Prevalence of Vitamin B-12 Deficiency in Type 2 Diabetes Mellitus Patients

Introduction

Type 2 diabetes mellitus (T2DM) is marked by the dysregulation of carbohydrate, lipid, and protein metabolism, stemming from compromised insulin secretion, insulin resistance, or a combination of both.¹ Among the three primary diabetes types, T2DM is significantly more prevalent, constituting over 90% of all cases, surpassing the occurrences of both type 1 diabetes mellitus (T1DM) and gestational diabetes. In recent decades, our understanding of the development and advancement of T2DM has undergone swift evolution. Despite the heightened susceptibility of numerous diabetic patients to vitamin B-12 deficiency, this potential co-morbidity is frequently overlooked.² For instance, a significant number of diabetic patients are prescribed metformin. This medication leads to a reduction in serum vitamin B-12 levels and is linked to the occurrence of vitamin B-12 deficiency.³ Furthermore, nearly half of diabetic patients are aged 60 years or older, and within this age bracket, the prevalence of metabolically confirmed B-12 deficiency varies from 12% to 23%. Given these risk factors, identifying majority of individuals with diabetes could assist in determining whether primary care physicians should contemplate screening for B-12 deficiency among diabetic patients.⁴ According to the screening criteria set by World Health Organization, it is deemed appropriate to screen for a condition if it represents a substantial health concern. Tests are available to identify the condition in its early, treatable stage.⁵ Neuropathy is a potential health issue associated with Vitamin B-12 deficiency, with nearly 30% of diabetic individuals aged 40 years and above experiencing diminished sensation in their feet.

In most situations, diabetic neuropathy symptoms overlap with paresthesia, impaired vibration sense, and impaired proprioception. Hence, B-12 deficiency-induced nerve damage may confuse or contribute to diabetic peripheral neuropathy. They identify the correct aetiology of neuropathy because simple vitamin B-12 replacement may reverse neurologic symptoms improperly ascribed to hyperglycemia.⁷ Vitamin B-12 deficiency is conservatively diagnosed by laboratory findings of low serum vitamin B-12 levels, typically in megaloblastic anaemia. However, subclinical B-12 deficiency may often be present with normal serum B-12 levels and hematologic parameters. The present study aimed to find the prevalence of vitamin B-12 deficiency in patients with T2DM and study the association of age, gender, body mass index, diet, glycaemic control, metformin use, and alcoholism in T2DM patients.

Materials and Methods

A hospital-based cross-sectional study was undertaken at the Diabetes Centre of a Medical Research Centre. A total of 105 T2DM patients were enrolled in the study over a 12 month period, from September 2021 to August 2022. Complete clinical history, physical examination, and routine investigations were conducted. All the findings were recorded in a Proforma. Fasting blood samples were withdrawn, and vitamin B-12 was estimated using the electrochemiluminescence immunoassay method (ECLIA). The serum values of 200 pg/mL were defined as vitamin B-12 deficiency. The Chi-square test and t-test were used for statistical analysis.

Results

A total of 105 patients were enrolled in the study. The essential clinical features, viz. age, body mass index (BMI), vitamin B-12, and HbA1C, are represented in Table 1.

The overall prevalence of vitamin B-12 deficiency was 22.85% (n=24). We noticed a gender-specific prevalence in males (27.39%) and females (12.50%) with X2=2.80. Figure 1 shows the categorical representation of the age groups with respective T2DM and vitamin B-12 deficiency.

The highest prevalence rate was recorded in the age group between 40 to 49 years (31.57%), P <0.742. The association between vitamin B-12 and BMI was noted highest (38.46%) in BMI 25 to 29.99 kg/m2 as compared to BMI <24.99 (13.46%) and BMI >30 (14.28%). The association was found to be significant (P <0.014). Similarly, metformin and vitamin B-12 were studied to check the improvement in the patients with T2DM and vitamin B-12 deficiency; the results are represented in Figure 2.

The diet pattern and vitamin B-12 deficiency were recorded. The vegetarian group was 26.2%, and the non-vegetarian was 18.18% (P <0.337). The association of vitamin B-12 deficiency was noted in alcoholics (33.33%) and non-alcoholics (19.75%) and was found to be non-significant (P=0.160). Similarly, no association was observed in the glycemic (14.28%) (HbA1c) and vitamin B-12 deficiency (23.46%) group (P <0.495).

Discussion

This is the first cross-sectional study conducted at a single tertiary centre in North Karnataka, specifically designed to identify the prevalence of B-12 deficiency in patients with type 2 diabetes.⁵ Our cohort identified 22.85% of type 2 diabetic patients with B-12 deficiency. However, it is possible to infer the prevalence of B-12 deficiency in diabetic patients from previous studies.⁶ While the clinical implications of the 22.85% prevalence of B-12 deficiency in the diabetic population remain uncertain, it is important to investigate the potential role of B-12 deficiency as a contributor to peripheral neuropathy in this group. Nervous system damage, ranging from mild to severe, affects sixty to seventy percent of diabetic patients, with peripheral neuropathy being the most prevalent form.^7-9 The highest prevalence was recorded in the age group between 40 to 49 years (31.57%). This study found a relative increase in the prevalence of B-12 deficiency and suggested the possibility that a portion of peripheral neuropathy cases in diabetic patients could be linked to insufficient B-12 levels. Numerous studies have indicated that the supplementation of vitamin B-12 has been effective in ameliorating both somatic and autonomic symptoms associated with diabetic neuropathy.¹⁰

Vegetarians who find it challenging to get enough vitamin B-12 in their diets may need vitamin B-12 tablets for life. There are two types of vitamin B-12 injections: Cyanocobalamin and Hydroxycobalamin. Cyanocobalamin must be given once a month, whereas hydroxycobalamin can be given every three months. Good sources of vitamin B-12 include meat, salmon, eggs, milk and other dairy products.

The cross-sectional design of our study constrains us from characterizing a population. Consequently, the insights pertinent to our secondary objectives were confined to establishing associations. Nonetheless, the main objective was to establish the prevalence of B-12 deficiency within the diabetic population, and a cross-sectional study was deemed appropriate for this purpose. A cross-sectional study is appropriate.^10-12 Further investigations will be required to establish causation. Furthermore, the debate revolves around the exclusive reliance on biochemical markers to define B-12 deficiency. Although heightened levels of methylmalonic acid have been associated with clinical indications of B-12 deficiency, our evaluation did not include an assessment for signs of megaloblastic anemia or neuropathic diseases. Hence, the clinical significance of the metabolically confirmed B-12 deficiency in our patient group remains uncertain. Lastly, individuals identified as B-12 deficient in our study were not subjected to follow-up examinations to evaluate the impact of supplemental vitamin B-12 treatment or to gauge the normalization of B-12 and methylmalonic acid levels. Such follow-up assessments could have provided valuable confirmation of the diagnosis of vitamin B-12 deficiency.

Conclusion

The high prevalence of B-12 deficiency among diabetic patients, estimated at 22.8%, raises a pertinent question as to whether such deficiency should be identified in all patients. Nonetheless, the therapeutic outcomes of asymptomatic B-12 deficiency have not yet been determined, thus rendering the benefits of such treatment unknown. Primary care physicians should be aware that as many as one-fifth of their diabetic patients may experience B-12 deficiency. They should take this into account when addressing co-morbidities, especially neuropathy. Additional research is required to ascertain whether screening and subsequent treatment can prevent the onset of peripheral neuropathy in individuals with type 2 diabetes before advocating for universal screening. Finally, empirical multi-vitamin therapy warrants exploration as a potential approach to mitigating B-12 deficiency among the type 2 diabetes population.

Conflict of interest

Nil

Financial support

Nil