Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics.

Etheresia Pretorius,Antoinette V Buys,Prashilla Soma,Natasha Vermeulen,Janette Bester,Sajee Alummoottil,Douglas B Kell

doi:10.1186/s12933-015-0192-5

Etheresia Pretorius, Antoinette V Buys + Show 5 more

Open Access

https://doi.org/10.1186/s12933-015-0192-5

Copy DOI

Abstract

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen, as induced in vitro by added thrombin, leads not to the common ‘spaghetti-like’ structures but to dense matted deposits. Type 2 diabetes is a known inflammatory disease. In the present work, we found that the axial ratio of the erythrocytes of poorly controlled (as suggested by increased HbA1c levels) type 2 diabetics was significantly increased, and that their fibrin morphologies were again highly aberrant. As judged by scanning electron microscopy and in the atomic force microscope, these could be reversed, to some degree, by the addition of the iron chelators deferoxamine (DFO) or deferasirox (DFX). As well as their demonstrated diagnostic significance, these morphological indicators may have prognostic value.

Highlights

Type II diabetes mellitus causes an ever-increasing burden on health care [1,2,3,4]
Type II diabetes is associated with three main glycaemic disorders: chronic hyperglycaemia; glycaemic variability; and iatrogenic hypoglycaemia [7], and comorbidities including dyslipidemia [8,9,10,11] and hypertension [12,13]
We have shown that RBCs in type II diabetes have a changed shape, as well as a decreased membrane roughness [93,94,106] and that RBCs can rapidly adapt in a changed environment, including during an addition of glucose to healthy RBCs [107]

Summary

Introduction

Type II diabetes mellitus causes an ever-increasing burden on health care [1,2,3,4]. The prevalence for all agegroups worldwide was estimated to be 2.8% in 2000 and predicted to increase to 4.4% in 2030 [5]. Among adults in the US, the prevalence of undiagnosed diabetes is currently 4.1% and prediabetes a staggering 35.6% [6]. Type II diabetes is associated with three main glycaemic disorders: chronic hyperglycaemia; glycaemic variability; and iatrogenic hypoglycaemia [7], and (frequently) comorbidities including dyslipidemia (high cholesterol levels) [8,9,10,11] and hypertension [12,13]. Diabetes is associated with (low-grade) systemic inflammation [27,28,29]. We know that there are important links between oxidative stress, a changed inflammatory marker profile (inflammation), the development of diabetes type II as well as, vascular dysfunction: Pretorius et al Cardiovascular Diabetology (2015) 14:30

Methods

Results

Conclusion