|EDITORIAL - FROM THE EDITORS DESK
|Year : 2015 | Volume
| Issue : 3 | Page : 227-228
Rejuvenating the failing heart in diabetics: Role of growth differentiation factor-11
Subir K Maulik
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||23-Feb-2016|
Subir K Maulik
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
|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 Jul 20];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. 
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. 
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." 
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! 
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 19 th century.  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.  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. , 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.  On the other hand, exposing a young animal to circulating factors from an older animal can inhibit skeletal muscle function  and neural functions  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.  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.  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.
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