Increased Early Postprandial Glucagon Concentrations in Humans With Newly Diagnosed Type 2 Diabetes and Steatotic Liver Disease.

Background: Higher visceral adipose tissue (VAT) volume is associated with greater risk for the development of type 2 diabetes (T2D). Although VAT volume and prevalence of T2D vary by sex and race, differences in VAT volumes that are associated with the identification of individuals with prevalent T2D across these groups has not been fully examined. Objective: Our goal was to determine VAT volume cut points that maximize true positive, true negative, and optimal identification of individuals with T2D according to sex and race. Methods: Data were examined from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a multi-center longitudinal study of the development of cardiovascular risk in black and white men and women ages 18-30 years at baseline. In 2010-2011, the Year 25 exam was performed (43-55 years). VAT (cm 3 ) was quantified by computed tomography based on two 5 mm contiguous slices at the level of the 4 th -5 th lumbar vertebra (n=3,161). T2D was defined based on the presence of fasting plasma glucose ≥126 mg/dL, 2-hour post load blood glucose ≥200 mg/dL, HbA1c ≥6.5% and/or diabetes medication use. Receiver operating characteristic (ROC) curve analysis was used to identify VAT cut points associated with identification of T2D. Results: Prevalence of T2D at the year 25 exam ranged from 8.8% in white women to 17.7% in black men; mean (SD) VAT volume ranged from 113.5 (79.9) cm 3 in white women to 170.2 (80.2) in white men. White men exhibited the highest cut points of VAT volume needed to identify cases of T2D (26-35% higher) and black women exhibited the lowest cut points (4-36% lower) for true positive, true negative, and optimal identification of T2D compared to other race and sex groups (Table 1). Conclusions: Although the utility of VAT volume to identify individuals with T2D is modest [[Unable to Display Character: –]] likely a result of other unaccounted metabolic risk factors [[Unable to Display Character: –]] these cross-sectional findings display race and sex differences in the VAT volume cut points associated with prevalent T2D.

Visceral Adipose Tissue Attacks Beyond the Liver: Esophagogastric Junction as a New Target

Introduction: While the relationship between obesity and cardiovascular disease (CVD) is well-established, mechanisms underlying this relationship are not well elucidated. Hypothesis: Our hypothesis is that visceral adipose tissue (VAT) volume, aortic inflammation and the risk of subsequent cardiovascular events are linked together. Methods: Individuals who underwent 18F-FDG PET/CT imaging were included. VAT volume, subcutaneous adipose tissue (SAT) volume and aortic FDG uptake were measured while blinded to clinical data. Cardiovascular events were adjudicated by independent cardiologists. Thereafter, the relationship between VAT volume and aortic FDG activity and cardiovascular events was evaluated using Cox proportional hazard models. Results: The final analysis included 415 patients with a median age of 55 (P25-P75: 45-65) years and a median BMI of 26.4 (P25- P75: 23.4-30.9) kg/m2. VAT and SAT volume were significantly higher in obese individuals. 32 subjects experienced cardiovascular event during a median follow-up of 4 years. Cox proportional hazard models showed that VAT volume was a associated with cardiovascular events (hazard ratio, HR (95% CI): 1.15 (1.06-1.25, p<0.001). This remained significant after correcting for age, BMI and aortic TBR (p<0.05). SAT was not predictive of cardiovascular events. VAT volume was associated with arterial inflammation (r=0.29, p<0.001, Figure 1). The combination of high aortic inflammation and high VAT volume was associated with significant worse survival (p<0.05). Conclusions: We observed that VAT volume is a predictor of subsequent cardiovascular events. Moreover, our results indicate a link between visceral adipose tissue volume and arterial inflammation, which may explain some of VAT's association with cardiovascular events.

Background: Higher visceral adipose tissue (VAT) volume is associated with greater risk for hypertension (HTN). Although VAT volume and prevalence of HTN vary by sex and race, the differences in VAT volumes associated with identification of individuals with prevalent HTN across these groups is unclear. Objective: To determine VAT volume cut points that maximize true positive, true negative and optimal identification of prevalent HTN and to compare the cut points across sex and race groups. Methods: Data were examined from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a multi-center longitudinal study of the development of cardiovascular risk in black and white men and women ages 18-30 years at baseline. In 2010-11, the Year 25 exam was performed (43-55 years) and VAT volume (cm3) was quantified by computed tomography based on two 5 mm contiguous slices at the level of the 4th-5th lumbar vertebra (n=3,153). HTN was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg and/or anti-hypertension medication use. Receiver operating characteristic (ROC) curve analysis was used to identify VAT volume cut points associated with true positive, true negative and optimal identification of prevalent HTN. Results: Year 25 prevalence of HTN ranged from 18.2% (white women) to 49.4% (black women); mean VAT volume ranged from 113.5 cm3 (white women) to 172.1 cm3 (white men). White males exhibited the highest VAT volumes (22-36% higher) and black women exhibited the lowest VAT volumes (3-50% lower) associated with true positive, true negative and optimal identification of HTN compared to other race/sex groups (Table 1). VAT volumes associated with HTN among black participants were generally lower than those exhibited for whites. Conclusions: Although the utility of VAT alone to identify HTN cases is modest - likely a result of unaccounted HTN confounders - these findings display the distinct race- and sex-specific differences in VAT volumes associated with prevalent HTN in middle age adults.

The aim of the present study was to examine whether the association of waist girth to visceral adipose tissue (AT) accumulation was altered by weight loss in abdominally obese men. We studied 45 dyslipidemic abdominally obese men (45.4 +/- 6.2 years of age; body mass index [BMI], 31.3 +/- 3.0 kg/m(2); waist circumference, 103.4 +/- 7.6 cm; total cholesterol, <6.72 mM; triglycerides, > or =1.7 mM but < or =5.65 mM; high density lipoprotein cholesterol, < or =1.2 mM). Each of them followed nutritional recommendations combined with a prescription of gemfibrozil (1200 mg/d) or a placebo for 1 year. After 6 months, a training exercise program was added at a frequency of four sessions of 60 minutes per week at 50% of maximal oxygen uptake. In response to the 1-year intervention program, men showed significant reductions in body weight, BMI, waist circumference, and in the partial volume of visceral and abdominal subcutaneous AT measured from two abdominal computed tomography scans performed at lumbar vertebra (L)2 to L3 and L4 to L5 levels. No change in waist-to-hip ratio was observed. Changes in visceral AT were strongly correlated with changes in body weight, BMI, and waist circumference (0.83 < r < 0.85; p < 0.001). However, a weak association was noted between waist-to-hip ratio and changes in visceral AT (r = 0.40; p < 0.05). There was no change in slopes or in intercepts before and after treatment in the relationships between volume or area of abdominal AT and anthropometric markers. Despite a greater level of the partial volume of subcutaneous AT than of the partial volume of visceral AT at baseline (p < 0.001), the greater relative reduction in the visceral AT volume in comparison with the subcutaneous AT volume suggested a preferential mobilization of visceral AT with weight loss in these abdominally obese men. The close relationship between changes in the partial volume of visceral AT and changes in cross-sectional areas of visceral AT measured at L2 to L3 (r = 0.94; p < 0.001) or L4 to L5 (r = 0.88; p < 0.001) suggests that a single computed tomography scan performed at L2 to L3 or L4 to L5 could predict changes in the partial volume of visceral AT secondary to weight loss.

Background: Computed tomography (CT) attenuation of abdominal fat as measured by Hounsfield units (HU) is associated with the composition of fat such as adipocyte size, vascularity, and fibrosis and has been associated with varying degrees of cardiometabolic risk. The objective of this study was to determine if fat quality, evaluated by CT attenuation of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), is prospectively associated with incident cardiovascular disease (CVD) and all cause mortality outcomes independent of absolute VAT and SAT volumes. Methods: Participants were drawn from offspring and third-generation cohorts from the multidetector computed tomography sub-study of the Framingham Heart Study (n=3324, 48% women, mean age of 51 years). SAT and VAT volumes were acquired by manually outlining the abdominal muscular wall separating the visceral from the subcutaneous fat depot. The average HU of each depot were recorded. Cardiovascular risk factors were measured using standard definitions. The outcomes of interest were incident CVD, all cause mortality, non-cardiovascular deaths and cancer deaths. Information on cause of death was obtained from death certificates, medical records and family members. Cox proportional hazard models were used to determine the association between VAT and SAT HU and the outcomes of interest. We adjusted for standard CVD risk factor covariates, secondarily for BMI, and then for VAT or SAT volumes. Results: There were a total of 111 incident CVD events, 85 deaths including 69 non-cardiovascular deaths and 45 cancer deaths in up to 23,047 person-years of follow-up. A one standard deviation (SD) increment in VAT attenuation was associated with a multivariable adjusted hazard ratio (HR) for all cause mortality of 1.40 (95% CI 1.12-1.75, p=0.003), which was strengthened after additional adjustment for BMI (HR 1.53, 95% CI 1.21-1.93, p&lt;0.001) and VAT volume (HR 1.99, 95% CI 1.47-2.69, p&lt;0.001). Non-cardiovascular death accounted for the majority of this trend and remained significant in all three models, including after adjustment for VAT volume (HR 1.97, 95% CI 1.42-2.75, p&lt;0.001). More specifically VAT HU was associated with cancer deaths (HR 1.96, 95% CI 1.29-2.98, p=0.001). Conversely, we observed no association between VAT HU and incident CVD in the multivariable model (HR 0.83, 95% CI (0.67, 1.04) p=0.11) or after additional adjustment for BMI or VAT volume. Similar results were found for SAT HU. Conclusions: CT attenuation of both VAT and SAT is associated with all-cause mortality, non-cardiovascular death and cancer death. These associations highlight how indirect indices of fat quality can potentially add to our understanding of the complications of obesity.

We evaluated the associations between metabolic parameters with visceral adipose tissue (VAT) volume in women with prediabetes or type 2 diabetes (T2DM), and we compared the VAT volume with the VAT area. We enrolled women aged > 20 years with prediabetes or T2DM, who underwent oral glucose tolerance test and whose VAT was evaluated using computed tomography (CT) at our institution between 2017 and 2019. All participants underwent unenhanced spiral CT with a 3-mm slice thickness from the level of the diaphragm to the level of the mid-thigh. The two VAT areas were defined as the free drawn area on the levels of the umbilicus and L2 vertebra. The VAT areas were also manually drawn from the level of the diaphragm to the level of the pelvic floor and were used to calculate the VAT volumes by summing all areas with a slice thickness of 3 mm after setting the attenuation values from −45 to −195 Hounsfield Unit. All metabolic characteristics, except blood pressure, were significantly correlated with the VAT volume. The VAT areas measured at the level of the L2 vertebra and umbilicus were correlated with serum triglyceride, high-density lipoprotein cholesterol, and Framingham steatosis index alone. Multivariable regression analyses revealed that the VAT volume was significantly associated with several metabolic parameters. In conclusion, in women with prediabetes and T2DM, the VAT volume acquired from CT-based calculation has more significant correlations with metabolic risk factors compared with the VAT area.

Visceral adipose tissue (VAT) plays an important role in the pathogenesis of insulin resistance (IR), prediabetes and type 2 diabetes. However, VAT volume alone might not be the best marker for insulin resistance and prediabetes or diabetes, as a given VAT volume may impact differently on these metabolic traits based on body height, gender, age and ethnicity. In a cohort of 1295 subjects from the Tübingen Diabetes Family Study (TDFS) and in 9978 subjects from the UK Biobank (UKBB) undergoing magnetic resonance imaging for quantification of VAT volume, total adipose tissue (TAT) in the TDFS, total abdominal adipose tissue (TAAT) in the UKBB, and total lean tissue (TLT), VAT volume and several VAT-indices were investigated for their relationships with insulin resistance and glycemic traits. VAT-related indices were calculated by correcting for body height (VAT/m:VAT/body height; VAT/m2:VAT/(body height)2, and VAT/m3:VAT/(body height)3), TAT (%VAT), TLT (VAT/TLT) and weight (VAT/WEI), with closest equivalents used within the UKBB dataset. Prognostic values of VAT and VAT-related indices for insulin sensitivity, HbA1c levels and prediabetes/diabetes were analyzed for males and females. Males had higher VAT volume and VAT-related indices than females in both cohorts (p < 0.0001) and VAT volume has shown to be a stronger determinant for insulin sensitivity than anthropometric variables. Among the parameters uncorrected VAT and derived indices, VAT/m3 most strongly correlated negatively with insulin sensitivity and positively with HbA1c levels and prediabetes/diabetes in the TDFS (R2 = 0.375/0.305 for females/males for insulin sensitivity, 0.178/0.148 for HbA1c levels vs., e.g., 0.355/0.293 and 0.144/0.133 for VAT, respectively) and positively with HbA1c (R2 = 0.046/0.042) in the UKBB for females and males. Furthermore, VAT/m3 was found to be a significantly better determinant of insulin resistance or prediabetes than uncorrected VAT volume (p < 0.001/0.019 for females/males regarding insulin sensitivity, p < 0.001/< 0.001 for females/males regarding HbA1c). Evaluation of several indices derived from VAT volume identified VAT/m3 to correlate most strongly with insulin sensitivity and glucose metabolism. Thus, VAT/m3 appears to provide better indications of metabolic characteristics (insulin sensitivity and pre-diabetes/diabetes) than VAT volume alone.

A large proportion of HIV-infected patients on antiretroviral medication develop insulin resistance, especially in the context of fat redistribution. This study investigates the interrelationships among fat distribution, hepatic lipid content, and insulin resistance in HIV-infected men. We performed a cross-sectional analysis of baseline data from 23 HIV-infected participants in three prospective clinical studies. Magnetic resonance spectroscopy was used to quantify hepatic lipid concentrations. Magnetic resonance imaging was used to quantify whole-body adipose tissue compartments: that is, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes, as well as the intermuscular adipose tissue (IMAT) subcompartment and the omental-mesenteric adipose tissue (OMAT) and retroperitoneal adipose tissue (RPAT) subcompartments of VAT. The homeostasis model for assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin concentrations. Hepatic lipid content correlated significantly with total VAT (r = 0.62, P = 0.0014), but not with SAT (r = 0.053, P = 0.81). In univariate analysis, hepatic lipid content was associated with the OMAT (r = 0.67, P = 0.0004) and RPAT (r = 0.53, P = 0.009) subcompartments; HOMA-IR correlated with both VAT and hepatic lipid contents (r = 0.61, P = 0.057 and r = 0.68, P = 0.0012, respectively). In stepwise linear regression models, hepatic lipid had the strongest associations with OMAT and with HOMA-IR. Hepatic lipid content is associated with VAT volume, especially the OMAT subcompartment, in HIV-infected men. Hepatic lipid content is associated with insulin resistance in HIV-infected men. Hepatic lipid content might mediate the relationship between VAT and insulin resistance among treated, HIV-infected men.

BackgroundDiets restricted in carbohydrates may be beneficial for diabetes management. However, without reducing energy intake, carbohydrate restriction results in increased protein and fat intake. Understanding how this macronutrient substitution is associated with adipose tissue distribution is important to prevent diabetes progression. Therefore, the aim was to investigate the isocaloric substitution of carbohydrates with fat and protein in relation to subcutaneous (SAT) and visceral adipose tissue (VAT) and hepatic lipid (HL) content in individuals with recent-onset type 1 (T1D) and type 2 diabetes (T2D), accounting for macronutrient quality.MethodsThis cross-sectional analysis includes participants with T1D (n = 137) and T2D (n = 170) from the German Diabetes Study (GDS). Dietary macronutrient intake was derived from dietary information assessed with a validated food frequency questionnaire. SAT and VAT were measured with magnetic resonance (MR) imaging, while HL content with 1H MR spectroscopy. Isocaloric substitution analyses based on multivariable linear regression models were conducted to examine the replacement of total and higher glycemic index (GI) carbohydrates in energy percent (En%) with total fat, monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fatty acids (SFA), and protein in regard to SAT, VAT and HL content.ResultsIn individuals with T1D, substituting carbohydrates with total fat was not associated with SAT, while substituting carbohydrates with protein demonstrated higher SAT [β (95% CI) per 5 En%: 3100 cm3 (25, 6200)]. In individuals with T2D, replacing carbohydrates with total fat or protein showed no association with SAT and VAT. However, substituting carbohydrates with PUFA was associated with lower VAT [-970 cm3 (-1900, -40)] and HL content [-3.3% (-6.9, 0.4)], while replacing carbohydrates with SFA was associated with higher HL content [2.4% (-0.6, 5.4)]. Substituting carbohydrates with protein was associated with lower HL content in individuals with T2D [-2.4% (-4.9, 0.0)], mainly driven by plant-based protein. There were no substantial differences between the replacement of total and higher GI carbohydrates.ConclusionsThe quality of substituted nutrients may play an important role for adipose tissue and HL accumulation in individuals with T2D. Particularly, integrating PUFAs and plant-based proteins into the diet seems beneficial for VAT and HL content.

BackgroundVisceral adiposity is a risk factor for many chronic diseases. Existing methods to quantify visceral adipose tissue volume using computed tomographic (CT) images often use a single slice, are manual, and are time consuming, making them impractical for large population studies. We developed and validated a method to accurately, rapidly, and robustly measure visceral adipose tissue volume using CT images.MethodsIn-house software, Medical Executable for the Efficient and Robust Quantification of Adipose Tissue (MEERQAT), was developed to calculate visceral adipose tissue volume using a series of CT images within a manually identified region of interest. To distinguish visceral and subcutaneous adipose tissue, ellipses are drawn through the rectus abdominis and transverse abdominis using manual and automatic processes. Visceral and subcutaneous adipose tissue volumes are calculated by counting the numbers of voxels corresponding to adipose tissue in the region of interest. MEERQAT’s ellipse interpolation method was validated by comparing visceral adipose volume from 10 patients’ CT scans with corresponding results from manually delineated scans. Accuracy of visceral adipose quantification was tested using a phantom consisting of animal fat and tissues. Robustness of the method was tested by determining intra-observer and inter-observer coefficients of variation (CV).ResultsThe mean difference in visceral adipose tissue volume between manual and elliptical delineation methods was -0.54 ± 4.81%. In the phantom, our measurement differed from the known adipose volume by ≤ 7.5% for all scanning parameters. Mean inter-observer CV for visceral adipose tissue volume was 0.085, and mean intra-observer CV for visceral adipose tissue volume was 0.059.ConclusionsWe have developed and validated a robust method of accurately and quickly determining visceral adipose tissue volume in any defined region of interest using CT imaging.

The correlation between visceral adipose tissue volume (VATV), hepatic proton-density fat fraction (PDFF), and pancreatic PDFF has been previously studied to predict the presence of type 2 diabetes mellitus (T2DM). This study investigated VATV quantitation in patients with T2DM, prediabetes, and normal glucose tolerance (NGT) using MRI to assess the roles of VATV, hepatic, and pancreatic PDFF in predicting the presence of T2DM. Forty-eight patients with a new clinical diagnosis of T2DM (n=15), prediabetes (n=17), or NGT (n=16) were included and underwent abdominal magnetic resonance imaging (MRI) scanning with the iterative decomposition of water and fat with echo asymmetry and least square estimation image quantification (IDEAL-IQ) sequencing. VATV was obtained at the level of the 2nd and 3rd lumbar vertebral bodies (VATV L2 and VATV L3) where the sum of VATV L2 and VATV L3 (total VATV) were computed, respectively. Also, pancreatic and hepatic fat content was quantified by measuring the PDFF. The receiver operating characteristic (ROC) curve and binary logistics regression model analysis were employed to evaluate their ability to predict the presence of T2DM. The VATV L2, VATV L3, and total VATV values of the T2DM group were significantly higher than the prediabetes and NGT groups (P<0.05). There was no statistically significant difference between the values of VATV L2, VATV L3, and total VATV between the prediabetes and NGT groups (P>0.05). The ROC curve showed the areas under the curve for VATV L2, VATV L3, total VATV, hepatic PDFF, and pancreatic PDFF were 0.76, 0.80, 0.80, 0.79, and 0.75, respectively, in predicting the presence of T2DM (P<0.01). The ROC curves of VATV L2, VATV L3, total VATV, hepatic PDFF, and pancreatic PDFF failed to predict the presence of prediabetes and NGT (P>0.05). The binary logistics regression model analysis revealed that only VATV L3 was independently associated with the incidence of T2DM (P=0.01 and OR =1.01). The sensitivity, specificity, and total accuracy were 80.00%, 88.20%, and 84.40%, respectively. Compared with hepatic PDFF, pancreatic PDFF, VAVT L2, and total VATV, VAVT L3 was the better predictor of T2DM.

To evaluate the relationship of abdominal muscle lean tissue and adipose tissue volumes with prediabetes and diabetes. We measured abdominal muscle composition in 3170 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who underwent computed tomography (CT) at Year 25 of follow-up (ages, 43-55 years). Multinomial regression analysis was used to evaluate the associations of CT-measured intermuscular adipose tissue (IMAT), lean muscle tissue (lean) and visceral adipose tissue (VAT) volumes with diabetes at any point during the CARDIA study, newly detected prediabetes, prior history of prediabetes, and normal glucose tolerance. Models were adjusted for potential confounding factors: age, sex, race, height, smoking status, hypertension, hyperlipidaemia, cardiorespiratory fitness and study centre. Higher IMAT, lean and VAT volumes were all separately associated with a higher prevalence of prediabetes and diabetes. Inclusion of VAT volume in models with both IMAT volume and lean volume attenuated the association of IMAT with both prediabetes and diabetes, but higher lean volume retained its association with prediabetes and diabetes. Individuals in the highest IMAT quartile, coupled with VAT in its lower three quartiles, had a higher prevalence of diabetes, but not of prediabetes, than those with both IMAT and VAT in their respective lower three quartiles. Adjusting for cardiorespiratory fitness did not substantially change the findings. Higher IMAT volume was associated with a higher prevalence of diabetes even after adjustment for VAT volume. However, further study is warranted to understand the complicated relationship between abdominal muscle and adipose tissues.

Increased body mass index is associated with an increased risk of venous thrombosis. However, recent data have highlighted that visceral adipose tissue (VAT) volume may be a better marker of cardiometabolic risk. This study aimed to investigate the relationship between VAT volume and venous thromboembolism (VTE) risk and explore whether increased VAT volume is associated with VTE risk. We performed a cross-sectional study using magnetic resonance imaging (MRI) data from the UK Biobank. The association between VTE incidence and VAT measured by MRI from 39 144 UK Biobank patients was analyzed by ridge regression accounting for covariates including age and sex. VAT volume, as measured by MRI, was demonstrated to be associated with an increased risk of VTE (odds ratio [OR], 4.020; 95% CI, 3.752-4.287 per dm3). Moreover, we observed a significant association of VAT volume with VTE risk in both those who were overweight (VAT high-OR, 1.589; 95% CI, 1.317-1.860; VAT medium-OR, 1.303; 95% CI, 1.054-1.552) and those who were obese (VAT high-OR, 3.222; 95% CI, 2.971-3.473). Notably, the strongest association of VAT was observed in those with obesity. These data demonstrate, for the first time, that VAT volume is associated with an increased risk of VTE and, importantly, has a stronger association with VTE risk compared with that of body mass index.

BackgroundPeople with Type 2 Diabetes (T2D) and obesity have ectopic fat deposition and are at increased risk of heart failure with preserved Ejection Fraction (HFpEF). HFpEF is typified by impaired...