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Others * Long-term metformin use * Proton pump inhibitors (reduce acid absorption) Pathophysiology * Impaired DNA synthesis megaloblastic anemia * Accumulation of methylmalonic acid nerve damage Clinical features Hematological * Fatigue, pallor * Shortness of breath * Megaloblastic anemia Neurological (key distinguishing feature) * Peripheral neuropathy (tingling, numbness) * Loss of vibration and position sense * Ataxia (unsteady gait) * Cognitive changes Severe untreated cases irreversible nerve damage Others * Glossitis (smooth, beefy red tongue) * Mild jaundice Investigations * Serum vitamin B12 * CBC macrocytic anemia ( MCV) * Blood film hypersegmented neutrophils * methylmalonic acid (specific for B12 deficiency) * homocysteine Differentiate from folate deficiency * Both megaloblastic anemia * Only B12 neurological symptoms Management Replacement therapy * Hydroxocobalamin (preferred IM) * Frequent doses initially, then maintenance * Oral B12 if mild and absorption intact Important rule Never give folate alone if B12 deficiency is possible may worsen neurological damage Prevention * Adequate diet (meat, eggs, dairy) * Supplementation in vegans * Monitor high-risk patients (elderly, post-surgery)

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Methods C57BL/6J mice and Sirt1 +/ mice were treated with exenatide (24 nmol/kg) or an NaCl solution (154 mmol/l) control i.p

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