Effect of dietary prebiotic supplementation on advanced glycation, insulin resistance and inflammatory biomarkers in adults with pre-diabetes: a study protocol for a double-blind placebo-controlled randomised crossover clinical trial

Abstract

BackgroundAdvanced glycation endproducts (AGEs) contribute to the development of vascular complications of diabetes and have been recently implicated in the pathogenesis of diabetes. Since AGEs are generated within foodstuffs upon food processing, it is increasingly recognised that the modern diet is replete with AGEs. AGEs are thought to stimulate chronic low-grade inflammation and promote oxidative stress and have been linked to the development of insulin resistance. Simple therapeutic strategies targeted at attenuating the progression of chronic low-grade inflammation and insulin resistance are urgently required to prevent or slow the development of type 2 diabetes in susceptible individuals. Dietary modulation of the human colonic microbiota has been shown to confer a number of health benefits to the host, but its effect on advanced glycation is unknown. The aim of this article is to describe the methodology of a double-blind placebo-controlled randomised crossover trial designed to determine the effect of 12 week consumption of a prebiotic dietary supplement on the advanced glycation pathway, insulin sensitivity and chronic low-grade inflammation in adults with pre-diabetes.Methods/DesignThirty adults with pre-diabetes (Impaired Glucose Tolerance or Impaired Fasting Glucose) aged between 40–60 years will be randomly assigned to receive either 10 grams of prebiotic (inulin/oligofructose) daily or 10 grams placebo (maltodextrin) daily for 12 weeks. After a 2-week washout period, study subjects will crossover to receive the alternative dietary treatment for 12 weeks. The primary outcome is the difference in markers of the advanced glycation pathway carboxymethyllysine (CML) and methylglyoxal (MG) between experimental and control treatments. Secondary outcomes include HbA1c, insulin sensitivity, lipid levels, blood pressure, serum glutathione, adiponectin, IL-6, E-selectin, myeloperoxidase, C-reactive protein, Toll-like Receptor 4 (TLR4), soluble receptor for AGE (sRAGE), urinary 8-isoprostanes, faecal bacterial composition and short chain fatty acid profile. Anthropometric measures including BMI and waist circumference will be collected in addition to comprehensive dietary and lifestyle data.DiscussionPrebiotics which selectively stimulate the growth of beneficial bacteria in the human colon might offer protection against AGE-related pathology in people at risk of developing type 2 diabetes.Trial registrationAustralia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000130763.

The Therapeutic Potential of Resistant Starch in Modulation of Insulin Resistance, Endotoxemia, Oxidative Stress and Antioxidant Biomarkers in Women with Type 2 Diabetes: A Randomized Controlled Clinical Trial

“…Prebiotics via several mechanisms can improve glycemic status and inflammation. Suppression of the levels of free fatty acids (FFAs) through short-chain fatty acids (acetate, propionate and butyrate) [23] returns to the basal expression levels of transcription factors involved in lipogenesis (sterol regulatory element-binding protein [SREBP-1c]), cholesterol metabolism (SREBP-2, liver X receptors) and fatty acid oxidation (peroxisome proliferator-activated receptor alpha [24] ), reductions of endotoxin levels [25] and decreased oxidative stress [26] , which could improve insulinemic effects. Non-significant changes in FPG may be attributed to lack of RS effect, as a prebiotic, on basal hepatic glucose production [27] .…”

Anti-glycation properties of the aqueous extract solutions of dried algae products and effect of lactic acid fermentation on the properties

“…It was originally described as a receptor for protein adducts formed by AGEs that accumulate in diseases such as diabetes and renal failure (Zill, Günther, Erbersdobler, Fölschb, & Faista, 2001). Recently, the inhibitory effect of dietary prebiotic supplementation on advanced glycation was found to be correlated with intestinal microbiota (Kellow et al, 2014). It can be considered that not only low-molecular-weight compounds but also high-molecularweight compounds in the algal AESs, as well as LAB, ameliorate the AGE-related damages with some intestinal microbiota.…”

“…The anti-glycation properties of the probiotics Lactobacillus acidophilus and Bifidobacterium infantis were recently reported (Stancu, Sanda, Rogoz, & Sima, 2012). Furthermore, one study reported that the prebiotics inulin and oligofructose ameliorated the AGE-related pathology of adult volunteers with pre-diabetes (Kellow, Coughlan, Savige, & Reid, 2014).…”

Therapeutic Modification of the GI Microbiome

“…The research team, headed by the same lead researcher as the abovementioned study, concluded that prebiotics might offer protection against advanced glycation endproducts-related pathology, which contributes to the pathogenesis of diabetes and its vascular complications in persons at risk of developing type 2 diabetes. 45 The researchers noted that the modern Western diet is replete with AGEs in processed foods.…”