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SYSTEMATIC REVIEW
Received 2 October 2012; received in revised form 18 February 2013; accepted 21 April 2013
Available online 17 June 2013
KEYWORDS Abstract Aim: The aim of the present meta-analysis was to investigate the long-term effects
Cardiovascular risk of glycemic index-related diets in the management of obesity with a special emphasis on the
factors; potential benefits of low glycemic index/load (GI/GL) in the prevention of obesity-associated
Glycemic index; risks.
Glycemic load; Data synthesis: Electronic searches for randomized controlled trials (RCTs) comparing low gly-
Meta-analysis cemic index/load versus high glycemic index/load diets were performed in MEDLINE, EMBASE
and the Cochrane Library. Outcome of interest markers included anthropometric data as well
as biomarkers of CVD and glycemic control. Study specific weighted mean differences were
pooled using a random effect model. 14 studies were included in the primary meta-analysis.
Weighted mean differences in change of C-reactive protein [WMD: 0.43 mg/dl, (95% CI
0.78 to 0.09), p Z 0.01], and fasting insulin [WMD: 5.16 pmol/L, (95% CI 8.45 to
1.88), p Z 0.002] were significantly more pronounced in benefit of low GI/GL diets. However
decrease in fat free mass [WMD: 1.04 kg (95% CI 1.73 to 0.35), p Z 0.003] was significantly
more pronounced following low GI/GL diets as well. No significant changes were observed for
blood lipids, anthropometric measures, HbA1c and fasting glucose. Sensitivity analysis was per-
formed for RCTs excluding subjects with type 2 diabetes. Decreases in C-reactive protein and
fasting insulin remained statistically significant in the low GI/GL subgroups.
Conclusions: The present systematic review provides evidence for beneficial effects of long-
term interventions administering a low glycemic index/load diet with respect to fasting insulin
* Corresponding author. Tel.: þ43 1 4277 54956; fax: þ43 1 4277 9549.
E-mail address: lukas.schwingshackl@univie.ac.at (L. Schwingshackl).
0939-4753/$ - see front matter ª 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.numecd.2013.04.008
700 L. Schwingshackl, G. Hoffmann
and pro-inflammatory markers such as C-reactive protein which might prove to be helpful in
the primary prevention of obesity-associated diseases.
ª 2013 Elsevier B.V. All rights reserved.
Methods
Literature search
Figure 1 Risk of bias assessment tool. Across trials, infor-
Queries of literature were performed using the electronic mation is either from trials at a low risk of bias (green), or from
databases MEDLINE (between 1966 and February 2013), trials at unclear risk of bias (yellow), or from trials at high risk
EMBASE (between 1980 and February 2013), and the of bias (red). (For interpretation of the references to color in
Cochrane Trial Register (until February 2013) with re- this figure legend, the reader is referred to the web version of
strictions to randomized controlled trials, but no this article.)
Glycemic index/load and risk of CVD 701
Data extraction and statistical analysis means were used to calculate standard deviations, ac-
cording the guidelines by the Cochrane Handbook [20].
The following data were extracted from each study: the first
author’s last name, publication year, study duration, partici- Results
pant’s sex and age, BMI, % diabetics, sample size, drop outs,
values of GI/GL at the end of the study, outcomes and post
mean values or differences in mean of two time point values Literature search
with corresponding standard deviation. For each outcome
measure of interest, a meta-analysis was performed in order Altogether, 15 studies extracted from 2170 articles met the
to determine the pooled effect of the intervention in terms of inclusion criteria, and 14 of them were included in the
weighted mean differences (WMDs) between the post- quantitative analysis [24e37]. The paper by Raatz et al.
intervention (or differences in means) values of the LGI/LGL [38] reported no appropriate follow-up data and was
and HGI/HGL groups. Combining both the post-intervention considered for qualitative analysis only. The detailed steps
values and difference in means in one meta-analysis is a of the meta-analysis article selection process are described
legitimate method described by the Cochrane Collaboration as a flow diagram in Fig. 2.
[20]. All data were analyzed using the REVIEW MANAGER 5.1
software, provided by the Cochrane Collaboration (http:// Study characteristics
ims.cochrane.org/revman). Forest plots were generated to
illustrate the study-specific effect sizes along with a 95% CI. All studies included were RCTs with a duration ranging be-
Heterogeneity between trial results was tested with a stan- tween 24 and 68 weeks, published between 2005 and 2011
dard c2 test. The I2 parameter was used to quantify any and enrolling a total of 2344 participants (65% women, 35%
inconsistency: I2 Z [(Q d.f.)]/Q 100%, where Q is the c2 men). General study characteristics are summarized in
statistic and d.f. is its degrees of freedom. A value for I2 >50% (Supplementary Information Tables 1, 2).
was considered to represent substantial heterogeneity [21]. Since type 2 diabetes mellitus (T2D) was not defined as an
RCTs within this systematic review differ with respect to the exclusion criteria, four studies included subjects with T2D
exact GI or GL values used in the interventions. In order to [25e27,32]. In the LGI/LGL groups, the range for glycemic
detect a possible doseeresponse relationship between inter- index was 30e76, while glycemic load varied between 75 and
study variations of LGI/LGL and HGI/HGL characteristics and 148. The corresponding data for HGI/HGL protocols were
changes in all outcome parameters, respectively, a random- 53e85.6 (glycemic index) and 95e280 (glycemic load).
effects meta-regression was performed. The p-values for The pooled estimate of effect size for the effects of LGI/
differences in effects between the covariates were obtained LGL as compared to HGI/HGL on all outcomes is summa-
using the metareg function of STATA 12.0 (Stata-Corp, College rized in Table 1 (Forest plots Supplemental Figures 1e12).
Station, TX. USA). Two sided p-values <0.05 were considered
to be statistically significant. Funnel plots were used to assess
potential publication bias (e.g. the tendency for studies that Outcome parameters
yield statistically significant results to be more likely to be
submitted and accepted for publication). To determine the Anthropometric data
presence of publication bias, we assessed the symmetry of the Decrease in FFM was significantly more prominent following
funnel plots in which mean differences were plotted against LGI/LGL dietary protocols as compared to their HGI/HGL
their corresponding standard errors. Additionally, Begg’s and counterparts [Weighted mean difference (WMD) 1.04 kg
Egger regression tests were performed [22,23]. Raw data were (95% CI 1.73 to 0.35), p Z 0.003] (I2 Z 0%). No signifi-
available from 2 RCTs [24,25]. In one trial [24], the LGI diet cant changes were observed for weight [0.62 kg (95% CI
was approached by two different kinds of intervention: one 1.28 to 0.03), p Z 0.06] (I2 Z 0%) and WC [0.06 cm (95% CI
included the LGI setting in a low fat (LF) protocol, while the 0.83 to 0.96), p Z 0.89] (I2 Z 0%).
other combined LGI with an high monounsaturated fat (MUFA)
regime. Both types of LGI diets were included in the meta- Blood lipids
analysis via a separate comparison of LGI/LF versus HGI/LF, No significant changes were observed for TC [1.22 mg/dl
LGI/MUFA versus HGI/MUFA. The same procedure was done (95% CI 5.62 to 3.19), p Z 0.59] (I2 Z 44%) and LDL-C
for another RCTwhich compared LGI/LP (low protein) vs. HGI/ [0.29 mg/dl (95% CI 4.45 to 3.86), p Z 0.89] (I2 Z 54%),
LP and LGI/HP (high protein) vs. HGI/HP. This was done in HDL-C [0.73 mg/dl (95% CI 0.23 to 1.69), p Z 0.14] (I2 Z 0%)
order to minimize a potential confounder of LF, MUFA, LP and and TG [0.86 mg/dl (95% CI 5.65 to 3.93), p Z 0.72]
HP respectively, when comparing LGI and HGI diets. Data (I2 Z 0%) between LGI/LGL vs. HGI/HGL diets.
extraction was conducted independently by both authors,
with disagreements resolved by consensus. Glycemic control and CRP
Decreases in CRP were more pronounced in the LGI/LGL
groups as compared to their HGI/HGL counterparts [WMD:
Missing data 0.43 mg/dl (95% CI 0.78 to 0.09), p Z 0.01] (I2 Z 54%)
(Fig. 3). Concerning biomarkers of glycemic control, levels of
Data processing for this review required the input of the FI were significantly more attenuated by LGI/LGL diets as
mean and standard deviation (SD) of post-intervention compared to the HGI/HGL settings [WMD: 5.16 pmol/L (95%
values or differences in means. When SD was not avail- CI 8.45 to 1.88), p Z 0.002] (I2 Z 48%) (Fig. 4). None
able [26e28], standard errors and confidence intervals for significant changes were observed for FG [WMD: 0.49 mg/dl
702 L. Schwingshackl, G. Hoffmann
Table 1 Pooled estimates of effect size (95% confidence intervals) expressed as weighted mean difference for the effects of
LGI/LGL vs. HGI/HGL diets on anthropometric and cardiovascular risk factors as well as glycemic control.
Outcomes No. of studies Sample size WMD 95% CI p-Values Inconsistency I2 Egger test
Weight (kg) 14 1770 0.62 [1.28, 0.03] 0.06 0% p Z 0.289
Weighta (kg) 10 1338 0.54 [1.22, 0.13] 0.11 0%
WC (cm) 8 1234 0.06 [0.83, 0.96] 0.89 0% p Z 0.516
WCa (cm) 5 1012 0.20 [1.22, 0.82] 0.70 0%
TC (mg/dl) 13 1672 1.22 [5.62, 3.19] 0.59 44% p Z 0.216
TCa (mg/dl) 9 1254 1.63 [6.36, 3.11] 0.50 42%
LDL-C (mg/dl) 14 1737 0.29 [4.45, 3.86] 0.89 54% p Z 0.441
LDL-Ca (mg/dl) 10 1321 0.66 [5.21, 3.89] 0.78 55%
HDL-C (mg/dl) 14 1734 0.73 [0.23, 1.69] 0.14 0% p Z 0.460
HDL-Ca (mg/dl) 10 1317 0.74 [0.38, 1.86] 0.19 5%
TG (mg/dl) 14 1735 0.86 [5.65, 3.93] 0.72 0% p Z 0.152
TGa (mg/dl) 10 1317 0.87 [5.98, 4.24] 0.74 0%
CRP (mg/dl) 5 1204 0.43 [0.78, 0.09] 0.01 0% p Z 0.386
CRPa (mg/dl) 3 905 0.41 [0.76, 0.06] 0.02 0%
FG (mg/dl) 10 1511 0.49 [1.28, 2.25] 0.59 52% p Z 0.420
FGa (mg/dl) 7 1147 0.77 [0.88, 2.43] 0.36 50%
FI (pmol/L) 9 1132 5.16 [8.45, 1.88] 0.002 48% p Z 0.008
FIa (pmol/L) 7 978 5.19 [9.05, 1.32] 0.008 56%
HbA1c (%) 4 421 0.09 [0.52, 0.33] 0.67 72% p Z 0.958
FFM (kg) 3 413 1.04 [1.73, 0.35] 0.003 0% p Z 0.529
a
Sensitivity analysis excluding studies enrolling patients with type 2 diabetes mellitus. CRP Z high-sensitive C-reactive protein,
FFM Z fat free mass, FG Z fasting insulin, FI Z fasting insulin, HbA1c Z glycosylated hemoglobin, HDL-C Z high density lipoprotein-
cholesterol, LDL-C Z low density lipoprotein-cholesterol, TC Z total cholesterol, TG Z triacylglycerols, WC Z waist circumference,
WMD Z weighted mean differences.
Glycemic index/load and risk of CVD 703
Figure 3 Forest plot showing pooled WMD with 95% CI for CRP (mg/dl) for 5 randomized controlled LGI/LGL diet studies. For each
LGI/LGL study, the shaded square represents the point estimate of the intervention effect. The horizontal line joins the lower and
upper limits of the 95% CI of these effects. The area of the shaded square reflects the relative weight of the study in the respective
meta-analysis. The diamond at the bottom of the graph represents the pooled WMD with the 95% CI. Abbreviations: CRP Z high-
sensitive C-reactive protein, HGI/HGL Z high glycemic index/load, LGL/LGI Z low glycemic index/load.
(95% CI 1.28 to 2.25), p Z 0.59] (I2 Z 52%) and HbA1c [WMD: the present meta-analysis. It remains possible that small
0.09% (95% CI 0.52 to 0.33), p Z 0.67] (I2 Z 72%). studies yielding inconclusive data have not been published.
The Begg’s and Egger regression tests provided no evidence
Sensitivity analysis of substantial publication bias, beside FI (p Z 0.008) and
FM (p Z 0.037) (Table 1).
To investigate the effects of LGI/LGL diets on non-diabetic
subjects, a sensitivity analysis was performed excluding all Heterogeneity
RCTs enrolling patients with T2D [25e27,32]. A total of 10
studies remained [24,28e31,33e37]. Changes in CRP [WMD: Moderate to substantial heterogeneity was found with
0.41 mg/dl (95% CI 0.76 to 0.06), p Z 0.02] and FI respect to HbA1c (I2 Z 72%), FG (I2 Z 52%), LDL-C
[WMD: 5.19 pmol/L (95% CI 9.05 to 1.32), p Z 0.008] (I2 Z 54%), FI (I2 Z 48%), and TC (I2 Z 44%) (Table 1). In
remained to be significantly more pronounced following an spite of low heterogeneity, a random-effects meta-regres-
LGI/LGL regimen as compared to HGI/HGL diets. For FFM, sion was performed to examine the associations between
no sensitivity analysis was done due to the small number of LGI/LGL and HGI/HGL characteristics and changes in all
studies assessing this parameter. In addition, a subgroup outcomes, respectively. No statistically significant dos-
analysis was performed for studies with a BMI 30 kg/m2 vs. eeresponse relationship could be detected between gly-
BMI <30 kg/m2 and study length 52 weeks vs. <52 weeks. cemic index/glycemic load and changes in outcome
The sensitivity analysis shows overall more pronounced parameters, but marginal doseeresponse relationships
benefits of LGI/LGL diets (Supplemental Tables 3e6). could be detected for TG, GL (p Z 0.07) and GI (p Z 0.09),
respectively (Supplemental Figures 27, 28).
Publication bias
Discussion
All funnel plots are provided as Supplementary Material
(Supplemental Figures 13e26). The funnel plots indicate The present meta-analysis investigated the effects of gly-
moderate asymmetry, suggesting that publication bias cemic index/load on parameters of body composition and
cannot be completely excluded as a factor of influence on biomarkers of cardiovascular risk in long-term dietary
Figure 4 Forest plot showing pooled WMD with 95% CI for fasting insulin (pmol//L) for 9 randomized controlled LGI/LGL diet
studies. For each LGI/LGL study, the shaded square represents the point estimate of the intervention effect. The horizontal line
joins the lower and upper limits of the 95% CI of these effects. The area of the shaded square reflects the relative weight of the
study in the respective meta-analysis. The diamond at the bottom of the graph represents the pooled WMD with the 95% CI. Ab-
breviations: HGI/HGL Z high glycemic index/load, LGL/LGI Z low glycemic index/load.
704 L. Schwingshackl, G. Hoffmann
intervention studies with overweight and obese subjects. In would expect a decrease in fasting insulin in long-term
summary, decreases in C-reactive protein, fasting insulin interventional trials featuring reduced levels of inflamma-
and fat free mass were significantly more pronounced in the tory markers as observed in the present meta-analysis.
LGI/LGL diet groups as compared to their HGI/HGL coun- Systematic reviews of cohort studies suggested that HGI/
terparts, while all other parameters under investigation HGL diets are associated with an increased risk for the
were affected in a comparable fashion. Thus, changes in development and manifestation of diabetes and CVD
HbA1c levels did not differ between both groups, which is in [16,54]. Taken together, the results of the present review
contrast to data from other meta-analyses reporting a suggest that LGI/LGL dietary protocol represent a valuable
beneficial influence of LGI/LGL regimens on this predictor tool in overweight and obesity especially with regard to the
of CVD [12,13]. This discrepancy might be explained at prevention of obesity-associated diseases like T2D and CVD.
least in part by the fact that these systematic reviews However, decreases in FFM values turned out to more
included data from short-term RCTs enrolling both patients prominent following LGI/LGL protocols. Reductions in lean
with T2D and T1D. The present meta-analysis was focused body mass are a common problem observed in hypo-caloric
on the long-term effects of GI/GL on overweight and obese dietary interventions. The consecutive adaptations in basal
individuals. Therefore, studies incorporating patients with metabolic rate represent an important obstacle in weight
T1D had to be excluded leaving only a small number of 4 management. Therefore, the present findings might
studies assessing HbA1c. Following sensitivity analyses represent a serious side-effect of an LGI/LGL regimen. One
including non-diabetic subjects only, changes in CRP and FI should keep in mind that assessment of FFM was done in
remained statistically significant. Chronic, low-grade only three studies selected for this meta-analysis.
inflammation is regarded to play a major role in the path- Removing the study with the largest weight [28] yielded
ophysiology of obesity and its associated diseases such as non-significant results (data not shown). It is by no means
CVD with CRP representing an independent risk factor for intended to create a bias in this way. Rather, the authors of
the development of CVD [39,40]. The increase of CRP in the relevant study referred to technical limitations of
obesity can be explained by macrophage infiltration into measuring FFM via dual-energy X-ray absorptiometry. They
the expanded adipose tissue and subsequent increases in conclude that attenuation of FFM could be attributed to
the production and release of macrophage-derived pro-in- fluid loss in addition to changes in lean tissue. Nonetheless,
flammatory cytokines such as interleukin-6 (IL-6) and tumor decreases in FFM remain an issue which might be resolved
necrosis factor-a (TNF-a) [41,42]. The low-grade inflam- by a combination of dietary interventions and exercise, e.g.
matory process might be involved in insulin resistance and resistance training [55].
endothelial dysfunction thereby providing a model linking Funnel plots for this systematic review showed moderate
obesity and cardiovascular disease [43]. Low GI foods were asymmetry suggesting that publication bias cannot be
shown to reduce postprandial glycemia in overweight/ completely excluded as a confounder of the present meta-
obese [44] as well as T2D subjects [45]. These findings analysis (e.g. lack of published studies with inconclusive
might in itself provide an explanation for the link between results). A major limitation of nutritional intervention trials
glycemic index of foods and anti-oxidative capacity [46]. is the heterogeneity of various aspects and characteristics
Inconsistent relationships between GI and CRP have of the study protocols. In the present analysis, variations
been demonstrated in observational as well as interven- could be observed regarding type(s) of diets used, setups of
tional studies. Griffith et al. [47] reported no correlation LGI/LGL and HGI/HGL diets, study population (i.e. over-
between GI/GL and CRP in a prospective study in normal weight, obese, T2D, abnormal glucose metabolism). To in-
weight individuals, while in the subgroup with overweight crease the power of GI/GL intake for the present analyses,
and obesity, HGL was even associated with lower levels of data from food frequency questionnaires, 24 h dietary re-
circulating CRP. In a cross-sectional analysis of two joint calls or 3e7 day dietary protocols at the end of the study
observational studies performed in the Netherlands, Du were used when available. However, variations in GI/GL
et al. [48] found a positive association between GI/GL and still represent a potential confounder of the outcome
CRP described as “borderline significant” by the authors. measures. In addition, not all of the studies provided in-
Likewise, correlations between GI/GL and CRP were found formation on the quality of their respective setup (e.g.
to be small but of considerable clinical importance in the method of randomization, follow-up protocol with reasons
assessment of the Women’s health Initiative data [49,50]. for withdrawal) demanding a conservative interpretation of
With respect to TNF-a and IL-6, calculations of GI/GL from results.
dietary data of the PREDIMED study revealed a significant In conclusion, the present meta-analysis provides evi-
correlation between high GI/GL and plasma levels of dence for a beneficial effect of long-term diets adopting a
both cytokines at baseline. In a randomized cross-over low glycemic index protocol with respect to pro-
study by Vrolix and co-workers [51], pro-inflammatory inflammatory markers such as CRP and to fasting insulin.
markers such as CRP, TNF-a or IL-6 were not affected by Despite the limitations mentioned, LGI/LGL regimen might
GI. In contrast, Neuhouser et al. [52] found a significant represent a useful tool in primary prevention of obesity and
decrease in CRP in obese volunteers subjected to an LGI obesity-related complications. Therefore, this regimen
dietary protocol. Moreover, the combination of aerobic should not be categorically removed from the dietary of-
exercise with either an LGI or an HGI diet resulted in ferings for people looking for a preventive measure against
significant decreases in TNF-a and IL-6 in the LGI sub- these risks. However, further insights into this topic require
groups only [53]. additional long-term RCTs implementing clearly defined low
When regarding chronic, low-grade inflammation as a and high GI/GL quantities and focusing on biomarkers of
connecting link between obesity and insulin resistance, one obesity-induced inflammation, e.g. adipokines.
Glycemic index/load and risk of CVD 705
[29] Ebbeling CB, Leidig MM, Feldman HA, Lovesky MM, [42] Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM.
Ludwig DS. Effects of a low-glycemic load vs low-fat diet in Increased adipose tissue expression of tumor necrosis factor-
obese young adults: a randomized trial. JAMA: The Journal of alpha in human obesity and insulin resistance. The Journal
the American Medical Association 2007;297:2092e102. of Clinical Investigation 1995;95:2409e15.
[30] Ebbeling CB, Leidig MM, Sinclair KB, Seger-Shippee LG, [43] Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive
Feldman HA, Ludwig DS. Effects of an ad libitum low- protein in healthy subjects: associations with obesity, insulin
glycemic load diet on cardiovascular disease risk factors in resistance, and endothelial dysfunction: a potential role for
obese young adults. The American Journal of Clinical Nutri- cytokines originating from adipose tissue? Arteriosclerosis,
tion 2005;81:976e82. Thrombosis, and Vascular Biology 1999;19:972e8.
[31] Philippou E, Bovill-Taylor C, Rajkumar C, Vampa ML, [44] Botero D, Ebbeling CB, Blumberg JB, Ribaya-Mercado JD,
Ntatsaki E, Brynes AE, et al. Preliminary report: the effect of Creager MA, Swain JF, et al. Acute effects of dietary glyce-
a 6-month dietary glycemic index manipulation in addition to mic index on antioxidant capacity in a nutrient-controlled
healthy eating advice and weight loss on arterial compliance feeding study. Obesity (Silver Spring) 2009;17:1664e70.
and 24-hour ambulatory blood pressure in men: a pilot study. [45] Wolever TM, Gibbs AL, Chiasson JL, Connelly PW, Josse RG,
Metabolism: Clinical and Experimental 2009;58:1703e8. Leiter LA, et al. Altering source or amount of dietary car-
[32] Ma Y, Olendzki BC, Merriam PA, Chiriboga DE, Culver AL, bohydrate has acute and chronic effects on postprandial
Li W, et al. A randomized clinical trial comparing low- glucose and triglycerides in type 2 diabetes: Canadian trial of
glycemic index versus ADA dietary education among in- Carbohydrates in Diabetes (CCD). Nutrition, Metabolism, and
dividuals with type 2 diabetes. Nutrition 2008;24:45e56. Cardiovascular Diseases: NMCD 2013;23:227e34.
[33] Sichieri R, Moura AS, Genelhu V, Hu F, Willett WC. An 18-mo [46] Ceriello A. Postprandial hyperglycemia and diabetes com-
randomized trial of a low-glycemic-index diet and weight plications: is it time to treat? Diabetes 2005;54:1e7.
change in Brazilian women. The American Journal of Clinical [47] Griffith JA, Ma Y, Chasan-Taber L, Olendzki BC, Chiriboga DE,
Nutrition 2007;86:707e13. Stanek 3rd EJ, et al. Association between dietary glycemic
[34] Gogebakan O, Kohl A, Osterhoff MA, van Baak MA, Jebb SA, index, glycemic load, and high-sensitivity C-reactive protein.
Papadaki A, et al. Effects of weight loss and long-term Nutrition 2008;24:401e6.
weight maintenance with diets varying in protein and gly- [48] Du H, van der AD, van Bakel MM, van der Kallen CJ, Blaak EE,
cemic index on cardiovascular risk factors: the diet, obesity, van Greevenbroek MM, et al. Glycemic index and glycemic
and genes (DiOGenes) study: a randomized, controlled trial. load in relation to food and nutrient intake and metabolic
Circulation 2011;124:2829e38. risk factors in a Dutch population. The American Journal of
[35] Armendariz-Anguiano AL, Jimenez-Cruz A, Bacardi- Clinical Nutrition 2008;87:655e61.
Gascon M, Hurtado-Ayala L. Effect of a low glycemic load on [49] Levitan EB, Cook NR, Stampfer MJ, Ridker PM, Rexrode KM,
body composition and Homeostasis Model Assessment Buring JE, et al. Dietary glycemic index, dietary glycemic
(HOMA) in overweight and obese subjects. Nutricion hospi- load, blood lipids, and C-reactive protein. Metabolism:
talaria: organo oficial de la Sociedad Espanola de Nutricion Clinical and Experimental 2008;57:437e43.
Parenteral y Enteral 2011;26:170e5. [50] Bullo M, Casas R, Portillo MP, Basora J, Estruch R,
[36] Das SK, Gilhooly CH, Golden JK, Pittas AG, Fuss PJ, Garcia-Arellano A, et al. Dietary glycemic index/load and
Cheatham RA, et al. Long-term effects of 2 energy-restricted peripheral adipokines and inflammatory markers in elderly
diets differing in glycemic load on dietary adherence, body subjects at high cardiovascular risk. Nutrition, Metabolism,
composition, and metabolism in CALERIE: a 1-y randomized and Cardiovascular Diseases: NMCD 2013:443e50.
controlled trial. The American Journal of Clinical Nutrition [51] Vrolix R, Mensink RP. Effects of glycemic load on metabolic
2007;85:1023e30. risk markers in subjects at increased risk of developing
[37] Venn BJ, Perry T, Green TJ, Skeaff CM, Aitken W, Moore NJ, metabolic syndrome. The American Journal of Clinical
et al. The effect of increasing consumption of pulses and Nutrition 2010;92:366e74.
wholegrains in obese people: a randomized controlled trial. [52] Neuhouser ML, Schwarz Y, Wang C, Breymeyer K,
Journal of the American College of Nutrition 2010;29:365e72. Coronado G, Wang CY, et al. A low-glycemic load diet re-
[38] Raatz SK, Torkelson CJ, Redmon JB, Reck KP, Kwong CA, duces serum C-reactive protein and modestly increases adi-
Swanson JE, et al. Reduced glycemic index and glycemic load ponectin in overweight and obese adults. The Journal of
diets do not increase the effects of energy restriction on Nutrition 2012;142:369e74.
weight loss and insulin sensitivity in obese men and women. [53] Kelly KR, Haus JM, Solomon TP, Patrick-Melin AJ, Cook M,
The Journal of Nutrition 2005;135:2387e91. Rocco M, et al. A low-glycemic index diet and exercise
[39] Devaraj S, Singh U, Jialal I. Human C-reactive protein and the intervention reduces TNF(alpha) in isolated mononuclear
metabolic syndrome. Current Opinion in Lipidology 2009;20: cells of older, obese adults. The Journal of Nutrition 2011;
182e9. 141:1089e94.
[40] Ridker PM, Morrow DA. C-reactive protein, inflammation, and [54] Ma XY, Liu JP, Song ZY. Glycemic load, glycemic index and
coronary risk. Cardiology Clinics 2003;21:315e25. risk of cardiovascular diseases: meta-analyses of prospective
[41] Lee DE, Kehlenbrink S, Lee H, Hawkins M, Yudkin JS. Getting studies. Atherosclerosis 2012;223:491e6.
the message across: mechanisms of physiological cross talk [55] Stiegler P, Cunliffe A. The role of diet and exercise for the
by adipose tissue. American Journal of Physiology Endocri- maintenance of fat-free mass and resting metabolic rate
nology and Metabolism 2009;296:E1210e29. during weight loss. Sports Med 2006;36:239e62.