Insulin Resistance Is Not Increased in Inflammatory Bowel Disease Patients but Is Related to Non-Alcoholic Fatty Liver Disease

Background: Insulin resistance (IR) has been linked to inflammatory states. The aim of this study was to determine whether IR is increased in a cohort of inflammatory bowel disease (IBD) patients with low disease activity. We additionally intended to establish which factors were the determinants of IR in this population, including the presence of nonalcoholic fatty liver disease (NAFLD). Methods: Cross-sectional study encompassing 151 IBD patients and 174 non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices based on homoeostatic model assessment (HOMA2) were assessed in patients and controls. Liver stiffness as measured by transient elastography, and the presence of NAFLD detected via ultrasound were additionally assessed. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients and controls, and to determine which predictor factors were associated with IR in IBD patients. Results: Neither HOMA2-IR (beta coef. -0.26 {95%CI -0.64-0.13}, p = 0.19) nor HOMA2-%B (beta coef. 15 {95%CI -14-44}, p = 0.31) indexes differed between patients and controls after fully multivariable analysis. Among classic IR risk factors, obesity, abdominal circumference, and triglycerides significantly and positively correlated with IR indexes in IBD patients. However, most features related to IBD, such as disease patterns, disease activity, and inflammatory markers, were not associated with IR. The presence of NAFLD was independently and significantly associated with beta cell dysfunction in patients with IBD (HOMA2-B grade 4, 251 ± 40 vs. grade 1, 107 ± 37, p = <0.001). Conclusions: IR is not increased in IBD patients with low disease activity compared to controls. However, the presence of NAFLD favors the development of IR in patients with IBD.This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional-FEDER-(Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083)

Carotid Plaque Assessment Reclassifies Patients with Inflammatory Bowel Disease into Very-High Cardiovascular Risk

The addition of carotid ultrasound into cardiovascular (CV) risk scores has been found to be effective in identifying patients with chronic inflammatory diseases at high-CV risk. We aimed to determine if its use would facilitate the reclassification of patients with inflammatory bowel disease (IBD) into the very high-CV-risk category and whether this may be related to disease features. In this cross-sectional study encompassing 186 IBD patients and 175 controls, Systematic Coronary Risk Evaluation (SCORE), disease activity measurements, and the presence of carotid plaques by ultrasonography were assessed. Reclassification was compared between patients and controls. A multivariable regression analysis was performed to evaluate if the risk of reclassification could be explained by disease-related features and to assess the influence of traditional CV risk factors on this reclassification. After evaluation of carotid ultrasound, a significantly higher frequency of reclassification was found in patients with IBD compared to controls (35% vs. 24%, p = 0.030). When this analysis was performed only on subjects included in the SCORE low-CV-risk category, 21% IBD patients compared to 11% controls (p = 0.034) were reclassified into the very high-CV-risk category. Disease-related data, including disease activity, were not associated with reclassification after fully multivariable regression analysis. Traditional CV risk factors showed a similar influence over reclassification in patients and controls. However, LDL-cholesterol disclosed a higher effect in controls compared to patients (beta coef. 1.03 (95%CI 1.02-1.04) vs. 1.01 (95%CI 1.00-1.02), interaction p = 0.035) after adjustment for confounders. In conclusion, carotid plaque assessment is useful to identify high-CV risk IBD patients.Funding: This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016 and by Fondo Europeo de Desarrollo Regional—FEDER—(Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083)

QRISK3 performance in the assessment of cardiovascular risk in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) has been described as an independent risk factor for the development of cardiovascular (CV) disease. Since the QRESEARCH risk estimator version 3 (QRISK3) calculator was recently proposed to assess CV in the general population, our objective was to compare the predictive ability of QRISK3 with that of a well-established European CV risk calculator, the Systematic Coronary Risk Assessment (SCORE), to identify the presence of subclinical carotid atherosclerosis in patients with IBD. In all, 186 patients with IBD and 178 controls were recruited. The presence of subclinical atherosclerosis was evaluated by carotid ultrasound to identify carotid plaque and the thickness of the carotid intima-media (cIMT). QRISK3 and SCORE were calculated. The relationship of QRISK3 and SCORE with each other and with the presence of subclinical carotid atherosclerosis (both carotid plaque and cIMT) was studied in patients and controls. SCORE (0.2 (interquartile range 0.1-0.9) vs. 0.4 (0.1-1.4), p = 0.55) and QRISK3 1.7 ((0.6-4.6) vs. 3.0 (1.0-7.8), p = 0.16) absolute values did not differ between patients and controls. QRISK3 and SCORE correlated equally with cIMT within both populations. However, SCORE correlation with cIMT was found to be significantly lower in patients with IBD when compared to controls (Spearman's Rho 0.715 vs. 0.587, p = 0.034). Discrimination analysis of both calculators with carotid plaque was similar within both populations. Nevertheless, in patients with IBD, QRISK3 showed a trend toward a higher discrimination (QRISK3 area under the curve 0.812 (95%CI 0.748-0.875) vs. SCORE 0.790 (95%CI 0.723-0.856), p = 0.051). In conclusion, QRISK3 discrimination for subclinical atherosclerosis is optimal and equivalent to that of SCORE in IBD patients. However, our findings highlight the role of QRISK3 as an appropriate tool for the assessment of CV risk in patients with IBD.Funding: This work was supported by a grant to I.F-A. from the Spanish Ministry of Health, Subdirección General de Evaluación y Fomento de la Investigación, Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, and by Fondo Europeo de Desarrollo Regional-FEDER-(Fondo de Investigaciones Sanitarias, FIS PI14/00394, PI17/00083)

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis.

INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.This work was funded by grants from the Instituto de Salud Carlos III (PI12/01481; PI19/01050). Project PI19/ 01050 is funded by Instituto de Salud Carlos III (ISCIII) and co funded by the European Union. CIBEREHD is funded by the Insti tuto de Salud Carlos III and Beca Marató de TV3 (201932-30). Parts of this work were also supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncología de Catalunya (XBTC) and by the Hospital Clínics Premi Fi de Residència (G.J). None of the funding parties has been involved in collection, analysis, and interpretation of the data

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis

Introduction: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. Methods: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). Results: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). Discussion: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression

Clinical and Pathological Characterization of Lynch-Like Syndrome

Background & aims: Lynch syndrome is characterized by DNA mismatch repair (MMR) deficiency. Some patients with suspected Lynch syndrome have DNA MMR deficiencies but no detectable mutations in genes that encode MMR proteins-this is called Lynch-like syndrome (LLS). There is no consensus on management of patients with LLS. We collected data from a large series of patients with LLS to identify clinical and pathology features. Methods: We collected data from a nationwide-registry of patients with colorectal cancer (CRC) in Spain. We identified patients whose colorectal tumors had loss of MSH2, MSH6, PMS2, or MLH1 (based on immunohistochemistry), without the mutation encoding V600E in BRAF (detected by real-time PCR), and/or no methylation at MLH1 (determined by methylation-specific multiplex ligation-dependent probe amplification), and no pathogenic mutations in MMR genes, BRAF, or EPCAM (determined by DNA sequencing). These patients were considered to have LLS. We collected data on demographic, clinical, and pathology features and family history of neoplasms. The χ2 test was used to analyze the association between qualitative variables, followed by the Fisher exact test and the Student t test or the Mann-Whitney test for quantitative variables. Results: We identified 160 patients with LLS; their mean age at diagnosis of CRC was 55 years and 66 patients were female (41%). The Amsterdam I and II criteria for Lynch syndrome were fulfilled by 11% of cases and the revised Bethesda guideline criteria by 65% of cases. Of the patients with LLS, 24% were identified in universal screening. There were no proportional differences in sex, indication for colonoscopy, immunohistochemistry, pathology findings, or personal history of CRC or other Lynch syndrome-related tumors between patients who met the Amsterdam and/or Bethesda criteria for Lynch syndrome and patients identified in universal screening for Lynch syndrome, without a family history of CRC. Conclusions: Patients with LLS have homogeneous clinical, demographic, and pathology characteristics, regardless of family history of CRC

Insulin Resistance Is Not Increased in Inflammatory Bowel Disease Patients but Is Related to Non-Alcoholic Fatty Liver Disease

Background. Insulin resistance (IR) has been linked to inflammatory states. The aim of this study was to determine whether IR is increased in a cohort of inflammatory bowel disease (IBD) patients with low disease activity. We additionally intended to establish which factors were the determinants of IR in this population, including the presence of nonalcoholic fatty liver disease (NAFLD). Methods. Cross-sectional study encompassing 151 IBD patients and 174 non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices based on homoeostatic model assessment (HOMA2) were assessed in patients and controls. Liver stiffness as measured by transient elastography, and the presence of NAFLD detected via ultrasound were additionally assessed. A multivariable regression analysis was performed to evaluate the differences in IR indexes between patients and controls, and to determine which predictor factors were associated with IR in IBD patients. Results. Neither HOMA2-IR (beta coef. −0.26 {95%CI −0.64–0.13}, p = 0.19) nor HOMA2-%B (beta coef. 15 {95%CI −14–44}, p = 0.31) indexes differed between patients and controls after fully multivariable analysis. Among classic IR risk factors, obesity, abdominal circumference, and triglycerides significantly and positively correlated with IR indexes in IBD patients. However, most features related to IBD, such as disease patterns, disease activity, and inflammatory markers, were not associated with IR. The presence of NAFLD was independently and significantly associated with beta cell dysfunction in patients with IBD (HOMA2—B grade 4, 251 ± 40 vs. grade 1, 107 ± 37, p = &lt;0.001). Conclusions. IR is not increased in IBD patients with low disease activity compared to controls. However, the presence of NAFLD favors the development of IR in patients with IBD