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To determine whether cardiovascular morbidity and mortality in individuals with type 2 diabetes can be reduced by long-term weight reduction, achieved by an ILI (intensive lifestyle intervention) that includes diet, physical activity and behavior modification.

• Type 2 Diabetic participants were 45 to 74 years of age ( this was changed to 55 to 74 years during the second recruitment to increase the anticipated cardiovascular event rate)
• BMI over 25
• BMI over  27 if taking insulin
• A1C under 11%
• Blood pressure under 160/100
• Triglyceride under 600
• For participants not taking prescription medications that would affect heart rate response to exercise, baseline test was considered valid if the individual completed a maximal graded exercise test and achieved at least 85% of age-predicted maximal heart rate and a minimum of four metabolic equivalents (METS)
• For participants taking prescription medications that would affect heart rate response during exercise, the baseline test was considered valid if the individual achieved an RPE of at least 18 and a minimum of four mets.

• Type 2 diabetics under 44 years of age or older than 75
• Type 2 diabetics with a BMI under 25
• Type 2 diabetics taking insulin with BMI over 26
• Type 2 diabetics with an A1C of 11% or more
• Type 2 diabetics with a blood pressure at 160/100 or greater
• Type 2 diabetics with a triglyceride of 600 or more
• Type 2 diabetics that did not meet graded exercise test
• Type 1 diabetics.

 

Recruitment

• Screening occurred from 16 centers nationwide
• The goal was to recruit approximately equal amounts of men and women, with more than 33% from racial and ethnic minority groups.

Design

• Participants were randomly-assigned with equal probability to either the ILI (intensive lifestyle intervention or the DSE (diabetes support and education) comparison condition
• Randomization was stratified by clinical center.

Blinding

Yes.

Intervention

Before randomization, all study participants were required to complete a two-week run-in period that included successful self-monitoring of diet and physical activity, then they were provided an initial session of diabetes education.

The ILI Intervention Group

• During Months One to Six, participants were seen weekly with three group meetings and one individual session per month
• During Months Seven to 12, group sessions were provided every other week and the monthly individual session was continued. Sessions were led by an inter-disciplinary team
• Calorie-restriction was the primary method of achieving weight-loss
• The physical activity program prescribed relied heavily on home-based exercise with gradual progression
• The ILI included a "tool box" approach to help the participants maintain the study's weight-loss and activity goals.

The DSE group

• Subjects were invited to three additional group sessions during the first year
• A standard protocol was used which provided information and discussion related to diet, physical activity and social support
• The DSE group were not weighed at the sessions and received no counseling in behavioral strategies for changing diet and activity.

Statistical Analysis

• Cross-sectional differences between participants assigned to the ILI and DSE conditions were assessed using ANCOVA and logistic regression, with adjustment for clinical center.
• Changes in outcome measures from baseline to one year were compared using ANCOVA and Mantel-Haenszel tests.

Timing of Measurements

Baseline and one year.

Dependent Variables

• Weight: Digital scale
• Blood pressure: Seated and measured in duplicate using an automated device after a five-minute rest 
• Fitness: Sub-maximal exercise test measured in METS 
• A1C: Measured by dedicated ion exchange high-performance liquid chromatography instrument
• Fasting serum glucose: Measured enzymatically on a Hitachi 917 autoanalyzer using hexokinase and glucose-6-phosphate dehydrogenase
• Total serum cholesterol: Measured enzymatically, using methods standardized to the Centers for Disease Control and Prevention reference methods
• Total serum triglycerides: Same as above
• LDL-cholesterol: Calculated by the Friedewald equation
• HDL-cholesterol: Analyzed by whole plasma with dextran sulfate minus Mg
• Metabolic syndrome diagnosis: Criteria proposed by the National Cholesterol Education Program Adult Treatment Program 111 Panel.

Independent Variables

ILI education group, which includes weight-loss intervention with diet modification and increased physical activity, modeled on group behavioral programs.

Control Variables

• Usual care conditions that included diabetes support and education, which included one initial diabetic education session and three additional group sessions during the first year
• Participants were not weighed and received no counseling in behavioral strategies.

Initial N

• 5,145 participants
• 3,063 women
• 2,082 men
• ILI Group: 2,570
• DSE Group: 2,575.

Attrition (Final N)

4,959 (96%).

Age

• ILI Group: 58.6±6.8 years
• DSE Group: 58.9±6.9 years.

Ethnicity

• African-American: 15.6%
• American Indian or Alaskan Native: 5.5%
• Asian or Pacific Islander: 25%
• Hispanic or Latino: 13.2%
• Non-Hispanic white: 63.2%
• Other or multiple: 1.9%.

Anthropometrics

Groups were similar

• 14% reported hx of CVD
• 94% met NCEP ATP III definition for metabolic syndrome
• 15.3% were taking insulin
• 87.3% were taking diabetes medications (including insulin)
• 51% were on lipid-lowering medication
• A BMI of at least 30.0kg per m² was present in 85% of participants.

Location

16 Medical centers in the US.

 

Variables	Treatment Group Changes from Baseline to Year One	Control Group Changes from Baseline to Year One	Statistical Significance of Group Difference
A1C	-0.64±0.02	-0.14±0.02	P<0.001
Fasting Glucose	-21.5±0.9	-7.2±0.9	P<0.001
HDL	3.4±0.2	1.4±0.1	P<0.001
Triglyceride	-30.3±2.0	-14.6±1.8	P<0.001
Metabolic Syndrome	-14.7±0.8	-7.1±0.7	P<0.001

Other Findings

• Within the ILI group, 37.8% met the individual weight-loss goal (over 10% of initial weight) and 55.2% met the group goal (over 7%), compared with 3.2% and 7.0% of DSE participants, respectively. These weight-losses were accompanied by greater mean reductions in waist circumference in the ILI than DSE group.
• Fitness tended to increase in both groups, however increases were more prevalent and tended to be larger among the ILI participants. After covariate adjustment for weight changes, the fitted mean difference in fitness increases between groups remained statistically significant (15.9% for ILI vs. 10.8% for DSE; P<0.001)
• During the first year, use of glucose lowering medicines among the ILI participants decreased from 86.5% to 78.6%, whereas it increased with the DSE group from 86.5% to 88.7% (P<0.001)
• Use of lipid-lowering drugs increased in both groups, however the increase was significantly smaller among the ILI group (P<0.001).

• At one year, the ILI participants had a significantly greater weight-loss and cardiovascular fitness, as compared to the DSE group. The ILI group also had a significantly greater decrease in the number of medications used to treat their diabetes. The ILI group had a higher percentage of participants that met their A1C, blood pressure and lipid goals.
• The authors stated that it appears that individuals with diabetes, especially those on insulin, may have more difficulty losing weight and then keeping it off than those without diabetes. The larger weight-loss in this study, compared to prior clinical trials, may be due to the combination of group and individual contact, the higher physical activity goal or the more intense dietary intervention, which included not only calorie and fat restrictions, but also structured meal plans, each of which has previously been associated with successful weight-loss and maintenance.
• The authors stated that at the one-year marker, the change in risk factors of the ILI group had potential cardiovascular benefits, but that it will take several additional years to determine whether the initial weight-loss will be maintained and whether the favorable risk factor changes translate into reduced cardiovascular events.

Government:

Dept. of Health and Human Services

• This study did demonstrate statistically significant better results for weight-loss in type 2 diabetics and reduction in cardiovascular disease risk factors with the ILI group, compared to the DSE group. The ILI group had a closely-monitored program, consisting of a caloried deficit diet, increased physical activity and behavior modification. They were also seen more often: Weekly the first six months and biweekly from Months Seven to 12. The DSE group were invited to only three group sessions the first year after the initial two-week run period and the study did not state how many participants did return for those three additional sessions.
• Intense monitoring of participants that include behavior modification, is more likely to deliver positive behavior changes. This would be expected from the ILI group. Since research states that 95% of people who try to lose weight usually gain the weight back, this clinical trial needs to continue to follow these participants for more than one year to see if the results continue to be favorable. An ongoing education support system for the ILI participants may also help to maintain their weight-loss and reduce their risk for cardiovascular disease.