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Common Risk Factors Include: Northern European descent Age over 50 years Autoimmune disorders (e.g., thyroid disease, type 1 diabetes) Long-term use of acid-suppressing medications Strict vegetarian or vegan diets History of gastric or intestinal surgery Pathophysiology of Pernicious Anemia The development of pernicious anemia follows a predictable sequence: Autoimmune destruction of gastric parietal cells Reduced or absent intrinsic factor production Failure to absorb vitamin B12 in the terminal ileum Impaired DNA synthesis in bone marrow Production of large, dysfunctional red blood cells Reduced oxygen-carrying capacity Over time, vitamin B12 deficiency also affects the nervous system , leading to neurological symptoms

The Lancet Psychiatry, 2(1), 38-48

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The differential is not marginal it is the difference between a compound that ran a full clinical program and failed to prove efficacy, and one that has demonstrated both efficacy and cardiovascular benefit in some of the largest obesity trials ever conducted