Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES

<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12_low/high and MMA_low/high (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA_highB12_high) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA_lowB12_low, MMA_lowB12_high, MMA_highB12_low, and MMA_highB12_high groups were1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>

Cobalamin Intake and Related Biomarkers: Examining Associations With Mortality Risk Among Adults With Type 2 Diabetes in NHANES

<a><b>Objective</b></a> Despite periodical monitoring of cobalamin (vitamin B12) in metformin-treated diabetic patients is recommended, the cobalamin-associated mortality benefits or risks remains unclear. We investigated the association between cobalamin intake and related biomarkers and mortality risk in diabetic adults using metformin or not. <p><b>Methods</b> This study included 3,277 adults with type 2 diabetes from NHANES and followed up until December 31, 2015. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% CIs for mortality risk.</p> <p><b>Results </b>Among 3,277 participants, 865 all-cause deaths occurred during a median follow-up of 7.02 years. There was no robust relationship between all-cause mortality and serum cobalamin, intakes from foods or cobalamin supplements regardless of metformin treatment (each p ≥0.120). The doubling of methylmalonic acid (MMA, a cobalamin-deficiency marker) was significantly associated with higher all-cause (HR 1.31 95%CI 1.18–1.45, p <0.001) and cardiac mortality (HR 1.38 95%CI 1.14–1.67, p =0.001). Cobalamin sensitivity was assessed by the combination of binary B12_low/high and MMA_low/high (cutoff values: cobalamin 400 pg/ml and MMA 250nmol/L). Patients with decreased cobalamin sensitivity (MMA_highB12_high) had the highest mortality risk. The multivariable-adjusted HRs (95%CIs) of all-cause mortality in MMA_lowB12_low, MMA_lowB12_high, MMA_highB12_low, and MMA_highB12_high groups were1.00 (reference), 0.98 (0.75–1.28), 1.49 (1.16–1.92), and 1.96 (1.38–2.78), respectively. That association was especially significant in metformin nonusers.</p> <p><b>Conclusions</b> Serum and dietary cobalamin were not associated with reduced mortality. Decreased cobalamin sensitivity was significantly associated with all-cause and cardiac mortality, particularly among metformin nonusers.</p>

Cobalamin deficiency and pathogenesis of neurological disorders

The brief review deals with the specific value of B vitamins for the nervous system, the mechanisms of transport and metabolic functions of cobalamin, pathogenetic theories related to vitamin B12 deficiency such as canonical biochemical theory and the theory of dysregulation of cytokines and growth factors; the hyperhomocysteinemic component of cerebral small vessel disease as one of the most common types of degenerative disorders of the central nervous system has been mentioned; the types of disorders associated with cobalamin deficiency that underlie its neurological manifestations have been described.

CLINICOETIOLOGICAL EVALUATION OF THE PATIENTS OF MACROCYTIC ANEMIA PRESENTING AT A TERTIARY CARE CENTRE IN KUMAON REGION OF UTRRAKHAND

INTRODUCTION: Macrocytosis is common in various clinical settings and it is found in approximately 1.7– 3.6% of people admitted for care for any cause [1, 2, 3]. Macrocytic anemia is generally classified as megaloblastic or nonmegaloblastic anemia. The causes of macrocytosis fall into two groups: (a) deficiency of vitamin B12 (cobalamin) or folate (or rarely abnormalities of their metabolism) in which the bone marrow is megaloblastic and (b) other causes,in which the bone marrow is usually normoblastic.A high level of suspicion,proper elicitation of the history and thorough examination and investigation of the patient helps in the diagnosis of macrocytic anemia. AIM AND OBJECTIVES: To evaluate the etiology of macrocytic anemia at a tertiary care centre. To determine the etiology of macrocytic anemia.To evaluate clinical manifestations associated with macrocytic anemia. MATERIAL AND METHOD: This 21 month Cross sectional observational study was carried out in OPD/IPD Department of Medicine, Government Medical College Haldwani (Uttarakhand). Full clinical examination and information regarding alcohol intake, dietary habit, drug intake, thyroid disorder and other comorbid illnesses was obtained.All patients were investigated with a completeHaemogramLiver function tests Serum TSH fasting vitamin B12 was measured Ultrasound as and when required. RESULT: In this study106 patients were taken 58 (45.3% ) were male and 48(54.7%) were females. Mean age was 44.83+16.85 years.Hemoglobin and MCV was in the range of 6.42 ± 2.09,(108.24 ± 7.10) respectively .The majority of patient,28 (52.83%) had vit B12 level in the range of 101 – 200 pg/ml,The majority of patients,44 (41.1%) had LDH level in the range of 281 – 1000 IU/L . CONCLUSION: In this study, there was a preponderance of young people.Vegetarians were most susceptible to MA especially cobalamin deficiency. Nutritional deficiency was the most common cause of MA, followed by alcohol and alcoholic liver disease.Data regarding the magnitude of the problem in different parts of India and the factors that might influence its incidence were lacking. Macrocytic anemia must be considered in the differential diagnosis of patients presenting with pyrexia of unknown origin,mild icterus or pancytopenia.

Important reminder: nitrous oxide (N2O) as a cause of functional vitamin B12 deficiency

A 32-year-old woman who misused multiple substances, including nitrous oxide (N2O), sought medical advice after she subacutely developed bilateral lower extremity weakness without a sensory level but with ataxia—her significant other developed similar symptoms with vitamin B12 deficiency due to N2O intake. Laboratory results revealed macrocytic anaemia despite normal B12 and folate levels, with serum markers pointing towards functional cobalamin deficiency. Spinal MRIs and cerebrospinal fluid analysis were unremarkable. Our patient was treated with vitamin B12 supplementation with an encouraging response.