Chronic Passive Heating in Individuals With T2DM

The Effect of Chronic Passive Heating on Insulin Sensitivity and Cardiovascular Function in People With Type 2 Diabetes Mellitus: A Pre- and Post-test Trial

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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes
• Intervention / Treatment: Procedure: Passive heating

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Hampshire
    • Portsmouth, Hampshire, United Kingdom, PO1 2ER
      • Department of Sport and Exercise Science

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female (post-menopausal) aged 35 years or above.
• Diagnosed with T2DM as defined by the WHO (≥48 mmol/mol).
• Participant is willing and able to give informed consent for participation in the study.
• Participant is 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 mmHg)
• Taking any medication which may interfere with data interpretation or safety
• Who have had a myocardial infarction or cerebro-vascular event
• Any cardiac abnormalities which restrict hard exercise
• Current smokers or who have stopped within 3 months
• Participant is unable to understand and/or fully cooperate with the study protocol
• Any other serious medical condition which would interfere with data interpretation or safety will be excluded from participation.
• Skin ulcerations
• Eczema
• Pre-existing postural hypertension
• Existing cardiac diseases (identified during screening)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Passive heating; 8-12 x1 h water immersion (to the clavicle, @40 °C, rectal temperature ~38.5 °C and <39 °C) sessions over a period of 14 days.	Procedure: Passive heating; 8-12 x1 h water immersion (to the clavicle, @40 °C, rectal temperature ~38.5 °C and <39 °C) sessions over a period of 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity	Does chronic passive heating improve insulin sensitivity? Calculated using the QUICKI for fasting and Gutt for post-prandial, with glucose and insulin concentrations. A higher value means they have better insulin sensitivity.	Change from pre (day 1) - post 8-12 days of 1 hour of passive heating

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Glucose Concentration	Does chronic passive heating reduce plasma [glucose]?	pre - post following 8-12 days of 1 hour of passive heating
Plasma eHSP70 Concentration	Does chronic passive heating increase plasma [eHSP70]?	pre - post following 8-12 days of 1 hour of passive heating
Plasma IL-6 Concentration	Does chronic passive heating reduce plasma [IL-6]?	pre - post following 8-12 days of 1 hour of passive heating
Plasma IL-10 Concentration	Does chronic passive heating increase plasma [IL-10]?	pre - post following 8-12 days of 1 hour of passive heating
Resting Metabolic Rate	Does chronic passive heating reduce plasma resting metabolic rate?	pre - post following 8-12 days of 1 hour of passive heating
Flow Mediated Dilation	Does chronic passive heating improve macrovascular function? Measured via ultrasound	pre - post following 8-12 days of 1 hour of passive heating
Cutaneous Vascular Conductance	Does chronic passive heating improve microvascular function? Assessed via iontophoresis or the forearm with ACh and Insulin, Area under the curve is the unit. (CVC = skin flux/MAP; flux/mmHg-1)	pre - post following 8-12 days of 1 hour of passive heating
Resting Heart Rate	Does chronic passive heating reduce resting heart rate?	pre - post following 8-12 days of 1 hour of passive heating
Stroke Volume Index	Does chronic passive heating increase stroke volume? Measured noninvasively via thoracic impedance	pre - post following 8-12 days of 1 hour of passive heating
Cardiac Output Index	Does chronic passive heating increase cardiac output? Measured noninvasively via thoracic impedance. L/min/m2 is the unit.	pre - post following 8-12 days of 1 hour of passive heating
TNF-alpha	TNF-alpha	Pre- v post 8-12 1 h hot water immersions
Butyric Acid	Butyric acid	Pre- v post 8-12 1 h hot water immersions
SBP	Systolic blood pressure	Pre- v post 8-12 1 h hot water immersions
DBP	Diastolic blood pressure	Pre- v post 8-12 1 h hot water immersions
MAP	Mean arterial pressure	Pre- v post 8-12 1 h hot water immersions
NOX	Nitrates + nitrites	Pre- v post 8-12 1 h hot water immersions

Collaborators and Investigators

• Sponsor: University of Portsmouth
• Collaborators: Portsmouth Hospitals NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to release IPD, until all avenues of further funding have been exhausted.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No