Diabetes Management In Cardiovascular Diseases: Anwar C Varghese Prof D Rajasekaran’s Unit

Diabetes management in cardiovascular diseases Anwar C Varghese Prof D Rajasekaran’s unit

• Magnitude of the problem • Management of diabetes mellitus in ACS • Management of diabetes in CAD patients • Diabetes and cardiac

Magnitude of the problem • Diabetes confers as much CV risk as a previous MI • Men have 2 times the risk; women upto 4. • Account for majority of the disease in younger men and premenopausal women. • Worse prognosis after an acute coronary syndrome • 80% of deaths among diabetic patients are from CHD Management of Diabetes with Acute Myocardial Infarction (AMI)

Early mortality from acute MI

Hyperglycemia as prognostic indicator • Hyperglycemia on admission for acute MI indicated increased mortality. • FPG is a strong predictor of mortality

Mortality and CHF after MI

Wahab NN, Cowden EA, Pearce NJ, on behalf of the ICONs Investigators: Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J Am Coll

FPG and 30 day mortality after acute MI

Suleiman M, Hammerman H, Boulos M, et al: Fasting glucose is an important independent risk factor for 30-day mortality in patients with acute myocardial infarction: A prospective study. Circulation 111:754-760, 2005

Reasons for the poor prognosis • Reluctance to apply clinical measures like beta blockers. • Clustering of other risk factors • The lipid rich atherosclerotic plaques  more vulnerable to rupture • overexpression of receptor for advanced glycation end products (RAGE) more metalloproteinase activity which destabilize plaques.

Reasons for the poor prognosis • Increased levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and atheromas which rduce fibrinolysis, increase thrombus formation, and accelerate plaque formation • Increased endothelin activity and reduced prostacyclin and nitric oxide activity, lead to abnormal control of blood flow

Management of ACS in diabetes mellitus Aspirin resistance • failure to reduce adhesiveness of platelets • related to poor metabolic control • aspirin, 150 mg, 1 week reduced platelet adhesiveness in 69 % of the nondiabetic patients but in only 29 % of the patients with type 2 diabetes (p = 0.0006) Braunwald’s heart disease

Beta blockers • Under prescribed due fear of hypoglycemia, worsening of metabolic status • New studies confirm the greater benefit derived by diabetics • Noncardioselective beta blocker carvedilol associated with better metabolic control. • Beta blockers restore sympathovagal balance in autonomic neuropathy • Decrease fatty acid utilization within the myocardium, reducing oxygen demand

Glycemic control • • • • • • • •

What is the drug to be used? Insulin How to give insulin? Intravenous infusion How long to give iv insulin? At least 24 hours What is the target? Tight glycemic control (4-7 mmol/dl)

• Stop oral hypoglycaemic agents. • Infuse 10% Dextrose iv at 15 mls / hour for at least 24 hours. • Commence iv insulin infusion at 1u / hour. • Check BG hourly . • Aim for BG of 4 – 7 mmol/l by adjusting the insulin infusion rate. • Institute all normal post-infarct procedures and drug interventions using standard criteria (ACE inhibitor, oral beta blockers, statins, aspirin, etc). • The serum potassium should be monitored closely. Potassium supplements can be given either orally or iv. The serum

How to treat after the acute phase? • If prior OHA or Insulin regime seemed adequate, then continue the same. • If prior OHA regime was giving poor control, consider insulin • If prior insulin regime was giving poor control, consider

Hypoglycemia and mortality

Hypoglycemia • Detrimental to the recovering myocardium by causing beta adrenergic stimulation and lack of metabolic substrate. • Hypoglycaemia during admission may increase re-infarction rates. • Predisposes to fatal arrhythmias.

Glucose-insulin-potassium (GIK) solution • regaining favor as a method to influence myocardial metabolism positively during treatment of MI • polarizing agent maintaining electrical stability • attenuate the rise in free fatty acids (FFAs) during MI, shifts myocardial oxidative metabolism from FFAs to glucose oxidation. • Has antiinflammatory and

Treatment of diabetes in CAD Sulfonylureas • Associated with fear of loss of ischemic preconditioning • Blockage of K+-ATP channels in myocardium • UKPDS findings strongly disprove this theory

Thiazolidinediones not recommended for use in patients with NYHA Class III or IV CHF causes fluid retention Used in diabetic cardiomyopathy

Metformin • Contraindicated in patients requiring pharmacological treatment of CHF • Cardiac failure increase lactic acidosis due to

CABG vs. Coronary stenting • Higher restenosis rates and worse long-term outcomes after PTCA • CABG may provide better outcomes than standard PTCA, especially in patients

Diabetes and cardiac failure Diabetics 2.5 times more likely to develop cardiac failure Increased mortality in cardiac failure patients; especially in ischemic cardiomyopathy diabetes and ischemic heart disease interact to accelerate the progression of myocardial dysfunction 1 % increase in average HbA1C was associated with a 16 percent increase in CHF

Diabetes-specific factors related to CHF • Advanced glycation end products (AGES) Accumulation of AGE-modified extracellular matrix results in loss of elasticity of the vessel wall and interfere with myocardial function. • Myocardial calcium handling  slows Ca removal from the cytoplasm in diastole increasing diastolic stiffness. • Myocardial metabolism  the diabetic heart have exaggerated impairment of ATP generation during ischemia.

Diabetes-specific factors related to CHF Coronary microcirculation • Endothelial dysfunction (reduced synthesis of the vasodilator nitric oxide), • abnormal angiogenic response Failure of ischemic preconditioning

Diabetic cardiomyopathy • Diabetic cardiomyopathy affects the myocardium in diabetic patients eventually leading to LVH and diastolic and systolic dysfunction. • The concept is based upon the idea that diabetes is the factor which leads to changes at the cellular level, leading to structural abnormalities • DCM may overlap with CAD and hypertension