Ghrelin is a novel growth hormone-releasing peptide, originally identified in the rat stomach as the endogenous ligand for the growth hormone secretagogue-receptor (GHS-R1a). Ghrelin is involved in the regulation of GH release, but it has recently been suggested that ghrelin may have other actions, including effects on appetite, carbohydrate metabolism, heart, kidney, pancreas, gonads, and cell proliferation. The distribution of ghrelin, its functional receptor (type 1a) and the unspliced, non-functional GHS-R type 1b mRNA expression was investigated in various human tissues using classical and real-time reverse transcription and polymerase chain reaction. GHS-R1a was predominantly expressed in the pituitary and at much lower levels in the thyroid gland, pancreas, spleen, myocardium and adrenal gland. In contrast, ghrelin was found in the stomach, other parts of the gut and, indeed, in all the tissues studied (adrenal gland, atrium, breast, buccal mucosa, esophagus, Fallopian tube, fat tissue, gall bladder, human lymphocytes, ileum, kidney, left colon, liver, lung, lymph node, muscle, muscle, myocardium, ovary, pancreas, pituitary, placenta, prostate, right colon, skin, spleen, testis, thyroid, and vein). GHS-R1b expression was also widespread in all tissues studied. The significance of the widespread tissue distribution of ghrelin remains to be determined. These data suggest that ghrelin might have widespread physiological effects via different, partly unidentified, subtypes of the GHS-R in endocrine and non-endocrine tissues.

Leptin is a robust indicator of BMI and insulin levels, both basal and stimulated, but does not change acutely following food. Fasting causes a proportionately greater decline in leptin levels in lean subjects than in obese subjects. Circulating leptin is inversely correlated with the activity of the hypothalamo-pituitary-adrenal axis: whether this is a direct influence of leptin on hypothalamo-pituitary-adrenal activity, or whether both are indirect indicators of body fat stores, requires further investigation.

Ghrelin is a recently recognized gut-brain peptide originally derived from the gastric mucosa. It stimulates growth hormone release, increases appetite and facilitates fat storage, and may interact with glucose metabolism. We studied the ghrelin gene in a group of 70 tall and obese children (mean age 9.4 year, Z body mass index [BMI] and Z height >3 and/or BMI percentile >99%). We found 10 single nucleotide polymorphisms. One common polymorphism of the ghrelin gene, which corresponds to an amino acid change in the tail of the prepro-ghrelin molecule, was significantly associated with children with a higher BMI (P = 0.001), and with lower insulin secretion during the first part of an oral glucose tolerance test (P = 0.05) although no difference in glucose levels was noted. This might suggest increased insulin sensitivity, although this is not supported by the lack of difference in fasting and 2 hour insulin levels; alternatively, this may be indicative of impaired first phase insulin secretion. These data suggest that variations in the ghrelin gene contribute to obesity in children and may modulate glucose-induced insulin secretion.

BackgroundSepsis is usually accompanied by changes of body temperature (Tb), but whether fever and hypothermia predict mortality equally or differently is not fully clarified. We aimed to find an association between Tb and mortality in septic patients with meta-analysis of clinical trials.MethodsWe searched the PubMed, EMBASE, and Cochrane Controlled Trials Registry databases (from inception to February 2016). Human studies reporting Tb and mortality of patients with sepsis were included in the analyses. Average Tb with SEM and mortality rate of septic patient groups were extracted by two authors independently.ResultsForty-two studies reported Tb and mortality ratios in septic patients (n = 10,834). Pearson correlation analysis revealed weak negative linear correlation (R2 = 0.2794) between Tb and mortality. With forest plot analysis, we found a 22.2% (CI, 19.2–25.5) mortality rate in septic patients with fever (Tb > 38.0°C), which was higher, 31.2% (CI, 25.7–37.3), in normothermic patients, and it was the highest, 47.3% (CI, 38.9–55.7), in hypothermic patients (Tb < 36.0°C). Meta-regression analysis showed strong negative linear correlation between Tb and mortality rate (regression coefficient: -0.4318; P < 0.001). Mean Tb of the patients was higher in the lowest mortality quartile than in the highest: 38.1°C (CI, 37.9–38.4) vs 37.1°C (CI, 36.7–37.4).ConclusionsDeep Tb shows negative correlation with the clinical outcome in sepsis. Fever predicts lower, while hypothermia higher mortality rates compared with normal Tb. Septic patients with the lowest (< 25%) chance of mortality have higher Tb than those with the highest chance (> 75%).

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adverse effects may occur with the use of metformin 8. Alternatively, the potential role of modifications in the gut microbiome had been explored as a new complementary therapeutic strategy 9. Clinical evidence supports the hypothesis that the modulation of the gut microbiota by probiotics could be effective in prevention and management of diabetes 10,11. Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The healthy human body contains such microbes physiologically; and they can be obtained in forms of over-the-counter food supplements as well. Over the last few years, probiotics, especially the lactobacillus species were shown to be effective in the therapy of type 2 diabetes 12. In type 2 diabetes, gut microbiome is found to be different from that in the healthy population. In a human study, the amount of Firmicutes bacteria was lower, whereas the number of Bacteroides and Proteobacteria is higher in the gastrointestinal tract of patients with type 2 diabetes compared to non-diabetic persons 13. According to the study 13 , the ratio of Bacteriodes and Firmicutes species had positive correlation with decreased insulin resistance, however, causality has not been proven yet. Following innovative dietary strategies, it seems possible to maintain euglycemia by normalizing the altered microbiome, and to prevent long-term micro-and macrovascular complications of type 2 diabetes 9. Although, there have been numerous bacterial species investigated in the therapy of type 2 diabetes, no consensus has been obtained regarding the effectivity and the most effective species. For instance, an earlier meta-analysis suggested, that the intake of certain Lactobacillus species, such as L. fermentum, L. ingluviei and L. acidophilus can lead to weight gain, while the ingestion of L. gasseri and L. plantarum might end up in weight loss both in animal and human studies 14. Previous meta-analysis in this field were not conducted with assessment of the evidence quality levels and the number of identified trials that met their inclusion criteria was relatively low (7-12 trials) 15-19. Two meta-analysis found no significant effects of probiotics on lipid profile 16,19 and two meta-analysis found decreased indexes of lipid profiles 17,18. These contradictory reports on the effect of probiotics inspired us to conduct an updated meta-analysis to assess the effect of probiotic therapies in diabetes mellitus type 2 exclusively from randomized controlled trials. Materials and methods Protocol and registration. This meta-analysis was reported according to the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines 20. Pre-specified protocol of this meta-analysis was published in the Prospero Center for Reviews and Dissemination (PROSPERO) under the registration number of CRD42019137997.

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IntroductionThe incidence of acute pancreatitis (AP) and the prevalence of metabolic syndrome (MetS) are growing worldwide. Several studies have confirmed that obesity (OB), hyperlipidemia (HL), or diabetes mellitus (DM) can increase severity, mortality, and complications in AP. However, there is no comprehensive information on the independent or joint effect of MetS components on the outcome of AP. Our aims were (1) to understand whether the components of MetS have an independent effect on the outcome of AP and (2) to examine the joint effect of their combinations.MethodsFrom 2012 to 2017, 1435 AP cases from 28 centers were included in the prospective AP Registry. Patient groups were formed retrospectively based on the presence of OB, HL, DM, and hypertension (HT). The primary endpoints were mortality, severity, complications of AP, and length of hospital stay. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated.Results1257 patients (55.7 ± 17.0 years) were included in the analysis. The presence of OB was an independent predictive factor for renal failure [OR: 2.98 (CI: 1.33–6.66)] and obese patients spent a longer time in hospital compared to non-obese patients (12.1 vs. 10.4 days, p = 0.008). HT increased the risk of severe AP [OR: 3.41 (CI: 1.39–8.37)], renal failure [OR: 7.46 (CI: 1.61–34.49)], and the length of hospitalization (11.8 vs. 10.5 days, p = 0.020). HL increased the risk of local complications [OR: 1.51 (CI: 1.10–2.07)], renal failure [OR: 6.4 (CI: 1.93–21.17)], and the incidence of newly diagnosed DM [OR: 2.55 (CI: 1.26–5.19)]. No relation was found between the presence of DM and the outcome of AP. 906 cases (mean age ± SD: 56.9 ± 16.7 years) had data on all four components of MetS available. The presence of two, three, or four MetS factors increased the incidence of an unfavorable outcome compared to patients with no MetS factors.ConclusionOB, HT, and HL are independent risk factors for a number of complications. HT is an independent risk factor for severity as well. Components of MetS strongly synergize each other’s detrimental effect. It is important to search for and follow up on the components of MetS in AP.