Folate and vitamin B12 status is associated with insulin resistance and metabolic syndrome in morbid obesity

Abstract

Background: Low vitamin B12 and high folate during pregnancy are associated with visceral obesity and insulin resistance in offspring. In the general population, high folate exacerbates the increase of methylmalonic acid, a marker of vitamin B12 deficiency. However, the influence of vitamin B12 and folate and their related markers on insulin resistance and metabolic syndrome remains unknown in severe obesity.

Aim: To evaluate the influence of vitamin B12 and folate on HOMA-IR and components of metabolic syndrome in severe obesity.

Methods: 278 consecutive obese patients were assessed prospectively for HOMA-IR, red blood cell (RBC) folates, homocysteine and methylmalonic acid. We compared the associations with the components of metabolic syndrome during the preoperative multidisciplinary evaluation (period-1) and before bariatric surgery (period-2).

Results: The HOMA-IR was higher in patients with highest tertile of RBC and either lowest tertile of plasma B12 or highest tertile of MMA (p < 0.034 and 0.011, respectively). Lg HOMA-IR was negatively correlated with Lg homocysteine (p < 0.0001) and positively correlated with Lg serum folate (p < 0.001). The independent predictors for HOMA-IR at period 2 were either BMI and homocysteine (model 1 without serum folate, p = 0.010 and p = 0.002, respectively) or BMI and MMA (model 2 without homocysteine, p = 0.030 and p = 0.004, respectively). Age and RBC folate remained independently associated with the number of metabolic syndrome components (p = 0.006 and 0.020, respectively).

Conclusions: RBC folate, homocysteine, and MMA predict HOMA-IR in severe obesity. Our findings challenge the benefit of folate fortified food in severe obesity, in particular in patients with a deficit of vitamin B12. The cohort study was registered at clinicaltrials.gov as NCT02663388.

Keywords: Folates; HOMA-IR; Obesity.