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 from cardiovascular disease. Medical nutrition therapy is recommended for the treatment of diabetes; however, these recommendations have not been updated to target the inflammatory component, which can be affected by diet and lifestyle. To assess the current state of 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 Science databases from January 2000 to May 2012 yielded 786 articles. The final 16 studies met the selection criteria including randomized control 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. The Mediterranean diet demonstrated the most clinically significant reduction in glycosylated hemoglobin (HbA1c). Information on best dietary guidelines for inflammation and glycemic control in individuals with T2D is lacking. Continued research is warranted.
Thirty-five percent of Americans who are aged 20 years and older have type 2 diabetes (T2D) [
One underlying pathophysiological process resulting from poor lifestyle habits is inflammation. Inflammation is present prior to the development of T2D and cardiovascular disease (CVD), contributing to evidence to support the “common soil” hypothesis, which is a reference to the common risk factors for the development of these two diseases [
Although the published literature is populated with articles and systematic reviews demonstrating the relationship between dietary patterns, individual dietary factors, and incidence of diabetes [
This review targeted adults (≥18 years) diagnosed with T2D. All studies that included a dietary intervention, either exclusively 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 following databases were searched: PubMed, CINAHL, Scopus, and Web of Science. Keywords used in the search were combinations of the “diet,” “chronic inflammation,” “type 2 diabetes,” “C-reactive protein,” “interleukins,” and “tumor necrosis factor” (TNF). A health sciences librarian was consulted on the selection of these search terms. The search was conducted on articles published between January 2000 (the year of the first appearance of diet, inflammation, and T2D in the literature) and May 2012. Studies were limited to only those written in the English language. Studies that focused on prevention of T2D were excluded, as they did not offer data to assist in the exploration of how diet relates to the inflammatory process within the pathogenesis of T2D. Other exclusion criteria were studies that focused on supplements alone or exercise without an evaluation of, or comparison to, diet.
The search produced 371 studies in PubMed, 265 studies in Web of Science, and 150 studies in CINAHL (see Figure
PRISMA flowchart.
Each study was read twice to ensure identification of salient topics for analysis. Three tables were created to aid synthesis of the data. Table
Study methods, details, and outcomes.
Author/year/ |
Study design and methods | Variables | Instruments | Intervention details | Important methodological flaws/bias noted | Data analysis | Outcomes related to inflammation, glycemic control, and diet |
---|---|---|---|---|---|---|---|
Brinkworth et al. (2004), Australia [ |
2-group pretest/posttest design with randomization, longitudinal follow-up. |
Inflammatory markers: hs-CRP, IL-6, urinary 15-keto-dihyro-PGF. |
Dual X-ray absorptiometry. |
(1) 8 weeks of 30% energy restriction, |
No control for confounding variables (i.e. differences in weight loss, changes in medications over the study period). |
Repeated measures ANOVA. |
There was a decrease in CRP for both groups of 14% ( |
| |||||||
Giannopoulou et al. (2005), U.S. [ |
3-group pretest-posttest design with randomization. |
Inflammatory markers: |
24 hour recalls. |
(1) Diet only: high MUFA |
Exercise intervention was “supervised” but not specified how. |
Descriptive data: 2-way ANOVA with post hoc analysis where appropriate. |
For all groups: |
| |||||||
Marfella et al. (2006), Italy [ |
RCT. |
Inflammatory markers: TNF- |
24-hr dietary recall: at first visit. |
Both groups advised 2000 kcal/day diet similar to Mediterranean diet. |
Only 115 patients completed the study (8 died). |
One-way ANOVA for baseline, then Scheffe’s test to compare pairs of data. |
Significant higher levels of TNF |
| |||||||
Wolever et al. (2008), Canada [ |
3-group pre-test/post-test design with randomization. |
Inflammatory markers: CRP. |
3-day food diary records collected 7 times during the 12 month period. |
12 months in length. All subjects advised “heart healthy” diet. High-GI diet: avoid low-GI foods, eat low-fat foods. |
No control group. |
General linear mixed model. Stats CRP used log-transformed data presented as means and CI’s. |
CRP in low-GI diet 29% lower than high-GI diet. |
| |||||||
Barnard et al. (2009), United States [ |
2 group pretest-posttest design. |
Inflammatory markers: |
24 hour recalls |
Initial 1-hr meeting with dietician for each group. Then, 22 weekly group sessions specific to group. Optional sessions every two weeks for the remaining 52 weeks. |
Not all analyses were performed only using those participants with good adherence. Good adherence not defined. |
Repeated measures ANOVA for HbA1c (as ITT) using time, diet group, and interaction between time × diet with HbA1c as DV. |
After adjustment for medication changes, LDL and non-HDL cholesterol values decreased, and more so in the vegan group. |
| |||||||
Dostlova et al. (2009), Czech Republic [ |
Quasi experimental one group with two comparison groups (monitored in the hospital). |
Inflammatory markers: CRP. |
No measure of adherence to diet. | 2-week very-low-calorie diet. |
Highly controlled environment for study. No adverse events reported. |
One-way ANOVA followed by post hoc tests. |
For women with T2DM ( |
| |||||||
Kozłowska et al. (2010), Poland [ |
Quasiexperimental one group pretest/posttest design. |
Inflammatory markers: TNF- |
DEXA scan for body composition. |
Intervention diet: 20% energy deficit 0.8–1 g/kg ideal body weight, 30% cal from fat, 60% cal from CHO. |
No mention of how dietary intake was measured, just reported in a chart (Table |
Pearson or Spearman’s tests for correlations. |
No correlations between food intake and inflammatory markers made. |
| |||||||
Vetter et al. (2010), U.S. [ |
Ancillary group in an RCT. |
Inflammatory markers: |
24-hour recalls. |
Randomly assigned to groups. |
24-hour recall assessed, but not used to assess adherence to the prescribed diet. |
Log-transformed data: leptin, adiponectin, and TNF |
Inflammatory markers: |
| |||||||
Azadbakht et al. (2011), study conducted in Iran [ |
Crossover intervention design with randomization. |
Inflammatory markers: CRP. |
3d dietary recall to assess adherence to the prescribed diet. |
8-week crossover study with randomization to control or DASH diet. Control diet had fewer PUFA. |
Unclear how study was conducted, not easy to follow methods. R/o carryover effects. |
Assessing effect of intervention: paired |
Patients who received the DASH diet showed a reduction in CRP, plasma fibrinogen, and liver transferase enzymes. |
| |||||||
Bozzetto et al. (2011), Italy [ |
Preexperimental posttest only Cross-over with randomization |
Inflammatory markers: CRP. |
Nothing provided in paper. |
Diets were isoenergetic: both had kcal of 948 per day. Randomized, crossover design. |
No details given concerning dietary advisement. Dietary adherence not measured. |
Paired |
Diet and inflammation: after intervention, fasting CRP values were not significantly different between study diets, although CRP did decrease significantly after the MUFA meal ( |
| |||||||
Davis et al. (2011), [ |
2-group pre-test/post-test clinical trial subgroup of larger trial. |
Inflammatory markers: CRP, IL-6. |
EndoPat to measure peripheral microvascular endothelial function. | Total 24 weeks: subjects randomized to receive either a low-carbohydrate, Atkins-style diet or a low-fat diet (similar to DPP diet). Participants received structured menus for the 1st two weeks. Medications were adjusted based on a predefined algorithm. |
No control group. |
CRP and IL-6 were log-transformed. |
Low-fat diet: CRP decreased from 4.0 to 3.0 ( |
| |||||||
Itsiopoulos et al. (2010), Australia [ |
Randomized cross-over (2 groups pretest, posttest). |
Inflammatory markers: CRP, homocysteine. |
Health and lifestyle questionnaire (not defined). |
Intervention was a Mediterranean diet for 12 weeks, then crossover (24 weeks total). |
No washout period between diet periods. Measurement tools not standardized. |
Data from the two diets were pooled. |
Significant reduction in HbA1c in the intervention diet. |
| |||||||
Khoo et al. (2011), Australia [ |
2 group pretest-posttest design with randomization. |
Inflammatory markers: CRP, IL-6, and soluble E-selectin. |
Food diaries to monitor compliance. |
Diet compliance monitored every 2–4 weeks. |
Adherence not reported or used in analysis, although diet diaries were used. |
Maximum likelihood repeated measures mixed models to compare pre/post measures. |
Inflammation: significant decrease in CRP (at 8 and 52 wk), E-Selectin (at 8 and 52 wk), and IL-6 (at 8 wk only) in HP diet group ( |
| |||||||
Mraz et al. (2011), |
Quasiexperimental design with two comparison groups. |
Inflammatory markers: CRP, IL-6, TNF, IL-8, CCL-2. |
Nothing provided in paper. | Only obese women with DM were given the IV diet; a 2-week 600 kcal/day diet. All patients were hospitalized. | No adverse events or medication changes reported from the intervention period. |
Paired |
TNF- |
| |||||||
Åsgård et al. (2007), Sweden [ |
Cross-sectional design. |
Inflammatory markers: hs-CRP, IL-6, urinary 15-keto-dihyro-PGF. |
3-day diet recall with precoded instrument that was altered for this study (originally it was for 7 days). |
NA | No limitations section in paper. |
Spearman correlation coefficients with |
IL-6 lower with higher levels of carotenoids ( |
| |||||||
Qi et al. (2006), U.S. [ |
Nested cohort in longitudinal analytic study of the Nurses’ Health Study. |
Inflammatory markers: CRP, TNF-R2, |
Semiquantitative food frequency questionnaire. |
No intervention. | “Whole grains were previously described” but the paper referred to was written by different authors and was in a study about men. No limitations section. |
Associations evaluated with linear regression. |
Women with higher intakes of whole grains, bran, and cereal fiber had lower levels of CRP and TNF after adjusting for age, BMI, lifestyle, and dietary covariates. |
Quality Assessment tool and scores.
Article | Aims | Methods | Diet of interest | Recruitment | Inflammation | Confounding variables | Missing | Conclusions | Quality rating | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|
(1 pt) | (1 pt each) | well-defined? (1 pt each) | (1 pt) | (1 pt) | (1 pt) | data/attrition (1 pt) | (2 pts) | (out of 12 pts) | ||||
1st Author | Clearly described | Read | Repr | Ad | TO | Diet | Discussed | Measures appropriate | Controlled | Properly handled | Appropriate | Total |
| ||||||||||||
Åsgård | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 7 |
Itsiopoulos | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 7 |
Davis | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 2 | 9 |
Qi | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 2 | 8 |
Dostlova | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 5 |
Azadbakht | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 2 | 10 |
Bozzetto | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 2 | 6 |
Giannopoulou | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 2 | 8 |
Barnard | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 8 |
Wolever | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 9 |
Vetter | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 4 |
Kosłowska | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 4 |
Marfella | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 5 |
Khoo | 1 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 7 |
Mraz | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 4 |
Brinkworth | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 10 |
Note. Ad: adherence; Diet: dietary intervention defined; Read: readability; Repr: reproducibility; TO: appropriate use of temporal ordering.
Experimental studies: characteristics and results of data abstraction.
Author/year/ |
Design |
Study length |
Subjects | Dietary intervention | Outcomes |
Quality | |||
---|---|---|---|---|---|---|---|---|---|
Diet details | Control for weight loss differences? | ΔCRP | ΔHbA1c% | Other | |||||
Brinkworth et al. (2004), Australia [ |
2 group pretest/posttest comparison design with randomization | 64 |
|
Low-protein (15%) |
Yes |
|
|
NA | 10 |
| |||||||||
Giannopoulou et al. (2005), U.S. [ |
3-group, pretest-posttest with randomization | 14 |
|
Diet only |
No |
|
NS Δ | NS Δ in TNF- |
8 |
| |||||||||
Marfella et al. (2006), Italy [ |
RCT | 52 |
|
Wine: 4 oz. per day + Mediterranean diet |
No |
|
|
TNF- |
5 |
| |||||||||
Wolever et al. (2008), Canada [ |
3 groups, pretest-posttest with randomization | 52 |
|
High GI |
Yes |
Low GI-diet: |
NS difference between groups, HbA1c rose during intervention |
NA | 9 |
| |||||||||
Barnard et al. (2009), U.S. [ |
2 groups, pretest-posttest | 74 |
|
Vegan diet |
Yes |
|
|
|
8 |
| |||||||||
Dostlova et al. (2009), Czech Republic [ |
Quasi-experimental one group with two comparison groups (monitored in the hospital) | 2 | T2DM group |
Very-low-calorie diet (550 kcal/day) | No |
|
Fasting glucose |
HOMA: |
5 |
| |||||||||
Kozłowska et al. (2010), Poland [ |
Quasi-experimental (one-group pretest-posttest) | 8 |
|
Low energy/Low protein diet (20% energy deficit, 0.8–1.0 g/kg) |
No |
|
|
|
4 |
| |||||||||
Vetter et al. (2010), U.S. [ |
RCT subgroup | 26 |
|
Low-carb |
No | Not measured |
|
TNF- |
4 |
| |||||||||
Azadbakht et al. (2011), study conducted in Iran. [ |
Cross-over with randomization (with 4 week washout period) | 8 |
|
DASH diet |
Yes |
|
No measure of glycemic control | Fibrinogen: |
10 |
| |||||||||
Bozzetto et al. (2011), |
Preexperimental posttest only. Cross-over with randomization |
4 |
|
High-carb/high-fiber/low GI |
No | MUFA meal: |
No measure of glycemic control | NA | 6 |
| |||||||||
Davis et al. (2011), |
2 groups pretest-posttest with randomization subgroup of larger trial |
24 |
|
Low-fat (DPP diet) |
Yes, weight loss equal between groups | Low-fat: |
|
IL-6 ns |
9 |
| |||||||||
Itsiopoulos et al. (2010), Australia [ |
Cross-over with randomization |
24 |
|
Mediterranean Diet: |
No |
|
|
HOMA, |
7 |
| |||||||||
Khoo et al. (2011), Australia [ |
2 groups pretest-posttest with randomization |
52 |
|
Low-calorie diet |
No | Low-calorie: NS |
Not provided, change in plasma glucose was ns. | IL-6 |
7 |
| |||||||||
Mraz et al. (2011), Czech Republic [ |
Quasi-experimental design with two comparison groups |
2 |
|
Very-low-calorie diet |
No |
|
Not provided |
|
4 |
Note: CRP: C-reactive protein; HbA1c: glycosylated hemoglobin; F: females; M: males;
Cross-sectional studies: characteristics and results of data abstraction.
Author/yr/country | Design | Dietary assessment | Subjects | Dietary component of interest | Measurements | Quality rating | ||
---|---|---|---|---|---|---|---|---|
CRP | IL-6 | TNF | ||||||
Åsgård et al., (2007), Sweden [ |
Crosssectional | 3-day dietary survey; precoded |
|
Fruit and vegetable intake |
|
|
NA | 7 |
| ||||||||
Qi et al. (2006), |
Crosssection of a cohort in prospective longitudinal study | Semiquant FFQ |
|
Whole grains, germ, and bran |
|
NA |
|
8 |
Note: CRP: C-reactive protein; IL-6: interleukin-6; TNF: tumor necrosis factor-alpha; F: females; M: males;
Articles retrieved for review were assessed for quality of study conduct and reporting [
Studies were grouped by design method to differentiate results sections for accurate synthesis [
Several experimental studies demonstrated a reduction of systemic inflammation following an intervention of a prescribed diet in patients with T2D. Four of the studies with higher quality scores (≥9) demonstrated a significant association between diet and inflammation. Three of these four contained a low-fat (≤30% of energy from fat) dietary component [
Several other studies also demonstrated reductions in CRP with dietary interventions, albeit with lower quality scores, and with ranges between 4 and 8. Khoo et al. [
Following on the premise that increased fat mass in T2D contributes to inflammation, three other studies implemented diets that were low or very low in energy content [
Marfella et al. [
In contrast, there were several diets that did not alter inflammatory marker expression significantly. These included the high-carbohydrate/high-fiber/low-glycemic index diet [
The two cross-sectional studies included in this analysis examined associations between two different aspects of diet and differed significantly in terms of quality in reporting. Åsgård et al. [
The positive influence of a dietary intervention on glycemic control [
The great variability between studies decreases the ability to draw definitive conclusions about associations between diet, inflammation, and T2D; however, particular themes emerged that are worth noting both from this review and in light of previous research. First, of the ten different diets prescribed that were low in fat, both within and across studies, eight of those diets led to significant reductions in inflammatory markers. These included the DASH diet [
Previous reports from the Whitehall and PREDIMED studies indicated that diets high in MUFA and polyunsaturated fatty acids (PUFAs) were correlated with decreased CRP [
Dietary patterns, as opposed to specific aspects of diet, have also been shown to correlate with levels of chronic inflammatory markers, but this concept was not adequately examined in the selected studies. For example, the western dietary pattern, characterized by a high consumption of sugary drinks, red meat, and poultry and a low consumption of fruits, vegetables, and fiber, was correlated with higher levels of CRP in two large cross-sectional studies conducted in the US [
The impact of diet on the metabolic milieu of T2D is evident from the results of this integrative review and others. However, statistical significance does not necessarily translate into clinical significance or meaningfulness. For example, of the two studies that were able to demonstrate a significantly reduced HbA1c following the prescribed diet, one failed to report baseline values of glycemic control, [
To further increase their clinical relevance, it is important for studies implementing dietary changes to examine sustainability of the prescribed diet. Although both studies of VLCD reported significant decreases in inflammatory markers, such a diet is not sustainable and is likely harmful for the individuals as evidenced by the significant increase in TNF-
Due to the limited availability of data for analysis on this topic and the suboptimal quality of reporting within the studies, the results of this integrative review are inconclusive. Many of the studies reviewed suffered from significant methodological shortcomings. First, most of the studies had small sample sizes, with a range between 12 and 162 (mean sample size of 53, and median of 32), limiting the power of the intervention to detect an effect. The two studies with the largest sample sizes implemented the low-glycemic-index diet and Mediterranean diet with wine and showed significant reduction in inflammatory marker expression [
Second, several studies did not include transparent definitions of the dietary intervention, rendering it difficult to infer specific dietary factors that decrease inflammation from the results. In previous studies with healthy volunteers, decreased inflammation was correlated with several individual dietary factors including fiber, antioxidant vitamins such as vitamin C and carotenoids, and fruit and vegetable intake. For example, in large prospective studies, whole grain intake has been associated with both decreased inflammatory markers [
A third and final gap in knowledge related to this topic is adherence and change over time. Though several studies included in this study were longitudinal, the longest study was 74 weeks, which does not necessarily indicate that benefits obtained will be sustained in the long-term. This issue was highlighted in the study by Brinkworth et al. [
There are several limitations of this integrative review. First, the review is limited to the published literature, so it is subject to publication bias. Several authors were contacted via email with requests for unpublished research, but none were available. Second, the articles reviewed for analysis only included a population with diagnosed T2D. This limited the available literature on the influence of diet on inflammation and glycemic control markedly. There is merit in restriction of the search to this population, given that their inflammatory markers will be elevated relative to the general population and would, therefore, benefit from dietary 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 does not address the mechanism of action underlying reduction of systemic inflammation following a dietary intervention. Discussion of such is beyond the scope of this paper. The review by Visioli et al. [
Given the limitations of the findings and the inconclusive results reached by this review, it is clear that more rigorous research is needed. The present level of evidence on this topic is Level III, given that most of the studies were quasiexperimental. This paper, therefore, increases the level of evidence by providing an integrative review of the available research. However, disparate methods of reporting findings have rendered synthesis of extant findings difficult and unnecessarily labor-intensive. Studies should adhere to the transparent reporting standards outlined by the Consolidated Standards of Reporting Trials [
Medical nutrition therapy is one aspect of prevention and care of T2D recommended by the ADA. Although the DPP demonstrated a reduction in the incidence of T2D following the adaptation of lifestyle changes, there have been few studies examining the influence of dietary interventions on inflammation and glycemic control in individuals with established T2D in the US. It is important to conduct these studies domestically because of the diversity of the populations affected by this disease and the increasing rates of T2D. For example, further analysis of the results from the DPP revealed an attenuated benefit from the intervention in non-Hispanic Black women, highlighting the need for an understanding of the complex sociocultural factors influencing the African American population [
None of the studies included in this review used a theoretical framework to guide the research, which could have contributed to the disparate findings of the included studies. Theoretical frameworks guide research questions and facilitate the process of asking a complete question. Considering that T2D is both a metabolic and inflammatory disease, it is imperative to design studies that address both of these issues in the methods and the outcome measures. For example, if an intervention of a high MUFA diet is implemented, it may be helpful not only to address inflammatory markers in the outcome measures, but also other influences on inflammation that could confound results such as physical activity, socioeconomic status, environmental stressors, and genetic factors as suggested by Kang’s Biobehavioral Model of Stress and Inflammation [