Although it is considered that the pathogenesis of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) is primarily due to chronic hyperglycemia resulting in vascular changes and retinal ischemia, the red blood cells (RBCs) disorders might also represent an important pathophysiological risk factor.
OBJECTIVE
To evaluate whether the RBC properties contribute to DR development and progression in T2DM.
METHODS
This prospective observational study comprised 247 persons with T2DM free of DR or with non proliferative DR without any signs of anaemia. The patients were reacessed after 60-months.
RESULTS
The mean age of our study population was 56 years, 54.9% males with diabetes duration of 11,18±1,28 years. During the follow up, 16 (5.84%) participants developed non proliferative DR and 9 (3.64%) progressed to PDR while the mean corpuscular volume (MCV) and red cell distribution width (RDW) MCV rose. Both MCV and RDW correlated positively with HbA1c (r = 0,468, p = 0.003 and r = 0.521, p < 0.001), while Cox regression analysis revealed that besides age, diabetes duration, HbA1c, hypertension and dyslipidemia presence, MCV and RDW are also associated with the risk of DR development and progression (HR 1.057 and 1.237, p < 0.001).
CONCLUSIONS
We clearly demonstrated that RBC’s characteristics might represent a risk factor for DR development and progression.
KahnR, WeirG, KingG. et al., Ocular complications of diabetes mellitus. In Joslin’s Diabetes Mellitus, 901e21, LWW, Baltimore, Md, USA, 14th, 2005.
3.
KleinR, KleinBE, MossSE, DavisMD, DeMetsDL. The Wisconsin epidemiologic study of diabetic retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984; 102(4): 520–6.
4.
EngermanRL. Pathogenesis of diabetic retinopathy. Diabetes. 1989; 38(10): 1203–6.
5.
RobinsonR, BarathiVA, ChaurasiaSS, WongTY, KernTS. Update on animal models of diabetic retinopathy: From molecular approaches to mice and higher mammals. Dis Model Mech. 2012; 5(4): 444–-56. doi:10.1242/dmm.009597.
6.
BabuN, SinghM. Influence of hyperglycemia on aggregation, deformability and shape parameters of erythrocytes. Clin Hemorheol Microcirc. 2004; 31: 273–80.
7.
BertramB, WolfS, ArendO, SchulteK, PeschTW, JungF, KiesewetterH, ReimM. Blood rheology and retinopathy in adult type I Diabetes Mellitus. Clin Hemorheol. 1992; 12: 437–48.
8.
KoscielnyJ, LatzaR, WolfS, KiesewetterH, JungF. Early rheological and microcirculatory changes in children with type I diabetes mellitus. Clin Hemorheol Microcirc. 1998; 19: 134–9.
9.
SolakY, YilmazMI, SaglamM, et al., Mean corpuscular volume is associated with endothelial dysfunction and predicts composite cardiovascular events in patients with chronic kidney disease. Nephrology (Carlton). 2013; 18(11): 728–35. doi: 10.1111/ne12130.
10.
ArendO, WolfS, JungF, BertramB, PöstgensH, ToonenH, ReimM. Retinal microcirculation in patients with diabetes mellitus: Dynamic and morphological analysis of perifoveal capillary network. Brit J Ophthalmol. 1991; 75: 514–18.
11.
RendellM, FoxM, KnoxS, LastovicaJ, KirchainW, MeiselmanHJ. Effects of glycemic control on red cell deformability determined by using the cell transit time analyzer. J Lab Clin Med. 1991; 117(6): 500–4.
12.
KDIGO. Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kid Int Suppl. 2012; 2013(3): 5–140.
13.
TravesetA, RubinatE, OrtegaE, et al., Lower Hemoglobin Concentration Is Associated with Retinal Ischemia and the Severity of Diabetic Retinopathy in Type 2 Diabetes. Journal of Diabetes Research. 2016; 2016: 3674946. doi: 10.1155/2016/3674946.
14.
Ethical guidelines for publication in Clinical Hemorheology and Microcirculation: Update 2016. Clin Hemorheol Microcirc. 2016; 63(1): 1–2.
15.
DavisMD, FisherMR, GangnonRE, et al., Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early treatment diabetic retinopathy study report 18. Investigative Ophthalmology and Visual Science. 1998; 39(2): 233–52.
16.
QiaoQ, Keinänen-KiukaanniemiS, LääräE. The relationship between hemoglobin levels and diabetic retinopathy. Journal of Clinical Epidemiology. 1997; 50(2): 153–8. doi: 10.1016/S0895-4356(96)00335-6.
17.
IraceC, ScarinciF, ScorciaV, et al., Association among low whole blood viscosity, haematocrit, haemoglobin and diabetic retinopathy in subjects with type 2 diabetes. British Journal of Ophthalmology. 2011; 95(1): 94–8. doi: 10.1136/bjo.2009.172601.
18.
ShorbSR. Anemia and diabetic retinopathy. American Journal of Ophthalmology. 1985; 100(3): 434–6. doi: 10.1016/0002-9394(85)90508-2.
19.
MalandrinoN, WuWC, TaveiraTH, WhitlatchHB, SmithRJ. Association between red blood cell distribution width and macrovascular and microvascular complications in diabetes. Diabetologia. 2012; 55(1): 226–35.
20.
MagriCJ, FavaS. Red blood cell distribution width and diabetes-associated complications. Diabetes Metab Syndr. 2014; 8(1): 13–7.
21.
HsiehY-P, ChangC-C, KorC-T, YangY, WenY-K, ChiuP-F. The Predictive Role of Red Cell Distribution Width in Mortality among Chronic Kidney Disease Patients. Cheng J-T, ed. PLoS One. 2016; 11(12): e0162025. doi: 10.1371/journal.pone.0162025.
22.
StrattonIM, AdlerAI, NeilHAW, et al., Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ: British Medical Journal. 2000; 321(7258), 405–12.
23.
YangF, YeJ, PomerantzK, StewartM. Potential modification of the UKPDS risk engine and evaluation of macrovascular event rates in controlled clinical trials. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2013; 6: 247–56.
24.
O’ConnorPJ, Ismail-BeigiF. Near-Normalization of Glucose and Microvascular Diabetes Complications: Data from ACCORD and ADVANCE. Therapeutic Advances in Endocrinology and Metabolism. 2011; 2(1): 17–26.
25.
NguyenDV, ShawLC, GrantMB. Inflammation in the pathogenesis of microvascular complications in diabetes. Front Endocrinol (Lausanne). 2012; 3: 170. doi: 10.3389/fendo.2012.00170.eCollection2012.
26.
MillerJA, GravalleseE, BunnHF. Nonenzymatic glycosylation of erythrocyte membrane proteins, Relevance to diabetes. J Clin Invest. 1980; 65(4): 896–901. doi: 10.1172/JCI109743.
27.
AgrawalR, SmartT, Nobre-CardosoJ, et al., Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique. Scientific Reports. 2016; 6: 15873. doi: 10.1038/srep15873.
28.
SosaJM, NielsenND, VignesSM, ChenTG, ShevkoplyasSS. The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network. Clinical hemorheology and microcirculation. 2014; 57(3): 291–305.
29.
VayáA, SarnagoA, FusterO, AlisR, Romagnoli. Influence of inflammatory and lipidic parameters on red blood cell distribution width in a healthy population. Clin Hemorheol Microcirc. 2015; 59(4): 379–85. doi: 10.3233/CH-141862.
