The effects of nitrate on brown fat fraction and activation in older adults with type 2 diabetes: A randomised, double-blind, placebo-controlled crossover trial.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterised by chronic hyperglycaemia, whilst obesity is a major risk factor which increases morbidity and mortality. Treatments that alter white adipose tissue to express a metabolically active brown adipose phenotype in rats may offer adjunct treatment in people with T2DM. Aim: To investigate whether inorganic nitrate supplementation from beetroot juice (BJ) alters brown adipose tissue (BAT) fat fraction and activation in humans. Methods: Thirteen older adults with T2DM (glycated haemoglobin [HbA1c]: 58±13 mmol·mol⁻¹; body mass index: 29.1±3.1 kg·m⁻²) completed a double-blind, randomised, balanced, placebo-controlled crossover study. Outcome measures (including BAT fat fraction; activation; plasma [nitrate] and [nitrite]) were assessed before and after 14 days of 140 mL·day⁻¹ BJ containing inorganic nitrate (~12.4 mmol·L⁻¹) or a placebo (~0.1 mmol·L⁻¹). Magnetic resonance imaging (MRI) and infrared thermography (IRT) were performed to image supraclavicular BAT following a rested cooling protocol, consisting of 60 minutes’ exposure via a cold-water (8.1±1.2°C) perfused jacket. Respiratory parameters, including respiratory exchange ratio (RER) and mean skin temperature, were measured during the cooling protocol to confirm participants were not shivering. Results: BJ significantly increased venous plasma [nitrate] and [nitrite] versus placebo (P<0.001) but did not affect BAT fat fraction (P=0.650) or activation (P=0.152). Cooling significantly reduced mean skin temperature in BJ (−0.8±0.7°C) and placebo (−0.6±0.6°C) (P<0.001), and RER remained representative of non-shivering thermogenesis throughout (0.88±0.05 a.u.). Conclusion: Fourteen days of nitrate supplementation did not increase BAT fat fraction or activation in older adults with T2DM.