EAL

NC: Diabetes Management (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine whether a lifestyle-intervention program or the administration of metformin would prevent or delay the development of type 2 diabetes.

Inclusion Criteria:

At least 25 years of age
Body mass index of at least 24 or 22 in Asians
Plasma Fasting Glucose of 95mg to 125mg per dL and two-hour 75-gram oral glucose load of 140mg to 199mg per dL.

Exclusion Criteria:

Persons taking medications that may alter glucose tolerance
Persons with illnesses that could seriously reduce their life expectancy or their ability to participate in the trial.

Description of Study Protocol:

Recruitment

Persons from 27 medical clinics that were at high risk for diabete.

Design

Enrollment to allow for half the participants from racial or ethnic minority groups
A four-step screening process was used
Eligible participants were randomly assigned to one of three interventions.

Blinding Used

Assignments to metformin or placebo were double-blinded.

Intervention

Standard Lifestyle Recommendations plus metformin at 850mg BID
Standard Lifestyle Recommendations plus placebo BID
Intensive Lifestyle Intervention Program.

Statistical Analysis

P-values
Confidence intervals
Life-table method
Log rank test
Fixed-effects models.

Data Collection Summary:

Timing of Measurements

Baseline
Six months
One year
1.5 years
Two years
2.5 years
Three years
3.5 years
Four years.

Dependent Variables

Body weight in kilograms
BMI
Physical activity: Self-reported; assessed with the Modifiable Activity Questionnaire
Mean fasting glucose
Glycosylated hemoglobin
Oral glucose load: 75-gram glucose load
Diet: Nutrients assessed with the use of a modified version of the Block food frequency questionnaire
Development of diabetes.

Independent Variables

Metformin group
Intensive Lifestyle Intervention Group.

Control Variables

Placebo Group.

Description of Actual Data Sample:

Initial N: 3,234 (32.3% male, 67.7% female)
Attrition (final N): 2,991 (92.5%)
Mean age: 51 years.
Ethnicity: 55% Caucasian, 45% minority
Other relevant demographics: Unsure
Anthropometrics: Groups were similar
Location: 27 medical centers.

Summary of Results:

Variables		Treatment Group with Metformin Incidence of Diabetic Cases in 100 Persons per Year	Treatment Group with Lifestyle Incidence of Diabetic Cases in 100 Persons per Year	Control Group Incidence of Diabetic Cases in 100 Persons per Year	Statistical Significance of Group Difference
Fasting Glucose	95-109 mg/dL	5.5 cases	2.9 cases	6.4 cases	Metformin vs control
Fasting Glucose	110-125 mg/dL	12.3 cases	8.8 cases	22.3 cases	P<0.05
Incidence of Diabetes		23.2 cases in 100 persons per year	14.7 cases in 100 persons per year	33.5 cases in 100 persons per year	Differences between Lifestyle and Control P<0.05

Other Findings

The incidence of diabetes was reduced by 58% with the Lifestyle Intervention Group, compared to the control
The incidence of diabetes was reduced by 31% with the Metformin Group, compared to the control
Metformin was less effective in persons with lower base-line body mass index or a lower fasting plasma glucose concentration than in those with higher values
Reduction in the average fasting plasma glucose concentration was similar in the Lifestyle Intervention and Metformin Groups, but the Lifestyle Intervention Group had a greater effect than metformin on glycosylated hemoglobin
A larger proportion of participants in the Lifestyle Intervention Group had normal post-load glucose values at follow-up.

Author Conclusion:

The authors concluded that their study showed that treatment with metformin and modification of lifestyle were two highly effective means of delaying or preventing type 2 diabetes
The lifestyle intervention was particularly effective, with one case of diabetes prevented per seven persons treated for three years.

Funding Source:

Not-for-profit

Reviewer Comments:

There was lots of data to sort through, which was not assessed at the end of the study in a complete table
The study was not designed to test the relative contributions of dietary change, increased physical acitivity and weight loss to the reduction in the risk of diabetes
It was also confusing with the long duration of the study and that all participants stopped at different times.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	Yes
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	Yes
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	???
	6.6.	Were extra or unplanned treatments described?	???
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	???
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	???
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	Yes
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	N/A
	10.2.	Was the study free from apparent conflict of interest?	???