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Cardio Diabetes Medicine 2017 Diabetes and Heart Are Inseparable Partners - How & Why 77

effects on heart. The contraindication to use in HF of relative increases in mortality hazard ranging from
was removed from all U.S. metformin product la- 30% to 60% .Pathophysiologic Abnormalities Asso-
bels in 2006, on the basis of demonstrated clinical ciated with Cardiac Dysfunction, Congestive Heart
safety and observational associations of improved Failure, and Adverse Outcomes in Diabetes are Sym-
cardiovascular outcomes in the HF cohort among pathetic nervous system activation, Renin-angioten-
metformin-treated patients,thus making metformin sin-aldosterone system activation, Increased sodium
the first line of diabetic drug therapy unless contra and free water retention, Decreased vascular compli-
indicated. Concerns persist, however, about the use ance, Elevated endothelin levels, Loss of “dipping”
of sulfonylureas in CVD cohorts, driven by the weight nocturnal blood pressure pattern , Increased free
gain associated with the drugs, the increased risk for fatty acid levels ,Dysregulated myocardial glucose
hypoglycemia and commensurate stimulation of the and fatty acid metabolism,Increased left ventricular
adrenergic stress-response system with potential ad- hypertrophy or mass via myocyte hypertrophy, Depo-
verse CVD effects, and the potential of these drugs sition of advanced glycation end products in extra-
to inhibit so-called ischemic preconditioning through cellular matrix, Increased cardiac fibrosis,Increased
blockade of myocardial KATP channels. In animal cardiac steatosis.
models of MI, activation of myocardial KATP chan-
nels reduces infarct size—an effect termed ischemic
preconditioning that is blocked by sulfonylureas.
Saxagliptin like DPP 4 inhibitors and Thiazolidine-
diones were associated with increase risk of heart
failure. As expected, insulin use was associated with
more hypoglycemia and weight gain.Dopaminne ag-
onist were used in trials which showed decrease in
cardiac morbidity but the data was sparse to extrap-
olate to general population. After decades of inves-
tigation, this combination of glucose, insulin, and
potassium has become known as GIK therapy, and
the focus of attention has shifted from the polarizing
effects to the direct effects of insulin, including pro-
motion of myocardial glucose oxidation, reduction
of circulating nonesterified free fatty acids that may
contribute to myocardial injury through an increased
oxygen demand associated with free fatty acid me-
tabolism and resultant accumulation of toxic free
fatty acid metabolites, improved coagulation param-
eters, and anti-inflammatory effects. The group with
diabetes has derived much greater absolute benefit
from thrombolytic therapy than non diabetic patients.
Although initial success rates in diabetic and nondi-
abetic patients are similar, diabetic patients exhibit
higher restenosis rates after PCI and worse long-term
outcomes. The GP IIb/IIIa antagonists have demon-
strated similar or increased efficacy in the setting of
PCI in patients with diabetes compared with nondia-
betic patients, both in stable and unstable coronary
disease.
Treatment of a diabetic patient’s heart failure re-
HEART FAILURE: semble those in nondiabetic patients: preservation of
myocardial function, relief of pulmonary congestion,
Diabetes mellitus and insulin resistance before the slowing of the progression of the disease. effect of
development of diabetes also are strong and inde- ACE inhibitors for primary prevention of HF in high-
pendent risk factors for HF, with an associated two- risk cohorts of patients with diabetes demonstrates
to fivefold increased risk. once HF is present, dia- an 18% relative risk reduction. use of ARBs was as-
betes portends an especially adverse prognosis for sociated with significant reduction for incident HF
subsequent morbidity and mortality, with estimates commensurate with the treatment effect observed

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