Investigating the Effects of Diet-Induced Pre-Diabetes on the Functioning of Calcium-Regulating Organs in Male Sprague Dawley Rats: Effects on Selected Markers

Naidoo, Karishma; Ngubane, Phikelelani; Khathi, Andile

doi:10.3389/fendo.2022.914189

Cited by 8 publications

(5 citation statements)

References 62 publications

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“…Animal models have been observed to mirror human disease conditions, making them extensively utilized for studying physiological systems and human disease states [221][222][223]. A high fat high carbohydrate and 15% fructose diet-induced animal model of prediabetes has been found to mimic the human condition [224].…”

Section: Hpa Axis Function In Prediabetesmentioning

confidence: 99%

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)‐ Associated Hypothalamic‐Pituitary‐Adrenal (HPA) Axis Dysregulation: Exploring Links to Pregestational Prediabetes

Ngema,

Xulu,

Ngubane

et al. 2024

Preprint

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A growing body of research has identified fetal risk factors associated with adult diseases that form the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. This theory proposes a critical developmental period during which the fetus is highly susceptible to specific environmental influences that significantly impact health from short to long term. Maternal stress and T2DM during pregnancy are among these influences, likely leading to fetal overexposure to glucocorticoids and suggesting a shared pathway between maternal dysregulated HPA axis and fetal environmental insults. Studies demonstrate that prenatal glucocorticoid exposure alters fetal HPA axis function, affecting brain function, tissue glucocorticoid availability, and fetal growth in utero. These programmed changes, such as altered HPA axis function and reduced fetal growth, contribute to metabolic disorders persisting into adulthood. T2DM is preceded by a prediabetic state, often asymptomatic, which shares similar pathophysiological complications with T2DM, including HPA axis dysregulation observed in animals. Therefore, investigating prediabetes during pregnancy alongside maternal HPA axis function and its effects on fetal outcomes is crucial, as these areas remain understudied. This review aims to synthesize existing literature on pre-existing T2DM during pregnancy, its links to fetal programming via HPA axis changes, and possible links to pregestational prediabetes.

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Section: Hpa Axis Function In Prediabetesmentioning

confidence: 99%

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)‐ Associated Hypothalamic‐Pituitary‐Adrenal (HPA) Axis Dysregulation: Exploring Links to Pregestational Prediabetes

Ngema,

Xulu,

Ngubane

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Animal models have been observed to mirror human disease conditions, making them extensively utilizable for studying physiological systems and human disease states [ 178 , 179 ]. A high-fat, high carbohydrate and 15% fructose diet-induced animal model of prediabetes has been found to mimic the human condition [ 38 ].…”

Section: Prediabetesmentioning

confidence: 99%

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes

Ngema,

Xulu,

Ngubane

et al. 2024

Biomedicines

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Research has identified fetal risk factors for adult diseases, forming the basis for the Developmental Origins of Health and Disease (DOHaD) hypothesis. DOHaD suggests that maternal insults during pregnancy cause structural and functional changes in fetal organs, increasing the risk of chronic diseases like type 2 diabetes mellitus (T2DM) in adulthood. It is proposed that altered maternal physiology, such as increased glucocorticoid (GC) levels associated with a dysregulated hypothalamic-pituitary-adrenal (HPA) axis in maternal stress and T2DM during pregnancy, exposes the fetus to excess GC. Prenatal glucocorticoid exposure reduces fetal growth and programs the fetal HPA axis, permanently altering its activity into adulthood. This programmed HPA axis is linked to increased risks of hypertension, cardiovascular diseases, and mental disorders in adulthood. With the global rise in T2DM, particularly among young adults of reproductive age, it is crucial to prevent its onset. T2DM is often preceded by a prediabetic state, a condition that does not show any symptoms, causing many to unknowingly progress to T2DM. Studying prediabetes is essential, as it is a reversible stage that may help prevent T2DM-related pregnancy complications. The existing literature focuses on HPA axis dysregulation in T2DM pregnancies and its link to fetal programming. However, the effects of prediabetes on HPA axis function, specifically glucocorticoid in pregnancy and fetal outcomes, are not well understood. This review consolidates research on T2DM during pregnancy, its impact on fetal programming via the HPA axis, and possible links with pregestational prediabetes.

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“…These changes not only compromise renal hemodynamics, but also facilitate the onset of tubular and glomerular damage, which establishes the foundation for the initial phases of chronic kidney disease [274]. Moreover, renal injury and dysfunction are further aggravated by prediabetes-induced dyslipidemia, oxidative stress, and the activation of the renin-angiotensin-aldosterone system (RAAS), which increases the likelihood of developing overt type 2 diabetes and severe CKD [275]. To slow the progression of CKD and related comorbidities, early intervention strategies targeting metabolic and aging-related pathways, as well as biomarkers like transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), and fibroblast growth factor-23 (FGF-23), are crucial.…”

Section: The Negative Effects Of Senescence and Pre-diabetes On Renal...mentioning

confidence: 99%

Identification of Putative Causal Relationships between Blood-Based Biomarkers and Prediabetes-Induced Senescence: A Comprehensive Review

Mbatha,

Mushebenge,

Khathi

2024

Physiologia

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Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors such as folate, B12, and osteocalcin. Not only do these biomarkers serve as indicators of senescence but they also actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual’s life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, the in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

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Investigating the Effects of Diet-Induced Pre-Diabetes on the Functioning of Calcium-Regulating Organs in Male Sprague Dawley Rats: Effects on Selected Markers

Cited by 8 publications

References 62 publications

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)‐ Associated Hypothalamic‐Pituitary‐Adrenal (HPA) Axis Dysregulation: Exploring Links to Pregestational Prediabetes

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)‐ Associated Hypothalamic‐Pituitary‐Adrenal (HPA) Axis Dysregulation: Exploring Links to Pregestational Prediabetes

A Review of Fetal Development in Pregnancies with Maternal Type 2 Diabetes Mellitus (T2DM)-Associated Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation: Possible Links to Pregestational Prediabetes

Identification of Putative Causal Relationships between Blood-Based Biomarkers and Prediabetes-Induced Senescence: A Comprehensive Review

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