The Role of Prebiotics in Diabetes Mellitus
June 1, 2015
By William C. Haas, III, MD, MBA
Carolinas Medical Center, Department of Family Medicine, Charlotte, NC
Dr. Haas reports no financial relationships relevant to this field of study.
SYNOPSIS: Inulin supplementation may reduce levels of systemic inflammation and improve glycemic control in female patients with type 2 diabetes mellitus.
SOURCE: Dehghan P, et al. Inulin controls inflammation and metabolic endotoxemia in women with type 2 diabetes mellitus: A randomized-controlled clinical trial. Int J Food Sci Nutr 2014;65:117-123.
Summary Points
- Systemic inflammation plays an important role in chronic disease states such as diabetes.
- High-performance inulin supplementation may decrease systemic inflammation and improve glycemic control.
The pathophysiology of type 2 diabetes mellitus extends beyond the chronic elevation of plasma glucose levels. Ongoing, subclinical inflammation contributes to β-cell dysfunction and insulin resistance, which is driven by cytokines such as tumor necrosis factor alpha (TNF-α), interlukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP).1 Growing evidence suggests that the gut microbiota plays an important role in the development of systemic inflammation and metabolic disorders such as obesity and diabetes mellitus.2 An unhealthy balance of bacteria in the gastrointestinal tract favors the production of lipopolysacaride (LPS) and results in a state of metabolic endotoxemia.
Prebiotics, non-digestible fiber compounds and other oligosaccharides, can potentially modulate the activity of advantageous bacteria in the large bowel, thereby decreasing inflammation and metabolic endotoxemia. High-performance inulin (HP inulin), a prebiotic with a mix of long-chain inulin-type fructans, has been associated with positive shifts in the gut microbiota.3 Given the limited number of human studies on the topic, a group of researchers designed a randomized, double-blind, placebo-controlled trial to assess the effect of HP inulin supplementation on inflammatory biomarkers and metabolic endotoxemia in women with type 2 diabetes. The primary outcomes measured were change in hs-CRP, TNF-α, IL-10, and LPS, while secondary outcomes included change in weight, fasting blood sugar, hemoglobin A1c, fasting insulin, and insulin resistance.
Sixty-five female patients with type 2 diabetes mellitus were recruited from a single endocrinology clinic associated with an academic medical center. Inclusion criteria included a diagnosis of diabetes for more than 6 months, current use of antidiabetic medication (metformin and glibenclamide), body mass index (BMI) > 25 kg/m2, and a normal dietary pattern. A “normal dietary pattern” was not clearly defined, but dietary intake was evaluated by a nutritionist, pre- and post-intervention. Exclusion criteria were more extensive and included a history of gastrointestinal, cardiovascular, renal, thyroid, liver, or pancreatic disease, as well as women who were pregnant or lactating. Additionally, patients were excluded if they consumed any one of the following within a 2-week period prior to the study: prebiotic/probiotic supplements, antibiotics, antacids, alcohol, anti-diarrheal, anti-inflammatory, lipid-lowering, or laxative medications. After exclusion criteria were applied, 54 patients were left for randomization.
Using a block randomization procedure based on BMI and age, patients were randomly divided into two groups. The intervention group received 10 g/day of HP insulin and the control group received 10 g/day of maltodextrin. The principle investigator, statistician, and patients were all blinded to allocation. In addition to their allocated supplement, patients also received two anti-diabetic drugs, metformin and glibenclamide. Blood samples were collected and analyzed for inflammatory (hs-CRP, TNF-α, IL-10, and LPS) as well as glycemic markers (fasting blood sugar, hemoglobin A1c, fasting insulin, and insulin resistance) at baseline and again after 8 weeks of supplementation.
Among the 54 patients randomized, 49 completed the trial with 24 in the intervention group and 25 in the control group. Data analysis was performed on patients completing the intervention with no mention of an intent-to-treat analysis. No significant differences were noted between the groups with regard to baseline characteristics, including age, weight, height, BMI, and duration of diabetes. The control group was noted to have a higher consumption of fiber intake at baseline compared to the intervention group, but no differences were otherwise noted for total caloric intake, carbohydrates, protein, or fat consumed. The glycemic indices were similar between the groups at baseline; however, the inflammatory biomarkers hs-CRP and LPS were significantly lower in the HP inulin group compared to the intervention group at baseline (8.0 vs 13.0 ng/mL and 21.4 vs 25.5 EU/mL, respectively; P < 0.05).
After the intervention, total energy and fat intake decreased significantly in the intervention group while remaining unchanged in the control group. The change in dietary intake was correlated with a 2.6 kg weight reduction in the HP inulin group (P < 0.05), but no change in the control group. With regard to primary outcomes, the inulin group experienced significant decreases in levels of hs-CPR (-35.6%), TNF-α (-23.0%), and LPS (-27.9%). On the other hand, inflammatory biomarkers did not change significantly in the control group. With regard to secondary outcomes of glycemic status, all indices improved significantly in the intervention group compared to baseline, including a 15.1 mg/dL reduction in fasting blood sugar, a 0.7 mmol/mol reduction in HbA1c, and a 39.5% reduction in insulin resistance (P < 0.05). No significant changes were noted in glycemic status among patients in the control group.
COMMENTARY
Low levels of chronic, systemic inflammation are now known to be an important factor underlying many chronic disease states, including type 2 diabetes. Emerging research continues to highlight the possible link between the gut microbiota and inflammation. The research by Dehghan and colleagues addressed one way of positively influencing the gut microbiota in an effort to reduce systemic inflammation. Their results, in fact, suggest that supplementation with the prebiotic HP inulin decreases inflammatory markers along with many common indices of glycemic control. Interestingly, HP supplementation also resulted in decreased total energy intake as well as a reduction in weight and BMI, findings that have been mixed in other studies.4 Although the exact mechanism for appetite suppression and weight reduction are unclear, the fermentation of inulin is hypothesized to increase gut satiety hormones, including GLP-1, PPY, and ghrelin, which may also account for the improvements in glycemic control. The effect of inulin supplementation on systemic inflammation and metabolic endotoxemia has not been as well-studied in diabetic patients. One of the major proposed mechanisms for improvement involves changes in the gut microbiota toward strains of bacteria that are more anti-inflammatory and produce less lipopolysacaride.
Despite advancing our understanding of inulin’s effect on inflammation and metabolic endotoxemia, the research methodology should be reviewed before reaching a conclusion. An important premise of the study, mainly the ability of inulin to alter the gut microbiota toward an anti-inflammatory state, was not directly tested. Adequate attention was given to markers of inflammation and glycemic control; however, direct evaluation of gut and fecal microbial composition did not occur, leaving unanswered questions regarding inulin’s mechanism of action. Aside from not capturing data pertaining to the gut microbiota, the broad exclusion criteria, particularly excluding those with various comorbid conditions, may have artificially selected a population with less underlying systemic inflammation. In theory, the results may have yielded more significant reductions, but the effect on inulin supplementation on the many diabetics with end-organ damage is unknown. Finally, although the baseline difference in weight was not statistically different between the groups, the inulin group was approximately 5 kg heavier than the placebo group prior to the intervention. A heavier starting weight in the inulin group may have resulted in a more pronounced change in inflammation and glycemic control, as individuals with higher body weight are believed to have a greater disturbance in their gut microbiota as well as a greater insulin resistance.
Ultimately, the researchers developed a rather well-designed and rigorous study evaluating the effect of high-performance inulin on inflammation and glycemic control. Although other studies have found mixed results regarding glycemic status with inulin, the present study is one of the first to evaluate the effect of inulin on systemic inflammation in type 2 diabetics. Based on their findings, inulin could be considered as a sound adjunctive treatment option for diabetics of moderate duration managed on oral therapy alone without other significant comorbid conditions. As a supplement, inulin can be easily sourced online and costs around $10-15 per month for the daily amount supplemented in the study. Naturally, inulin can be found in many plants, including garlic, onions, yams, and chicory, although the quantity required to consume would be limiting in some foods. Despite the altered composition of high-performance inulin to contain long-chained, high-molecular weight carbohydrates, a word of caution should be advised for patients suffering from irritable bowel syndrome, as fermentable short-chain carbohydrates may be a gastrointestinal irritant in some of these patients.
References
- Goldberg RB. Cytokine and cytokine-like inflammation markers, endothelial dysfunction and imbalanced coagulation in development of diabetes and its complications. J Clin Endocinol Metab 2009;94:3171-3182.
- Cani PD, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes 2008;57:1470-1481.
- Kolida S, Gibson GR. Prebiotic capacity of inulin-type fructans. J Nutr 2007;137(11 Suppl):2503s-2506s.
- Dewulf EM, et al. Insight into the prebiotic concept: Lessons from an exploratory, double blind intervention study with inulin-type fructans in obsess women. Gut 2013;62:1112-1121.
Inulin supplementation may reduce levels of systemic inflammation and improve glycemic control in female patients with type 2 diabetes mellitus.
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