitrosourea compounds
Type2- info
No immunological component
Genetic- 90% concordance
Environmental- obesity (central/truncal), physical inactivity (they are independent of each other), HTN, dyslipidemia, gestational DM
1: insulin resistance
-PI3 kinase signaling pathway**: translocation of GLUT4 to cell membrane
-adipocytes secreting adipokinase decrease sensitivity to insulin (high in obesity) (whereas Adiponectin increases responsiveness of cells to insulin)
2: decreased insulin secretion
-initially the secretion is high-> burns out
3: increased hepatic glucose production
-lack of insulin
dx- what glucose tests mean
Fasting glucose level: high due to increased hepatic gluconeogenesis
Post-prandial glucose level: high due to insulin defect
DM- sx
Polyuria: osmotic diuresis
Polyphagia- no glucose going into peripheral tissue
Polydipsia- thirsty
Change of vision-> hyperosmolarity of fluid in eyes
Delayed heeling of wound: hyperglycemia cause protein dysfunction, low blood supply
Weight loss: enegy is peed out
Fungal infections: skin folds, btw toes
Bacterial infections: tons of food for the bugs and low immune response
DM- exam
Orthostatic hypertension Waist hip ratio BMI Skin findings: Acanthosis nigricans (also for Cushings), etc Neurological exams Foot exam**
DM- dx
1: Fasting glucose level (>126mg/dL)(native americans >116mg/dL)**
2: HbA1c (keep it as close to 6.5 as possible)
3: Random glucose (>200mg/dL)
- Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG): both indicate higher risk for type II
DM- complication; DKA
1: DKA
- more in type1
- due to low level of insulin, high production of free fatty acid. Glucagon shifts metabolic pathway by CPT1 (Carnitine Palmatoyl Transferase puts FFA into mitochondrial matrix) to produce more ketone bodies
- Triggering factors: inadequate insulin, severe stress (pneumonia, MI, stroke, cocaine use, etc)
- altered sensorium: low intracellular fluid in brain due to hyperosmolarity
- dry tongue
- Kussumaul breathing (to breathe off the excess CO2)
- Acetone in breath (fruity odor)
- gastroparesis
- diuresis: all the electrolytes are low except K+ due to acidosis-> H+ is exchanged for K+ out the cell (when rx DKA, have K+ drip in case of K+ pumped back into cells)**
- high TG and VLDL
- blood glucose: 500-600mg/dL, Osmolality: 300-320
- Amylase increase: stimulation of salivary gland
- rx: insulin & K+ drip**
DM- complication- Non-Ketotic Hyperosmolar State (NKHS)
Never lack of insulin No sx until its too late (elderly pts with Type II DM*) -Blood glucose: >1200, Osmolarity: >350 Higher mortality Altered sensorium: shrunk brain cells Triggers are the same as DKA rx: same as DKA
DM- complication- acute
1: DKA
2: NKHS
DM- complication- chronic
more in Type2 (longer asx phase and delayed dx)
factors affecting the chronic complication
-duration
-glycemic control
what?
-vascular
–microvascular (retinopathy, neuropathy, nephropathy)
–macrovascular (CAD, CVD, PVD)
-nonvascular
–Dermatological, Glaucoma
DM- chronic complication- cc
All caused by sustained level of hyperglycemia
1: AGEs: advanced glycosylation end product (endothelial lesion)
2: Sorbitol (neuronal damage)
3: DAG mediated Protein kinase C (collagen 4 formation)
4: Fructose 6 phosphate (kidneys- fibronectin formation of mesangial cell-> nephrosclerosis)
Retinopathy
Retinopathy- 10yrs starts to appear 2 phases -non-proliferating phase --dot and blot hemorrhages** --microaneurysms --Cotton wool spot (area of ischemia) --exudates -proliferating phase --neovascularization** (cc ischemia-> VEGF-A)-> retinal detachment or vitreous hemorrhage (rx laser photocoagulation)
