DiRECT
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Clinical Question
In adult patients with type 2 diabetes, does structured dietary intervention improve control and/or reduce remission?
Bottom Line
Patients receiving intensive weight management in combination with routine primary care achieve remission of type 2 diabetes and can be taken off antidiabetic drugs.
Major Points
Type 2 diabetes has affected 422 million adults worldwide. It is associated with weight gain and accumulation of fat within the liver and pancreas, both in adults and adolescents. The twin cycle hypothesis showed that by limiting a person’s diet to 600-700 kcal/day, the liver fat and insulin resistance returned to normal over the course of 7 days and pancreas fat over 8 weeks. Continuing to follow this diet, the improvements remained steady over the course of 6 months. Using this, DiRECT wanted to test whether managing weight would result in continuous remission.
A cluster-randomized trial was conducted at 49 primary care practices, where 306 patients were enrolled. 149 patients received the intervention of following Counterweight-Plus weight management, and 149 patients were in the control group. The goal was to lose and maintain at least 15 kg while continuing with their normal physical activity, as well as discontinuing their antidiabetic and antihypertensive medications. At the end of 12 months, the mean body weight fell by 10 kg for the intervention group and 1 kg for the control. 68 participants from intervention and 6 participants from control achieved remission, while no remission was reached by those who gained weight.
Results from this study show that remission of type 2 diabetes is possible. Using similar methods in a primary care setting is possible to help patients reach remission as well. DiRECT has been criticized for not accounting for medication dose changes, 25% intervention dropout rate, and lack of midpoint data and adverse effects.
Guidelines
As of January 2016, the ADA diabetes guidelines for type 2 diabetes include lifestyle management as first-line therapy for most individuals[1].
Design
- Open-label cluster-randomized trial
- Stratified
- N= 306
- Intervention (n=149)
- Control(n=149)
- Setting: 49 primary care practices in Scotland and the Tyneside region of England
- Enrollment: July 25th, 2014- August 5th, 2016
- Follow-up:12 months
- Analysis: Intention-to-treat
- Primary Outcomes: Reduction in weight of 15kg or more, and remission of Type 2 diabetes defined as a HbA1c <48 mmol/mol
Population
Inclusion Criteria
- 20-65 years
- Diagnosed with type 2 diabetes in last 6 years
- BMI 27-45 kg/m2
Revised Inclusion Criteria
- Most recent HbA1c > 6.0%, <6.5% keep antidiabetic medication
Exclusion Criteria
- Current insulin use
- HbA1c > 12%
- Weight loss > 5kg in last 6 months
- Recent eGFR <30mL/min/1.732m2
- Severe/unstable heart failure
- Participate in other Randomized Control Trials
- Substance use
- Known cancer
- Myocardial infarction within last 6 months
- Learning difficulties
- Current treatment with anti-obesity drugs
- Presence of eating disorder or purging behavior
- Pregnancy or pregnancy consideration
- Hospital admission for depression or use of antipsychotic drugs
Revised Exclusion Criteria
- Achieved non-diabetic HbA1c
Baseline Characteristics
- Female 66 (44%)
- Median Age 52.9
- BMI 35.1
- Weight 101 kg
- Time since diabetes diagnosis 3.0 years
Interventions
- Diabetes care based on current guidelines and standards from National Institute of Health and Care excellence and Scottish Intercollegiate Guidelines Network
- Counterweight-Plus weight management program
- Discontinuation of oral antidiabetics and antihypertensives
- Can be reintroduced based on national clinical guidelines
- Total diet replacement using a low energy formula diet for 3-5 months (825-853 kcal/day; 59% carbohydrate, 13% fat, 26% protein, 2% fiber)
- Structure food intervention for 2-8 weeks (〜50% carbohydrate, 35% total fat, 15% protein)
- Physical activity strategies introduced (goal: up to 15,000 steps/day)
- Ongoing structured program with monthly visits
- Discontinuation of oral antidiabetics and antihypertensives
Outcomes
Primary Outcomes
- Proportion achieving a 15kg weight loss at 12 months
- 24% intervention vs. 0% control (p<0.0001) NNT=5
- Proportion achieving remission at 12 months
- 46% intervention vs. 4% control (p<0.0001, odds ratio 19.7, 95% Cl 7.8-49.8) NNT=3
Secondary Outcomes
(Mean Differences from Baseline to 12 Months)
- Quality of Life (EQ-5D)
- +7.2 point improvement intervention vs -2.9 point control (95% CI 2.5-10.3; p=0.0012)
- Serum Lipids
- - 0.31 mmol/L intervention vs +0.09 mmol/L in control (95% CI 11-20%; p<0.0001)
- Weight
- -10 kg change intervention vs -1 kg change control (95% CI -10.3 to -7.3; p<0.0001)
- HbA1c (mmol/mol)
- -9.6% change intervention vs. + 1.4% change control (95% CI -12.1 to -6.5; p<0.0001)
- HbA1c (%)
- -0.9% change intervention vs. + 0.1% change control (95% CI -1.1- to -0.59; p<0.0001)
- Number of Prescribed oral antidiabetic medications
- -0.8% change intervention vs. + 0.2% change control (95% CI -1.11 to -0.84; p<0.0001)
- Number of Prescribed antihypertensive medications
- -0.6% change intervention vs. + 0.1% change control (95% CI -0.75 to -0.42; p=0.0001)
- Systolic Blood Pressure (mm Hg)
- -1.3% change intervention vs. -1.7% change control (95% CI -4.5 to 3.3; p=0.7710)
Subgroup Analysis
Adverse Events
- Number of participants with any serious adverse event
- 7 (4%) intervention group vs. 2 (1%) control group NNH=33
Criticisms
- Data collection only occurred at baseline and 12 months; midpoint adverse events and data were not assessed.
- Program for intervention group resulted in 25% dropout.
- Participant medication dose changes not accounted for.
Funding
Diabetes UK funded this study as a Strategic Research Initiative. Cambridge Weight Plan provided the formula diet.