EAL

PDM: Prediabetes (2013)

Citation:

Dyson PA, Hammers MS, Morris RJ, Holman RR, Turner RC, on behalf of the Fasting Hyperglycaemia Study Group. The Fasting Hyperglycaemia Study: II. Randomized controlled trial of reinforced healthy-living advice in subjects with increased but not diabetic fasting plasma glucose. Metabolism, 1997; 46 (12) Suppl 1: 50-55.

PubMed ID: 9439560

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To study the effects of both lifestyle changes and sulfonylurea therapy in a factorial two-by-two design.

Inclusion Criteria:

Self-referred subjects thought to be at risk of developing non-insulin-dependent diabetes meliltus (NIDDM) and with fasting plasma glucose (FPG) in the range of 5.5mmol to 7.7mmol per L on two consecutive tests, two weeks apart.

Exclusion Criteria:

Self-referred subjects who did not meet the inclusion criteria for FPA on two consecutive tests, two weeks apart.

Description of Study Protocol:

Recruitment: Subjects were recruited in two French and three English centers. Subjects were self-referred with at least one risk factor for NIDDM.
Design: Randomized controlled trial.
Blinding use: Implied with laboratory measures. Completed food diaries were coded by a single dietitian blinded to the subject's therapy allocation.

Intervention

Basic Healthy-Living Advice Group: Were provided written dietary information and seen by a physician who advised weight loss if BMI was over 25kg/m² and to increase physical activity: Subjects were seen every three months for assessment of glycemia, but health-living advice was not reiterated
Reinforced Healthy-Living Advice Group: Were seen by a dietitian and advised to change their diet in line with the nutritional recommendations of the British Diabetes Association (BDA)
- Specific advice was given on limiting total fat intake and increasing consumption of unrefined CHO and dietary fiber
- Individual energy requirements were calculated using the BDA formula
- Subjects with a BMI over 22kg/m² were advised to lose weight and were given energy prescription providing 500kcal to 700kcal less than their calculated energy expenditure
- Subjects with a BMI of 22 or less were advised to maintain their current weight and diet
- Subjects were seen by a dietitian and a fitness instructor every three months and were required to completed three-day food records and daily exercise diaries (type of exercise, duration and frequency) before each clinic visit.

Statistical Analysis

Paired T-test, descriptive statistics and Mann-Whitney U-test were used to compare continuous variables between baseline and one-year post-intervention between the two groups
Cochran-Mantel-Haenszel test and Spearman rank correlation coefficient were used for the categorical data
All analyses were performed on an intention-to-treat.

Data Collection Summary:

Timing of Measurements

All subjects were asked to record dietary intake prior to randomization and at the end of the one-year study
All subjects were asked to participate in a physical fitness assessment test at baseline and at the end of the one-year study
All subjects were seen at baseline, six weeks and every three months up to one year, for determination of body weight, FPG and blood pressure
All subjects had HbA1c, insulin, triglycerides, HDL-C, LDL-C and total cholesterol, fructosamine and C-peptide measured at baseline and at one-year post-study.

Dependent Variables

Body weight and waist-to-hip ratio
Blood samples analyzed for FPG, HbA1c, insulin, triglycerides, HDL-C, LDL-C and total cholesterol, fructosamine and C-peptide
Blood pressure
Physical fitness assessment, using VO_2max, calculated from heart rate response to a 10-minute bicycle ergometer test.

Independent Variables

Randomization into either a Basic Healthy-Living Advice Group or a Reinforced Healthy-Living Advice Group, in a factorial design with allocation to sulfonyurea or a Control Group who recieved either a placebo or no tablets
Subjects recorded their dietary intake for three consecutive days using a self-explanatory diet diary.

Description of Actual Data Sample:

Initial N

227: 41% male, 59% female

111 in Reinforced Healthy Living Advice Group
116 in Basic Healthy Living Advice Group.

Attrition (Final N)

201 subjects completed the study (89%)
26 dropouts
Subjects allocated to reinforced advice vs. basic advice showed a greater tendency to withdraw from the study (16% vs. 7%, P=0.03). The 11% who withdrew from the study had similar values for body weight, waist-to-hip ratio, measures of glycemia, lipid profiles and blood pressure, compared with subjects who were evaluated for one year, although significantly fewer subjects were male (23% vs. 44%, P=0.04) and more had been allocated to reinforced advice vs. basic advice (69% vs. 46%, P=0.03).

Age

50±9 years.

Ethnicity

French and English.

Other Relevant Demographics

FPG: 6.0mmol per L (5.8 to 6.4).

Anthropometrics

There were no significant differences at baseline between groups except for triglyceride (1.34mmol vs. 1.11mmol per L, P=0.03).

Location

French medical centers at Lyon and Toulouse
English medical centers at Exeter, Leicester and Oxford.

Summary of Results:

Both Reinforced and Basic Advice Groups had a significant mean reduction in body weight (1.5kg) at three months, although the weight subsequently returned to baseline
80 (86%) of the Reinforced Advice Group and 85 (79%) of the Basic Advice Group were advised to lose weight, however from baseline to one year, weight change was not significant for either group: In a secondary analysis at one year, excluding subjects allocated to sulfonylurea, there was a significant reduction in mean body weight of 1.2kg (P<0.01) with no difference between those in the Reinforced or Basic Advice Groups (80.7kg to 79.4kg vs. 82.2kg to 81.1kg, respectively)
At one year, the Reinforced Group (N=78) decreased their kcal intake by 283kcal (CI, -394 to -173; P<0.001), compared to the Basic Advice Group (N=100) who also decreased their kcal intake by 203kcal (CI, -313 to -93; P<0.001); a net difference of 80kcal, which was not significant between the two groups
At one year, the Reinforced Group (N=78) decreased their percentage fat intake 3.5% (CI, -5.3 to -1.7; P<0.001), compared to the Basic Advice Group (N=100) who also decreased their percentage fat intake by 1.4 (CI, -3.0 to -0.2; not significant); a net difference of -2.1% in fat intake between the two groups, which was significant (P<0.04)
Of the subjects (N=112) tested for VO_2max, the Reinforced Advice Group showed a significantly greater increase (P=0.01) in VO_2max (fitness) than the Basic Advice Group: The VO_2max increase in the Reinforced Advice Group was positively correlated with the mean level of exercise reported in the diaries (R_s=0.39, P=0.005)
No significant change was noted in blood pressure, FPG or HDL-C for either group
HbA_1c in the Reinforced Group (N=85) decreased by -0.1 (CI, -0.2 to 0.0; P<0.05) and by -0.1 (CI, -0.2 to 0.0; P<0.01) in the Basic Advice Group (N=103), with no signficant difference between the groups
Cholesterol in the Reinforced Advice Group (N=92) decreased by -0.2 (CI, -0.3 to -0.1; P<0.01) and by -0.2 (CI, -0.3 to 0.0; P<0.001) in the Basic Advice Group (N=104), although there was no significant difference between the two groups
LDL in the Reinforced Advice Group (N=92) decreased by 0.1 (CI, -0.2 to 0.0; P<0.01) compared to -0.02 (CI, -0.3 to -0.1; P<0.001) in the Basic Advice Group (N=104), which was not significant between the two groups
Insulin sensitivity, as assessed by CIGMA, increased significantly in the Reinforced Advice Group (51% to 61%, P<0.01), but not in the Basic Advice Group (54% to 57%, NS) and the comparative change was not significant between the two groups
There were no differences in waist-to-hip ratio or blood pressure between groups. Lipid and renal outcomes were not reported.

Author Conclusion:

Authors suggest that lifestyle changes required to produce a significant reduction in glycemia in subjects with IFG are difficult to achieve, but some realistic and flexible changes including physical fitness and reducing fat intake are possible and should be encouraged.

Funding Source:

Government:

Medical Research Council, London UK

Industry:

Servier Laboratories, Slough, UK

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

Subjects were self-referred
The specifics about the Sulfonylurea Group were not explained, so that aspect of the study design and methods was unclear
Significant differences between groups at baseline, as well as between drop-outs and completers
Specific exclusion criteria were not identified and the inclusion criteria was somewhat unclear, i.e., use of medications to control blood sugars, other disease conditions, etc.
Method of randomization was not identified
Confounders were not accounted for, therefore the statistical analysis was incomplete, i.e., therapy or treatment changes during the intervention.

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?		???
	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?	No
	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?		No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	No
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	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?		No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	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?	N/A
	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?		???
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	No
	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?	No
	6.6.	Were extra or unplanned treatments described?	No
	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?	No
	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?		???
	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?	No
	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)?	No
	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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes