Correlation between Real-Time Microvascular Abnormalities and Whole Blood Viscosity (WBV) in Type-2 Diabetes Mellitus (T2DM) Patients.

Abstract

Novel technologies were used to study the microvascular abnormalities in Type-2 diabetes mellitus (T2DM) patients and to correlate these real-time pathological complications with whole blood viscosity (WBV) over a wide range of shear rates (1–1,000s−1). Computer-assisted intravital microscopy (CAIM) was used to non-invasively and objectively quantify the microvascular abnormalities in the conjunctival microcirculation in T2DM patients (n=12; age range = 45 to 68) and healthy non-diabetic control subjects, with the medical history of each subject blinded to the investigators. Fifteen recognizable microvascular abnormalities existed in T2DM patients and not in the control subjects, though not all the abnormalities were found in each patient. A severity index (SI) -- the arithmetic sum of microvascular abnormalities in each patient quantified via CAIM -- was computed to give a score to correlate with medical history, WBV and shear rates. T2DM SI (6.9±1.7) differed significantly (P<0.01) from control SI (0.6±0.7) and correlated significantly with disease severity, but not with the duration of the disease since diagnosis. The results, together with results from a previous study, lend support to the hypothesis that diabetic complications may have occurred in the pre-diabetic period; indicative of the existence of a “time window” before the onset of clinically detectable hyperglycemia. To adequately assess WBV to correlate with T2DM SI, a computer-assisted scanning capillary viscometer, the Rheolog™, was used to generate a viscosity profile for each patient or control subject over a range of shear rates (1 to 1,000s−1) using one 3-ml citrated venous blood sample from each subject. Based on the viscosity profiles generated, WBV of T2DM patients at various shear rates differed significantly from control values. For example, averaged WBV of T2DM patients at a shear rate of 300s−1 (4.01±0.33cp) differed significantly (P<0.02) from averaged WBV of control subjects (3.34±0.05cp). WBV correlated with SI of T2DM patients, disease severity and medical records. This correlation may have unique clinical implications - it can be used to study shear-stress induced pathogenesis on endothelial dysfunction in various vascular diseases and in early detection of T2DM in carriers (e.g. siblings of T2DM patients) before clinical diagnosis of T2DM during the pre-diabetic “time window” of early detection. Follow-up studies on the correlation between real-time microvascular abnormalities (SI), disease severity, WBV and shear rates in Alzheimer's Disease patients and in early detection of T2DM are in progress.