To investigate whether increased physical activity would have effects on glycemia, blood pressure, lipid profile, insulin resistance and insulin secretion additional to those yielded by an intensified dietary intervention or usual care in individuals with newly diagnosed type 2 diabetes.

• Diagnosed with diabetes within the previous five to eight months
• Older than 30 years old at time of diagnosis.

• Age older than 80 years
• HbA1c concentration greater than 10%
• Blood pressure higher than 180/100mm Hg
• LDL-cholesterol concentration higher than 4mmol per L
• Body mass index (BMI) lower than 25kg/m²
• Weight greater than 180kg
• Use of weight loss drugs
• Taking a sulfonylurea at the maximum dose
• Unstable angina
• Myocardial infarction within the previous three months
• Inability to increase physical activity
• Pregnancy or planning to become pregnant.

Recruitment

• Recruitment done by:
  • Searching the records databases of 217 general practices
  • Community-based education programs
  • Direct advertising.
• Screening was done via telephone by a research nurse
• Potentially eligible individuals were invited to attend a face-to-face assessment to confirm eligibility at least two weeks before randomization (Visit One):
  • Visit One: Obtained informed consent, recorded clinical history and physical examination
  • Visit Two: One-mile walk test to assess fitness
  • Visit Three: Remeasure values for baseline variables (baseline visit)
  • Visit Four: Between baseline and randomization, patients were seen by a study doctor.

Design

Multi-center, parallel-group, randomized controlled trial. Patients were randomized via computer allocation to a 2:5:5 ratio to usual care, an intensive diet intervention or the intensive diet intervention plus activity. Allocation was stratified by center and minimized by age, sex, fitness, route into the study and blood pressure.

Blinding Used

• Group allocation remained concealed by the trial coordinator until patients attended Visit Four, when they saw a dietitian who telephones to get the next code
• Dietitians, nurses and patients were aware of allocation, but doctors were not
• Any changes in treatment for diabetes, blood pressure and lipid profile were made by a doctor who was unaware of treatment allocation and according to a strict trial protocol to keep the risk of performance bias to a minimum.

Intervention

• Usual Care Group (Control Group): Standard dietary and exercise advice after randomization and at the end of the study, with reviews by a study doctor and nurse at baseline, six months and 12 months
• Intensive Diet Intervention Group:
  • The goal was to lose 5% to 10% of patient's initial body weight and to maintain the weight loss throughout the study
  • Guidance was provided on foods lower in energy density, fat content and glycemic index
  • Goals were negotiated individually with each patient during their first session with the dietitian and were reviewed at each visit
  • Dietitian visits were one hour at randomization and then 30 minutes at months three, six, nine and 12
  • Nurse visits were 30 minutes long every six weeks weeks throughout the study (a total of nine visits). Fifteen minutes was spent reinforcing diet and the other 15 minutes were spent discussing any other issues.
• Intensive Diet and Physical Activity Group:
  • Same dietary intervention as those in the intensive diet group
  • Additionally, asked to do 30 minutes brisk walking on at least five days per week, in addition to current level of physical activity
  • Each patient was given a pedometer and a folder containing motivating literature and pages for recording daily physical activity (pedometer readings)
  • Activity targets were gradually increased over five weeks then maintained for the rest of the study
  • During the nurse visits, 15 minutes was spent discussing dietary issues and 15 minutes spent discussing the diary entries for physical activity for physical activity.
• For all groups, the study handled management of type 2 diabetes, blood pressure and lipid profile
• During the first six months of the study, treatment was only changed if:
  • Fasting blood glucose concentration rose to more than 12mmol per L
  • Patients became symptomatic
  • Blood pressure was higher than 160/90mm Hg at any visit.
• During the second six months, patients were treated as appropriate to maintain the following targets:
  • HbA1c concentration lower than 7.4%
  • Blood pressure lower than 140/85mm Hg
  • Total cholesterol concentration lower than 4mmol per L
  • HDL-concentration higher than 1mmol per L
  • LDL-concentration lower than 2mmol per L
  • Concentration of triglycerides lower than 2.0mmol per L.

Statistical Analysis

• Descriptive statistics and tests were used to assess those patients randomized to those assessed for eligibility but not randomized
• Descriptive statistics were used to compare the randomized groups at baseline
• Primary outcome was assessed by intention to treat without imputation
• Multi-variable linear regression was used to compare the intensive diet and intensive diet plus activity groups for each of the primary outcomes at six months, with adjustment for the baseline value of the outcome, study center and minimization of variables
• Secondary models were adjusted for any variables showing imbalance at baseline
• Similar regression models were used to investigate secondary comparisons of each intervention group vs. usual care for the three primary outcomes with Bonferroni correction, for secondary outcomes with linear or logistic regression models dependent on outcome type, and primary and secondary outcomes at 12-month follow-up
• Use of drugs for the treatment of diabetes, hypertension and lipid regulation were investigated with logistic (medication vs. no medication) and linear (daily prescribed dose as percentage of the maximum) regression models
• Sub-group analysis was conducted by including interaction terms in the following regression models:
  • Each of the primary outcomes at six months by:
    • Sex
    • Baseline age
    • HbA1c concentration
    • Physical activity
    • Time since diagnosis.
  • BMI at six months and baseline
  • Insulin resistance at six months by baseline BMI
  • Insulin resistance at six months by baseline insulin resistance.

Timing of Measurements

Recruitment was between December 2005 and September 2008. Follow-up was completed in September 2009.

Dependent Variables

• Primary endpoint consisted of improvements in HbA1c concentration and blood pressure six months after randomization
• Insulin resistance and insulin secretion were measured by homeostasis model assessment
• Secondary outcomes were:
  • Insulin resistance and insulin secretion
  • Lipid profile
  • Physical activity (daily recordings of pedometer use and by accelerometry at baseline, six months and 12 months)
  • Body composition (weight, percentage of fat and bioimpedance)
  • Waist circumference and hip circumference 
  • Medication use at six and 12 months. 

Independent Variables

• In both Intensive Diet Intervention Group and Intensive Diet and Physical Activity Group:
  • Dietary guidance: One hour at randomization and then 30 minutes at months three, six, nine and 12
  • Nurse visits: The visits are for 30 minutes, every six weeks throughout the study (a total of nine visits). A total of 15 minutes was spent reinforcing diet and 15 minutes spent discussing any other issues (or physical activity in the Intensive Diet and Physical Activity Group).
• Usual Care Group (Control Group): Seen at baseline, six months and 12 months.

Initial N

• A total of 1,634 were initially screened by telephone
• A total of 712 were eligible for face-to-face screening
• A total of 700 were screened
• A total of 593 were enrolled and randomized in the study:
  • N=99 assigned to usual care
  • N=248 assigned to intensive dietary support
  • N=246 assigned to intensive dietary support and activity.

Attrition (Final N)

A total of 579 were available for analysis of primary endpoints at 12 months:

• N=93 were assigned to usual care
• N=246 were assigned to intensive dietary support
• N=240 were assigned to intensive dietary support and activity.

Age

Ethnicity

Other Relevant Demographics

Anthropometrics

Characteristics of all enrolled patients in all groups were similar at baseline.

Location

• Recruitment took place in Southwest England
• The study was done in five secondary care National Health Service (NHS) trusts:
  • Taunton and Somerset NHS Foundation Trust
  • University Hospitals Bristol NHS Foundation Trust
  • North Bristol NHS Trust
  • Gloucestershire Hospitals NHS Trust
  • Weston Area Health NHS Trust.

Key Findings

The chart above shows primary outcomes at six and 12 months.

• The intention-to-treat comparison showed no differences between the intensive diet intervention and the intensive diet intervention plus activity for any primary outcomes
• Mean HbA1c concentrations were significantly lower at six and 12 months in patients who received either study intervention than in those who received usual care.

Other Findings

• The mean number of steps taken daily by patients in the intensive diet plus activity group had increased by 17% at six months from 6,399 (SD 3,056) to 7,680 (SD 2,818), and this level of activity was maintained at 12 months (7,621, SD 2,778)
• The number of patients overall who were active nearly doubled from baseline to 12 months (9.1% at baseline vs. 18.1% at 21 months
• The interventions had no effect on blood pressure
• The effects of both study interventions on HbA1c concentrations had weakened slightly at 12 months, but remained significant compared with usual care
• Differences between groups for the secondary outcomes were similar to those for the primary outcomes in that the intensive diet intervention and intensive diet intervention plus activity groups did not differ substantially, and outcomes in both were better than those in the control group for weight, reduction in waist circumference and hip circumference, bioimpedance and insulin resistance
• Improvements were also seen in both study intervention groups at six months in concentrations of HDL-cholesterol and triglycerides, more so in the intensive diet and activity group than in the intensive diet alone group, although values were similar at 12 months
• Use of diabetes medications did not differ between the three groups at six months, but participants in the usual care group were more likely to be taking a diabetes medication at 12 months
• Use of drugs to control blood pressure and lipid profile did not differ at six or 12 months between the three groups
• The intensive diet intervention plus activity seemed to yield better results for HbA1c concentration (P=0.007), BMI (P=0.04), and insulin resistance (P<0.001) in patients who had high baseline values than for those with low baseline values
• For systolic blood pressure (P=0.015) and, to a lesser degree, diastolic blood pressure (P=0.119), this intervention became less effective with increasing age at baseline.

• Intensive dietary support soon after the diagnosis of type 2 diabetes is beneficial
• This degree of dietary input (6.5 hours additional time over the 12 months of the study, consisting of two hours with a dietitian and 4.5 hours with a nurse) improved glycemic control and weight loss, and reduced need for drug treatment compared with usual care
• The additional activity program did not further improve outcomes
• This supports the redesign of diabetes services to increase dietary management at an early stage.