Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04858321 |
| Other study ID # |
006 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 24, 2021 |
| Est. completion date |
December 19, 2022 |
Study information
| Verified date |
April 2023 |
| Source |
University of Portsmouth |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Type 2 diabetes mellitus (T2DM) is a metabolic condition characterized by chronic
hyperglycemia and progressive insulin resistance, which progressively lead to macro- and
microvascular damage and subsequent impairments in blood pressure (BP) control. Therapeutic
approaches to manage T2DM focus on improving glycaemic control and BP and include
pharmaceutical treatments (e.g. Metformin and insulin), physical activity and exercise, and
calorie restriction. However, pharmaceutical interventions can be expensive and are
associated with low adherence. Although exercise and diet programs have been shown to be
effective, like pharmaceutical interventions, they often have poor adherence in people with
T2DM. With the number of people with T2DM (464 million) continuing to rise and expected to
reach 700 million by 2045, the costs associated with the clinical management of this
condition are likely to become unsustainable. There is, therefore, a need to explore the
potential of alternative interventions. In particular, interventions which may be cheaper
than clinical management and have better adherence than exercise, and hypoglycemic agents, to
improve glycemic control and deleterious cardiovascular manifestations of this condition.
Passive heating may be one such intervention with therapeutic potential.
Description:
Current estimates suggest 422 million people worldwide live with a form of diabetes, of which
~ 90% have type 2 diabetes mellitus (T2DM). The total direct and indirect cost of care for
individuals with diabetes in the UK is £23.7 billion, equating to ~ 20% of the annual NHS
budget, this figure is expected to rise to ~£39.8 billion by the year 2035. Approximately
85-90% of cases of T2DM arise from a poor lifestyle and obesity, with the remaining 10-15%
resulting from genetic predispositions. Current interventions include pharmaceutical
treatments, exercise and calorie restrictive diets, which aim to improve glycaemic control.
However, pharmaceutical interventions carry a high financial cost, while exercise and diet
programmes have a low adherence rate in individuals with T2DM. With the prevalence of T2DM
continuing to increase, the costs associated with the clinical care of these individuals are
likely to become unsustainable. Simple, inexpensive interventions to improve the clinical
profile of this group are therefore needed.
One emerging potential therapy to improve glucose homoeostasis is passive heating.
Preliminary evidence suggests passive heating may have beneficial effects for metabolic
health in animal models and in humans. In 1999, the use of hot tubs (38-41°C , 30 mins / day
for 3 weeks) was shown to reduce fasting plasma glucose concentrations by ~14% (1.3 mmol.L-1)
and decrease HbA1c by ~10-11 mmol/mol in 8 individuals with T2DM. Given the rate of turnover
in haemoglobin this reduction is surprising as the treatment period was run over 3 weeks and
the total haemoglobin turnover takes ~115 days. While more recent work has been conducted
into the effects of a single bout of passive heating in healthy adults and individuals with
T2DM (including ourselves, under review), none have been done on chronic heating since
Hooper. Hooper postulated that an increase in skeletal muscle blood flow may be responsible
for this increased glucose clearance, citing evidence that this can modulate insulin mediated
glucose uptake. Other mechanisms have also been purported, but have yet to be elucidated,
including; increased insulin sensitivity, altered inflammatory response, activation of heat
shock proteins (HSP), altered gut microbiome and butyrate. Repeated passive heating results
in transient increases in deep body temperature and may improve glucose homeostasis via
similar mechanisms to exercise.
Regular aerobic exercise also improves macro- and microvascular function, muscle oxygenation,
autonomic function, cardiorespiratory fitness, lung function and delays age related muscle
loss. Acute exercise studies show that insulin sensitivity after 1h of moderate exercise does
not change, however, insulin sensitivity appears to be improved following bouts longer than
an hour or performed at greater intensity. Increases in insulin sensitivity have a
curvilinear relationship with energy expenditure and could also be due to greater HSP
expression. However, it is unrealistic for people with T2DM to perform this level of
activity. Passive heating may be one supplemental exercise mimetic to augment improvements in
insulin sensitivity, cardiorespiratory fitness and muscle strength, and function.
The investigators recently provided evidence that acute passive heating in poeple with T2DM
(currently under review for publication) is well tolerated and increases extracellualr
[HSP70], and energy expenditure, and reduce diabstolic blood pressure. There is a growing
body of evdience that suggests passive heating may improve many facets of human physiology,
however, the mechanisms that underpin these benefits have yet to be established and future
research needs to explore these further.
