EAL

PDM: Prediabetes (2013)

Citation:

Lankinen M, Schwab U, Kolehmainen M, Paananen J, Poutanen K, Mykkanen H, Seppanen-Laakso T, Gylling H, Uusitupa M, Oresic M. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: The Sysdimet study. PLos One. 2011; 6(8): e22646.

PubMed ID: 21901116

Study Design:

Randomized Controlled Trial

Class:

A - Click here for explanation of classification scheme.

Quality Rating:

POSITIVE: See Quality Criteria Checklist below.

Research Purpose:

To investigate the synergistic effects of whole grain and low-insulin-response grain products, fatty fish and bilberries on glucose metabolism and plasma lipidomic profile in people with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) and features of metabolic syndrome. Also, to study if increased plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content is related the improved glucose metabolism.

Inclusion Criteria:

Volunteers recruited from the Kuopio region of Finland
Aged 40 to 70 years
Impaired glucose metabolism (fasting glucose 5.6mmol to 6.9mmol per L or two-hour oral glucose tolerance test 7.8mmol to 11.0mmol per L)
At least two of the following:
- BMI: 26kg/m² to 39kg/m²
- Waist circumference: 102cm or more for men and 88cm or more for women
- Serum triglycerides: 1.7mmol or more per L
- HDL: Less than 1.0mmol per L in men and less than 1.3mmol per L in women
- Blood pressure: 130/85mm Hg or more or the use of medication for hypertension.

Exclusion Criteria:

Potential participants were excluded for not meeting the inclusion criteria (N=58), declining to participate (N=5) and other reasons (N=14).

Description of Study Protocol:

Recruitment

Individuals were recruited throughout the Kuopio region.

Design

Randomized controlled trial. Participants were randomly assigned to Treatment 1, Treatment 2 or Control group for a 12-week intervention.

Blinding Used

Implied with measurements.

Intervention

Treatment 1 subjects consumed a Healthy Diet including low glycemic index carbohydrates (20% to 25% of total energy intake), fatty fish (three times per week) and bilberries (three portions per day)
Treatment 2 subjects consumed a Whole Grain Enriched Diet (WGED) including low glycemic index carbohydrates and a high-fiber whole grain oat biscuit
Control subjects were instructed to eat lower fiber carbohydrates than their usual intake.

Statistical Analysis

SPSS Statistical Software (version 14.0, SPSS Inc., Chicago, IL)
Normality of distributions based on histograms
Linear mixed-effect models, base-10 logarithmic scales
Benjamin-Hochburg false discovery rate (FDR), P<0.05 significant
Spearman rank correlation and linear regression model
Kruskal-Wallis test.

Data Collection Summary:

Timing of Measurements

Measurements made at baseline and 12 weeks.

Dependent Variables

Fasting glucose (mmol per L)
Glucose 2 hour (mmol per L)
Fasting insulin (mU per L)
Insulin 2 hour (mU per L)
Area Under the Curve for glucose (mmol per L, calculated)
Area Under the Curve for insulin (mU per L, calculated)
Homeostasis model of insulin resistance [HOMA-IR, calculated from (fasting glucose X fasting insulin) divided by 22.5]
Insulinogenic Index [IGI, calculated from (insulin 30 minutes to insulin zero minutes) divided by (glucose 30 minutes to glucose zero minutes)]
Quantitative Insulin Sensitivity Check Index [QUICKI, calculated from one divided by (1g10 insulin zero minutes, mU per L) + 1g10 (glucose zero minutes, mg per dL)].

Independent Variables

Treatment 1 subjects consumed a Healthy Diet including low glycemic index carbohydrates (20% to 25% of total energy intake), fatty fish (three times per week) and bilberries (three portions per day)
Treatment 2 subjects consumed a Whole Grain Enriched Diet (WGED) including low glycemic index carbohydrates and a high-fiber whole grain oat biscuit
Control subjects were instructed to eat lower fiber carbohydrates than their usual intake
Dietary intake was monitored in self-reported food records including daily intake of test specified interventions and four-day food records conducted during the run in and three times during the intervention period.

Description of Actual Data Sample:

Initial N: 208 assessed for eligibility
Attrition (final N): 131 randomized for treatment, 106 completed study (81%)
Age: 59±7 years
Ethnicity: Not specified, residents of Finland
Other relevant demographics: Medication use similar across treatment groups.

Anthropometrics

	Healthy Diet, N=37	WGED, N=34	Control, N=35
Gender, male/female	17/20	17/17	18/17
Age	58±7	58±8	59±7
BMI	31.1±3.6	31.4±3.4	31.0±3.6
Fasting glucose	6.1±0.5	6.1±0.4	6.2±0.5
Serum triglycerides	1.6±0.6	1.5±0.8	1.5±0.8

Location: Kuopio, Finland.

Summary of Results:

Key Findings

Benjamini-Hochberg False Discovery Rate (FDR) Significance of Change in Glucose and Insulin Parameters from Baseline to End of 12-week Intervention (*Significant)

	Healthy Diet	WGED	Control
Fasting glucose	0.71	0.99	0.81
Glucose, two-hour	0.027*	0.058	0.81
Fasting insulin	0.37	0.16	0.81
Insulin, two-hour	0.69	0.16	0.95
AUC for glucose	0.027*	0.16	0.84
AUC for insulin	0.64	0.57	0.89
HOMA-IR	0.43	0.16	0.89
IGI	0.076	0.99	0.89
QUICKI	0.37	0.16	0.81
Disposition index	0.08	0.99	0.82

Other Findings

Body weight remained constant in all groups and all groups were similar at baseline
Compliance with diets was good per self-reported intake
Healthy Diet group had increased EPA, DHA, alpha-linoleic acid and fiber intake compared to Control
WGED group had decreased total fat and increased fiber compared to Control
Of the total 364 lipids identified and quantified, 25 lipids were significantly changed when comparing Healthy Diet and WGED intervention groups to Control group
Regression model revealed significant association between the changes in plasma EPA and DHA with changes in IGI (R=0.366, P=0.009 and R=0.379, P=0.006) and DI (R=0.366, P=0.009 and R=0.382, P=0.006).
In the Healthy Diet group, plasma proportion of n-3 long-chain PUFAs increased (P<0.05) compared to the other groups
Blood pressure and renal outcomes not studied.

Author Conclusion:

A diet with high intake of whole grain and low insulin response grain products, fatty fish and bilberries appeared to improve glucose metabolism and altered plasma lipidomic profile markedly, while exclusive carbohydrate modification caused only minor changes. EPA and DHA may have an independent association with glucose metabolism. The impact of the healthy diet intervention did not alter insulin resistance but instead improved insulin secretion. This occurred only in the highest quartiles of EPA and DHA changes.

Funding Source:

Government:	VTT Technical Research Centre of Finland
University/Hospital:	University of Eastern Finland, Kuopio University Hospital
In-Kind support reported by Industry:	Yes

Reviewer Comments:

This study includes a thorough analysis of fatty acids and lipidomics
Control group was actually a modest treatment group by reduction of potential usual fiber intake
Authors note the impact of bilberry consumption could not be independently correlated due to lack of biomarker.

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?	No
	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?	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
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)?	N/A
	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?	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