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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.
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Automonitorização da Glicemia , Glicemia , Imageamento por Ressonância Magnética , Pâncreas , Humanos , Feminino , Masculino , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Adulto , Glicemia/análise , Glicemia/metabolismo , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 1/sangue , Tecido Adiposo/diagnóstico por imagem , Monitoramento Contínuo da GlicoseRESUMO
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.
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Cetose , Estado Pré-Diabético , Ácido 3-Hidroxibutírico , Adulto , Colesterol , HDL-Colesterol , LDL-Colesterol , Estudos Cross-Over , Feminino , Humanos , Cetose/diagnóstico , Masculino , Estado Pré-Diabético/diagnóstico , TriglicerídeosRESUMO
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.
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Diabetes Mellitus Tipo 2 , Pancreatite , Estado Pré-Diabético , Doença Aguda , Estudos de Coortes , Citocinas , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Estudos Longitudinais , Pancreatite/metabolismo , Estado Pré-Diabético/complicações , Estado Pré-Diabético/metabolismo , Estudos ProspectivosRESUMO
BACKGROUND: Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. METHODS: We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0-8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. RESULTS: Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. CONCLUSIONS: Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.
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Deficiência de Vitamina D , Adulto , Criança , Pré-Escolar , Haplótipos , Humanos , Prevalência , Estações do Ano , África do Sul , Vitamina D , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologia , Proteína de Ligação a Vitamina D/genética , Adulto JovemRESUMO
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.
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Carboidratos da Dieta/administração & dosagem , Insulina/metabolismo , Pancreatite/patologia , Doença Aguda , Adulto , Idoso , Glicemia , Composição Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/metabolismoRESUMO
BACKGROUND: Iron deficiency (ID) is a major public health burden in African children and accurate prevalence estimates are important for effective nutritional interventions. However, ID may be incorrectly estimated in Africa because most measures of iron status are altered by inflammation and infections such as malaria. Through the current study, we have assessed different approaches to the prediction of iron status and estimated the burden of ID in African children. METHODS: We assayed iron and inflammatory biomarkers in 4853 children aged 0-8 years from Kenya, Uganda, Burkina Faso, South Africa, and The Gambia. We described iron status and its relationship with age, sex, inflammation, and malaria parasitemia. We defined ID using the WHO guideline (ferritin < 12 µg/L or < 30 µg/L in the presence of inflammation in children < 5 years old or < 15 µg/L in children ≥ 5 years old). We compared this with a recently proposed gold standard, which uses regression-correction for ferritin levels based on the relationship between ferritin levels, inflammatory markers, and malaria. We further investigated the utility of other iron biomarkers in predicting ID using the inflammation and malaria regression-corrected estimate as a gold standard. RESULTS: The prevalence of ID was highest at 1 year of age and in male infants. Inflammation and malaria parasitemia were associated with all iron biomarkers, although transferrin saturation was least affected. Overall prevalence of WHO-defined ID was 34% compared to 52% using the inflammation and malaria regression-corrected estimate. This unidentified burden of ID increased with age and was highest in countries with high prevalence of inflammation and malaria, where up to a quarter of iron-deficient children were misclassified as iron replete. Transferrin saturation < 11% most closely predicted the prevalence of ID according to the regression-correction gold standard. CONCLUSIONS: The prevalence of ID is underestimated in African children when defined using the WHO guidelines, especially in malaria-endemic populations, and the use of transferrin saturation may provide a more accurate approach. Further research is needed to identify the most accurate measures for determining the prevalence of ID in sub-Saharan Africa.
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Anemia Ferropriva/epidemiologia , África , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
BACKGROUND: It remains unclear whether improving iron status increases malaria risk, and few studies have looked at the effect of host iron status on subsequent malaria infection. We therefore aimed to determine whether a child's iron status influences their subsequent risk of malaria infection in sub-Saharan Africa. METHODS: We assayed iron and inflammatory biomarkers from community-based cohorts of 1309 Kenyan and 1374 Ugandan children aged 0-7 years and conducted prospective surveillance for episodes of malaria. Poisson regression models were fitted to determine the effect of iron status on the incidence rate ratio (IRR) of malaria using longitudinal data covering a period of 6 months. Models were adjusted for age, sex, parasitemia, inflammation, and study site. RESULTS: At baseline, the prevalence of iron deficiency (ID) was 36.9% and 34.6% in Kenyan and Ugandan children, respectively. ID anemia (IDA) affected 23.6% of Kenyan and 17.6% of Ugandan children. Malaria risk was lower in children with ID (IRR, 0.7; 95% confidence interval [CI], 0.6, 0.8; P < .001) and IDA (IRR, 0.7; 95% CI, 0.6, 0.9; P = .006). Low transferrin saturation (<10%) was similarly associated with lower malaria risk (IRR, 0.8; 95% CI, 0.6, 0.9; P = .016). However, variation in hepcidin, soluble transferrin receptors (sTfR), and hemoglobin/anemia was not associated with altered malaria risk. CONCLUSIONS: ID appears to protect against malaria infection in African children when defined using ferritin and transferrin saturation, but not when defined by hepcidin, sTfR, or hemoglobin. Additional research is required to determine causality. CLINICAL TRIALS REGISTRATION: ISRCTN32849447.
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Ferro/sangue , Malária/epidemiologia , Oligoelementos/sangue , Criança , Pré-Escolar , Monitoramento Epidemiológico , Feminino , Humanos , Lactente , Recém-Nascido , Quênia/epidemiologia , Estudos Longitudinais , Masculino , Estado Nutricional , Prevalência , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Uganda/epidemiologiaRESUMO
Exogenous supplementation with ketone beverages has been shown to reduce plasma glucose levels during acute nutritional ketosis. It remains to be investigated whether growth differentiation factor 15 (GDF-15)-an anorexigenic hormone-is involved in this process. The aim was to investigate the effect of a ketone ester beverage delivering ß-hydroxybutyrate (KEßHB) on plasma levels of GDF-15, as well as assess the influence of eating behaviour on it. The study was a randomised controlled trial (registered at clinicaltrials.gov as NCT03889210). Individuals were given a KEßHB beverage or placebo in a cross-over fashion. Blood samples were collected at baseline, 30, 60, 90, 120, and 150 min after ingestion. Eating behaviour was assessed using the three-factor eating questionnaire. GDF-15 levels were not significantly different (p = 0.503) after the KEßHB beverage compared with the placebo. This finding remained consistent across the cognitive restraint, emotional eating, and uncontrolled eating domains. Changes in the anorexigenic hormone GDF-15, irrespective of eating behaviour, do not appear to play a major role in the glucose-lowering effect of exogenous ketones.
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Ácido 3-Hidroxibutírico , Estudos Cross-Over , Fator 15 de Diferenciação de Crescimento , Cetose , Humanos , Fator 15 de Diferenciação de Crescimento/sangue , Masculino , Cetose/sangue , Adulto , Ácido 3-Hidroxibutírico/sangue , Feminino , Adulto Jovem , Bebidas , Glicemia/metabolismo , Comportamento AlimentarRESUMO
BACKGROUND: With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have been shown to have a glucose-regulating effect. However, whether they play a role in diabetes remission remains poorly understood. AIM: To investigate changes in plasma levels of PGDP in glycaemic responders versus non-responders. METHODS: The study was a randomised placebo-controlled trial comprising 18 adults with prediabetes (registered at www. CLINICALTRIALS: gov as NCT03889210). Following an overnight fast, participants consumed ketone ß-hydroxybutyrate (KEßHB)-supplemented beverage and placebo beverage in crossover manner. Serial blood samples were collected from baseline to 150 min at 30-min intervals. The endpoints were changes in glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, glucagon, and major proglucagon fragment (MPGF). Participants were stratified into the 'responders' and 'non-responders' subgroups based on their glycaemic changes following the ingestion of KEßHB. The area under the curve (AUC) was calculated to estimate the accumulated changes in the studied PGDP and compared using paired-t test between the KEßHB and placebo beverages. RESULTS: Responders had a significantly greater reduction in plasma glucose compared with non-responders following acute ketosis (p < 0.001). The AUC0-150 for oxyntomodulin was significantly lower following the KEßHB beverage compared with the placebo (p = 0.045) in responders, but not in non-responders (p = 0.512). No significant differences in AUCs0-150 were found for GLP-1, glicentin, glucagon, and MPGF in either responders or non-responders. CONCLUSION: Oxyntomodulin is involved in lowering plasma glucose and may play an important role in diabetes remission.
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OBJECTIVE: To comprehensively investigate the associations of pancreas fat content and size with circulating markers of iron metabolism. METHODS: A total of 116 individuals underwent magnetic resonance imaging and spectroscopy on a 3.0 Tesla scanner, exclusively for the purpose of the COSMOS research programme. Intra-pancreatic fat deposition, total pancreas volume, liver fat content, visceral and subcutaneous fat volumes were quantified. Plasma levels of hepcidin and ferritin were measured. Multiple linear regression analysis was conducted, adjusting for body mass index, age, and sex. RESULTS: Total intra-pancreatic fat deposition was inversely associated with hepcidin (ß = -0.54, 95 % confidence interval -1.02 to -0.07) whereas total pancreas volume was not associated with hepcidin (ß = 0.36, 95 % confidence interval -7.12 to 7.84) in the most adjusted model. Neither total intra-pancreatic fat deposition (ß = -0.03, 95 % confidence interval -0.39 to 0.33) nor total pancreas volume (ß = -1.02, 95 % confidence interval -6.67 to 4.63) was associated with ferritin in the most adjusted model. Subcutaneous fat, visceral fat, and liver fat were not associated with hepcidin. Subcutaneous fat was inversely associated with ferritin (ß = -0.06, 95 % CI -0.11 to -0.01) whereas visceral fat (ß = 0.05, 95 % CI -0.01 to 0.14) and liver fat (ß = 0.09, 95 % CI -0.04 to 0.34) were not associated with ferritin in the most adjusted model. CONCLUSIONS: Increased intra-pancreatic fat deposition, but not other fat depots, is associated with reduced circulating levels of hepcidin. Deranged iron metabolism may play a role in the pathogenesis of fatty change of the pancreas.
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Hepcidinas , Pâncreas , Humanos , Pâncreas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Ferritinas , FerroRESUMO
Background: Liver is well recognised as a metabolically active organ. While intra-pancreatic fat deposition (IPFD) is emerging as an important player in the whole-body metabolism, the interplay between the liver and IPFD has been poorly investigated. This study aimed to investigate the associations of liver blood tests and non-invasive tests for hepatic fibrosis with IPFD. Methods: Participants underwent a 3.0 Tesla magnetic resonance imaging to measure IPFD and map liver T1 (longitudinal relaxation time). Four liver tests were done on the same sample of blood. Hepatic fibrosis risk score (BARD) was calculated. Linear regression models were built, accounting for age, sex, visceral-to-subcutaneous fat ratio, and other covariates. Results: A total of 143 individuals were studied. In the most adjusted model, alkaline phosphatase (P < 0.001), alanine aminotransferase (P < 0.001), and γ-glutamyl transferase (P = 0.042) were significantly positively associated with IPFD. The BARD score was not significantly associated with IPFD in the most adjusted model (P = 0.295). T1 relaxation time of the liver was not significantly associated with IPFD in the most adjusted model (P = 0.782). Conclusions: Elevated alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transferase are associated with increased IPFD. Hepatic fibrosis does not appear to be associated with IPFD.
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(1) Background: There is a paucity of markers of iron metabolism in health and disease. The aim was to investigate the associations of iron metabolism with pancreas transverse water proton relaxation rate (R2water) in healthy individuals and people after an attack of pancreatitis. (2) Methods: All participants underwent a 3.0 T magnetic resonance imaging of the abdomen on the same scanner. High-speed T2-corrected multi-echo (HISTO) acquisition at single-voxel magnetic resonance spectroscopy and inline processing were used to quantify pancreas R2water. Habitual dietary intake of iron was determined using the EPIC-Norfolk food frequency questionnaire. Circulating levels of ferritin and hepcidin were measured. Generalised additive models were used, adjusting for age, sex, body mass index, and haemoglobin A1c. (3) Results: A total of 139 individuals (47 healthy individuals, 54 individuals after acute pancreatitis, and 38 individuals after chronic pancreatitis) were included. Total dietary intake of iron was significantly associated with pancreas R2water, consistently in healthy individuals (p < 0.001), individuals after acute pancreatitis (p < 0.001), and individuals after chronic pancreatitis (p < 0.001) across all the statistical models. Ferritin was significantly associated with pancreas R2water, consistently in healthy individuals (p < 0.001), individuals after acute pancreatitis (p < 0.001), and individuals after chronic pancreatitis (p = 0.01) across all adjusted models. Hepcidin was significantly associated with pancreas R2water in individuals after acute pancreatitis (p < 0.001) and individuals after chronic pancreatitis (p = 0.04) in the most adjusted model. (4) Conclusions: Pancreas R2water, corrected for T2, is related to iron metabolism in both health and pancreatitis. This non-invasive marker could be used for automated in vivo identification of intra-pancreatic iron deposition.
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Ferritinas , Pancreatite Crônica , Humanos , Prótons , Hepcidinas , Doença Aguda , Pâncreas , Abdome , FerroRESUMO
SCOPE: The main aim of the present study is to study the effect of acute ketosis on parameters of appetite regulation in prediabetes. METHODS AND RESULTS: This is a randomized controlled trial registered under ClinicalTrials.gov identifier NCT03889210. After an overnight fast, 18 adults with prediabetes are assigned to consume a ketone monoester (d-ß-hydroxybutyrate-(R)-1,3 butanediol) drink and a placebo drink in cross-over fashion. Blood samples are collected every 30 min, from baseline to 150 min. Paired t test is used to compare the total area under the curve (AUC) for the changes in parameters of appetite regulation (acylated ghrelin, peptide YY [PYY], and hunger) following both drinks. Significant elevation in blood ß-hydroxybutyrate from 0.2 to 3.5 mmol L-1 (p < 0.001) is achieved within 30 min. Acute ketosis does not result in statistically significant differences in the AUCs for ghrelin, PYY, and hunger. CONCLUSION: Acute ketosis consistently does not affect both objective and subjective parameters of appetite regulation in prediabetes.
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Cetose , Estado Pré-Diabético , Adulto , Humanos , Regulação do Apetite , Grelina , Ácido 3-Hidroxibutírico , Peptídeo YY , ApetiteRESUMO
After an attack of pancreatitis, individuals may develop metabolic sequelae (eg, new-onset diabetes) and/or pancreatic cancer. These new-onset morbidities are, at least in part, driven by low-grade inflammation. The aim was to study the profiles of cytokines/chemokines in individuals after an attack of pancreatitis. A commercially available panel including 31 cytokines/chemokines was investigated. Random forest classifier and unsupervised hierarchical clustering were applied to study participants (who had no persistent organ failure and did not require ICU admission) according to their cytokine/chemokine profiles. Pancreatitis-related characteristics, detailed body composition (determined using 3.0 T magnetic resonance imaging), markers of glucose, lipid, and iron metabolism, gut and pancreatic hormones, as well as liver and pancreatic enzymes, were compared between clusters. Bootstrap validation was employed. A total of 160 participants, including 107 postpancreatitis individuals (investigated at a median of 18 months after the last attack of pancreatitis) and 53 healthy volunteers, were studied. Twenty-two cytokines/chemokines were significantly different between postpancreatitis and health. Two distinct endotypes of individuals after an attack of pancreatitis were identified-?inflammatory" and ?noninflammatory." Sixteen cytokines/chemokines were significantly higher in the inflammatory endotype compared with the noninflammatory endotype. No cytokine/chemokine was significantly higher in the noninflammatory endotype. The inflammatory endotype was characterized by significantly elevated insulin (P= 0.001), glucose-dependent insulinotropic peptide (P = 0.001), peptide YY (P = 0.017), and ghrelin (P = 0.014). The noninflammatory endotype was characterized by significantly elevated hepcidin (P= 0.016). Pancreatitis-related factors, body composition, and other studied parameters did not differ significantly between the 2 endotypes. Individuals with a similar phenotype and clinical course of pancreatitis have differing cytokine/chemokine profiles after clinical resolution of the disease. People with the inflammatory endotype have distinct changes in the pancreatic and gut hormones known to be involved in the pathogenesis of new-onset morbidities after an attack of pancreatitis.
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Pancreatite , Aprendizado de Máquina não Supervisionado , Humanos , Pancreatite/patologia , Citocinas , Inflamação , Pâncreas/patologiaRESUMO
Background: D-ß-Hydroxybutyrate-(R)-1,3 butanediol - a non-racemic ketone monoester for ingestion - has emerged as an effective way to achieve acute nutritional ketosis. Whether white adipose tissue plays a role in effects of acute nutritional ketosis is largely unknown. Objective: To investigate the effects of acute nutritional ketosis on plasma levels of asprosin and leptin and if they are affected by abdominal fat phenotypes. Methods: The design was a randomised crossover trial. Participants received either the D-ß-hydroxybutyrate-(R)-1,3 butanediol monoester (KEßHB) drink or placebo drink. Blood samples were collected at baseline, 30, 60, 90, 120, and 150 minutes. 3.0 Tesla magnetic resonance imaging was used to measure visceral and subcutaneous fat volumes (VFV and SFV, respectively), intra-hepatic fat deposition (IHFD), and intra-pancreatic fat deposition (IPFD). Results: A total of 18 adults were randomised, with no drop-outs. There were no significant differences in plasma levels of asprosin and leptin (p = 0.808 and p = 0.907, respectively) between the KEßHB and placebo drinks. There was no effect of time, treatment, or interaction between time and treatment on asprosin and leptin. After stratification by the VFV/SFV ratio, IHFD, and IPFD, there were no differences in asprosin and leptin between the KEßHB and placebo drinks. Conclusion: Plasma levels of asprosin and leptin were not significantly affected by acute nutritional ketosis. Abdominal fat phenotypes did not significantly affect circulating levels of the two hormones. White adipose tissue does not appear to play a role in altering hormone levels during acute nutritional ketosis. The clinical trial registry number is NCT03889210 (https://clinicaltrials.gov).
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Cetose , Leptina , Humanos , Ácido 3-Hidroxibutírico , Imageamento por Ressonância Magnética , PâncreasRESUMO
INTRODUCTION: Ectopic fat deposition in the pancreas is involved in the pathogenesis of metabolic sequelae following an attack of pancreatitis. However, its relationship with the exocrine pancreas has never been explored in this setting. The aim was to investigate the associations between intra-pancreatic fat deposition (IPFD), pancreas size, and pancreatic enzymes. METHODS: This cross-sectional study recruited individuals with a history of acute pancreatitis and healthy controls. All participants underwent 3T magnetic resonance imaging, from which IPFD, total pancreas volume (TPV), and pancreas diameters (across the head, body, and tail) were measured independently by 2 raters in a blinded fashion. Circulating levels of pancreatic amylase, pancreatic lipase, and chymotrypsin were measured in a fasted state. A series of linear regression analyses was conducted, accounting for possible confounders. RESULTS: A total of 108 individuals with pancreatitis and 60 healthy controls were studied. There was a statistically significant difference in IPFD (p < 0.001), but not in TPV (p = 0.389), between the groups. In the post-pancreatitis group, IPFD was significantly inversely associated with pancreas tail diameter (ß = -0.736, p = 0.036 in the most adjusted model). In the control group, IPFD was significantly inversely associated with TPV (ß = -3.557, p = 0.026 in the most adjusted model). Levels of pancreatic amylase were significantly directly associated with pancreas tail diameter in the post-pancreatitis group (ß = 3.891, p = 0.042 in the most adjusted model), whereas levels of pancreatic lipase were significantly inversely associated with TPV in the control group (ß = -10.533, p = 0.024 in the most adjusted model). CONCLUSION: Increased IPFD in individuals after an attack of pancreatitis is associated with reduced pancreas tail diameter, which is in turn associated with reduced circulating levels of pancreatic amylase. The relationship between IPFD and the exocrine pancreas warrants further investigations.
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Pancreatite , Doença Aguda , Estudos Transversais , Humanos , Imageamento por Ressonância Magnética/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/complicações , Pancreatite/diagnóstico por imagemRESUMO
Vitamins have many established roles in human health. However, the role of habitual dietary intake of vitamins in glucose homeostasis in individuals after acute pancreatitis (AP) is yet to be elucidated. The aim was to investigate the associations between habitual intake of fat- and water-soluble vitamins/vitamers and markers of glucose metabolism (fasting plasma glucose (FPG), homeostasis model assessment insulin resistance (HOMA-IR) index, and homeostasis model assessment ß-cell function (HOMA-ß)) in individuals after AP. A total of 106 participants after AP were included in this cross-sectional study and were grouped based on glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Habitual intake of seven fat-soluble vitamins/vitamers and seven water-soluble vitamins were determined by the EPIC-Norfolk food frequency questionnaire. Multiple linear regression analyses were conducted using five statistical models built to adjust for covariates (age, sex, daily energy intake, visceral/subcutaneous fat volume ratio, smoking status, daily alcohol intake, aetiology of AP, number of AP episodes, cholecystectomy, and use of antidiabetic medications). In the NODAP group, three fat-soluble vitamins/vitamers (α-carotene, ß-carotene, and total carotene) were significantly associated with HOMA-ß. One water-soluble vitamin (vitamin B3) was also significantly associated with HOMA-ß in the NODAP group. None of the studied vitamins were significantly associated with FPG or HOMA-IR in the NODAP group. Prospective longitudinal studies and randomised controlled trials are now warranted to investigate if the observed associations between vitamin/vitamer intake and NODAP are causal and to unveil the specific mechanisms underlying their involvement with NODAP.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Pancreatite , Estado Pré-Diabético , Doença Aguda , Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Humanos , Pancreatite/metabolismo , Estado Pré-Diabético/metabolismo , Estudos Prospectivos , Vitamina A , Vitaminas , ÁguaRESUMO
OBJECTIVES: Dysregulation of iron homeostasis and exocrine pancreatic dysfunction are linked but remain undefined in individuals with a history of pancreatitis. The objective is to investigate the relationship between iron homeostasis and pancreatic enzymes in individuals after a pancreatitis attack. METHODS: This was a cross-sectional study of adults with a history of pancreatitis. Markers of iron metabolism (hepcidin and ferritin) and pancreatic enzymes (pancreatic amylase, pancreatic lipase, and chymotrypsin) were measured in venous blood. Habitual dietary iron intake data (total, heme, and nonheme iron) were collected. Multivariable linear regression analyses were performed while considering covariates. RESULTS: One hundred and one participants were studied at a median of 18 months after their last pancreatitis attack. Hepcidin was significantly associated with pancreatic amylase (ß coefficient, -6.68; 95% confidence interval, -12.88 to -0.48; P = 0.035) and heme iron intake (ß coefficient, 0.34; 95% confidence interval, 0.08 to 0.60; P = 0.012) in the adjusted model. Hepcidin was not significantly associated with pancreatic lipase or chymotrypsin. Ferritin was not significantly associated with pancreatic enzymes and dietary iron intake. CONCLUSIONS: An iron homeostasis-exocrine pancreas crosstalk exists in individuals after an attack of pancreatitis. The role of iron homeostasis in pancreatitis warrants high-quality purposely-designed studies.
Assuntos
Quimotripsina , Pancreatite , Adulto , Humanos , Ferro da Dieta , Estudos Transversais , Pancreatite/complicações , Ferro , Lipase , Amilases , Homeostase , PâncreasRESUMO
OBJECTIVES: To investigate the factors associated with the circulating levels of oxyntomodulin in healthy individuals and individuals after an episode of acute pancreatitis (AP). METHODS: Blood samples were collected from all participants after an overnight fast and analyzed for 28 biomarkers. Participants also underwent comprehensive body composition analysis on a 3-T magnetic resonance imaging scanner. Regression analyses were done to investigate the associations between oxyntomodulin and the studied factors. RESULTS: The study included 105 individuals who had a primary diagnosis of AP and 58 healthy individuals. Peptide YY (B coefficient, 0.094; 95% confidence interval [95% CI], 0.164-0.123), pancreatic polypeptide (0.048; 95% CI, 0.030-0.066), and leptin (0.394; 95% CI, 0.128-0.661) had significant associations with oxyntomodulin in healthy individuals. Peptide YY was the most prominent factor associated with oxyntomodulin, explaining 60% of its variance in health. Cholecystokinin (0.014; 95% CI, 0.010-0.018), amylin (-0.107; 95% CI, -0.192 to -0.021), and glycated hemoglobin (-0.761; 95% CI, -1.249 to -0.273) had significant associations with oxyntomodulin in individuals after AP. Cholecystokinin was the most prominent factor associated with oxyntomodulin, explaining 44% of its variance after AP. CONCLUSIONS: Factors affecting the circulating levels of oxyntomodulin are different in health and after AP. These insights will enable the determination of populations that benefit from oxyntomodulin therapeutics in the future.
Assuntos
Oxintomodulina , Pancreatite , Humanos , Pancreatite/diagnóstico , Peptídeo YY , Doença Aguda , ColecistocininaRESUMO
Vitamin D regulates the master iron hormone hepcidin, and iron in turn alters vitamin D metabolism. Although vitamin D and iron deficiency are highly prevalent globally, little is known about their interactions in Africa. To evaluate associations between vitamin D and iron status we measured markers of iron status, inflammation, malaria parasitemia, and 25-hydroxyvitamin D (25(OH)D) concentrations in 4509 children aged 0.3 months to 8 years living in Kenya, Uganda, Burkina Faso, The Gambia, and South Africa. Prevalence of iron deficiency was 35.1%, and prevalence of vitamin D deficiency was 0.6% and 7.8% as defined by 25(OH)D concentrations of <30 nmol/L and <50 nmol/L, respectively. Children with 25(OH)D concentrations of <50 nmol/L had a 98% increased risk of iron deficiency (OR 1.98 [95% CI 1.52, 2.58]) compared to those with 25(OH)D concentrations >75 nmol/L. 25(OH)D concentrations variably influenced individual markers of iron status. Inflammation interacted with 25(OH)D concentrations to predict ferritin levels. The link between vitamin D and iron status should be considered in strategies to manage these nutrient deficiencies in African children.