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Glucocrinology.

Byline: Sanjay Kalra, Gagan Priya and Yashdeep Gupta

Abstract

Diabetes is a complex syndrome, with multiple pathophysiologic connections. While the vasculometabolic aspects are certainly important, current discourse tends to ignore the endocrine facets of diabetes. We propose the term 'glucocrinology', to define the study of medicine that relates to the relationship of glycaemia with the endocrine system. Glucocrinology includes in its ambit, endocrinopathies that may cause secondary diabetes, coexist with metabolic syndrome, precipitate hypoglycaemia, lead to refractory hyperglycaemia, or simply coexist with diabetes. The concept also covers the role of endocrinotropic drugs in unmasking latent diabetes, worsening hyperglycaemia, or managing diabetes in specific situations, as well as antidiabetic drugs in modulating endocrine disease.

Highlighting glucocrinology as a distinct field will enhance the quality of diabetes care, by making it more holistic, comprehensive and clinically oriented. This article will be followed by gland-specific reviews of glucocrinology.

Keywords: Adrenal, Diabetes, Endocrinology, Gonads, Hormones, Metformin, Pituitary, Thyroid.

Endocrinology

Endocrinology is defined as the field of medicine that relates to the study of the endocrine system and hormones. The term 'hormones' was first coined by Starling and refers to chemical signals, secreted by the endocrine glands, that act on distant tissues to regulate their function. The endocrinologist is a physician trained in the diagnosis and management of disorders of the endocrine system.1 In recent decades, the field of endocrinology has expanded to understand the contribution of hitherto unidentified endocrine players such as the adipose tissue and gastrointestinal endocrine cells in physiology and pathophysiology.

Diabetes Mellitus

Recent years have witnessed an epidemic of endocrine and metabolic disease, including hypothyroidism, obesity, polycystic ovary syndrome and subfertility. The main driver of endocrinopathy in the modern world, however, is undisputedly diabetes.2 Diabetes mellitus is a complex syndrome, characterized by hyperglycaemia. The earlier understanding was that diabetes is a state of decreased insulin secretion and/ or insulin resistance with hyperglycaemia as the core abnormality. However, it is now recognized to be a multi-system disorder involving metabolic dysfunction, adiposopathy, chronic inflammation, endothelial dysfunction and oxidative stress and increased cardiovascular risk. Multiple pathophysiologic constructs have been developed to explain the etiopathogenesis of this condition.3,4

Endocrine Impact on Glucose Regulation

Chief among the players in the development of diabetes are the various endocrine glands. While diabetes is primarily understood as a disease of the endocrine pancreas, other endocrine glands including adipose tissue, gastrointestinal endocrine system, pituitary, parathyroid, thyroid, adrenals and gonads are associated with diabetes in multiple ways, in both the etiopathogenesis of diabetes and development of comorbid states. While the focus on the gut and adipose tissue as endocrine contributors in diabetes development has led to development of strategies towards better diabetes management, the contribution of other endocrine organs in disease pathogenesis remains ignored. The exploration of their role is likely to further open new avenues in diabetes management such as the development of 11-b hydroxysteroid dehydrogenase-1 (11-b HSD) inhibitors. The association of other endocrine players with diabetes is worthy of further study.

It may also lead to improved strategies at prevention of diabetes and prevention of long-term complications. It is this study that we define as glucocrinology. "Glucocrinology is the study of medicine that relates to the relationship of glycaemia with the endocrine system" Various aspects of glucocrinology are listed in Table-1. The discovery of insulin in 1921 by Banting, Best and McLeod was the turning point for endocrinology and the field of endocrinology and diabetes has witnessed several important developments over the decades.5 Since then, there have been significant developments in our understanding of endocrine organs and their functions, hormones, hormonal receptors, downstream signaling pathways. We have begun to understand the complex interplay between various endocrine glands and their secretions in health and disease. In Table-2, we enlist the important Nobel laureates for Physiology or Medicine whose work was related to the field of glucocrinology.

Table-1: Aspects of glucocrinology.

- Endocrinopathies may cause secondary diabetes:

- Acromegaly

- Cushing's syndrome

- Glucagonoma

- Pheochromocytoma

- Somatostatinoma

- VIPoma

- Hyperthyroidism

- Hyperaldosteronism

- Hyperparathyroidism

- Insulin resistance syndromes, type A and B

- Lipodystrophy

- Endocrinopathies may be associated with Metabolic syndrome:

- Polycystic ovary syndrome (PCOS)

- Hypothyroidism

- Subclinical Cushing's syndrome

- Endocrine dysfunction and diabetes may coexist:

- Autoimmune polyglandular syndromes

- Multiple endocrine neoplasia

- DIDMOAD syndrome

- Mitochondrial disorders, including MELAS

- Chance association

- Endocrine dysfunction may be the etiology of refractory hyperglycemia in diabetes:

- Hyperthyroidism

- Cushing's syndrome

- Acromegaly

- Comorbidities/ complications of diabetes may delay the diagnosis of endocrine

dysfunction:

- Hypertension - delayed diagnosis of pheochromocytoma or hyperaldosteronism

- Neuropathy - delayed diagnosis of hypothyroidism

- Obesity and metabolic syndrome - delayed diagnosis of Cushing's syndrome

- Endocrinopathies associated with increased risk of hypoglycaemia with diabetes

treatment:

- Adrenal insufficiency

- Hypothyroidism

- Growth hormone deficiency

- Combined pituitary hormone deficiency

- Endocrinotropic drugs may worsen diabetes/ exacerbate hyperglycaemia:

- Glucocorticoids

- Thyroid hormones

- Inotropes

- Growth hormone

- Oestrogen (high dose)

- Somatostatin/ Octreotide

- Endocrinotropic drugs may be used to manage diabetes:

- Bromocriptine

- Mifepristone

- 11-b HS1 Inhibitors

- Glucose lowering drugs may exhibit endocrine exaptation:

- Metformin reduces serum TSH

- Treatment of endocrine dysfunction may unmask latent diabetes:

- Addison's disease

- Hypothyroidism

Table-2: Nobel prizes in Glucocrinology.

Year###Nobel Laurate###Contribution

1923###Frederick Banting###Discovery of insulin.

###John Macleod

1947###Bernardo Alberto Houssay###Role of anterior pituitary hormone in sugar

###metabolism.

1947###Carl Ferdinand Cori###Discovery of the catalytic conversion of

###Gerty Theresa Cori, nee###glycogen, described the Cori cycle.

###Radnitz

1950###Edward Calvin Kendall###Discoveries relating to hormones of adrenal

###Tadeus Reichstein###cortex, their structure and biological effects.

###Philip Showalter Hench

1953###Hans Adolf Crebs###Discovery of the citric acid cycle in

###generation of ATP.

1953###Fritz Albert Lipmann###Discovery of co-enzyme A and its

###importance in intermediary metabolism.

1971###Earl W Southerland Jr###Mechanism of action of hormones and their

###second messengers.

1977###Rosalyn Yalow###Development of Radioimmunoassay.

###Demonstrated through use of radioactive

###iodine that type 2 diabetes is caused by

###body's inefficient use of insulin.

1985###Michael S Brown###Discovery concerning the regulation of

###Joseph L Goldstein###cholesterol metabolism.

Summary

In recent years, diabetes praxis has become increasingly algorithm based and number oriented. Coupled with a focus on glucocentric screening and monitoring, this has led to a neglect of holistic medicine. The concept of glucocrinology revives the importance of endocrinology and endocrinologists in diabetes management and further enhances our understanding of a multifaceted disorder, while opening new therapeutic and preventive targets. It also promotes a comprehensive and complete assessment and management of diabetes. This introductory article will be followed by detailed gland-specific reviews on various aspects of glucocrinology.

References

1. What is an Endocrinologist? Online. Cited on 1 October 2017. Available from URL: http://www.hormone.org/contact-a-health-professional/what-is-an-endocrinologist.

2. Zimmet PZ. Diabetes and its drivers: the largest e p i demicinhuman history. Clin Diabetes Endocrinol 2017; 3:1.

3. DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009; 58: 773-95.

4. Kalra S, Chawla R, Madhu SV. The dirty dozen of diabetes. Ind J Endocrinol Metab 2013; 17: 367.

5. Kalra S, Unnikrishnan AG, Jacob J. Endocrinology@ the Nobels. Ind J Endocrinol Metab. 2012 ; 16(Suppl 2): S138.
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Publication:Journal of Pakistan Medical Association
Date:Jun 30, 2018
Words:1404
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