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 Table of Contents  
Year : 2015  |  Volume : 1  |  Issue : 3  |  Page : 227-228

Rejuvenating the failing heart in diabetics: Role of growth differentiation factor-11

Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication23-Feb-2016

Correspondence Address:
Subir K Maulik
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2395-5414.177225

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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

How to cite this URL:
Maulik SK. Rejuvenating the failing heart in diabetics: Role of growth differentiation factor-11. J Pract Cardiovasc Sci [serial online] 2015 [cited 2019 Nov 12];1:227-8. Available from: http://www.j-pcs.org/text.asp?2015/1/3/227/177225

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 Top

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 19 th 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 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.

  References Top

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.  Back to cited text no. 1
Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: The Framingham study. Am J Cardiol 1974;34:29-34.  Back to cited text no. 2
Bell DS. Heart failure: The frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 2003;26:2433-41.  Back to cited text no. 3
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.  Back to cited text no. 4
Finerty JC. Parabiosis in physiological studies. Physiol Rev 1952;32:277-302.  Back to cited text no. 5
Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL. Physiological migration of hematopoietic stem and progenitor cells. Science 2001;294:1933-6.  Back to cited text no. 6
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.  Back to cited text no. 7
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.  Back to cited text no. 8
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.  Back to cited text no. 9
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 fibrosis. Science 2007;317:807-10.  Back to cited text no. 10
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.  Back to cited text no. 11
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.  Back to cited text no. 12
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