CME INDIA Case Presentation by by Dr B. Harish Darla, MRCP, Endo UK, MRCP, Medicine. FRCP, MNAMS, Internal Medicine, Post graduate Diploma in Diabetology and Endo, UK. Darla’s Health Care, Mysore, India.

CME INDIA Case Study:

42 yrs. old, Type 2 DM for 2 yrs. on Teneligliptin 20 mg od and Metformin 1000mg od, presented with Indigestion, 15 days, increased belching, retrosternal burning and redness of tongue since last 6 months’/E: Rends on the sides of tongue, papillae reduced.

CME INDIA Discussion:

Dr Prabhat Agarwal, Internist, Agra: Vitamin b complex deficiency. May be due to GERD.

Dr Santosh Malpani, Diabetologist, Nanded: Do B12 levels.

Dr Navneet Kumar, MDS, Ranchi: Looks like papular atrophy of the tongue. Also known as Atrophic Glossitis. For burning sensation Benzydamine Hydrochloride 0.15 percent Oral rinse before meal is effective. Multivitamins containing folic acid, vitamin b12, riboflavin is recommended.

Dr Himalya Jha, CMO, CGHS, Ranchi: CBC (MCV?). Could be Vitamin B12 deficiency. pt. could be on long term proton pump inhibitors or Indigestion and Burning sensation could be symptoms of B12 deficiency.

– Associated nail changes and IDA should be ruled out.

– B1, B2 and Folic acid deficiency should be ruled out.

Dr D P Khaitan, Consultant Physician, Gaya: I would like to know peripheral blood film study to exclude Pernicious anaemia.

Autoimmune /atrophic gastritis with pernicious anaemia is a coexisting condition.

Dermatological consultation to exclude.

There is also increased incidence of GERD due to B12 induced neuropathy.

D/D

• Metformin induced Vit. B12 deficiency with GERD
• Teneligliptin induced
• Pemphigoid sublingually / Vit. 12 associated glossitis

Provisional Diagnosis: Metformin induced Vit.B12 deficiency – This should be the clinical dictum if any patient on Metformin shows Vit. B12. Deficiency with clinical spectrum he /she should be tested for Vit. B12 and treated accordingly.

Dr Harish Darla, Mysore: That’s what my diagnosis was. I am thinking of Vit. B12 deficiency. Probably metformin induced, patient is non-vegetarian.

Dr Amit Kumar, Dermatologist, Ranchi: I agree with the diagnosis here that it is glossitis probably due to Vit B12 deficiency.

Dr Bhanu Pratap Singh, Internist, Siwan, Bihar: Metformin induced vit B12 deficiency is common (as much as 40% in pts taking Metformin), but simultaneously it should be ruled out if patient is taking any proton pump inhibitor, because it is quite commonly used, even by the patients themselves as over the counter drugs.

Dr Harish Darla, Mysore: No, he is not on any medication.

Dr N K Singh: What is ADA recommendation to monitor Vit. b12 with metformin.

Dr Ashu Rastogi, DM Endo PGI, Chandigarh: Annually in those on long term Metformin therapy. They have not defined what is long term. We presume more than 5 years.

Dr Raju Sharma, Jamshedpur: But don’t diabetic patients anyways get the B12 injection soon after starting of symptoms of neuropathy?

Dr Basab Ghosh, Agartala: Methylcobalamin is now used in abundance in diabetes clinics, so chances of Vit B12 deficiency is rarest.

Further Course

Vit.12 level and folic estimation was done:

Started on treatment with supplementation of Vit. B12 and folio acid.

After Treatment:

Common things are common – Think simple. Take home points:

1. Common things are common, patient who has been having the redness and burning sensation in the tongue since last 6mts, has been given multiple medications for the same with no relief. If we fail to get to the bottom of the problem, then it’s always advisable review the case from a new angle without any bias.
2. When patient is on long term metformin think of Vit. B 12 deficiency.
3. Post 1st dose of Vit. B12 injection, patient is feeling better and burning sensation reduced.
4. Vit. B12 deficiency is commonly seen in Vegetarian’s but can also be seen in Non-vegetarian’s as well.
5. Weather a combination of Metformin + Cyanocobalamin is advisable or not?

CME INDIA Learning Points:

• Chronic metformin use results in vitamin B12 deficiency in 30% of patients. Exhaustion of vitamin B12 stores usually occurs after twelve to fifteen years of absolute vitamin B12 deficiency.
• Several studies have shown that long-term use of metformin leads to malabsorption of vitamin B12, with a decrease in the concentration of serum vitamin B12 from 30% to 14%. Additionally, randomized control trials and cross-sectional studies have reported a decrease in serum vitamin B12 level between 9% and 52% with metformin use
• The mechanism by which metformin reduces serum vitamin B12 levels has not been elucidated, but the most likely hypothesis is that metformin interferes with calcium-dependent membrane action responsible for vitamin B12 intrinsic factor absorption in the terminal ileum.
• Some studies have reported that serum vitamin B12 levels were inversely related to the duration and dose of metformin use. Since large prospective studies have clarified this relationship recently, 2017 onwards American Diabetes Association treatment guidelines recommend regular monitoring of vitamin B12 levels in patients with diabetes taking metformin.
• Meanwhile, serum vitamin B12 may be an unreliable marker for overall vitamin B12 deficiency because of the variability in measurement methods.
• Vitamin B12 is involved in the activity of methylmalonyl-CoA mutase and the pathway for methionine synthase in cells. Intracellular vitamin B12 deficiency interferes with both of these pathways and increases MMA and homocysteine, which are biochemical indicators of metabolic efficacy. Therefore, if a decrease in serum vitamin B12 levels is not accompanied by an increase in MMA and homocysteine levels, this could be interpreted as a simple plasma decrease of vitamin B12 levels, rather than a true tissue deficiency.
• Some studies have reported that decreases in vitamin B12 after metformin treatment were only plasma decreases, without an increase in homocysteine levels
• Laboratory investigations with the establishment of low serum B₁₂ levels and elevated levels of methylmalonic acid (MMA) are the cornerstone of diagnostics, but normal levels of serum B₁₂ and MMA do not exclude symptomatic B₁₂ deficiency
• Lindenbaum et al reported a large series of 40 patients who had neurologic symptoms or psychiatric disorders caused by vitamin B₁₂ deficiency but who had no anemia or macrocytosis. Psychiatric symptoms may vary from depression to mania, psychosis, and occasionally suicidal thoughts
• Although the demonstration of low serum vitamin B₁₂ levels is considered diagnostic, there is a poor correlation between these levels and symptoms, and even people with vitamin B₁₂ levels below 140 pmol/L may not have symptoms.

CME INDIA Tail Piece:

• What are the classic presentations of Addison-Biermer disease?
• Approach :

Source: Am Fam Physician. 2017 Sep 15;96(6):384-389.

(Addison-Biermer’s anaemia is an autoimmune disease and the most common cause of vitamin B12 deficiency)

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