A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC).

BACKGROUND: Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. METHODS AND FINDINGS: The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of <0.05 was considered statistically significant. In multivariable-adjusted conditional logistic regression models with BMI used to define adiposity, compared with metabolically healthy/normal weight individuals, we observed a higher colorectal cancer risk among metabolically unhealthy/normal weight (odds ratio [OR] = 1.59, 95% CI 1.10-2.28) and metabolically unhealthy/overweight (OR = 1.40, 95% CI 1.01-1.94) participants, but not among metabolically healthy/overweight individuals (OR = 0.96, 95% CI 0.65-1.42). Among the overweight individuals, lower colorectal cancer risk was observed for metabolically healthy/overweight individuals compared with metabolically unhealthy/overweight individuals (OR = 0.69, 95% CI 0.49-0.96). These associations were generally consistent when waist circumference was used as the measure of adiposity. To our knowledge, there is no universally accepted clinical definition for using C-peptide level as an indication of hyperinsulinaemia. Therefore, a possible limitation of our analysis was that the classification of individuals as being hyperinsulinaemic-based on their C-peptide level-was arbitrary. However, when we used quartiles or the median of C-peptide, instead of tertiles, as the cut-point of hyperinsulinaemia, a similar pattern of associations was observed. CONCLUSIONS: These results support the idea that individuals with the metabolically healthy/overweight phenotype (with normal insulin levels) are at lower colorectal cancer risk than those with hyperinsulinaemia. The combination of anthropometric measures with metabolic parameters, such as C-peptide, may be useful for defining strata of the population at greater risk of colorectal cancer

Sense of vitality is associated with cardiovascular events in type 2 diabetes independently of traditional risk factors and arterial stiffness

Aims The aim of this study was to determine if single items in the quality of life questionnaire short form 36 (SF36) were associated with cardiovascular events in patients with type 2 diabetes mellitus (T2DM). Methods In 756 T2DM patients (260 women) from the CARDIPP study, nine questions from the domains vitality and well-being in SF36 were analysed. Patients, 55-66 years, were recruited in 2005-2008 and followed up until 31 December 2018 for the incidence of major adverse cardiovascular events (MACE), that is, myocardial infarction, stroke or cardiovascular death. Results Median follow-up time: 11.6 years, during which 119 (16%) MACE occurred. The SF36 items: seldom full of pep (HR 1.2, 95% CI: 1.1-1.4, p = 0.006), seldom a lot of energy (HR 1.3, 95%CI: 1.1-1.5, p &amp;lt; 0.001), worn out (HR 1.2, 95%CI: 1.0-1.4, p = 0.020) and seldom happy (HR 1.2, 95%CI: 1.0-1.4, p = 0.012) were independent risk factors for MACE in separate models, as well as male sex, diabetes duration, HbA(1c), sagittal abdominal diameter and aortic pulse wave velocity. The variables seldom full of pep and seldom a lot of energy remained associated with MACE when conducting separate analyses for sexes. Only seldom a lot of energy remained associated with MACE when all items from SF-36 were comprised in the same model. Conclusions One single question regarding energy levels from SF36 may be used as an independent risk factor for cardiovascular events in T2DM patients in primary care, for both men and women. This item may be included in future risk assessment for use in clinical practice for cardiovascular risk stratification of T2DM patients. Trial registration The study was registered in (NCT 01049737) in 14 January 2010.Funding Agencies|Medical Research Council in Southeast Sweden; Futurum; GE Healthcare; Swedish Heart-Lung Foundation; King Gustaf V and Queen Victoria Freemason Foundation; Swedish Research Council [12661]; County Council of Ostergotland; Linkoping University</p

A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes

Background: In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. less thanbrgreater than less thanbrgreater thanObjective: To study postprandial effects of three diets, during a single day, in NIDDM. less thanbrgreater than less thanbrgreater thanMethods: A low-fat diet (45-56 energy-% from carbohydrates), and a low-carbohydrate diet (16-24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32-35 energy-% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025-1080 kCal in men and 905-984 kCal in women. The test meals were consumed at a diabetes ward under supervision. less thanbrgreater than less thanbrgreater thanResults: Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (pandlt;0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35 +/- 2.2, of Mediterranean-style diet: 8.12 +/- 5.2, p=0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003). less thanbrgreater than less thanbrgreater thanConclusions: The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective

http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-102850 A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes

Background: In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. Objective: To study postprandial effects of three diets, during a single day, in NIDDM. Methods: A low-fat diet (45–56 energy- % from carbohydrates), and a low-carbohydrate diet (16–24 energy- % from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32–35 energy2 % from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025–1080 kCal in men and 905–984 kCal in women. The test meals were consumed at a diabetes ward under supervision. Results: Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (p,0.0005 for both AUC). The insulin-response following th

Education of the primary health care staff based on acceptance and commitment therapy is associated with reduced sick leave in a prospective controlled trial

Background: The use of cognitive behavioral therapy (CBT) to cope with mental distress and pain issues has helped many patients in primary health care in Sweden. However, the effects of CBT to reduce sick leave has not been equally convincing. Acceptance and Commitment Therapy (ACT) is an evolution of traditional CBT and we aimed to study if education based on ACT of the staff rather than the patients could reduce sick leave in primary health care. Methods: This was a prospective trial in 6 primary health care centers in Kalmar (total amount of registered subjects of 28,930) in which the staff (physicians, nurses and therapists) received group-based education according to ACT during 2018 and 2019. The effects were compared with 5 similarly sized control health care centers in the neighboring Region of Jonkoping in which no such education took place. The main aim was to study changes in sick leave in the 6 primary care centers of Kalmar and to keep track of more general trends by studying sick leave also in Jonkoping, letting sick leave in the year 2017 to be the reference period for both areas. Results: The staff at the health care centers in Kalmar reported to having attended a mean of 5.2 +/- 2 educational ACT-sessions with psychiatrist Kadowaki in Kalmar. Sick leave for ICD-10 F43 (reaction to severe stress and related adjustment-disorders) was reduced from a mean value of 28.7 +/- 9.1ongoing sick leaves/month in 2017 to 22.6 +/- 7.0 sick leaves/month in 2018 (-21%, p = 0.033) and to 18.1 +/- 10 sick leaves/month in 2019 (-37%, p = 0.038). The corresponding sick leave for any diagnosis (total sick leave) was reduced from 132 +/- 39 sick leaves/month in 2017 to 118 +/- 38 sick leaves/month in 2018 (-11%, p = 0.056) and to 102 +/- 37 sick leaves/month in 2019 (-21%, p = 0.021). The corresponding sick leave comparisons in the control health centers did not show any significant changes (all p-values &amp;gt;= 0.24). Conclusions: Total monthly mean sick leave was reduced 21% in the health care centers in Kalmar during the second year of the educational ACT intervention of the staff while it was unchanged in Jonkoping. This suggests a significant effect to induce a reduction in long-term sick leave for patients in primary health care in which the staff received education according to ACT. The results of this trial could serve as a basis for a randomized trial in order to ascertain causality.Funding Agencies|Linkoping University</p

Book Reviews

The following books are reviewed: Klaus-Peter Adam, Friedrich Avemarie och Nili Wazana (red.), Law and Narrative in the Bible and in Neighbouring Ancient Cultures (Josef  Forsling) Stephen P. Ahearne-Kroll, Paul A. Holloway och James A. Kelhoffer (red.), Women and Gender in Ancient Religions: Interdisciplinary Approaches (Hanna Stenström) Dale C. Allison, Volker Leppin, Choon-Leong Seow, Hermann Spieckermann, Barry Dov Walfish och Eric Ziolkowski (red.), Encyclopedia of the Bible and Its Reception, v. 3 (Göran Eidevall) Dale C. Allison, Volker Leppin, Choon-Leong Seow, Hermann Spieckermann, Barry Dov Walfish och Eric Ziolkowski (red.), Encyclopedia of the Bible and Its Reception, v. 5 (Mikael Larsson) Joseph L. Angel, Otherworldly and Eschatological Priesthood in the Dead Sea Scrolls (Torleif Elgvin) Eve-Marie Becker och Anders Runesson (red.), Mark and Matthew I: Comparative Readings: Understanding the Earliest Gospels in their First-century Settings (Tobias Hägerland) Bob Becking, Ezra, Nehemiah, and the Construction of Early Jewish Identity (Lena-Sofia Tiemeyer) April D. DeConick, Holy Misogyny: Why the Sex and Gender Conflicts in the Early Church Still Matter (Hanna Stenström)  Daniel R. Driver, Brevard Childs, Biblical Theologian: For the Church’ s One Bible (LarsOlov Eriksson) Göran Eidevall och Blaženka Scheuer (red.), Enigmas and Images: Studies in Honor of Tryggve N. D. Mettinger (Stig Norin) Weston W. Fields, The Dead Sea Scrolls: A Full History (Cecilia Wassén) Miriam Goldstein, Karaite Exegesis in Medieval Jerusalem: The Judeo-Arabic Pentateuch Commentary of Yūsuf ibn Nūḥ and Abū al-Faraj Hārūn (Lena- Sofia Tiemeyer) Leif Hongisto, Experiencing the Apocalypse at the Limits of Alterity (Hanna Stenström) Jan Joosten, The Verbal System of Biblical Hebrew: A New Synthesis Elaborated on the Basis of Classical Prose (Ulf Bergström) Christos Karakolis, Karl-Wilhelm Niebuhr och Sviatoslav Rogalsky (red.), Gospel Images of Jesus Christ in Church Tradition and in Biblical Scholarship (Mikael Sundkvist) Thomas Kazen, Issues of Impurity in Early Judaism (Cecilia Wassén) Chris Keith, Jesus’ Literacy: Scribal Culture and the Teacher from Galilee (Tobias Ålöw) Anthony Le Donne, The Historiographical Jesus: Memory, Typology, and the Son of David (Jennifer Nyström) Kenneth Liljeström (red.), The Early Reception of Paul (Martin Wessbrandt)  Aren M. Maeir, Jodi Magness and Lawrence H. Schiffman (ed.), ‘Go Out and Study the Land’ (Judges 18:2): Archaeological, Historical and Textual Studies in Honor of Hanan Eshel (Torleif Elgvin)  David L. Mathewson, Verbal Aspect in the Book of Revelation: The Function of Greek Verb Tenses in John’s Apocalypse (Jan H. Nylund) Robert K. McIver, Memory, Jesus, and the Synoptic Gospels (Jennifer Nyström) Sun Myung Lyu, Righteousness in the Book of Proverbs (Bo Johnson) Stefan Nordenson, Genom honom skapades allt: En exegetisk studie om Kristi preexistens och medlarfunktion i Nya testamentet (Hanna Stenström) Stefan Nordgaard Svendsen, Allegory Transformed: The Appropriation of Philonic Hermeneutics in the Letter to the Hebrews (Johannes Imberg) Donna Lee Petter, The Book of Ezekiel and Mesopotamian City Laments (Lena-Sofia Tiemeyer) Stanley E. Porter, Jeffrey T. Reed och Matthew Brook O’Donnell, Fundamentals of New Testament Greek (Jan H. Nylund) Stanley E. Porter och Jeffrey T. Reed, Fundamentals of New Testament Greek: Workbook (Jan H. Nylund) Karl Olav Sandnes, The Gospel ‘According to Homer and Virgil’: Cento and Canon (Maria Sturesson)    Tanja Schultheiss, Das Petrusbild im Johannesevangelium (Finn Damgaard)  William A. Tooman, Gog of Magog: Reuse of Scripture and Compositional Technique in Ezekiel 38–39 (Lena-Sofia Tiemeyer) Paul Trebilco, Self-designations and Group Identity in the New Testament (Rikard Roitto) Caroline Vander Stichele och Hugh Pyper (red.), Text, Image, and Otherness in Children’s Bibles: What Is in the Picture? (Mikael Larsson) Patricia Walters, The Assumed Authorial Unity of Luke and Acts: A Reassessment of the Evidence (Carl Johan Berglund) Amanda Witmer, Jesus, the Galilean Exorcist: His Exorcisms in Social and Political Context (Jennifer Nyström

Obesity is associated with coronary artery stenosis independently of metabolic risk factors : The population-based SCAPIS study

BACKGROUND AND AIMS: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. METHODS: In the SCAPIS study (50-65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. RESULTS: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34-1.62; p &lt; 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87-1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. CONCLUSIONS: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS

Plasma fetuin-A concentration, genetic variation in the AHSG gene and risk of colorectal cancer

Fetuin-A, also referred to as α2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 μg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 μg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development. What's new? Fetuin-A is a liver protein associated with insulin resistance, but with no defined role yet in colorectal cancer. In this prospective study, the authors uncover a modest linear association between fetuin-A levels and higher risk of colorectal cancer, but this was only observed in male participants. In addition, no association was observed between fetuin-A variants and colorectal cancer risk in a Mendelian randomization analysis, arguing against a direct role of fetuin-A in colorectal carcinogenesis