16. DM

Question 1

DM definition

Answer 1

DM is a heterogeneous metabolic disorder, characterized by chronic hyperglycaemia with disturbance of carbohydrate, fat and protein metabolism (WHO)
Literally means sweet siphone(i.e sweet urine)

Question 2

glut

Question 3

diagnostic criteria

Answer 3

fasting
pre 100-125
diabetic> 126

hemoglobin
pre 5.7-6.4
diabetic >6.5

2 hr plasma
pre 140-199
diabetic >200

random
diabetic
>200

Question 4

complications

Answer 4

microangiopathy- hemorgae
retinopathy
hypertension
atheroscelerosis - hyaline arteriolo
nephroscelerosis
peripheral neuropathy and peri. vascular
autonomic neuropathy

Question 5

Pathogenesis of Complications

Answer 5

Formation of advanced glycation end products (AGE):
Nonenzymatic reaction glucose with amino group of proteins
AGE crosslinked proteins are resistance to proteolytic digestion

Question 6

Biologic properties of AGE–RAGE complex

Answer 6

-ROS and NF-kB activation
- monocyte emigration
- cytokine and growth factor secretion
-↑ vascular permeability and procoagulant activity
-↑ ECM production and cellular proliferation

Question 7

AGE bind to plus how

Answer 7

to Y receptors in macrophage endothelial cells vascular smooth muscle

or without receptor to
intimal matrix proteins
BM collagen 4

Question 8

hyperglycemia increases de novo synthesis of what

Answer 8

DAG then protein kinase c

Question 9

Activation of protein kinase C downstream effects

Answer 9

VEGF production (induces neovascularization characterizing diabetic retinopathy)

↑activity of endothelin-1 and ↓activity of nitric oxide synthase (NOS) - net constriction

↑TGF- β fibrosis

↑PAI-1 - plasminogen activator inhibitor

↑proinflammatory cytokines by endothelium

Question 10

Diabetic nephropathy charachters

Answer 10

Microalbuminuria - (>30 mg/day but <300 mg/day)
Diffuse glomerulosclerosis and nodular glomerulosclerosis (Kimmelstiel Wilson disease)

Renal vascular lesions: Renal arteriosclerosis and atherosclerosis

Pyelonephritis including papillary necrosis (necrotizing papillitis) - because susceptible to infection

CKD

Question 11

diffuse glomeruloscelerosis

Answer 11

increased fibrosis of mesangial matrix
thick basement membrane

Question 12

nodular glomerylonephritis or kimmsel wilson lesion

Answer 12

nodular deposition in mesangial matrix

Question 13

benigh nephroscelerosis with surface apearance

Answer 13

hyaline arterioloscelerosis
leathery granulairty surface

Question 13

renal papillary necrosis cause plus presentation

Answer 13

cause SODA
sickle cell
obstructive pylonephritis
diabetes
analgesics

present with hematuria

Question 13

Diabetic retinopathy types

Answer 13

Nonproliferative retinopathy
Microaneurysms, retinal hemorrhages, and retinal exudates

Proliferative retinopathy
Neovascularization and fibrosis

Question 14

Diabetic Neuropathy pathogenesis

Answer 14

AGEs may interfere with normal protein function and activate inflammatory signaling
Injury by ROS and osmotic damage
Ischemic damage of the nerves

Question 15

Clinicopathologic patterns of diabetic neuropathy 3

Answer 15

Ascending distal symmetric sensorimotor polyneuropathy

Diabetic autonomic neuropathy (20% to 40%)

Asymmetric neuropathy(rare)

Question 16

Ascending distal symmetric sensorimotor polyneuropathy

Answer 16

Numbness, loss of pain sensation, difficulty with balance,
“positive” symptoms; paresthesias or dysesthesias
Foot and ankle fractures and chronic skin ulcers

Question 17

Diabetic autonomic neuropathy (20% to 40%)

Answer 17

Postural hypotension, neurogenic bladder and sexual dysfunction

Question 18

Asymmetric neuropathy(rare) cased ny

Answer 18

May be caused by microvascular disease

E.g mononeuropathy, cranial neuropathy, and radiculoplexus neuropathy

Question 19

Macroangiopathy list

Answer 19

-Cardiovascular disease is the leading cause of death

-Peripheral vascular disease lead to atrophy of skin and loss of hair of the lower extremities, claudication, nonhealing ulcers, and gangrene (leading cause of nontraumatic amputations)

-Cerebrovascular disease (strock)

Question 20

Body defense and Diabetes

Answer 20

↑susceptibility to infections of the skin and to tuberculosis, pneumonia, and pyelonephritis

Question 21

cause of decreased defense

Answer 21

decreased neutrophil function (chemotaxis, adherence to the endothelium, phagocytosis, and microbicidal activity),

impaired cytokine production by macrophages and

Poor blood supply

Question 22

gyperglycemia block - in neutrophil function and others

Answer 22

adgesion
NET formation
degranulation
opsonization
phagocytosis

Question 23

doesnt block or increases

Answer 23

macrophage to M2 macrophages