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Background: Diabetic sensorimotor polyneuropathy is one of the greatest risk factors for foot ulceration. The current study investigated the measurement properties of the Pressure-Specified Sensory Device in comparison with traditional threshold screening instruments, in several categories of sensory loss. Knowledge of these values may help to identify diabetics at risk for ulceration more reliably., Methods: A partially cross-sectional cohort study was carried out in patients with diabetes. Traditional instruments classified each patient into groups representing severity of diabetic sensorimotor polyneuropathy. Demographic characteristics, laboratory measures, and Pressure-Specified Sensory Device measurements were compared between groups. The Bland-Altman method was used to characterize reliability of the Pressure-Specified Sensory Device, and construct validity was determined by comparison with Semmes-Weinstein monofilaments., Results: One hundred fifty-five diabetic patients were measured. Fifteen patients had a diabetic ulcer in their medical history, seven patients were insensate to the 10-g monofilament and had diminished vibration sense (group 1), 34 patients had diminished vibration sense but no elevated cutaneous threshold (group 2), and 99 patients acted as controls (no elevated cutaneous threshold or diminished vibration sense, group 3). The Pressure-Specified Sensory Device distinguished these groups with one-point static cutaneous thresholds alone. Semmes-Weinstein monofilament and Pressure-Specified Sensory Device measurements were not interchangeable. Spatial discrimination (two-point static and two-point moving discrimination) by the Pressure-Specified Sensory Device was more reliable compared with one-point static discrimination. Semmes-Weinstein monofilament (force in grams and pressure in grams per square millimeter) correlations with Pressure-Specified Sensory Device measurements differed between groups., Conclusions: The Pressure-Specified Sensory Device is able to distinguish between categories of sensory loss. The Pressure-Specified Sensory Device is valid in measuring cutaneous thresholds and can reliably measure spatial discrimination at the feet., Clinical Question/level of Evidence: Diagnostic, II.

Objective: Postprandial lipemia has been linked to atherosclerosis and inflammation. Because leukocyte activation is obligatory for atherogenesis, leukocyte activation by triglyceride-rich lipoproteins (TRLs) was investigated., Methods and Results: The expression of CD11b and CD66b after incubation with glucose and native and artificial TRLs (NTRL and ATRL) in vivo and in vitro was evaluated by flowcytometry. Oral fat loading tests showed an increased expression of CD11b on monocytes and neutrophils and CD66b on neutrophils. In 11 volunteers, postprandial leukocytes became enriched with meal-derived fatty acids ([1-(13)C]16:0) suggesting uptake of exogenous fat. ApoB binding on leukocytes measured by flowcytometry in 65 subjects was highest on neutrophils and monocytes suggesting adherence of apoB-containing lipoproteins. Physiological concentrations of TRLs showed 62% increased neutrophil CD11b and a dose-dependent increased monocyte CD11b up to 84% in vitro. Incubations with lipid emulsions in the hypertriglyceridemic range showed a 5-fold increased monocyte CD11b expression, which was higher than the positive control (fMLP), and a dose-dependent 2- to 3-fold increased neutrophil CD11b and CD66b. The oxidative scavenger DMTU decreased the neutrophil CD66b expression by 36%., Conclusions: Acute hypertriglyceridemia is a leukocyte activator most likely by direct interaction between TRLs and leukocytes and uptake of fatty acids. TG-mediated leukocyte activation is an alternative proinflammatory and proatherogenic mechanism of hypertriglyceridemia in part associated to the generation of oxidative stress.

Objective: A functional acylation stimulating protein (ASP) receptor, C5L2, has been recently identified in ASP-responsive cells. Impaired ASP-mediated triglyceride synthesis has previously been described in a subset of hyperapolipoprotein B/familial combined hyperlipidemia subjects., Methods and Results: DNA sequencing of C5L2 coding region in 61 unrelated probands identified a heterozygous variant (G968-->T) in 1 subject, resulting in Ser323-->Ile substitution in the carboxyl terminal region. This variant was not detected in 2176 additional chromosomes by restriction fragment length polymorphism or fluorescence polarization genotyping. Eight family members of the proband were identified with one altered (+/-)C5L2 allele. Nine other family members had the wild-type (+/+)C5L2 sequence. The abnormal allele was associated with increased plasma triglyceride, plasma cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B and ASP. Of 23 subjects tested in cell-based ASP bioactivity assays, those with C5L2(+/-) variant (n = 2) had a 50% reduction in ASP-stimulated triglyceride synthesis, glucose transport and marked reduction in maximal binding (B(max)). By contrast, a C5L2(+/+) family member responded normally, as did hyperapolipoprotein B normal ASP subjects compared with C5L2(+/+) controls (n = 6)., Conclusions: The S323I variant may alter C5L2 function and might be one molecular basis contributing to familial combined hyperlipidemia.