Deciphering CT texture features of human visceral fat to evaluate metabolic disorders and surgery-induced weight loss effects.

BACKGROUND: Metabolic syndrome (MetS) is highly related to the excessive accumulation of visceral adipose tissue (VAT). Quantitative measurements of VAT are commonly applied in clinical practice for measurement of metabolic risks; however, it remains largely unknown whether the texture of VAT can evaluate visceral adiposity, stratify MetS and predict surgery-induced weight loss effects. METHODS: 675 Chinese adult volunteers and 63 obese patients (with bariatric surgery) were enrolled. Texture features were extracted from VATs of the computed tomography (CT) scans and machine learning was applied to identify significant imaging biomarkers associated with metabolic-related traits. FINDINGS: Combined with sex, ten VAT texture features achieved areas under the curve (AUCs) of 0.872, 0.888, 0.961, and 0.947 for predicting the prevalence of insulin resistance, MetS, central obesity, and visceral obesity, respectively. A novel imaging biomarker, RunEntropy, was identified to be significantly associated with major metabolic outcomes and a 3.5-year follow-up in 338 volunteers demonstrated its long-term effectiveness. More importantly, the preoperative imaging biomarkers yielded high AUCs and accuracies for estimation of surgery responses, including the percentage of excess weight loss (%EWL) (0.867 and 74.6%), postoperative BMI group (0.930 and 76.1%), postoperative insulin resistance (0.947 and 88.9%), and excess visceral fat loss (the proportion of visceral fat reduced over 50%; 0.928 and 84.1%). INTERPRETATION: This study shows that the texture features of VAT have significant clinical implications in evaluating metabolic disorders and predicting surgery-induced weight loss effects. FUNDING: The complete list of funders can be found in the Acknowledgement section.

Central pontine myelinolysis and the osmotic demyelination syndromes: an open and shut case?

Central pontine myelinolysis and extrapontine myelinolysis are collectively called the osmotic demyelination syndromes. Despite being described in 1959, there are several aspects of the disorder that remain an enigma. Animal models and neuroimaging techniques have allowed us to understand the condition better. From being a universally fatal disorder that was diagnosed post mortem, increased awareness, neuroimaging techniques and supportive care have enabled us to make the diagnosis ante-mortem. This has also led to a significant drop in associated mortality. The aim of this review is to highlight the clinical spectrum, neuroimaging findings, and recent developments.

Metabolic scoring in autoimmune epilepsy-Should APE scores be modified?

OBJECTIVE: We evaluate the potential utility of F-18 FDG-PET in addition to MRI in the diagnostic work-up of patients with autoimmune epilepsy (AE) and propose the inclusion of functional imaging in the antibody prevalence in epilepsy (APE) scoring system. METHODS: This was a retrospective analysis in 60 patients, diagnosed and treated for AE, of whom 40 were antibody negative (presumed AE) and 20 were antibody positive (definitive AE). All patients had undergone a dedicated brain and whole body FDG-PET in the department of Nuclear Medicine. RESULTS: In the antibody negative group, MRI supported a diagnosis of AE in 23 patients. Both MRI and PET were indicative in 12 cases, and standalone PET was positive in 8. While MRI alone was diagnostic in 57% (23/40), the combined yield of both modalities was 77% (31/40). When PET scores were added to assign the APE score in MRI negative cases, average APE score was 5.4. In the antibody positive group, MRI supported the diagnosis of AE in 7 patients. Both MRI and PET were positive in 4 patients and standalone PET was positive in 5 patients. While MRI alone was diagnostic in 35% (7/20), the combined yield of both modalities was 60% (12/20). When PET scores were added to assign the APE score in MRI negative cases, average APE score was 6.1. CONCLUSION: The inclusion of metabolic information from PET distinctly improved (the sensitivity of) APE scores to predict autoimmune origin even in antibody negative cases. A larger prospective study of similar type could justify adoption of FDG-PET into the standard diagnostic procedure.

Validation of Controlled Attenuation Parameter Measured by FibroScan as a Novel Surrogate Marker for the Evaluation of Metabolic Derangement.

Background/Objectives: Renaming non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) suggests a shift of emphasis to the accompanying metabolic disturbance. Controlled attenuation parameter (CAP) measured by FibroScan has been shown to be correlated with hepatic steatosis. We aim to validate its usefulness as a novel surrogate marker for evaluating metabolic derangement. Subjects/Methods: Volunteers were recruited from medical staff at our hospital to undergo CAP measurements. Anthropometrics, CAP, and laboratory assessments for metabolic profiles and insulin resistance were collected. CAP < 238 dB/m denoted no hepatic steatosis, 238 ≤ CAP ≤ 259 dB/m denoted mild, 260 ≤ CAP ≤ 291 dB/m denoted moderate, and CAP > 291 dB/m denoted severe hepatic steatosis according to previous reports. Results: Data of 824 participants were included for analysis. The age was 53.2 ± 15.4 years, body mass index (BMI) was 23.6 ± 3.1 kg/m2, 24.4% were male subjects, and 22.0% met the criteria for metabolic syndrome (MetS). Taking the group with CAP < 238 dB/m as control, subjects with mild, moderate, and severe hepatic steatosis had increased odds of MetS by 3.51-, 3.32-, and 5.12-fold, respectively, after adjusting for multiple confounders (p = 0.020). Metabolic profiles, insulin resistance, and presence of MetS were similar between normal-weight subjects with CAP ≥ 238 dB/m and overweight subjects with CAP < 238 dB/m. Even in subjects with no MetS components, those with CAP ≥ 238 dB/m had higher BMI, waist circumferences, uric acid, triglyceride, white blood cell count, and insulin resistance, whereas lower adiponectin and estimated glomerular filtration rate. Waist circumference [OR 1.11 (1.04, 1.18), p = 0.001] and homeostatic model assessment of insulin resistance (HOMA-IR) [OR 2.39 (1.18, 4.83), p = 0.016] were predictive of hepatic steatosis according to CAP ≥ 238 dB/m. Conclusions: CAP is a convenient, sensitive, and non-invasive indicator for metabolic derangement. Prospective studies are needed to further validate its usefulness as a surrogate marker for the transition of metabolic status over time.

Total-body PET Imaging: A New Frontier for the Assessment of Metabolic Disease and Obesity.

Obesity and associated metabolic syndrome are a global public health issue. Understanding the pathophysiology of this systemic disease is of critical importance for the development of future therapeutic interventions to improve clinical outcomes. The multiorgan nature of the pathophysiology of obesity presents a unique challenge. Total-body PET imaging, either static or dynamic, provides a vital set of tools to study organ crosstalk. The visualization and quantification of tissue metabolic kinetics with total-body PET in health and disease provides essential information to better understand disease physiology and potentially develop diagnostic and therapeutic modalities.

Magnetic resonance imaging patterns of subacute sclerosing panencephalitis may mimic metabolic disorders: clinical, electroencephalographic and imaging features of six cases.

Subacute sclerosing panencephalitis is a rare, devastating neurodegenerative encephalitis whose diagnosis and therapy are still in question. Atypical clinical presentation and heterogeneity of neuroimaging findings that have been initially confused with metabolic disorders have hampered early diagnosis. To describe a series of patients with subacute sclerosing panencephalitis with imaging findings mimicking metabolic disorders. A total of six patients with subacute sclerosing panencephalitis were diagnosed from January 2012 to December 2016 in whom a metabolic disorder was suspected on initial clinical and MRI findings. Detailed laboratory investigation was performed in all patients. All patients presented with atypical neurologic manifestations, including dystonia, syncopal attacks, involuntary limb movements, meaningless speech and ataxia. Magnetic resonance imaging abnormalities included bilateral putaminal, bilateral posterior periventricular white matter and diffuse or splenial corpus callosum involvement which are particularly unusual in SSPE and mostly observed in metabolic disorders. All patients had elevated cerebrospinal fluid Ig G measles antibodies. The diagnosis of subacute sclerosing panencephalitis through clinical and imaging features can be considerably challenging. It is crucial to differentiate it from metabolic disorders, since the management and clinical outcome are different.

IAEA contribution to the development of 64Cu radiopharmaceuticals for theranostic applications.

Copper-64 is a very attractive radioisotope with unique nuclear properties that allow using it as both a diagnostic and therapeutic agent, thus providing an almost ideal example of a theranostic radionuclide. A characteristic of Cu-64 stems from the intrinsic biological nature of copper ions that play a fundamental role in a large number of cellular processes. Cu-64 is a radionuclide that reflects the natural biochemical pathways of Cu-64 ions, therefore, can be exploited for the detection and therapy of certain malignancies and metabolic diseases. Beside these applications of Cu-64 ions, this radionuclide can be also used for radiolabelling bifunctional chelators carrying a variety of pharmacophores for targeting different biological substrates. These include peptide-based substrates and immunoconjugates as well as small-molecule bioactive moieties. Fueled by the growing interest of Member States (MS) belonging to the International Atomic Energy Agency (IAEA) community, a dedicated Coordinated Research Project (CRP) was initiated in 2016, which recruited thirteen participating MS from four continents. Research activities and collaborations between the participating countries allowed for collection of an impressive series of results, particularly on the production, preclinical evaluation and, in a few cases, clinical evaluation of various 64Cu-radiopharmaceuticals that may have potential impact on future development of the field. Since this CRP was finalized at the beginning of 2020, this short review summarizes outcomes, outputs and results of this project with the purpose to propagate to other MS and to the whole scientific community, some of the most recent achievements on this novel class of theranostic 64Cu-pharmaceuticals.

Pearls and Pitfalls of Metabolic Liver Magnetic Resonance Imaging in the Pediatric Population.

Recent advances in magnetic resonance imaging (MRI) technology have moved imaging beyond anatomical assessment to characterization of tissue composition. There are now clinically validated MRI-based quantitative techniques for assessing liver fat, iron, and fibrosis, and MRI is now routinely used in metabolic liver disease evaluation in both pediatric and adult patients. These MRI techniques provide noninvasive quantitation of liver metabolic biomarkers that are increasingly relied upon in the clinical management of pediatric patients with nonalcoholic fatty liver disease, metabolic syndrome, and hemochromatosis and/or hemosiderosis. This article provides a review of the clinical indications and technical parameters for performing metabolic liver MRI in the pediatric population, along with common pearls and pitfalls encountered during its performance.

Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.

Thiamine metabolism dysfunction syndrome (THMD) comprises a group of clinically and genetically heterogeneous encephalopathies with autosomal recessive inheritance. Four genes, SLC19A3, SLC25A19, SLC19A2, and TPK1, are associated with this disorder. This study aimed to explore the clinical, biochemical and molecular characteristics of seven Chinese patients with THMD. Targeted next-generation sequencing of mitochondrial DNA and nuclear DNA was used to identify the causative mutations. The patients presented with subacute encephalopathy between the ages of 1-27 months. Brain magnetic resonance imaging (MRI) revealed abnormalities in the basal ganglia, indicating Leigh syndrome. Urine α-ketoglutarate in five patients was elevated. In four patients, five novel mutations (c.1276_1278delTAC, c.265A > C, c.197T > C, c.850T > C, whole gene deletion) were found in SLC19A3, which is associated with THMD2. In two patients, four novel mutations (c.194C > T, c.454C > A, c.481G > A, and c.550G > C) were identified in SLC25A19, supporting a diagnosis of THMD4. In one patient, two novel mutations (c.395T > C and c.614-1G > A) were detected in TPK1, which is indicative of THMD5. The patients received thiamine, biotin, and symptomatic therapy, upon which six patients demonstrated clinical improvement. Our findings expanded the phenotypic and genotypic spectrum of THMD, with eleven novel mutations identified in seven Chinese patients. Early diagnosis and treatment have a significant impact on prognosis.

Age and sex affect deep learning prediction of cardiometabolic risk factors from retinal images.

Deep neural networks can extract clinical information, such as diabetic retinopathy status and individual characteristics (e.g. age and sex), from retinal images. Here, we report the first study to train deep learning models with retinal images from 3,000 Qatari citizens participating in the Qatar Biobank study. We investigated whether fundus images can predict cardiometabolic risk factors, such as age, sex, blood pressure, smoking status, glycaemic status, total lipid panel, sex steroid hormones and bioimpedance measurements. Additionally, the role of age and sex as mediating factors when predicting cardiometabolic risk factors from fundus images was studied. Predictions at person-level were made by combining information of an optic disc centred and a macula centred image of both eyes with deep learning models using the MobileNet-V2 architecture. An accurate prediction was obtained for age (mean absolute error (MAE): 2.78 years) and sex (area under the curve: 0.97), while an acceptable performance was achieved for systolic blood pressure (MAE: 8.96 mmHg), diastolic blood pressure (MAE: 6.84 mmHg), Haemoglobin A1c (MAE: 0.61%), relative fat mass (MAE: 5.68 units) and testosterone (MAE: 3.76 nmol/L). We discovered that age and sex were mediating factors when predicting cardiometabolic risk factors from fundus images. We have found that deep learning models indirectly predict sex when trained for testosterone. For blood pressure, Haemoglobin A1c and relative fat mass an influence of age and sex was observed. However, achieved performance cannot be fully explained by the influence of age and sex. In conclusion we confirm that age and sex can be predicted reliably from a fundus image and that unique information is stored in the retina that relates to blood pressure, Haemoglobin A1c and relative fat mass. Future research should focus on stratification when predicting person characteristics from a fundus image.

Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease.

Metabolic heart disease (MHD), which is strongly associated with heart failure with preserved ejection fraction, is characterized by reduced mitochondrial energy production and contractile performance. In this study, we tested the hypothesis that an acute increase in ATP synthesis, via short chain fatty acid (butyrate) perfusion, restores contractile function in MHD. Isolated hearts of mice with MHD due to consumption of a high fat high sucrose (HFHS) diet or on a control diet (CD) for 4 months were studied using 31 P NMR spectroscopy to measure high energy phosphates and ATP synthesis rates during increased work demand. At baseline, HFHS hearts had increased ADP and decreased free energy of ATP hydrolysis (ΔG~ATP ), although contractile function was similar between the two groups. At high work demand, the ATP synthesis rate in HFHS hearts was reduced by over 50%. Unlike CD hearts, HFHS hearts did not increase contractile function at high work demand, indicating a lack of contractile reserve. However, acutely supplementing HFHS hearts with 4mM butyrate normalized ATP synthesis, ADP, ΔG~ATP and contractile reserve. Thus, acute reversal of depressed mitochondrial ATP production improves contractile dysfunction in MHD. These findings suggest that energy starvation may be a reversible cause of myocardial dysfunction in MHD, and opens new therapeutic opportunities.

Increased 18F-FDG signal recovery from small physiological structures in digital PET/CT and application to the pituitary gland.

On conventional PET/CT, and under physiological conditions, the volume of the pituitary gland (PG) is small, and its metabolic activity is commonly comparable to the surrounding background level in 18F-FDG imaging. We compared the physiological 18F-FDG uptake of the PG in patients imaged with digital PET (dPET) and with conventional PET (cPET). Additionally, we performed phantom experiments to characterize signal recovery and detectability of small structures. We retrospectively included 10 dPET and 10 cPET patients and measured PG SUVmax, SUVmean and SUVratio (using cerebellum as reference). We imaged a modified NEMA/IEC phantom with both dPET and cPET (background activity 5 kBq/mL, and 3× and 5× higher concentrations in ∅2-20-mm spherical inserts). Mean recovery coefficients (RCmean) and signal-difference-to-noise-ratio (SDNR) were computed to assess lesion detectability. Patients imaged with dPET presented higher PG SUVmax and SUVratio (SUVR) compared to patients imaged with cPET (4.7 ± 2.05 vs. 2.9 ± 0.64, p = 0.004; and 0.62 ± 0.25 vs 0.39 ± 0.09, p = 0.029, respectively), while there was no difference for SUVmean (2.7 ± 1.32 vs 2.1 ± 0.44, p = 0.39). Thus, with a SUV readout scale of 0-5 g/mL, normal PG appeared abnormally hot with dPET, but not with cPET. Phantom evidenced higher RCmean in dPET compared to cPET. For both 3x and 5x measurements, lesion detectability according to size was systematically superior with dPET. In conclusion, patients imaged with dPET presented higher 18F-FDG physiological uptake of the PG as compared to patients imaged with cPET. These findings were supported by phantom experiments demonstrating superior signal recovery and small region detectability with dPET. Awareness of this new "higher" SUV of the normal 18F-FDG uptake of the PG is important to avoid potential pitfalls in image interpretation, notably in oncologic patients treated with immunotherapy, who are at increased risk to develop hypophysitis.

A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism.

BACKGROUND: Manganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity. CASE PRESENTATION: A 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up. CONCLUSION: The syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.

A Hungry Bone Syndrome Predicted by 18F-Fluorocholine PET/CT.

Predicting hungry bone syndrome (HBS) after surgical cure of primary hyperparathyroidism (PHPT) can be challenging. A 57-year-old man diagnosed with PHPT was assessed preoperatively by F-fluorocholine PET/CT. An intense and diffuse tracer uptake of the axial and peripheral skeleton was visualized, in addition to a pathologic uptake suggestive of hyperfunctioning parathyroid gland. After the removal of a parathyroid adenoma, a severe and prolonged HBS requiring high doses of calcium and active metabolites of vitamin D was observed. This observation suggests that intense and diffuse bone uptake on F-fluorocholine PET/CT could be a predictive factor for HBS in patients with PHPT.

Cardiometabolic Risk and Body Composition in Youth With Down Syndrome.

BACKGROUND AND OBJECTIVES: Whether BMI captures adiposity and cardiometabolic risk in Down syndrome (DS), a condition associated with obesity, short stature, and altered body proportions, is not known. We compared cardiometabolic risk measures in youth with DS and typically developing matched controls. METHODS: Youth with (n = 150) and without (n = 103) DS of comparable age (10-20 years), sex, race, ethnicity, and BMI percentile underwent whole-body dual-energy X-ray absorptiometry, fasting glucose, insulin, lipids, lipoprotein particles, inflammatory factors, and when BMI percentile ≥85, an oral glucose tolerance test. RESULTS: Sixty-four percent of youth with DS had BMI percentile ≥85. Among these, no difference in glucose, insulin, or insulin resistance was detected, but prediabetes was more prevalent with DS (26.4% vs 10.3%; P = .025) after adjustment for demographics, pubertal status, and BMI z score (odds ratio = 3.2; P = .026). Among all participants, those with DS had higher low-density lipoprotein cholesterol (median 107 [interquartile range 89-128] vs 88.5 [79-103] mg/dL; P < .00005), triglycerides (89.5 [73-133] vs 71.5 [56-104] mg/dL; P < .00005), non-high-density lipoprotein cholesterol (non-HDL-C; 128 [104-153] vs 107 [92-123] mg/dL; P < .00005), and triglycerides/HDL-C (2.2 [1.6-3.4] vs 1.7 [1.1-2.5] mg/dL; P = .0003) and lower levels of HDL-C (41 [36.5-47] vs 45 [37-53] mg/dL; P = .012). DS youth had higher high-sensitivity C-reactive protein, interleukin-6, small low-density lipoprotein particles (LDL-P), and total LDL-P, but similar LDL-P size. Youth with DS had less visceral fat (VFAT), fat mass, and lean mass for BMI z score, but greater VFAT at higher fat mass. However, VFAT did not fully explain the increased prevalence of dyslipidemia or prediabetes in youth with DS. CONCLUSIONS: Despite similar insulin resistance, youth with DS had greater prevalence of dyslipidemia and prediabetes than typically developing youth, which was not fully explained by VFAT.

Genomics and Radiogenomics in Inherited Neurometabolic Disorders - A Practical Primer for Pediatricians.

Advances in genetics has revolutionised the way we understand, diagnose and manage neurological disorders. Notwithstanding the fact that genetic confirmation has already become standard of care in routine clinical practice, radiological and clinical phenotyping has not diminished in value; in fact it has found an enhanced role in guiding and interpreting genetic test results. Inherited neurometabolic disorders are a prominent group of disorders which are seen commonly in clinical practice and many are potentially treatable. The concept of Radiogenomics is the bridge from phenotype to genotype and the strength of association varies widely across different inherited metabolic diseases. Understanding the strengths and limitations of these correlations forms the basis of success of multidisciplinary approach to diagnose these disorders. In this article authors give a brief overview of the genetic basis of a disease, available genetic tests and the prominent role of radiology in contemplating a diagnostic suspicion and guiding further confirmatory tests.

Regional fat depot masses are influenced by protein-coding gene variants.

Waist-to-hip ratio (WHR) is a prominent cardiometabolic risk factor that increases cardio-metabolic disease risk independently of BMI and for which multiple genetic loci have been identified. However, WHR is a relatively crude proxy for fat distribution and it does not capture all variation in fat distribution. We here present a study of the role of coding genetic variants on fat mass in 6 distinct regions of the body, based on dual-energy X-ray absorptiometry imaging on more than 17k participants. We find that the missense variant CCDC92S70C, previously associated with WHR, is associated specifically increased leg fat mass and reduced visceral but not subcutaneous central fat. The minor allele-carrying transcript of CCDC92 is constitutively more highly expressed in adipose tissue samples. In addition, we identify two coding variants in SPATA20 and UQCC1 that are associated with arm fat mass. SPATA20K422R is a low-frequency variant with a large effect on arm fat only, and UQCC1R51Q is a common variant reaching significance for arm but showing similar trends in other subcutaneous fat depots. Our findings support the notion that different fat compartments are regulated by distinct genetic factors.

Hyperpolarized 13C MRI: State of the Art and Future Directions.

Hyperpolarized (HP) carbon 13 (13C) MRI is an emerging molecular imaging method that allows rapid, noninvasive, and pathway-specific investigation of dynamic metabolic and physiologic processes that were previously inaccessible to imaging. This technique has enabled real-time in vivo investigations of metabolism that are central to a variety of diseases, including cancer, cardiovascular disease, and metabolic diseases of the liver and kidney. This review provides an overview of the methods of hyperpolarization and 13C probes investigated to date in preclinical models of disease. The article then discusses the progress that has been made in translating this technology for clinical investigation. In particular, the potential roles and emerging clinical applications of HP [1-13C]pyruvate MRI will be highlighted. The future directions to enable the adoption of this technology to advance the basic understanding of metabolism, to improve disease diagnosis, and to accelerate treatment assessment are also detailed.

Sex dimorphism in the distribution of adipose tissue and its influence on proinflammatory adipokines and cardiometabolic profiles in motor complete spinal cord injury.

Objective: We aimed to examine the influence of sex on the distribution of adipose tissue, as well as proinflammatory adipokine and cardiometabolic profiles, in chronic motor complete spinal cord injury (SCI). Design: Cross-sectional and correlational study. Setting: Academic rehabilitation hospital. Participants: Forty-seven individuals with chronic motor complete SCI classified according to sex (males: age 44.0 ± 10.9 y, body mass index (BMI) 27.2 ± 5.8, level of injury (LOI) C4 - L1; females: 42.0 ± 13.5 y, BMI 27.8 ± 6.6, LOI C4 - T11). Intervention: Not applicable. Outcome Measures: Visceral (VAT), subcutaneous (SAT), and total trunk (TTAT) adipose tissue volumes were assessed utilizing magnetic resonance imaging and a VAT:SAT ratio was calculated. Proinflammatory adipokines (tumor neurosis factor-α, interleukin-6, plasminogen activator inhibitor-1, thrombin-activatable fibrinolysis inhibitor, and high sensitivity c-reactive protein) and cardiovascular, carbohydrate, and lipid profiles were evaluated according to standard techniques. Results: VAT and VAT:SAT ratio were significantly greater in male participates with SCI (P ≤ 0.002), while SAT volume was significantly greater in female participants with SCI (P = 0.001). No difference was noted in TTAT between groups (P = 0.341). Male participants with SCI demonstrated lower high-density lipoprotein-cholesterol (HDLC) profiles and an elevated total cholesterol to HDLC ratio (P ≤ 0.003) compared with females. No other significant differences were found between groups concerning cardiometabolic profiles or proinflammatory adipokines; however, males exhibited poorer profiles overall. Proinflammatory adipokines significantly correlated with adipose tissue depots by sex (P < 0.05). Conclusion: The results show that sex influences the distribution of adipose tissue, and may influence proinflammatory and cardiometabolic profiles following SCI. The findings of this study highlight the need for further research with dietary modification and exercise to decrease health risks.

Serum testosterone levels may influence body composition and cardiometabolic health in men with spinal cord injury.

STUDY DESIGN: Cross-sectional study. OBJECTIVE: To establish the association between serum testosterone (T) levels, biomarkers of cardiometabolic health and regional body composition variables after spinal cord injury (SCI). SETTING: Medical research center. METHODS: Metabolic and body composition measurements were collected from thirty-six men with chronic motor complete SCI. Serum T, carbohydrate, and lipid profiles were measured after an overnight fast. Body composition was measured using anthropometrics, dual-energy X-ray absorptiometry, and magnetic resonance imaging. Participants were evenly classified into tertiles based on their serum T levels into low, mid-normal and normal ranges. RESULTS: Low, mid-normal, and normal range serum T were 288.8 ± 84.9 ng/dL, 461.0 ± 52.5 ng/dL and 648.0 ± 53.5 ng/dL, respectively. Low range serum T group had greater total (9.6%, P = 0.04) percentage fat mass and visceral adipose tissue (VAT) area (72%, P = 0.01) compared to normal range serum T group. Serum T was related to the absolute whole thigh muscle area (r = 0.40, P < 0.05) after controlling for body mass index. Serum T was negatively related to fasting plasma glucose (r = -0.46, P = 0.006) and insulin (r = -0.42, P = 0.01), HbA1c (r = -0.39, P = 0.02) and triglycerides (r = -0.36, P = 0.03). CONCLUSION: Men with low serum T have more unfavorable body composition and cardiometabolic health outcomes after SCI. Testosterone replacement therapy may serve as a potential strategy in preventing cardiometabolic disorders after SCI.