Effects of Cold-induced Shivering at Different Intensities on 24-hour Glucose Profiles in Pre-diabetic Individuals and Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- 24-hour area under the curve (AUC) for glucose
研究概览
简要总结
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.
详细描述
Participants will be recruited in and near the vicinity of Maastricht by advertising on local billboards, in local newspapers, public spaces, contacting previous participants who gave consent to be contacted again, and on the internet. Those who express interest will be invited for a screening. Upon arrival at the research facility, participant will sign an informed consent form (see chapter 11.2 for complete procedure). Subsequently, measurements of height, weight and blood pressure will be performed. The blood pressure measurement will be performed 3 times to obtain an average blood pressure value (to avoid measuring a peak or dip in the pressure). Furthermore, a 10-lead electrocardiogram (ECG) will be recorded and the subjects will fill out a medical history (see document F1.1). Following this, a two-hour oral glucose tolerance test (OGTT) will be performed to assess glucose tolerance (applies only for potential pre-diabetic subjects). Fasting blood sample (19 mL in total) from the T2DM patients will be obtain via venepuncture and no OGTT will be performed. After inclusion in the study, participants will undergo two study periods (period 1 and period 2) of eight days. During each period, participants will visit the research facilities three times.
Sample size:
The primary aim of this study is to determine if acute cold-induced shivering will decrease the area under the curve (AUC) for 24-hour glucose of individuals with a different degree of metabolic impairment, including pre-diabetic participants and patients with T2DM. Thus, the study will be powered accordingly to allow for detecting the expected minimal effect in both groups. It is expected to see a clinically meaningful decrease in AUC for 24-hour glucose of at least 15% in the pre-diabetic participants. Based on literature, investigators anticipate a more pronounced (20%) effect in 24-hour AUC for glucose in T2DM patients. To ensure that both groups are powered appropriately, the sample size calculation of the T2DM patients will be followed and 12 participants will be included in each group. When a drop-out rate of 20% is considered, investigators anticipate that up to 15 participants will need to be included in each group to reach this sample size. From experience with similar studies it is estimated that there will be a screening failure of 50% and 70% for the T2DM and pre-diabetes groups, respectively. Therefore, it is expected that researchers will need to screen 30 and 50 individuals, respectively, from each study population.
Use of co-interventions: to minimise the variability in blood glucose induced by diet, all participants will be asked to consume standardised meals during the two study periods. Additionally, subjects will be asked to avoid strenuous physical activity (e.g. walking long distances, stair climbing for >10 minutes or cycling for >30 min, hiking) or structured exercise during the study periods to minimize exercise induced variability in blood glucose. In addition, participants are asked to withstand from alcohol and caffeine-containing drinks 24 hours before and after cold exposure. Participants will be instructed to keep their normal sleeping pattern throughout the entire study. During wash-out participants are advised to maintain their normal dietary habits and activity pattern.
Measurements:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria for all subjects:
- •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
- •Additional inclusion criteria for pre-diabetic subjects:
- •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%
- •Additional inclusion criteria for type 2 Diabetes Mellitus patients:
- •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
- •diet treatment OR on an oral glucose lowering medication: metformin only or in combination with sulfonylurea agents and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months
排除标准
- •not meeting the respective inclusion criteria
- •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
- •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
- •Exclusion criteria specific for pre-diabetic subjects:
- •- Type 2 Diabetes Mellitus
- •Exclusion criteria specific for type 2 Diabetes Mellitus patients:
- •- being insulin-dependent and/or using SGLT2 inhibitor medications
结局指标
主要结局
24-hour area under the curve (AUC) for glucose
时间窗: 24-hour period before and after each shivering session
24-hour AUC for glucose expressed in mmol/L x min
次要结局
未报告次要终点