Acute Effects of Cold-induced Shivering on 24-hour the Glucose Profile in Metabolically Compromised Populations

NCT05576025 | Completed

• 2 other identifiers: NL.81053.068.22NL.81053.068.22 / METC 22-026
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 Diabetes Mellitus (T2DM) and its associated comorbidities pose a major health concern worldwide. Although lifestyle strategies, such as exercise and diet-induced weight loss are effective interventions to counteract the development and progression of the disease, its prevalence continues to increase. Therefore, alternative therapeutic strategies are warranted. One such method, which has increasingly been gaining attention, is cold exposure. Previously, investigators have shown that exposing T2DM patients to mild cold (14-16 oC) for 6 hours per day for 10 consecutive days enhanced their insulin sensitivity by \~43%. This remarkable improvement in insulin sensitivity was accompanied by robust GLUT4 translocation in the skeletal muscle of participants, which likely mediated the improvements in insulin-stimulated glucose uptake. Follow-up research suggested that a certain degree of muscle activation/shivering appears to be a prerequisite for the cold-induced enhancement in skeletal muscle insulin-stimulated glucose uptake. In humans however, very little information is available about the effects of shivering on glucose metabolism, especially in metabolically compromised individuals. Therefore, in this study, the aim to investigate the acute effects of (different intensities of) shivering on 24-hour glucose profiles in pre-diabetic individuals as well as in T2DM patients. For that purpose, a focus will be placed on clinically relevant glycaemic parameters by means of continuous glucose monitoring, which is increasingly being used in T2DM management and prevention.

Conditions

Type 2 Diabetes Mellitus; Pre-diabetes

Keywords

Lifestyle intervention; Cold exposure; Prevention; Treatment; Metabolic health; Glucose homeostasis

Outcome Measures

Primary Outcomes (1)

• 24-hour area under the curve (AUC) for glucose

  24-hour AUC for glucose expressed in mmol/L x min

  24-hour period before and after each shivering session

Other Outcomes (6)

• Average 24-hour interstitial glucose concentration

  24-hour period before and after cold exposures and 72-hour periods before/after cold exposures

• Time above range (TAR)

  Over a period of 72 hours before and after the two cold exposures

• Glucose variability

  72-hour period before and after each cold exposure and following each meal

Study Arms (2)

Period 1: Shivering intensity 1

EXPERIMENTAL

During Arm 1 of the study participants will undergo the first cold exposure at either mild or moderate shivering intensity (depending on the randomisation).

Other: Lifestyle intervention (cold exposure)

Period 2: Shivering intensity 2

EXPERIMENTAL

During Arm 2 of the study participants will undergo the second cold exposure at the alternative shivering intensity.

Other: Lifestyle intervention (cold exposure)

Interventions

Lifestyle intervention (cold exposure) OTHER

Participants will undergo two cold exposures with different shivering intensities. Mild shivering is defined as energy expenditure increased by 1.5-fold compared to the resting metabolic rate. Moderate shivering is 2.5-fold increase in metabolic rate.

Period 1: Shivering intensity 1; Period 2: Shivering intensity 2

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to be able to provide signed and dated written informed consent prior to any study specific procedures
• have suitable veins for cannulation or repeated venepuncture
• male, or postmenopausal (at least 1 year post cessation of menses) female
• aged 40 - 75 years
• have stable dietary habits (no weight loss or gain \>5 kg within the past 3 months)
• have no signs of active cardiovascular disease or liver malfunction
• have body mass index (BMI) \>= 27 and \<= 38 kg/m2
• Pre-diabetes based on one or a combination of the following criteria:
• Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after glucose drink consumption during OGTT in screening
• ImpairedFastingGlucose(IFG):Fastingplasmaglucose≥6.1mmol/land≤6.9 mmol/l
• Insulin Resistance: glucose clearance rate ≤ 360 mL/kg/min, as determined using OGIS120
• HbA1c of 5.7-6.4%
• being diagnosed with T2DM at least 1.5 years before the start of the study
• have well-controlled diabetes, i.e. HbA1c levels \< 8.5%
• have no signs of active diabetes-related co-morbidities, including active cardiovascular diseases, diabetic foot, polyneuropathy or retinopathy

You may not qualify if:

• participation in a clinical study with an investigational product during the last 3 months or as judged by the investigator
• uncontrolled hypertension
• having Hb \<8 mmol/L (men), Hb \<7 mmol/l (women)
• consuming alcohol \>2 servings per day (man) or \>1 servings per day (women)
• not wanting to be informed about unexpected medical findings during the screening
• being engaged in structured exercise \> 2h per week
• smoking
• being cold-acclimated, e.g. having taken daily extended cold baths, working in a refrigerated environment, or practicing regular cold-water swimming/showering within 1 month of starting the study
• \- Type 2 Diabetes Mellitus
• \- being insulin-dependent and/or using SGLT2 inhibitor medications

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

Maastricht University, Department of Nutrition and Movement Sciences

Maastricht, Limburg, 6200MD, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Glucose Intolerance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperglycemia

Study Officials

• Joris Hoeks

  Maastricht University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In a randomised cross-over design participants will be exposed to two different intensities of shivering thermogenesis, namely mild and moderate. There will be a wash-out period of at least 3 weeks between the interventions.

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: October 12, 2022
• Study Start: November 23, 2022
• Primary Completion: November 28, 2024
• Study Completion: November 28, 2024
• Last Updated: September 15, 2025

Record last verified: 2025-09

Locations

NL (1)