EAL

DF: Cardiovascular Disease (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine whether Konjac-mannan (KJM) fiber improves metabolic control, as measured by glycemia, lipidemia and blood pressure in high-risk type 2 diabetic patients.

Inclusion Criteria:

Diagnosed at least three years ago with
- Hyperlipidemia
- Hypertension and
- Type 2 diabetes (mean serum C-peptide 701±351pmol per L) .
On medication to control each of the above three risk factors
Consuming a National Cholesterol Education Program (NCEP) Step 2 Diet
Non-smoker
No alcohol consumption
Sedentary lifestyle.

Exclusion Criteria:

Family history of:

Premature CHD
Hypothyroidism
Renal disease
Hepatic disease
Gastrointestinal disease.

Description of Study Protocol:

Recruitment

Not described.

Design

Double-blind placebo controlled crossover design:

Eight-week baseline period: NCEP Step 2 ad libitum diet, documented by three non-consecutive days of food records every two weeks
Two three-week treatment periods separated by a two-week washout interval, over which another three-day food record was obtained. During the first treatment period, subjects were randomly assigned to either
- Konjac-mannam (KJM) treatment: Enriched with KJM fiber (N=5)
- Control treatment (WB): NCEP Step 2 metabolically-controlled diet, enriched with wheat bran fiber (N=6).
For the second treatment period, subjects were crossed over
Subjects were maintained on the same dosage of their medications throughout
Intervention compliance was measured through the return of uneaten foods to the laboratory during the first intervention period and changes were replicated for the second period.

Blinding Used

Double-blind.

Intervention

Both treatments consisted of a three-day rotating NCEP Step 2 diet with three meals per day, provided under metabolic conditions. All foods were pre-weighed, packaged and couriered to participants for consumption at home or at work. Energy intakes for weight maintenance were provided according to Lipid Research Clinics Tables with adjustment for physical activity.
Diet was supplemented using biscuits as the vehcle for consumption of:
- KJM flour: Active high-viscosity glucomannan, 15% other polysaccharides and 16% excipients by weight
- WB flour: Approximately 14g per day of WB fiber derived from standardized hard red wheat bran.
Subjects were instructed to eat an equal amount of biscuits along with an eight-ounce beverage as a snack three times daily, including once at bedtime
Total dietary fiber was administrated at two grams per 412kJ (100kcal) with a mean daily intake, according to energy intake, ranging from 24g to a plateau of 50g for those consuming 2,500kcal per day or more.

Statistical Analysis

Two-tailed Student’s T-test for paired data (proc univariate): Serum lipids, apolipoproteins, glycemia, blood pressure and body weight between
Bonferroni: Hochberg procedure for primary and secondary outcomes (adjustment for multiple comparisons)
Pearson correlations (confounding effects of body weight).

Data Collection Summary:

Timing of Measurements

The following were collected at baseline and Week Three of each of the diet periods:

Glucose
Insulin
Fructosamine
C-peptide
Serum lipids
Apolipoprotein
Blood pressure
Weight.

Dependent Variables

Glucose
Insulin
Fructosamine
C-peptide
Serum lipids
Apolipoprotein
Blood pressure
Weight.

Independent Variables

Type and quantity of fiber consumed.

Control Variables

Weight.

Description of Actual Data Sample:

Initial N: 11 (five men, six women)
Attrition (final N): None reported.

Age

Men: 62±8 years
Women: 59±7 years.

Ethnicity

Not reported.

Other Relevant Demographics

	Males	Females
Total cholesterol	6.2±0.4mmol/L	5.9±0.5mmol/L
HgbA1C	7.4±2.1%	8.3±3.0%
Blood pressure	1,139/78	136/82

All on lipid-lowering medications and metformin, many on insulin, antihypertensives.

Anthropometrics

Males: 133±33% IBW
Females: 143±22% IBW.

Location

St. Michael's Hospital Toronto, Canada.

Summary of Results:

Intake Before and After Study Period


		Baseline	KJM	WB
Total energy (kJ/d)		7,671±1,760	8,907±2,250	9,134±1,006
Available carbohydrate (%)		56.5±14.3	60.5±8.6	61.2±6.5
Total fiber (g/d)		27.4±14.2	39.3±11.4	40.1±12.5
	Soluble fiber (g/d)	8.1±2.7	23.1±4.1	8.3±2.4*
	Insoluble fiber (g/d)	17.8±4.2	16.7±3.6	29.8±4.8*

*P<0.001.

End Points of Metabolic Control During the KJM and WB Study Periods

Primary Outcomes	KJM Percentage Change (Week 3 to Week 0)	WB (Control) Percentage Change (Week 3 to Week 0)	Statistical Significance of Group Difference
Total cholesterol	-16±2.7	-4.9±3.7	0.025
LDL cholesterol	-25±3.9	-4.8±5.9	0.033
Total:HDL Cholesterol, mmol/L	-5.7±2.3	4.7±4.4	0.028
Apolipoprotein B	-14±3.4	-3.0±5.0	0.025
Fructosamine, mmol/L	-6.1±2.4	-0.5±1.4	0.007
Systolic BP, mmHg	-5.5±1.4	1.4±2.7	0.021
Weight, kg	-0.6±0.5	-0.6±0.4	0.05

Significant decrease in primary lipid endpoint (total:HDL cholesterol) between treatments (10±4.0%, P=0.034)
Significant decrease in primary glycemic endpoint (fructosamine) between treatments (5.7±1.7%, P=0.007)
Significant decrease in body weight in both diets.

Other Findings

Good compliance, average food consumption
- KJM: 93% diet calories prescribed; 88% (137g per day) biscuits
- WB: 95% of diet calories prescribed; 91% (142g per day) biscuits.
Secondary end points not significant after adjustment for multiple comparisons
- Body weight
- Total, LDL and HDL cholesterol
- Triglycerides
- Apolipoproteins A-1, B and their ratio
- Glucose
- Insulin
- Diastolic blood pressure.

Author Conclusion:

Supplementation with 0.7g per 100kcal soluble fiber in the form of KJM decreased surrogates of serum lipids (total cholesterol:HDL ratio) and glucose (fructosamine) as well as blood pressure in individuals with documented metabolic syndrome.

Funding Source:

Government:

NIMH, NIH

Reviewer Comments:

Small sample size: No power calculation for null findings on secondary outcomes
Good that they adjusted for multiple comparisons, given all the outcomes reported
Discussed ANCOVA, but unclear what the covariates were and it was not reported in the results. Likewise, discussed incorporating random subject effect and baseline measurements but didn't see where these were reported in the results.
Dicofarm funded the project and provided the biscuits.

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
	1.3.	Were the target population and setting specified?	Yes
	2.	Was the selection of study subjects/patients free from bias?	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
	2.1.	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?	N/A
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	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
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	3.	Were study groups comparable?	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
	3.1.	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?	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	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
	3.4.	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
	3.5.	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
	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.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	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%.)	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	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.	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
	5.1.	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
	5.2.	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
	5.3.	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
	5.4.	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
	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.	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
	6.1.	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
	6.2.	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
	6.3.	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
	6.4.	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
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments 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
	6.7.	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
	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.	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
	7.1.	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
	7.2.	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
	7.3.	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
	7.4.	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
	7.5.	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	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.	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
	8.1.	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
	8.2.	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
	8.3.	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
	8.4.	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
	8.5.	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
	8.6.	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
	9.	Are conclusions supported by results with biases and limitations taken into consideration?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	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.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes