Treating Type 2 Diabetes by Reducing Postprandial Glucose Elevations: A Paradigm Shift in Lifestyle Modification

Study Overview
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Brief Summary
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Conventional lifestyle modification in the management of type 2 diabetes focuses on weight loss, through caloric restriction and exercise, to reduce insulin resistance. This approach is limited because some people either do not need to lose weight, do not want to lose weight, cannot lose weight, or cannot maintain weight loss over a lifetime. This study proposes to evaluate the effectiveness of a lifestyle modification that focuses on reducing post-meal blood glucose (BG) elevations instead of weight loss. It works by teaching participants to: 1) choose low glycemic load foods that do not significantly increase their blood glucose, and 2) increase their routine physical activity after meals when it can offset post-meal blood glucose elevations. The study will also evaluate the role feedback about blood glucose fluctuations can play in improving the effectiveness of this program.

Detailed Description
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BACKGROUND: Type 2 diabetes (T2D) is a growing epidemic in the U.S. with devastating complications that result in major health and personal costs. To address this, the American Diabetes Association recommends a lifestyle program that focuses on weight loss through caloric restriction and exercise as an initial or an adjunct treatment to pharmacological interventions. However, its general applicability is limited because some individuals with T2D do not need to lose weight, do not want to lose weight, cannot lose weight, or cannot maintain weight loss over a lifetime. Recent research indicates that a major contributor to poor metabolic control is postprandial glucose (PPG) elevation. The researchers have developed a treatment option that focuses on reducing PPG without requiring weight loss. This lifestyle program is comprehensive, integrated, and efficient. Over 5 sessions, this program empowers individuals to use Glycemic load of food, Exercise, and Monitoring glucose (GEM) in a systematic manner. GEM's 1.03% HbA1c reduction compared favorably to both conventional weight loss (0.64% reduction with 42 sessions of Look AHEAD) and continual use of a first line medication (0.9% reduction with Metformin). When enhancing the quantity and quality of glucose feedback with Continuous Glucose Monitoring (CGM), GEM reduced HbA1c by 1.30%. AIMS: This project will determine how GEM compares to conventional weight reduction at short- and long-term follow-up in a large, representative sample of adults with type 2 diabetes. At the same time, the researchers will test a conceptual model based on a review of the literature postulating that the effects of GEM are modulated by the quality and quantity of glucose feedback. This has important implications for long-term maintenance; since the model proposes a cascade in which increasing either the quantity or quality of glucose feedback improves immediate behavior change through positive and negative glucose consequences. These contingencies may lead to improved PPG and insulin sensitivity, and in turn, improved metabolic control. This cascade may produce ancillary benefits that could help maintain long-term success, e.g. greater empowerment and fewer depressive symptoms. APPROACH: 200 participants with poorly controlled T2D will be randomized to 1 of 4 groups that manipulate both the focus on postprandial glucose and the quality and quantity of glucose feedback. Short- and long-term benefits will be assessed using medical, behavioral and psychological measures obtained at baseline, 3 months post-intervention and 12 months post-intervention. IMPACT: If GEM is shown to be effective and enduring, it will provide an alternative to the conventional weight-loss focused lifestyle modification. GEM has the potential to improve metabolic control, increase self-reliance, and slow disease progression. Because GEM is manual-based, it will be easy to deploy and will give it the potential to impact a large proportion of the adults with T2D.

Official Title
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Treating Type 2 Diabetes by Reducing Postprandial Glucose Elevations: A Paradigm Shift in Lifestyle Modification

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Behavioral: Weight reduction training
* Behavioral: PPG training
* Behavioral: discrete BG feedback
* Behavioral: continuous BG feedback


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with T2D in the last 10 years HbA1c >7.5% (sub-optimal T2D control) Between 21 and 80 years old Not blind Can read English Routinely uses a smart phone Exclusion Criteria: Takes insulin (participants may start insulin during the study if clinically indicated) Has taken medications that impede weight loss (e.g., prednisone) within the last 3 months Currently pregnant or contemplating pregnancy within the next 15 months Conditions that preclude increasing physical activity (e.g. severe neuropathy cardiovascular disease, chronic obstructive pulmonary disease/emphysema, osteoarthritis, stroke, or severe mental disease like manic depressive illness, severe depression, active substance abuse) Undergoing treatment for cancer History of lactic acidosis Marked renal impairment (eGFR < 45; stage 3b chronic kidney disease) Takes psychotropic medications that raise blood glucose (e.g. atypical antipsychotics) Cannot read English Blindness Cognitive impairment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: WR<br>Weight reduction training | Behavioral: Weight reduction training<br>* 6 one-hour sessions of conventional weight reduction training<br>|
| Active Comparator: GE<br>PPG training | Behavioral: PPG training<br>* Four 90-minute sessions of glycemic load and exercise training<br>|
| Experimental: GEM<br>PPG training + discrete BG feedback | Behavioral: PPG training<br>* Four 90-minute sessions of glycemic load and exercise training<br>Behavioral: discrete BG feedback<br>* Blood glucose feedback from structured self-monitoring of blood glucose<br>|
| Experimental: GEM+CGM<br>PPG training + continuous BG feedback | Behavioral: PPG training<br>* Four 90-minute sessions of glycemic load and exercise training<br>Behavioral: continuous BG feedback<br>* blood glucose feedback from continuous glucose monitoring<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in HbA1c | change in HbA1c from baseline measure | baseline, 3 months, and 12 months post-intervention | 
| change in medication | change in medication type or dose from baseline measures | baseline, 3 months, and 12 months post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in food choices (ASA24 survey) | ASA24 survey across 3 separate days in each time frame | baseline, 3 months, and 12 months post-intervention | 
| change in food choices (energy bar selection) | At assessment visits, subjects will choose between energy bars that do or dont support the intervention principles. | baseline, 3 months, and 12 months post-intervention | 
| change in physical activity (Fitbit activity monitor) | daily activity will be recorded | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (dietary habits questionnaire) | The Food Questionnaire | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (quality of life questionnaire) | WHOQO-BREF questionnaire | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (depression questionnaire) | Patient Health Questionnaire (PHQ-9) | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (numeracy questionnaire) | Numeracy Scale - measures how good one is with numbers | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (diabetes knowledge questionnaire) | Diabetes Knowledge Scale | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (empowerment questionnaire) | Diabetes Empowerment Scale | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (concerns about diabetes questionnaire) | Diabetes Distress Scale (Emotional Distress & Regimen Distress subscales) | baseline, 3 months, and 12 months post-intervention | 
| change in psychological functioning (attitude towards glucose monitoring questionnaire) | The Glucose Monitoring Satisfaction Survey (GMSS) | baseline, 3 months, and 12 months post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2, Continuous Glucose Monitoring, Lifestyle Modification