Taurine and Nitrate Supplementation on Thermoregulatory in T2DM

The Effect of Taurine and Nitrate Supplementation on Thermoregulatory Responses in People With Type 2 Diabetes Mellitus.

Anthropogenic warming is increasing the frequency and intensity of extreme heat events. Elevated temperatures raise the risk of mortality and hospital admissions, particularly among people with chronic illnesses such as type 2 diabetes mellitus (T2DM). Globally, around 530 million people live with T2DM , and in the United Kingdom nearly six million are affected, creating a substantial population vulnerable to heat related illness.

People with T2DM are at heightened risk of cardiovascular disease, which can impair cardiac output, a key component of thermoregulation, as it supports increased skin blood flow for heat dissipation. T2DM also attenuates eccrine sweat gland function, peripheral vasodilation, reducing evaporative cooling capacity. These physiological constraints highlight the need for effective strategies to improve heat tolerance in this group.

Recent evidence shows that exogenous taurine supplementation can enhance sweating in healthy individuals, potentially improving heat loss. This study will examine whether acute taurine supplementation, alone or combined with beetroot, can limit rises in core temperature in people with T2DM during an acute extreme heat exposure.

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.

Inclusion Criteria:

• Male or female (post-menopausal) aged 35 years or above.
• Diagnosed with T2DM as defined by the WHO (HbA1c ≥48 mmol/mol).
• Willing and able to give informed consent for participation in the study.
• Able to understand and fully cooperate with the study protocol.

Exclusion Criteria:

• Severe peripheral neuropathy (to the point to which they cannot sense temperature)
• Uncontrolled hypertension (≥180 systolic / 100 diastolic)
• Significant renal impairment (eGFR < 30)
• Diagnosed anhidrosis
• Taking any medication which may interfere with data interpretation or safety
• Who have had a myocardial infarction or cerebrovascular event
• Any cardiac abnormalities which restrict hard exercise
• Any allergies to the ingredients used in the supplements
• BMI >40
• Current smokers or who have stopped within 3 months
• Unable to understand and/or fully cooperate with the study protocol
• Any serious medical condition which would interfere with data interpretation or safety will be excluded from participation.
• Open wounds
• Skin ulcerations (that would interfere with data collection and interpretation or safety)
• Eczema (that would interfere with data collection and interpretation or safety)
• Pre-existing postural hypertension
• Existing cardiac diseases (identified during screening)
• Currently heat acclimated (repeated exposure to hot environments ≥3 sessions in the last 14-21 days)
• Prior heat related illness