Taurine and Nitrate Supplementation on Thermoregulatory in T2DM

Anthropogenic warming is increasing the likelihood of extreme heat events. These events, defined as periods of abnormally hot weather lasting several consecutive days, are predicted to rise in both temperature and frequency . Extreme heat increases global mortality with people suffering from chronic conditions being especially vulnerable. A growing body of evidence suggests excess mortality may partly result from increased cardiovascular strain. This is particularly relevant for people with Type 2 Diabetes Mellitus (T2DM) who have both an elevated cardiovascular mortality risk independent of heat stress and a compromised ability to regulate their body temperature during heat stress . This likely explains the increase in hospitalisation and mortality in people with T2DM typically observed during heat waves.

People with T2DM are characterised by progressive insulin resistance over a sustained period, reducing the body's ability to effectively metabolise glucose leading to chronic hyperglycaemia. Consequences of chronic hyperglycaemia are micro and macrovascular dysfunction which lead to an increase in cardiovascular disease (CVD) risk and mortality. Heat stress also produces greater heat strain in people with T2DM compared to the rest of the population . This is potentially derived through an attenuated thermoregulatory response to heat stress in people with T2DM, reducing heat dissipation due to impaired sweating, endothelial and cardiac function , skin blood flow and nitric oxide (NO) bioavailability. These factors increase the risk of heat-related illness. Importantly, advanced heat illness is driven in part by systemic inflammation which highlights the need for targeted interventions that can support endogenous anti inflammatory defences in individual with T2DM during exposure to high heat events.

One such intervention may be supplementation with taurine, an amino acid. Taurine shows promise as a thermoregulatory aid during extreme heat, as it promotes faster onset of sweating, greater sweat loss, reduced heat accumulation and enhanced evaporative cooling in healthy populations. As an antioxidant, taurine may also improve inflammation and redox balance by increasing NO bioavailability via increased stability of tetrahydrobiopterin (BH4) in NO synthase and reduced NO scavenging. Beetroot is another antioxidant rich supplement that also increases the bioavailability of NO via the stepwise reduction of nitrate to nitrite and subsequently to NO. Ultimately, this will improve macro and microvascular function in people with chronic disease and may help with thermoregulation during extreme heat. Taurine and nitrate are well tolerated even at high doses in long term clinical trials, whilst taurine's and nitrates capacity to stabilise mitochondrial function provides a biologically plausible means of reducing heat induced oxidative stress.

Taurine and nitrate may therefore offer safe, low-cost interventions to reduce oxidative stress and inflammation, to enhance blood flow and improve evaporative heat loss during heat stress. We hypothesise that taurine and nitrate supplementation will improve the sweating response and reduce the rate of core temperature rise compared to placebo in people with T2DM after exercise in acute heat event. Secondary hypotheses are that the supplements will improve: (1) macro and micro vascular function (2), skin blood flow and (3) redox balance.

• Local sweat rate: [Time frame: through study completion, average 1 week]
• Rectal temperature Trec [Time frame: through study completion, average 1 week]
• Skin temperature: Tsk [Time frame: through study completion, average 1 week]
• Mean Body temperature [Time frame: through study completion, average 1 week]
• Cardiac output [Time frame: through study completion, average 1 week]
• Macrovascular function [Time frame: Baseline and immediately post heating (3 hour post-baseline)]
• Microvascular function [Time frame: Baseline and immediately post heating (3 hour post-baseline)]
• Heart rate [Time frame: through study completion, average 1 week]
• Biomarkers [Time frame: Baseline and immediately post heating (3 hour post-baseline)]
• Muscle peripheral oxygenation [Time frame: through study completion, average 1 week]
• Hydration levels: [Time frame: Baseline and immediately post heating (3 hour post-baseline)]
• Thermal sensation [Time frame: through study completion, average 1 week]