Platelet function following induced hypoglycaemia in type 2 diabetes

Kahal, Hassan; Aburima, Ahmed; Spurgeon, Benjamin E. J.; Wraith, Katie S.; Rigby, Alan S.; Sathyapalan, Thozhukat; Naseem, Khalid M.; Atkin, Stephen L.

doi:10.1016/j.diabet.2018.04.004

Cited by 22 publications

(27 citation statements)

References 36 publications

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“…however, this study, together with other small mechanistic studies performed in patients with type 2 diabetes, 28,29 provides evidence of platelet and coagulation activation after a single hypoglycaemic event.…”

Section: Markers Of Endothelial Function and Inflammationsupporting

confidence: 58%

“…The present study has some limitations, including the fact that 14 people with diabetes could be considered a small patient group; however, this study, together with other small mechanistic studies performed in patients with type 2 diabetes, provides evidence of platelet and coagulation activation after a single hypoglycaemic event. Given the unpleasant side effects involved in participating in a hypoglycaemic clamp procedure, sample sizes need to be kept at a minimum for this type of mechanistic study.…”

Section: Discussionmentioning

confidence: 94%

“…Kahal et al investigated the effects of a single hypoglycaemic (2.8 mmol/L) episode on platelet reactivity in 10 people with type 2 diabetes. They demonstrated reduced platelet sensitivity to prostacyclin 24 hours after hypoglycaemia.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study

Aberer

Pferschy

Tripolt

et al. 2019

Diabetes Obesity Metabolism

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Aims To investigate the effect of hypoglycaemia on platelet and coagulation activation in people with type 2 diabetes. Materials and methods This monocentric, open, single‐arm, mechanistic trial included 14 people with established type 2 diabetes (four women, 10 men, age 55 ± 7 years, glycated haemoglobin concentration 51 ± 7 mmol/mol) receiving metformin monotherapy. A stepwise hyperinsulinaemic‐hypoglycaemic clamp experiment (3.5 and 2.5 mmol/L, for 30 minutes respectively) was performed, aiming to investigate platelet and coagulation activity during predefined plateaus of hypoglycaemia, as well as 1 day and 7 days later. Results While platelet activation assessed by light transmittance aggregometry did not significantly increase after the hypoglycaemic clamp procedure, the more sensitive flow cytometry‐based measurement of platelet surface activation markers showed hypoglycaemia‐induced activation 24 hours (PAC1posCD62Ppos, PAC1posCD63Ppos and PAC1posCD62PposCD63pos; P < .01) and 7 days after the hypoglycaemic clamp (P < .001 for PAC1posCD63pos; P < .01 for PAC1posCD62Ppos and PAC1posCD62PposCD63pos) in comparison to baseline. Coagulation markers, such as fibrinogen, D‐dimer, plasminogen activator inhibitor‐1, von Willebrand factor activity and factor VIII, were also significantly increased, an effect that was most pronounced 24 hours after the hypoglycaemic clamp. Conclusion A single event of insulin‐induced hypoglycaemia led to an increase in markers of platelet activation and coagulation in people with early stages of type 2 diabetes on metformin therapy. However, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycaemic episode.

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Section: Markers Of Endothelial Function and Inflammationsupporting

confidence: 58%

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study

Aberer

Pferschy

Tripolt

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…The clamp procedure was performed as previously described 24 . The insulin infusion rate was constant throughout the clamp [60 mU/body surface area (m 2 )/min], while the rate of the 20% dextrose infusion was adjusted every 5 minutes to achieve the target blood glucose level.…”

Section: Study Participants Healthy Individuals and T2dm Subjects Wementioning

confidence: 99%

“…The endothelium is important in maintaining vascular homeostasis 21 and endothelial dysfunction involves an impaired ability to regulate vascular tone together with anti-inflammatory and anticoagulatory alterations of the vasculature 22 . Moderate hypoglycemia has been shown to increase activation of prothrombotic and proinflammatory effects in type 1 diabetes 23 ; therefore, in this study, we examined inflammatory markers, oxidative stress and endothelial function following iatrogenic hypoglycemia in subjects with and without T2DM 24 .…”

mentioning

confidence: 99%

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Kahal

Halama

Aburima

et al. 2020

Sci Rep

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Intensive diabetes control has been associated with increased mortality in type 2 diabetes (T2DM); this has been suggested to be due to increased hypoglycemia. We measured hypoglycemia-induced changes in endothelial parameters, oxidative stress markers and inflammation at baseline and after a 24-hour period in type 2 diabetic (T2DM) subjects versus age-matched controls. Case-control study: 10 T2DM and 8 control subjects. Blood glucose was reduced from 5 (90 mg/dl) to hypoglycemic levels of 2.8 mmol/L (50 mg/dl) for 1 hour by incremental hyperinsulinemic clamps using baseline and 24 hour samples. Measures of endothelial parameters, oxidative stress and inflammation at baseline and at 24-hours post hypoglycemia were performed: proteomic (Somalogic) analysis for inflammatory markers complemented by C-reactive protein (hsCRP) measurement, and proteomic markers and urinary isoprostanes for oxidative measures, together with endothelial function. Between baseline and 24 -hours after hypoglycemia, 15 of 140 inflammatory proteins differed in T2DM whilst only 1 of 140 differed in controls; all returned to baseline at 24-hours. However, elevated hsCRP levels were seen at 24-hours in T2DM (2.4 mg/L (1.2-5.4) vs. 3.9 mg/L (1.8-6.1), Baseline vs 24-hours, P < 0.05). In patients with T2DM, between baseline and 24-hour after hypoglycemia, only one of 15 oxidative stress proteins differed and this was not seen in controls. An increase (P = 0.016) from baseline (73.4 ng/mL) to 24 hours after hypoglycemia (91.7 ng/mL) was seen for urinary isoprostanes. Hypoglycemia resulted in inflammatory and oxidative stress markers being elevated in T2DM subjects but not controls 24-hours after the event.While type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease 1 , strict glycemic control does not result in obvious cardiovascular benefit in people with T2DM 2-4 . A link between strict glycemic control, hypoglycemia and increased cardiovascular morbidity and mortality has been observed in clinical studies 5,6 . Although the underlying mechanism remains unclear, increased inflammatory cytokines and a leukocytosis are reported after hypoglycemia 7,8 , suggesting a link between hypoglycemia and inflammation.It is well recognized that oxidative stress leads to damage of proteins and deoxyribonucleic acid (DNA) 9 and contributes to the diabetic complications of retinopathy, nephropathy, neuropathy and cardiovascular disorders 10-13 , and is directly linked to vascular inflammation, precipitating both endothelial cell dysfunction and vascular damage 14 . Oxidative stress results from excessive generation of free radicals and/or deficient defense mechanisms 15 , and leads to a disturbance of the physiological redox state 16 . The membrane associated 1

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Clinical Cytometry for Platelets and Platelet Disorders

Frelinger

Spurgeon

2023

Clinics in Laboratory Medicine

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Platelet function following induced hypoglycaemia in type 2 diabetes

Abstract: Induced hypoglycaemia in T2DM enhances platelet hyperactivity through impaired sensitivity to prostacyclin at 24hours.

Cited by 22 publications

References 36 publications

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study

Hypoglycaemia leads to a delayed increase in platelet and coagulation activation markers in people with type 2 diabetes treated with metformin only: Results from a stepwise hypoglycaemic clamp study

Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects

Clinical Cytometry for Platelets and Platelet Disorders

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