DM: Prevention of Type 2 Diabetes (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
The purpose was to determine whether the progression of IGT to type 2 DM could be influenced in Asian Indian subjects.
Inclusion Criteria:
  • Nondiabetic but diagnosed as having IGT (according to WHO criteria of fasting glucose < 7.0 mmol/L; 2-hour gucose 7.8-11.0 mmol/L) on two occasions
  • No major illness
  • Aged 35 - 55 years
Exclusion Criteria:
  • Diagnosed type 2 diabetes (before entry into study).
  • Absence of IGT (according to WHO criteria).
  • < 35 years old or > 55 years of age
Description of Study Protocol:

Recruitment : Subjects recruited using work-place announcements and flyers from middle-class individuals working in service organizations (family members also allowed to participate). Recruited by screening for 2 hour post-glucose capillary glucose. Confirmed diagnosis with OGTT. 

Design: RCT

Blinding used: primary investigators blinded to interim results

Intervention:

  1. lifestyle modification (LSM)
  2. metformin (MET)
  3. lifestyle modification and metformin (LSM + MET)

Statistical Analysis

Reported mean and standard deviation for continuous variables. Inter-group comparisons tested by two-tailed ANOVA. Compared proportions by X2 analysis. Performed linear regresssion analysis to identify correlation between weight loss and change in plasma glucose. Used Cox proportional hazard analysis to determine proportion of subjects developing diabetes in each group and factors influencing progression. Independent variables in proportional hazard model included intervention groups in relation to control, sex, age, family history of diabets, BMI, waist circumference, baseline fasting and 2-hour glucose and corresponding insulin values, hypertension and smoking. Calculated absolute and relative risk reductions and 95% CIs of estimates. Statistical significance set at P< 0.05.

Data Collection Summary:

Timing of Measurements

  • OGTT and capillary blood glucose measured at baseline
  • Electrocardiogram at baseline and annual follow-up.
  • BMI calculated at baseline
  • Blood pressure recorded at baseline
  • Medication compliance (metformin) measured every 3 months by reviewing subject diaries and counting pills
  • Physical activity (of occupation, transportation to work and leisure activities) taken into account at baseline and all subjects asked to continue routine activities; Sedentary individuals advisd to walk briskly for at least 30 minutes per day
  • Counseling for diet, medication, physical activity explained individually at entry into study;
  • Biochemical assessments (OGTT, fasting serum lipid profile, plasma insulin) at baseline and every 6 months

Dependent Variables

  • Development of type 2 DM

Independent Variables

  • Treatment group 

Control Variables

 

Description of Actual Data Sample:

Initial N: 531 (421 males, 110 females)

Attrition (final N): 502

  1. Control group: 98.5% available for follow-up
  2. LSM: 91% available for follow-up
  3. MET: 96% available for follow-up
  4. LSM + MET: 94.6% available for follow-up

Age: 45.9± 5.7 years

Ethnicity: Indian

Other relevant demographics: groups alike on all baseline demographic characteristics except that a subgroup of individuals ages 50 - 55 in the lifestyle and metformin group had a higher family history of diabetes (P=0.031 by ANOVA)

Anthropometrics: BMI 25.8±3.5 kg/m2

Location: India

 

Summary of Results:


  Control LSM

MET

LSM + MET

Cumulative incidence of DM at year 3,

% (95% CI)

55.0 (46.0-63.5) 39.3 (30.4-48.5) 40.5 (32.0-49.7) 39.5 (30.9-48.9)

Absolute risk reduction,%

 -

 15.7

14.5 

15.5

Relative risk reduction,

% (95% CI)

 -

 28.5 (20.5-37.3)

26.4 (19.1-35.1)

28.2 (20.3-37.0)
P value vs. control (Cox regression) - 0.018 0.029 0.022
Number needed to treat for 3 years to prevent DM in one case - 6.4 6.9 6.5

 Other Findings

Weight:

  • Subjects in the control group had a significant incrase in weight at 12, 24 and 30/36 months relative to the baseline value (P<0.01). 
  • In the LSM group, significant weight increase was seen at 24 months (P<0.035).
  • No significant change in MET and LSM + MET groups.
  • For subjects in intervention groups who lost weight, weight reduction and change in plasma glucose not significantly correlated.
Adverse Events:
  • 22 subjects in the MET and LSM + MET groups reported symptoms of hypoglycemia when receiving 500 mg metformin twice daily; symptoms did not recur when dose reduced to 250 mg twice daily
Author Conclusion:
Lifestyle modifications and metformin were equally effective in reducing progression of IT to diabetes. Effectiveness was not enhanced by a combination of metformin and lifestyle modifications.
Funding Source:
Reviewer Comments:
Because results were so conclusive at intermediate review, 132 subjects who had completed 30 months (of the 36 month trial) were recalled for close-out OGTT at 30 months.
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? Yes
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.) Yes
  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? N/A
  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? Yes
  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? Yes
  6.6. Were extra or unplanned treatments described? N/A
  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? Yes
  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? Yes
  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)? Yes
  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? Yes
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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes