Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus

Bosco, Ornella; Vizio, Barbara; Gruden, Gabriella; Schiavello, Martina; Lorenzati, Bartolomeo; Cavallo‐Perin, P.; Russo, Isabella; Montrucchio, Giuseppe; Lupia, Enrico

doi:10.3390/ijms22137032

Cited by 6 publications

(9 citation statements)

References 68 publications

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“…Hyperglycemia induces secretion of TPO that potentiates agonist-induced activation of mature platelets. Levels positively correlate with blood glucose and level of control HbA1C [17].…”

Section: Hyperglycemiamentioning

confidence: 89%

“…In DM, the hyperglycemia acts through neutrophils to stimulate thrombopoietin (TPO) production in the liver and enhance megakaryocyte thrombopoiesis [16]. In T1DM, increased circulating TPO has been shown to be linked to elevated blood sugar levels and HbA1c HbA1C [17] providing evidence linking bone marrow megakaryopoiesis and metabolic state.…”

Section: Bone Marrow and Megakaryocytes In T1dmmentioning

confidence: 99%

“…Evaluation of platelets from T1DM patients has shown increased membrane surface expression of activation markers such as P-selectin, platelet-leukocyte aggregates (PLA)(platelet-monocyte, platelet-granulocytes) [17,40,41]. Importantly, it has been demonstrated that first relatives of T1DM patients at risk of T1DM have increased expression of P-selectin, CD63, and thrombospondin compared with at-no-risk controls [42].…”

Section: Membrane Surface Receptor Expression and Platelet-leukocyte ...mentioning

confidence: 99%

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Controversies in Platelet Functions in Diabetes Mellitus Type 1

Ogweno¹,

Murungi²

2023

Type 1 Diabetes in 2023 - From Real Practice to Open Questions

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Individuals with diabetes mellitus (DM) are at high risk of thrombosis in which hyperactive platelets are implicated. The platelet hyperactivity has been linked to hyperglycemia. This hypothesis is supported by studies in type II diabetes mellitus showing increased sensitivity of platelets to stimulating agonists in the context of tissue resistance to high-circulating insulin. However, controversy still exists regarding the altered platelet functions in type 1 diabetes mellitus (T1DM) and the link to modifying factors such as blood glucose, hyperlipidemia, metabolic acidosis and insulin treatment. Moreover, increased insulin dosage or treatment appears to have antagonistic actions: diminished functions at low doses and enhanced activation at high doses, the switch being attributable to insulin-like growth factor. The physiological role of insulin in suppressing platelet activation is lost in T1DM, a scenario that favors increased platelet sensitivity to stimulating agonists. Furthermore, the response to antiplatelet agents and statins is sub-optimal in diabetics presenting clinical and research knowledge gap regarding the ideal antiplatelet treatment in DM in general and T1DM in particular. This chapter reviews the unique characteristics of platelet functions in T1DM highlighting the controversial areas linking unique behavior of platelets and the abnormal response to therapeutic interventions.

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“…Hyperglycemia induces secretion of TPO that potentiates agonist-induced activation of mature platelets. Levels positively correlate with blood glucose and level of control HbA1C [17].…”

Section: Hyperglycemiamentioning

confidence: 89%

Section: Bone Marrow and Megakaryocytes In T1dmmentioning

confidence: 99%

Section: Membrane Surface Receptor Expression and Platelet-leukocyte ...mentioning

confidence: 99%

See 1 more Smart Citation

Controversies in Platelet Functions in Diabetes Mellitus Type 1

Ogweno¹,

Murungi²

2023

Type 1 Diabetes in 2023 - From Real Practice to Open Questions

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“…It has been shown that enhanced PLT reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin, a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature PLT by enhancing both activation and binding to leukocytes in response to different agonists ( 31 ). Cluster I in the DN group was found to have a somewhat increased PLT count, high frequency of DKA episodes/year, high MAU, prominent increase in HIF level, and prominent disturbances in apoptosis controlling factors BcL-xL and caspase-3.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Apoptotic, Clinical, and Laboratory Parameters in Type 1 Diabetes and Early Diabetic Nephropathy: Clustering and Potential Groups Evaluation for Additional Therapeutic Interventions

Ie.a.¹

2022

Jcrpe

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Objective: Type 1 diabetes (T1D) is one of the most prevalent chronic illnesses diagnosed in childhood. Diabetic nephropathy (DN) is one of the commonest complication of T1D. Therefore the development of specific treatment that arrests progression of DN based on an individual approach would be beneficial. Analysis of criteria of apoptosis, and clinical, and laboratory characteristics in T1D and early DN in the framework of clustering may be helpful in the identification of potential groups for additional therapeutic interventions. Methods: A survey of 104 children (62 males, 42 females) with T1D and DN aged 2 to 17 years in the Endocrinology unit of Clinical Pediatric Hospital No 6 (Kyiv, Ukraine) was performed. Clinical data (age, gender, disease duration, blood pressure), conventional laboratory markers including complete blood count, serum cholesterol, hemoglobin A1c (Hb1Ac), glomerular filtration rate (GFR), and microalbuminurea (MAU), and markers of apoptosis (BcL-xL, caspase-3) and transcriptional factor HIF-1alfa were analyzed. Results: A cluster group in T1D children was characterized by somewhat higher number of platelets (PLT) - 344.9±7.88·10 9 /L, increased GFR up to hyperfiltration level 124.5±8.86 mL/min/1.73 m 2 and decreased anti-apoptotic defense - BcL-xL 144.9±2.35 a.u. was identified. Children with DN may be divided into three groups based on age, body mass index, systolic blood pressure, PLT count, erthyrocyte sedimentation rate, albumin/globulin ratio, serum cholesterol, Hb1Ac, number of diabetic ketoacidosis (DKA) episodes, GFR, MAU, HIF-1alfa, Bcl-xL, caspase-3 levels. Among children with early DN a cluster characterized by the following parameters was found: PLT count - 311.±12.05·10 9 /L, frequency of DKA episodes - 4.82±0.26 episodes/year, MAU - 112.0±10.12 mm/24 h, HIF - 200.5±3.49 a.u., BcL-xL - 128.8±3.1 a.u., and caspase-3 - 159.6±5.5 a.u. Conclusion: Thus, we hypothesize that T1D pediatric patients with increased PLT count, hyperfiltration and reduced anti-apoptotic defense may represent a group for additional therapeutic interventions, such as antioxidants along with stndard therapies to achieve optimal glycemic control. Within the DN group there was a sub-group with somewhat increased PLT count, high frequency of DKA episodes/year, high MAU, prominent increase in HIF level, prominent disturbances in apoptosis controlling factors BcL-xL and caspase-3 tht may require additional therapeutic interventions, again including antioxidants, but may additionally benefit from anti-apoptotic effectors along with optimal glycemic control, and management of hypertension and albuminuria.

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“…7,8 The phenomenon of COVID-19 platelet activation is likely due to the association between inflammation/infection and platelet production. Platelet production and activation is driven by thrombopoietin, 9,10 which is upregulated by inflammatory cytokines activated in COVID-19 infection, such as interleukin-6. Platelets also possess cell surface receptors that contribute to immune cell interaction and function.…”

mentioning

confidence: 99%