Phases of Metabolic and Soft Tissue Changes in Months Preceding a Diagnosis of Pancreatic Ductal Adenocarcinoma

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Factors contributing to the risk of cardiovascular disease reflected by plasma adiponectin: data from the coronary risk factors for atherosclerosis in women (CORA) study

Objective

An inverse association of adiponectin with coronary heart disease (CHD) has been reported, but the results are inconsistent. We used data from the CORA study to investigate into plasma concentrations of adiponectin and factors that may mediate the link to incident CHD.

Design

The CORA study is a population-based case-control study on 200 women with incident CHD and 255 age-matched controls.

Results

Plasma concentrations of adiponectin were significantly lower in women with CHD (p < 0.0001), and in women with BMI ≥25 kg/m² (p < 0.02), even more so with central obesity (WHR ≥0.85), prevalent diabetes or insulin resistance (HOMA-IR ≥3.8), or low HDL-cholesterol (<50 mg/dl), and in smokers (each p < 0.0001). Adiponectin also correlated with intake of fruit and vegetables, meat and sausage and alcohol as dietary markers of cardiovascular risk. Strikingly, the trend towards lower adiponectin concentrations with increasing BMI or waist circumference was less marked than the difference of adiponectin between CHD cases and controls. In a logistic regression model the odds ratio of adiponectin of 0.943 per 1 μg/ml (CI 0.919-0.968, p < 0.0001) for risk of CHD was progressively reduced by elevated WHR, obesity-related risk factors, smoking, and dietary parameters.

Conclusions

Plasma adiponectin indicates protection from CHD in women that is attenuated by combined effects of central obesity and dependent risk factors, parameters of nutrition and smoking. Thus, the impact of adiponectin goes beyond its relation to central adiposity, but may also reflect independent effects of lifestyle.     

Differences in vitamin D concentration between metabolically healthy and unhealthy obese adults: Associations with inflammatory and cardiometabolic markers in 4391 subjects

AimThis study aimed to compare concentrations of serum 25-hydroxy vitamin D and inflammatory markers in metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO), and to determine whether the relationship between vitamin D levels and both cardiometabolic and inflammatory markers differs between MHO and MUO.MethodsThis cross-sectional study comprised 4391 obese subjects aged > 18 years. A panel of cardiometabolic and inflammatory markers, including anthropometric variables, glycaemic indices, lipid profiles, liver enzymes, homocysteine, C-reactive protein (CRP), fibrinogen and serum 25-hydroxy vitamin D levels, was investigated. All cardiometabolic and inflammatory markers in MHO and MUO as well as in vitamin D deficiency were compared.ResultsPrevalence of MHO was 41.9% in our obese subjects using International Diabetes Federation criteria. Considering insulin resistance and inflammation, the prevalence of MHO was 38.4%. Individuals with MHO had significantly higher vitamin D concentrations compared with MUO, and this difference in vitamin D status persisted after accounting for BMI and waist circumference. Subjects with MHO had significantly better metabolic status, lower liver enzymes, lower inflammatory markers and higher serum 25-hydroxy vitamin D than those with MUO. Associations between vitamin D levels and inflammatory and cardiometabolic markers differed according to MHO/MUO status. Among MUO subjects, vitamin D deficiency was associated with higher liver marker and homocysteine levels. Serum vitamin D was negatively associated with fasting plasma glucose and HbA_1c in MHO only.ConclusionSerum 25-hydroxy vitamin D levels were lower in MUO vs MHO, and reduced vitamin D concentrations were more strongly associated with cardiometabolic and inflammatory markers in MUO than in MHO subjects. These findings suggest that a deficiency in vitamin D could be a key component of MUO.     

Walnut-enriched diet reduces fasting non-HDL-cholesterol and apolipoprotein B in healthy Caucasian subjects: A randomized controlled cross-over clinical trial

Background

Walnut consumption is associated with reduced risk of coronary heart disease (CHD).

Objective

We assessed the effect of walnuts on lipid and glucose metabolism, adipokines, inflammation and endothelial function in healthy Caucasian men and postmenopausal women ≥ 50 years old.

Design

Forty subjects (mean ± SEM: age 60 ± 1 years, BMI 24.9 ± 0.6 kg/m²; 30 females) were included in a controlled, cross-over study and randomized to receive first a walnut-enriched (43 g/d) and then a Western-type (control) diet or vice-versa, with each lasting 8 weeks and separated by a 2-week wash-out. At the beginning and end of each diet phase, measurements of fasting values, a mixed meal test and an assessment of postprandial endothelial function (determination of microcirculation by peripheral artery tonometry) were conducted. Area under the curve (AUC), incremental AUC (iAUC) and treatment × time interaction (shape of the curve) were evaluated for postprandial triglycerides, VLDL-triglycerides, chylomicron-triglycerides, glucose and insulin.

Results

Compared with the control diet, the walnut diet significantly reduced non-HDL-cholesterol (walnut vs. control: − 10 ± 3 vs. − 3 ± 2 mg/dL; p = 0.025) and apolipoprotein-B (− 5.0 ± 1.3 vs. − 0.2 ± 1.1 mg/dL; p = 0.009) after adjusting for age, gender, BMI and diet sequence. Total cholesterol showed a trend toward reduction (p = 0.073). Fasting VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and glucose, insulin, HOMA-IR, and HbA1c did not change significantly. Similarly, fasting adipokines, C-reactive protein, biomarkers of endothelial dysfunction, postprandial lipid and glucose metabolism and endothelial function were unaffected.

Conclusion

Daily consumption of 43 g of walnuts for 8 weeks significantly reduced non-HDL-cholesterol and apolipoprotein-B, which may explain in part the epidemiological observation that regular walnut consumption decreases CHD risk.     

Greater impairment of postprandial triacylglycerol than glucose response in metabolic syndrome subjects with fasting hyperglycaemia

Objective

Studies have started to question whether a specific component or combinations of metabolic syndrome (MetS) components may be more important in relation to cardiovascular disease risk. Our aim was to examine the impact of the presence of raised fasting glucose as a MetS component on postprandial lipaemia.

Methods

Men classified with the MetS underwent a sequential test meal investigation, in which blood samples were taken at regular intervals after a test breakfast (t = 0 min) and lunch (t = 330 min). Lipids, glucose and insulin were measured in the fasting and postprandial samples.

Results

MetS subjects with 3 or 4 components were subdivided into those without (n = 34) and with (n = 23) fasting hyperglycaemia (≥ 5.6 mmol/l), irrespective of the combination of components. Fasting lipids and insulin were similar in the two groups, with glucose significantly higher in the men with glucose as a MetS component (P < 0.001). Following the test meals, there were higher maximum concentration (maxC), area under the curve (AUC) and incremental AUC (P ≤ 0.016) for the postprandial triacylglycerol (TAG) response in men with fasting hyperglycaemia. Greater glucose AUC (P < 0.001) and insulin maxC (P = 0.010) were also observed in these individuals after the test meals. Multiple regression analysis revealed fasting glucose to be an important predictor of the postprandial TAG and glucose response.

Conclusion

Our data analysis has revealed a greater impairment of postprandial TAG than glucose response in MetS subjects with raised fasting glucose. The worsening of postprandial lipaemic control may contribute to the greater CVD risk reported in individuals with MetS component combinations which include hyperglycaemia.     

Frequency of insulin resistance in nondiabetic adult Bangladeshi individuals of different obesity phenotypes

Insulin resistance (IR) is the corner stone of metabolic obesity. This cross-sectional analytical study was aimed to find out the frequency of IR in non-diabetic adult individuals of different obesity phenotypes that would help to implement preventive measures to avoid the cardiometabolic catastrophes.MethodsTotal 955 nondiabetic adult individuals were selected and categorized into six metabolic phenotypes by metabolic syndrome criteria in each BMI group (18.5–24.9-normal weight, 25-29.9-overweight, ≥30-obese). From them, metabolically obese normal weight, metabolically obese overweight, metabolically healthy obese and metabolically unhealthy obese were selected as Obesity phenotypes (N = 616).ResultsThe frequency of IR was found to be very high (60.2%) in total nondiabetic adult obese individuals (N = 616). Highest frequency of IR was found in MUO phenotype (76.3%), lowest frequency of IR was found in MONW phenotype (37.1%) and frequency of IR in MOOW and MHO phenotypes found to be identical but significantly (p < 0.0001) less than MUO and significantly (p < 0.0001) more than MONW phenotype. Among the obesity phenotypes, females were more insulin resistant than males (67.5% vs 48.1% respectively, p < 0.05). Frequency of IR found significantly (p < 0.05) more in female than male in all obesity phenotypes except in MUO phenotype where males found to show significantly (p < 0.05) higher frequency than females. Frequency of IR was significantly higher in younger (20–39 yrs) age group than 40–60 yrs age group (63.2% vs 53.5% respectively, p < 0.05).ConclusionIR is alarmingly high (60.2%) in nondiabetic adult obese individuals. Among different obesity phenotypes, it is highest (76.3%) in MUO and lowest (37.1%) in MONW.     

Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: A 4 year retrospective longitudinal study

Objective

Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men.

Materials and Methods

This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method.

Results

During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend < 0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30–2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR = 0.69, 95% confidence interval 0.48–0.99, P for trend = 0.041).

Conclusions

The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects.     

Metabolic syndrome associates with left atrial dysfunction

Background and aims

Obesity and metabolic syndrome (MetS) are risk factors of atrial fibrillation (AF), but limited data exist on their effect on left atrial (LA) function. The aim of the study was to evaluate the effects of cardiac, hepatic and intra-abdominal ectopic fat depots and cardiometabolic risk factors on LA function in non-diabetic male subjects.

Estrogen receptor protein content is different in abdominal than gluteal subcutaneous adipose tissue of overweight-to-obese premenopausal women

Objective

Premenopausal women demonstrate a distinctive gynoid body fat distribution and circulating estrogen status is associated with the maintenance of this adiposity patterning. Estrogen's role in modulation of regional adiposity may occur through estrogen receptors (ERs), which are present in human adipose tissue. The purpose of this study was to determine regional differences in the protein content of ERα, ERβ, and the G protein-coupled estrogen receptor (GPER) between the abdominal (AB) and gluteal (GL) subcutaneous adipose tissue of overweight-to-obese premenopausal women.

Materials/Methods

Biopsies of the subcutaneous AB and GL adipose tissue were performed in 15 premenopausal women (7 Caucasian/8 African American, 25.1 ± 1.8 years, BMI 29.5 ± 0.5 kg/m²). Adipose tissue protein content was measured by western blot analysis and correlation analyses were conducted to assess the relationship between ER protein content and anthropometric indices/body composition measurements.

Results

We found that ERα protein was higher in AB than GL (AB 1.0 ± 0.2 vs GL 0.67 ± 0.1 arbitrary units [AU], P = 0.02), ERβ protein was higher in GL than AB (AB 0.78 ± 0.12 vs GL 1.3 ± 0.2 AU, P = 0.002), ERα/ERβ ratio was higher in AB than GL (AB 1.9 ± 0.4 vs GL 0.58 ± 0.08 AU, P = 0.007), and GPER protein content was similar in AB and GL (P = 0.80) subcutaneous adipose tissue. Waist-to-hip ratio was inversely related to gluteal ERβ (r² = 0.315, P = 0.03) and positively related to gluteal ERα/ERβ ratio (r² = 0.406, P = 0.01).

Conclusions

These results indicate that depot specific ER content may be an important underlying determinant of regional effects of estrogen in upper and lower body adipose tissue of overweight-to-obese premenopausal women.     

High serum levels of C-reactive protein (CRP) predict beneficial decrease of visceral fat in obese females after sleeve gastrectomy

Background & aims

Gender-related differences represent an emerging investigation field to better understand obesity heterogeneity and paradoxically associated cardiovascular (CV) risk. Here, we investigated if high-sensitivity C-reactive protein (hs-CRP) might differently affect adiposity and predict the clinical response to bariatric surgery in obese males and females.

Antenatal antipsychotic exposure induces multigenerational and gender-specific programming of adiposity and glucose tolerance in adult mouse offspring

Second-generation antipsychotics (SGAs) are well known for their metabolic side effects in humans, including obesity and diabetes. These compounds are maintained during pregnancy to prevent the relapse of psychoses, but they readily diffuse across the placenta to the fetus, as documented with the widely-prescribed drug olanzapine (OLZ). However, observational studies have provided conflicting results on the potential impact of SGAs on fetal growth and body weight, and their effects on metabolic regulation in the offspring. For this reason, our study has tested whether antenatal exposure of CD1 mice to OLZ influenced metabolic outcomes in the offspring of the first (F1) and second (F2) generations. In F1 mice, OLZ antenatal treatment caused a decrease in neonatal body weight in both genders, an effect that persisted throughout life only in male animals. Interestingly, F1 female mice also displayed altered glucose homoeostasis. F2 mice, generated by mating normal males with F1 female mice exposed to OLZ during antenatal life, exhibited higher neonatal body weights which persisted only in F2 female animals. This was associated with expansion of fat mass and a concordant pattern of adipose tissue gene expression. Moreover, male and female F2 mice were glucose-intolerant. Thus, our study has demonstrated that antenatal OLZ exposure induces multigenerational and gender-specific programming of glucose tolerance in the offspring mice as adults, and points to the need for careful monitoring of children exposed to SGAs during pregnancy.     

Contribution of 20-year body mass index and waist circumference history to poor cardiometabolic health in overweight/obese and normal weight adults: A cohort study

Background and aimsWe investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW).Methods and resultsParticipants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991–1994, 1997–1999, 2002–2004, 2007–2009, and 2012–2013. Mean age in 2012–2013 was 69.3 years, with a range of 59.7–82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013–2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m²) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96–2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88–6.12). Greater duration was also related to higher risk of MUNW than MHNW.ConclusionBeing overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese.     

Evolution of subcutaneous adipose tissue fibrosis after bariatric surgery

AimObesity is associated with the development of metabolic complications such as insulin resistance (IR). The mechanisms leading to IR remain unclear. This study aimed to investigate the relationship between adipose tissue fibrosis and IR in obese patients before and after bariatric surgery.MethodsThirty-five obese patients awaiting bariatric surgery (12 with type 2 diabetes) were included in the study. Non-diabetic patients were classified as either insulin-sensitive (n = 11) or insulin-resistant (n = 12), based on the Matsuda insulin sensitivity index (ISI_Matsuda). Homoeostasis model assessment (HOMA-IR) was used for longitudinal evaluation of insulin resistance. Fibrosis was quantified by Masson's trichrome staining on microscopy, and mRNA levels of fibrosis-related genes were examined in subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies collected during and 6 months after bariatric surgery (SAT only).ResultsDespite their similar age, body mass index and fat mass, SAT fibrosis was significantly higher in diabetic vs insulin-sensitive patients (P < 0.05), and associated with IR as assessed by both ISI_Matsuda (r = −0.417, P = 0.038) and HOMA-IR (r = 0.464, P = 0.007) at baseline, whereas VAT fibrosis was not. Six months after surgery and significant weight loss, fibrosis levels remained unchanged in SAT, although IR was significantly reduced in all groups (P < 0.0001). No correlation was found between SAT fibrosis and IR after surgery.ConclusionOverall, these results show a significant but, most likely, transient association between SAT fibrosis and IR in obese humans.     

Association between abdominal fat distribution and coronary plaque instability in patients with acute coronary syndrome

Background and aimsThis study aimed to assess possible association of detailed abdominal fat profiles with coronary plaque characteristics in patients with acute coronary syndrome (ACS).Methods and resultsIn 60 patients with ACS, culprit arteries were evaluated at 1-mm intervals (length analyzed: 66 ± 28 mm) by grayscale and integrated backscatter intravascular ultrasound (IB-IVUS) before percutaneous coronary intervention. Standard IVUS indexes (as a volume index: volume/length), plaque components (as percent tissue volume) and fibrous cap thickness (FCT) were assessed by IB-IVUS. Plain abdominal computed tomography was performed to evaluate subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and VAT/SAT ratio. While SAT area only correlated with vessel volume (r = 0.27, p = 0.04), VAT area correlated positively with vessel (r = 0.30, p = 0.02) and plaque (r = 0.33, p = 0.01) volumes and negatively with FCT (r = −0.26, p = 0.049), but not with percent plaque volume and plaque tissue components. In contrast, higher VAT/SAT ratio significantly correlated with higher percent lipid (r = 0.34, p = 0.008) and lower percent fibrous (r = −0.34, p = 0.007) volumes with a trend toward larger percent plaque volume (r = 0.19, p = 0.15), as well as thinner FCT (r = −0.53, p < 0.0001). In the multiple regression analysis, higher VAT/SAT ratio was independently associated with higher percent lipid with lower percent fibrous volumes (p = 0.03 for both) and thinner fibrous cap thickness (p = 0.0001).ConclusionCoronary plaque vulnerability, defined as increased lipid content with thinner fibrous cap thickness, appears to be more related to abnormal abdominal fat distribution, or so-called hidden obesity, compared with visceral or subcutaneous fat amount alone in patients with ACS.