ShouldViscousFiberSupplementsBe Considered in DiabetesControl? Results From aSystematic Review andMeta-analysis of RandomizedControlled TrialsDiabetes Care 2019;42:755–766 | https://doi.org/10.2337/dc18-1126

OBJECTIVE

Evidence from randomized controlled trials (RCTs) suggests that viscous dietaryfiber may offer beneficial effects on glycemic control and, thus, an improvedcardiovascular disease risk profile. Our purpose was to conduct a systematic re-view and meta-analysis of RCTs to synthesize the therapeutic effect of viscousfiber supplementation on glycemic control in type 2 diabetes.

RESEARCH DESIGN AND METHODS

MEDLINE,Embase,andCochraneCentralRegisterofControlledTrialsweresearchedthrough 15 June 2018. We included RCTs ‡3 weeks in duration that assessed theeffects of viscous fiber on markers of glycemic control in type 2 diabetes. Twoindependent reviewers extracted data. Data were pooled using the generic inversevariance method and expressed as mean differences (MD) with 95% CIs. Hetero-geneity was assessed (Cochran Q statistic) and quantified (I2 statistic). The Gradingof Recommendations Assessment, Development, and Evaluation (GRADE) ap-proach was used to evaluate the overall certainty of the evidence.

RESULTS

Weidentified28eligible trial comparisons (n=1,394).Viscousfiberat amediandoseof∼13.1 g/day significantly reduced HbA1c (MD20.58% [95% CI20.88,20.28]; P =0.0002), fastingbloodglucose (MD20.82mmol/L [95%CI21.32,20.31];P=0.001),and HOMA-insulin resistance (IR) (MD 21.89 [95% CI 23.45, 20.33]; P = 0.02)compared with control and in addition to standard of care. The certainty ofevidence was graded moderate for HbA1c, fasting glucose, fasting insulin, andHOMA-IR and low for fructosamine.

CONCLUSIONS

Viscous fiber supplements improve conventional markers of glycemic controlbeyond usual care and should be considered in themanagement of type 2 diabetes.

1Clinical Nutrition and Risk Factor ModificationCentre, St. Michael’s Hospital, Toronto, Canada2Department of Nutritional Sciences, Faculty ofMedicine,UniversityofToronto, Toronto, Canada3Toronto 3D Knowledge Synthesis and Clini-cal Trials Unit, St. Michael’s Hospital, Toronto,Canada4Division of Endocrinology and Metabolism,St. Michael’s Hospital, Toronto, Canada5Li Ka Shing Knowledge Institute, St. Michael’sHospital, Toronto, Canada6Vuk Vrhovac University Clinic for Diabetes,Endocrinology and Metabolic Diseases, MerkurUniversity Hospital, University of Zagreb Schoolof Medicine, Zagreb, Croatia

Correspondingauthor: VladimirVuksan, v.vuksan@utoronto.ca

Received 23 May 2018 and accepted 19 Septem-ber 2018

This article contains Supplementary Data onlineat http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc18-1126/-/DC1.

E.J. and R.K. are co–first authors.

This article is part of a special article collectionavailable at http://care.diabetesjournals.org/evolution-nutritional-therapy.

© 2019 by the American Diabetes Association.Readers may use this article as long as the workis properly cited, the use is educational and notfor profit, and the work is not altered. More infor-mation is available at http://www.diabetesjournals.org/content/license.

Elena Jovanovski,1,2 Rana Khayyat,1,2

Andreea Zurbau,1,2 Allison Komishon,1

Nourah Mazhar,1,2

John L. Sievenpiper,1,2,3,4,5

Sonia Blanco Mejia,1,2,3

Hoang Vi Thanh Ho,1 Dandan Li,1,2

Alexandra L. Jenkins,1 Lea Duvnjak,6 and

Vladimir Vuksan1,2,4,5

Diabetes Care Volume 42, May 2019 755

EVOLU

TIONOFNUTR

ITIONALTH

ERAPY

Despite advancements in preventivemedicine and pharmacotherapy, diabe-tes remains an overwhelming healthproblem. Diet and lifestyle are amongthe main pillars in the management oftype 2 diabetes, with fiber consistentlyconsidered a significant component ofdietary interventions steering glycemiccontrol (1). However, a 2014 positionstatement from the American DiabetesAssociation (ADA) deemphasized the im-pact of fiber in diets, reporting its po-tential for glucoregulation as marginal,with modest improvements of 0.2–0.3%in HbA1c requiring “unrealistic” quanti-ties of .50 g/day (2,3).In contrast, there is a plethora of

clinical evidence on using soluble viscousdietary fiber supplements in the regula-tion of hyperglycemia and reduction ofconventional cardiovascular disease riskfactors (4–7). This has been reflected inthe 2018 ADA Standards of Medical Carein Diabetes, which recommends an in-crease in viscousfiber intake fromsourcessuch as oats, legumes, and citrus (8).Nonetheless, the commonly shared viewis that it is difficult to achieve a highdietary fiber intake within the contextof a conventional Western diet withoutthe use of fortified foods or addition offiber isolates (9,10). In response, manyisolated fiber supplements have beendeveloped and extensively studied overthe past three decades with the intentionof offering convenience of use and facil-itating clinical study of the potency of aconcentrated source, with a favorablerecord on glycemic benefits (11).Although the mechanisms of action

have yet to be elucidated, it is hypoth-esized that fiber isolates, such as guargum, b-glucan, or psyllium, have theability to increase viscosity in the hu-man gut and reduce the rate of nutri-ent absorption, and thus demonstrategreater potential to flatten the post-prandial glycemic and insulinemic re-sponses compared with nonviscous fibers(4,12,13). It is less certain, however,whether and to what extent the post-prandial effects are reliably reflected inlong-term improvements, such as reduc-tion in HbA1c. Therefore, the magnitudeof benefit from viscous fiber intake indiabetes management remains ambigu-ous and warrants comprehensive androbust assessment. Hence, the objectiveof this study was to evaluate, through asystematic review and meta-analysis of

randomized controlled trials (RCTs), theeffect of viscousdietaryfiber supplemen-tation on glycemic parameters in indi-viduals with type 2 diabetes receivingusual care.

RESEARCH DESIGN AND METHODS

Protocol and RegistrationThis study followed the guideline of theCochrane Handbook for Systematic Re-views of Interventions (14) and resultswere reported in accordance with thePreferred Reporting Items for Sys-tematic Reviews and Meta-Analyses(PRISMA) (15). The protocol is availableat ClinicalTrials.gov (NCT02629263).

Data Sources and SearchesMEDLINE, Embase, and the CochraneCentral Register of Controlled Trialswere searched using the strategy pre-sented in Supplementary Table 1 toidentify RCTs that investigated theeffect of viscous fiber on glycemic out-comes in individuals with type 2 diabetes.The searchwasperformed through 15 June2018. A manual search of the referencesof included trials supplemented the elec-tronic search. No language restrictionswere applied.

Study SelectionIncluded RCTs were those conductedin individuals with type 2 diabeteswith $3 weeks duration (16) that in-vestigated the effect of viscous fibersupplementation (b-glucan, guar gum,konjac, psyllium, pectin, xanthan gum,locust bean gum, alginate, agar) com-pared with an appropriate control (i.e.,fiber-free supplement or one containinginsoluble fiber, background diet, pla-cebo) on at least one of these glycemicmeasures: HbA1c, fasting glucose, fast-ing insulin, HOMA-insulin resistance(IR), and fructosamine. For multiarmtrials, we included the groups that al-lowed us to isolate the effect of vis-cous fiber supplements from controltreatments. Trials that precluded theisolation of the effect of the viscousfiber because it was incorporated intoa fiber mixture or included as part ofa complex dietary pattern, or becauseof lack of comparison with a calorie-matched control, were excluded. Glyce-mic outcomes criteria were determinedin accordance with the ADA and Diabe-tes Canada Clinical Practice Guidelines(17,18).

Data Extraction and QualityAssessmentUsing a standardized proforma, two in-dependent reviewers (R.K. and N.M.)assessed articles and extracted relevantdata from each report, including fibertype, study design (crossover or parallel),participant characteristics, comparator,dose, duration, background diet, compli-ancemeasures, statistical analysis, coun-try of conducted research, and fundingsources. Disagreement between reviewerswas resolved by consensus or when nec-essary by a third reviewer. If b-glucanwas not reported, viscous fiber from oatb-glucan was conservatively estimated at5% (19). The mean and SD were extractedfor HbA1c, fasting glucose, fasting insulin,fructosamine, and HOMA-IR at changefrom baseline for both control and inter-vention groups. When SD values were notreported, they were calculated from avail-able data (95% CIs or SEM) using standardformulae (14). Authors were contactedfor additional information where neces-sary (20,21).

The Cochrane risk-of-bias tool was usedto assess the study risk of bias (14). Do-mains of bias assessment include sequencegeneration, allocation concealment, blind-ing, incomplete outcome data, and selec-tive outcome reporting. The study wasconsidered low risk of bias when propermethods were taken to reduce bias, highrisk of bias when improper study methodslikely affected the true outcome, and un-clear risk of bias when insufficient infor-mation was provided to permit judgmentof bias level.

Data Synthesis and AnalysisReview Manager (RevMan) version 5.3(The Nordic Cochrane Centre, TheCochrane Collaboration, Copenhagen,Denmark) was used for primary dataanalyses and Stata version 14 (StataCorp,College Station, TX) for subgroup, dose-response, and publication bias analyses.The difference between change-from-baseline values for intervention andcontrol arms was derived from each trialfor the end points of HbA1c, fasting glu-cose, fasting insulin, fructosamine, andHOMA-IR. When change from baselinewas not reported, the mean and SD forbaseline and end values were used to cal-culate change from baseline for both con-trol and intervention groups. WhenHOMA-IR was not reported, it was calcu-lated using the equation (HOMA-IR = fasting

756 Viscous Fiber and Diabetes Diabetes Care Volume 42, May 2019

insulin (microU/L) 3 fasting glucose(mmol/L)/22.5) (22). A previously pub-lished formula was used to derive SD forcalculated values of HOMA-IR (23). Ifchange-from-baseline values were notavailable, end-of-treatment values wereused. For multiarm trials, a weighted av-erage was used to create a single pairwisecomparison and to reduce the unit-of-analysis error. A correlation coefficient of0.50 was assumed for SD of crossovertrials. Sensitivity analysis was conductedwith the use of different correlation co-efficient values (0.25 and 0.75) to test forthe robustness of the effect size. Pooledanalyses were conducted using the genericinverse variance method with random-effectsmodels.When data from,5 trialswere available, fixed-effects modelswere used. Data were expressed as meandifference (MD) with 95% CI and signifi-cance was considered as P , 0.05. Inter-study heterogeneity was assessed usingthe Cochran Q statistic and quantified usingthe I2 statistic, with I2 $50% indicatingsubstantial heterogeneity and P , 0.10significance (14). If .10 studies were in-cluded for an outcome, sources of het-erogeneity were explored with a priorisubgroup analyses for baseline values ofHbA1c, fasting glucose, and HOMA-IR, aswell as for dose, design, duration, fibertype, and foodmatrix (i.e., powder, capsule,food source) with P, 0.05 significance. Apost hoc analysis was also conducted forbaseline BMI. To determine whether anysingle study exerted particular influenceon the overall results, an additional sen-sitivity analysis was performed by re-moving each study individually fromthe meta-analysis and recalculating theeffect size of the remaining studies. Dose-response analysis was performed usingmeta-regressions to generate linear andnonlinear dose estimates using theMKSPLINE procedure, with P , 0.05significance. Visual inspection of funnelplots was used to assess publication biasand formally tested using Egger andBegg tests, where P , 0.05 was consid-ered evidence for small-study effects. Iffunnel plot asymmetry was suspected,the Duval and Tweedie “trim and fill”method was performed to impute missingstudy data and correct for asymmetry.

Grading of the EvidenceThe Grading of Recommendations As-sessment, Development, and Evalua-tion (GRADE) approach (24) was used

to assess the overall certainty of theevidence. Quality can be graded asvery low, low, moderate, or high. Evi-dence obtained from RCTs receivesan initial grade of high. Scores can bedowngraded based on study limitations(assessed by the Cochrane risk-of-biastool), inconsistency (substantial unex-plained heterogeneity, I2 .50%, P ,0.10), indirectness (presence of factorsthat limit the generalizability of the find-ings), imprecision (CI for the effect esti-mates that are wide or cross a minimallyimportant difference for benefit or harm),and publication bias (significant evidenceof small-study effects).

RESULTS

Search ResultsFigure 1 shows the flow of the literature.Our initial search yielded 2,716 pub-lications, of which 66 articles werereviewed in full and 27 (28 trial com-parisons) were included in the final anal-ysis (n = 1,394) (20,21,25–49). Twentytrial comparisons reported on HbA1c(n = 1,148) (21,25,27,29–35,37–42,44,47–49), 28 on fasting glucose (n =1,394) (20,21,25–48), 9 on fasting insulin(n = 228) (21,25,26,29,35,38,41,46,48),and 2 on fructosamine (n = 23) (42,46),and 11 trial comparisons reported onHOMA-IR directly or reported enough

All Reports Identified in Literature Search: 2,716MEDLINE (1946 to 15 June 2018): 938

Embase (1947 to 15 June 2018): 733The Cochrane Library (to 15 June 2018): 1,042

Manual Search: 3

Reports Reviewed in Full: 66

Reports Excluded Based on Title and/or Abstract: 2,650Duplicate Reports: 1,191Abstracts: 4Acute Studies: 11Animal or In Vitro Studies: 25 Editorials/Letters: 16Guidelines/Recommendations: 7Intervention: 866Invalid End point: 152Not a Randomized Controlled Trial: 2Observational Studies: 81Population: 113Reports, Reviews, & Meta-Analyses: 173Summaries & Supplementary Materials: 9

Reports Included: 27 (n = 1,156)HbA1c (n = 910)

Fasting Insulin Fasting Glucose (n = 1,156)

(n = 228)Fructosamine (n = 23)HOMA-IR (n = 414)

Reports Excluded: 39Acute Studies: 6Insufficient Data to Determine Viscous Fiber: 5Intervention: 7Invalid End point: 1Not a Randomized Controlled Trial: 14Population: 4Not Published: 1Inadequate Control: 1

Figure 1—Flow of the literature.

care.diabetesjournals.org Jovanovski and Associates 757

information for calculation (n = 652)(21,25,26,29,35,37–39,41,46,48).

Trial CharacteristicsTable 1 shows the characteristics of in-cluded studies. The majority of trialswere conducted in an outpatient setting,with 15 (54%) in Europe, 5 (18%) in Asia,2 (7%) in North America, 4 (14%) inthe Middle East, and 2 (7%) in SouthAmerica. Of the included trials, 15 (54%)were crossover design and 13 (46%)parallel design. The median age of par-ticipants was 60 years (range 48–67),with a median BMI of 27 kg/m2 (range26–32). Themedian dose of viscous fibersupplementation for all included trialswas 13.1 g/day (range 2.55–21.0) andmedian duration was 8 weeks (range3–52). The Cochrane risk-of-bias tool(Supplementary Fig. 1) showed that 25trials (90%) had unclear risk of bias andthree trials (10%) had low risk of bias forsequence generation. All trials (100%) hadunclear risk of bias for allocation conceal-ment. Seventeen trials (61%) had low riskof bias, 8 trials (29%) unclear risk, and3 trials (10%) high risk of bias for blinding.Sixteen trials (57%) had low risk of bias,8 trials (29%) unclear risk, and 4 (14%) highrisk of bias for incomplete outcome data.The majority of trials (96%) had low

risk but one (4%) had high risk of biasfor selective outcome reporting. Fund-ing sources included agency for 6 trials(21%), industry for 5 (18%), agency-industry for 5 (18%), and were not re-ported for 12 (43%).

Effect on HbA1c

Figure 2 shows the effect of viscous fibersupplementation on HbA1c in individ-uals with diabetes. A median dose of10.9 g/day for a median duration of 8weeks resulted in a significant reductionin HbA1c (MD 20.58% [95% CI 20.88,20.28]; P = 0.0002) compared withcontrol, with evidence of substantial in-terstudy heterogeneity (I2 = 91%, P ,0.00001). Systematic removal of individ-ual studies did not alter the results orexplain heterogeneity. The use of differ-ent levels of correlation coefficients(0.25 and 0.75) for crossover studies didnot influence the HbA1c effect or hete-rogeneity in the overall pooled results.Supplementary Table 2 and Sup-

plementary Fig. 2 show the results ofcontinuous and categorical a priori andpost hoc subgroup analyses for HbA1c.

Continuous meta-regression analyses didnot reveal an effect of dose, duration,baseline fasting glucose, or baselineBMI. Categorical meta-regression analy-ses, however, revealed a greater reduc-tion in trials with higher baseline HbA1cvalues (between-subgroup difference20.70% [21.36, 20.03]; P = 0.04),with residual I2 = 84%.

Effect on Fasting GlucoseFigure 3A shows the effect of viscousfiber supplementation on fasting glucosein individuals with diabetes. Comparedwith control, a median dose of 13.1 g/dayfor a median duration of 8 weeks resultedin a significant reduction in fasting glu-cose (MD20.82 mmol/L [95% CI21.32,20.31]; P = 0.001) with evidence ofsubstantial heterogeneity (I2 = 92%, P ,0.00001). Systematic removal of in-dividual studies did not alter results orexplain heterogeneity. The use of differ-ent levels of correlation coefficients(0.25 and 0.75) for crossover studiesdid not influence the fasting glucoseeffect or heterogeneity in the overallpooled results.

Continuous and categorical a prioriand post hoc subgroup analyses didnot reveal any significant subgroupeffects and failed to explain hetero-geneity (Supplementary Table 2 andSupplementary Fig. 3).

Effect on Fasting InsulinFigure 3B shows the effect of viscous fi-ber supplementation on fasting insulin inindividuals with diabetes. With a mediandose of 15.0 g/day and median durationof 8 weeks, no significant effect on fast-ing insulin was observed (MD 217.56pmol/L [95% CI 237.54, 2.42]; P = 0.08)compared with control, with substan-tial interstudy heterogeneity (I2 = 90%,P , 0.00001). Removal of Abutair et al.(25) during our sensitivity analyses re-duced overall heterogeneity (I2 = 43%,P = 0.09) and modified the effect size(MD 29.18 pmol/L [218.97, 0.60];P = 0.07). The use of different levelsof correlation coefficients (0.25 and0.75) for crossover studies did not in-fluence the fasting insulin effect or het-erogeneity in the overall pooled results.

Continuous and categorical a prioriand post hoc subgroup analyses werenot performed for fasting insulin as,10trial comparisons were available foranalyses.

Effect on HOMA-IRFigure 3C shows the effect of viscousfiber supplementation on HOMA-IR inindividuals with diabetes. Amedian doseof 10.5 g/day for a median duration of6 weeks significantly reduced HOMA-IR(MD 21.89 [95% CI 23.45, 20.33];P = 0.02) compared with control, withsubstantial evidence of interstudy het-erogeneity (I2 = 94%, P , 0.00001).Removal of Abutair et al. (25) duringsensitivity analyses reduced overall het-erogeneity (I2 = 63%, P = 0.004) andmodified the effect on HOMA-IR (MD21.07 [21.88, 20.26]; P = 0.01). Theuse of different levels of correla-tion coefficients (0.25 and 0.75) forthe crossover studies did not influencethe HOMA-IR effect or heterogeneity inthe overall pooled results.

Supplementary Table 2 and Sup-plementary Fig. 4 show the findingsof a priori and post hoc subgroup anal-yses for HOMA-IR. Continuous meta-regression analysis revealed that theeffect of viscous fiber on HOMA-IR ismodified by baseline values (MD20.42 [20.67, 20.16]; P , 0.01), withresidual I2 = 72%. Categorical meta-regression analysis was consistent withthese findings, revealing a greater re-duction in trials with higher baselineHOMA-IR values (between-subgroupdifference 23.49 [25.85, 21.14];P , 0.01), with a residual I2 = 67%.Additional subgroup analyses were notsignificant.

Effect on FructosamineFigure 3D shows the effect of viscousfiber supplementation on fructosaminein individuals with type 2 diabetes. Onlytwo trials reported on this outcomemeasure, with a median dose of 13.2g/day andmedian duration of 7.5 weeks.Compared with control, no significanteffect was observed for fructosamine(MD 20.12 mmol/L [95% CI 20.39,0.14]; P = 0.37) and no evidence ofinterstudy heterogeneity was present(I2 = 0%, P = 0.60). Systematic removalof individual studies and the use ofdifferent levels of correlation coeffici-ents (0.25 and 0.75) for crossover stud-ies did not influence the fructosamineeffect or heterogeneity.

Continuous and categorical a prioriand post hoc subgroup analyses werenot performed as,10 trial comparisonswere available for analyses.

758 Viscous Fiber and Diabetes Diabetes Care Volume 42, May 2019

Table

1—Characteristicsofincludedtrialco

mpariso

ns

Study

Participants*

M:F

Age*y

BMI*

Kg/m

2

Baseline

HbAlc*

%(m

moL/mol)

BaselineFG

*mmoL/L

Design

Duration

wk

Viscous

Fiber

Control

Dose*†

g/d

Food

Matrix

Diet

Funding

Coun

try

Abutair,20

1636

47.5‡

31.7

C:8.5(69)

C:8.7

P8

psyllium

no

10.5

powder

usual

n/r

Palestine

18M:18F

T:8.5(69)

T:9.0

n/r

psyllium

Abutair,2018

3647.5

n/r

n/r

8.9

P8

psyllium

no

10.5

powder

usual

n/r

Palestine

18M:18F

n/r

psyllium

Aro,1981

953

n/r

n/r

C:11.5

C12

guargum

wheat

21granules

usual

A-I

Finland

5M:4F

T:10

.6DB

flour

Baker,1988

30C:64.3

n/r

C:11.9

(107)

C:11.7

P9

guargum

n/r

15tablets

usual

n/r

United

n/r

T:59

.1T:

12.0

(108

)T:

12.1

SBKingdom

Chen

,2003

2264

25.5

n/r

9.1

C4

konjac

cornstarch

3.6

capsules

NCEP

A-I

Taiwan

10M:12F

DB

Chuang,

1992

1354.9

25.8

7.9(63)

10.6

C8

guargum

n/r

15powder

liquid

ATaiwan

n/r

DB

meals

Cugnet-Anceau,

2010

53C:61

.8C:29

.0C:7.5(58)

C:8.4

P8

b-glucan

soup

3.5

enriched

usual

ASw

eden

n/r

T:61

.9T:

30.5

T:7.3(56)

T:8.8

DB

soups

Dall’Alba,

2013

44C:63.6

C:29.3

C:7.0(53)

C:7.9

P6

guargum

n/r

10powder

usual

A-I

Brazil

27M:17F

T:60

.5T:

30.2

T:6.9(52)

T:7.4

OL

Feinglos,2013

33C:56.5

n/r

C:7.6(60)

C:11.8

P12

psyllium

fiber-free

10.2

n/r

restricted

n/r

United

n/r

TA:61

.8TA

:7.4(57)

TA:11

.2DB

placebo

States

TB:64

.8TB

:79

(63)

TB:10

.3

Fuessl,1987

1861.3

30.1

C:9.3(78)

9.1

C4

guargum

wheatbran

15granules

usual

AUnited

12M:6F

T:9.7(83)

DB

Kingdom

Holm

an,1987

2954.2

26.5

n/r

n/r

C8

guargum

n/r

15tablets

n/r

IUnited

24M:5F

n/r

Kingdom

Laajam

,1990

3951.5

31.2

11.4

(101)

12.5

C4

guargum

beef

15granules

usual

n/r

Saudi

11M:28F

DB

gelatin

Arabia

Lalor,1990

1956.5

31.5

n/r

10.9

C12

guargum

n/r

15granules

usual

A-I

United

8M:11F

DB

Kind

om

Li,20

1622

859

27C:8.1(65)

C:9.5

P52

b-glucan

no

3.98

oat

low-fat

IChina

n/r

TA:8.4(68)

TA:9.9

n/r

b-glucan

high-

fiber

TB:8.3(67)

TB:9.7

Liatis,20

0941

C:66

.5C:27

.0C:6.9(52)

C:7.7

P3

b-glucan

no

b-glucan

3bread

usual

n/r

Greece

n/r

T:60

.2T:

29.6

T:7.3(56)

T:8.8

DB

Con

tinu

edon

p.76

0

care.diabetesjournals.org Jovanovski and Associates 759

Table

1—Continued

Study

Participants*

M:F

Age*y

BMI*

Kg/m

2

Baseline

HbAlc*

%(m

moL/mol)

BaselineFG

*mmoL/L

Design

Duration

wk

Viscous

Fiber

Control

Dose*†

g/d

Food

Matrix

Diet

Funding

Coun

try

Ma,

2013

186

57.5‡

C:26

.6C:9.7(83)

C:9.5

P4

b-glucan

no

2.55

oat

SDI

IChina

n/r

TA:26

.6TA

:9.9(85)

TA:10

.1SB

b-glucan

TB:26

.7TB

:9.8(84)

TB:10

.1

McG

eoch,2013

2760.9

31.5

6.8(51)

n/r

C8

b-glucan

no

4oat-based

usual

AUnited

18M:9F

NB

b-glucan

products

Kingdom

Niemi,1988

1863

27C:11.4

(101)

C:12.5

C12

guargum

micro-crystalline

cellulose

15n/r

usual

A-I

Finland

n/r

T:12

.1(109

)T:

11.7

DB

Peterson,1987

1660

27.3

C:11.3

(100)

C:9.7

C6

guargum

noguar

16.6

granules

usual

AUnited

10M:6F

T:11

.2(99)

T:9.5

n/r

gum

Kingdom

Rodriguez-M

oran,

1998

123

C:56.5

C:28.6

n/r

C:7.8

P6

psyllium

micro-crystalline

cellulose

15powder

low-fat

n/r

Mexico

55M:68F

T:57

.0T:

29.1

T:10

.7DB

Sels,1993

1262

25.8

11.3

(100)

9.8

C12

guargum

HFcontrolbread

11.2

bread

usual

n/r

Netherlands

6M:6F

n/r

Uusitupa,

1990

947.8

n/r

n/r

10.6

C4

guargum

wheatflour

15granules

usual

n/r

Finland

4M:5F

DB

Uusitupa,

1989

39C:60.9

n/r

C:9.4(79)

C:12.8

P12

guargum

wheatflour

15granules

usual

AFinland

13M:26F

T:60

.1T:

8.9(74)

T:12

.2DB

Uusitupa,

1984

1762

n/r

n/r

9.7

C18

guargum

wheatflour

21granules

usual

n/r

Finland

n/r

DB

Vuksan,19

9911

M:62

n/r

M:7.4(57)

C:9.3

C3

konjac

wheatbran

15.1

biscuit

NCEP

ICanada

5M:6F

F:59

F:8.3(67)

T:9.6

DB

Wolffenbutt,1992

1262

25.8

11.3

(100)

9.8

C12

guargum

controlbread

11.2

powder

usual

n/r

Netherlands

6M:6F

n/r

Ziai,2005

36C:53.6

C:27.5

C:9.1(76)

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760 Viscous Fiber and Diabetes Diabetes Care Volume 42, May 2019

Dose-Response AnalysesThere was no significant evidence of adose-response effect (SupplementaryFigs. 5 and 6). Visual inspection ofdata suggests doses .10 g/day maybe more effective in HOMA-IR improve-ment, but the difference in slopes for,10 vs. .10 g/day was not significant(P = 0.06). Because of insufficient data,dose-response analyses could not beconducted for fructosamine and onlylinear analysis was performed for fast-ing insulin.

Publication BiasSupplementary Fig. 7 shows the funnelplots for HbA1c, fasting glucose, andHOMA-IR. Visual inspection of funnelplots suggests no asymmetry in HbA1cand fasting glucose and mild asymmetryin HOMA-IR. Formal testing with theEgger and Begg tests was not significantfor evidence of small-study effects. Trimand fill analyses were conducted forHOMA-IR, identifying four additionalstudies imputed to adjust for funnelplot asymmetry (Supplementary Fig.8). Inclusion of imputed studies resulted

in an adjusted MD of 22.67 (95%CI 24.17, 21.18), P , 0.01, suggestingevidence of small-study effects. Publi-cation bias was not assessed for fast-ing insulin and fructosamine as therewere ,10 trial comparisons available.

Grading of the EvidenceSupplementary Table 3 shows the sum-mary of the GRADE assessment for eachoutcome. The effect estimates for HbA1c,fasting glucose, fasting insulin, and HOMA-IR were graded as moderate qualitybased on downgrades of serious incon-sistency for HbA1c, fasting glucose, andHOMA-IR and serious imprecision forfasting insulin. Evidence for fructosaminewas graded low quality owing to down-grades for very serious imprecision.

CONCLUSIONS

This systematic review and meta-analysisquantified the effect of viscous fibersupplementation on indices of glycemiccontrol in 28 RCT comparisons involv-ing individuals with type 2 diabe-tes. Pooled analyses demonstrate an

absolute reduction of 0.58% in HbA1c,0.82 mmol/L in fasting blood glucose,and 1.89 in HOMA-IR following a mediandose of ;13.1 g/day for a median du-ration of ;8 weeks. No significant ef-fects were revealed for fasting insulinand fructosamine. Subgroup analysesrevealed those with higher baselineHbA1c and HOMA-IR values appear toshow greater reductions. There did notappear to be any subgroup effects ofdose, design, duration, baseline BMI,fiber type, or the form of intervention.

Results from our analyses suggest thatviscous fiber may be clinically meaningfulin the management of type 2 diabetes,with reductions in HbA1c exceeding theU.S. Food and Drug Administrationthreshold of $0.3% established fornew antihyperglycemic drug develop-ment (50). Our findings build on thoseof an earlier systematic review andmeta-analysis by Silva et al. (51), whoreported a decrease of 0.52% in HbA1cand 0.55 mmol/L in fasting blood glucosein type 2 diabetes patients following ahigh intake of various types of dietaryfiber, including soluble and insoluble

Figure 2—The effect of viscous fiber supplementation in individuals with type 2 diabetes on primary outcome HbA1c. Diamond represents the pooledeffect estimate for overall analysis. Data are represented as MD with 95% CI, using the generic inverse variance random-effects model. Interstudyheterogeneity quantified by I2 with significance P , 0.10.

care.diabetesjournals.org Jovanovski and Associates 761

Figure 3—The effect of viscous fiber supplementation in individuals with type 2 diabetes on secondary outcomes: fasting glucose (A), fasting insulin(B), HOMA-IR (C), and fructosamine (D). Diamond represents the pooled effect estimate for overall analysis. Data are represented as MD with95% CI, using the generic inverse variance random-effects and fixed-effects models. Interstudy heterogeneity is quantified by I2 with significanceP , 0.10.

762 Viscous Fiber and Diabetes Diabetes Care Volume 42, May 2019

sources, from 12 RCTs. Although the tworeviews cannot be directly comparedgiven the variation in study inclusioncriteria, it is interesting that there wasa similar reduction in HbA1c, suggest-ing that the benefits observed by Silvaet al. (51) may be mostly attributed toviscous fiber. Despite this similarity,grouping viscous soluble and insolublefiber does not provide a reliable estimateof metabolic benefit as it is analogousto grouping therapeutic entities with dif-ferent physiochemical and, hence, phys-iological characteristics. While insolublefiber seems to have specific application,likely in the area of colonic health andstool bulking, viscous fibers appear tohave pleiotropic effects metabolically, asthey improve glycemic control, lipid lev-els, blood pressure, and possibly weight,in addition to potential prebiotic activity(52). Conversely, the strong and con-sistent paradoxical association of non-viscous cereal fiber and whole-grainconsumption to reduced type 2 diabetesincidence from prospective cohort data

remains of important clinical interest(53). Although residual confounding mightpreclude a potential case for causality,the recently hypothesized link of modu-lating gut microbiota by extended cerealfiber intake deserves further investigation(54). The protective role of cereal fiberagainst type 2 diabetes should thereforenot be overlooked and fits within abroader public health case for increasingoverall dietary fiber intake.

The variable efficacy of fiber on gly-cemic control was first highlighted in aseminal study in which Jenkins et al. (55)compared the response to an oral glu-cose tolerance test supplemented withfive fiber types varying in level of viscos-ity. A positive correlation was foundbetween the viscosity of the fiber typeand reduction in peak postprandial bloodglucose and insulin concentrations (55).This benefit was abolished when fiberwas hydrolyzed to its nonviscous form(55). Thus, through its effect in chang-ing the rate of nutrient delivery andendocrine response, viscous fiber intake

resulted in flattening of the glycemicresponse and reduced insulin require-ments, ultimately leading to a reductionin HbA1c, as observed in the presentanalysis. More recently, Chandaliaet al. (56) demonstrated that an effectivelevel of intake can be achieved by con-suming fiber-rich foods. In that study,they found that doubling fiber intakeabove the level recommended byADA at the time achieved a powerfulreduction in 24-h blood glucose andhyperinsulinemia (56). The authors con-cluded that these effects seem to bepredominantly a result of increasingthe viscous fiber foods from the typicallyrecommended 8 g/day in the control armto 25 g/day in the test arm, a differencethat approximates the median effectivedose of 13.1 g/day seen in the currentstudy. Further supporting the case forviscosity, a study comparing severaltypes of viscous fiber supplements re-vealed that themost viscousfiber, konjacglucomannan, resulted in the greatestreduction of postprandial blood glucose

Figure 3dContinued.

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(57). These acute benefits were trans-lated to long-term metabolic improve-ments in individuals with type 2 diabetesand metabolic syndrome (46,58), as wellas lipid lowering in healthy individuals,compared with lower viscosity fibers in-cluding insoluble fiber or wheat brancontrol (52). Similarly, a 6-month inter-vention study in participants with met-abolic syndrome showed no glycemicbenefits on the American Heart Associ-ation Step II diet, but theadditionof 7g/dayof psyllium fiber led to a sustained im-provement in glycemic and insulinemicresponse, including a significant reduc-tion of 0.6% in HbA1c (59).Despite a relatively small quantity of

viscous fiber being required to obtainclinically meaningful benefits in diabetes,the main challenge remains how to in-corporate it into foods while preservingsensory characteristics. From a palat-ability standpoint, semimoist foods in-cluding crisp breads, crackers, muffins,and biscuits are suggested to be themost suitable vehicles for optimal fiberdelivery (60).Even though the prevalent notion is to

favor food rather than supplement useas a primary source of fiber, the use of thelatter would allow one to achieve the goalof an individualized eating plan even inthe absence ofmajor dietary restrictions,such as in the context of lack of willing-ness or ability of an individual to change(8). Notably, with the exception of onestudy where treatment was through dietonly, studies included in our analysisutilized fiber supplements as the in-tervention, with antihyperglycemic oralmedication and insulin having notbeen altered throughout the study pe-riod. This suggests that the effect ofviscous fiber, primarily through supple-ments, seen within the pooled analysisis beyond that of standard pharmaceu-tical therapy.The current study has several

strengths. Importantly, to our knowledgethis is one of the largest and mostcomprehensive systematic reviews andmeta-analyses of RCTs on dietary fiber, inparticular investigating the isolated ef-fect of viscous fiber sources in diabetes.No prior study had differentiated die-tary fiber on the basis of viscosity butrather had done so on the basis of thegravimetrics. Furthermore, the majorityof trials in this study reported glycemiccontrol end points as the primary

outcome and the study included trialsspanning multiple countries, thereby al-lowing for generalizability of findings andreducing potential confounders associ-ated with a single geographic location.Finally, the overall quality and strengthof evidence was assessed using theGRADE approach.

Limitations of this analysis should alsobe recognized when interpreting thefindings. First, we downgraded the cer-tainty of the evidence for serious incon-sistency in the estimates across trials forsome of the assessed outcomes. This wasdue to evidence of heterogeneity thatcould not be explained by sensitivity andsubgroup analyses. Further, the certaintyof the evidence was downgraded forserious and very serious imprecision.Although the 95% CI of the pooled effectestimate for some of our outcomes didnot overlap with our minimally importantdifference for harm (i.e., did not containevidence for harm), the upper bound ofthe 95% CI included 0. The number ofparticipants for the fructosamine out-come was also less than the optimalinformation size criterion,which resultedin an additional downgrade for impreci-sion owing to insufficient power. Due tothe small number of observations forsome outcomes, meta-regression analy-ses could not be conducted, limiting ourexploration of these outcomes. Addition-ally, of the included trials, only 11 had aduration of 12 weeks or longer and 13trials were less than 8 weeks in length.Given the conventional estimate thatHbA1c reflects blood glucose levels inthe preceding three months, inclusionof shorter trials potentially underesti-mated the effect size, as they may nothave been of sufficient duration. Thecertainty of evidence was not down-graded for indirectness as subgroupanalyses revealed no effect modulationby duration. It was also not downgradedfor risk of bias as plausible selectionbias was unlikely to seriously alter theresults. Finally, there was evidence ofpublication bias. Although visual inspec-tion of the funnel plots suggestedasymmetry for HOMA-IR and trim andfill analyses suggested small-study ef-fects, we elected not to downgradefor publication bias, as Egger and Beggtests were not significant and the ad-justed pooled effect estimate after trimand fill analyses did not change direc-tion or significance.

Balancing the strengths and limita-tions, we graded the overall certaintyof available evidence as moderate forHbA1c, fasting glucose, fasting insulin,and HOMA-IR and low for fructosamine.

ConclusionThis study illustrated that viscous fibersupplementation improved conventionalmarkers of glycemic control beyondusual care in individuals with type 2diabetes. Future dietary guidelinesshould be revisited in light of thesefindings, although taking into consider-ation the limitations raised by GRADE.Additional high-quality RCTs are requiredto further explore the effect by fiber typeand to optimize the incorporation ofhighly viscous supplements into thedaily diet.

Acknowledgments. The authors thank TerukoKishibe, Information Specialist, Scotiabank HealthScience Library at St. Michael’s Hospital, forher help in the development of search termsused.Funding and Duality of Interest. R.K. and N.M.have received funding from the King AbdullahScholarship Program, Saudi Arabia. J.L.S. wasfunded by a PSI Graham Farquharson KnowledgeTranslation Fellowship; Canadian Diabetes As-sociation Clinician Scientist Award; CanadianInstitutes of Health Research Institute of Nutri-tion, Metabolism and Diabetes/Canadian Nutri-tion Society New Investigator Partnership Prize;and Banting & Best Diabetes Centre Sun LifeFinancial New Investigator Award. J.L.S. has alsoreceived research support from Diabetes Can-ada, the American Society for Nutrition, CalorieControl Council, INC International Nut and DriedFruit Council Foundation, National Dried FruitTrade Association, the Tate and Lyle NutritionalResearch Fund at the University of Toronto, andthe Glycemic Control and Cardiovascular Diseasein Type 2 Diabetes Fund at the University ofToronto (a fund established by the Alberta PulseGrowers). He has received speaker fees and/orhonoraria from Diabetes Canada, the CanadianNutrition Society, Dr. Pepper Snapple Group,Dairy Farmers of Canada, Sprim Brasil, White-Wave Foods, Rippe Lifestyle, mdBriefcase, Al-berta Milk, FoodMinds LLC, Memac Ogilvy &Mather LLC, PepsiCo, The Ginger Network LLC,International Sweeteners Association, NestleNutrition Institute, Pulse Canada, Canadian So-ciety for Endocrinology andMetabolism (CSEM),and GI Foundation. He has ad hoc consultingarrangements with Winston & Strawn LLP, Per-kins Coie LLP, and Tate & Lyle. He is a member ofthe European Fruit Juice Association ScientificExpert Panel. He is on the clinical practice guide-lines expert committees of Diabetes Canada, theEuropean Association for the Study of Diabetes(EASD), and theCanadianCardiovascular Society,aswell as anexpertwritingpanel of theAmericanSociety for Nutrition. He serves as an unpaid

764 Viscous Fiber and Diabetes Diabetes Care Volume 42, May 2019

scientific advisor for the Food, Nutrition, andSafety Program and the Technical Committee onCarbohydrates of the International Life ScienceInstitute North America. He is a member of theInternational Carbohydrate Quality Consortium,Executive Board Member of the Diabetes andNutrition Study Group (DNSG) of the EASD, anddirector of the Toronto 3D Knowledge Synthesisand Clinical Trials Foundation. His wife is anemployeeofUnileverCanada.A.L.J. is part ownerand Vice President at Glycemic Index Laborato-ries, Inc. (GI Labs), a contract research organi-zation. L.D. has previously received honoraria forspeaking and consultancy and grants for attend-ing scientific conferences from Abbott, Amgen,AstraZeneca, Boehringer Ingelheim, Eli Lilly,Merck, Merck Sharp & Dohme, Novo Nordisk,Novartis, Sanofi, Servier, andTakeda. V.V. holds aresearch grant from the Canadian Diabetes As-sociation for study of dietary intervention in-cluding viscous soluble fiber and holds theCanadian (2,410,556) and American (7,326,404)patents on themedical use of viscous fiber blendfor reducing blood glucose for treatment ofdiabetes, increasing insulin sensitivity, and re-ducing systolic blood pressure and blood lipids.None of the sponsors had a role in any as-

pect of the current study, including design andconduct of the study; collection, management,analysis, and interpretation of the data; andpreparation, review, and approval of the man-uscript or decision to publish.Author Contributions. E.J., A.Z., A.K., H.V.T.H.,and V.V. designed the research. R.K. and N.M.conducted the research. R.K., A.K., J.L.S., S.B.M.,and D.L. performed or assisted in performing thestatistical analysis of the data. E.J., R.K., A.Z., A.K.,A.L.J., and L.D. wrote the manuscript draft. E.J.,J.L.S., and V.V. had primary responsibility for thefinal content. All authors contributed to thecritical revision of the manuscript for importantintellectual content and approved the final man-uscript.Prior Presentation. Parts of this work werepresented in abstract and poster form at the2017 CSEM/Diabetes Canada Professional Con-ference and Annual Meetings, Edmonton,Canada, 1–4 November 2017, and in abstractform and short oral presentation at the DNSG-EASD 36th Symposium on Diabetes and Nutri-tion, Opatija, Croatia, 27–30 June 2018.

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