Investigating the Early Life Determinants of Type-II Diabetes Using a Project Talent-Medicare Linked Data-set

Horner, Elizabeth Mokyr; Strombotne, Kiersten L.; Huang, Alison; Lapham, Susan

doi:10.1016/j.ssmph.2018.01.004

Cited by 6 publications

(5 citation statements)

References 61 publications

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“…Low early-life SES showed a clear, strong, association with individual metabolic profiles that was not true for current SES [97]. This result has been replicated by another study that highlighted the effect of SES during adolescence on the development of T2D up to fifty years later [98]. More recently, Chandan et al (2020) reported a retrospective population-based cohort of 80,657 adults that had been exposed to ELA and 161,314 unexposed controls.…”

Section: Early Life Origins Of Covid Co-morbiditiesmentioning

confidence: 85%

The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

Holuka

Merz

Fernandes

et al. 2020

IJMS

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A poor socioeconomic environment and social adversity are fundamental determinants of human life span, well-being and health. Previous influenza pandemics showed that socioeconomic factors may determine both disease detection rates and overall outcomes, and preliminary data from the ongoing coronavirus disease (COVID-19) pandemic suggests that this is still true. Over the past years it has become clear that early-life adversity (ELA) plays a critical role biasing the immune system towards a pro-inflammatory and senescent phenotype many years later. Cytotoxic T-lymphocytes (CTL) appear to be particularly sensitive to the early life social environment. As we understand more about the immune response to SARS-CoV-2 it appears that a functional CTL (CD8+) response is required to clear the infection and COVID-19 severity is increased as the CD8+ response becomes somehow diminished or exhausted. This raises the hypothesis that the ELA-induced pro-inflammatory and senescent phenotype may play a role in determining the clinical course of COVID-19, and the convergence of ELA-induced senescence and COVID-19 induced exhaustion represents the worst-case scenario with the least effective T-cell response. If the correct data is collected, it may be possible to separate the early life elements that have made people particularly vulnerable to COVID-19 many years later. This will, naturally, then help us identify those that are most at risk from developing the severest forms of COVID-19. In order to do this, we need to recognize socioeconomic and early-life factors as genuine medically and clinically relevant data that urgently need to be collected. Finally, many biological samples have been collected in the ongoing studies. The mechanisms linking the early life environment with a defined later-life phenotype are starting to be elucidated, and perhaps hold the key to understanding inequalities and differences in the severity of COVID-19.

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Section: Early Life Origins Of Covid Co-morbiditiesmentioning

confidence: 85%

The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

Holuka

Merz

Fernandes

et al. 2020

IJMS

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“…Reports from ourselves and others of early life adversity have shown effects on either the metabolic profile, obesity, or type 2 diabetes [ 96 , 97 , 98 ]. Socioeconomic status in early life has a similar effect [ 15 ], and is associated with T2D 50 years later [ 99 ]. ELA also predisposes individuals towards a chronic inflammatory phenotype [ 98 , 100 , 101 , 102 ].…”

Section: Early Life Adversitymentioning

confidence: 99%

The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances

Seal

Turner

2021

IJMS

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The physiological response to a psychological stressor broadly impacts energy metabolism. Inversely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA), and sympathetic nervous system activation. Glucocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of energy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance, and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, and the most prominent are early life adversity, or exposure to traumatic stress. We hypothesise that when the HPA axis is so disturbed after early life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

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“…ELA and obesity play a role in the subsequent development of insulin resistance and type 2 diabetes (T2D). Low SES in early life induces a diabetogenic metabolic profile in adulthood, while current SES does not appear to do so (Hostinar et al, 2017, Horner et al, 2018. Furthermore, exposure to ELA is a major risk factor for T2D, as well as cardiovascular disease and "a significant proportion of the cardio-metabolic and diabetic disease burden may be attributable to maltreatment" (Chandan et al, 2020).…”

Section: Biological Components and Consequences Of Elamentioning

confidence: 99%

Is Early Life Adversity a Trigger towards Inflammageing?

Merz¹,

Turner²

2021

Preprint

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There are many ‘faces’ of early life adversity (ELA), such as childhood trauma, institutionalization, abuse or exposure to environmental toxins. These have been implicated in the onset and severity of a wide range of chronic non-communicable diseases later in life. The later-life disease risk has a well-established immunological component. This raises the question as to whether accelerated immune-ageing mechanistically links early-life adversity to the lifelong health trajectory resulting in either ‘poor’ or ‘healthy’ ageing. Here we examine observational and mechanistic studies of ELA and inflammageing, highlighting common and distinct features in these two life stages. Many biological processes appear in common including reduction in telomere length, increased immuno-senescence, metabolic distortions and chronic (viral) infections. We propose that ELA shapes the developing immune, endocrine and nervous system in a non-reversible way, creating a distinct phenotype with accelerated immuno-senescence and systemic inflammation. We believe that ELA acts as an accelerator for inflammageing and age-related diseases. Furthermore, we now have the tools and cohorts to be able to dissect the interaction between early life adversity and later life phenotype. This should, in the near future, allow us to identify the ecological and mechanistic processes that are involved in ‘healthy’ or accelerated immune-ageing.

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Investigating the Early Life Determinants of Type-II Diabetes Using a Project Talent-Medicare Linked Data-set

Cited by 6 publications

References 61 publications

The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

The COVID-19 Pandemic: Does Our Early Life Environment, Life Trajectory and Socioeconomic Status Determine Disease Susceptibility and Severity?

The ‘Jekyll and Hyde’ of Gluconeogenesis: Early Life Adversity, Later Life Stress, and Metabolic Disturbances

Is Early Life Adversity a Trigger towards Inflammageing?

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