A 66-year-old woman with a 10-year-history of type 2 diabetes mellitus comes to the office because of unsteadiness. She stumbles occasionally and has had several near-fall episodes over the last 6 months. Her other medical problems include hypertension and hyperlipidemia. Her medications include aspirin, lisinopril, metformin, sitagliptin, and a statin. She was diagnosed with diabetic neuropathy one year ago. She was also told that she spills protein in her urine.
Her blood pressure is 133/70 mm Hg supine and 135/76 mm Hg while standing, and her pulse is 82/min. Her body mass index is 32 kg/m². Pinprick and vibration sensations are decreased in both feet. Ankle reflexes are absent bilaterally.
Laboratory results are as follows:

Which of the following most likely contributed to this patient's current condition?

Question

A 66-year-old woman with a 10-year-history of type 2 diabetes mellitus comes to the office because of unsteadiness. She stumbles occasionally and has had several near-fall episodes over the last 6 months. Her other medical problems include hypertension and hyperlipidemia. Her medications include aspirin, lisinopril, metformin, sitagliptin, and a statin. She was diagnosed with diabetic neuropathy one year ago. She was also told that she spills protein in her urine.
Her blood pressure is 133/70 mm Hg supine and 135/76 mm Hg while standing, and her pulse is 82/min. Her body mass index is 32 kg/m². Pinprick and vibration sensations are decreased in both feet. Ankle reflexes are absent bilaterally.
Laboratory results are as follows:

Which of the following most likely contributed to this patient's current condition?

Quizplus · Accepted Answer

This patient's presentation (low vitamin B₁₂ level, macrocytic anemia, and associated neurologic symptoms) is consistent with B₁₂ deficiency. Although this patient may have diabetic peripheral neuropathy, B₁₂ deficiency is most likely contributing to her neurologic dysfunction. Metformin reduces intestinal absorption of vitamin B₁₂ by up to 30%. The mechanism is thought to involve impaired calcium-dependent binding of the intrinsic factor-B₁₂ complex to its receptor, thus decreasing ileal absorption. The risk of developing vitamin B₁₂ deficiency increases with older patients, higher metformin doses, and longer durations of treatment. Neurologic symptoms may appear before anemia develops. ₁₂ ₁₂ ₁₂ ₁₂ ₁₂ Small amounts of vitamin B₁₂ present in daily multivitamin supplements do not protect against the development of vitamin B₁₂ deficiency in metformin-treated patients. As a result, patients taking metformin should be routinely monitored for B₁₂ deficiency. Increased calcium intake may improve vitamin B₁₂ absorption. ₁₂ ₁₂ ₁₂ ₁₂ (Choice A) Cardiovascular autonomic neuropathy can result in recurrent falls and presyncopal episodes due to orthostatic hypotension. However, this patient's blood pressure does not drop upon standing. Small intestine bacterial overgrowth (SIBO) resulting from gastrointestinal autonomic neuropathy (decreased motility) can contribute to vitamin B₁₂ deficiency. (Choice B) Vitamin B₁₂ deficiency is not generally seen with jejunal villous atrophy because the absorption of vitamin B₁₂ occurs in the terminal ileum. In patients with jejunal villous atrophy (eg, celiac disease), iron and vitamin D deficiencies are common. ₁₂ ₁₂ (Choice D) Pancreatic atrophy usually presents with steatorrhea. Although deficiency of fat soluble vitamins and vitamin B₁₂ may occur with pancreatic atrophy, clinically significant deficiency is not very common except for vitamin D deficiency. ₁₂ (Choice E) Proteinuria does not usually cause vitamin B₁₂ deficiency. Heavy proteinuria can cause iron and vitamin D deficiency due to urinary losses of transferrin and vitamin D binding protein. ₁₂ Educational objective: The risk of developing vitamin B₁₂ deficiency is increased in patients treated with metformin. The risk increases with older patients, higher metformin doses, and longer durations of treatment. Metformin is thought to impair the terminal ileal absorption of vitamin B₁₂ by inhibiting calcium-dependent binding of the intrinsic factor-B₁₂ complex to its receptor. ₁₂ ₁₂ ₁₂ __________ References: Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: the National Health and Nutrition Examination Survey, 1999-2006. (http://www.ncbi.nlm.nih.gov/pubmed/22179958) Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. (http://www.ncbi.nlm.nih.gov/pubmed/10977010) Risk factors of vitamin B12 deficiency in patients receiving metformin. (http://www.ncbi.nlm.nih.gov/pubmed/17030830)

A 66-Year-Old Woman with a 10-Year-History of Type 2 Diabetes