RESUMEN
Holistic management of pancreatitis means that gastroenterologists in the 21st Century should think beyond improving in-hospital outcomes of pancreatitis alone. In particular, there is considerable room for optimizing the management of new-onset diabetes, exocrine pancreatic insufficiency, and other metabolic sequelae of pancreatitis. The present article provides state-of-the-art information on classification, terminology, and burden of the common sequelae of pancreatitis. A high-risk group of patients with pancreatitis is identified, which is positioned to benefit the most from the metabolic sequelae surveillance program introduced in this article. The program involves continuous follow-up after pancreatitis diagnosis, with the focus on early identification of new-onset diabetes after pancreatitis and exocrine pancreatic insufficiency. The metabolic sequelae surveillance program is scalable and has the potential to reduce the burden of pancreatitis through tertiary prevention in the decades to come.
RESUMEN
AIM: To investigate the relationship of fat in the pancreas with time spent in different glycaemic ranges. METHODS: Abdominal magnetic resonance imaging at 3.0 Tesla was used to quantify fat in the pancreas as both continuous [i.e. intra-pancreatic fat deposition (IPFD)] and binary (i.e. fatty change of the pancreas vs. normal pancreas) variables. Dexcom G6 devices were used to collect continuous glucose monitoring data every 5 min over a continuous 7-day period. Time above range (TAR), time in range (TIR) and time below range were computed. Statistical models were built to adjust for age, sex, body composition, and other covariates in linear regression analysis and analysis of covariance. RESULTS: In total, 38 individuals were studied. IPFD was significantly associated with TAR (p = .036) and TIR (p = .042) after adjustment for covariates. For every 1% increase in IPFD, there was a 0.3 unit increase in TAR and a decrease in TIR. Individuals with fatty change of the pancreas, when compared with those with normal pancreas, had significantly higher TAR (p = .034) and lower TIR (p = .047) after adjustment for covariates. Neither IPFD (p = .805) nor fatty change of the pancreas (p = .555) was associated with time below range after adjustment for covariates. CONCLUSION: Increased fat in the pancreas is associated with excessive glycaemic variability. Fatty change of the pancreas may contribute to heightening the risk of cardiovascular diseases.
Asunto(s)
Monitoreo Continuo de Glucosa , Páncreas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tejido Adiposo/diagnóstico por imagen , Glucemia/análisis , Diabetes Mellitus Tipo 1/sangre , Imagen por Resonancia Magnética , Páncreas/diagnóstico por imagen , Páncreas/patologíaRESUMEN
AIMS/HYPOTHESIS: The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS: All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS: A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION: At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.
Asunto(s)
Hígado , Análisis de Mediación , Humanos , ColesterolRESUMEN
Surveillance of mucinous pancreatic cysts is a key to reducing pancreatic cancer risk and detecting malignancy early. However, while the management of cysts with high-risk and worrisome features is fairly straightforward, surveillance of patients with low-risk branch-duct intraductal papillary mucinous neoplasms has long presented gastroenterologists with the challenging question of discontinuation of surveillance. Up-to-date evidence supports the cessation of follow-up in these patients depending on both interval stability of the cyst and cyst size. Based on these criteria, discontinuation of surveillance at either 5 years or 10 years is recommended. Oversurveillance of patients with pancreatic cysts in the absence of high-risk and worrisome features is discouraged.
Asunto(s)
Quiste Pancreático , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/patología , Páncreas/patologíaRESUMEN
AIM: To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD). METHODS: All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition. RESULTS: A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD. CONCLUSION: Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.
Asunto(s)
Resistencia a la Insulina , Páncreas , Humanos , LDL-Colesterol , Páncreas/diagnóstico por imagen , Colesterol , Índice de Masa Corporal , Triglicéridos , HDL-ColesterolRESUMEN
INTRODUCTION: Increased intrapancreatic fat deposition (IPFD) has emerged as a harbinger of pancreatic cancer and chronic pancreatitis. Although it is well recognized that diseases of the exocrine pancreas often lie on a continuum (with acute pancreatitis preceding the development of chronic pancreatitis and/or pancreatic cancer), whether increased IPFD predisposes to acute pancreatitis is unknown. This study aimed to compare fat depositions in the pancreas (as well as the liver and skeletal muscle) between individuals who developed first attack of acute pancreatitis and healthy individuals. METHODS: This was a matched case-control study nested into population-based cohort. MRI on a single 3 T scanner was used to quantify intrapancreatic, liver, and skeletal muscle fat depositions using the same protocols in all study participants. Binary logistic regression with adjustment for body mass index and other possible confounders was performed. RESULTS: Fifty individuals with first attack of nonnecrotizing acute pancreatitis comprised the case group and 100 healthy individuals comprised the control group. A 1% increase in IPFD (but not the other fat depositions) was significantly associated with a more than 30% higher chance of developing first attack of acute pancreatitis, consistently in both the unadjusted ( P = 0.004) and all adjusted models. Furthermore, a 1% increase in IPFD (but not the other fat depositions) was significantly associated with up to a 27% higher chance of developing first attack of acute pancreatitis in individuals with normotriglyceridemia, consistently in both the unadjusted ( P = 0.030) and all adjusted models. DISCUSSION: Increased IPFD may predispose to the development of acute pancreatitis. This opens up opportunities for reducing the burden of acute pancreatitis by means of primary prevention.
Asunto(s)
Neoplasias Pancreáticas , Pancreatitis Crónica , Enfermedad Aguda , Estudios de Casos y Controles , Humanos , Hígado , Músculo Esquelético/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagenRESUMEN
BACKGROUND: Ketone monoester ß-hydroxybutyrate (KEßHB) ingestion has emerged as an effective method of inducing acute ketosis. Although evidence suggests that KEßHB can offer several therapeutic benefits, whether KEßHB affects lipid profile is still unknown. AIMS: The primary aim was to study the effect of KEßHB on plasma lipid profile in individuals with prediabetes. The secondary aim was to investigate the role of saturated fat intake in that effect. METHODS: This study was a randomized controlled trial with cross-over design. Following an overnight fast, 18 adults (six women and 12 men) with prediabetes (diagnosed based on the American Diabetes Association criteria) ingested a single dose of KEßHB drink or placebo drink. Blood samples were collected every 30 min, from baseline to 150 min. Outcome variables included changes in total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, remnant cholesterol, triglycerides, and the triglycerides to HDL cholesterol ratio. The area under the curve (AUC) over 150 min was calculated for each outcome following ingestion of the drinks. Habitual saturated fat intake was ascertained using the EPIC-Norfolk food frequency questionnaire. RESULTS: Significant elevation of blood ß-hydroxybutyrate from 0.2 mmol/L to 3.5 mmol/L (p < 0.001) was achieved within 30 min. Acute ketosis resulted in significantly lower AUCs for remnant cholesterol (p = 0.022) and triglycerides (p = 0.022). No statistically significant differences in the AUCs for total cholesterol, HDL cholesterol, LDL cholesterol, and the triglycerides to HDL cholesterol ratio were found. The changes in remnant cholesterol and triglycerides were statistically significant in individuals with high, but not low, habitual saturated fat intake. CONCLUSION: Acute ketosis had no untoward effect on plasma lipid profile. Moreover, it led to significantly reduced circulating levels of remnant cholesterol and triglycerides. This paves the way for investigating whether exogenous ketone supplementation reduces cardiovascular disease risk (via its actions on triglyceride-rich lipoproteins) in at-risk populations. Trial registration: ClinicalTrials.gov, NCT03889210.
Asunto(s)
Cetosis , Estado Prediabético , Ácido 3-Hidroxibutírico , Adulto , Colesterol , HDL-Colesterol , LDL-Colesterol , Estudios Cruzados , Femenino , Humanos , Cetosis/diagnóstico , Masculino , Estado Prediabético/diagnóstico , TriglicéridosRESUMEN
BACKGROUND/PURPOSE: Acute inflammation of the pancreas often leads to metabolic sequelae, the most common of which is new-onset prediabetes (and, ultimately, diabetes). However, there is a lack of studies on predictors of this sequela. The aim was to investigate whether cytokines/chemokines measured at baseline are predictive of new-onset prediabetes after acute pancreatitis (NOPAP). METHODS: This was a prospective longitudinal cohort study (as part of the LACERTA project) that included 68 individuals with non-necrotising acute pancreatitis who had no diabetes mellitus. Of them, 17 individuals had prediabetes at baseline and during follow-up, 37 individuals had normoglycaemia at baseline and during follow-up, and 14 individuals had normoglycaemia at baseline and developed NOPAP during follow-up. A commercially available human cytokine/chemokine multiplex kit was used to measure a total of 28 analytes at baseline. Multinomial regression analyses were conducted to investigate the associations between the cytokines/chemokines and the three study groups. RESULTS: Interleukin-1ß and interferon γ significantly predicted progression to NOPAP with an odds ratio (95% confidence interval) of 1.097 (1.002, 1.201) and 1.094 (1.003, 1.192), respectively (after accounting for age, sex, body mass index, and aetiology of acute pancreatitis). None of the studied cytokines/chemokines showed statistically significant associations with the antecedent prediabetes group (after accounting for the above covariates). CONCLUSION: Elevated levels of interleukin-1ß and interferon γ in acute pancreatitis individuals with normoglycaemia at baseline may predict progression to NOPAP during follow-up.
Asunto(s)
Diabetes Mellitus Tipo 2 , Pancreatitis , Estado Prediabético , Enfermedad Aguda , Estudios de Cohortes , Citocinas , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Estudios Longitudinales , Pancreatitis/metabolismo , Estado Prediabético/complicaciones , Estado Prediabético/metabolismo , Estudios ProspectivosRESUMEN
BACKGROUND: The clinical relevance of excess intrapancreatic fat deposition (IPFD) is increasingly appreciated. Leptin and ghrelin are key players in the regulation of food intake, energy balance, and body fat mass. The aim was to investigate the associations of the leptin/ghrelin ratio and its components with IPFD. METHODS: All participants underwent magnetic resonance imaging on a 3T scanner to quantify IPFD. Both fasting and postprandial blood samples were analyzed for leptin and acylated ghrelin. Linear regression analysis was conducted, accounting for visceral/subcutaneous fat volume ratio, glycated hemoglobin, and other covariates. RESULTS: A total of 94 participants (32 women) with a median age of 56 (interquartile range 44-66) years were studied. Their median IPFD was 9.6% (interquartile range 8.8-10.4%). In the fasted state, the leptin/ghrelin ratio (ß = 0.354; 95% confidence interval 0.044-0.663; p = 0.025, in the most adjusted model) and leptin (ß = 0.040; 95% confidence interval 1.003-1.078; p = 0.035, in the most adjusted model) were significantly associated with IPFD. Ghrelin in the fasted state was not significantly associated with IPFD. In the postprandial state, the leptin/ghrelin ratio, leptin, and ghrelin were not significantly associated with IPFD. CONCLUSION: Fasting circulating levels of leptin are directly associated with IPFD. Purposely designed mechanistic studies are warranted to determine how high leptin may contribute to excess IPFD.
Asunto(s)
Ayuno , Ghrelina , Leptina , Adulto , Anciano , Ayuno/metabolismo , Femenino , Ghrelina/metabolismo , Humanos , Leptina/metabolismo , Imagen por Resonancia Magnética , Persona de Mediana Edad , Periodo Posprandial/fisiologíaRESUMEN
BACKGROUND: The potential of a ketone monoester (ß-hydroxybutyrate; KEßHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEßHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown. OBJECTIVES: The primary objective was to investigate the effect of KEßHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides. METHODS: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of ß-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEßHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [ß-hydroxybutyrate (ßHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time. RESULTS: Blood ßHB concentrations increased to 3.5 mmol/L within 30 minutes after KEßHB supplementation. Plasma glucose AUC was significantly lower after KEßHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEßHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1. CONCLUSIONS: Ingestion of the KEßHB-supplemented drink acutely increased the blood ßHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEßHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.
Asunto(s)
Ácido 3-Hidroxibutírico/administración & dosificación , Glucemia/metabolismo , Cetosis/etiología , Estado Prediabético/sangre , Estado Prediabético/dietoterapia , Ácido 3-Hidroxibutírico/sangre , Adulto , Anciano , Péptido C/sangre , Estudios Cruzados , Suplementos Dietéticos , Femenino , Polipéptido Inhibidor Gástrico/sangre , Glucagón/sangre , Péptido 1 Similar al Glucagón/sangre , Humanos , Insulina/sangre , Polipéptido Amiloide de los Islotes Pancreáticos/sangre , Cetosis/sangre , Masculino , Persona de Mediana Edad , Método Simple CiegoRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to delineate risk factors for the development of diabetes in patients with chronic pancreatitis. The natural history including progression to diabetes and complications that develop once diabetes occurs in chronic pancreatitis is also reviewed. RECENT FINDINGS: Studies have found that predictors of diabetes in chronic pancreatitis include both risk factors for type 2 diabetes (e.g., obesity, genetic variants) as well as pancreas-specific factors (e.g., pancreatic calcification, exocrine insufficiency). Rates of diabetes in chronic pancreatitis are strongly related to the duration of chronic pancreatitis, reflecting progressive dysfunction and damage to the insulin-secreting beta cells. Patients with diabetes and chronic pancreatitis experience an excess burden of complications, including higher all-cause and cancer-related mortality. SUMMARY: The high incidence and significant impact of diabetes on the morbidity and mortality of patients with chronic pancreatitis highlights the urgent need for clinically applicable models to predict diabetes in those with chronic pancreatitis, allowing efforts for targeted interventions to prevent diabetes. Research being carried out in the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer holds promise to fulfill these goals.
Asunto(s)
Diabetes Mellitus Tipo 2 , Neoplasias Pancreáticas , Pancreatitis Crónica , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Páncreas , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/etiología , Pancreatitis Crónica/epidemiología , Pancreatitis Crónica/etiología , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: Diabetes secondary to pancreatic diseases (i.e., acute pancreatitis, chronic pancreatitis, and pancreatic cancer) is increasingly studied, but remains challenging to distinguish from type 2 diabetes (T2DM). We review the clinical significance and potential biomarkers that may help differentiate these types of diabetes. RECENT FINDINGS: Recent studies have identified several complications (including nonvascular) that occur more frequently in patients with diabetes secondary to acute and chronic pancreatitis than T2DM, and biomarkers to differentiate these types of diabetes. There have been advances that may enable the enrichment of a population of adults with new onset diabetes to potentially screen for occult pancreatic cancer, but efforts are needed to identify and validate promising diagnostic biomarkers. SUMMARY: High-quality studies are needed to more precisely understand the risk factors and natural course of diabetes secondary to pancreatic diseases. Mechanistic and interventional studies are awaited to provide insights that will distinguish diabetes secondary to pancreatic diseases and refine the management of hyperglycemia in this patient population.
Asunto(s)
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Enfermedades Pancreáticas , Neoplasias Pancreáticas , Pancreatitis , Enfermedad Aguda , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Humanos , Enfermedades Pancreáticas/diagnóstico , Enfermedades Pancreáticas/etiología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/diagnósticoRESUMEN
OBJECTIVES: Current knowledge of the link between dietary carbohydrate intake and insulin regulation in individuals after an attack of pancreatitis is limited. We aimed to investigate the associations between dietary carbohydrate intake and insulin traits in post-pancreatitis versus healthy individuals, taking into account intrapancreatic fat deposition (IPFD). METHODS: All participants underwent magnetic resonance imaging (using the same protocol and 3T scanner) to quantify IPFD. Dietary carbohydrate intake was assessed using a validated 131-item food frequency questionnaire. Insulin, HOMA-IR, HOMA-ß were determined in the fasted state. Linear regression and effect modification analyses were conducted in unadjusted and adjusted models (accounting for age, sex, body mass index, daily energy intake, use of anti-diabetic medications, and recurrence of acute pancreatitis). RESULTS: The study included 111 post-pancreatitis individuals (categorized into low IPFD (n = 33), moderate IPFD (n = 40), high IPFD (n = 38)) and 47 healthy controls. In the high IPFD group, starch intake was negatively associated with fasting insulin and HOMA-ß in both the unadjusted (p < 0.001 both) and fully adjusted models (p < 0.001 both); and with HOMA-IR in the fully adjusted model (p < 0.001) only. Total sugar intake was positively associated with fasting insulin (p = 0.015) and HOMA-ß (p = 0.007) in the fully adjusted model but not associated with HOMA-IR. None of the above associations was statistically significant in the low IPFD, moderate IPFD, and healthy controls groups. The studied associations were more pronounced in the high IPFD group but not in the moderate IPFD or low IPFD groups (when compared with the healthy controls group). CONCLUSIONS: Dietary carbohydrate intake is differentially associated with insulin traits in individuals after an attack of pancreatitis and the associations are modified by IPFD. These findings will be helpful for the development of dietary guidelines specifically for individuals after an attack of pancreatitis.
Asunto(s)
Carbohidratos de la Dieta/administración & dosificación , Insulina/metabolismo , Pancreatitis/patología , Enfermedad Aguda , Adulto , Anciano , Glucemia , Composición Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pancreatitis/diagnóstico , Pancreatitis/metabolismoRESUMEN
OBJECTIVES: To systematically review published studies on the use of radiomics of the pancreas. METHODS: The search was conducted in the MEDLINE database. Human studies that investigated the applications of radiomics in diseases of the pancreas were included. The radiomics quality score was calculated for each included study. RESULTS: A total of 72 studies encompassing 8863 participants were included. Of them, 66 investigated focal pancreatic lesions (pancreatic cancer, precancerous lesions, or benign lesions); 4, pancreatitis; and 2, diabetes mellitus. The principal applications of radiomics were differential diagnosis between various types of focal pancreatic lesions (n = 19), classification of pancreatic diseases (n = 23), and prediction of prognosis or treatment response (n = 30). Second-order texture features were most useful for the purpose of differential diagnosis of diseases of the pancreas (with 100% of studies investigating them found a statistically significant feature), whereas filtered image features were most useful for the purpose of classification of diseases of the pancreas and prediction of diseases of the pancreas (with 100% of studies investigating them found a statistically significant feature). The median radiomics quality score of the included studies was 28%, with the interquartile range of 22% to 36%. The radiomics quality score was significantly correlated with the number of extracted radiomics features (r = 0.52, p < 0.001) and the study sample size (r = 0.34, p = 0.003). CONCLUSIONS: Radiomics of the pancreas holds promise as a quantitative imaging biomarker of both focal pancreatic lesions and diffuse changes of the pancreas. The usefulness of radiomics features may vary depending on the purpose of their application. Standardisation of image acquisition protocols and image pre-processing is warranted prior to considering the use of radiomics of the pancreas in routine clinical practice. KEY POINTS: ⢠Methodologically sound studies on radiomics of the pancreas are characterised by a large sample size and a large number of extracted features. ⢠Optimisation of the radiomics pipeline will increase the clinical utility of mineable pancreas imaging data. ⢠Radiomics of the pancreas is a promising personalised medicine tool in diseases of the pancreas.
Asunto(s)
Procesamiento de Imagen Asistido por Computador , Neoplasias Pancreáticas , Diagnóstico por Imagen , Humanos , Páncreas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , PronósticoRESUMEN
BACKGROUND: It is unknown whether cholecystectomy for acute pancreatitis (AP) affects the risk of post-pancreatitis diabetes mellitus (PPDM). We aimed to investigate the associations between cholecystectomy, recurrent biliary events prior to cholecystectomy, and the risk of PPDM in patients with AP. METHODS: Using New Zealand nationwide data from 2007 to 2016, patients with first admission for AP were identified (n = 10,870). Cholecystectomy was considered as a time-dependent exposure. Timing of cholecystectomy was categorized as same-admission, readmission, and delayed cholecystectomy. Recurrent biliary events prior to cholecystectomy were identified. Multivariable Cox regression analyses were conducted. RESULTS: Among 2147 patients who underwent cholecystectomy, 141 (6.6%) developed PPDM. Overall, cholecystectomy was not significantly associated with the risk of PPDM (adjusted hazard ratio, 1.14; 95% confidence interval, 0.94-1.38). Delayed cholecystectomy was significantly associated with an increased risk of PPDM (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.83). Patients who had 2 or ≥3 recurrent biliary events prior to cholecystectomy were at a significantly increased risk of PPDM. CONCLUSION: Cholecystectomy in general was not associated with the risk of PPDM in patients with AP. Two or more repeated attacks of AP (or other biliary events) were associated with a significantly increased risk of PPDM.
Asunto(s)
Diabetes Mellitus , Pancreatitis , Enfermedad Aguda , Colecistectomía/efectos adversos , Estudios de Cohortes , Humanos , Pancreatitis/diagnóstico , Pancreatitis/epidemiología , Pancreatitis/etiologíaRESUMEN
PURPOSE OF REVIEW: To provide an overview of mediators involved in the pathogenesis of postacute pancreatitis diabetes mellitus. RECENT FINDINGS: The 'holistic prevention of pancreatitis' framework has brought to the fore the sequelae of not only end-stage chronic pancreatitis and extensive pancreatic necrosis but also mild acute pancreatitis. Insights from the DORADO project have provided a wealth of information on the signalling molecules that do and do not affect glucose metabolism in individuals after mild acute pancreatitis and have challenged conventional views of the pathogenesis of postpancreatitis diabetes mellitus. SUMMARY: Growing evidence compels a reconsideration of the dogma that mechanical ß-cell destruction (and the resulting insulin deficiency) is the only underlying mechanism of postpancreatitis diabetes mellitus. Chronic low-grade inflammation, ß-cell compensation, lipolysis, altered secretion of gut hormones, and changes in iron metabolism characterize postacute pancreatitis diabetes mellitus. Some of these are druggable targets that offer novel opportunities to reduce the burden of pancreatitis through tertiary prevention.
Asunto(s)
Diabetes Mellitus , Pancreatitis , Enfermedad Aguda , Humanos , Insulina , Pancreatitis/etiologíaRESUMEN
BACKGROUND: Tobacco smoking and alcohol consumption are established risk factors for diseases of the pancreas. With the recent advances in imaging modalities (such as magnetic resonance (MR) imaging), opportunities have arisen to study pancreas size, in both health and disease. Studies investigating the relationship between tobacco smoking, alcohol consumption, and total pancreas volume (TPV) - a holistic measure of pancreatic exocrine reserve - are lacking. The aim of the present study was to investigate the associations between MR-derived TPV and tobacco smoking/alcohol consumption. METHODS: This cross-sectional study recruited individuals with a history of pancreatitis and healthy controls. A validated questionnaire was used to ascertain current and lifetime tobacco smoking and alcohol consumption. TPV was quantified using MR images by two independent raters. Generalized additive models and linear regression analyses were conducted and adjusted for demographic, metabolic, and pancreatitis-related factors. RESULTS: A total of 107 individuals following pancreatitis and 38 healthy controls were included. There was no statistically significant difference in TPV between any of the tobacco smoking/alcohol consumption categories of individuals following pancreatitis and healthy controls, in both unadjusted and adjusted analyses. In individuals following pancreatitis, multivariate linear regression found no association between TPV and 7 smoking- and alcohol-related variables. Sensitivity analyses constrained to individuals who did not abstain from either smoking or drinking following their first attack of pancreatitis did not yield statistical significance with TPV. In post-hoc analysis, age was significantly inversely associated with TPV in the most adjusted model (pâ¯=â¯0.016). CONCLUSIONS: This is the first study to investigate the association between tobacco smoking, alcohol consumption, and MR-derived TPV following pancreatitis. It appears that age, but not tobacco smoking or alcohol consumption, is associated with a significantly reduced TPV.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Páncreas/patología , Pancreatitis/patología , Fumar Tabaco/efectos adversos , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
OBJECTIVE: Pancreatitis often represents a continuous inflammatory process, from the first episode of acute pancreatitis (FAP) to recurrent acute pancreatitis (RAP) to chronic pancreatitis (CP). Psoas muscle size is a validated surrogate for global skeletal mass, changes in which are associated with inflammation. The objective was to investigate psoas muscle size in individuals following FAP, RAP, and CP, as well as its associations with pro-inflammatory cytokines. METHODS: Individuals following pancreatitis and healthy individuals were recruited. All participants underwent magnetic resonance imaging, from which psoas muscle volume was derived independently by two raters in a blinded fashion. Circulating levels of four major cytokines (interleukin-6, tumour necrosis factor-α, C-C motif chemokine ligand 2, and leptin) were measured. Five linear regression additive models were built to adjust for possible confounders (age, sex, body composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and endocrine and exocrine pancreatic functions). RESULTS: A total of 145 participants were enrolled. A significant downward trend in psoas muscle volume was observed between healthy controls and individuals following FAP, RAP, and CP in all adjusted models (p = 0.047, 0.005, 0.004, and < 0.001). Leptin was significantly associated with psoas muscle volume in all models (ß = - 0.16, p = 0.030 in the most adjusted model). The other studied cytokines were not significantly associated with psoas muscle volume. CONCLUSIONS: Psoas muscle size is significantly reduced along the continuum from FAP to RAP to CP. Leptin appears to be one of the factors implicated in this. Further studies are warranted to investigate the relationship between skeletal muscle and inflammation of the pancreas. KEY POINTS: ⢠First acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis were associated with progressively reduced psoas muscle size. ⢠The findings were independent of age, sex, body fat composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and exocrine and endocrine functions of the pancreas. ⢠The mechanism underlying the observed findings may involve hyperleptinaemia.
Asunto(s)
Imagen por Resonancia Magnética/métodos , Pancreatitis/patología , Músculos Psoas/diagnóstico por imagen , Músculos Psoas/patología , Anciano , Biomarcadores , Estudios Transversales , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Páncreas/patologíaRESUMEN
AIM: To investigate the pancreatic hormone responses to mixed meal test, in particular changes in insulin secretion, insulin sensitivity, and their interrelationship, in individuals with new-onset prediabetes or diabetes after non-necrotizing acute pancreatitis (NODAP) compared with healthy controls. METHODS: Twenty-nine individuals with NODAP and 29 age-and sex-matched healthy controls were recruited. All participants (after fasting for at least 8 h) were given 12 oz. of BOOST drink and blood samples were collected before and after stimulation to measure insulin, C-peptide, glucagon, and pancreatic polypeptide. Indices of insulin sensitivity (HOMA-IS, 1/fasting insulin, Raynaud, and Matsuda) and insulin secretion (HOMA-ß, Stumvoll, insulinogenic index 30' and 60') were calculated. Repeated measures analyses were conducted in the unadjusted and adjusted models. RESULTS: Insulin and C-peptide levels were significantly higher in individuals with NODAP compared with controls during mixed meal test in both the unadjusted (P=0.001 for both) and adjusted (P=0.004 and P=0.006, respectively) models. HOMA-IS (P=0.005), 1/fasting insulin (P=0.018), Raynaud index (P=0.018), and Matsuda index (P=0.021) were significantly lower in individuals with NODAP, whereas HOMA-ß (P=0.028) and Stumvoll index (P=0.013) were significantly higher. Glucagon and pancreatic polypeptide levels did not differ significantly between NODAP and controls during mixed meal test in both the unadjusted (P=0.345 and P=0.206, respectively) and adjusted (P=0.359 and P=0.158, respectively) models. CONCLUSIONS: Decreased insulin sensitivity, ß-cell compensation, and no significant change in postprandial levels of glucagon and pancreatic polypeptide characterize NODAP. The above findings may help develop an evidence-based protocol with a view to optimize control of glucose homeostasis in NODAP.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Pancreatitis , Estado Prediabético , Enfermedad Aguda , Glucemia , Humanos , Insulina , Hormonas Pancreáticas , Pancreatitis/diagnóstico , Pancreatitis/etiología , Estado Prediabético/diagnósticoRESUMEN
Ectopic fat and abdominal adiposity phenotypes have never been studied holistically in individuals after acute pancreatitis (AP). The aim of the study was to investigate phenotypical differences in ectopic fat and abdominal fat between individuals after AP (with and without diabetes) and to determine the role of pancreatitis-related factors. Eighty-four individuals were studied cross-sectionally after a median of 21.5 mo since last episode of AP and were categorized into "diabetes" and "no diabetes" groups. Twenty-eight healthy volunteers were also recruited. With the use of magnetic resonance imaging, intrapancreatic fat percentage, liver fat percentage, visceral fat volume (VFV), subcutaneous fat volume, and visceral-to-subcutaneous (V/S) fat volume ratio were quantified. Analysis of variance was used to investigate the differences in these phenotypes between the groups. All analyses were adjusted for age and sex. Linear regression analysis was used to investigate the association between pancreatitis-related factors and the studied phenotypes. Intrapancreatic fat percentage was significantly higher in the diabetes group (10.2 ± 1.2%) compared with the no diabetes (9.2 ± 1.7%) and healthy volunteers (7.9 ± 1.9%) groups (P < 0.001). VFV was significantly higher in the diabetes (2,715.3 ±1,077.6 cm3) compared with no diabetes (1,983.2 ± 1,092.4 cm3) and healthy volunteer (1,126.2 ± 740.4 cm3) groups (P < 0.001). V/S fat volume ratio was significantly higher in the diabetes (0.97 ± 0.27) compared with no diabetes (0.68 ± 0.42) and healthy volunteer (0.52 ± 0.34) groups (P = 0.001). Biliary AP was associated with significantly higher intrapancreatic fat percentage (ß = 0.67; 95% CI, 0.01, 1.33; P = 0.047). C-reactive protein levels during hospitalization for AP were associated with significantly higher VFV (ß = 3.32; 95% CI, 1.68, 4.96; P < 0.001). In conclusion, individuals with diabetes after AP have higher intrapancreatic fat percentage, VFV, and V/S fat volume ratio. Levels of C-reactive protein during AP are significantly associated with VFV, whereas biliary AP is significantly associated with intrapancreatic fat percentage. NEW & NOTEWORTHY Individuals with diabetes after acute pancreatitis have significantly higher intrapancreatic fat percentage and visceral fat volume compared with individuals without diabetes after acute pancreatitis and healthy controls. C-reactive protein levels during hospitalization for acute pancreatitis and biliary etiology of acute pancreatitis are associated with significantly larger visceral fat and pancreatic fat depots, respectively.