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Improving Insulin Sensitivity in Patients With Type 2 Diabetes Via Repeated Cold-induced Shivering Thermogenesis

4 maggio 2026 aggiornato da: Denis Blondin, Université de Sherbrooke

Type 2 Diabetes Mellitus (T2DM) is a widespread health condition characterized by impaired ability of the body to maintain glucose homeostasis. This impairment often leads to secondary complications, including heart disease, high blood pressure, and poor quality of life. While exercise and healthy eating are effective strategies in managing and preventing T2DM, data shows that long-term adherence to these methods are poor - especially among elderly, individuals with obesity and/or with physical limitations.

This clinical study explores cold exposure with shivering as a novel strategy to improve blood sugar control and heart health. In earlier research, spending time in mildly cold environments (around 15-17°C) for a few hours a day improved insulin sensitivity of T2DM patients. Interestingly, these benefits only occurred when the cold caused mild shivering. In a recent 10-day cold acclimation study with overt shivering for minimally 1 hour/day, we observed improved glucose tolerance in participants with overweight/obesity, as well as improved fasting lipid profiles. These results indicate that when accompanied with sufficient level of muscle activation, repeated exposure to cold can beneficially affect both glucose and lipid levels - both of which are impaired in people with T2DM.

In this study, we hypothesise that a 10-day cold acclimation with shivering will improve the (peripheral) insulin sensitivity of patients with T2DM, accompanied by enhanced skeletal muscle FA uptake and oxidation as assessed via the 11C palmitate uptake.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

In a longitudinal design, participants will be exposed to a 10-day cold acclimation with daily shivering. Several metabolic read-out parameters will be evaluated before, during and after the intervention.

On their first visit (Visit 1) participants will arrive to the research facility to receive a physical activity, ambulatory blood pressure and continuous glucose monitors. Around 48 hours following Visit 1, participants will return (Visit 2) for the baseline two-step hyperinsulinaemic-euglycaemic clamp (HEC) measurement, used to assess their hepatic and peripheral insulin sensitivity. Within 1 week after Visit 2 the acclimation period with 10 consecutive daily shivering sessions will start (Visits 3 - 12). During the first (Visit 3) and last (Visit 12) cold exposure sessions organ-specific fatty acid uptake, and oxidative vs. non-oxidative metabolism will be determined using [11C]-palmitate PET/CT. Additionally, indirect calorimetry and regular blood sampling will be performed. During cold exposures 2 to 9, heat loss will be assessed by measuring change in water temperature perfused through the cold exposure suit. In addition, skin temperature, as well as surface electromyography and blood pressure measurements will be performed on days 3, 5, 7 and 9 (Visits 5, 7, 9 and 11) during the acclimation period. On the last cold exposure day participants will be provided a standard dinner to be consumed in the evening before Visit 13. Around 16h following Visit 12, i.e. the day after, participant will return for the post-intervention HEC (Visit 13). At the end of Visit 13, participants will be supplied with an activity and ABP monitors for the post-intervention measuremends. Finally, participants will return to the research centre ~42-45h after Visit 13 for the close-out visit (Visit 14) during which the two monitors will be collected.

Tipo di studio

Interventistico

Iscrizione (Stimato)

15

Fase

  • Non applicabile

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Canada
    • Quebec
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Reclutamento
        • Centre de Recherche du CHUS
        • Contatto:
        • Sub-investigatore:
          • André Carpentier

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • Patients are able to provide signed and dated written informed consent prior to any study specific procedures
  • Women are post-menopausal (defined as at least 1 year post cessation of menses)
  • Aged ≥ 40 years and ≤ 75 years
  • Patients should have suitable veins for cannulation or repeated venipuncture
  • Body mass index (BMI) 25-38 kg/m2
  • Stable dietary habits (no weight loss or gain >5kg in the past 3 months)
  • Diagnosed with T2D at least 1.5 years before the start of the study
  • Relatively well-controlled T2D: HbA1c < 8.5%
  • Oral glucose-lowering medication: metformin alone or in combination with sulfonylurea agents and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months. In case of GLP-1 agonist medication treatment inclusion will be discussed with the dependent physician.
  • No signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy
  • No signs of active liver or kidney malfunction

Exclusion Criteria:

  • Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
  • Participate in sports of physical activity at a moderate- to high-intensity more than 3 times a week, or as judged by the investigator
  • 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
  • Unstable body weight (weight gain or loss > 5 kg in the last three months)
  • Alcohol consumption of >2 servings per day for man and >1 servings per day for women
  • Smoking
  • Being insulin-dependent and/or using SGLT2 inhibitor medications
  • Patients with congestive heart failure and and/or severe renal and or liver insufficiency
  • Men: Hb <8.4 mmol/L, Women: Hb <7.8 mmol/l
  • A medical doctor will judge participation eligibility based on the medical history questionnaire, medication use and fasting blood parameters. If the medical doctor advises that a patient cannot participate, the patient will be excluded from enrolment.
  • Being pregnant
  • Having participated in another study involving PET/CT scanning in the past 1 year

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Scienza basilare
  • Assegnazione: N / A
  • Modello interventistico: Assegnazione di gruppo singolo
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Cold acclimation with shivering
This is a single-arm longitudinal study with a 10-day cold acclimation intervention period. Pre- and post-intervention measurements will be obtained before and after the 10-day period.
Comportamentale: Cold exposure with shivering
Cold exposure which elicits a minimally 80% increase in the baseline metabolic rate of participants.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Whole-body insulin sensitivity measured as glucose infusion rate (GIR) in µmol/kg/min during the stable period of the low- and high-insulin phase of the clamp.
Lasso di tempo: At baseline and Day 13.

1) Hepatic insulin sensitivity measured as percent EGP suppression in µmol/kg/min; 2) Peripheral insulin sensitivity measured as Rd in µmol/kg/min.

Determined by means of a hyperinsulinaemic-euglycaemic clamp.
At baseline and Day 13.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
11-C palmitate uptake and oxidation in liver and skeletal muscle, expressed in µmol/g/min
Lasso di tempo: At Day 3 and Day 12.
Determined by means of PET-CT scanning with a cervico-thoracic dynamic acquisition with 1-[11C]-palmitate (175 MBq).
At Day 3 and Day 12.

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
24-hour systolic and diastolic blood pressure and heart rate
Lasso di tempo: 24-hour period before the baseline clamp (i.e. visit 2) and 24-hour period after the post-acclimation clamp (i.e. visit 13).
24-hour ambulatory blood pressure before and after the 10-day cold acclimation
24-hour period before the baseline clamp (i.e. visit 2) and 24-hour period after the post-acclimation clamp (i.e. visit 13).
Plasma metabolites
Lasso di tempo: Day 2 and Day 13 for insulin stimulated conditions, and Day 3 and Day 12 for cold-stimulated conditions.
  1. In the fasted state plasma metabolites such as glucose, insulin, free fatty acids, triglycerides, inflammatory markers, liver enzymes, etc. will be measured
  2. Under cold- and insulin-stimulated conditions circulating metabolites and hormones during the first and last cold exposure, as well as during the hyperinsulinaemic euglycaemic clamp will be measured
Day 2 and Day 13 for insulin stimulated conditions, and Day 3 and Day 12 for cold-stimulated conditions.
Average 24-hour interstitial glucose concentrations
Lasso di tempo: 24-hour period before Day 2 and after Day 13.
24-hour interstitial glucose values measured under normal living conditions via continuous glucose monitors
24-hour period before Day 2 and after Day 13.
Energy expenditure
Lasso di tempo: During hyperinsulinaemic euglycaemic clamp: at baseline and day 13 During cold exposure: Day 3 and Day 12

Energy expenditure will be assessed via indirect calorimetry before and after the 10-day acclimation during:

  • Baseline (room temperature)
  • Cold exposure
  • Baseline phase of the hyperinsulinaemic euglycaemic clamp
  • Low- and high-insulin phase of the hyperinsulinaemic euglycaemic clamp
During hyperinsulinaemic euglycaemic clamp: at baseline and day 13 During cold exposure: Day 3 and Day 12
Substrate (CHO and fat) oxidation
Lasso di tempo: During hyperinsulinaemic euglycaemic clamp: at baseline and day 13 During cold exposure: Day 3 and Day 12

CHO and fat oxidation will be assessed via indirect calorimetry before and after the 10-day acclimation during:

  • Baseline (room temperature)
  • Cold exposure - Baseline phase of the hyperinsulinaemic euglycaemic clamp
  • Low- and high-insulin phase of the hyperinsulinaemic euglycaemic clamp
During hyperinsulinaemic euglycaemic clamp: at baseline and day 13 During cold exposure: Day 3 and Day 12
Skin temperature
Lasso di tempo: Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Skin temperature will be assessed via skin thermistors attached to 12 different locations around the body
Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Shivering intensity
Lasso di tempo: Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Muscle activity at baseline and during cold exposure will be assessed via electromyography sensors placed on up to 8 different muscle groups.
Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Morning blood pressure
Lasso di tempo: Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Systolic and diastolic blood pressure will be assessed by means of an automated office blood pressure device.
Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Morning heart rate
Lasso di tempo: Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12
Morning heart rate will be assessed by means of an automated office blood pressure device.
Day 3, Day 5, Day 7, Day 9, Day 11 and Day 12

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Université de Sherbrooke

Collaboratori

Maastricht University Medical Center

Investigatori

  • Investigatore principale: Denis P. Blondin, PhD, Université de Sherbrooke

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

24 settembre 2025

Completamento primario (Stimato)

31 ottobre 2026

Completamento dello studio (Stimato)

31 maggio 2027

Date di iscrizione allo studio

Primo inviato

9 settembre 2025

Primo inviato che soddisfa i criteri di controllo qualità

4 maggio 2026

Primo Inserito (Effettivo)

7 maggio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

7 maggio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

4 maggio 2026

Ultimo verificato

1 maggio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 2025-5718

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

IPD from published manuscript will be provided upon reasonable request and dependent upon specific permission from the Comité d'éthique de la recherche du CIUSSS de l'Estrie-CHUS. In addition, the study protocol, statistical analysis plan and informed consent form may also be available upon reasonable request and approval from the Comité d'ethique de la recherche du CIUSSS de l'Estrie-CHUS.

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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