Diabetes
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To determine the effects of acute metabolic acidosis and alkalosis on leucine metabolism in vivo, mongrel dogs were infused with [1-14C]leucine for 8 h, along with NaCl, HCI, or NaHCO3 over the last 4 h. Arterial pH did not change from the basal value during NaCl infusion but decreased (P less than .01) and increased (P less than .01) during HCl and NaHCO3 infusions, respectively. Total leucine carbon entry did not change from the basal value during saline infusion but increased (P less than .01) with acidosis and decreased (P less than .05) with alkalosis. ⋯ During alkalosis decreased (P less than .01) leucine oxidation. During acidosis, total plasma essential and nonessential amino acid concentrations increased (P less than .05), whereas during alkalosis, total plasma essential and nonessential amino acid concentrations decreased (P less than .05). These studies suggest that acute alterations in arterial pH may affect the regulation of protein metabolism in vivo and must be considered in the interpretation of results from experiments in which alterations of acid-base homeostasis may have occurred.
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Pupillary unrest (fluctuations in pupil size) was measured by infrared television videopupillography in 80 insulin-dependent diabetic patients (age 25-43 yr, diabetes duration 0-35 yr) and 26 control subjects (age 26-39 yr). In darkness, pupillary unrest was 21% less in diabetic subjects than in controls. During prolonged and brief illumination, pupillary unrest was 35 and 37% less in diabetic subjects than in controls, respectively, and in both cases the unrest was inversely correlated to the duration of diabetes. ⋯ Pupil size in darkness was 19% smaller in diabetic subjects than in controls, and in diabetic subjects it was positively correlated to the unrest in darkness and during prolonged and brief illumination. None of the pupillary abnormalities showed correlation to biomicroscopic changes in the iris. The autonomic nervous system abnormalities reflected in the pupil in longstanding diabetes are 1) a reduction in pupillary unrest in light and in darkness, more pronounced in light, 2) a reduction in the ability to maintain miosis in continuous light, and 3) a reduction in size.
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The stability and longevity of the polyethylene-polypropylene glycol-stabilized insulin have been tested in vitro and in vivo in an implanted insulin-infusion device, the programmable implantable medication system (PIMS). In vitro tests demonstrated long-term compatibility with refill cycles of up to 3 mo, with a preparation of 400 U/ml. Total test period in vitro was 3.2 device-yr (combined time of device use). ⋯ There has been no insulin blockage of the catheter of active pumps after 5.1 dog-yr (combined time of trials) of trials (up to 5 mo between refills in a single dog). Structural stability of insulin was analyzed by high-performance liquid chromatography. On average, 90.8% of the insulin sampled from the reservoir in vivo was native insulin, with an average of 96.2% retention of active forms.
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Comparative Study
Diminished flare response in neuropathic diabetic patients. Comparison of effects of substance P, histamine, and capsaicin.
The flare response in skin largely depends on an intact primary sensory fiber, the C-fiber. We measured the flare response to the intradermal injection of substance P, histamine, and capsaicin in control subjects and in diabetic patients with and without clinically obvious polyneuropathy. ⋯ Alternatively, dysfunction of the mast cell or vascular reactivity may contribute to the diminished flare. Because C-fibers participate in nociception in addition to the flare response, the findings of this study, by a method that permits a quantifiable measurement of the function of peripheral sensory neurons in diabetic subjects, has potential usefulness in evaluating sensory neuropathy in diabetic patients.
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Circulating insulin autoantibodies (INSAAb) were measured in discordant monozygotic twins, first-degree relatives, and other groups at "high risk" for the development of insulin-dependent diabetes mellitus (IDDM), and these results correlated with both islet cell antibody (ICAb) status and beta cell function. INSAAb were positive in 31.6% (12 of 38) ICAb-positive subjects but in only 3.1% (3 of 97) ICAb-negative subjects (X2 = 22.4; P less than 0.001). ⋯ Eight of 15 subjects detected to be INSAAb positive have thus far progressed to clinical IDDM (X2 = 18.3; P less than 0.001). Thus, autoantibodies reactive with the insulin molecule (1) appear to constitute an additional serologic marker of ongoing autoimmunity and development of IDDM, and (2) may reflect heterogeneity in the pathogenesis of IDDM.