Inflammatory mediators are induced by dietary glycotoxins, a major risk factor for diabetic angiopathy

Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-α/β-actin mRNA ratio was 1.4 ± 0.5 on H-AGE and 0.9 ± 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 ± 429 and 698 ± 347 ng/ml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-α rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects

End-Of-Life Decision Making: A Qualitative Study of Elderly Individuals

OBJECTIVE: To identify the desired features of end-of-life medical decision making from the perspective of elderly individuals. DESIGN: Qualitative study using in-depth interviews and analysis from a phenomenologic perspective. SETTING: A senior center and a multilevel retirement community in Los Angeles. PARTICIPANTS: Twenty-one elderly informants (mean age 83 years) representing a spectrum of functional status and prior experiences with end-of-life decision making. MAIN RESULTS: Informants were concerned primarily with the outcomes of serious illness rather than the medical interventions that might be used, and defined treatments as desirable to the extent they could return the patient to his or her valued life activities. Advanced age was a relevant consideration in decision making, guided by concerns about personal losses and the meaning of having lived a “full life.” Decision-making authority was granted both to physicians (for their technical expertise) and family members (for their concern for the patient's interests), and shifted from physician to family as the patient's prognosis for functional recovery became grim. Expressions of care, both by patients and family members, were often important contributors to end-of-life treatment decisions. CONCLUSIONS: These findings suggest that advance directives and physician-patient discussions that focus on acceptable health states and valued life activities may be better suited to patients' end-of-life care goals than those that focus on specific medical interventions, such as cardiopulmonary resuscitation. We propose a model of collaborative surrogate decision making by families and physicians that encourages physicians to assume responsibility for recommending treatment plans, including the provision or withholding of specific life-sustaining treatments, when such recommendations are consistent with patients' and families' goals for care