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Introduction A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. Methods All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. Results A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. Conclusion These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease.

Circulating microRNAs (miRNAs) have been proposed as type 2 diabetes biomarkers, and they may be a more sensitive way to predict development of the disease than the currently used tools. Our aim was to identify whether circulating miRNAs, added to clinical and biochemical markers, yielded better potential for predicting type 2 diabetes. The study included 462 non-diabetic patients at baseline in the CORDIOPREV study. After a median follow-up of 60 months, 107 of them developed type 2 diabetes. Plasma levels of 24 miRNAs were measured at baseline by qRT-PCR, and other strong biomarkers to predict diabetes were determined. The ROC analysis identified 9 miRNAs, which, added to HbA1c, have a greater predictive value in early diagnosis of type 2 diabetes (AUC = 0.8342) than HbA1c alone (AUC = 0.6950). The miRNA and HbA1cbased model did not improve when the FINDRISC was included (AUC = 0.8293). Cox regression analyses showed that patients with low miR-103, miR-28-3p, miR-29a, and miR-9 and high miR-30a-5p and miR-150 circulating levels have a higher risk of disease (HR = 11.27; 95% CI = 2.61–48.65). Our results suggest that circulating miRNAs could potentially be used as a new tool for predicting the development of type 2 diabetes in clinical practice.

[Purpose] To investigate the effects of the consumption of Maillard reaction products (MRPs) from bread crust (BC) on iron, copper and zinc body retention and tissue distribution, determining whether these effects are related to the molecular weight of browning products., [Methods] During an 88-day study period, rats were fed a Control diet or diets containing BC as source of MRPs, its soluble high or low molecular weight fractions (BC, LMW or HMW diets). A mineral balance was conducted throughout the experiment to determine iron, copper and zinc retention. At day 88, animals were killed, blood was drawn for haemoglobin determination and some organs removed to analyse minerals., [Results] Copper and zinc balances were unchanged, and scant modification detected in their body delivery. However, the Fe retention rate from the diet increased (13, 22 and 32 % for BC, LMW and HMW diets), and a parallel higher Fe body concentration was observed (13–18 % higher than the Control group). Incoming iron accumulated particularly in the liver, femur and small intestine, but functional iron tended to decrease, as reflected by haemoglobin levels., [Conclusions] The long-term intake of BC or derivatives did not produce a notable effect on copper or zinc balances, although slightly increased iron retention rate and the body concentration of this mineral were observed. Iron accumulated in some organs, but the production of haemoglobin was not improved. In view of the differences observed between the effects of BC and its derivatives, our results underline the importance of working with real food matrices, where the joint presence of different components modulates the in vivo final effects.

Our aim was to analyze the influence of the prolonged consumption of Maillard reaction prod-ucts (MRPs) from the glucose-lysine model system, on calcium and magnesium bioavailability and on tissue distribution in female rats. A long-term study (88 days) was conducted, in which two groups of rats (n = 12) were fed either a Control diet or one including 3 % glucose-lysine MRPs (GL90 diet). During the experimental period, the global balance was determined; calcium apparent absorption, retention, and bioavailability were stable after consumption of the assayed MRPs (37 % and 38 % for the Control and GL90 groups, respectively). Consequently, there was no change in calcium tissue distribution. During the final week, an additional balance was performed, following urine and feces collection, which showed calcium bioavailability to be stable. During the same period, magnesium apparent absorption and retention increased, leading to higher digestibility and bioavailability. However, these variations could be isolated events of little significance, since overall there were no variations in magnesium body content or retention (73 mg and 75 mg for the Control and GL90 groups, respectively). This conclusion was supported by the stability of the magnesium content and its concentration in the organs. These findings are in line with those of previous studies, which have reported the low affinity of these metals to form MRP complexes.

We investigate the effects of consumption of MRPs from the glucose-lysine model system heated 15°C-90 min on protein digestibility and its utilisation in young (3-week) and adult (12-week) rats. Nitrogen faecal excretion significantly increased after MRP consumption, especially during the third week. Protein digestibility was lower in both age groups studied, but the utilisation was unaffected. Parallelly, the nitrogen retention and its net utilisation for the entire experimental period did not vary. In young rats the faecal nitrogen exceeded the amount of ingested nitrogen coming from MRPs, suggesting that digestibility of undamaged nitrogen was affected. The same action is suspected in adult animals, but the results were not quantitatively conclusive, and therefore the effect should be moderate in this period.

Traditionally the effects of dietary Maillard reaction products (MRPs) on food intake and body weight have been described in different studies, but few investigations have been conducted to analyse the main contributors responsible. We studied the effects of long-term consumption of MRPs from bread crust (BC) on rat growth, investigating the efficiency of diet and protein utilization. Different soluble and insoluble fractions of BC were studied to analyse the possible contributors. Additionally, the colour of the faecal material and the amount of fluorescent MRPs in the urine were measured in order to demonstrate MRP excretion. Six groups of rats were fed the following diets for 88 days: control (AIN-93G diet); bread dough (BD) and BC (containing 10% of BD or BC, respectively); low and high molecular weight (LMW-HMW) (containing soluble compounds from BC with <5 kDa and >5 kDa, respectively); insoluble (containing insoluble compounds from BC). Dietary MRPs tended to reduce the food intake and body weight significantly after consumption of more complex compounds (HMW and insoluble). The L*-value in the faeces decreased in animals fed BC and its derivatives, providing evidence of the presence of MRPs. The fluorescence associated with MRP excretion in urine was higher when the LMW diet was consumed, suggesting the easier absorption and clearance of the smaller compounds of BC.

Maillard reaction products (MRP) consumption has been related with the development of bone degenerative disorders, probably linked to changes in calcium metabolism. We aimed to investigate the effects of MRP intake from bread crust on calcium balance and its distribution, and bone metabolism. During 88 days, rats were fed control diet or diets containing bread crust as source of MRP, or its soluble high molecular weight, soluble low molecular weight or insoluble fractions (bread crust, HMW, LMW and insoluble diets, respectively). In the final week, a calcium balance was performed, then animals were sacrified and some organs removed to analyse calcium levels. A second balance was carried out throughout the experimental period to calculate global calcium retention. Biochemical parameters and bone metabolism markers were measured in serum or urine. Global calcium bioavailability was unmodified by consumption of bread crust or its isolate fractions, corroborating the previously described low affinity of MRP to bind calcium. Despite this, a higher calcium concentration was found in femur due to smaller bones having a lower relative density. The isolate consumption of the fractions altered some bone markers, reflecting a situation of increased bone resorption or higher turnover; this did not take place in the animals fed the bread crust diet. Thus, the bread crust intake does not affect negatively calcium bioavailability and bone metabolism.

Our aim was to investigate the effects of Maillard reaction products (MRPs) from bread crust (BC) on bone composition and its mechanical properties, determining whether any such effects are related to the molecular weight of different MRPs. For 88 days after weaning rats were fed a control diet or diets containing BC, or its soluble low molecular weight (LMW), soluble high molecular weight (HMW) or insoluble fractions. Animals' food consumption and body weights were monitored. After sacrifice, the femur, pelvic bone and tibia were removed for composition, physical and biomechanical properties analysis. It was found that body and femur weights, density, volume and organic matrix decreased, whereas pentosidine increased after consumption of experimental diets, especially in the HMW and insoluble groups (104.7 and 102.9 mmol mol(-1) collagen) vs. the control group (41.7 mmol mol(-1) collagen). Bone stiffness fell by 50% in the LMW, HMW and insoluble groups and failure load and energy to failure tended to decrease in the same animals after MRPs intake. Consumption of diets containing assayed MRPs during growth leads to lower bone size and introduces some changes in its mechanical behavior which appear to be related to an increase in the pentosidine level of bone.