Association between central non-dipping pattern and platelet morphology in adults with type 1 diabetes without cardiovascular disease: a cross-sectional study

Kulecki, Michał; Naskręt, Dariusz; Kamińśki, Mikołaj; Kasprzak, Dominika; Lachowski, Pawel; Klause, Daria; Kozłowska, Maria; Flotyńska, Justyna; Uruska, Aleksandra; Zozulińska‐Ziółkiewicz, Dorota

doi:10.1038/s41598-021-94414-y

Cited by 2 publications

(2 citation statements)

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“…These changes can be reversed by melatonin [ 57 , 58 ], highlighting the importance of pineal melatonin in the circadian optimization of pancreatic β-cell function. Circadian dysregulation is also intimately linked to a diverse array of T1DM symptomatology [ 59 ], including nocturnal non-dipping blood pressure increasing kidney disease [ 60 ], cardiac autonomic neuropathy [ 61 ], platelet morphology [ 62 ], microvascular complications [ 63 ], and patterned immune activity [ 64 ], whilst circadian variation in basal insulin requirement can be an early marker of autoimmune polyendocrine syndromes in T1DM [ 65 ]. Such data highlight the role of alterations in the circadian rhythm in T1DM pathophysiology.…”

Section: Wider T1dm Pathophysiologymentioning

confidence: 99%

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Anderson¹

2023

IJMS

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Type 1 diabetes mellitus (T1DM) arises from the failure of pancreatic β-cells to produce adequate insulin, usually as a consequence of extensive pancreatic β-cell destruction. T1DM is classed as an immune-mediated condition. However, the processes that drive pancreatic β-cell apoptosis remain to be determined, resulting in a failure to prevent ongoing cellular destruction. Alteration in mitochondrial function is clearly the major pathophysiological process underpinning pancreatic β-cell loss in T1DM. As with many medical conditions, there is a growing interest in T1DM as to the role of the gut microbiome, including the interactions of gut bacteria with Candida albicans fungal infection. Gut dysbiosis and gut permeability are intimately associated with raised levels of circulating lipopolysaccharide and suppressed butyrate levels, which can act to dysregulate immune responses and systemic mitochondrial function. This manuscript reviews broad bodies of data on T1DM pathophysiology, highlighting the importance of alterations in the mitochondrial melatonergic pathway of pancreatic β-cells in driving mitochondrial dysfunction. The suppression of mitochondrial melatonin makes pancreatic β-cells susceptible to oxidative stress and dysfunctional mitophagy, partly mediated by the loss of melatonin’s induction of PTEN-induced kinase 1 (PINK1), thereby suppressing mitophagy and increasing autoimmune associated major histocompatibility complex (MHC)-1. The immediate precursor to melatonin, N-acetylserotonin (NAS), is a brain-derived neurotrophic factor (BDNF) mimic, via the activation of the BDNF receptor, TrkB. As both the full-length and truncated TrkB play powerful roles in pancreatic β-cell function and survival, NAS is another important aspect of the melatonergic pathway relevant to pancreatic β-cell destruction in T1DM. The incorporation of the mitochondrial melatonergic pathway in T1DM pathophysiology integrates wide bodies of previously disparate data on pancreatic intercellular processes. The suppression of Akkermansia muciniphila, Lactobacillus johnsonii, butyrate, and the shikimate pathway—including by bacteriophages—contributes to not only pancreatic β-cell apoptosis, but also to the bystander activation of CD8+ T cells, which increases their effector function and prevents their deselection in the thymus. The gut microbiome is therefore a significant determinant of the mitochondrial dysfunction driving pancreatic β-cell loss as well as ‘autoimmune’ effects derived from cytotoxic CD8+ T cells. This has significant future research and treatment implications.

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Section: Wider T1dm Pathophysiologymentioning

confidence: 99%

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Anderson¹

2023

IJMS

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“…The activation and aggregation of platelets are potential factors contributing to the increased risk of thrombosis in patients with hypertension (16)(17)(18). Some studies have indicated a potential correlation between MPV and blood pressure (19,20). However, despite these investigations conducted, the current clinical evidence regarding the association between PIs and stroke remains inconclusive and lacks longitudinal studies.…”

Section: Introductionmentioning

confidence: 99%

The impact of platelet indices on ischemic stroke: a Mendelian randomization study and mediation analysis

Li,

Xiang,

Xue

et al. 2023

Front. Neurol.

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IntroductionPlatelet indices (PIs) are hematological parameters that indicate the number, morphology, and activation of platelets. Although some clinical trials suggest an association between PIs and the risk of stroke, the lack of robust evidence is attributed to confounding effects and reverse causation.ObjectiveThis study aimed to evaluate the association between PIs and stroke risk through Mendelian randomization (MR) while exploring the mediating effect of blood pressure in this association.MethodsWe identified genetic variants associated with PIs, including platelet count (PLT), platelet distribution width (PDW), mean platelet volume (MPV), and platelet crit (PCT), in the UK Biobank (n = 350,474). Relevant genome-wide association studies were utilized to gather summary statistics pertaining to the traits of interest. We primarily used the inverse-variance weighted analysis to obtain estimates for individual causal power.ResultWe observed a positive correlation between genetically predicted increases in PCT levels with the stroke onset [PCT: OR (95%CI) = 1.113(1.047, 1.183), p < 0.001]. However, no significant causal relationship was found between PLT, PDW, and MPV and the risk of stroke [PLT: OR (95%CI) = 1.037(0.979, 1.098), p = 0.221; PDW: OR (95%CI) = 0.973(0.923, 1.024), p = 0.294; MPV: OR (95%CI) = 0.990(0.945, 1.038), p = 0.675]. Multivariable MR analyses and mediation analysis found that the proportion mediated by systolic blood pressure (SBP) is 23.71% [95%CI (10.85–33.31%)] and the proportion mediated by diastolic blood pressure (DBP) is 28.09% [95%CI (12.92–39.63%)].ConclusionThis large MR study presents evidence for the potential causal relationship between the PCT level and the risk of ischemic stroke, which might be mediated by blood pressure.

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Association between central non-dipping pattern and platelet morphology in adults with type 1 diabetes without cardiovascular disease: a cross-sectional study

Cited by 2 publications

References 63 publications

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

The impact of platelet indices on ischemic stroke: a Mendelian randomization study and mediation analysis

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