Blood viscosity and plasma proteins influencing it are increased in Type I diabetes in the DCCT

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The Diabetes Control and Complications Trial (DCCT), an NIH-sponsored study at 29 institutions in the U.S. and Canada, was designed to examine the effects of intensive management in type I diabetes. Between 1983 and 1989, 1441 patients with and without mild retinopathy (primary and secondary) were randomized into two major treatment groups, intensively and conventionally treated patients. Retinopathy, nephropathy, and neuropathy were assessed periodically in each patient. In this study, levels of fibrinogen, haptoglobin, albumin and total protein were measured and viscosity of fresh blood was simultaneously evaluated in 45 local DCCT patients. Viscosity was measured at 17 rotation rates arranged logarithmically from .03 to 300 inverse seconds shear rate on blood adjusted to 41 % hematocrit by the addition or removal of its own plasma. Blood's time-based flow properties --- transient resistance and viscoelasticity --- were also assessed. Blood viscosity showed the greatest elevation (10 to 19%) in the 0.08-2.0 inverse second shear rate range. Increased low shear rate blood viscosity was found to be linked to fibrinogen and hemoglobin Alc levels. In addition to steady flow blood viscosity measurement, blood's time-based flow properties were also assessed at 15 inverse seconds shear rate. Transient resistance was increased 30% in diabetes; its elevation was found to be linked to both fibrinogen level and low shear blood viscosity. Diabetic blood's viscoelasticity at this high shear rate was much less strikingly increased than its transient resistance. Viscoelastic strain energy was correlated with fibrinogen, low shear viscosity, haptoglobin, and albumin level. Interleukin-6 (IL-6), a potent stimulator of fibrinogen and haptoglobin synthesis in hepatocytes in culture, was found to be elevated in diabetes, indicating that it is the likely mediator of the observed plasma protein changes. The altered blood flow properties observed in this well-characterized group of type 1 diabetes mellitus patients may playa role in development of diabetic complications.