Pathology: Diabetes Mellitus

Front 1

Why is Diabetes Mellitus classified as a systemic dz?

Back 1

It has multiple organ involvement

Front 2

Primary causes of diabetes (idiopathic) inlcude?

Back 2

-Type I (IDDM)
-Types II (NIDDM)
-Genetic defects of beta-cell function
-Genetic defects in insulin action

Front 3

Can pregnant women get diabetes?

Back 3

They can suffer from gestational diabetes

Front 4

Many people suffer from impaired glucose tolerance/insulin resisance which is classified as?

Back 4

Metabolic syndrome
-5-10% per year progress to Type 2 DM
-25% population

Front 5

What are secondary causes diabetes symptoms?

Back 5

Hemochromatosis, Pancreatitis, etc.

Front 6

Why is Diabetes Mellitus classified as a systemic dz?

Back 6

It has multiple organ involvement

Front 7

Primary causes of diabetes (idiopathic) inlcude?

Back 7

-Type I (IDDM)
-Types II (NIDDM)
-Genetic defects of beta-cell function
-Genetic defects in insulin action

Front 8

Can pregnant women get diabetes?

Back 8

They can suffer from gestational diabetes

Front 9

Many people suffer from impaired glucose tolerance/insulin resisance which is classified as?

Back 9

Metabolic syndrome
-5-10% per year progress to Type 2 DM
-25% population

Front 10

What are secondary causes diabetes symptoms?

Back 10

Hemochromatosis, Pancreatitis, etc.

Front 11

Why is Diabetes Mellitus classified as a systemic dz?

Back 11

It has multiple organ involvement

Front 12

Primary causes of diabetes (idiopathic) inlcude?

Back 12

-Type I (IDDM)
-Types II (NIDDM)
-Genetic defects of beta-cell function
-Genetic defects in insulin action

Front 13

Can pregnant women get diabetes?

Back 13

They can suffer from gestational diabetes

Front 14

Many people suffer from impaired glucose tolerance/insulin resisance which is classified as?

Back 14

Metabolic syndrome
-5-10% per year progress to Type 2 DM
-25% population

Front 15

What are secondary causes diabetes symptoms?

Back 15

Hemochromatosis, Pancreatitis, etc.

Front 16

Which is more common, Type I or Type II DB?

Back 16

Type 1: 10-20%
Type 2: 80-90% (1/2 cases undiagnosed)

Front 17

"Juvenile" DB?

Back 17

Type 1 (IDDM)

Front 18

What causes Type I IDDM?

Back 18

Destruction of
BETA cells and abscence of insulin

Front 19

What are some factors that could cause IDDM (Type I)

Back 19

genetics (HLA) linked
Multifactors
Autoimmunity- T-cell mediated
Enviro. insult (?viral)

Front 20

What are some auto-antibodies present w/ Type I DM?

Back 20

islet cell
GAD65 (glutamic acid decarboxylase)
IA-2
IA-2 beta (tyrosine phosphatases)
Insulin
(one or more present 85-90% patients

Front 21

Major danger Type I DM?

Back 21

Prone to ketoacidosis?

Front 22

What age does Type I DM occur?

Back 22

Typically in children, youth, but can occur at nay age

Front 23

"Adult Onset" diabetes

Back 23

Type 2 (NIDDM)

Front 24

What causes Type 2 NIDDM

Back 24

peripheral RESISTANCE to Insulin and DECREASED secretion by beta-cells, may not be insulin dependnt

Front 25

Type 2 DM is associated w/ what factors?

Back 25

genetics (comples-multiple genes)
obesity
Gestational diabetes
metabolic syndrome

Front 26

Who is Type 2 DM most commonly seen in?

Back 26

adults, but being seen w/ increase frequency in children

Front 27

What are the abdominal obesity waist criteria for metabolic syndrome?

Back 27

>40 in males
>35 in females

Front 28

Triglycerides for metabolic syndrome?

Back 28

>150 mg/dL

Front 29

HDL cholesterol for metabolic syndrome?

Back 29

<40mg/DL males
<50 mg/DL females

Front 30

blood pressure metabolic syndrome?

Back 30

>130/>85

Front 31

Fasting glucose?

Back 31

>100 mg/dL

Front 32

big danger of metabolic syndrome?

Back 32

increased risk of cardiovascular DZ

Front 33

Complications of DM:
Renal (Nephropathy)

Back 33

Polyuria/Polydipsia
Hypertension
Renal Failure

Front 34

Complications of DM:
Cardiovascular System?

Back 34

Infarcts- heart, kidney, etc
Hypertension

Front 35

Complications of DM:
Eye?

Back 35

Blindness
Cataracts

Front 36

Complications of DM:
Skin?

Back 36

Ulcers
Vascular Insuffieciency/gangrene

Front 37

Complications of DM:
Neurologic system (Neuropathy)?

Back 37

Plyneuropathy-sensory, motor
Strokes

Front 38

Complications of DM:
GI system?

Back 38

Impaired motility
Bacterial overgrowth

Front 39

Complications of DM:
Urogenital system?

Back 39

impotence
bladder dysfunction

Front 40

Complications of DM:
Immune System

Back 40

Infections-kidney, skin, etc

Front 41

What are some signs of hyperglycemia in DM?

Back 41

-abnormal fasting glucose or oral GTT
-non-enzymatic glycosylation (Hgb A1c)
-increased intra-cellular glucose
-increased fatty acid metabolism-ketoacidosis

Front 42

What are some signs of Hyperlipidemia in DM?

Back 42

-increased LDL cholesterol
-decreased HDL cholesterol

Front 43

What are some signs of Renal dysfunction in DM?

Back 43

Glucosuria
Proteinuria (albumin=mico-albuminuria)
Axotemia (creatinine/urea) = renal insufficiency

Front 44

How do you test renal sufficiency?

Back 44

Azotemia (creatinine/urea)

Front 45

For DM dx, what must you have?

Back 45

Symptoms of DM + glucose > 200 mg/dL

Front 46

For DM dx, what must you have Fasting Glucose??

Back 46

>126 mg/dL

Front 47

For DM dx, what must you have ??? gm OGTT, 2 hr glucose?

Back 47

75 gm OGTT
2 hr glucose >200mg/dL

Front 48

For DM dx, what must you have Hgb A1c?

Back 48

>6.5% (glycosylated Hb)

Front 49

Gestational DB uses slightly different criteria than DM, what is 1 hour glucose and OGTT?

Back 49

1 hour glucose post 50 gm OGTT >140 (screen)
*3 hour 100 gm OGTT: abnormal response

Front 50

Gestational DB uses slightly different criteria than DM, what is 3 hour glucose and OGTT?

Back 50

*3 hour 100 gm OGTT: abnormal response

Front 51

What are those cases termed that are not normal but do not meet the other criteria?

Back 51

Impaired Glucose Tolerance

Front 52

What is the fasting glucose levels for Impaired glucose tolerance?

Back 52

Fasting glucose between 100-126 now being guide

Front 53

What is the fasting glucose levels for Hgb A1c:

Back 53

>6.0 but <6.5%

Front 54

What is significant about the HbA1c being >6%, 2hPG (mg/dl) >185, and FPG (mg/dl) >116

Back 54

These numbers tend to correlate w/ increasing # of people who suffer from Retinopathy

Front 55

DM vs non-DM pre-meal glucose?

Back 55

DM: 80-120
non-DM: <110

Front 56

DM vs non-DM bedtime glucose?

Back 56

non-DM: <120
DM: 100-140

Front 57

DM vs non-DM HgbA1c %?

Back 57

non-DM: <6%
DM <7
Actions >8

Front 58

With glucose meter, what does a diabetic patient glucose levels look like?

Back 58

lots of variance, poor to moderate control of blood glucose levels

Front 59

Are glucometers perfect for monitoring blood glucose?

Back 59

No
-w/in +/- 15% of lab values
-may not be accurate if Hct <20 or >60%
*when in doubt, recheck lucose on plasma at lab

Front 60

What are 3 things involved in the Pathogenesis of DM complications?

Back 60

-AGE (advanced glycosylation endproducs) glycosylation of compounds
-Activation of Protein Kinase C
-Hyperglycemia and Polyol Pathways

Front 61

What is an Amadori Product?

Back 61

glucose+protein becomes an Amadori product b/4 undergoing the final step to become an AGE (advanced glycosylation endproduct)

Front 62

What is an AGE?

Back 62

Protein CROSSLINKS via Glycosylation End Products

Front 63

What is considered Gold Standard for measuring AGES?

Back 63

Glycosylate Hemoglobins-HPLC

Front 64

What are a few chemical effects of AGEs?

Back 64

-Cross-link polypeptides (eg collagen)
-Traps non-glycosylated proteins (LDL, Ig's, Complement)-CV risk
-Confer resistance to proteolytic digestion

Front 65

How does AGE increase atherosclerosis process?

Back 65

Induce lipid oxidation

Front 66

How does AGE make one at risk for infections, risk for thrombosis?

Back 66

Inactivate Nitric oxide
*note, AGE can also bind nucleic acids, which is overall bad news

Front 67

What is the major biologicl downside to ages?

Back 67

Bind to AGE receptors on ENDOTHELIAL, MONOCYTES, and MESENCHYMAL CELLS
-->INFLAMMATORY PROCESS MEDIATORS

Front 68

Upon bending to AGE receptors on endothelial, monocytes, and mesenchymal cells, what happens?

Back 68

Induces:
-monocyte emigration
-Cytokins and growth factor secretion
-increased vascular permeabiltiy
-pro-coagulant activity (thrombosis)
-enhanced cellular proliferation
-enhanced extra-cellular matrix (ECM) production
-pro=inflammatory factors

Front 69

What does AGE induced monocyte emigration lead to?

Back 69

-inflammation, atherosclerosis

Front 70

What does AGE induced cytokine and growth factor secretion lead to release of?

Back 70

IGF-1
TGF-b
PDGF
VEGF

Front 71

What does AGE induced pro-coagulant activity lead to?

Back 71

Thrombosis

Front 72

Hyperglycemia stimulates prodcution of diacyl glycerol (DAG), which activates?

Back 72

DAG activates Protein Kinase C

Front 73

What are some of the actions of Protein Kinase C?

Back 73

-Production pro-angiogenic factors
-Increased vasoconstrictor and decreased vasodilator
-Profibrogenic factors
-Pro-coagulant activity
-Pro-inflammatory factors

Front 74

What are some pro-angiogenic factors that Protein Kinase C leads to the release of?

Back 74

VEGF (vascular endothelial growth factor)
-Neovascularization of retinal vessels (bad w/ eye issues)

Front 75

What vasoconstrictor is increased w/ protein kinase C activation?

Back 75

Endothelin-1

Front 76

Activity of what vadodilator is decreased w/ protein kinase C activation??

Back 76

Vasodialtor endothelial nitric oxide synthase

Front 77

What are some profibrogenic factors increased by protein kinase C activation?

Back 77

TGF-beta, transforming growth factor

Front 78

How does protein kinase C activation affect pro-coagulants?

Back 78

Increased Plasminogen Activator (PAI-1)
*reduced fibrinolysis

Front 79

When there is too much glucose, the aldose reductase can convert it to?

Back 79

Sorbitol

Front 80

Why is sorbitol bad?

Back 80

1. Reduce glutathione production due to decreased NADPH and susceptibility to oxidative stress
-Increased cellular osmolarity

Front 81

What are some cells that can suffer from sorbitol induced cellular osmolarity

Back 81

Schwann cells - nerves
Pericytes- retinal vessels

Front 82

Sorbitol increase can result in what problems?

Back 82

Neuropathy (schwann cells)
Micro-aneurysms and cataracts (Retinal vessels)

Front 83

What type of DM findings go w/ Islets of Langerhans (beta cells) findings of:
-No change

Back 83

in some

Front 84

What type of DM findings go w/ Islets of Langerhans (beta cells) findings of:
-beta cell degranulation

Back 84

most

Front 85

Inflammation (insulitis)

Back 85

DM-1 (lymphocytes

Front 86

What type of DM findings go w/ Islets of Langerhans (beta cells) findings of:
-beta cell loss

Back 86

DM-1
DM-2

Front 87

What type of DM findings go w/ Islets of Langerhans (beta cells) findings of:
-islet/beta cell hyalinization/fibrosis

Back 87

DM-1

Front 88

What type of DM findings go w/ Islets of Langerhans (beta cells) findings of:
islet/beta cell amyloid (amylin) depostion

Back 88

DM-2

Front 89

What type of DM findings go w/ Islets of Langerhans (beta cells) findings of:
Beta cell hyperplasia

Back 89

infants of diabetic moms

Front 90

Hyalization/fibrosis of islets seen in?

Back 90

Type 1

Front 91

Inflammatory infiltrate (lymphs) seen in?

Back 91

Type I (insulitis)

Front 92

Amyloid deposits seen in (non-immunoglobulin amyloid proteins = amylin, secreted w/ insulin)

Back 92

Type 2

Front 93

Key diff. histologically pancreas type 1 vs type 2:
lymphocyte infiltrate w/ fibrosis/hyalinization

Back 93

type 1:

Front 94

Key diff. histologically pancreas type 1 vs type 2:
amyloid deposition

Back 94

Type 2

Front 95

DM-anatomic findings: vessels?

Back 95

*diabetic micro-angiopathy -diffuse small vessel/basement membrane thickening
*Hyalinization of capillary/arteriolar walls=glomerulosclerosis and arteriosclerosis
*Aneurysm formation
*Atherosclerosis-diffuse large vessels

Front 96

Where might you observe Diabetic Micro-angiopathy (basement membrane thickening)

Back 96

-plasma proteins, basement membrane material (glycosylated)
-skin, muscles, retina, glomeruli, etc

Front 97

DM, where might you observe hyalinization of capillary/arteriolar walls?

Back 97

Glomerulosclerosis (kidney)
Arteriolosclerosis, skin

Front 98

Where might you observe Aneurysm formation w/ DM?

Back 98

caused by structural cell loss
-Retinal aneurysms, hemorrhages, exudates, thrombosis

Front 99

Where might you observe atherosclerosis with DM?

Back 99

Diffuse large vessels
-atheromatous plaques, accelerated atherosclerosis
-ischemia, infarcts-heart, brain, kidney, extremities
-aneurysm/rupture-aorta
-hypertension

Front 100

What is micro-albuminuria?

Back 100

Albumin measured at low levels in urine
-can observe proteinuria in DB

Front 101

What is normal proteinuria

Back 101

24 hr <30
timed <20
random <30

Front 102

What is micro vs. macro proteinuria?

Back 102

24 hr 30-300 vs >300
timed 20-200 vs >200
random 30-300 vs >300

Front 103

What can renal glomerulosclerosis cause?

Back 103

Diffuse glomerulosclerosis
Nodular glomerulosclerosis

Front 104

What can renal Nephrosclerosis cause?

Back 104

Arteriosclerosis
-afferent and efferent arteriolar hyalination

Front 105

What is the buzzword for Nodular glomerulosclerosis in the kidney?

Back 105

Kimmelstiel-Wilson lesion

Front 106

What are some traits of Glomeruloslerosis/nephrosclerosis?

Back 106

-Fibrosis: glomerular hyalizantion/fibrosis
-inflammatory infiltrate (leukocytes)
-Atrophy o fthe nephron unit
-cortical thinning (granular)
-End-stage: renal failure

Front 107

Does the nephron unit become larger or smaller in response to glomerulosclerosis/nephrosclerosis?

Back 107

atrophies

Front 108

What can you grossly observe with about cortical atrophy (secondary to glomerulosclerosis/nephrosclerosis)?

Back 108

Cortical thinning
-Granular cortical surface (from all of the fibrosis)

Front 109

What can happen to the eyes as a result of DM small vessel problems?

Back 109

Retinopathy
-basement membrane thickening
-micro-aneurysm formation
-Hermorrhage, exudates, thrombosis
-neovascularization
-cataracts

Front 110

What can happen to skin as a result of DM small vessel problems?

Back 110

Ulcers
Gangrene

Front 111

Why can neovascularization resultant of DM in the eye be a problem?

Back 111

significant impairment in vision

Front 112

What can happen in the kidney papillary as a result of DM?

Back 112

Papillary Tip necrosis
Small vessel Dz->
Ischemia ->
Coagulative necrosis
>>repair/fibrosis/scarring

Front 113

What is the characteristic of kidney chronic pyelonephritis caused by DM?

Back 113

-sclerotic (hyalinized glomeruli)
-Atrophic nephron unit
**BLADDER DYSFUNCTION and UTIs!!!

Front 114

Pyelonephritis: chronic or acute?
-Fibrinous necrosis/exudate
-Neutrophilic infiltrate
-Repair/fibrosis-scarring

Back 114

Acute pyelonephritis

Front 115

Pyelonephritis: chronic or acute?
-Fibrosis: glomerular hyalinzation/fibrosis; Medullary fibrosis
-inflammatory infiltrate (lymphocytes)
-Atrophy of nephron unit
-Cortical thinning/medullary loss

Back 115

Chronic pyelonephritis

Front 116

what can be grossly observed w/ chronic pyelonephritis?

Back 116

-Cortical/medullary scarring

Front 117

What/where are some places that are more prone to infection as a result of DM?

Back 117

Yeast (skin, bladder, throat)

Front 118

Overall, what condition can DM cause in the cardiovascular system?

Back 118

Atherosclerosis

Front 119

As a result of DM, increased growth factors (smooth muscle proliferation), increased ECM production, AGE's - protein trapping lead to?

Back 119

Intimal thickening (hyperplasia)

Front 120

As a result of DM, increased LDL, oxidized lipids, and monocyte activation can lead to?

Back 120

Media atheromas

Front 121

As a result of DM, increased pro-coagulants can lead to?

Back 121

Thrombosis

Front 122

As a result of DM, ischemia and infarcts can lead to?

Back 122

myocardial infarcts
Cerebral infarcts
bowel infarcts
Ischemic skin ulcers/gangrene
Extremity infarcts/gangrene - amputations

Front 123

What can happen to the Aorta as a result of DM?

Back 123

Aneurysm/rupture

Front 124

How can you treat DM?

Back 124

-insulin (injections or pumps)
-oral hypoglycemics (type II diabetics0
-islet cell or pancreas transplants

Front 125

What are some of the impacts of tight control/treatment of DM?

Back 125

-reduced renal dz
-reduced cardiovascular dz
-reduced retinopathy
-reduced neuropathy