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

4 de mayo de 2026 actualizado por: 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.

Descripción general del estudio

Estado

Reclutamiento

Condiciones

Intervención / Tratamiento

Descripción detallada

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 de estudio

Intervencionista

Inscripción (Estimado)

15

Fase

  • No aplica

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

  • Canadá
    • Quebec
      • Sherbrooke, Quebec, Canadá, J1H 5N4
        • Reclutamiento
        • Centre de Recherche du CHUS
        • Contacto:
        • Sub-Investigador:
          • André Carpentier

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

  • Adulto
  • Adulto Mayor

Acepta Voluntarios Saludables

No

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Ciencia básica
  • Asignación: N / A
  • Modelo Intervencionista: Asignación de un solo grupo
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 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.
Conductual: Cold exposure with shivering
Cold exposure which elicits a minimally 80% increase in the baseline metabolic rate of participants.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
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.
Periodo de tiempo: 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.

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
11-C palmitate uptake and oxidation in liver and skeletal muscle, expressed in µmol/g/min
Periodo de tiempo: 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.

Otras medidas de resultado

Medida de resultado
Medida Descripción
Periodo de tiempo
24-hour systolic and diastolic blood pressure and heart rate
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Université de Sherbrooke

Colaboradores

Maastricht University Medical Center

Investigadores

  • Investigador principal: Denis P. Blondin, PhD, Université de Sherbrooke

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Actual)

24 de septiembre de 2025

Finalización primaria (Estimado)

31 de octubre de 2026

Finalización del estudio (Estimado)

31 de mayo de 2027

Fechas de registro del estudio

Enviado por primera vez

9 de septiembre de 2025

Primero enviado que cumplió con los criterios de control de calidad

4 de mayo de 2026

Publicado por primera vez (Actual)

7 de mayo de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

7 de mayo de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

4 de mayo de 2026

Última verificación

1 de mayo de 2026

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • 2025-5718

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Descripción del plan 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.

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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