Diabetes complications (review w/ handout)

Question 1

Morbidity from Diabetes

Answer 1

Diabetic CVD (2-6 fold higher risk of heart disease in diabetes)
Diabetic retinopathy
Diabetic nephropathy
Diabetic amputations

CVD is leading cause of death in diabetes

Most common reason for hospitalization

Question 2

Men vs women: survival post MI diabetic m vs f

Answer 2

Women with diabetes, post MI is more devastating than men

Question 3

Factors accelerating atherosclerosis in diabetes

Answer 3

Hyperinsulinemia
insulin resistance leading to:
Glucose intolerance
increased triglycerides, Decreased HDL chol, increased BP
Small, dense, LDL, Increased PAI-1

Leads to macrovascular disease: eg coronary heart disease

Question 4

Atherogenic factors

Answer 4

hypertension
hyperlipidemia
hyperglycemia
smoking

impacts endothelial cells

In diabetes:
Impaired endothelial cells:
-activates platelets
-activates monocytes, turns them to mac (foam cell)
-LDL crosses
-pro-inflammatory cycles–>atherosclerosis

Question 5

Lipid and Lipoprotein abnormalities in DM

Answer 5

-Hypertriglyceridemia (VLDL, IDL, remnants)
-decreased HDL chol
-lipoprot comp:
increased TG, increased chol/lecithin
-glycation/oxidation
-small dense LDL (40-70y, should be on agent lowering LDL if w/ diabetes)
-increased Lp(a) (renal disease)

Question 6

Cholesterol lowering in diabetes

Answer 6

• treat as if they have CVD
• decreases plaque progression, nonfatal CV events
• All people with diabetes between 40-75 should be on a statin

Question 7

Hypertension in Diabetes

Answer 7

definition: SBP> 140 and or DBP >90
target: 140/90
HTN contributes to all complications of DM

Question 8

Complications of DM

Answer 8

Microvascular complications:
retinopathy
neuropathy
nephropathy

Question 9

Cells without ability to manage excess glucose

Answer 9

In neurons, sensitive kidney or endothelial cells, or eye cells: no ability to protect themselves from excess glucose.
Glucose can shunt into polyol or hexosamine pathway: advanced glycosylation of proteins, lipids, DNA

Question 10

Polyol pathway

Answer 10

glucose–>sorbitol (via aldose reductase)
sorbitol–>fructose (sorbital dehydrogenase)

aldose reductase is a therapeutic target

Question 11

Advanced glycation end-products

Answer 11

• interfere with basement membrane function
• squelch nitric oxide and impair vasodilation
• Bind to AGE cellular recep (produc of matrix prot like type IV collagen by renal mesangial cells; exp of adhesion molecs on endothelial cells; produc of growth factor like VEGF)

-intracellular AGEs can crosslink and disrup DNA func and repair

Question 12

Protein Kinase C

Answer 12

• inhibition in people isn’t very effective
• lots of PKCs, work many different ways (“bad guys” in eye vs heart are different)

-hyperglycemia plus AGEs plus diacylglycerol degen, etc contribute to PKC activation leading to effects in retina, vasculature, kidney, heart

Question 13

Brownlee unifying hypothesis

Answer 13

• links pthways

- demonstrates overwhelmed mitochondria, produces ROS, DNA damage, etc

Question 14

Retinopathy

Answer 14

diabetes is the leading cause of blinding in US

Pathogenesis:

• pericyte drop-out
• loss of autoregulation of blood flow to retinal capillary bed
• capillary drop out
• basement membrane thickening
• leakage of intravascular fluids leading to soft and hard exudates
• hypoxic stress and local produc of cytokines and growsth factors (VEGF)
• neovascularization and proliferative retinopathy

Question 15

Stages of diabetic retinopathy

Answer 15

1. early preproliferative
2. mild preproliferative
3. severe preproliferative (time for intervention, can preserve 70% of vision)
4. early proliferative
5. neovascularization disc/elsewhere
6. macular edema

Question 16

is retinopathy preventable?

Answer 16

yes
annual ophtalmologic examinations–>early intervention
-good blood sugar control

Question 17

Additional ocular compliations of dm

Answer 17

macular edema (photocoag, steroids, VEGF inhibitors effective)

• corneal ulceration
• glaucoma
• cataracts

Question 18

Nephropathy

Answer 18

diabetes is primary cause

• VERY long preclinical phase with normal or supranormal GFR
• proteinuria is critical marker of impending serious renal disease
• w/o tx, decline in GFR is rapid

Question 19

Nephropathy pathogenesis

Answer 19

• hyperfiltration (secondary to the increased osmotic load of hyperglycemia)
• intrarenal and peripheral htn
• basement membrane thickening
• mesangial proliferation
• golmerular obliteration

**use microalbumin to screen (not GFR or creatinine)

Question 20

Interventions for nephropathy

Answer 20

Slowing progression:
ACE-I
Metabolic control
Protein restriction

Question 21

Types of diabetic neuropathy

Answer 21

• mononeuritis multiplex
• distal symmetric polyneuropathy (most concerning, “stocking glove neuropathy”, hyperesthesia, parasthesia; high risk for amputation once you can’t feel feet)
• autonomic neuropathy
• diabetic amyotrophy (inflammatory form of girdle neuropathy; very painful, better in 18 months but disabled during that time)

Question 22

Diabetic foot disease

Answer 22

• impaired blood flow and sensation to extremities
• high incidence of mechanical trauma nd infectious complications leading to amputation and hospitalization
• largely preventable by appropriate footwear, exam, and education