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Editorial
Rejuvenating the Failing Heart in Diabetics: Role of Growth
Differentiation Factor‑11
Diabetes mellitus (DM) with or without coronary artery
disease (CAD) and hypertension enhances the risk of heart
failure (HF), and there is substantial evidence supporting a
specific diabetic cardiomyopathy, which might also increase
predisposition to HF.[1]
The Framingham study strongly established the epidemiologic
link between DM and HF. The risk of HF was found to increase
2.4‑fold in men and 5‑fold in women.[2]
The presence of diabetes also makes a poor prognosis in HF
patients who have mortality rates about twice those of the
nondiabetic population. Bell remarked HF in diabetics as “the
frequent, forgotten, and often fatal complication of diabetes.”[3]
Tight glycemic control is associated positively with the primary
prevention of HF. In newly diagnosed diabetics, a 1% reduction
in hemoglobin A1c (HbA1c) was found to be associated with
a 16% risk reduction in the development of HF![4]
Standard drug therapies of HF, like angiotensin‑converting-
enzyme inhibitors, beta blockers, and mineralocorticoid
receptor antagonists are equally effective in individuals with or
without diabetes. However, whether or not various antidiabetic
drugs are effective in controlling the development of
cardiovascular (CV) risks, including HF is not well established.
Insulin causes sodium retention and thiazolidinediones add to
the risk of HF. CV safety evaluations of newer glucose‑lowering
agents have revealed surprising results of an increased risk of
hospital admission, for HF of diabetic patients, who were
receiving the dipeptidylpeptidase‑4 inhibitor, saxagliptin.
Therefore, there is a continuous quest for targets which will
prevent the development of CV complications, especially HF.
Rejuvenation Factors and Heart Failure
Accumulating evidence strongly suggests that various systemic
rejuvenation factors profoundly influence tissue aging, and
HF, which occurs more frequently as a consequence of it,
in addition to other precipitating factors. Some of these
evidences have been apparent from the experimental models
of parabiosis, which was first carried in the 19th century.[5] In
parabiosis, two small animals, like mice are joined surgically,
in such a way that they share blood circulation with rapid
and continuous exchange of cells and other factors via their
common circulatory systems.[6] The paired animals may be
of same age (isochronic) or of different ages (heterochronic).
Parabiosis is considered as a powerful model to determine
whether circulating factors can alter tissue function, especially
aging.[7,8] Very interesting observations were made from
heterochronic parabiosis experiments. These suggest that
© 2015 Journal of the Practice of Cardiovascular Sciences | Published by Wolters Kluwer ‑ Medknow
blood‑borne factors from a young animal can considerably alter
the function of aging tissues, like the restoration of function of
aging skeletal muscle cells.[9] On the other hand, exposing a
young animal to circulating factors from an older animal can
inhibit skeletal muscle function[10] and neural functions[8] in
the young animal.
More recently, Loffredo et al. demonstrated reversal of
age‑related cardiac hypertrophy by exposing the heart to
a young circulatory milieu. Their study suggested that the
cardiac hypertrophy of aging is at least in part attributed
to some circulating factors, and more precisely to growth
differentiation factor‑11 (GDF‑11), a transforming growth
factor β family member that can heal age‑related cardiac
hypertrophy. The authors suggested that there is at least one
hormonal factor which might be responsible for age‑related
diastolic HF.[11] Administration of GDF‑11 protein in aged
mice caused reduction of heart weight and cardiac hypertrophy
without affecting cardiac function. It suggests that GDF‑11 is
a negative regulator of cardiac hypertrophy.
In the present issue of JPCS, Adela et al.[12] have shown that
plasma GDF‑11 levels were decreased in Indian patients of
diabetes and diabetes with CV complications. They measured
plasma GDF‑11 levels from 89 age‑matched (35–65 years)
subjects. The study consisted of patients with Type 2 diabetes
mellitus (T2DM), T2DM with hypertension, CAD alone, CAD
with (T2DM‑CAD, n = 20), and age‑matched healthy controls.
HbA1c, fasting blood sugar, creatinin, lipid profile, uric acid,
and systolic and diastolic blood pressure were measured in all
the patients. The sample size of the study may not be adequate
to arrive at a definite conclusion on the association, in addition
to the fact that correlation between GDF‑11 and development
CV complications in diabetics needs further well‑designed
studies.
The present study provides useful information about the role
of GDF‑11 in CV risk stratification in diabetics, which might
be useful in their clinical management. The study also suggests
possibilities of restoring the levels of circulating GDF‑11 to
normal and improving cardiac function in patients of diabetic
CV disease.
Subir K. Maulik
Department of Pharmacology, All India Institute of Medical Sciences,
New Delhi, India
Address for correspondence:
Dr. Subir K. Maulik,
Department of Pharmacology, All India Institute of
Medical Sciences, New Delhi, India.
E‑Mail: skmaulik@gmail.com
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Maulik: Rejuvenation, Diabetes and Growth Differentiation Factor
References
1. Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW,
Grishman A. New type of cardiomyopathy associated with diabetic
glomerulosclerosis. Am J Cardiol 1972;30:595‑602.
2. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive
heart failure: The Framingham study. Am J Cardiol 1974;34:29‑34.
3. Bell DS. Heart failure: The frequent, forgotten, and often fatal
complication of diabetes. Diabetes Care 2003;26:2433‑41.
4. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA,
et al. Association of glycaemia with macrovascular and microvascular
complications of type 2 diabetes (UKPDS 35): Prospective observational
study. BMJ 2000;321:405‑12.
5. Finerty JC. Parabiosis in physiological studies. Physiol Rev 1952;32:277‑302.
6. Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL.
Physiological migration of hematopoietic stem and progenitor cells.
Science 2001;294:1933‑6.
7. Ruckh JM, Zhao JW, Shadrach JL, van Wijngaarden P, Rao TN,
Wagers AJ, et al. Rejuvenation of regeneration in the aging central
nervous system. Cell Stem Cell 2012;10:96‑103.
8. Villeda SA, Luo J, Mosher KI, Zou B, Britschgi M, Bieri G, et al. The
ageing systemic milieu negatively regulates neurogenesis and cognitive
function. Nature 2011;477:90‑4.
9. Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL,
Rando TA. Rejuvenation of aged progenitor cells by exposure to a
young systemic environment. Nature 2005;433:760‑4.
10. Brack AS, Conboy MJ, Roy S, Lee M, Kuo CJ, Keller C, et al. Increased
Wnt signaling during aging alters muscle stem cell fate and increases
228 Journal of the Practice of Cardiovascular Sciences ¦ September‑December 2015 ¦ Volume 1 ¦ Issue 3
fibrosis. Science 2007;317:807‑10.
11. Loffredo FS, Steinhauser ML, Jay SM, Gannon J, Pancoast JR,
Yalamanchi P, et al. Growth differentiation factor 11 is a circulating factor
that reverses age‑related cardiac hypertrophy. Cell 2013;153:828‑39.
12. Adela R, Reddy PN, Banerjee SK. Alteration of plasma growth
differentiation factor‑11 levels in type 2 diabetes patients with
cardiovascular complications: A pilot study. J Pract Cardiovasc Sci
2015;1:262-6.
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How to cite this article: Maulik SK. Rejuvenating the failing heart in
diabetics: Role of growth differentiation factor-11. J Pract Cardiovasc Sci
2015;1:227-8.