The multi-systemic nature of diabetes mellitus: Genotype or phenotype?

Ewing, Graham Wilfred; Parvez, Syed Hasan

doi:10.4297/najms.2010.2444

Cited by 25 publications

(27 citation statements)

References 116 publications

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“…Grakov's Strannik technology performs two fundamental functions: (i) as a screening technology [9] which is able to determine the onset and progression of pathologies in all main organs (typically 15 pathologies per organ in the 30 main organs), each pathology being defined in terms of its genotype and its phenotype [10]; and (ii) to treat the most destabilised physiological system thereby reestablishing optimum autonomic stability and homeostasis [11]. Such a technology is an extraordinary development which initial research has indicated appears to be more advanced than any current technology(s) [12,13].…”

Section: Discussionmentioning

confidence: 99%

Advancing The Biomedical Paradigm

Ewing¹

2017

Insights in Biomed

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Section: Discussionmentioning

confidence: 99%

Advancing The Biomedical Paradigm

Ewing¹

2017

Insights in Biomed

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“…Both the genetic and phenotypic processes which influence pathological onset or progression have to be quantified [2,3]. This is immensely significant when diagnosing diabetes.…”

Section: E Most Medical Tests Consider Only a Portion Of A Normalmentioning

confidence: 99%

“…In most patients diabetes presents as a combination of genotype and phenotype influencing the function of the cells of the islets of Langerhans [2,3]. This occurs because the genetic expression of proteins (in this case insulin)…”

Section: Dmentioning

confidence: 99%

The Limitations of Big Data in Healthcare

Ewing¹

2017

MOJPB

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It has become commonplace in modern society to collect and process large bodies of data in order to establish trends in the data and thereby identify business opportunities, areas of cost-saving, etc. This article questions whether, in the healthcare context, the data sets from biomarker-type tests are reliable indicators of dysfunction and whether the processing of such data sets can be expected to identify significant areas for improvement in the clinical context which would lead to significant improvements and cost-savings regarding the diagnosis and treatment of morbidity. In particular, there is not yet an accepted understanding of the mechanisms which are responsible for maintaining the body's highly regulated function therefore the idea that the current plethora of diagnostic tests can be accurate measures of the rate of pathological onset of a particular medical condition(s) is only an assumption and may have significant inherent limitations.The development of the first mathematical model of the autonomic nervous system by Grakov leads us to question basic assumptions upon which modern medicine is based and whether large-scale data mining of available data sets will lead to a better understanding e.g. (i) Is the biomarker the cause or the consequence of the condition? (ii) Does the marker relate to the genotype, phenotype or neither? (iii) How does the brain regulate the autonomic nervous system and the coherent function of the organ networks/physiological systems?

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“…In order to understand the issue in greater detail we must consider (i) the fundamental relationship between genotype (protein expression) and the wider influence of environmental factors i.e. non-genetic or phenotype [27] and, (ii) the mechanisms which the brain uses to regulate the body's function [28] and vice versa ( Figure 1). …”

Section: The Relationship Between Sensory Input and Biological Inputmentioning

confidence: 99%

The Framework of a Mathematical Model of the Autonomic Nervous System and Physiological Systems: Using the Neuroregulation of Blood Glucose as an Example

Ewing¹

2015

J Comput Sci Syst Biol

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IntroductionOur sense perception enables us to eat the correct amounts of food and, under normal circumstances, we cease eating when we have eaten sufficient food, and we drink sufficient to sati sfy the body 's need for liquid. We breathe at the normal expected rate, our heart pumps at the expected rate and maintain the normal level of blood pressure, our body maintains the normal levels of acidity and temperature, we sleep for 7-8 hours per night, etc. This suggests that the body is being regulated by a biological control mechanism of enormous sophistication and complexity, which has an enormous processing capacity; however as we age, and particularly as we age beyond 50 years, the mechanism which maintains our function become increasingly less able to sustain the levels of oxygen, blood glucose, blood cell content and a myriad of other biological components which the brain requires to function [1]. The i nnate g enetic c apacity o f key o rgans d eclines a nd r esults in shortages of proteins, hormones, etc. This h as a k nock-on e ffect affecting one biological sequence after another.The cumulative effect of our lifetime of experiences, due to environmental and biological factors, influences the function and/ or stability of the autonomic nervous system and ultimately the function of our DNA and genes [2]. The level of genetic expression of the proteins (genotype) which we require to sustain our function declines and the rate at which these expressed proteins subsequently react (phenotype) also declines i.e. the ability of the body to cope with extreme events declines.There are two fundamentally significant biological issues at play: (i) the genetic ability to express proteins (ii) the body's physiological demand i.e. the phenotype or influence of the environment. In the case of diabetes, in particular type 2 diabetes, this is the regulation of Blood Glucose. The greater the level of hyperglycaemia the greater is the associated demand for insulin. The development of a medical condition occurs when the environmental demand exceeds the body's innate capacity [3] i.e. the prevailing supply and/or level of insulin is insufficient to metabolise the excess of blood glucose. By contrast, the lower the level of hypoglycaemia, which occurs in type 1 diabetes, the lower is the demand/need for insulin. If there is insufficient blood glucose the excess of highly reactive insulin will seek an alternative substrate and ultimately results in damage to the peripheral blood vessels e.g. in particular to the brain, eyes, legs and feet.The evidence suggests that this regulatory process is performed by the brain via the process of neuroregulation [4][5][6]. This is a best-fit process which takes into account the prevailing state of development or physiological damage to a part of the brain, degeneration or damage to an organ (or limb), and the prevailing inter-cellular environment i.e. the feedback of biochemical signals from the viscera. AbstractDespite the immense advances of medical research there remains a fundamental theo...

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The multi-systemic nature of diabetes mellitus: Genotype or phenotype?

Cited by 25 publications

References 116 publications

Advancing The Biomedical Paradigm

Advancing The Biomedical Paradigm

The Limitations of Big Data in Healthcare

The Framework of a Mathematical Model of the Autonomic Nervous System and Physiological Systems: Using the Neuroregulation of Blood Glucose as an Example

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