Circulatory miRNA biomarkers of metabolic syndrome.

AIMS: Circulatory microRNAs (c-miRNAs) exert important roles in the molecular dysregulation of cardio-metabolic diseases. However, little is known whether dysregulated miRNA expression occurs when risk factors are elevated, as in the metabolic syndrome (MetS). This study quantified c-miRNA expression in individuals with MetS compared to healthy, further examining the relationship of gene pathways with the underlying pathogenesis. METHODS: Expression of 26 miRNAs was quantified in plasma from 40 women (20 healthy and 20 MetS) and 39 men (20 healthy and 19 MetS) by qPCR. In silico analysis was performed to investigate biological effects of the dysregulated miRNAs. Dysregulated miRNA expression was further validated in an independent cohort of 20 women (10 healthy and 10 MetS). RESULTS: Regression model adjusted for age and sex identified miR-15a-5p, miR-17-5p, miR-370-3p and miR-375 as important predictors of MetS presence. Analysis of predictive miRNAs in the validation cohort strengthened the relationship with miR-15a-5p and miR-17-5p expression. These miRNAs share genes involved in the regulation of metabolic pathways including insulin, wnt, fatty acid metabolism and AMPK. CONCLUSIONS: miR-15a-5p and miR-17-5p were identified as predictive biomarkers of MetS, irrespective of sexes, further demonstrating the relationship of c-miRNAs to known pathways of metabolic disturbances present in cardio-metabolic diseases.

A method for assessing real time rates of dissolution and absorption of carbohydrate and other food matrices in human subjects.

We prepared pasta of differing physical dimensions but identical chemical composition that contained two monosaccharide probes (lactulose and mannitol) that are absorbed passively and promptly excreted in urine. We showed that the rates of their liberation from the pasta under simulated gastric and small intestinal conditions largely depended upon the rate of digestion of the starchy matrix. We showed, in 20 female subjects, that excretion of mannitol was slower from the pasta with the larger particle size. Hence, after consumption of either the powdered pasta or the simple solution of probe sugars, the mass of mannitol excreted between 1 and 2½ hours was greater than that excreted between 2½ and 4 hours. However these masses did not differ significantly after consumption of the pasta pellets. These differences were not reflected in the concurrent patterns of variation in either serum glucose or insulin taken over 120 minutes, their levels being similar for pasta pellets and powder with their peak values occurring synchronously during the first hour. Hence feeding test foods impregnated with lactulose and mannitol probes provided a reproducible and practical means of assessing the timing of digestion of the carbohydrate matrix and showed that this was more protracted than suggested by post prandial glucose levels. Further, the transit times calculated on a basis of the ratios of the two marker sugars could identify that the prolongation of digestion of larger particles was not accompanied by retention of digesta in particular segments of the gut.

The effect of aspirin and smoking on urinary excretion profiles of lactulose and mannitol in young women: toward a dynamic, aspirin augmented, test of gut mucosal permeability.

BACKGROUND: We explored the temporal dynamics of the lactulose mannitol test and the influence of a single dose of aspirin. METHODS: Twenty healthy female volunteers each received 600 mg aspirin or placebo in random sequence and were subsequently dosed with 10 g lactulose and 5 g mannitol, their urine collected every half hour for 6h. KEY RESULTS: The lactulose:mannitol ratios (LMR) of urine samples collected over the entire 6-h period were significantly higher than those collected in the first 3 h. Greater quantities of mannitol were excreted over the first than the subsequent 3 h. A similar pattern of temporal variation in mannitol excretion was found in smokers and non-smokers and was maintained following administration of a single 600 mg dose of aspirin. The rates at which lactulose was excreted were relatively constant over the entire 6 h period of collection, but mean levels were increased over the entire 6 h following the administration of aspirin. The effect of aspirin did not differ significantly between smokers and non-smokers. CONCLUSIONS & INFERENCES: While the LMR test is sufficiently sensitive to reproducibly detect the increase in intestinal permeability resulting from a single 600 mg oral dose of aspirin, the temporal patterns of excretion of mannitol and lactulose differ both in the presence and absence of aspirin. Hence, variation in sampling period and in method of dosage are likely to influence the result and it is preferable to examine the patterns of absorption of component sugars separately with due regard to the method of dosage.