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Hindawi Publishing CorporationJournal of Nutrition and MetabolismVolume 2012, Article ID 542698, 21 pagesdoi:10.1155/2012/542698

Review Article

Diet, Inflammation, and Glycemic Control in Type 2 Diabetes:An Integrative Review of the Literature

Sarah Y. Nowlin, Marilyn J. Hammer, and Gail D’Eramo Melkus

College of Nursing, New York University, 726 Broadway, 10th Floor, New York, NY 10003, USA

Correspondence should be addressed to Sarah Y. Nowlin, [email protected]

Received 9 August 2012; Accepted 19 September 2012

Academic Editor: Maria Luz Fernandez

Copyright © 2012 Sarah Y. Nowlin et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Type 2 diabetes (T2D) is a growing national health problem affecting 35% of adults ≥20 years of age in the United States.Recently, diabetes has been categorized as an inflammatory disease, sharing many of the adverse outcomes as those reported fromcardiovascular disease. Medical nutrition therapy is recommended for the treatment of diabetes; however, these recommendationshave not been updated to target the inflammatory component, which can be affected by diet and lifestyle. To assess the current stateof evidence for which dietary programs contain the most anti-inflammatory and glycemic control properties for patients with T2D,we conducted an integrative review of the literature. A comprehensive search of the PubMed, CINAHL, Scopus, and Web of Sciencedatabases from January 2000 to May 2012 yielded 786 articles. The final 16 studies met the selection criteria including randomizedcontrol trials, quasiexperimental, or cross-sectional studies that compared varying diets and measured inflammatory markers.The Mediterranean and DASH diets along with several low-fat diets were associated with lower inflammatory markers. TheMediterranean diet demonstrated the most clinically significant reduction in glycosylated hemoglobin (HbA1c). Information onbest dietary guidelines for inflammation and glycemic control in individuals with T2D is lacking. Continued research is warranted.

1. Background

Thirty-five percent of Americans who are aged 20 yearsand older have type 2 diabetes (T2D) [1]. The etiologybehind such impressive statistics is complex but can beattributed in part to recent changes in the lifestyle choicesof Americans, including changes in habitual diet. The WhatWe Eat in America (WWEIA) report, based on data obtainedfrom the National Health and Nutrition Examination Survey(NHANES), demonstrated that grains (mainly refined) havecontributed to the bulk of the rise in caloric intake inthe US in the last 60 years [2]. Increased consumption ofadded sugars, processed grains, and saturated fat contributedto excess weight gain, which is an influential risk factorin the development of T2D [3, 4]. In fact, results fromimplementation of the Diabetes Prevention Program (DPP)illuminated that up to 58% of diabetes can be preventedthrough lifestyle changes alone, including changes in diet [5].

One underlying pathophysiological process resultingfrom poor lifestyle habits is inflammation. Inflammation is

present prior to the development of T2D and cardiovasculardisease (CVD), contributing to evidence to support the“common soil” hypothesis, which is a reference to thecommon risk factors for the development of these twodiseases [6]. CVD is one of the major complications andcauses of death in persons with T2D, supporting thishypothesis [7]. The Multi-Ethnic Study of Atherosclerosis(MESA) showed that higher levels of the inflammatorymarkers, C-reactive protein (CRP) and interleukin (IL)-6,were associated with an increased risk of developing T2D [8].Chronic inflammation in T2D initiates with states of obesity,hyperglycemia, insulin resistance, and the overexpressionof proinflammatory proteins like CRP and cytokines (IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α)) [9].These proinflammatory molecules activate the cells of innateimmunity, which cause damage to tissues in the vasculature,adipose tissue, and pancreas. Acute responses through thisproinflammatory pathway are needed for tissue damagerepair and can improve function in tissues such as thepancreas, for example; however, chronic expression can

2 Journal of Nutrition and Metabolism

lead to pathological changes which result in disease [9].These changes clinically manifest as CVD, nephropathy, andsymptomatic T2D, as the innate immune system attemptsto repair the damaged tissue. Moreover, inflammation isstimulated in times of stress, which can be induced byenvironmental, behavioral, individual, and psychosocial fac-tors [10] and diet-induced hyperglycemia and hypertriglyc-eridemia [4]. Hyperglycemia and hypertriglyceridemia aresignificant stressors that have also been shown to causechronic inflammation and contribute to the pathogenesis ofT2D [4].

2. Problem and Research Aims

Although the published literature is populated with arti-cles and systematic reviews demonstrating the relationshipbetween dietary patterns, individual dietary factors, andincidence of diabetes [11, 12], the primary literature linkinginflammation to diet and T2D is minimal. One of thefew reported areas is with the Mediterranean-style diet,which has been associated with lower inflammatory markersand decreased incidence of T2D [12, 13]. Although severalreviews have investigated the effects of diet for T2D control,few disclosed the association with underlying inflammatoryresponses. Therefore, the aim of this study was to presentan integrative review of the published literature on theassociations between dietary intake and markers of chronicinflammation in patients with T2D. This review and synthe-sis of the relevant literature seeks to answer the followingresearch question: what is the current state of the scienceregarding the association between diet and inflammation inestablished T2D?

3. The Literature Search

This review targeted adults (≥18 years) diagnosed withT2D. All studies that included a dietary intervention, eitherexclusively or as part of an intervention, were included.Eligibility criteria included diet, inflammatory markers,and T2D evaluated in randomized clinical trial (RCT),quasiexperimental, or cross-sectional studies. The followingdatabases were searched: PubMed, CINAHL, Scopus, andWeb of Science. Keywords used in the search were combina-tions of the “diet,” “chronic inflammation,” “type 2 diabetes,”“C-reactive protein,” “interleukins,” and “tumor necrosisfactor” (TNF). A health sciences librarian was consulted onthe selection of these search terms. The search was conductedon articles published between January 2000 (the year ofthe first appearance of diet, inflammation, and T2D in theliterature) and May 2012. Studies were limited to only thosewritten in the English language. Studies that focused onprevention of T2D were excluded, as they did not offerdata to assist in the exploration of how diet relates to theinflammatory process within the pathogenesis of T2D. Otherexclusion criteria were studies that focused on supplementsalone or exercise without an evaluation of, or comparison to,diet.

4. Search Outcomes

The search produced 371 studies in PubMed, 265 studies inWeb of Science, and 150 studies in CINAHL (see Figure 1).Titles and abstracts were initially screened. Among these,19 studies met the full inclusion criteria. The full textfrom these articles was carefully reviewed. Six more studieswere discarded. Two were eliminated because they includedpredominantly healthy subjects in a cross-sectional study;one was eliminated because it included exercise only, onewas eliminated due to its focus on prevention of T2D,and two were eliminated because they focused on acuteresponses to dietary interventions. Three additional studieswere identified by hand-searching reference lists of theselected articles. A final total of 16 papers were includedfor critical analysis with synthesis of findings. Experimentaland nonexperimental studies were included in the analysis.In this integrative review, two studies were cross-sectional[14, 15], two were experimental [16, 17], and twelve werequasiexperimental, as follows: three were crossover experi-mental designs [18–20], three were pretest-posttest designswith only one group [21–23], and six were pretest-posttestdesigns with two or more comparison groups [24–29]. Morethan half of the studies were international with one fromthe Middle East, one from Canada, three from Australia,and six from Europe. The other five were from the US. Allwere published in English. All subjects in the cross-sectionalstudies had a diagnosis of T2D, while several experimentalstudies utilized healthy and/or obese controls. Acceptablemeasures for inflammation included serum evaluations ofCRP, IL-6, TNF, or a combination of one or more of thesewith other markers of inflammation.

5. Methods

Each study was read twice to ensure identification of salienttopics for analysis. Three tables were created to aid synthesisof the data. Table 1 is an overview of information for broadtopics created to aid in abstracting those aspects that weredefinitive in interpreting the implications of the findings.From this table, it became clear that each study reportedinflammatory markers at different time points (e.g., somestudies did not report baseline values), which was infor-mative for the data reduction process. Quality assessmentratings were established, and each article was scored basedon these criteria (Table 2). Tables 3 and 4 contain the resultsof data abstraction and synthesis, respectively.

5.1. Quality Assessment. Articles retrieved for review wereassessed for quality of study conduct and reporting [30].Quality assessment scores were assigned based on 11 ques-tions designed to capture the essence of the study design,methods, and analyses (Table 2). The quality score for eachquestion was assigned based on how well the article fulfilledthe expectations. A score of 0 represented absence of thecriteria in question, and a score of 1 designated fulfillment ofeach criterion. These categories included aims, methods (3questions), diet (3 questions), inflammatory measures, andanalysis (2 questions). There was also one question related

Journal of Nutrition and Metabolism 3

3 articles found through searching references

16 articles included in final

synthesis

PubMed = 371 articles, CINAHL = 150 articles,and web of science= 265 articles;

titles and abstracts searched

2 articles identified by hand-searching

reference section of selected articles

19 full-text articles pulled and reviewed

6 articles discarded:

(1) included exercise,

(2) 2 did not separatehealthy/T2DM pts,

(3) incidence,

(4) not tx focused.

Figure 1: PRISMA flowchart.

to results and conclusions with a rating of 0–2, with 2 beingof highest quality, which was weighted more heavily due toits importance in interpretation of the study findings. Thehighest achievable score was 12.

5.2. Data Reduction. Studies were grouped by design methodto differentiate results sections for accurate synthesis [30].Studies were first grouped into experimental (n = 14) andcorrelational (n = 2). Studies were then further delineatedby diet categories of association with inflammation and thosewith a focus on diabetes control (glycemic control). Tables 3and 4 detail these findings.

6. Results

6.1. Association between Diet and Inflammation. Severalexperimental studies demonstrated a reduction of systemicinflammation following an intervention of a prescribed dietin patients with T2D. Four of the studies with higher qualityscores (≥9) demonstrated a significant association betweendiet and inflammation. Three of these four contained alow-fat (≤30% of energy from fat) dietary component [18,25, 26]. Azadbakht et al. [18] implemented the DietaryApproaches to Stop Hypertension (DASH) diet in aneight-week crossover intervention study. The DASH diet ischaracterized by a high intake of whole grains, fruits, andvegetables, while limiting sodium intake (<2400 mg/day)[18]. After controlling for weight reduction, there wasa statistically significant decrease in mean CRP in theintervention group compared to the control group (P =.03) [18]. The low-fat low-protein diet implemented byBrinkworth et al. [25] is almost identical in macronutrientcomposition to the DASH diet (see Table 3). After 64 weeksof following this diet with minimal dietary counseling,

participants demonstrated a drop in CRP levels, that iscomparable to that which was found in the Azadbakht et al.[4] study group, which reached statistical significance (P =.04) [25]. The control group in this study received a high-protein, low-fat diet, which also caused a decrease in CRP,and there was not a significant difference in the mean changein CRP between groups (P = .61) [25]. Similarly, Davis etal. [26] demonstrated that after following an interventionof either a low-fat or low-carbohydrate diet for 24 weeks,CRP was only found to be significantly reduced in the low-fat diet arm (P = .01) and not in the low-carbohydrate arm(P = .94). Wolever et al. [29] showed that after 52 weeksof following a low-glycemic-index, low-fat diet (∼30% ofenergy intake from fat), CRP was reduced from baseline by29% compared to a high-glycemic-index, low-carbohydratediet that was also high in monounsaturated fat (MUFA)(P < .05). Wolever et al. [29] also examined the interactionof diet and time but found no significant effect of time or dieton CRP levels (see Table 1). Of these four studies, only Daviset al. [26] did not report adherence to the prescribed diet. Allfour studies were controlled for differences in weight loss.

Several other studies also demonstrated reductions inCRP with dietary interventions, albeit with lower qualityscores, and with ranges between 4 and 8. Khoo et al. [28]used a crossover design and randomly assigned participantsinto one of two groups for 8 weeks. One group began on alow-calorie diet and the other a high-protein low-fat diet foreight weeks, then both groups continued on the high-proteinlow-fat diet for 44 weeks (see Table 1) [28]. Mean-CRP levelswere reduced significantly only in the high-protein, low-fat diet at 52 weeks (P < .01) [28]. Although diet diarieswere collected throughout the study period, adherence tothe diet was not reported. Bozzetto et al. [19] conducted arandomized crossover trial with only 12 participants, but theanalysis revealed a decreasing mean-CRP level with fasting,


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ialo

fca

rboh

ydra

tes

indi

abet

es(C

CD

),a

1-y

con

trol

led

tria

lofl

ow-

glyc

emic

-in

dex

diet

ary

carb

ohyd

rate

inty

pe2

diab

etes

:n

oeff

ect

ongl

ycat

edh

emog

lobi

nbu

tre

duct

ion

inC

-rea

ctiv

epr

otei

n.

3-gr

oup

pre-

test

/pos

t-te

stde

sign

wit

hra

ndo

miz

atio

n.

Sam

ple:N=

162.

Subj

ects

wer

ead

ult

sag

e35

–75

y/o

wit

hty

pe

2di

abet

esan

da

BM

Iof

24–4

0.

Infl

amm

ator

ym

arke

rs:

CR

P.G

lyce

mic

con

trol

:in

sulin

sen

siti

vity

(HO

MA

scor

e),f

asti

ng

glu

cose

,fas

tin

gin

sulin

,H

bA1c

.D

iet:

mac

ron

utr

ien

tin

take

.O

ther

s:lip

idpr

ofile

,w

eigh

t,bl

ood

pres

sure

,fr

eefa

tty

acid

s.C

RP

:log

-tra

nsf

orm

ed(t

hos

ew

hos

est

atin

dose

sw

ere

chan

ged

duri

ng

the

stu

dyw

ere

not

incl

ude

din

the

anal

ysis

ofC

RP,

lipid

s,an

dlip

opro

tein

s).

3-da

yfo

oddi

ary

reco

rds

colle

cted

7ti

mes

duri

ng

the

12m

onth

per

iod

.K

eyfo

oddi

arie

sfr

om91

%of

subj

ects

.

12m

onth

sin

len

gth

.A

llsu

bjec

tsad

vise

d“h

eart

hea

lthy

”di

et.

Hig

h-G

Idi

et:a

void

low

-GI

food

s,ea

tlo

w-f

atfo

ods.

Low

-GI

diet

:ex

chan

geh

igh

-GI

food

sfo

rlo

w-G

Ifo

ods,

eat

low

-fat

food

s.Lo

w-C

HO

:dec

reas

eSF

Ain

take

,in

crea

seM

UFA

inta

ke.

Indi

vidu

aldi

etar

yco

un

selin

gpr

ovid

edat

2an

d4

wee

ks,t

hen

ever

y4

wee

ks.

No

con

trol

grou

p.

Gen

eral

linea

rm

ixed

mod

el.S

tats

CR

Pu

sed

log-

tran

sfor

med

data

pres

ente

das

mea

ns

and

CI’s

.T

ime

trea

ted

asa

regr

essi

onva

riab

le.

Mod

elco

vari

ates

:ag

e,B

MI,

sex,

and

cen

ter

that

corr

elat

edsi

gnifi

can

tly

wit

hth

ere

spon

seva

riab

le.

Tim

e×

diet

:in

tera

ctio

ns.

∗ dat

afo

rsu

bjec

tsth

atw

ere

excl

ude

dfr

oman

alys

isw

ere

incl

ude

du

pu

nti

lth

ep

oin

tth

eyw

ere

drop

ped.

Con

side

red

MA

R.

CR

Pin

low

-GI

diet

29%

low

erth

anh

igh

-GI

diet

.C

RP

was

1.95

(1.6

8,2.

27)

for

the

low

-GI

diet

,2.7

5(2

.33,

3.24

)fo

rth

eh

igh

-GI

diet

,an

d2.

35(2

.01,

2.75

)fo

rth

elo

w-C

HO

diet

(P<.0

5fo

rdi

ffer

ence

ingr

oups

).C

RP

incr

ease

dw

ith

hig

h-G

Idi

et.

HbA

1cro

sefr

om6.

1to

6.3%

,bu

tbe

twee

ngr

oup

effec

ton

HbA

1c

was

NS

from

diet

:hig

hG

IH

bA1c=

6.34±

0.05

,lo

wG

IH

bA1c=

6.34±

0.05

,low

GI

HbA

1c=

6.35±

0.05

.Si

gnifi

can

teff

ect

ofti

me

onw

eigh

t,bu

tn

otsi

gnifi

can

tly

diff

eren

tbe

twee

ndi

etgr

oups

.


Ta

ble

1:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

titl

e

Stu

dyde

sign

and

met

hod

sV

aria

bles

Inst

rum

ents

Inte

rven

tion

deta

ilsIm

port

ant

met

hod

olog

ical

flaw

s/bi

asn

oted

Dat

aan

alys

isO

utc

omes

rela

ted

toin

flam

mat

ion

,gly

cem

icco

ntr

ol,a

nd

diet

Bar

nar

det

al.

(200

9),U

nit

edSt

ates

[24]

.A

low

-fat

vega

ndi

etan

da

conv

enti

onal

diab

etes

diet

inth

etr

eatm

ent

ofty

pe2

diab

etes

:ara

ndo

miz

ed,

con

trol

led,

74-w

eek

clin

ical

tria

l.

2gr

oup

pret

est-

post

test

desi

gn.

Sam

ple:N=

99Su

bjec

tsw

ere

adu

lts

wit

hty

pe2

diab

etes

.(1

)V

egan

diet

.(2

)C

onve

nti

onal

AD

Adi

et(2

003

guid

elin

es).

Infl

amm

ator

ym

arke

rs:

CR

P.G

lyce

mic

con

trol

:H

bA1c

,fas

tin

gpl

asm

agl

uco

se.

Oth

ers:

lipid

profi

le,

wei

ght,

BM

I,w

aist

circ

um

fere

nce

,al

bum

in,b

lood

pres

sure

.D

ieta

ryad

her

ence

:ve

gan

-no

anim

alpr

odu

cts

in24

-hre

calls

,low

fat,

low

chol

este

rol

conv

enti

onal

-fol

low

ing

pres

crib

eden

ergy

rest

rict

ion

s,lo

wSF

A.

Bot

hgr

oups

:att

ende

dat

leas

t10

ofth

e22

wee

kly

diet

ary

info

sess

ion

s.

24h

our

reca

lls×7

.3-

day

diet

ary

reco

rd×4

.Pe

dom

eter

.B

ouch

ard

3-da

yph

ysic

alac

tivi

tyre

cord

.

Init

ial1

-hr

mee

tin

gw

ith

diet

icia

nfo

rea

chgr

oup.

Th

en,2

2w

eekl

ygr

oup

sess

ion

ssp

ecifi

cto

grou

p.O

ptio

nal

sess

ion

sev

ery

two

wee

ksfo

rth

ere

mai

nin

g52

wee

ks.

Med

icat

ion

sw

ere

adju

sted

for

safe

tyby

anen

docr

inol

ogis

t.

Not

alla

nal

yses

wer

epe

rfor

med

only

usi

ng

thos

epa

rtic

ipan

tsw

ith

good

adh

eren

ce.

Goo

dad

her

ence

not

defi

ned

.O

nly

CR

Pm

easu

red,

was

not

apr

imar

yfo

cus

ofth

est

udy

.

Rep

eate

dm

easu

res

AN

OV

Afo

rH

bA1c

(as

ITT

)u

sin

gti

me,

diet

grou

p,an

din

tera

ctio

nbe

twee

nti

me×

diet

wit

hH

bA1c

asD

V.

Bet

wee

nsu

bjec

tt-

test

sfo

ral

lDV

sto

dete

ctsi

gnifi

can

tch

ange

sfr

omba

selin

eto

74w

eeks

(or

un

til

last

mea

sure

men

t)an

dpa

ired

-com

pari

son

t-te

sts.

Aft

erad

just

men

tfo

rm

edic

atio

nch

ange

s,LD

Lan

dn

on-H

DL

chol

este

rolv

alu

esde

crea

sed,

and

mor

eso

inth

eve

gan

grou

p.C

RP

decr

ease

dsi

gnifi

can

tly

inbo

thgr

oups

,bu

tn

odi

ffer

ence

betw

een

grou

ps.

Dos

tlov

aet

al.

(200

9),C

zech

Rep

ubl

ic[2

1].

Incr

ease

dse

rum

con

cen

trat

ion

sof

mac

roph

age

inh

ibit

ory

cyto

kin

e-1

inpa

tien

tsw

ith

obes

ity

and

type

2di

abet

esm

ellit

us:

the

infl

uen

ceof

very

-low

-cal

orie

diet

.

Qu

asie

xper

imen

talo

ne

grou

pw

ith

two

com

pari

son

grou

ps(m

onit

ored

inth

eh

ospi

tal)

.Sa

mpl

e:to

talN

=54

Gro

up

no.

1(c

ompa

riso

n):

(n=

17)

obes

e,n

ondi

abet

icw

omen

.G

rou

pn

o.2

(tre

atm

ent

grou

p):(n=

14)

obes

ew

omen

w/t

ype

2D

M.

Gro

up

no.

3(c

ompa

riso

n):

(n=

23)

hea

lthy

lean

wom

en.

Infl

amm

ator

ym

arke

rs:

CR

P.G

lyce

mic

con

trol

:gl

uco

se,h

omeo

stas

ism

odel

asse

ssm

ent

ofin

sulin

resi

stan

ce(H

OM

A-I

R).

Oth

ers:

MIC

-1le

vels

lipid

s,B

MI,

body

fat

com

posi

tion

.A

not

her

prim

ary

focu

sof

the

stu

dyw

asto

test

leve

lsof

mac

roph

age

inh

ibit

ory

cyto

kin

e-1

(MIC

-1)

and

mR

NA

expr

essi

onof

MIC

-1in

subc

uta

neo

us

and

visc

eral

fat.

No

mea

sure

ofad

her

ence

todi

et.

2-w

eek

very

-low

-cal

orie

diet

.O

nly

obes

ew

omen

wit

han

dw

ith

out

DM

wer

egi

ven

the

IVdi

et;

a2-

wee

k55

0kc

al/d

aydi

et.A

llpa

tien

tsw

ere

hos

pita

lized

.

Hig

hly

con

trol

led

envi

ron

men

tfo

rst

udy

.No

adve

rse

even

tsre

por

ted.

Not

asu

stai

nab

lein

terv

enti

onfo

rlo

ng-

term

use

.T

he

subs

tudy

exam

inin

gM

IC-1

mR

NA

expr

essi

onw

asto

tally

un

rela

ted

toth

e3

grou

psre

ceiv

ing

the

inte

rven

tion

,an

dth

ese

pati

ents

wer

ere

ceiv

ing

surg

ery

and

can

not

beco

mpa

red.

On

e-w

ayA

NO

VA

follo

wed

bypo

sth

octe

sts.

Spea

rman

corr

elat

ion

sp

erfo

rmed

toev

alu

ate

the

rela

tion

ship

ofM

IC-1

expr

essi

onto

oth

erva

riab

les.

For

wom

enw

ith

T2D

M(n=

14),

sign

ifica

nt

chan

ges

inth

efo

llow

ing

para

met

ers

wer

eob

serv

edaf

ter

the

VLC

D:B

MI,

chol

este

rol,

TG

s,gl

uco

se,i

nsu

lin,C

RP,

and

HO

MA

-IR

.


Ta

ble

1:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

titl

e

Stu

dyde

sign

and

met

hod

sV

aria

bles

Inst

rum

ents

Inte

rven

tion

deta

ilsIm

port

ant

met

hod

olog

ical

flaw

s/bi

asn

oted

Dat

aan

alys

isO

utc

omes

rela

ted

toin

flam

mat

ion

,gly

cem

icco

ntr

ol,a

nd

diet

Koz

łow

ska

etal

.(2

010)

,Pol

and

[22]

.A

dipo

nec

tin

,re

sist

in,a

nd

lept

inre

spon

seto

diet

ary

inte

rven

tion

indi

abet

icn

eph

ropa

thy.

Qu

asie

xper

imen

talo

ne

grou

ppr

etes

t/po

stte

stde

sign

.Sa

mpl

e:N=

17Su

bjec

tsw

ere

obes

ew

ith

T2D

M,a

llto

okan

tihy

pert

ensi

ves,

anti

diab

etic

dru

gs,

phos

phat

ebi

nde

rs,a

nd

diu

reti

cs.S

tudy

dura

tion

was

8w

eeks

.

Infl

amm

ator

ym

arke

rs:

TN

F-α

,CR

PG

lyce

mic

con

trol

:in

sulin

sen

siti

vity

(HO

MA

scor

e),i

nsu

lin,

HbA

1c.

Die

t:n

otm

easu

red.

Oth

ers:

adip

onec

tin

,re

sist

in,l

epti

n,t

otal

prot

ein

,met

abol

icra

teu

sin

gox

ygen

and

CO

2

mea

sure

men

ts.

DE

XA

scan

for

body

com

posi

tion

.

Inte

rven

tion

diet

:20

%en

ergy

defi

cit

0.8–

1g/

kgid

ealb

ody

wei

ght,

30%

calf

rom

fat,

60%

calf

rom

CH

O.

Con

sult

wit

hdi

etic

ian

Q2w

k.

No

men

tion

ofh

owdi

etar

yin

take

was

mea

sure

d,ju

stre

port

edin

ach

art

(Tab

le2)

.N

oco

ntr

olgr

oup.

Smal

lsam

ple

size

,w

eak

desi

gn.

Pear

son

orSp

earm

an’s

test

sfo

rco

rrel

atio

ns.

Rep

eate

dm

easu

res.

Stu

den

t’st-

test

orW

ilcox

onm

atch

edpa

irs.

No

corr

elat

ion

sbe

twee

nfo

odin

take

and

infl

amm

ator

ym

arke

rsm

ade.

Aft

erin

terv

enti

on,

resi

stin

(P<.0

3)an

dT

NF-α

(P=.0

023)

con

cen

trat

ion

sw

ere

sign

ifica

ntl

yde

crea

sed.

Res

isti

nco

nce

ntr

atio

ns

wer

eco

rrel

ated

wit

hT

NF

(r=.5

1,P<.0

38).

Vet

ter

etal

.(2

010)

,U.S

.[17

].E

ffec

tof

alo

w-c

arbo

hydr

ate

diet

vers

us

alo

w-f

atca

lori

e-re

stri

cted

diet

onad

ipok

ine

leve

lsin

obes

edi

abet

icpa

rtic

ipan

ts.

An

cilla

rygr

oup

inan

RC

T.Sa

mpl

e:N=

79.

Part

icip

ants

wer

eob

ese,

wit

hty

pe2

diab

etes

,ou

tpat

ien

t.(1

)Lo

w-c

arb

diet

.(2

)Lo

w-f

atdi

et.

Infl

amm

ator

ym

arke

rs:

lept

in,a

dipo

nec

tin

,T

NF-α

.All

mea

sure

dby

bloo

dsa

mpl

es.

Gly

cem

icco

ntr

ol:

HbA

1c,i

nsu

lin,f

asti

ng

bloo

dgl

uco

se.A

llm

easu

red

bybl

ood

sam

ples

.D

iet:

24h

rre

call.

Oth

ers:

wei

ght,

BM

I,ra

ce,a

ge,g

ende

r,di

abet

esre

late

dm

edic

atio

ns,

pres

ence

ofC

AD

,sm

okin

gst

atu

s.

24-h

our

reca

lls.

Nu

trib

ase

Man

agem

ent

soft

war

eto

esta

blis

hm

icro

/mac

ron

utr

ien

tco

nte

nt

ofin

take

.

Ran

dom

lyas

sign

edto

grou

ps.

Firs

tm

onth

:di

etic

ian

-led

wee

kly

grou

pse

ssio

ns

for

each

grou

p.Fo

llow

ing

mon

ths:

mon

thly

grou

pse

ssio

ns.

Giv

enh

ando

uts

,sa

mpl

em

enu

s,re

cip

es,e

tc.

24-h

our

reca

llas

sess

ed,b

ut

not

use

dto

asse

ssad

her

ence

toth

epr

escr

ibed

diet

.H

igh

attr

itio

nra

te(5

4.9%

).D

emog

raph

icva

riab

les

betw

een

thos

ew

ho

did

and

did

not

com

plet

est

udy

wer

en

otsi

gnifi

can

tly

diff

eren

t.N

odi

scu

ssio

nof

how

mis

sin

gda

taw

ere

han

dled

.N

odi

ffer

ence

inm

acro

nu

trie

nt

inta

kebe

twee

ngr

oups

,alt

hou

ghit

shou

ldh

ave

been

.

Log-

tran

sfor

med

data

:lep

tin

,ad

ipon

ecti

n,a

nd

TN

Fα.

Rep

eate

dm

easu

res

AN

OV

A(w

ith

tim

e×

diet

grou

p)u

sed

toco

mpa

rech

ange

inw

eigh

t,ad

ipok

ines

,an

ddi

etar

yin

take

.M

ult

iple

linea

rre

gres

sion

tode

scri

beas

soci

atio

ns

betw

een

wei

ght

loss

and

chan

ges

inad

ipok

ine

valu

es.

Infl

amm

ator

ym

arke

rs:

CR

Pn

otm

easu

red.

TN

F-α

:dec

reas

edi

dn

otdi

ffer

wit

hti

me

(P=.3

4)or

betw

een

grou

ps(P=.4

75).

Gly

cem

icco

ntr

ol:

HbA

1c:d

eclin

ein

HbA

1c

was

not

sign

ifica

ntl

ydi

ffer

ent

betw

een

grou

ps(n

oP

valu

epr

ovid

ed).

Oth

ers:

wei

ght:

decl

ined

sign

ifica

ntl

yov

erti

me

(P<.0

01),

how

ever

,it

was

not

diff

eren

tbe

twee

ngr

oups

(P=.1

81).

Lept

in:d

eclin

edi

dn

otdi

ffer

sign

ifica

ntl

ybe

twee

ngr

oups

.A

dipo

nec

tin

:in

crea

sedi

dn

otdi

ffer

sign

ifica

ntl

ybe

twee

ngr

oups

Wei

ght

loss

sign

ifica

ntl

yas

soci

ated

wit

hch

ange

sin

lept

in(r=.3

6)an

dT

NF-α

(r=−.

29).


Ta

ble

1:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

titl

e

Stu

dyde

sign

and

met

hod

sV

aria

bles

Inst

rum

ents

Inte

rven

tion

deta

ilsIm

port

ant

met

hod

olog

ical

flaw

s/bi

asn

oted

Dat

aan

alys

isO

utc

omes

rela

ted

toin

flam

mat

ion

,gly

cem

icco

ntr

ol,a

nd

diet

Aza

dbak

ht

etal

.(2

011)

,stu

dyco

ndu

cted

inIr

an[1

8].

Th

eD

ieta

ryA

ppro

ach

esto

Stop

Hyp

erte

nsi

onea

tin

gpl

anaff

ects

C-r

eact

ive

prot

ein

,co

agu

lati

onab

nor

mal

itie

s,an

dh

epat

icfu

nct

ion

test

sam

ong

typ

e2

diab

etic

pati

ents

.

Cro

ssov

erin

terv

enti

onde

sign

wit

hra

ndo

miz

atio

n.

Sam

ple:N=

31,

Con

ven

ien

cesa

mpl

eof

adu

lts

wit

hty

pe2

diab

etes

atth

eSh

ahee

dM

otah

ariH

ospi

talo

fFo

olad

shah

r.

Infl

amm

ator

ym

arke

rs:

CR

P.G

lyce

mic

con

trol

:n

otm

easu

red.

Die

t:m

acro

nu

trie

nt

inta

ke.

Oth

ers:

ALT

,AST

,AL

P,bi

liru

bin

.

3ddi

etar

yre

call

toas

sess

adh

eren

ceto

the

pres

crib

eddi

et.

Mon

thly

3-da

yph

ysic

alac

tivi

tydi

ary.

8-w

eek

cros

sove

rst

udy

wit

hra

ndo

miz

atio

nto

con

trol

orD

ASH

diet

.C

ontr

oldi

eth

adfe

wer

PU

FA.

En

ergy

inta

kein

divi

dual

lyta

ilore

d.M

onth

lyvi

sits

.4-

wee

kw

ash

out

per

iod

.

Un

clea

rh

owst

udy

was

con

duct

ed,n

otea

syto

follo

wm

eth

ods.

R/o

carr

yove

reff

ects

.N

om

enti

onof

how

lon

gea

chdi

etw

asm

ain

tain

ed,i

fth

ere

was

aw

ash

out

peri

od,o

rw

hyth

ose

wh

oh

adle

ftth

epr

otoc

olle

ft(r

/ofa

tigu

eeff

ect)

.

Ass

essi

ng

effec

tof

inte

rven

tion

:pai

red

t-te

stw

ith

and

wit

hou

tad

just

men

tfo

rw

eigh

t.G

rou

psco

mpa

red

usi

ng

a%

chan

geca

lcu

lati

on.

Pati

ents

wh

o“d

evia

ted

from

the

stu

dypr

otoc

ol”

wer

en

otin

clu

ded

inth

ean

alys

is(p

.108

4).

Pati

ents

wh

ore

ceiv

edth

eD

ASH

diet

show

eda

redu

ctio

nin

CR

P,pl

asm

afi

brin

ogen

,an

dliv

ertr

ansf

eras

een

zym

es.

Th

ese

redu

ctio

ns

wer

esi

gnifi

can

tan

dre

mai

ned

sign

ifica

nt

afte

rad

just

ing

for

the

effec

tof

wei

ght.

Boz

zett

oet

al.

(201

1),I

taly

[19]

.T

he

asso

ciat

ion

ofh

s-C

RP

wit

hfa

stin

gan

dpo

stpr

andi

alpl

asm

alip

ids

inpa

tien

tsw

ith

type

2di

abet

esis

disr

upt

edby

diet

ary

mon

oun

satu

rate

dfa

tty

acid

s.

Pre

exp

erim

enta

lpos

ttes

ton

lyC

ross

-ove

rw

ith

ran

dom

izat

ion

(no

was

hou

t).

Sam

ple:

12pa

rtic

ipan

tsw

ith

type

2di

abet

esH

bA1c

ingo

odco

ntr

ol.

4w

eeks

onea

chdi

et.N

ow

ash

out

per

iod

men

tion

ed.

Infl

amm

ator

ym

arke

rs:

CR

P.G

lyce

mic

con

trol

:n

otm

easu

red.

Die

t:n

otm

easu

red.

Oth

ers:

trig

lyce

ride

-ric

hlip

opro

tein

s(c

hylo

mic

ron

s,la

rge

VL

DL

,sm

allV

LD

L),

chol

este

rola

nd

trig

lyce

ride

.

Not

hin

gpr

ovid

edin

pape

r.

Die

tsw

ere

isoe

ner

geti

c:bo

thh

adkc

alof

948

per

day.

Ran

dom

ized

,cr

osso

ver

desi

gn.

CH

O/fi

ber/

low

-GI:

C52

%,

MU

FA17

%,

GI

58%

.

Hig

h-M

UFA

diet

:C

45%

,M

UFA

23%

,G

I88

%.

No

deta

ilsgi

ven

con

cern

ing

diet

ary

advi

sem

ent.

Die

tary

adh

eren

cen

otm

easu

red.

Con

fou

ndi

ng

vari

able

sn

otex

plor

ed.

Bod

yw

eigh

tdi

dn

otch

ange

sign

ifica

ntl

yov

erth

est

udy

per

iod,

but

itsh

ould

hav

ech

ange

d,

con

side

rin

gth

elim

ited

calo

ric

pres

crip

tion

.

Pair

edt-

test

sto

iden

tify

diff

eren

ces

inou

tcom

em

easu

res

betw

een

the

two

diet

s(g

rou

psw

ere

mer

ged

for

anal

ysis

).R

epea

ted

mea

sure

sA

NO

VA

toev

alu

ate

diff

eren

ces

inpo

stpr

andi

alte

stin

g(m

ult

iple

test

s).T

hey

clai

mn

oca

rryo

ver

effec

tw

asde

tect

ed.

Die

tan

din

flam

mat

ion

:af

ter

inte

rven

tion

,fa

stin

gC

RP

valu

esw

ere

not

sign

ifica

ntl

ydi

ffer

ent

betw

een

stu

dydi

ets,

alth

ough

CR

Pdi

dde

crea

sesi

gnifi

can

tly

afte

rth

eM

UFA

mea

l(P

<.0

5),n

otth

eC

HO

/fibe

rm

eal.


Ta

ble

1:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

titl

e

Stu

dyde

sign

and

met

hod

sV

aria

bles

Inst

rum

ents

Inte

rven

tion

deta

ilsIm

port

ant

met

hod

olog

ical

flaw

s/bi

asn

oted

Dat

aan

alys

isO

utc

omes

rela

ted

toin

flam

mat

ion

,gly

cem

icco

ntr

ol,a

nd

diet

Dav

iset

al.

(201

1),[

26].

Diff

eren

tial

effec

tsof

low

-car

bohy

drat

ean

dlo

w-f

atdi

ets

onin

flam

mat

ion

and

endo

thel

ial

fun

ctio

nin

diab

etes

.

2-gr

oup

pre-

test

/pos

t-te

stcl

inic

altr

ials

ubg

rou

pof

larg

ertr

ial.

Sam

ple:

subj

ects

wer

eob

ese

wit

hty

pe

2di

abet

esw

ith

anH

bA1c

betw

een

6%an

d11

%.

N=

5163

%of

subj

ects

wer

eB

lack

inbo

thdi

etgr

oups

,in

the

low

-car

bgr

oup,

11%

ofth

esu

bjec

tsw

ere

His

pan

ic.

Infl

amm

ator

ym

arke

rs:

CR

P,IL

-6.

Gly

cem

icco

ntr

ol:

glu

cose

,HbA

1c.

Oth

ers:

endo

thel

ial

fun

ctio

n(s

-IC

AM

,so

lubl

eE

-sel

ecti

n),

and

reac

tive

hyp

erem

icp

erip

her

alar

teri

alto

nom

etry

,wei

ght,

lipid

s.

En

doPa

tto

mea

sure

per

iph

eral

mic

rova

scu

lar

endo

thel

ial

fun

ctio

n.

Tota

l24

wee

ks:

subj

ects

ran

dom

ized

tore

ceiv

eei

ther

alo

w-c

arbo

hydr

ate,

Atk

ins-

styl

edi

etor

alo

w-f

atdi

et(s

imila

rto

DP

Pdi

et).

Part

icip

ants

rece

ived

stru

ctu

red

men

us

for

the

1st

two

wee

ks.

Med

icat

ion

sw

ere

adju

sted

base

don

apr

edefi

ned

algo

rith

m.

Die

tw

asre

info

rced

ever

y6

wee

ksat

sch

edu

led

visi

ts.

No

con

trol

grou

p.N

om

easu

reof

adh

eren

ceto

pres

crib

eddi

et.

CR

Pan

dIL

-6w

ere

log-

tran

sfor

med

.U

npa

ired

t-te

sts

(or

Wilc

oxon

ran

k)u

sed

tode

tect

diff

eren

ces

inpa

ram

eter

outc

omes

betw

een

diet

ary

arm

s.Pe

arso

nor

Spea

rman

corr

elat

ion

s.

Low

-fat

diet

:CR

Pde

crea

sed

from

4.0

to3.

0(P=.0

1).

Low

-car

bdi

etdi

dn

otca

use

asi

gnifi

can

tch

ange

inC

RP

(P=.9

4).

Low

-car

bdi

et:s

ICA

Mde

crea

sed

from

234

to19

9(P=.0

01),

E-s

elec

tin

decr

ease

dfr

om92

to82

(P=.0

5).

Itsi

opou

los

etal

.(2

010)

,Au

stra

lia[2

0].

Can

the

Med

iter

ran

ean

diet

low

erH

bA1c

inty

pe2

diab

etes

?R

esu

lts

from

ara

ndo

miz

edcr

oss-

over

stu

dy.

Ran

dom

ized

cros

s-ov

er(2

grou

pspr

etes

t,po

stte

st).

Sam

ple:N=

31Su

bjec

tsre

cru

ited

from

new

spap

erh

ad“w

ell-

con

trol

led”

typ

e2

diab

etes

.

Infl

amm

ator

ym

arke

rs:

CR

P,h

omoc

yste

ine.

Gly

cem

icco

ntr

ol:

HO

MA

,HbA

1c,f

asti

ng

glu

cose

.O

ther

:h

eigh

t,ag

e,pl

asm

afa

tty

acid

s,24

-hr

uri

ne

albu

min

and

crea

tin

ine,

wei

ght,

wai

st-h

ipra

tio,

intr

aabd

omin

alad

ipos

eti

ssu

e(I

AA

T),

BP.

Hea

lth

and

lifes

tyle

ques

tion

nai

re(n

otde

fin

ed).

Seve

n-d

aydi

etre

cord

(com

plet

edby

part

icip

ant)

.U

sed

chan

ges

inpl

asm

ale

vels

ofse

vera

ldiff

eren

tca

rote

noi

dsto

chec

kco

mpl

ian

cew

ith

the

IVdi

et.

Inte

rven

tion

was

aM

edit

erra

nea

ndi

etfo

r12

wee

ks,t

hen

cros

sove

r(2

4w

eeks

tota

l).

70%

ofin

terv

enti

ondi

etm

eals

prep

ared

and

prov

ided

inbu

lkfo

rfr

ee.A

dvis

edto

eat

3se

rvin

gsfr

uit

sp

erda

y.

No

was

hou

tp

erio

dbe

twee

ndi

etpe

riod

s.M

easu

rem

ent

tool

sn

otst

anda

rdiz

ed.

Oliv

eoi

lcom

pany

prov

ided

the

oliv

eoi

l,m

ayle

adto

bias

edre

sult

s.U

nde

rpow

ered

.

Dat

afr

omth

etw

odi

ets

wer

epo

oled

.R

epea

ted-

mea

sure

sA

NO

VA

.U

sed

anin

tera

ctio

nte

rmto

con

trol

for

abse

nce

ofw

ash

out

per

iod

.

Sign

ifica

nt

redu

ctio

nin

HbA

1cin

the

inte

rven

tion

diet

.Tr

end

tow

ard

decr

ease

inH

OM

Aan

dB

MI.

Incr

ease

inpl

ant

food

inta

ke.


Ta

ble

1:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

titl

e

Stu

dyde

sign

and

met

hod

sV

aria

bles

Inst

rum

ents

Inte

rven

tion

deta

ilsIm

port

ant

met

hod

olog

ical

flaw

s/bi

asn

oted

Dat

aan

alys

isO

utc

omes

rela

ted

toin

flam

mat

ion

,gly

cem

icco

ntr

ol,a

nd

diet

Kh

ooet

al.

(201

1),A

ust

ralia

[28]

.C

ompa

rin

geff

ects

ofa

low

-en

ergy

diet

and

ah

igh

-pro

tein

low

-fat

diet

onse

xual

and

endo

thel

ial

fun

ctio

n,u

rin

ary

trac

tsy

mp

tom

s,an

din

flam

mat

ion

inob

ese

diab

etic

men

.

2gr

oup

pret

est-

post

test

desi

gnw

ith

ran

dom

izat

ion

.Sa

mpl

e:co

nven

ien

cesa

mpl

eof

31W

hit

em

enw

ith

type

2di

abet

esan

der

ecti

ledy

sfu

nct

ion

.R

ando

mly

assi

gned

toei

ther

mod

ified

low

-cal

orie

diet

(LC

D)

orh

igh

-pro

tein

low

-fat

diet

(HP

diet

)fo

r8

wee

ks.

Aft

erfi

rst

8w

eeks

,all

subj

ects

wer

epl

aced

onth

eH

Pdi

etfo

rth

ere

mai

nin

g44

wee

ks.

Infl

amm

ator

ym

arke

rs:

CR

P,IL

-6,a

nd

solu

ble

E-s

elec

tin

.G

lyce

mic

con

trol

:qu

anti

tati

vein

sulin

sen

siti

vity

chec

kin

dex

(QU

ICK

I),g

luco

se,

insu

lin.

Die

t:co

mpl

ian

ce,n

otu

sed

inan

alys

is.

Oth

ers:

andr

ogen

leve

ls,e

rect

ilefu

nct

ion

,se

xual

desi

re,a

nd

low

eru

rin

ary

trac

tsy

mpt

oms.

Food

diar

ies

tom

onit

orco

mpl

ian

ce.

IIE

F-5,

Sexu

alD

esir

eIn

ven

tory

,In

tern

atio

nal

Pro

stat

eSy

mpt

omSc

ale.

Die

tco

mpl

ian

cem

onit

ored

ever

y2–

4w

eeks

.LC

D:2

liqu

idm

eals

per

day

plu

ssm

all

mea

lfor

tota

lof

900

kcal

/day

.H

Pdi

et:3

00g

lean

mea

t/po

ult

ry/fi

sh,3

serv

ings

/day

ofce

real

s/br

ead

and

low

-fat

dair

yfo

ods,

and

two

fru

itan

dve

geta

ble

serv

ings

/day

.Sh

ould

indu

cea

600

kcal

defi

cit

from

diet

.A

llsu

bjec

tsre

ceiv

edm

enu

plan

s,re

cipe

s,an

dco

okin

gad

vice

.A

ctiv

ity

was

not

rest

rict

ed.

Adh

eren

cen

otre

port

edor

use

din

anal

ysis

,alt

hou

ghdi

etdi

arie

sw

ere

use

d.M

ajor

focu

sof

the

stu

dyw

asse

xual

and

endo

thel

ial

fun

ctio

n.

Han

dlin

gof

mis

sin

gda

tan

otdi

scu

ssed

.

Max

imu

mlik

elih

ood

rep

eate

dm

easu

res

mix

edm

odel

sto

com

pare

pre/

pos

tm

easu

res.

Use

dti

me×

diet

inte

ract

ion

.Po

sth

ocpa

irw

ise

test

sm

ade.

Infl

amm

atio

n:

sign

ifica

nt

decr

ease

inC

RP

(at

8an

d52

wk)

,E

-Sel

ecti

n(a

t8

and

52w

k),a

nd

IL-6

(at

8w

kon

ly)

inH

Pdi

etgr

oup

(P<.0

1),b

ut

not

LCD

grou

p.G

lyce

mic

con

trol

:in

sulin

sen

siti

vity

(QU

ICK

I)si

gnifi

can

tim

prov

edin

LCD

grou

p,bu

tn

otH

Pdi

et(P

<.0

1).P

lasm

agl

uco

sedi

dn

otim

prov

esi

gnifi

can

tly

inei

ther

grou

p.O

ther

:sig

nifi

can

tly

wei

ght

loss

inbo

thgr

oups

.

Mra

zet

al.

(201

1),

Cze

chR

epu

blic

[23]

.T

he

effec

tof

ave

ry-l

ow-c

alor

iedi

eton

mR

NA

expr

essi

onof

infl

amm

atio

n-

rela

ted

gen

esin

subc

uta

neo

us

adip

ose

tiss

ue

and

per

iph

eral

mon

ocyt

esof

obes

epa

tien

tsw

ith

typ

e2

diab

etes

.

Qu

asie

xper

imen

tal

desi

gnw

ith

two

com

pari

son

grou

ps.

Sam

ple:N=

35w

omen

only

.Th

ein

terv

enti

onw

ason

lyim

plem

ente

din

the

12ob

ese

wom

enw

ith

T2D

M.

Two

oth

erco

ntr

olgr

oups

:15

hea

lthy

wom

en,a

nd

8ob

ese

wom

enw

ith

out

T2D

M.

Inte

rven

tion

last

ed2

wee

ksan

dw

asco

ndu

cted

ina

hos

pita

lse

ttin

gfo

rcl

ose

mon

itor

ing.

Infl

amm

ator

ym

arke

rs:

CR

P,IL

-6,T

NF,

IL-8

,C

CL-

2.G

lyce

mic

con

trol

:gl

uco

se,H

bA1c

,in

sulin

.D

iet:

non

e.O

ther

s:su

bcu

tan

eou

sad

ipos

eti

ssu

efo

rm

RN

Aex

pres

sion

ofch

emot

acti

cfa

ctor

s,lip

idpr

ofile

,ad

ipon

ecti

n,l

epti

n,

resi

stin

,wei

ght,

BM

I,an

dag

e.

Not

hin

gpr

ovid

edin

pape

r.

On

lyob

ese

wom

enw

ith

DM

wer

egi

ven

the

IVdi

et;a

2-w

eek

600

kcal

/day

diet

.All

pati

ents

wer

eh

ospi

taliz

ed.

No

adve

rse

even

tsor

med

icat

ion

chan

ges

repo

rted

from

the

inte

rven

tion

per

iod.

Inad

equ

ate

deta

ilof

the

inte

rven

tion

.N

odi

scu

ssio

nof

poss

ible

cau

ses

for

the

abn

orm

alfi

ndi

ng

ofin

crea

sed

TN

Ffo

llow

ing

the

inte

rven

tion

.

Pair

edt-

test

orW

ilcox

onsi

gned

-ran

kte

stu

sed

tode

tect

diff

eren

ces

betw

een

mea

sure

men

tspr

e/po

stin

terv

enti

on.

TN

F-α

leve

lsw

ere

sign

ifica

ntl

yin

crea

sed

inT

2DM

wom

enaf

ter

2w

eeks

offo

llow

ing

the

VLC

D(P

<.0

5fo

rpr

e/p

ostΔ

).H

bA1c

not

asse

ssed

afte

rin

terv

enti

on(o

nly

2w

eeks

).μΔ

inC

RP

pre/

post=

.94

mg/

L,P<.0

5.μΔ

inIL

-6pr

e/po

st=

.8pg

/mL

,P<.0

5.


Ta

ble

1:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

titl

e

Stu

dyde

sign

and

met

hod

sV

aria

bles

Inst

rum

ents

Inte

rven

tion

deta

ilsIm

port

ant

met

hod

olog

ical

flaw

s/bi

asn

oted

Dat

aan

alys

isO

utc

omes

rela

ted

toin

flam

mat

ion

,gly

cem

icco

ntr

ol,a

nd

diet

Asg

ard

etal

.(2

007)

,Sw

eden

[14]

.H

igh

inta

keof

fru

itan

dve

geta

bles

isre

late

dto

low

oxid

ativ

est

ress

and

infl

amm

atio

nin

agr

oup

ofpa

tien

tsw

ith

typ

e2

diab

etes

.

Cro

ss-s

ecti

onal

desi

gn.

Sam

ple:

53pa

rtic

ipan

tsre

cru

ited

from

new

spap

er.T

ype

2di

abet

esw

ith

HbA

1c<

10%

,40–

75yr

,B

MI<

35,a

nd

stab

lebo

dyw

eigh

t×3

mon

ths.

Infl

amm

ator

ym

arke

rs:

hs-

CR

P,IL

-6,u

rin

ary

15-k

eto-

dihy

ro-P

GF.

Gly

cem

icco

ntr

ol:

glu

cose

,HbA

1c,i

nsu

lin(b

asel

ine

desc

ript

ive

stat

son

ly).

Die

t:fr

uit

and

vege

tabl

ein

take

,α

-toc

oph

erol

,γ-

toco

pher

ol,

asco

rbat

e,α

-car

oten

e,β

-car

oten

e,lu

tein

,ly

cope

ne.

Oth

ers:

oxid

ativ

est

ress

and

chro

mos

omal

dam

age

mar

kers

.

3-da

ydi

etre

call

wit

hpr

ecod

edin

stru

men

tth

atw

asal

tere

dfo

rth

isst

udy

(ori

gin

ally

itw

asfo

r7

days

).P

rogr

amu

sed

tode

term

ine

mic

roan

dm

acro

nu

trie

nt

con

ten

tfr

omfo

odre

calls

,n

ame

ofpr

ogra

mn

otpr

ovid

ed.

NA

No

limit

atio

ns

sect

ion

inpa

per.

No

adju

stm

ents

for

age

orw

eigh

t.T

he

stu

dypa

rtic

ipan

tsw

ere

sim

ilar,

but

wei

ght

hig

her

infe

mal

es.T

his

part

icip

ant

grou

pan

swer

eda

new

spap

er,m

aybe

mor

ein

tere

sted

indi

et,t

hei

rdi

etw

asin

acco

rdan

cew

ith

the

Nor

dic

reco

mm

enda

tion

s.Lo

wer

mea

nH

bA1c

atba

selin

e(<

6.2%

).

Spea

rman

corr

elat

ion

coeffi

cien

tsw

ith

P<.0

1co

nsi

dere

dsi

gnifi

can

t.Fo

rco

rrel

atio

ns

wit

hin

flam

mat

ion

orox

idat

ive

stre

ss,

sign

ifica

nce

valu

ew

asse

tto

<.0

5.W

ilcox

ontw

osa

mpl

ete

sts

use

dw

ith

non

-nor

mal

lydi

stri

bute

dda

tato

dete

rmin

edi

ffer

ence

sbe

twee

nge

nde

rs.

IL-6

low

erw

ith

hig

her

leve

lsof

caro

ten

oids

(P<.0

1),b

ut

not

wit

hth

ela

rger

food

grou

pin

gsof

fru

its

and

vege

tabl

es.

γ-to

coph

erol

had

posi

tive

corr

elat

ion

wit

hC

RP.

Qie

tal

.(20

06),

U.S

.[15

].W

hol

e-gr

ain

,br

an,a

nd

cere

alfi

ber

inta

kes

and

mar

kers

ofsy

stem

icin

flam

mat

ion

indi

abet

icw

omen

.

Nes

ted

coh

ort

inlo

ngi

tudi

nal

anal

ytic

stu

dyof

the

Nu

rses

’H

ealt

hSt

udy

.Sa

mpl

e:N=

902

Wom

enbe

twee

n30

–55

wit

hty

pe2

diab

etes

asde

fin

edby

Nat

ion

alD

iabe

tes

Dat

agr

oup

(dia

gnos

ism

ade

prio

rto

1997

).

Infl

amm

ator

ym

arke

rs:

CR

P,T

NF-

R2,

Gly

cem

icco

ntr

ol:n

otas

sess

ed.

Die

t:gl

ycem

iclo

ad,

glyc

emic

inde

x,qu

inti

les

ofin

crea

sin

gin

take

ofw

hol

egr

ain

s,br

an,c

erea

lfibe

r,to

tal

fibe

ran

dge

rmQ

1–Q

5.O

ther

s:en

doth

elia

lfu

nct

ion

(s-I

CA

M,

solu

ble

E-s

elec

tin

)ox

idat

ive

stre

ssan

dch

rom

osom

alda

mag

em

arke

rs.

Sem

iqu

anti

tati

vefo

odfr

equ

ency

ques

tion

nai

re.

Qu

esti

onn

aire

from

the

Nu

rse’

sH

ealt

hSt

udy

toco

llect

anth

ropo

met

ric

and

lifes

tyle

data

.

No

inte

rven

tion

.

“Wh

ole

grai

ns

wer

epr

evio

usl

yde

scri

bed”

but

the

pape

rre

ferr

edto

was

wri

tten

bydi

ffer

ent

auth

ors

and

was

ina

stu

dyab

out

men

.No

limit

atio

ns

sect

ion

.D

ata

colle

cted

betw

een

1989

-199

0.O

nly

wom

enin

clu

ded.

Ass

ocia

tion

sev

alu

ated

wit

hlin

ear

regr

essi

on.

Inta

keof

diet

ary

vari

able

sas

sign

edto

quin

tile

s.In

flam

mat

ory

valu

eslo

g-tr

ansf

orm

edan

dm

edia

nva

lue

assi

gned

for

each

ofth

e5

quin

tile

s.A

dju

sted

for

age,

BM

I,sm

okin

g,al

coh

ol,p

hysi

cal

acti

vity

,asp

irin

use

,H

bA1c

,dx

ofhy

per

ten

sion

orhy

per

chol

este

role

mia

,po

stm

enop

ausa

lh

orm

one

use

,gl

ycem

icin

dex

and

mag

nes

ium

.

Wom

enw

ith

hig

her

inta

kes

ofw

hol

egr

ain

s,br

an,a

nd

cere

alfi

ber

had

low

erle

vels

ofC

RP

and

TN

Faf

ter

adju

stin

gfo

rag

e,B

MI,

lifes

tyle

,an

ddi

etar

yco

vari

ates

.


Ta

ble

2:Q

ual

ity

Ass

essm

ent

tool

and

scor

es.

Art

icle

Aim

sM

eth

ods

Die

tof

inte

rest

Rec

ruit

men

tIn

flam

mat

ion

Con

fou

ndi

ng

vari

able

sM

issi

ng

Con

clu

sion

sQ

ual

ity

rati

ng

(1pt

)(1

ptea

ch)

wel

l-de

fin

ed?

(1pt

each

)(1

pt)

(1pt

)(1

pt)

data

/att

riti

on(1

pt)

(2pt

s)(o

ut

of12

pts)

1st

Au

thor

Cle

arly

desc

ribe

dR

ead

Rep

rA

dT

OD

iet

Dis

cuss

edM

easu

res

appr

opri

ate

Con

trol

led

Pro

per

lyh

andl

edA

ppro

pria

teTo

tal

Asg

ard

10

11

00

11

01

17

Itsi

opou

los

11

01

11

11

00

07

Dav

is1

10

11

01

11

02

9Q

i1

10

11

10

11

02

8D

ostl

ova

10

01

00

01

10

15

Aza

dbak

ht

11

01

11

11

10

210

Boz

zett

o1

00

00

11

10

02

6G

ian

nop

oulo

u1

10

01

10

11

02

8B

arn

ard

01

01

11

11

01

18

Wol

ever

11

01

11

01

11

19

Vet

ter

01

00

10

00

10

14

Kos

łow

ska

10

00

10

01

00

14

Mar

fella

11

00

10

01

00

15

Kh

oo1

10

11

01

10

01

7M

raz

10

00

10

01

00

14

Bri

nkw

orth

11

11

11

11

01

110

Not

e.A

d:ad

her

ence

;Die

t:di

etar

yin

terv

enti

onde

fin

ed;R

ead:

read

abili

ty;R

epr:

repr

odu

cibi

lity;

TO

:app

ropr

iate

use

ofte

mpo

ralo

rder

ing.

Journal of Nutrition and Metabolism 13T

abl

e3:

Exp

erim

enta

lstu

dies

:ch

arac

teri

stic

san

dre

sult

sof

data

abst

ract

ion

.

Au

thor

/yea

r/co

un

try

Des

ign

Stu

dyle

ngt

h(w

eek)

Subj

ects

Die

tary

inte

rven

tion

Ou

tcom

esQ

ual

ity

rati

ng

Die

tde

tails

Con

trol

for

wei

ght

loss

diff

eren

ces?

ΔC

RP

ΔH

bA1c

%O

ther

Bri

nkw

orth

etal

.(2

004)

,Au

stra

lia[2

5]

2gr

oup

pret

est/

post

test

com

pari

son

desi

gnw

ith

ran

dom

izat

ion

64

N=

38F=

61%

M=

39%

μag

e=

61.8

Low

-pro

tein

(15%

)C

HO

55%

Fat

30%

vers

us

Hig

h-p

rote

in(3

0%)

CH

O40

%Fa

t30

%

Yes

Wei

ght

P=.6

1di

ffer

ence

betw

een

diet

s,bu

tov

eral

lde

crea

seP=.0

4Lo

w-p

rote

in:

pre:

4.2

post

(64

wk)

:3.6

Hig

h-p

rote

in:

pre:

5.0

post

(64

wk)

:3.8

P=.3

8∗

Low

-pro

tein

:pr

e:6.

2po

st(6

4w

k):6

.6H

igh

-pro

tein

:pr

e:6.

5po

st(6

4w

k):6

.6

NA

10

Gia

nn

opou

lou

etal

.(20

05),

U.S

.[2

7]

3-gr

oup,

pret

est-

post

test

wit

hra

ndo

miz

atio

n

14N=

33Fe

mal

eon

lyμ

age=

57

Die

ton

lyC

HO

40%

Fat

40%

(MU

FA30

%)

Exe

rcis

eon

lyD

iet

and

exer

cise

No

P<.0

1fo

ral

lth

ree

grou

psN

ora

wda

taav

aila

ble

NSΔ

NSΔ

inT

NF-α

orIL

-6fo

ral

lth

ree

grou

ps8

Mar

fella

etal

.(2

006)

,Ita

ly[1

6]R

CT

52

N=

115

M/F

data

not

give

nμ

age=

35.8

Win

e:4

oz.p

erda

y+

Med

iter

ran

ean

diet

Con

trol

grou

p:n

ow

ine

+M

edit

erra

nea

ndi

et

No

P<.0

1∗

Ch

ange

sin

raw

CR

Pva

lues

not

avai

labl

e

P=

NS∗

Ch

ange

sin

HbA

1c

Win

e:−1

.1±

0.06

Con

trol

:−1.

2±

0.7

TN

F-αP<.0

1∗

Ch

ange

sin

raw

TN

Fva

lues

not

avai

labl

eIL

-6P<.0

1∗

Ch

ange

sin

raw

IL-6

valu

esn

otav

aila

ble

5

Wol

ever

etal

.(2

008)

,Can

ada

[29]

3gr

oups

,pr

etes

t-po

stte

stw

ith

ran

dom

izat

ion

52

N=

162

F=

54%

M=

46%

μag

e=

59.9

Hig

hG

ILo

wG

ILo

wC

HO

CH

O20

%–2

5%Fa

tn

otpr

ovid

ed,

but

hig

hM

UFA

inLo

w-C

HO

diet

Yes

BM

I

Low

GI-

diet

:P<.0

5(d

iffer

ent

inμ

CR

Ppo

stin

terv

enti

onbe

twee

nlo

wan

dh

igh

GI

diet

s)po

stin

terv

enti

onμ

:H

igh

GI:

2.75

Low

GI:

1.95

Low

CH

O:2

.35

NS

diff

eren

cebe

twee

ngr

oups

,H

bA1c

rose

duri

ng

inte

rven

tion

Hig

hG

I:6.

34Lo

wG

I:6.

34Lo

wC

HO

:6.3

5

NA

9

Bar

nar

det

al.

(200

9),U

.S.[

24]

2gr

oups

,pr

etes

t-po

stte

st74

N=

99F=

61%

M=

39%

μag

e=

55.7

Veg

andi

etC

HO

75%

Fat

10%

Con

ven

tion

alA

DA

diet

C60

–70%

Fat<

7%sa

tura

ted

fat

Yes

Wei

ght

chan

ge

P=.6

5∗

Veg

an:(P<.0

1)−1

.9±

0.6.

Con

ven

tion

al:

(P<.0

1)−2

.4±

0.13

P=.0

3∗

(on

lyu

sin

gda

tapr

ior

tom

edia

nad

just

men

ts)

Veg

an:

(P<.0

1)−0

.4±

0.14

Con

ven

tion

al:

(P=

NS)

0.01±

0.8

P=.0

1To

talc

hol

este

rol

decr

ease

dm

ore

inve

gan

grou

p

8


Ta

ble

3:C

onti

nu

ed.

Au

thor

/yea

r/co

un

try

Des

ign

Stu

dyle

ngt

h(w

eek)

Subj

ects

Die

tary

inte

rven

tion

Ou

tcom

esQ

ual

ity

rati

ng

Die

tde

tails

Con

trol

for

wei

ght

loss

diff

eren

ces?

ΔC

RP

ΔH

bA1c

%O

ther

Dos

tlov

aet

al.

(200

9),C

zech

Rep

ubl

ic[2

1]

Qu

asi-

expe

rim

enta

lon

egr

oup

wit

htw

oco

mpa

riso

ngr

oups

(mon

itor

edin

the

hos

pita

l)

2

T2D

Mgr

oup

n=

14F

only

μag

e=

56.1

Ver

y-lo

w-c

alor

iedi

et(5

50kc

al/d

ay)

No

P<.0

5(Δ

inμ

CR

Ppr

e:13

.2±

3.5/

post

:7.

1±

2.4)

Fast

ing

glu

cose

P<.0

5(Δ

inμ

fast

ing

glu

cose

pre/

post

)

HO

MA

:P<.0

55

Koz

łow

ska

etal

.(2

010)

,Pol

and

[22]

Qu

asi-

exp

erim

enta

l(o

ne-

grou

ppr

etes

t-po

stte

st)

8

N=

17F=

41%

M=

59%

μag

e=

66.6

Low

ener

gy/L

owpr

otei

ndi

et(2

0%en

ergy

defi

cit,

0.8–

1.0

g/kg

)C

HO

60%

F30

%

No

P=.7

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3-hour postprandial, and 6-hour postprandial following 4weeks of a diet high in MUFAs, compared to the alternatediet which was high in carbohydrates and fiber with a lowglycemic index (P < .05) [19]. A study by Giannopoulouet al. [27] also demonstrated the anti-inflammatory effectsof a diet high in MUFAs (see Table 1). This study was 14weeks long, and comparison groups included an exercise-only group and a group that was prescribed exercise as wellas the high MUFA diet. All three groups demonstrated asignificant reduction in mean-CRP at final data collection(P < .01); however, there was not a significant difference inthis reduction between groups [27]. It is interesting to notehere that the diet and exercise group did not have a greaterdecrease in inflammatory markers than the diet-only group.These results indicate that exercise may not add benefit toimproving inflammatory markers in patients with T2D. Inanother longitudinal study, Barnard et al. [24] randomized99 participants to receive either a low-fat vegan diet or aconventional American Diabetes Association (ADA) diet for74 weeks. Results showed a significant reduction of CRPwithin groups (P < .01 for each group) but a nonsignificantdifference between the two diet groups [24], perhaps dueto the similar macronutrient content of the two dietaryinterventions.

Following on the premise that increased fat mass inT2D contributes to inflammation, three other studies imple-mented diets that were low or very low in energy content[21–23]. Kozłowska et al. [22] implemented a diet with a20% energy deficit and low protein for eight weeks withouta comparison group. This diet did not produce a significantreduction in CRP; however, the 17 participants did exhibitsignificantly lower TNF-α levels (P = .002) following theintervention [22]. Additional two studies implemented twoweeks of a very-low-calorie diet (VLCD) with obese subjectswith T2D in highly controlled hospital environments [21,23]. Dostlova et al. [21] demonstrated a significant dropin mean-CRP after two weeks of following a VLCD diet(P < .05). Mraz et al. [23] found that 2 weeks of a VLCDsignificantly decreased mean-CRP (P < .05), as well asdecreased IL-6 levels (P < .05). Although significant resultswere found, such diets cannot be maintained, and as such thelong-term effects are not known.

Marfella et al. [16] conducted an RCT in Italy withtwo groups that were advised to follow a Mediterranean-style diet. The Mediterranean diet is characterized by threeservings of fruits and six servings of vegetables or wildleafy greens per day [31]. Fish is consumed 5 to 6 timesper week and contributes to the main source of fat, whichis monounsaturated and polyunsaturated. The interventiongroup consumed 4 oz. of red wine per day, while the controlgroup abstained from alcohol. Results revealed significantlygreater reductions in CRP (P < .01), TNF-α (P < .01), andIL-6 (P < .01) in the intervention group compared to thecontrol group after the 52-week study period [16].

In contrast, there were several diets that did notalter inflammatory marker expression significantly. Theseincluded the high-carbohydrate/high-fiber/low-glycemicindex diet [19], the low-carbohydrate diet implemented byDavis et al. [26], the low-carbohydrate and DPP-style diet

implemented by Vetter et al. [17], and the Mediterraneandiet [20].

The two cross-sectional studies included in this analysisexamined associations between two different aspects of dietand differed significantly in terms of quality in reporting.Asgard et al. [14] quantified fruit and vegetable intake, whileQi et al. [15] categorized whole grain, germ, and bran intakeinto quintiles. Qi et al. demonstrated a significant associationbetween CRP and the dietary intake of interest, showingthat with increasing quintiles of cereal fiber intake, CRP wassignificantly lower (P for trend = .03) [15]. This inverserelationship was also present between TNF-α and cerealfiber intake (P for trend = .01). Asgard et al. [14] alsodemonstrated a significant inverse correlation between alpha(α) and beta (β) carotenoids (foods that contain vitamin A)and inflammation (r = −.41 and r = −.36, resp.).

6.2. Diet Influences Glycemic Control. The positive influenceof a dietary intervention on glycemic control [16, 20, 21, 24,27] was examined in five studies. Dostlova et al. [21] mea-sured fasting blood glucose (FBG) as a proxy for glycemiccontrol and demonstrated a significant improvement inFBG following the two-week dietary intervention of a very-low-calorie diet (P < .05). Itsiopoulos et al. [20] alsodemonstrated an improvement in glycemic control followinga 24-week crossover intervention with a Cretan Mediter-ranean diet as evidenced by a significantly reduced meanglycosylated hemoglobin (HbA1c) (P = .012), compared tothe control diet which was the participants’ normal eatingpattern. Both studies also demonstrated improvement in thehomeostatic model assessment (HOMA) score, a measureof insulin resistance (see Table 1), although this change wasnot statistically significant following the Mediterranean diet[20, 21]. A third study by Barnard et al. [24] found thatafter following a vegan diet for 72 weeks, subjects hadsignificantly improved HbA1c levels compared to those whofollowed a conventional diet as recommended by the ADA(P = .03) (see Table 3). A Mediterranean diet was alsoimplemented by Marfella et al. [16], along with either fourounces per day of red wine or no alcohol. HbA1c levelswere not significantly different between the two groups;however, the mean change in HbA1c was greater than inall other studies included in this review (−1.1% for theintervention group and −1.2% for the control group) [16].The clinical significance of such a large change in HbA1c willbe discussed later. Finally, Giannopoulou et al. [27] reportedthat although none of the intervention groups demonstrateda significant improvement in HbA1c, both the diet-only anddiet and exercise groups had a significant reduction in fastingglucose levels (P < .05 for both groups). Interestingly, onlythe two interventions with exercise produced a significantreduction in insulin resistance [27].

7. Discussion

The great variability between studies decreases the abilityto draw definitive conclusions about associations betweendiet, inflammation, and T2D; however, particular themes


emerged that are worth noting both from this review andin light of previous research. First, of the ten different dietsprescribed that were low in fat, both within and acrossstudies, eight of those diets led to significant reductions ininflammatory markers. These included the DASH diet [18],the low-fat DPP-style diet [26], the low-energy low-proteindiet [22], the vegan and ADA diets [24], the high-proteinlow-fat diet [28], and both the high-protein and low-proteindiets [25]. However, this review also supported the hypothe-sis that the high-MUFA diet decreased inflammation.

Previous reports from the Whitehall and PREDIMEDstudies indicated that diets high in MUFA and polyunsat-urated fatty acids (PUFAs) were correlated with decreasedCRP [32, 33] and IL-6 [33], while diets high in saturated fattyacids were positively correlated with CRP [32]. High intakeof PUFA was also inversely correlated with incidence of T2Din the Nurse’s Health Study [3]. Therefore, it was not sur-prising that the High-MUFA diet showed anti-inflammatoryeffects in the diabetic population [16, 19, 20, 29]. Bozzetto etal. [19] lacked baseline values for participants; therefore, it isnot appropriate to infer causality for a change in CRP overthe 4 weeks of the study period, but rather only in the acutepostprandial response. Unfortunately, glycemic control wasnot concurrently assessed.

Dietary patterns, as opposed to specific aspects of diet,have also been shown to correlate with levels of chronicinflammatory markers, but this concept was not adequatelyexamined in the selected studies. For example, the westerndietary pattern, characterized by a high consumption ofsugary drinks, red meat, and poultry and a low consumptionof fruits, vegetables, and fiber, was correlated with higherlevels of CRP in two large cross-sectional studies conductedin the US [34, 35].

The impact of diet on the metabolic milieu of T2Dis evident from the results of this integrative review andothers. However, statistical significance does not necessarilytranslate into clinical significance or meaningfulness. Forexample, of the two studies that were able to demonstratea significantly reduced HbA1c following the prescribed diet,one failed to report baseline values of glycemic control,[20] and the other only demonstrated a mean reductionof 0.4% [24]. While this result is statistically significant, itmight not result in improvement in long-term outcomes ofT2D, as demonstrated by findings from the United KingdomProspective Diabetes Study [36], which showed that a 1%reduction in HbA1c levels can lead to improvements inlong-term outcomes and decreased mortality [36]. Theimplementation of a Mediterranean-style diet and a glass ofred wine per day produced a mean decrease in HbA1c of1.1% (±0.06) [16]. The control group that did not receivethe red wine intervention but did follow a Mediterraneandiet had a similar decrease in HbA1c, as well as CRP, TNF-α, and IL-6 [16]. The reductions in HbA1c were not foundto be significantly different between intervention and controlgroups, though the drop in this important glycemic markeris clinically relevant, as it points to decreased incidence ofdiabetes-related complications and decreased mortality [36].

To further increase their clinical relevance, it is impor-tant for studies implementing dietary changes to examine

sustainability of the prescribed diet. Although both studiesof VLCD reported significant decreases in inflammatorymarkers, such a diet is not sustainable and is likely harmfulfor the individuals as evidenced by the significant increasein TNF-α following the 2-week VLCD implemented by Mrazet al. [23]. The rationale behind this intensive diet is rapidimprovement in metabolic parameters. The lack of long-term followup of the selected patients prevents us fromextrapolating from these findings that patients will havesustained results. In fact, the crossover experimental studyby Khoo et al. [28] illuminates that after 52 weeks of theprescribed diets, the group that initially received a low-calorie diet did not show a significant decrease in CRP,while the group that was prescribed the high-protein, low-fat diet for all 52 weeks did achieve significant reductionsin CRP. This highlights that there may not be merit behindthe rapid weight-loss from calorie-restricted programs in theaforementioned studies.

7.1. Gaps in Knowledge in the State of the Science. Due tothe limited availability of data for analysis on this topic andthe suboptimal quality of reporting within the studies, theresults of this integrative review are inconclusive. Many of thestudies reviewed suffered from significant methodologicalshortcomings. First, most of the studies had small samplesizes, with a range between 12 and 162 (mean sample size of53, and median of 32), limiting the power of the interventionto detect an effect. The two studies with the largest samplesizes implemented the low-glycemic-index diet and Mediter-ranean diet with wine and showed significant reductionin inflammatory marker expression [16, 29]. Only threestudies included in this integrative review conducted a poweranalysis [18, 24, 29], and one conducted a retrospectivepower analysis [25], which is paramount in substantiatingfindings or validating the need for further research if thefindings were insignificant.

Second, several studies did not include transparentdefinitions of the dietary intervention, rendering it difficultto infer specific dietary factors that decrease inflammationfrom the results. In previous studies with healthy volunteers,decreased inflammation was correlated with several individ-ual dietary factors including fiber, antioxidant vitamins suchas vitamin C and carotenoids, and fruit and vegetable intake.For example, in large prospective studies, whole grain intakehas been associated with both decreased inflammatory mark-ers [37] and decreased incidence of T2D [38]. Of the threeexperimental studies in the current review that indicatedwhole grains as an aspect of the diet, only one demonstrateddecreased CRP levels following the intervention [18]. Sim-ilarly, the cross-sectional study examining intake of wholegrains showed an inverse association between increasingintake of cereal fiber and CRP levels [15]. However, onestudy that implemented a high-carbohydrate, high-fiber dietand another that implemented a Cretan-Mediterranean diet,both of which are high in fiber, failed to demonstrate adecrease in CRP following the intervention [19, 20].

A third and final gap in knowledge related to thistopic is adherence and change over time. Though several


studies included in this study were longitudinal, the longeststudy was 74 weeks, which does not necessarily indicatethat benefits obtained will be sustained in the long-term.This issue was highlighted in the study by Brinkworth etal. [25] in which two low-fat diets, one low-protein, andone high-protein were prescribed to 38 participants withregular dietary counseling for the first 12 weeks. At 12weeks, HbA1c had decreased by 9.4% (P < .001) in bothgroups [39]. Results in glycemic control were attenuated,however, at 64 weeks due to the fact that participants hadnot received regular dietary counseling between weeks 12 and64 [25]. Recidivism such as this will likely be experienced inother long-term studies, underscoring the need for consistentcounseling as well as followup in long-term studies thatrequire behavior change [40].

7.2. Limitations. There are several limitations of this integra-tive review. First, the review is limited to the published litera-ture, so it is subject to publication bias. Several authors werecontacted via email with requests for unpublished research,but none were available. Second, the articles reviewed foranalysis only included a population with diagnosed T2D.This limited the available literature on the influence of dieton inflammation and glycemic control markedly. There ismerit in restriction of the search to this population, giventhat their inflammatory markers will be elevated relative tothe general population and would, therefore, benefit fromdietary changes in a more clinically significant way. However,this strength may have limited the conclusions in this paper.Finally, it should be noted that this integrative review doesnot address the mechanism of action underlying reductionof systemic inflammation following a dietary intervention.Discussion of such is beyond the scope of this paper. Thereview by Visioli et al. [41] concluded that antioxidants,essential fatty acids, and plant extracts have been shown toreduce systemic inflammation. Extrapolating results fromthis integrative review to make inferences about specificnutrient effects is not possible; however, it can be inferredthat nutrient content of the Mediterranean, vegan, and ADAdiets may contain more of those qualities mentioned in thereview [41].

7.3. Implication for Future Research. Given the limitationsof the findings and the inconclusive results reached by thisreview, it is clear that more rigorous research is needed. Thepresent level of evidence on this topic is Level III, giventhat most of the studies were quasiexperimental. This paper,therefore, increases the level of evidence by providing anintegrative review of the available research. However, dis-parate methods of reporting findings have rendered synthesisof extant findings difficult and unnecessarily labor-intensive.Studies should adhere to the transparent reporting standardsoutlined by the Consolidated Standards of Reporting Trials[42]. Researchers should also focus their efforts on increasingvalidity and reliability in research conduct. Adherence todietary interventions needs to be reported and included inanalysis of the findings, possibly by including a measure ofadherence as a regression variable. Failure to include this

critical factor could explain the variability in the findings ofthis integrative review, for a dose response is a likely influencein the success or failure of an intervention effect. Adequately-powered, high quality studies examining the associationbetween dietary intake and inflammation in T2D are alsoneeded.

Medical nutrition therapy is one aspect of preventionand care of T2D recommended by the ADA. Although theDPP demonstrated a reduction in the incidence of T2Dfollowing the adaptation of lifestyle changes, there have beenfew studies examining the influence of dietary interventionson inflammation and glycemic control in individuals withestablished T2D in the US. It is important to conductthese studies domestically because of the diversity of thepopulations affected by this disease and the increasingrates of T2D. For example, further analysis of the resultsfrom the DPP revealed an attenuated benefit from theintervention in non-Hispanic Black women, highlightingthe need for an understanding of the complex socioculturalfactors influencing the African American population [43].Studies examining the current dietary practices of individu-als diagnosed with T2D are necessary, with a particular focuson differences in culturally-bound beliefs surrounding diet,food, and health.

None of the studies included in this review used atheoretical framework to guide the research, which couldhave contributed to the disparate findings of the includedstudies. Theoretical frameworks guide research questionsand facilitate the process of asking a complete question.Considering that T2D is both a metabolic and inflammatorydisease, it is imperative to design studies that address both ofthese issues in the methods and the outcome measures. Forexample, if an intervention of a high MUFA diet is imple-mented, it may be helpful not only to address inflammatorymarkers in the outcome measures, but also other influenceson inflammation that could confound results such as physicalactivity, socioeconomic status, environmental stressors, andgenetic factors as suggested by Kang’s Biobehavioral Modelof Stress and Inflammation [10]. It is unclear from theaforementioned studies how exercise, stress, and geneticscontributed to the metabolic and inflammatory outcomesmeasured, and larger, more rigorous studies are needed thatcontrol these variables. Finally, based on the results of theaforementioned studies, RCTs using participants with T2Dare needed for which the nutrition content of the dietaryintervention has been optimized for the treatment of T2D.This includes high intake of fruits and vegetables that arehigh in flavonoids, which Gonzalez-Castejon and Rodriguez-Casado [44] report in their review on phytochemicals tohave anti-inflammatory and antioxidant activities that mayimprove the metabolic status of individuals with T2D.The Mediterranean diet is an extremely palatable diet richin fruits, vegetables, fiber, and olive oil which has beenshown with and without the addition of alcohol to improveinflammation, prevent the onset of T2D, and improveglycemic control in established T2D [16, 41, 44]. More high-quality RCTs implementing this diet are needed to providethe evidence base for modifying clinical practice guidelinesin medical nutrition therapy for patients with T2D.


References

[1] Centers for Disease Control and Prevention, National DiabetesFact Sheet: National Estimates and General Information onDiabetes and Prediabetes in the United States, U.S. Departmentof Health and Human Services, Centers for Disease Controland Prevention, Atlanta, Ga, USA, 2011.

[2] D. Grotto and E. Zied, “The standard American diet and itsrelationship to the health status of Americans,” Nutrition inClinical Practice, vol. 25, no. 6, pp. 603–612, 2010.

[3] J. Salmeron, F. B. Hu, J. E. Manson et al., “Dietary fat intakeand risk of type 2 diabetes in women,” American Journal ofClinical Nutrition, vol. 73, no. 6, pp. 1019–1026, 2001.

[4] A. Astrup and N. Finer, “Redefining type 2 diabetes: “Dia-besity” or “obesity dependent diabetes mellitus”?” ObesityReviews, vol. 1, no. 2, pp. 57–59, 2000.

[5] W. C. Knowler, E. Barrett-Connor, S. E. Fowler et al.,“Reduction in the incidence of type 2 diabetes with lifestyleintervention or metformin,” The New England Journal ofMedicine, vol. 346, no. 6, pp. 393–403, 2002.

[6] M. P. Stern, “Diabetes and cardiovascular disease: the “com-mon soil” hypothesis,” Diabetes, vol. 44, no. 4, pp. 369–374,1995.

[7] R. C. Turner, H. Millns, H. A. W. Neil et al., “Risk factorsfor coronary artery disease in non-insulin dependent dia-betes mellitus: United Kingdom prospective diabetes study(UKPDS: 23),” British Medical Journal, vol. 316, no. 7134, pp.823–828, 1998.

[8] A. G. Bertoni, G. L. Burke, J. A. Owusu et al., “Inflammationand the incidence of type 2 diabetes: the Multi-Ethnic Studyof Atherosclerosis (MESA),” Diabetes Care, vol. 33, no. 4, pp.804–810, 2010.

[9] B. B. Duncan, M. I. Schmidt, J. S. Pankow et al., “Low-grade systemic inflammation and the development of type2 diabetes: the atherosclerosis risk in communities study,”Diabetes, vol. 52, no. 7, pp. 1799–1805, 2003.

[10] D. H. Kang, M. Rice, N. J. Park, A. Turner-Henson, and C.Downs, “Stress and inflammation: a biobehavioral approachfor nursing research,” Western Journal of Nursing Research, vol.32, no. 6, pp. 730–760, 2010.

[11] C. M. Kastorini and D. B. Panagiotakos, “Dietary patternsand prevention of type 2 diabetes: from research to clinicalpractice—a systematic review,” Current Diabetes Reviews, vol.5, no. 4, pp. 221–227, 2009.

[12] M. A. Martınez-Gonzalez, C. De La Fuente-Arrillaga, J. M.Nunez-Cordoba et al., “Adherence to Mediterranean diet andrisk of developing diabetes: prospective cohort study,” BMJ,vol. 336, no. 7657, pp. 1348–1351, 2008.

[13] F. Centritto, L. Iacoviello, R. di Giuseppe et al., “Dietarypatterns, cardiovascular risk factors and C-reactive proteinin a healthy Italian population,” Nutrition, Metabolism andCardiovascular Diseases, vol. 19, no. 10, pp. 697–706, 2009.

[14] R. Asgard, E. Rytter, S. Basu, L. Abramsson-Zetterberg, L.Moller, and B. Vessby, “High intake of fruit and vegetables isrelated to low oxidative stress and inflammation in a group ofpatients with type 2 diabetes,” Scandinavian Journal of Foodand Nutrition, vol. 51, no. 4, pp. 149–158, 2007.

[15] L. Qi, R. M. Van Dam, S. Liu, M. Franz, C. Mantzoros, and F. B.Hu, “Whole-grain, bran, and cereal fiber intakes and markersof systemic inflammation in diabetic women,” Diabetes Care,vol. 29, no. 2, pp. 207–211, 2006.

[16] R. Marfella, F. Cacciapuoti, M. Siniscalchi et al., “Effect ofmoderate red wine intake on cardiac prognosis after recent

acute myocardial infarction of subjects with Type 2 diabetesmellitus,” Diabetic Medicine, vol. 23, no. 9, pp. 974–981, 2006.

[17] M. L. Vetter, A. Wade, L. G. Womble, C. Dalton-Bakes, T.A. Wadden, and N. Iqbal, “Effect of a low-carbohydrate dietversus a low-fat, calorie-restricted diet on adipokine levelsin obese, diabetic participants,” Diabetes, Metabolic Syndromeand Obesity, vol. 3, pp. 357–361, 2010.

[18] L. Azadbakht, P. J. Surkan, A. Esmaillzadeh, and W. C.Willett, “The dietary approaches to stop hypertension eatingplan affects C-reactive protein, coagulation abnormalities, andhepatic function tests among type 2 diabetic patients,” Journalof Nutrition, vol. 141, no. 6, pp. 1083–1088, 2011.

[19] L. Bozzetto, C. De Natale, L. Di Capua et al., “The associationof hs-CRP with fasting and postprandial plasma lipids inpatients with type 2 diabetes is disrupted by dietary monoun-saturated fatty acids,” Acta Diabetologica. In press.

[20] C. Itsiopoulos, L. Brazionis, M. Kaimakamis et al., “Can theMediterranean diet lower HbA1c in type 2 diabetes? Resultsfrom a randomized cross-over study,” Nutrition, Metabolismand Cardiovascular Diseases, vol. 21, no. 9, pp. 740–747, 2010.

[21] I. Dostlova, T. Roubcek, M. Brtlov et al., “Increasedserum concentrations of macrophage inhibitory cytokine-1 in patients with obesity and type 2 diabetes mellitus:the influence of very low calorie diet,” European Journal ofEndocrinology, vol. 161, pp. 397–404, 2009.

[22] L. Kozłowska, A. Rydzewski, B. Fiderkiewicz, A. Wasinska-Krawczyk, A. Grzechnik, and D. Rosołowska-Huszcz,“Adiponectin, resistin and leptin response to dietaryintervention in diabetic nephropathy,” Journal of RenalNutrition, vol. 20, no. 4, pp. 255–262, 2010.

[23] M. Mraz, Z. Lacinova, J. Drapalova et al., “The effect ofvery-low-calorie diet on mRNA expression of inflammation-related genes in subcutaneous adipose tissue and peripheralmonocytes of obese patients with type 2 diabetes mellitus,”Journal of Clinical Endocrinology and Metabolism, vol. 96, no.4, pp. E606–E613, 2011.

[24] N. D. Barnard, J. Cohen, D. J. A. Jenkins et al., “A low-fatvegan diet and a conventional diabetes diet in the treatmentof type 2 diabetes: a randomized, controlled, 74-wk clinicaltrial,” American Journal of Clinical Nutrition, vol. 89, no. 5, pp.1588S–1596S, 2009.

[25] G. D. Brinkworth, M. Noakes, B. Parker, P. Foster, and P.M. Clifton, “Long-term effects of advice to consume a high-protein, low-fat diet, rather than a conventional weight-lossdiet, in obese adults with Type 2 diabetes: one-year follow-upof a randomised trial,” Diabetologia, vol. 47, no. 10, pp. 1677–1686, 2004.

[26] N. J. Davis, J. P. Crandall, S. Gajavelli et al., “Differential effectsof low-carbohydrate and low-fat diets on inflammation andendothelial function in diabetes,” Journal of Diabetes and ItsComplications, vol. 25, pp. 371–376, 2011.

[27] I. Giannopoulou, B. Fernhall, R. Carhart et al., “Effects ofdiet and/or exercise on the adipocytokine and inflammatorycytokine levels of postmenopausal women with type 2 dia-betes,” Metabolism, vol. 54, no. 7, pp. 866–875, 2005.

[28] J. Khoo, C. Piantadosi, R. Duncan et al., “Comparing effectsof a low-energy diet and a high-protein low-fat diet onsexual and endothelial function, urinary tract symptoms,and inflammation in obese diabetic men,” Journal of SexualMedicine, vol. 8, pp. 2868–2875, 2011.

[29] T. M. S. Wolever, A. L. Gibbs, C. Mehling et al., “The CanadianTrial of Carbohydrates in Diabetes (CCD), a 1-y controlledtrial of low-glycemic-index dietary carbohydrate in type 2


diabetes: no effect on glycated hemoglobin but reduction inC-reactive protein,” American Journal of Clinical Nutrition, vol.87, no. 1, pp. 114–125, 2008.

[30] R. Whittemore and K. Knafl, “The integrative review: updatedmethodology,” Journal of Advanced Nursing, vol. 52, no. 5, pp.546–553, 2005.

[31] J. Moschandreas and A. Kafatos, “Food and nutrient intakesof Greek (Cretan) adults. Recent data for food-based dietaryguidelines in Greece,” British Journal of Nutrition, vol. 81,supplement 2, pp. S71–S76, 1999.

[32] R. Clarke, M. Shipley, J. Armitage, R. Collins, and W. Harris,“Plasma phospholipid fatty acids and CHD in older men:whitehall study of London civil servants,” British Journal ofNutrition, vol. 102, no. 2, pp. 279–284, 2009.

[33] J. Salas-Salvado, A. Garcia-Arellano, R. Estruch et al., “Com-ponents of the mediterranean-type food pattern and seruminflammatory markers among patients at high risk for cardio-vascular disease,” European Journal of Clinical Nutrition, vol.62, no. 5, pp. 651–659, 2008.

[34] T. T. Fung, F. B. Hu, M. A. Pereira et al., “Whole-grain intakeand the risk of type 2 diabetes: a prospective study in men,”American Journal of Clinical Nutrition, vol. 76, no. 3, pp. 535–540, 2002.

[35] E. Lopez-Garcia, M. B. Schulze, J. E. Manson et al., “Consump-tion of (n-3) fatty acids is related to plasma biomarkers ofinflammation and endothelial activation in women,” Journalof Nutrition, vol. 134, no. 7, pp. 1806–1811, 2004.

[36] American Diabetes Association, “Implications of the UnitedKingdom prospective siabetes study,” Diabetes Care, vol. 25,pp. S28–S32, 2002.

[37] Y. Ma, J. R. Hebert, W. Li et al., “Association between dietaryfiber and markers of systemic inflammation in the Women’sHealth Initiative Observational Study,” Nutrition, vol. 24, no.10, pp. 941–949, 2008.

[38] S. Liu, M. J. Stampfer, F. B. Hu et al., “Whole-grain con-sumption and risk of coronary heart disease: results from theNurses’ Health Study,” American Journal of Clinical Nutrition,vol. 70, no. 3, pp. 412–419, 1999.

[39] B. Parker, M. Noakes, N. Luscombe, and P. Clifton, “Effect ofa high-protein, high-monounsaturated fat weight loss diet onglycemic control and lipid levels in type 2 diabetes,” DiabetesCare, vol. 25, no. 3, pp. 425–430, 2002.

[40] M. S. Song and H. S. Kim, “Intensive management program toimprove glycosylated hemoglobin levels and adherence to dietin patients with type 2 diabetes,” Applied Nursing Research, vol.22, no. 1, pp. 42–47, 2009.

[41] F. Visioli, A. Poli, D. Richard, and R. Paoletti, “Modula-tion of inflammation by nutritional interventions,” CurrentAtherosclerosis Reports, vol. 10, no. 6, pp. 451–453, 2008.

[42] K. F. Schulz, D. G. Altman, and D. Moher, “CONSORT, 2010Statement: updated guidelines for reporting parallel grouprandomised trials,” Journal of Clinical Epidemiology, vol. 63,pp. 813–814, 2010.

[43] D. S. West, T. Elaine Prewitt, Z. Bursac, and H. C. Felix,“Weight loss of black, white, and Hispanic men and womenin the diabetes prevention program,” Obesity, vol. 16, no. 6,pp. 1413–1420, 2008.

[44] M. Gonzalez-Castejon and A. Rodriguez-Casado, “Dietaryphytochemicals and their potential effects on obesity: areview,” Pharmacological Research, vol. 64, pp. 438–455, 2011.

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