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302 Diabetic Cardiomyopathy :
Mechanisms, Diagnosis and Treatment

tension, obesity, coronary artery disease or dyslip- of symptoms and signs. There appears to be a long
idemia. The close correlation between diabetes and subclinical course in most patients before the devel-
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heart failure has been demonstrated in many studies. opment of symptoms. 7
In the United Kingdom Prospective Diabetes Study
(UKPDS) an increased prevalence of heart failure was Pathophysiology
recorded in patients with diabetes mellitus type 2, There are two main types of cardiomyopathy: (1) pri-
correlating with levels of glycosylated hemoglobin mary cardiomyopathy, where the cardiac function
(HbA1c). The incidence of heart failure is 2.3 cases is aggravated by a defect in the heart itself, and (2)
per 1000 person-years in patients with HbA1c<6% in secondary cardiomyopathy, where cardiac perfor-
contrast to 11.9 per 1000 person-years in patients with mance is affected because of a systemic syndrome.
significantly high HbA1c (>10%). There are identifiable Cardiomyopathy leads to heart failure, which can be
risk factors for developing diabetic cardiomyopathy, either diastolic heart failure, with preserved ejection
such as increased HbA1c, high body mass index, fraction, or systolic heart failure, with reduced ejec-
advanced age, use of insulin, proteinuria, the coex- tion fraction. Diabetes can lead to heart failure, not
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istence of coronary artery disease and/or peripheral only by augmenting the impact of classical cardio-
target organ diseases such as retinopathy and ne- vascular risk factors (e.g. accelerating the appearance
phropathy. In a large case-control study, Bertoni et and progression of coronary artery disease through
al tested the hypothesis that diabetes mellitus was macroangiopathy), but also via a direct deleterious
independently associated with idiopathic cardiomy- effect on the myocardium per se. This condition is
opathy. After adjusting for age, sex, race, and hyper- known as diabetic cardiomyopathy, defined as the
tension, diabetes mellitus was significantly associat- presence of myocardial involvement in patients with
ed with idiopathic cardiomyopathy (relative risk 1.58, diabetes, characterized by dilatation and hypertrophy
95% CI 1.55–1.62). Similarly in a large population-based of the left ventricle, with the concomitant appearance
cohort study, the Reykjavik Study, Thrainsdottir et al of diastolic and/or systolic dysfunction, and its pres-
explored the associations between heart failure and ence is independent of the coexistence of ischemic
abnormal glucose regulation (impaired glucose tol- or hypertensive or valvular heart disease. Myocardial
erance or impaired fasting glucose). The odds ratio fibrosis and myocyte hypertrophy are the most fre-
was 2.8 (95% CI 2.2–3.6) for the association between quently proposed mechanisms to explain cardiac
diabetes mellitus type 2 and heart failure and 1.7 (95% changes in diabetic cardiomyopathy. Several studies
CI 1.4–2.1) for the association between abnormal glu- have shown that diabetes causes defects in cellu-
cose regulation and heart failure.
lar calcium transport, defects in myocardial contrac-
tile proteins, and an increase in collagen formation,
DEFINITIONS which result in anatomic and physiological changes
Diabetic cardiomyopathy refers to a disease process in the myocardium.
which affects the myocardium in diabetic patients
causing a wide range of structural abnormalities Myocardial fibrosis
eventually leading to LVH [left ventricular (LV) hy- Myocardial fibrosis, as initially described by Rubler
pertrophy] and diastolic and systolic dysfunction or et al and confirmed in histological studies in both
a combination of these. The concept of diabetic car- experimental subjects and humans, is a major con-
diomyopathy is based upon the idea that diabetes is sequence of the adverse effects of diabetes melli-
the factor which leads to changes at the cellular level, tus in the heart. Newer echocardiographic techniques
leading to structural abnormalities as outlined above. should be used in order to evaluate the myocardial
We know that diabetic patients are at increased risk collagen content and its pivotal role in cardiac func-
of hypertension and CAD; however, the idea of the tion. Backscatter is an ultrasound tissue characteriza-
existence of a diabetic cardiomyopathy suggests that tion technique, based on the measurement of myo-
changes can occur and be detected without the pres- cardial tissue echoreflectivity, that is related to myo-
ence of these other factors. Therefore patients with cardial collagen content. Di Bello et al demonstrated
hypertension and CAD may well have myocardial an increase in myocardial echodensity, as assessed
changes related to these disease processes, but a by the integrated backscatter index, in 26 insulin-de-
specific cardiomyopathy may also affect the myocar- pendent diabetic normotensive patients compared
dium secondary to diabetes causing a synergistic ad- with 17 age- and sex-matched control subjects. Fang
verse effect as seen with a combination of diabetes et al confirmed these results using backscatter in a
and hypertension. Diabetic cardiomyopathy can be larger study. Biomarkers of collagen synthesis (pro-
subclinical or apparent depending on the presence

GCDC 2017