Endo Part 8

Front 1

2 modified human insulins:

Back 1

1. Regular insulin

2. NPH

Front 2

difference between Regular insulin and NPH:

Back 2

NPH has slower onset, longer duration

Front 3

rapid-acting insulin: take it right before

Back 3

a meal

Front 4

3 rapid-acting insulin analogues:

Back 4

1. Aspart

2. Glulisine

3. Lispro

(peak time = 1 hour)

Front 5

2 long-lasting insulin analogues:

Back 5

1. Glargine
(taken once every 24 hours)

2. Detemir

Front 6

Detemir's duration of action is between:

Back 6

NPH and Glargine

Front 7

in general, lower doses of insulin:

Back 7

peak FASTER,

while higher doses last longer

Front 8

3 types of insulin regimens:

Back 8

1. Twice-daily Split-Mixed
(Regular and NPH)

2. Multiple Daily Insulin Injections (MDI)
(3 Regular injections, 1 NPH at the end of the night)

3. MDI: Glargine and 3 Lispro's

Front 9

remember that:

(2)

Back 9

1. body's FPG is determined mainly by the prior night’s long- or intermediate- acting insulin

2. the pre-lunch, pre-supper, and bedtime insulins are determined by the *short*-acting insulin dose at the **previous meal**

Front 10

basal insulin via Glargine =>

Back 10

suppression of glucose production between meals and overnight,

while bolus (prandial/during-meal) insulin limits hyperglycemia

Front 11

insulin therapy in DM1 begins with:

Back 11

this basal and bolus approach

- in DM2, they start with basal only, and continue with their other diabetes meds

Front 12

"dawn phenomenon" =

Back 12

natural, modest rise in glucose in early morning due to peaks of GH and cortisol

Front 13

insulin use might induce:

Back 13

lipoatrophy or lipohypertrophy

Front 14

insulin pump =

Back 14

continuous, basal insulin

- slightly elevated in the morning due to dawn phenomenon,

- slightly lowered in the middle of the night due to physiological inc. in sensitivity to insulin

Front 15

***main medical risks of insulin therapy = ***

(2)

Back 15

hypoglycemia,

wt. gain

Front 16

when to repeat glucose reading:

Back 16

if they are on the lower end of high sugar

- need to make sure 20% variation of meters isn't taking you from high to nl

Front 17

Microvascular dz/eye dz won’t occur:

Back 17

so soon in DM1 - will only develop later

Front 18

high TG’s, low HDL, and HTN ~~

Back 18

DM2,

NOT 1

Front 19

Primary polydipsia ~~

Back 19

dilute SERUM osm too (<300)

Front 20

hydroxyapatite =

Back 20

Ca2+PO4

Front 21

"microvasculature" =

Back 21

caps and arterioles

Front 22

chronic complications of DM appear over:

Back 22

YEARS

Front 23

complications of DM occur in cells which do NOT require:

Back 23

insulin for glucose uptake

- i.e. insulin-independent cells, i.e. all but adipose and muscle cells

ESP. those unable to regulate glucose uptake

Front 24

4 cells that in particular don't regulate glucose metabolism well:

Back 24

1. endothelial cells

2. neurons

3. Schwann cells

4. mesangial cells

=>=> vascular, neural, and renal complications

Front 25

excessive glucose overloads a cell's glucose metabolism pathway, dysregulating the ETC; =>

Back 25

INC. in ROS, beyond ability to remove them

=> oxidative stress

=> impaired function, detrimental effect, s/ts cell death

Front 26

meanwhile, ROS inhibits a key glycolytic enzyme,

Back 26

GAPDH

=> shunts glucose metabolism to other pathways

Front 27

1 of the 4 alternate glucose pathways increases:

Back 27

ROS

Front 28

pathway 2 of 4 results in:

(4)

Back 28

1. inc. ECM

2. dec. fibrinolysis => vasc. occlusion

3. vasoconstriction

4. inc. athero

=> STENOSIS

Front 29

ECM includes:

(2)

Back 29

collagen, fibronectin

Front 30

pathway 3 of 4 results in:

(3)

Back 30

1. all of the effects of 2/4

2. +angiogenesis

3. +gene expression of pro-inflammatory mlcls

Front 31

pathway 4 of 4 results in:

(5)

Back 31

1. inc. in AGE
(advanced glycosylation end-products)

2. dec. elasticity

3. inc. permeability

4. inc. inflam. cytokines,

5. dec. VEGF

Front 32

at first, the nonenzymatic glycosylation of proteins that leads to AGE is:

Back 32

reversible

- later, becomes irreversible

Front 33

altogether, the effects of the four alternate pathways cause the following in the microvasculature:

(4)

Back 33

1. vasoconstriction

2. inc. ECM, BM

3. inc. permeability
=> edema, exudates

4. plasma prots, AGE trapped in the ECM

Front 34

ultimately, the effects at the microvasculature =>

Back 34

narrowed lumen and thickened wall

=> ischemia

=> tissue necrosis, poor wound healing

Front 35

histo of microangiopathy =

Back 35

hyaline thickening of microvasculature

(also seen in benign HTN - *not unique to DM*)

Front 36

hyaline thickening is composed of:

(3)

Back 36

BM,

ECM changed into AGE,

leaked plasma prots changed into AGE

Front 37

***microangiopathy is found throughout the body, but especially in:***

(3)

Back 37

1. retina

2. peripheral nerves

3. kidney

Front 38

in the kidney, hyaline thickening is called:

Back 38

arteriolosclerosis

Front 39

diabetic nephropathy in the kidney =>

(4)

Back 39

1. glomerulosclerosis

2. arteriolosclerosis
(=> ischemia)

3. inc. risk of inf. => pyelonephritis

4. papillary necrosis

Front 40

Glomerulosclerosis =>

(4)

Back 40

1. inc. BM

2. inc. mesangium

3. +/- KW nodules

4. proteinuria
(= nephrotic syndrome)

Front 41

7 features of diabetic retinopathy:

Back 41

1. thickened capillary BM

2. loss of pericytes (regenerative vessel cells)

3. aneurysms
(vessel wall weakened)

4. hemorrhages
(vessel wall weakened)

5. exudates
(↑vascular wall permeability)

6. stenosis => ischemia

7. neovascularization
(↑VEGF => angiogenesis)

Front 42

3 features of diabetic peripheral neuropathy:

Back 42

1. microangiopathy

2. demyelination
(due to ischemia, apoptosis via ROS of Schwann cells)

3. axon degeneration (all axon sizes)
(due to ischemia to neurons, Schwann cells)

Front 43

compared to microangiopathy , the only difference in the pathogenesis of macroangiopathy =

Back 43

the inciting cause of oxidative stress

- in macroangiopathy, insulin-R adipocytes release FFA's which are readily taken up by macrovascular endo cells (but NOT microvascular endo)

mitochondrial oxidation of FFA's leads to ↑↑ROS

Front 44

apart from the changes as a result of the 4 pathways, in macroangiopathy, INC. ROS inhibits:

Back 44

NOS and prostacyclin synthetase (*anti-atherosclerotic enzymes*)

=> *accelerated athero in large and medium arteries*

(which is why athero is such a big issue for DM)

Front 45

athero of DM can lead to:

(3)

Back 45

1. MI

2. PVD

3. CVA

Front 46

special note about MI in DM:

Back 46

can be SILENT due to neuropathy

Front 47

diabetic ulcers are the result of:

Back 47

BOTH micro- and macroangiopathy

(stenosis in one and athero in the other => ischemia, poor wound healing)

Front 48

diabetic ulcers ALWAYS start:

Back 48

in the toes

Front 49

5 features of Non-proliferative DM:

Back 49

1. 95% of pts

2. **progressive** microangiopathy

3. => microaneurysms on fundoscope

4. *cotton-wool spots* if severe

5. venous beading (funny-looking vessels)

Front 50

Proliferative DR ~~

(2)

Back 50

1. neovascularization

2. scarring

Front 51

2 serious complications of Proliferative DR:

Back 51

1. vitreal hemorrhage
(blood in the back of the eye)

2. retinal detachment

Front 52

primary cause of vision loss in DM2 =

Back 52

Clinically Significant Macular Edema (CSME)

Front 53

CSME =

Back 53

inc. permeability, leakage, and accumulation of intra-retinal fluid

=> lipid exudates from damaged retinal capillaries and microaneurysms

Front 54

Proliferative DR is caused by:

Back 54

ischemia,

while the other 2 are caused by leakage

Front 55

**ALWAYS measure:

Back 55

microalbuminemia

- progresses to proteinuria which is always accompanied by renal HTN
=> edema
=> easy progression to renal failure

Front 56

microalbuminuria is detected by:

Back 56

spot urine albumin-to-Cre ratio

Front 57

stages of albuminuria:

Back 57

Micro: 30-300

Macro: >300

Nephrotic Range: >3000

Front 58

Stage 4 ESRD =

Back 58

eGFR 15-29

- nephrology consult needed

Stage 5 = ESKD

Front 59

menstruation causes transient:

Back 59

microalbuminuria

Front 60

non-glycemic interventions for nephropathy:

(3)

Back 60

1. BP management

2. ACEI's or ARB’s

3. low protein diet

Front 61

the higher the mA, the higher risk of:

Back 61

CV death

- steeper than relationship of CV death to eGFR

Front 62

if you have DM, you have as high a CV risk factor as:

Back 62

history of an MI

Front 63

controlling glucose decreases:

Back 63

microangiopathy

Front 64

MODY = Maturity Onset Diabetes of the Young =

Back 64

"type-1-like" diabetes that *doesn't progress to requiring insulin*

Front 65

4 features of MODY:

Back 65

1. ~~adolescence/YA (< 25 years)
(can be diagnosed later as well)

2. runs through several generations

3. **often responds to diet/exercise, while some may need pills and/or insulin as well**

4. AD

Front 66

what does the genetic defect in MODY result in?

Back 66

impaired glucose sensing (impaired glucokinase)

OR

(more likely) impaired insulin production (via impaired TF's)

Front 67

MODY is the ONLY known:

Back 67

monogeneic form of diabetes in adults

Front 68

GDM =

Back 68

diabetes diagnosed during pregnancy that is **not clearly overt diabetes**

Front 69

GDM classically appears after:

Back 69

week 20

Front 70

in those with established DM2, screen for GDM at:

Back 70

first prenatal visit

- in others, screen at 24-28 weeks

Front 71

biggest risk of GDM for the fetus =

Back 71

macrosomia

= large for gestational age

Front 72

complications of macrosomia delivery:

(3)

Back 72

1. C-section

2. palsies

3. bone fractures

Front 73

other risks of GDM for the fetus:

(4)

Back 73

1. RDS

2. hypoglycemia

3. polycythemia

4. hypocalcemia

Front 74

3 risks of GDM for mom:

Back 74

1. C-section rates higher

2. association with HTN

3. risk for DM later in life

Front 75

***unlike pregnancies complicated by pre-existing DM, in GDM there is NO:***

(2)

Back 75

1. NO significant inc'd risk for fetal anomalies

2. NO significant inc'd maternal microvascular complications

Front 76

**normal FPG = **

Back 76

70-100

Front 77

**remember: 80–90% of women with mild GDM can be managed with:**

Back 77

lifestyle therapy alone (regardless of method of dx)

Front 78

How should women with GDM be followed after delivery?

Back 78

2-hr OGTT at 6-12 weeks, using non-preg criteria

- if normal, screen every 3 years as per us. (HbA1c, FPG)

Front 79

chronic pancreatitis =

Back 79

persistent destruction of the pancreatic parenchyma, replaced by fibrosis

- lesions generally start in the exocrine gland, with islets attacked later on

Front 80

clinical course of chronic pancreatitis and diabetes:

(4)

Back 80

1. diabetes appears after several years of recurrent attacks of upper abdominal pain and pancreatic enzyme elevation

2. **by the time diabetes appears, pain has often disappeared**

3. low serum insulin levels => treatment with insulin

4. => infrequent ketosis, frequent insulin-induced hypoglycemia

Front 81

CFRD = Cystic Fibrosis Related Diabetes =

Back 81

impaired insulin secretion with **variable degree of insulin resistance**

Front 82

4 features of CFRD:

Back 82

1. 50% of CF patients > 30 years old

2. insulin R is highest with illness, particularly with antibiotics or steroids

3. R even more prevalent after lung transplant

4. **insulin needs can vary (in the same individual)** from none, to insulin at meals only, to continuous high dose therapy

Front 83

complications of CFRD:

(3)

Back 83

1. M/M higher

2. can develop microvascular complications
(eye, kidney, neuro dz)

3. risk of macrovascular dz is LOW

Front 84

Treatment for all CFRD (for now) is:

Back 84

INSULIN

Front 85

LADA = “Latent AI Diabetes in Adults:”

(3)

Back 85

1. AB+ with slow progression to AI Beta-cell failure

2. may not require insulin for months or years

3. “Type 1.5 diabetes”, “ADA”, “Type 1 DM in adults”

Front 86

KPD = “Ketosis-prone (type 2) diabetes:”

(5)

Back 86

1. Antibody-variable (often negative), no HLA association

2. Diabetic ketoacidosis at presentation, but later insulin INdependent

3. commonly ~black or Hispanic

4. obese

5. strong family history of DM