Chapter 12 - Diabetes

Question 1

Cause of T1DM

Answer 1

Autoimmune destruction of beta cell 1) islet cell autoantibodies 2) insulin autoantibody 3) antiglutamic acid decarboxylase antibody 4) antibody to tyrosine phosphatase IA-2 and IA-2beta

Question 2

T1DM associated with

Answer 2

1) Lupus 2) RA 3) Hashimoto thyroiditis

Question 3

Rate of T1DM vs T2DM

Answer 3

T1DM 5-10% T2DM 90-95%

Question 4

Heritability of insulin sensitivity

Answer 4

40-50%

Question 5

Effect of diabetes on CAD, CVA, PAD

Answer 5

CAD = 50% higher mortality after MI CVA = less chance of recanalization and higher risk of hemorrhagic transformation; less likely for discharge home and independence PAD = complicated by neuropathy, microvascular disease, delay healing and diagnosis

Question 6

Function of NO

Answer 6

1) vasodilation 2) reduce production of proinflammatory chemokine and cytokine

Question 7

Hyperglycemia on cellular endothelial level

Answer 7

Increase ROS production –> oxidative stress –> inactivate endothelium-derived NO

Question 8

Effects of diabetes on cellular level

Answer 8

FIGURE 12.1

Question 9

diabetes on platelets

Answer 9

1) increase GlbIb and GlbIIb/IIIa exspression 2) increase vWF and platelet-fibrin interaction 3) increase procoagulant factors: factor VIII, thrombin, tissue factor 4) decrease edogenous anticoagulants and fibrin inhibitors: thrombomodulin, protein c, plasminogen activator inhibitor 1

Question 10

Treatment algorithm for diabetes and PAD

Answer 10

1) smk cessation program 2) HTN < 140/90 3) A1C < 7 4) LDL < 70 mg/dl 5) antiplatelet (ASA or plavix) 6) ACEi 7) beta blocker 8) statins 9) cilostazol if I.C. 10) exercise rehab program 11) foot care

Question 11

Reasons to revascularize diabetic foot

Answer 11

1) incapacitating claudication 2) limb salvage 3) vasculogenic impotence

Question 12

Reasons to amputate in diabetic

Answer 12

1) beyond salvage 2) revasc surgery too risky 3) life expectancy low 4) functional limitation diminish benefit of salvage

Question 13

SVS recommendation on preventing diabetic foot ulceration

Answer 13

1) annual foot exam by specialist 2) inclusion of Semmes-Weinstein test for neuropathy 3) family education about foot care 4) custom footware in high risk patients ( neuropathy, foot deformity, prev amputation) 5) glycemic control A1C < 7%

Question 14

ACCORD, ADVANCE and VADT trials

Answer 14

Failed to prove that aggressive glycemic control is better in fact caused higher mortality and stopped early in ACCORD recommendation is now < 7%

Question 15

Metformin MOA A1c reduction adverse effect

Answer 15

Biguanide Decrease hepatic glucose production 1-2% lactic acidosis, decrease B12

Question 16

Sulfonylureas MOA A1c reduction adverse effect

Answer 16

Glyburide, glipizide, glimepiride bind sulfonylurea receptors on pancreatic islet cells –> stimulate insulin release 1-2% AE: hypoglycemia, weight gain

Question 17

Glinides MOA A1c reduction adverse effect

Answer 17

nateglinide bind sulfonylurea 1-2% AE: hypoglycemia weight gain

Question 18

alpha-glucosidase inhibitor MOA A1c reduction adverse effect

Answer 18

Acarbose, miglitol slows gut carb absorption 0.5-1% AE: gas bloating

Question 19

Thiazolidinediones MOA A1c reduction adverse effect

Answer 19

Rosiglitazone, pioglitazone activates PPAR gamma to increase insulin sensitivity and reduce hepatic glucose production 1-1.5% AE: weight gain, edema, bone loss

Question 20

Incretin modulators MOA A1c reduction adverse effect

Answer 20

GLP-1 mimetics exenatide increase glucose-dependent insulin secretion decrease glucagon delay gastric emptying 1% AE: n/v

Question 21

DPP-4 inhibitors MOA A1c reduction adverse effect

Answer 21

Sitagliptin Saxagliptin inhibit degradation of endogenous GLP-1 enhance effect of incretins 0.6-0.8%

Question 22

Amylin analogues MOA A1c reduction adverse effect

Answer 22

Pramlintide Decrease glucagon secretion and delayed gastric emptying 0.4-0.6% AE: n/v

Question 23

insulin MOA A1c reduction adverse effect

Answer 23

increase insulin supply no limit on aic reduction AE: hypoglycemia, weight gain, edema

Question 24

Bypass angioplasty revascularization investigation 2 diabetes (BARI 2D)

Answer 24

insulin sensitization strategy superior for reducing PAD, need for LE revasc and amputation

Question 25

PROACTIVE trial

Answer 25

Pioglitazone reduce leg amputations

Question 26

ADA algorithm for diabetes medication

Answer 26

1) lifestyle intervention 2) metformin if necessary to achieve A1C \< 7 3) sulfonylurea or insulin as 2nd med 4) other second-tier can be used if needed

Question 27

Heart protection study HPS

Answer 27

1) 3000 subjects 2) simvastatin vs placebo 3) simvastatin reduce CAD, CVA, need for revasc

Question 28

Collaborative atorvastatin diabetes study (CARDS)

Answer 28

1) patients with DM and HTN, retinopathy, smk, micro or macroalbuminuria 2) atorvastatin vs placebo 3) 30% reduction in composite CV event

Question 29

Appropriate blood-pressure control in diabetes (ABCD) trial

Answer 29

strict BP leads to reduced MI, stroke and CV death

Question 30

Antiplatelet in diabetes trials

Answer 30

1) Early treatment diabetic retinopathy trial 2) prevention of pregression of arterial disease and diabetes (POPADAD) 3) japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial

Question 31

ADA/AHA recommendation on ASA for patients with diabetes if:

Answer 31

1) men \> 50 and women \> 60 2) one risk factor: - smk - HTN - lipid - FHx of premature CVD - albuminuria

Question 32

Clopidogrel vs aspirin in patients at risk of ischemic events (CAPRIE) trial

Answer 32

1) 3866 patients 2) NSTEMI, CVA, PAD 3) asa vs plavix 4) plavix reduces CV events more

Question 33

SVS guidelines on antiplatelet in diabetic

Answer 33

recommend for PAD not clear on diabetes if no clear risk then use it

Question 34

Claudication: exercise vs endoluminal revasc (CLEVER) trial

Answer 34

randomized patients 25% had diabetes walking time improved in exercise group QOL improved in stenting group SUPERvised exercise therapy or immediate PTA for I.C. with iliac artery obstruction (SUPER) trial is ongoing

Question 35

Cilostazol key points

Answer 35

1) 3 month trial at 100 mg BID 2) improves walking distance 3) SE: HA, nausea, diarrhea, pain, infection, resp, palpitation, arrhythmia, edema - 5% 4) contraindicated in CHF or severe renal/hepatic failure

Question 36

SVS on cilostazol, pentoxifylline and statin in diabetes and PAD

Answer 36

Cilostazol - trial 3 month at 100 mg bid Pentoxifylline - try if they cannot have cilostazol Statin - use it

Question 37

ACEi in diabetes and PAD

Answer 37

Ramipril improves walking distance SE: persistent cough