Chapter 12 - Diabetes Flashcards
Cause of T1DM
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
T1DM associated with
1) Lupus 2) RA 3) Hashimoto thyroiditis
Rate of T1DM vs T2DM
T1DM 5-10% T2DM 90-95%
Heritability of insulin sensitivity
40-50%
Effect of diabetes on CAD, CVA, PAD
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
Function of NO
1) vasodilation 2) reduce production of proinflammatory chemokine and cytokine
Hyperglycemia on cellular endothelial level
Increase ROS production –> oxidative stress –> inactivate endothelium-derived NO
Effects of diabetes on cellular level
FIGURE 12.1
diabetes on platelets
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
Treatment algorithm for diabetes and PAD
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
Reasons to revascularize diabetic foot
1) incapacitating claudication 2) limb salvage 3) vasculogenic impotence
Reasons to amputate in diabetic
1) beyond salvage 2) revasc surgery too risky 3) life expectancy low 4) functional limitation diminish benefit of salvage
SVS recommendation on preventing diabetic foot ulceration
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%
ACCORD, ADVANCE and VADT trials
Failed to prove that aggressive glycemic control is better in fact caused higher mortality and stopped early in ACCORD recommendation is now < 7%
Metformin MOA A1c reduction adverse effect
Biguanide Decrease hepatic glucose production 1-2% lactic acidosis, decrease B12
Sulfonylureas MOA A1c reduction adverse effect
Glyburide, glipizide, glimepiride bind sulfonylurea receptors on pancreatic islet cells –> stimulate insulin release 1-2% AE: hypoglycemia, weight gain
Glinides MOA A1c reduction adverse effect
nateglinide bind sulfonylurea 1-2% AE: hypoglycemia weight gain
alpha-glucosidase inhibitor MOA A1c reduction adverse effect
Acarbose, miglitol slows gut carb absorption 0.5-1% AE: gas bloating
Thiazolidinediones MOA A1c reduction adverse effect
Rosiglitazone, pioglitazone activates PPAR gamma to increase insulin sensitivity and reduce hepatic glucose production 1-1.5% AE: weight gain, edema, bone loss
Incretin modulators MOA A1c reduction adverse effect
GLP-1 mimetics exenatide increase glucose-dependent insulin secretion decrease glucagon delay gastric emptying 1% AE: n/v
DPP-4 inhibitors MOA A1c reduction adverse effect
Sitagliptin Saxagliptin inhibit degradation of endogenous GLP-1 enhance effect of incretins 0.6-0.8%
Amylin analogues MOA A1c reduction adverse effect
Pramlintide Decrease glucagon secretion and delayed gastric emptying 0.4-0.6% AE: n/v
insulin MOA A1c reduction adverse effect
increase insulin supply no limit on aic reduction AE: hypoglycemia, weight gain, edema
Bypass angioplasty revascularization investigation 2 diabetes (BARI 2D)
insulin sensitization strategy superior for reducing PAD, need for LE revasc and amputation
PROACTIVE trial
Pioglitazone reduce leg amputations
ADA algorithm for diabetes medication
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
Heart protection study HPS
1) 3000 subjects 2) simvastatin vs placebo 3) simvastatin reduce CAD, CVA, need for revasc
Collaborative atorvastatin diabetes study (CARDS)
1) patients with DM and HTN, retinopathy, smk, micro or macroalbuminuria 2) atorvastatin vs placebo 3) 30% reduction in composite CV event
Appropriate blood-pressure control in diabetes (ABCD) trial
strict BP leads to reduced MI, stroke and CV death
Antiplatelet in diabetes trials
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
ADA/AHA recommendation on ASA for patients with diabetes if:
1) men > 50 and women > 60 2) one risk factor: - smk - HTN - lipid - FHx of premature CVD - albuminuria
Clopidogrel vs aspirin in patients at risk of ischemic events (CAPRIE) trial
1) 3866 patients 2) NSTEMI, CVA, PAD 3) asa vs plavix 4) plavix reduces CV events more
SVS guidelines on antiplatelet in diabetic
recommend for PAD not clear on diabetes if no clear risk then use it
Claudication: exercise vs endoluminal revasc (CLEVER) trial
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
Cilostazol key points
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
SVS on cilostazol, pentoxifylline and statin in diabetes and PAD
Cilostazol - trial 3 month at 100 mg bid Pentoxifylline - try if they cannot have cilostazol Statin - use it
ACEi in diabetes and PAD
Ramipril improves walking distance SE: persistent cough
