Diabetes Complications -Malchoff

Question 1

Diabetes: a syndrome with multiple causes characterized these two things

Answer 1

1. increased peripheral catabolism
2. increased glucose production by the liver

Question 2

Type of defect in Type 1 vs. Type 2

Answer 2

Type 1: autoimmune destruction of beta cells

Type 2: polygenic/epigenic/environmental causes leading to increased resistant to insulin and progressive pancreatic beta-cell failure

Question 3

Diabetec definitions for:

• Fasting plasma glucose (mg/dl)
• 2 hr post 75 g of glucose
• A1C

if two tests are not conrcordant in an individual, the tests are repated and worser nuber is accepted/considered correct

Answer 3

• Fasting (mg/dl): >126
• 2 hr post 75 g of glucose: >200
• A1C >/= 6.5

Question 4

hemoglobin A1C

• what is it
• what does it indicate

Answer 4

• glycated hemoglobin: glucose gets attached to RBC by glycation (non-enzymatic process); the more glucose around, the more glycated hemoglobin, the higher the A1C
• indicates blood glucose for 100 days (life span of RBC-might be affected if spleen is removed, causing RBCs to last longer)

Question 5

6% A1C level corresponse to what mean serum glucose level? (in mg/dl)

Answer 5

6% = 126 mg/dl

Question 6

List the 3 main (overarching) complications of diabetes

Answer 6

1. Ketoacidosis, hyperosmolar coma
2. Microvascular disease
3. Macrovascular disease

Question 7

Major macrovascular disease in diabetes complications

-subsets of this

Answer 7

ATHEROSCLEROSIS

• MI
• CVA
• Peripheral vascular disease (gangrene, renal artery stenosis)

*these mechanisms aren’t understood very well yet*

Question 8

3 main types of microvascular disease caused by diabetes complications

Answer 8

1) neuropathy
2) retinopathy
3) nephropathy

Question 9

mortality vs. morbidity in diabetes

Answer 9

Mortality: macrovascular disease (MI, CVA)

Morbidity: microvascular disease (nephro-, neuro-, retinopathy)

Question 10

• Diabetes
• Impaired fasting glucose (pre-DM)
• normal

Which are positive in microvascular vs macrovascular in terms of risk based?

Answer 10

Diabetes is positive for both, but only macrovascular is also positive in IFG (normal is negative in both)

Question 11

best type of control for complications in Type 2 DM

Answer 11

Blood pressure control

bigger bang for buck: statistically significant for percent reduction in microvascular, macrovascular, and death

Question 12

Results of cumulate incidence of Mi + CVA in type 1 DM: conventional vs intensive therapy for 6.5 years

Answer 12

Intensive therapy had slightly lower incidences, but not that amazing compared to conventional

Question 13

LDL control reduces atherosclerotic cardiovascular disease. Which drugs work? (include their MOA)

Answer 13

• Statins: HMG CoA reductase inhibitors, decrease cholesterol synthesis, lower LDL cholesteraol
• Fibrates: PPAR-alpha agonists (promotes uptake and catabolism of FAs), decrease VLDL synthesis

Ezetimibe MAY NOT AFFECT ASCVD (reduces GI cholesterol absoprtion)

Question 14

Study about niacin

Answer 14

While niacin raises HDL by 30%, it fails to prevent ASCVD

Question 15

Study about N-3 Fatty Acids (omega-3)

Answer 15

they decrease TG by 15 mg/dL, but fail to prevent ASCVD or ASCVD death in diabetic patients

Question 16

Treatment rational for macrovascular disease prevention (3)

Answer 16

1. BP control (<140/<80)
2. LDL cholesterol and TG control (< 100 mg/dl)
3. Blood sugar control (<7.0%)

Question 17

A1C levels in patients with established coronary artery disease

Answer 17

Probably harmful for A1C to be <6.5% due to hypoglycemia.

Studies show that this can actually kill pt due to hypoglycemic episodes: if you have atherosclerosis in the heart and you have a hypoglycemic episode, you release catecholamines which will constrict your coronary arteries even more, potentially causing MI, arrythmia, death.

Question 18

Retinopathy (3) and comments on its effects/therapy

Answer 18

1. microaneurysms
2. hemorrhages
3. exudates

does not threaten vision, no directed retinal therapy required, BP and DM control delay/prevent progression

Question 19

What are microaneurysms? Why do they develo?

Answer 19

Microaneurysms are aneurysms of capillaries:

• ​high glucose concentrations hurt the pericytes that line retinal capillaries
• pericytes die
• microaneurysms are first step of DM retinopathy

Question 20

What type of retinopathy threatens vision? What is treatment?

Answer 20

Proliferative Retinopathy

• growth of new vessels
• bleeding threatens vision
• laser panretinal photocoagulation causes regression/prevents blindness
  
  • scatter treatment over wider area of retina: laser heat to seal/destroy leaky blood vessels

Question 21

Proliferative Retinopathy and vascular endothelial growth factor

-describe the process of damage to new proliferation and the treatment

Answer 21

microvascular damage –> decreased retinal oxygen + nutrient delivery –> increased growth factor production –> proliferation of new blood vessels

injections of intra-vitreous VEGF antibody (Bevacizumab) caused rapid improvement after 1 week

Question 22

What is macular edema?

What does it cause, what doesn’t it cause?

Is it treatable?

Answer 22

• swelling or thickening of the eye under the macula
• causes decreased acuity, but DOES NOT cause blindness (think about when youre underwater, blurry AF but you can still see…)
• treatable with VEGF inhibitors (injected directly into the vitreous)

Question 23

What two problems with the eye do not response to improved blood sugar control?

Answer 23

1. proliferative retinopathy
2. macular edema

Question 24

What is the leading cause of dialysis?

Answer 24

Diabetic nephropathy

Question 25

Progression of Diabetic Nephropathy (3)

Answer 25

1. Microalbuminuria
2. Proteinuria
3. Decreased GFR/Cr clearance and increased serum creatinine

Question 26

Microalbuminuria:

• definition
• test
• prognosis after 5 years

Answer 26

• definition: 21 to 500 mg albumin / g Cr
• test: spot urine or 24 hour collection
• prognosis after 5 years: 1/3 normalize, 1/3 stable, and 1/3 progress to next stage of disease

Question 27

• Definition of proteinuria
• importance of this stage

Answer 27

• > 500 mg
• at this point, there is a progressive and irreversible **decline in GFR **(creatinine clearance)
• proteinuria continues to increase until the GFR is very low

Question 28

What slows the decline of decreased GFR and progression to dialysis? What does not control the decline?

Answer 28

BP control (<130/80) slows the decline

blood sugar control does not slow the decline and progression to dialysis in a pt with established nephrotic

Question 29

Kimmelstiel-Wilson Disease

Answer 29

Nodular glomerulosclerosis of DM.

Nodules of pink hyaline material form in regions of glomerular capillary loops in the glomerulus.

This is due to increase in mesangial matrix: damage due to non-enzymatic glycosylation of proteins

Question 30

Pathophysiology of diabetic neuropathic ulcers + treatment

Answer 30

• caused by nerve damage
• sensation nerves dont work well, and longest nerves are affected first (ones that go to feed)
• get pressure sores, don’t feel them, develop calluses, soft tissue breakdown, open wound, infection
• open wound + bone infection + diabetes = amputation (osteomyelitis) is only way to cure the infectio
• abx dont go to dead bone and no vasculature going there, so they don’t help

Question 31

What causes distal gangrene in DM?

Answer 31

this is a macrovascular disease, as compared to the microvascular neruopathic ulcers.

Lack of vascular supply –> poor wound healing

Question 32

Antihypertensive agents + order of addition

Answer 32

1. ACE inhibitor or ARB (or hydroclorothiazide for low renin HTN)

2+3. HCTZ or beta blocker

4. Calcium blocker
5. alpha blocker