A Feasibility Study of Optimal Non-Pharmacological Lifestyle Modifications in People With Type 2 Diabetes (ON LiMiT)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Feasibility testing of GP recruitment & safety procedures - quantitative assessment
研究概览
简要总结
The overall aim of this study is to examine the feasibility of a 12-month, two-arm lifestyle intervention to induce and maintain remission of type 2 diabetes (T2D). The findings from the feasibility study will inform the recruitment, design and delivery of the interventions in a 5-arm, 24-month randomised controlled trial.
详细描述
Studies on T2D remission have reported varying rates of remission, often around 50% in intervention groups. These studies typically involve individuals with a recent T2D diagnosis, usually within six to ten years of diagnosis, with intervention periods most commonly lasting between twelve and twenty-four months, though durations have ranged from six to sixty months. Lifestyle interventions combining dietary changes and increased physical activity generally yield modest remission rates, but maintaining adherence over time remains challenging. Trials that include an initial phase of a very low-calorie diet, followed by ongoing structured support, tend to report higher remission rates. This emphasizes the critical role of significant and sustained weight loss. However, the most effective combination of dietary, exercise, and behavioral support strategies remains to be determined.
In addition to calorie restriction, changes in dietary composition may influence the underlying mechanisms of T2D. For instance, reducing carbohydrate intake can promote ketone production, affecting liver glucose production and improving glycemic control. Higher protein intake has been linked to an improved insulin response. Replacing saturated fats with polyunsaturated fats and increasing dietary fiber may also support glucose metabolism. However, it remains unclear whether carbohydrate-reduced or carbohydrate-rich diets are more effective in supporting long-term remission following initial weight loss.
Physical activity, particularly high-intensity exercise, plays a key role in reducing the risk of T2D, supporting weight management, and improving remission rates when combined with dietary interventions. Significant improvements in blood glucose control are usually seen with regular moderate-to-high-intensity exercise.
Moreover, there is considerable variation-or sometimes an absence-in the inclusion of key lifestyle intervention components, such as specific dietary and exercise protocols, as well as levels of supportive activities. This inconsistency complicates effective care provision for healthcare professionals and makes it difficult for individuals with T2D to adhere to non-pharmacological management recommendations.
Despite the known benefits of lifestyle modifications, initiating and maintaining these changes is challenging due to barriers such as a lack of support, motivation, and knowledge about nutrition and portion sizes. Involving individuals with T2D in designing and evaluating interventions may improve adherence, reduce participant burden, and increase the feasibility and scalability of lifestyle programs for wider implementation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Building on previous findings from T2D remission studies involving VLCD interventions, the study include individuals with recently diagnosed T2D who are overweight or obese and not receiving insulin therapy. This subgroup has demonstrated the greatest benefit from significant weight loss. Participants using GLP-1 receptor agonists (GLP-1 RAs) are eligible, provided their weight has been stable for at least three months prior to inclusion. Individuals on insulin therapy will be excluded. Allowing GLP-1 RA use enhances the study's generalizability, as approximately 29% of people with T2D in Denmark are currently treated with these medications.
- •Inclusion Criteria:
- •Diagnosis of T2D. Treatment lifestyle changes, oral anti-diabetic medication including metformin, and/or sulfonylureas and/or DPP-4 inhibitors and/or SGLT2 inhibitors and/or incretin-based medication
- •HbA1c between 36-86 mmol/mol
- •T2D duration of ≤6 years
- •BMI ≥27 kg/m2
- •Body weight changes over 3 months ≤3 kg
排除标准
- •Insulin treatment within 6 months prior to screening (any type)
- •Heart failure (ejection fraction ≤40%) and treated with SGLT-2i (current or planned)
- •Cardiovascular disease, including previous heart attack or stroke, for which incretin-based therapy and/or an SGLT-2i has been prescribed.
- •Kidney disease (eGFR <60 ml/min/1,73m² and/or albuminuria (≥30 mg/g) for at least three months) and treated with SGLT-2i (current or planned)
- •Physical comorbidity, which precludes the physical activity during intervention
- •Dietary restrictions or allergies making the participant unable to adhere to the dietary interventions
- •Unable to comply with trial procedures and/or interventions
- •Alcohol/drug abuse
- •Planned or present pregnancy/fertility treatment, or lack of contraception during reproductive age
- •Unstable psychiatric disease that is deemed to impede participation in the project
- •Diagnosed with binge eating disorder
- •Participation (present or planned) in other clinical trials including lifestyle or pharmacy trials for any condition
- •If HbA1c ≥60 mmol/mol and the participant is on 2 or more anti-diabetic drugs and has a positive GAD65 and/or stimulated C-peptide <800 pM
研究组 & 干预措施
CH-rich diet with exercise
A CH-rich diet combined with an exercise programme (n=12)
干预措施: CH-rich diet with exercise (Other)
CH-reduced diet with exercise
A CH-redcued diet combined with an exercise programme (n=12)
干预措施: CH-reduced diet with exercise (Other)
结局指标
主要结局
Feasibility testing of GP recruitment & safety procedures - quantitative assessment
时间窗: Through study completion, an average of 52 weeks.
The recruitment of GPs will be assessed based on the number who express interest, attend instruction and sign collaboration agreements. The reasons for GP non-participation or withdrawal will be documented and, if possible, the GPs will be interviewed. Contacts with GPs that are safety-related, and their responses, including the outcomes of medication changes, will be recorded.
Feasibility testing of participant recruitment & retention
时间窗: Through study completion, an average of 52 weeks.
Registered numbers of: individuals expressing interest in the project, participants completing pre-screening (telephone interview) and in-person screening, participants included in the study, drop-outs and completers. Reasons for exclusion or withdrawal will be documented.
Feasibility testing of intervention participation - qualitative assessment
时间窗: Through study completion, an average of 52 weeks.
Group-based diet and exercise sessions will be observed to assess how the intervention is delivered in practice and how participants engage with the activities. Field notes will document group dynamics, adherence to session protocols, and contextual factors. Field notes will also inform interview guides and supplement interview data.
Feasibility testing of acceptability and experiences
时间窗: Through study completion, an average of 52 weeks plus a 3-month follow-up interview with participants.
Interviews with participants, dieticians and exercise instructors.
Feasibility testing of exercise adherence
时间窗: 3 sessions pr. week, from week 13 to 52.
Adherence is assessed based on self-report and measured (wearable heart rate monitor) using study app and calculated as number of completed sessions / total prescribed sessions.
Feasibility testing of GP experiences and study procedures - qualitative assessment
时间窗: Through study completion, an average of 52 weeks.
Interviews with one GP or staff member from each participating clinic will explore experiences with study procedures, including barriers and opportunities related to recruitment and medication discontinuation, as well as any unintended consequences.
Feasibility testing of intervention participation - quantitative assessment
时间窗: Through study completion, an average of 52 weeks.
The degree of implementation of intervention activities and the extent of participant engagement will be measured by tracking attendance and completion of planned intervention components, including intervention visits, supervised and unsupervised exercise sessions, phone calls, at-home measurements, group-based education sessions, and peer support activities. Data will be collected via REDCap (8.10.18, Vanderbilt University, TN, USA) and study logs to quantify the proportion of completed versus scheduled activities for each participant.
Feasibility testing of protocol adherence - number of days with deviations
时间窗: Through study completion, an average of 52 weeks.
Total number of days during which participants did not adhere to the planned intervention protocol or experienced protocol deviations during the three intervention phases.
Feasibility testing of diet adherence
时间窗: Baseline, weeks 18, 24, 36, and 52.
Derived from myfood24 dietary recalls collected over three consecutive days at pre-specified time points. A recall day is adherent if E% carbohydrate is within the arm-specific target ±10 E%. Participant-level percent compliance at each time point is calculated as (adherent recall days / valid recall days) × 100.
次要结局
- Evaluation of dietary screener to assess adherence(Every 2 weeks from week 15 to week 52.)
- GAD65 Antibodies (U/mL)(Measured at screening.)
- Height (m)(Measured at baseline.)
- Exercise intensity (Rate of Perceived Exertion Scale)(3 sessions pr. week, from week 13 to week 52.)
- Fat free mass (kg)(Measured at baseline, weeks 12, 18, and 52.)
- Fat percentage (%)(Measured at baseline, weeks 12, 18, and 52.)
- Bone mass (kg)(Measured at baseline, weeks 12, 18, and 52.)
- Heart rate (bpm)(Measured from weeks 16 to 51 during exercise sessions.)
- Cardiac rhythm (ECG)(Measured at baseline.)
- Fat mass (kg)(Measured at baseline, weeks 12, 18, and 52.)
- Hip circumference (cm)(Measured at baseline, weeks 12, 18, and 52.)
- Waist/hip ratio(Measured at baseline, weeks 12, 18, and 52.)
- Marker of kidney function - Creatinine (μmol/L)(Measured at baseline, weeks 12, 18, and 52.)
- Dietary intake(Measured at baseline, weeks 18, 24, 36, and 52.)
- Diabetes remission(Measured at weeks 12, 18, 30, 42, and 52.)
- Body weight (kg)(Changes from baseline to the end of the intervention measured at four time points (baseline, weeks 12, 18, and 52).)
- Achieved clinically relevant weight loss (≥10%)(Measured at baseline, weeks 12, 18, and 52.)
- HbA1c (mmol/mol and %)(Measured at screening, baseline, weeks 12, 18, 30, 42, and 52.)
- Marker of kidney function - eGFR (mL/min)(Measured at baseline, weeks 12, 18, and 52.)
- Marker of kidney function - Potassium (mmol/L)(Measured at baseline, weeks 12, 18, and 52.)
- Marker of kidney function - Sodium (mmol/L)(Measured at baseline, weeks 12, 18, and 52.)
- Plasma Albumin (g/L)(Measured at baseline, weeks 12, 18, and 52.)
- Plasma Hemoglobin (g/L)(Measured at baseline, weeks 12, 18, and 52.)
- White Blood Cells (10⁹/L)(Measured at baseline, weeks 12, 18, and 52.)
- Body weight (kg)(Time frame: Collected once weekly from week 1 to 52.)
- Body mass index (kg/m^2)(Measured at baseline, weeks 12, 18, and 52.)
- Gut Microbiome Composition(Collected at baseline, weeks 12, 18, and 52.)
- Urine spot samples for dietary biomarkers (home collection)(Collected at weeks 18, 24, 36, 42, and 52)
- Urine Albumin-to-Creatinine Ratio (at site)(Measured at baseline, weeks 12, 18, and 52.)
- Saliva microbiome composition(Collected at baseline, weeks 12, 18, and 52.)
- Metabolites - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Glucometabolic and gut hormones (pmol/L and pmol/L*min) - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Insulin Sensitivity - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- β-Cell Function - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Hepatic First-Pass Insulin Extraction - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Metabolic Insulin Clearance - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Subjective appetite sensations - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Physical activity(Measured at baseline, weeks 12, 18, and 52.)
- Waist circumference (cm)(Measured at baseline, weeks 12, 18, and 52.)
- Marker of liver function - Degree of liver fibrosis (kPa)(Measured at baseline, weeks 12, 18, and 52.)
- Marker of liver function - Degree of liver steatosis (dB/m)(Measured at baseline, weeks 12, 18, and 52.)
- Marker of liver function - FIB-4 Index(Measured at baseline, weeks 12, 18, and 52.)
- Cognition(Measured at baseline, weeks 12, and 52.)
- Food choice - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Food attention - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Food reaction time (ms) - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Explicit liking - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Implicit wanting - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Peak oxygen uptake (ml O2/min)(Measured at baseline, weeks 12, 18, and 52.)
- Explicit wanting - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Unspecified exploratory outcome - Food preferences and food reward(Measured at baseline, weeks 12, 18, and 52.)
- Systolic blood pressure (mmHg)(Measured at baseline, weeks 12, 18, and 52.)
- Diastolic blood pressure (mmHg)(Measured at baseline, weeks 12, 18, and 52.)
- Resting heart rate (bpm)(Measured at baseline, weeks 12, 18, and 52.)
- Cardiorespiratory fitness (ml O2/min/kg)(Measured at baseline, weeks 12, 18, and 52.)
- Time-in-range (% 3.9-10.0 mmol/L)(Measured at baseline, weeks 1 and 51.)
- Time-below-range (% <3.9 mmol/L)(Measured at baseline, weeks 1 and 51.)
- Time-above-range (% >10.0 mmol/L)(Measured at baseline, weeks 1 and 51.)
- Coefficient of variation (CV) of glucose concentrations(Measured at baseline, weeks 1 and 51.)
- Self-reported quality of life(Measured at baseline, weeks 12 and 52.)
- Self-reported health-related quality of life(Measured at baseline, weeks 12 and 52.)
- Changes in sum score of The 25-item Bodily Distress Syndromes (BDS) checklist(Measured at baseline, weeks 12 and 52.)
- Changes in symptom cases(Measured at baseline, weeks 12 and 52.)
- Self-reported diabetes distress(Measured at baseline, weeks 12 and 52.)
- Self-reported loneliness(Measured at baseline, weeks 12 and 52.)
- Self-reported sleep quality(Measured at baseline, weeks 12 and 52.)
- Self-reported self-efficacy for nutrition change(Measured at baseline, weeks 12 and 52.)
- Systemic vascular resistance - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Self-reported social support for eating habits(Measured at baseline, weeks 12 and 52.)
- Self-reported food addiction(Measured at baseline, weeks 12 and 52.)
- Adverse events(Through study completion, an average of 52 weeks.)
- Exercise intensity (%VO2peak)(Measured at baseline, weeks 12, 18, and 52.)
- Cardiac output - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Heart rate and its variability - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Blood pressure and its variability - Mixed Meal Tolerance Test(Measured at baseline (using three differing meal compositions), and at weeks 12, 18 and 52 (using the selected meal composition).)
- Timing - sleep pattern(Measured from weeks 16-51 (GPS-based smartwatch) and at baseline, weeks 12, 18, and 52 (SENS Motion).)
- Duration - sleep pattern(Measured from weeks 16-51 (GPS-based smartwatch) and at baseline, weeks 12, 18 and 52 (SENS Motion).)
- Variability - sleep pattern(Measured from weeks 16-51 (GPS-based smartwatch) and at baseline, weeks 12, 18 and 52 (SENS Motion).)
- Efficiency - sleep pattern(Measured from weeks 16-51 (GPS-based smartwatch) and at baseline, weeks 12, 18 and 52 (SENS Motion).)
- Wakefulness - sleep pattern(Measured from weeks 16-51 (GPS-based smartwatch) and at baseline, weeks 12, 18 and 52 (SENS Motion).)
- Home blood pressure(Measured at baseline, at weeks 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, 42, 48, and 52.)
- Resting heart rate measured at home(Measured at baseline, at weeks 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, 42, 48, and 52.)
- Self-measured blood glucose(Measured at baseline, at weeks 1, 2, 3, 4, 8, 12, 18, 24, 30, 36, 42, 48, and 52.)
研究者
Jonas Salling Quist
Senior Researcher and Associate Professor
Steno Diabetes Center Copenhagen