Characteristics of Vitamin B12 Deficiency in Adult Chinese Patients with Type 2 Diabetes and the Implication of Metformin

Abstract

Vitamin B12 deficiency remains a worldwide health problem in the 21st century. The advent of metabolite assays in the last few decades further expands the population with subclinical or tissue deficiency and thus the magnitude of the problem. The increasing recognition of its association with the use of metformin raises another controversy for clinicians regarding detection and treatment of vitamin B12 deficiency. Since the clinical use of metformin in 1957, malabsorption of vitamin B12 in diabetic patients treated with metformin was first noted in 1969 (Berchtold et al., 1969). Subsequent studies revealed both short-term and longterm use of metformin induces malabsorption of vitamin B12 and causes decreased serum vitamin B12 concentrations in 10% to 30% of diabetic patients (Tomkin et al., 1971; Bauman et al., 2000; Wulffele el al., 2003; Hermann et al., 2004). A randomized placebo controlled Dutch trial recently reconfirmed this finding and demonstrated treatment with metformin for a mean of 4.3 years resulted not only in a 19% persistent and progressive reduction of mean serum vitamin B12 concentrations, but also raised serum homocysteine concentrations (de Jager et al., 2010). Other case-control and cross-sectional studies identified duration and dosage of metformin use as risk factors for vitamin B12 deficiency (Ting et al., 2006). It is believed that if individuals with type 2 diabetes receiving metformin develop low serum vitamin B12 concentrations, a stage of asymptomatic tissue deficiency, would eventually progress to symptomatic clinical deficiency, as evidenced by reports of megaloblastic anaemia caused by metformin-related vitamin B12 malabsorption, unless they are duly treated (Gilligan, 2002; Filioussi et al., 2003; Liu et al., 2006). Metformin is now extensively used as the first line pharmacological agent for glycaemic control especially following the favourable results of the United Kingdom Prospective Diabetes Study (UKPDS 34) in 1998. This coupled with the rising incidence of type 2 diabetes in many parts of the world constitutes a driving force for relevant parties to make appropriate recommendations or guidelines concerning the detection and treatment of vitamin B12 deficiency among diabetic patients on metformin. Although the haematological and neurological manifestations of overt or clinical vitamin B12 deficiency are easy to diagnose, they are often overlooked and attributed to diabetic complications or aging among diabetic patients.