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308 Diabetic Cardiomyopathy :
Mechanisms, Diagnosis and Treatment

to reduce mortality rates and lower all-cause hospi- blocker (ARB), a beta-blocker, and a mineralocorti-
tal admissions. According to some studies, insulin coid receptor antagonist (MRA)—are the most import-
use was considered to be a risk factor for develop- ant pharmacological agents for the treatment ofall
ing heart failure. However, those studies were ret- patients with heart failure and reduced LV ejection
rospective and non-randomized. Consequently, it is fraction, including those with diabetes mellitus. They
not possible to determine whether insulin treatment are usually combined with a diuretic for relieving con-
truly increases the risk of heart failure, or identifies gestion and may also be supplemented by ivabra-
a higher-risk diabetic patient. Pioglitazone causes an dine.
increase in body weightand fluid retention in 5-10%
of patients who use this drug. As a consequence, Angiotensin-converting enzyme inhibitors
it might worsen heart failure and increase the num- and angiotensin receptor blockers
ber of hospitalizations. There is growing evidence to
support the use of incretin-based therapies (GLP1 An ACE-I is indicated in diabetes mellitus type 2
agonists and antagonists of DPP4) for reducing car- and heart failure, since it improves symptoms and
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diovascular complications in diabetes. In an animal reduces mortality. The beneficial effects of ARBs are
model of atherosclerosis, GLP-1 significantly reduced equivalent to those of ACE-I, according to subgroup
plaque burden. Apart from anti-atherogenic effects, analyses of clinical trials, and therefore an ARB can
the GLP1 pathway may also have cardioprotective be used as an alternative in ACE-I-intolerant patients.
properties. Increased activation of the GLP-1 axis can When ACE-I and ARBs are used in patients with di-
improve weight loss and lipid profile, and can lower abetes mellitus, monitoring of kidney function and
blood pressure. Moreover, in a small, non-random- potassium is mandatory ,since nephropathy is a fre-
ized study, GLP-1 infusion was associated with a sig- quent occurrence.
nificant improvement in ejection fraction in patients
who presented with acute myocardial infarction and Beta-blockers
reduced LV function. Additional data are needed to Beta-blockers are the standard of care in patients
provide important information about the use of these with systolic heart failure. A subgroup analysis of
agents for the prevention and treatment of diabetic the MERIT-HF trial showed that beta-blockers re-
cardiovascular complications. One of the most hot- duce mortality and hospital admissions and improve
ly debated clinical questions in diabetes is whether symptoms, without significant differences between
intensive glycemic control is associated with better diabetes mellitus type 2 and non-diabetic patients.
cardiovascular outcomes, and how low we should go Beta-blockers recommended in heart failure and di-
in pursuing glycemic targets. The Diabetes Control abetes mellitus type 2 are metoprolol succinate in
and Complication Trial (DCCT) and the United King- the slow release form (MERIT-HF), bisoprolol (Cardiac
dom Prospective Diabetes Study (UKPDS) provided Insufficiency Bisoprolol Study [CIBIS II]), and carve-
consistent evidence that intensive glycemic control dilol (Carvedilol Prospective Randomized Cumulative
prevents the development and progression of mi- Survival [COPERNICUS] and Carvedilol Or Metopro-
crovascular complications in patients with type 1 or lol European Trial [COMET]). Adverse effects of be-
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type 2 diabetes. However, the Action to Control Car- ta-blockers in patients with diabetes mellitus type 2
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diovascular Risk in Diabetes (ACCORD), the Action and heart failure include: a) hypoglycemia, especially
in Diabetes and Vascular Disease (ADVANCE), and with non cardioselective regimens, and b) negative
the Veterans’ Administration Diabetes (VADT) trials metabolic effects (hypoglycemia, dyslipidemia and
revealed no significant effect of intensive glycemic decreased insulin sensitivity).
control on mortality or on amelioration of cardiovas-
cular events. The 2013 ESC Guidelines on diabetes, Mineralocorticoid receptor antagonists
pre-diabetes, and cardiovascular diseases consider An MRA is recommended for all patients with per-
tight glycemic control (HbA1c<7%) as a class I indica- sisting symptoms (New York Heart Association Class
tion to decrease microvascular complications and II-IV) and an LV ejection fraction ≤35%, despite treat-
class IIa for the prevention of cardiovascular disease. ment with an ACE-I (or, if not tolerated, an ARB) and
a beta-blocker, to reduce the risk of heart failure hos-
Heart failure treatment pitalization and premature death (Class IA).98 The
According to the 2013 ESC Guidelines on diabetes, benefit of spironolactone and eplerenone on mortal-
pre-diabetes, and cardiovascular diseases, three ity did not differ between patients with and without
neurohormonal antagonists—an angiotensin-convert- diabetes mellitus type 2 and heart failure. Monitoring
ing enzyme inhibitor (ACE-I) or angiotensin receptor of kidney function and potassium is mandatory, be-

GCDC 2017