Ultrasound-guided percutaneous core needle biopsy of abdominal subcutaneous fat for diagnosing amyloidosis: comparison with bone marrow biopsy.

BACKGROUND: Patients with underlying hematologic malignancy have a higher risk of developing systemic amyloidosis, which worsens their prognosis. Histopathologic detection of amyloid deposits in tissue biopsy specimens is the only diagnostic method for amyloidosis. PURPOSE: To compare the efficacy of ultrasound-guided percutaneous core needle biopsy (USPCB) of abdominal subcutaneous fat with that of bone marrow biopsy (BMB) for diagnosing amyloidosis. MATERIAL AND METHODS: A total of 90 consecutive patients with underlying hematologic disorders who underwent both USPCB of abdominal subcutaneous fat and BMB for suspicion of amyloid deposition during a 10-year period were included in this retrospective study. RESULTS: The sensitivity and specificity of detecting amyloid deposition were 85.7% and 100%, respectively, with USPCB as opposed to 4.8% and 100%, respectively, with BMB, and the sensitivity was significantly higher with USPCB (P < 0.001). The mean number of times USPCB was performed was 3.3. There were no major complications associated with USPCB. The sensitivity of detecting amyloidosis was not different between the 18-G needle group and the 14-G group (100% vs. 80%; P = 0.623). Logistic regression analysis revealed that acquiring more cores from USPCB and thinner fat tissues were statistically significant factors that affected the diagnostic accuracy of USPCB for amyloid detection. CONCLUSION: The sensitivity of amyloid deposition was significantly higher with USPCB of abdominal subcutaneous fat than BMB. Acquiring more cores by multiple biopsies instead of using a larger bore needle and thin subcutaneous fat pad may be a favorable factor for the diagnostic accuracy of USPCB.

Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women.

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS-) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS- and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS.

Proteomic Signatures of Human Visceral and Subcutaneous Adipocytes.

CONTEXT: Adipose tissue distribution is a key factor influencing metabolic health and risk in obesity-associated comorbidities. OBJECTIVE: Here we aim to compare the proteomic profiles of mature adipocytes from different depots. METHODS: Abdominal subcutaneous (SA) and omental visceral adipocytes (VA) were isolated from paired adipose tissue biopsies obtained during bariatric surgery on 19 severely obese women (body mass index > 30 kg/m2) and analyzed using state-of-the-art mass spectrometry. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to investigate proteome signature properties and to examine a possible association of the protein expression with the clinical data. RESULTS: We identified 3686 protein groups and found 1140 differentially expressed proteins (adj. P value < 0.05), of which 576 proteins were upregulated in SA and 564 in VA samples. We provide a global protein profile of abdominal SA and omental VA, present the most differentially expressed pathways and processes distinguishing SA from VA, and correlate them with clinical and body composition data. We show that SA are significantly more active in processes linked to vesicular transport and secretion, and to increased lipid metabolism activity. Conversely, the expression of proteins involved in the mitochondrial energy metabolism and translational or biosynthetic activity is higher in VA. CONCLUSION: Our analysis represents a valuable resource of protein expression profiles in abdominal SA and omental VA, highlighting key differences in their role in obesity.

Changes in abdominal subcutaneous adipose tissue phenotype following menopause is associated with increased visceral fat mass.

Menopause is associated with a redistribution of adipose tissue towards central adiposity, known to cause insulin resistance. In this cross-sectional study of 33 women between 45 and 60 years, we assessed adipose tissue inflammation and morphology in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) across menopause and related this to menopausal differences in adipose tissue distribution and insulin resistance. We collected paired SAT and VAT biopsies from all women and combined this with anthropometric measurements and estimated whole-body insulin sensitivity. We found that menopause was associated with changes in adipose tissue phenotype related to metabolic dysfunction. In SAT, postmenopausal women showed adipocyte hypertrophy, increased inflammation, hypoxia and fibrosis. The postmenopausal changes in SAT was associated with increased visceral fat accumulation. In VAT, menopause was associated with adipocyte hypertrophy, immune cell infiltration and fibrosis. The postmenopausal changes in VAT phenotype was associated with decreased insulin sensitivity. Based on these findings we suggest, that menopause is associated with changes in adipose tissue phenotype related to metabolic dysfunction in both SAT and VAT. Whereas increased SAT inflammation in the context of menopause is associated with VAT accumulation, VAT morphology is related to insulin resistance.

Superficial vs Deep Subcutaneous Adipose Tissue: Sex-Specific Associations With Hepatic Steatosis and Metabolic Traits.

CONTEXT: Subcutaneous adipose tissue (SAT) is not homogeneous, as the fascia scarpa separates the deep SAT (dSAT) from the superficial SAT (sSAT). OBJECTIVE: The aim of this study is to evaluate the sex-specific associations of sSAT and dSAT with hepatic steatosis and metabolic syndrome in overweight individuals. METHODS: We recruited 285 individuals with a body mass index (BMI) greater than or equal to 27 and aged 55 to 81 years. Abdominal magnetic resonance imaging was performed around level L4 to L5 to measure visceral adipose tissue (VAT), dSAT, and sSAT volumes. The amount of hepatic fat was quantified by MR spectroscopy. RESULTS: Men had significantly higher volumes of VAT (122.6 cm3 vs 98.7 cm3, P < .001) and had only half the volume of sSAT compared to women adjusted for BMI (50.3 cm3 in men vs 97.0 cm3 in women, P < .001). dSAT correlated significantly with hepatic fat content in univariate analysis (standardized ß = .190, P < .05), while VAT correlated significantly with hepatic steatosis in a multivariate model, adjusted for age, alcohol use, and other abdominal fat compartments (standardized ß = .184, P = .037). Moreover, dSAT in men correlated negatively with HDL cholesterol (standardized ß = -0.165, P = .038) in multivariate analyses. In women with a BMI between 30 and 40, in a multivariate model adjusted for age, alcohol use, and other abdominal fat compartments, VAT correlated positively (standardized ß = -.404, P = .003), and sSAT negatively (standardized ß = -.300, P = .04) with hepatic fat content. CONCLUSION: In men, dSAT is associated with hepatic steatosis and adverse metabolic traits, such as lower HDL cholesterol levels, whereas in women with obesity sSAT shows a beneficial relation with respect to hepatic fat content.

The value of sex-specific abdominal visceral fat as measured via CT as a predictor of clear renal cell carcinoma T stage.

Although much is known about how adipose tissue affects the development of clear cell renal carcinoma (ccRCC), little information is available for the utility of sex-specific abdominal visceral fat composition as a predictor of clear cell renal carcinoma (ccRCC) T stage. We conducted CT-based sex-specific abdominal fat measurements in ccRCC patients to assess whether VFA distribution could predict the ccRCC T stage. In total, 253 patients (182 males and 71 females) from our hospital with pathologically confirmed ccRCC (178 low T-stage and 75 high T-stage) were retrospectively reviewed for the present study. Computed tomography (CT) scans were assessed using ImageJ to differentiate between the visceral and subcutaneous fat areas (VFA and SFA), after which the relative VFA (rVFA) and total fat area (TFA) were computed. The relationships between these fat area-related variables, patient age, sex, and BMI, and ccRCC T stage were then evaluated through univariate and multivariate logistic regression analysis to clarify the association between general or sex-specific abdominal visceral fat and T stage. Following adjustment for age, males with high T stage ccRCC exhibited an increased rVFA as compared to males with low T stage ccRCC, with the same relationship being observed among females. This association between rVFA and high T stage was confirmed through both univariate and multivariate models. As thus, sex-specific visceral fat composition is a reliable independent predictor that can identify both male and female patients with high T stage ccRCC.

Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity.

White adipose tissue (WAT) is an essential regulator of energy storage and systemic metabolic homeostasis. Regulatory networks consisting of immune and structural cells are necessary to maintain WAT metabolism, which can become impaired during obesity in mammals. Using single-cell transcriptomics and flow cytometry, we unveil a large-scale comprehensive cellular census of the stromal vascular fraction of healthy lean and obese human WAT. We report new subsets and developmental trajectories of adipose-resident innate lymphoid cells, dendritic cells and monocyte-derived macrophage populations that accumulate in obese WAT. Analysis of cell-cell ligand-receptor interactions and obesity-enriched signaling pathways revealed a switch from immunoregulatory mechanisms in lean WAT to inflammatory networks in obese WAT. These results provide a detailed and unbiased cellular landscape of homeostatic and inflammatory circuits in healthy human WAT.

Abdominal subcutaneous fat quantification in obese patients from limited field-of-view MRI data.

Different types of adipose tissue can be accurately localized and quantified by tomographic imaging techniques (MRI or CT). One common shortcoming for the abdominal subcutaneous adipose tissue (ASAT) of obese subjects is the technically restricted imaging field of view (FOV). This work derives equations for the conversion between six surrogate measures and fully segmented ASAT volume and discusses the predictive power of these image-based quantities. Clinical (gender, age, anthropometry) and MRI data (1.5 T, two-point Dixon sequence) of 193 overweight and obese patients (116 female, 77 male) from a single research center for obesity were analyzed retrospectively. Six surrogate measures of fully segmented ASAT volume (VASAT) were considered: two simple ASAT lengths, two partial areas (Ap-FH, Ap-ASIS) and two partial volumes (Vp-FH, Vp-ASIS) limited by either the femoral heads (FH) or the anterior superior iliac spine (ASIS). Least-squares regression between each measure and VASAT provided slope and intercept for the computation of estimated ASAT volumes (V~ASAT). Goodness of fit was evaluated by coefficient of determination (R2) and standard deviation of percent differences (sd%) between V~ASAT and VASAT. Best agreement was observed for partial volume Vp-FH (sd% = 14.4% and R2 = 0.78), followed by Vp-ASIS (sd% = 18.1% and R2 = 0.69) and AWFASIS (sd% = 23.9% and R2 = 0.54), with minor gender differences only. Other estimates from simple lengths and partial areas were moderate only (sd% > 23.0% and R2 < 0.50). Gender differences in R2 generally ranged between 0.02 (dven) and 0.29 (Ap-FH). The common FOV restriction for MRI volumetry of ASAT in obese subjects can best be overcome by estimating VASAT from Vp-FH using the equation derived here. The very simple AWFASIS can be used with reservation.

A Human Randomized Controlled Trial Comparing Metabolic Responses to Single and Repeated Hypoglycemia in Type 1 Diabetes.

AIMS: Hypoglycemia hinders optimal glycemic management in type 1 diabetes (T1D). Long diabetes duration and hypoglycemia impair hormonal counter-regulatory responses to hypoglycemia. Our study was designed to test whether (1) the metabolic responses and insulin sensitivity are impaired, and (2) whether they are affected by short-lived antecedent hypoglycemia in participants with T1D. MATERIALS AND METHODS: In a randomized, crossover, 2x2 factorial design, 9 male participants with T1D and 9 comparable control participants underwent 30 minutes of hypoglycemia (p-glucose < 2.9 mmol/L) followed by a euglycemic clamp on 2 separate interventions: with and without 30 minutes of hypoglycemia the day before the study day. RESULTS: During both interventions insulin sensitivity was consistently lower, while counter-regulatory hormones were reduced, with 75% lower glucagon and 50% lower epinephrine during hypoglycemia in participants with T1D, who also displayed 40% lower lactate and 5- to 10-fold increased ketone body concentrations following hypoglycemia, whereas palmitate and glucose turnover, forearm glucose uptake, and substrate oxidation did not differ between the groups. In participants with T1D, adipose tissue phosphatase and tensin homolog (PTEN) content, hormone-sensitive lipase (HSL) phosphorylation, and muscle glucose transporter type 4 (GLUT4) content were decreased compared with controls. And antecedent hypoglycemic episodes lasting 30 minutes did not affect counter-regulation or insulin sensitivity. CONCLUSIONS: Participants with T1D displayed insulin resistance and impaired hormonal counter-regulation during hypoglycemia, whereas glucose and fatty acid fluxes were intact and ketogenic responses were amplified. We observed subtle alterations of intracellular signaling and no effect of short-lived antecedent hypoglycemia on subsequent counter-regulation. This plausibly reflects the presence of insulin resistance and implies that T1D is a condition with defective hormonal but preserved metabolic responsiveness to short-lived hypoglycemia.

Interesting case of an abdominal wall Merkel cell carcinoma highlighting the importance of developing an Australian clinical practice guideline.

A 66-year-old Australian male farmer was referred for management of an asymptomatic, rapidly expanding, anterior abdominal wall mass. It was firm and well circumscribed. There were no overlying skin changes, constitutional symptoms or weight loss. His medical history included small bowel obstruction and resection from a Meckel's diverticulitis and a 40-pack-year smoking history. Core biopsy was suggestive of a neuroendocrine tumour and Gallium-68-Dodecane-Tetraacetic-Acid (68GaTate) positron emission tomography revealed an avid solitary lesion confined to the subcutaneous space in the left anterior abdominal wall. Wide local excision was performed, and histopathology revealed Merkel cell carcinoma (MCC). Although classically regarded as a primary cutaneous neuroendocrine tumour, MCC may originate from the subcutaneous fat without obvious skin involvement. Older patients with asymptomatic, rapidly enlarging lesions, particularly if immunosuppressed, with significant ultraviolet sunlight exposure, should raise a high index of suspicion for MCC. Like melanoma, non-metastatic MCC should be treated aggressively for best prognosis.

The Transcriptomic Evidence on the Role of Abdominal Visceral vs. Subcutaneous Adipose Tissue in the Pathophysiology of Diabetes in Asian Indians Indicates the Involvement of Both.

The roles of abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) in the molecular pathogenesis type-2 diabetics (T2D) among Asian Indians showing a "thin fat" phenotype largely remains obscure. In this study, we generated transcription profiles in biopsies of these adipose depots obtained during surgery in 19 diabetics (M: F ratio, 8:11) and 16 (M: F ratio 5:11) age- and BMI-matched non-diabetics. Gene set enrichment analysis (GSEA) was used for comparing transcription profile and showed that 19 gene sets, enriching inflammation and immune system-related pathways, were upregulated in diabetics with F.D.R. <25% and >25%, respectively, in VAT and SAT. Moreover, 13 out of the 19 significantly enriched pathways in VAT were among the top 20 pathways in SAT. On comparison of VAT vs. SAT among diabetics, none of the gene sets were found significant at F.D.R. <25%. The Weighted Gene Correlation Analysis (WGCNA) analysis of the correlation between measures of average gene expression and overall connectivity between VAT and SAT was significantly positive. Several modules of co-expressed genes in both the depots showed a bidirectional correlation with various diabetes-related intermediate phenotypic traits. They enriched several diabetes pathogenicity marker pathways, such as inflammation, adipogenesis, etc. It is concluded that, in Asian Indians, diabetes pathology inflicts similar molecular alternations in VAT and SAT, which are more intense in the former. Both adipose depots possibly play a role in the pathophysiology of T2D, and whether it is protective or pathogenic also depends on the nature of modules of co-expressed genes contained in them.

Cathepsin gene expression in abdominal subcutaneous adipose tissue of obese/overweight humans.

Cathepsin L1 (CTSL1) and B (CTSB) are lysosomal proteases, of which the expression and activity are impaired in adipose tissue (AT) of obese rodents, indicating AT lysosomal dysfunction. Here we assess the relation between abdominal subcutaneous AT (SCAT) CTSL1 and CTSB gene expression (qRT-PCR), body composition and tissue-specific insulin resistance in 77 overweight/obese (BMI: 225.6-38.6 kg/m2) well phenotyped men and women (61 M/16 F). A two-step hyperinsulinemic-euglycemic clamp was performed to assess AT, hepatic and skeletal muscle insulin sensitivity. Our data show that reduced CTSB expression is associated with markers of insulin resistance (standardized ß = -0.561, p < 0.001), independent of adiposity, while CTSL1 expression is only associated with markers of body composition. Our data suggest the presence of lysosomal dysfunction in SCAT of obese humans with an impaired glucose homoeostasis. However, this needs to be investigated in more detail in future mechanistic studies.

Electrochemolipolysis of Human Adipose Tissue.

Importance: Body fat contouring procedures have increasingly grown in popularity over the years. As such, there is a need for inexpensive, minimally invasive, and simple fat reduction/contouring technique. Objective: To examine the acid-base and histological changes in ex vivo human adipose tissue after electrochemolipolysis (ECL). Design, Setting, and Participants: Panniculus tissue specimens obtained after abdominoplasty procedures were tumesced with normal saline. Two platinum needle electrodes were inserted into each sample and connected to a DC power supply. Voltage (3-6 V) was varied and applied for 5 min. Specimens were sectioned through a sagittal midline across both electrode insertion sites and immediately stained with pH-sensitive dye. A numerical algorithm was used to calculate the area of the dye color change for each dosimetry pair. Samples were also evaluated utilizing light microscopy (hematoxylin and eosin). An ex vivo human adipose tissue model was used for evaluating the effects of ECL. Results: Acidic and basic pH was appreciated surrounding the anode and cathode insertion sites, respectively. The effect was spatially localized and dose dependent. Statistical analysis of these data showed no significant difference between the mean area of the pH disturbance generated at the anode compared with the cathode at 3 V for 5 min (6.04 mm2 vs. 2.95 mm2, p = 0.40, 95% CI -4.8 to 11). A significantly greater area of pH disruption was generated at the cathode versus the anode in groups 4 V for 5 min (14.7 mm2 vs. 5.00 mm2, p = 0.032, 95% CI 0.93-19), 5 V for 5 min (15.5 mm2 vs. 6.72 mm2, p = 0.019, 95% CI 1.6-16), and 6 V for 5 min (22.5 mm2 vs. 10.0 mm2, p = 0.047, 95% CI 0.22-25). Acute structural changes in adipocytes were observed in all specimens. Vascular damage with adjacent adipocyte necrosis was prominent at the cathode site in group 6 V for 5 min. Conclusions and Relevance: ECL at the studied dosimetry parameters induced acid and base changes in human adipose tissue, suggesting its potential use in nonsurgical fat reduction as an ultralow cost alternative to current lipolytic devices and pharmaceuticals. Level of Evidence: NA.

The Association of Abdominal Adiposity With Mortality in Patients With Stage I-III Colorectal Cancer.

BACKGROUND: The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancer patients, and such associations may vary by patient sex. METHODS: This cohort included 3262 stage I-III colorectal cancer patients. Visceral and subcutaneous adipose tissues were quantified using computed tomography. The primary endpoint was all-cause mortality. Restricted cubic splines estimated statistical associations with two-sided P values. RESULTS: Visceral adipose tissue was prognostic of mortality in a reverse L-shaped pattern (nonlinear P = .02); risk was flat to a threshold (∼260 cm2) then increased linearly. Subcutaneous adipose tissue was prognostic of mortality in a J-shaped pattern (nonlinear P < .001); risk was higher at extreme (<50 cm2) but lower at intermediate values (>50 to ≤560 cm2). Patient sex modified the prognostic associations between visceral adipose tissue (Pinteraction = .049) and subcutaneous adipose tissue (Pinteraction = .04) with mortality. Among men, visceral adiposity was associated with mortality in a J-shaped pattern (nonlinear P = .003), whereas among women, visceral adiposity was associated with mortality in a linear pattern (linear P = .008). Among men, subcutaneous adiposity was associated with mortality in an L-shaped pattern (nonlinear P = .01), whereas among women, subcutaneous adiposity was associated with mortality in a J-shaped pattern (nonlinear P < .001). CONCLUSIONS: Visceral and subcutaneous adipose tissue were prognostic of mortality in patients with colorectal cancer; the shape of these associations were often nonlinear and varied by patient sex. These results offer insight into the potential biological mechanisms that link obesity with clinical outcomes in patients with cancer, suggesting that the dysregulated deposition of excess adiposity is prognostic of mortality.

Paradoxical adipose hyperplasia after noninvasive radiofrequency treatment: A novel report and review.

The past decade has experienced a surge in the frequency of nonsurgical procedures, including injectables, skin rejuvenation, and nonsurgical fat reduction. Nonsurgical fat reduction methods include cryolipolysis (Coolsculpting), ultrasound (Vaser Shape), laser (Liposonix), and radiofrequency (Vanquish). These methods generally produce good results, with cryolipolysis gaining much popularity over the past few years. Multiple reports of paradoxical adipose hyperplasia have been reported with Coolsculpting, with an incidence of 0.025% to 1%. This entity has never been reported with other methods of nonsurgical fat reduction, including noninvasive radiofrequency (Vanquish). We present a case of paradoxical adipose hyperplasia in a 57-year-old male following treatment with noninvasive radiofrequency (Vanquish) to the abdomen. He was treated with power-assisted liposuction to the abdomen and flanks. This is the first case in the literature of paradoxical adipose hyperplasia in a patient treated with this form of noninvasive fat reduction.

Histological Analysis of the Effect of ATX-101 (Deoxycholic Acid Injection) on Subcutaneous Fat: Results From a Phase 1 Open-Label Study.

BACKGROUND: ATX-101 is approved for submental fat reduction. OBJECTIVE: To characterize the histological effect of ATX-101 injection into subcutaneous fat. METHODS: This Phase 1 open-label study enrolled 14 adults to receive injections of ATX-101 into abdominal fat at varying concentrations (0.5%, 1.0%, 2.0%, or 4.0%), volumes (0.2 or 0.4 mL), spacing (0.7, 1.0, or 1.5 cm), and time points before scheduled abdominoplasty (1, 3, 7, or 28 days). During abdominoplasty, tissue was excised and preserved for histology. RESULTS: All injection paradigms resulted in histological changes confined to the subcutaneous layer, which were more prominent at higher concentrations and independent of volume and spacing. Key features at Day 1 after injection were adipocytolysis, blood vessel injury, neutrophilic inflammation, and lysis of locally present neutrophils. At Day 3, inflammation was reduced versus Day 1, and hemorrhage and lipid lake formation (at higher concentrations) were observed. Day 7 samples exhibited prominent adipocytolysis, mild inflammation, lipid-laden macrophages in the septae, and repair of vascular injury. At Day 28, inflammation was largely resolved and prominent features were septal thickening, neovascularization, and atrophy of fat lobules. CONCLUSION: Subcutaneous injection of ATX-101 induces adipocytolysis and local inflammation with septal thickening and resolution of inflammation by 28 days after injection.

Expansion and Impaired Mitochondrial Efficiency of Deep Subcutaneous Adipose Tissue in Recent-Onset Type 2 Diabetes.

CONTEXT/OBJECTIVE: Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D. DESIGN/PATIENTS: Male patients with recently-diagnosed T2D and healthy male controls (CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass, and age (n = 14 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry. We assessed mitochondrial efficiency (coupling: state 3/4o; proton leak: state 4o/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging. RESULTS: T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44%, and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (P < 0.01) and AT IS (P < 0.05), 73% and 31% higher HCL (P < 0.05), and DSAT-thickness (P < 0.001), but similar hepatic IS compared with CON. Mitochondrial efficiency was ~22% lower in SSAT and DSAT of T2D patients (P < 0.001) and ~8% lower in SSAT vs DSAT (P < 0.05). In both fat depots, mitochondrial coupling correlated positively with muscle IS and metabolic flexibility (r ≥ 0.40; P < 0.05), proton leak correlated positively (r ≥ 0.51; P < 0.01) and oxidative capacity negatively (r ≤ -0.47; P < 0.05) with fasting free fatty acids (FFA). Metabolic flexibility correlated positively with SAT-oxidative capacity (r ≥ 0.48; P < 0.05) and negatively with DSAT-thickness (r = -0.48; P < 0.05). DSAT-thickness correlated negatively with mitochondrial coupling in both depots (r ≤ -0.50; P < 0.01) and muscle IS (r = -0.59; P < 0.01), positively with FFA during clamp (r = 0.63; P < 0.001) and HCL (r = 0.49; P < 0.01). CONCLUSIONS: Impaired mitochondrial function, insulin resistance, and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver.

Pancreatic fat necrosis in a 10-year-old girl: A case report and review of the literature.

We report here a case of a young girl with pancreatitis and pancreatic fat necrosis (PFN). This condition is rare in the pediatric age group, and its etiopathogenesis is different from disease in adults. Whereas PFN in adults typically results from pancreatitis secondary to pancreatic duct obstruction, alcohol abuse, and pancreatic adenocarcinoma, in children it appears to arise in a setting of systemic disease, often involving a genetic disorder.