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

2026年5月4日 更新者: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.

調査の概要

状態

募集

条件

詳細な説明

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.

研究の種類

介入

入学 (推定)

15

段階

  • 適用できない

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

    • Quebec
      • Sherbrooke、Quebec、カナダ、J1H 5N4
        • 募集
        • Centre de Recherche du CHUS
        • コンタクト:
        • 副調査官:
          • André Carpentier

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

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

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか?

デザインの詳細

  • 主な目的:基礎科学
  • 割り当て:なし
  • 介入モデル:単一グループの割り当て
  • マスキング:なし(オープンラベル)

武器と介入

参加者グループ / アーム
介入・治療
実験的: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.
Cold exposure which elicits a minimally 80% increase in the baseline metabolic rate of participants.

この研究は何を測定していますか?

主要な結果の測定

結果測定
メジャーの説明
時間枠
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.
時間枠: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.

二次結果の測定

結果測定
メジャーの説明
時間枠
11-C palmitate uptake and oxidation in liver and skeletal muscle, expressed in µmol/g/min
時間枠: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.

その他の成果指標

結果測定
メジャーの説明
時間枠
24-hour systolic and diastolic blood pressure and heart rate
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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
時間枠: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

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

捜査官

  • 主任研究者:Denis P. Blondin, PhD、Université de Sherbrooke

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2025年9月24日

一次修了 (推定)

2026年10月31日

研究の完了 (推定)

2027年5月31日

試験登録日

最初に提出

2025年9月9日

QC基準を満たした最初の提出物

2026年5月4日

最初の投稿 (実際)

2026年5月7日

学習記録の更新

投稿された最後の更新 (実際)

2026年5月7日

QC基準を満たした最後の更新が送信されました

2026年5月4日

最終確認日

2026年5月1日

詳しくは

本研究に関する用語

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

はい

IPD プランの説明

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.

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米国FDA規制機器製品の研究

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この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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