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Cardio Diabetes Medicine 2017 309

cause of the increased risk of nephropathy in pa- occur in subjects at risk of developing diabetes as
tients with diabetes mellitus. 32 well as in those with Type II diabetes. Furthermore,
it has been associated with impaired reactivity in the
Diuretics skin microcirculation of these subjects. 35
These drugs are useful for the relief of dyspnea and
edema in heart failure with fluid retention, irrespec- Summary and conclusion
tive of the ejection fraction, although there is no ev- Though the existence of diabetic cardiomyopathy
idence of a reduction in mortality or morbidity. Loop has been often questioned, the evidences are now
diuretics are recommended, rather than thiazides, strong enough to support its entity. Diabetic cardio-
because of their better glycemic profile. myopathy encompasses the spectrum from sub-clin-
ical disease to full blown syndrome of CHF. The
Ivabradine pathophysiology of thecondition remains to be fully
The SHIFT trial, involving 6558 patients with heart elucidated. Metabolic disturbances, interstitial fibro-
failure, in sinus rhythm and with heart rate ≥70 bpm sis, cardiomyocyte loss, small vessel disease, and
(3241 on ivabradine; 30% with diabetes mellitus type cardiac autonomic neuropathy have been incriminat-
2), demonstrated that ivabradine significantly re- ed. Prominent functional sequelae include diastolic
duced cardiovascular deaths and hospital admissions and systolic dysfunction. Though no specific thera-
for worsening heart failure. The beneficial difference peutic strategies can be recommended, good glycae-
was similar in a pre-specified subgroup analysis of mic control and judicious use of ACE inhibitors and
patients with and without diabetes mellitus. Finally, calcium channels blockers are viable options. Newer
the presence of diabetes mellitus is not a contrain- insight into molecular basis of the disease will help
dication for cardiac resynchronization therapy and/ us formulate appropriate drug therapy.
or cardiac transplantation in patients with advanced
systolic heart failure. Heart failure with preserved References
33
LV ejection fraction is a primary phenotype in dia- 1. Kochupilai N. Clinical Endocrinology in India. Current Sci 2000; 79: 1061-
betes, and therapy to improve the prognosis of this 7.
type of heart failure is in general still under intensive 2. King H, Aubert RE, Herman WH. Global burden of diabetes 1995-2025
investigation. : Prevalence, numerical estimates and projection. Diabetes Care 1998;
21: 1414-31.
NEW THERAPEUTIC DIRECTIONS 3. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart
failure: The Framingham Study. Am J Cardiol 1974; 34: 29-34.
PARP inhibitors: PARP-1 is a member of the PARP
enzyme family and is one of the most abundant nu- 4. Zhi YF, Johannes BP, Marwick JH. Diabetic Cardiomyopathy: Evidences,
mechanism and therapeutic implications. Endocrine Reviews 2004; 25
clear proteins which functions as a DNA-nick-sensor (4): 543-67
enzyme. Recently in endothelial cells, hyperglycae- 5. Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC
mia-induced overproduction of mitochondrial super- Jr. Heart failure prevalence, incidence, and mortality in the elderly with
oxide has been shown to cause DNA strand breaks, diabetes. Diabetes Care. 2004; 27: 699-703.
leading to an activation of PARP which inhibits GAP- 6. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with mac-
DH (glyceraldehyde-3-phosphate dehydrogenase). rovascular and microvascular complications of type 2 Diabetes (UKPDS
This leads to the accumulation of glucose and other 35): prospective observational study. Brit Med J. 2000; 321: 405-412.
glycolytic intermediates prior to their entry into the 7. Factor, S. M., Bhan, R., Minase, T., Wolinsky, H. and Sonnenblick, E. H.
Krebscycle.These intermediaries activate a number of (1981) Hypertensive diabetic cardiomyopathy in the rat: an experimental
major transducers of hyperglycaemic damage (poly- model of human disease. Am. J. Pathol. 102, 219–228
34
ol pathway, AGE formation and PKCβ activation). In 8. Elliott P, Andersson B, Arbustini E, et al. Classification of the cardiomy-
addition to the direct cytotoxic pathway regulated by opathies: a position statement from the European Society Of Cardiology
DNA injury and PARP activation, PARP also modu- Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2008;
29: 270-276.
lates the course of cardiovascular inflammation and
injury by regulating the activation of NF-κBand in- 9. Shimizu M, Umeda K, Sugihara N, et al. Collagen remodelling in myocardia
of patients with diabetes. J ClinPathol. 1993; 46: 32-36.
ducing over-expression of ET (endothelin)-1 and ET
receptors. Blocking PARP activity with two different 10. Cai L, Li W, Wang G, Guo L, Jiang Y, Kang YJ. Hyperglycemia-induced
competitive PARP inhibitors provides a ‘magic bul- apoptosis in mouse myocardium: mitochondrial cytochrome C-mediated
caspase-3 activation pathway. Diabetes. 2002; 51: 1938-1948.
let’ approach as it blocks activation of all the major
pathways thought to mediate tissue damage in dia- 11. Libby P, Bonow RO, Mann DL, Zipes DP. Braunwald’s Heart Disease, 8th
Edition. Saunders.
betes. Thus far, PARP activation has been shown to

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