Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. Vitamin B12 or cobalamin is a water soluble vitamin that plays a very fundamental role in DNA synthesis, optimal haemopoesis and neurological function. The clinical picture of vitamin B12 deficiency hence, is predominantly of features of haematological and neurocognitive dysfunction. Vitamin B12 exerts its physiological effects through mediating two principal enzymatic pathways i.e. the methylation process of homocysteine to methionine and the conversion of methylmalonyl coenzyme A (CoA) to succinyl-CoA. Vitamin B12 as a co-factor facilitates the methylation of homocysteine to methionine which is later activated into S-adenosyl-methionine that donates its methyl group to methyl acceptors such as myelin, neurotransmitters and membrane phospholipids. Metabolically significant vitamin B12 deficiency hence will result in disruption of the methylation
process
and
accumulation
of
intracellular
and
serum
homocysteine.
Hyperhomocysteinemia has been shown to have potentially toxic effects on neurones and the vascular endothelium. This reaction is also essential in the conversion of dietary folate (methyltetrahydrofolate) to its active metabolic form, tetrahydrofolate. Vitamin B12 is also essential in the synthesis of monoamines or neurotransmitters like serotonin and dopamine. Vitamin B12 is an essential micronutrient required in DNA synthesis, cellular repair and normal haemopoesis together with other micronutrients like folate and iron. Compelling evidence demonstrates that hyperhomocysteinemia is also associated with an increased risk of cardiovascular events due to its cellular and vasculo-toxic effects. Clinical and biochemical vitamin B12 deficiency is highly prevalent among patients with both types 1 and 2 DM. Metformin use has been unequivocally demonstrated as the prime factor associated with vitamin B12 deficiency among patients with T2DM. Studies assessing type 2 diabetic patients on metformin have reported the prevalence of vitamin B12 deficiency to range
from 5.8% to 33%. Metformin use as the very superior glycemic lowering effect, but also has for long been shown to decrease vitamin B12 levels. The risk of developing metformin associated vitamin B12 deficiency is greatly influenced by increasing age, metformin dose and duration of use. Type 1 DM (T1DM) is an auto immune condition that results from auto immune destruction of insulin secreting beta cells of the pancreas. Vitamin B12 deficiency due to pernicious anemia, resulting from chronic autoimmune gastritis, occurs frequently among patients with T1DM. Gastric autoimmunity like PCA and AIF especially among T1DM patients with GAD-65 and thyroid peroxidase antibodies increases the propensity to developing vitamin B12 deficiency. All patients deficient of vitamin B12 should receive replacement therapy with either oral or parenteral vitamin B12. Replacement therapy with daily intra muscular or oral vitamin B12 in the dose of 100μg for a week and then monthly is satisfactory. Future large and well designed studies on screening for vitamin B12 deficiency, vitamin B12 supplementation and optimal supplementation dose among type 1 and type 2 diabetic patients are warranted to help guide formulation of guidelines in diabetes clinical care. Annual screening for vitamin B12 deficiency using more sensitive methods like serum homocysteine and methylmalonic acid concentrations (in clinical settings where they are accessible) and supplementation should be adopted among diabetic patients with specific risk factors of vitamin B12 deficiency.
Kekurangan vitamin B12 pada pasien diabetes mellitus: skrining rutin dan suplemen sudah dibenarkan?
Kekurangan vitamin B12 secara biokimia dan klinis telah dibuktikan sangat umum pada pasien dengan tipe 1 dan tipe 2 diabetes mellitus. Vitamin B12 atau cobalamin adalah vitamin yang larut air yang memainkan peran yang sangat penting dalam sintesis DNA, hemopoesis optimal dan fungsi neurologis. Gambaran klinis defisiensi vitamin B12 karenanya, adalah sebagian besar dari fitur disfungsi hematologis dan neurokognitif . Vitamin B12 merupakan mikronutrien penting yang diperlukan dalam sintesis DNA , perbaikan sel dan haemopoesis biasa bersama-sama dengan mikronutrien lain seperti folat dan besi.
Vitamin B12 digunakan melalui mediasi dua jalur enzimatik utama yaitu proses metilasi
homosistein menjadi metionin dan konversi metilmalonil koenzim A ( CoA ) untuk suksinil CoA. Vitamin B12 sebagai co - faktor memfasilitasi metilasi homosistein menjadi metionin yang kemudian diaktifkan ke S - adenosyl - metionin yang menyumbangkan gugus metil untuk metil akseptor seperti myelin , neurotransmiter dan membran fosfolipid . Kekurangan vitamin B12 metabolik yang signifikan akan berakibat terganggunya proses metilasi dan akumulasi intraseluler dan serum homosistein . Hyperhomocysteinemia telah terbukti memiliki efek yang berpotensi toksik pada neuron dan endotel vaskular . Reaksi ini juga penting dalam konversi folat diet ( metil - tetrahydrofolate ) ke level aktif metabolisme bentuk , tetrahydrofolate . Vitamin B12 juga penting dalam sintesis neurotransmitter monoamina atau seperti serotonin dan dopamin . Kekurangan vitamin B12 klinis dan biokimia sangat umum di antara pasien dengan kedua tipe 1 dan 2 DM . Penggunaan metformin telah tegas menunjukkan sebagai faktor utama yang terkait dengan defisiensi vitamin B12 antara pasien dengan DMT2 . Studi menilai pasien diabetes tipe 2 pada metformin telah melaporkan prevalensi defisiensi vitamin B12 berkisar dari 5,8 % menjadi 33 % . Metformin digunakan untuk menurunkan efek glikemik, tetapi juga telah lama telah terbukti menurunkan kadar vitamin B12 . Risiko metformin terkait kekurangan vitamin B12 sangat dipengaruhi oleh bertambahnya usia , dosis metformin dan durasi penggunaan . DM tipe 1 ( T1DM ) adalah kondisi auto imun yang dihasilkan dari kerusakan auto imun dari sel mensekresi insulin beta pankreas . Defisiensi vitamin B12 karena anemia pernisiosa ,
akibat gastritis autoimun kronis , sering terjadi antara pasien dengan T1DM . Autoimunitas pada lambung seperti PCA dan AIF khususnya di antara pasien dengan GAD T1DM - 65 dan antibodi tiroid peroksidase meningkatkan kecenderungan kekurangan vitamin B12 . Semua pasien kekurangan vitamin B12 harus menerima terapi penggantian dengan baik lisan atau parenteral vitamin B12 . Terapi penggantian dengan intramuscular harian atau oral vitamin B12 dalam dosis 100μg selama seminggu dan kemudian bulanan cukup memuaskan. Penelitian besar pada skrining untuk defisiensi vitamin B12 telah dirancang, suplemen vitamin B12 dan suplemen dosis optimal antara tipe 1 dan tipe 2 pasien diabetes dijamin untuk membantu formulasi panduan pedoman dalam perawatan klinis diabetes . Skrining tahunan untuk defisiensi vitamin B12 dengan menggunakan metode yang lebih sensitif seperti homosistein serum dan konsentrasi asam methylmalonic ( dalam pengaturan klinis di mana mereka dapat diakses ) dan suplemen harus diadopsi di antara pasien diabetes dengan faktor risiko tertentu dari kekurangan vitamin B12 .
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