Office of Naval Research Contract N00014-88-c-0118 Technical Report 9 4-09 Whole Blood Viscosity in Individuals with Insulin-dependent Diabetes Mellitus: Exploring the Role of the Porous Bed Viscometer

Title: Whole blood viscosity in individuals with insulin-dependent diabetes mellitus: Exploring the role of the porous bed viscometer Objective: The study was performed to evaluate the capacity of a porous bed viscometer (PBV) to demonstrate differences in blood viscosity in patients with diabetes mellitus and to investigate the • role that various cellular and plasma components play in determining blood viscosity at physiologic shear rates. Research, Design and Methods: A prospective, technician-blinded study comparing recruited insulin-dependent diabetic patients and non-diabetic control individuals was performed at a tertiary-care referral hospital and its associated outpatient clinic. Thirty insulin-dependent diabetic individuals were compared with twenty-three non-diabetic individuals. Blood specimens were drawn from all individuals in a similar fashion and samples were analyzed in a blinded fashion for a panel of serum and cellular components and blood viscosity utilizing a PBV. Results: The PBV was able to demonstrate that differences in hematocrit are responsible for the majority of blood viscosity variability. Diabetic status played a small but statistically significant role in explaining some of the variability in blood viscosity, as did fibrinogen. Conclusions: This study supports previous reports which suggest that individuals with insulindependent diabetic mellitus have a higher blood viscosity than should be expected on the basis of hematocrit and fibrinogen alone. In addition, the study demonstrates that the PBV is a sensitive device, providing reproducible measurements of whole blood viscosity at low shear rates. The porous bed viscometer could be used for large numbers of examinations with relative ease of use, safety and cost. WHOLE BLOOD VISCOSITY IN INDIVIDUALS WITH INSULIN-DEPENDENT DIABETES MELLITUS: EXPLORING THE ROLE OF THE POROUS BED VISCOMETER INTRODUCTION Abnormalities in blood viscosity have been implicated in the clinical manifestations of a number of diseases. The relationship between blood viscosity and pathophysiology is readily apparent when it represents the effect of a single blood component, such as red blood cells in polycythemia vera or fibrinogen in hyperfibrinogenemia (1). In contrast, the relationship between multiple factors such as hematocrit, plasma fibrinogen levels and blood viscosity have not been consistently demonstrated in individuals with diabetes (2,3,4,5,6,7,8). In addition to precision, sensitivity and sample size, the methodology for measuring blood viscosity has also contributed to difficulty in analysis. The traditional technique relies on measurement of the resistance that blood exhibits when placed in a container between a rotating and stationary surface. Artifacts associated with this technique can mislead investigation (9,10). First, separation of the cellular and plasma components of blood can occur within the container leading the viscometer to measure the viscosity of a fluid which is not uniformly mixed. Second, viscosity measurements are dependent on the shear rate applied to the fluid in question. The physiologically important shear rates are probably those which are equivalent to shear rates which are present in the microvascular tree, on the order of 10-30 seconds". Rotational devices generally are less accurate at these low shear rates. A recently introduced device may successfully address several of these problems(11,12, 13,14,15). The whole blood porous bed viscometer (PBV) is an inexpensive, disposable, simpleto-use device which has been shown to accurately estimate the viscosity of whole blood at rates comparable results. First, the device has been demonstrated to provide accurate, reproducible measurements which discriminate between small differences in viscosity between specimens. Second, the PBV is a simplified method of measurement compared to more traditional methods and coupled with its relatively low cost-per-test allows for the study of large numbers of samples. In this way smaller differences can be statistically demonstrated by testing larger numbers of individuals. An added advantage of the PBV over more traditional devices such as the cone-plate viscometer or the capillary tube method is that the PBV measures whole blood using a shear rate around 20 seconds ", a more physiological rate, and in a manner that eliminates the problems of separation that plague rotational devices. Lastly, the disposable, self-contained design reduces " risks of blood-borne infection and drastically reduces equipment maintenance. This study was undertaken to examine the capacity of the PBV to demonstrate differences in blood viscosity in patients with patients with diabetes mellitus and to investigate the role that various cellular and plasma components play in determining blood viscosity at this shear