Morphometric analysis of Corpus Callosum in autistic and typically developing Indian children.

Corpus callosum (CC) is the largest commissural white matter bundle in the brain, responsible for the integration of information between hemispheres. Reduction in the size of the CC structure has been predominantly reported in children with autism spectrum disorder (ASD) compared to typically developing children (TD). However, most of these studies are based on high-functioning individuals with ASD but not on an inclusive sample of individuals with ASD with varying abilities. Our current study aimed to examine the CC morphometry between children with ASD and TD in the Indian population. We also compared CC morphometry in autistic children with autism severity, verbal IQ (VIQ) and full-scale IQ (FSIQ). T1-weighted structural images were acquired using a 3T MRI scanner to examine the CC measures in 62 ASD and 17 TD children. The length and height of the CC and the width of genu were decreased in children with ASD compared to TD. There was no significant difference in CC measures based on autism severity, VIQ or FSIQ among children with ASD. To our knowledge, this is the first neuroimaging study to include a significant number (n = 56) of low-functioning ASD children. Our findings suggest the atypical interhemispheric connectivity of CC in ASD.

Can epicardial and pericardial adipose tissue volume predict the presence and severity of coronary artery disease?

Purpose: Excessive accumulation of free fatty acids in the coronary arteries can lead to coronary artery disease (CAD). Quantification of epicardial adipose tissue (EAT) and pericardial adipose tissue (PAT) is beneficial to understand its relationship with CAD, hypertension (HT), and diabetes. Material and methods: This retrospective study included 54 patients who underwent CT coronary angiogram using a multidetector row CT scanner. The EAT and PAT volumes from cardiac images were quantified using Image J software. The severity of CAD was graded using the CAD-RADS score. Results: Twenty-nine patients had no CAD, 21 patients had significant CAD, and 4 patients had insignificant CAD. Out of 21 patients with significant CAD, 14 had involvement of multiple coronary arteries. The EAT and PAT volumes were higher in patients with HT, DM, CAD-present group and significant-CAD-present group, but this was not statistically significant except the PAT volume with respect to diabetes. Significant correlation was found between EAT volume and calcium score (p = 0.035) and between EAT volume and total cholesterol level (p = 0.017). Significant differences in the EAT volumes were found in different CAD-RADS categories in the right coronary artery (RCA). From the threshold values, it was observed that CAD can develop in LAD even at lower of EAT and PAT volumes. Conclusions: Quantification of EAT and PAT volumes is beneficial in understanding its relationship with the presence and severity of coronary artery disease and its risk factors.

Evaluation of Radiation Dose Reduction and its Effect on Image Quality for Different Flat-Panel Detectors.

Purpose: To evaluate the image quality of semi-anatomical chest radiographs acquired using low radiation doses from seven different flat-panel detector (FPD) systems. Materials and Methods: Radiographs of a semi-anatomical chest phantom were acquired at 70 and 110 kVp using 7 different FPDs from 5 vendors. Radiation doses were measured using a dose-area-product (DAP) meter. To standardize measurements across all FPDs, DAP value of 51.05 µGym2 obtained at 70 kVp and 9.43 µGym2 at 110 kVp was used as reference in this study. Radiation doses were reduced by manually adjusting mAs for both tube potentials in all FPD systems to achieve acceptable image quality. Contrast-to-noise ratio, signal-to-noise ratio and figure of merit (FOM) in lung, heart, and diaphragm for all images were analyzed. Results: In comparison with set standard protocol, radiation dose reduction of 20%, 21%, 21.6%, 59.5%, 60.7%, 62.2%, and 67.6% with optimal image quality was observed in Prognosys Prorad, GE Definium 8000, Siemens Fusion, Fujifilm FGX, Fujifilm FGXR, Philips Digital Diagnost and Siemens Aristos at 70 kVp. At 110 kVp, dose reduction of 15.7% and 34.8% was possible only for Philips Digital Diagnost and Siemens Aristos. FOM was high at 110 kVp even when radiation doses were reduced by a factor 2 when compared to 70 kVp in all digital radiography systems. Conclusion: This study demonstrates the feasibility of using a semi-anatomical chest phantom in the optimization of radiation dose and image quality. The FOM was a good indicator in assessing image quality between different detectors.

An Atypical Form of Diabetes Among Individuals With Low BMI.

OBJECTIVE: Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes. RESEARCH DESIGN AND METHODS: State-of-the-art metabolic studies were used to characterize Indian individuals with "low BMI diabetes" (LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically matched groups: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy. RESULTS: The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D. CONCLUSIONS: These studies are the first to demonstrate that LD individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation.

Ultrasound and magnetic resonance imaging for the detection of blood: An ex-vivo study.

OBJECTIVES: Early detection of bleeding into a joint is crucial in patients with haemophilia. This study was designed to evaluate the sensitivity of ultrasonography (USG) and magnetic resonance imaging (MRI) to detect the presence of blood in small concentrations in a simulated model to mimic joint bleeding. MATERIALS AND METHODS: Different concentrations of blood in plasma, varying from 0.1% to 45%, were collected in 10-ml plastic syringes and imaged using 12 and 18 MHz USG transducers and with 1.5T and 3T MRI scanners, at different intervals of time following dilution. The images were scored for the presence of blood by four experienced radiologists who were blinded to the concentration of blood. RESULTS: Within the first 2 h, the 18 MHz transducer was able to detect blood consistently up to 0.5%, whereas the 12 MHz transducer could consistently identify blood up to 1.4%. After the first 12 h, both transducers were able to detect blood up to 0.5% concentration. However, at concentrations below 0.5%, there was discordance in the ability to detect blood, with both transducers. There was no correlation between the signal intensities of MRI images and concentration of blood, at different time intervals, irrespective of the magnetic field strength. CONCLUSIONS: Detection of blood using the USG is dependent on variables such as the concentration of blood, frequency of the transducer used and timing of the imaging. As the concentration of blood decreases below 0.5%, the discordance between the observers increases, implying that the detection limit of USG affects its reliability at lower concentrations of blood. Caution is urged while interpreting USG imaging studies for the detection of blood in symptomatic joints.

Estimation of Anatomical Dimensions of the Thorax from Computed Tomography Images of the Adult and Pediatric Indian Population for Developing Optimal Radiological Protocols.

Purpose: Ionizing radiation has been extensively used for medical diagnosis since its discovery in 1895; however, excessive use can lead to deleterious effects. Prior knowledge on radiological protocols based on simulations would be a practical tool for optimal use of radiation. Materials and Methods: Scan length of the thorax was measured from computed tomography (CT) topographic images and cross-sections at three levels of the thorax were measured from tomographic images of 500 adults and 340 children who had undergone CT thorax examinations using Centricity workstation software. The effective diameter (ED) of the thorax was calculated from anterio-posterior (AP) and transverse anatomical dimensions. Results: A 17% increase in scan length was observed for 6-10 years age group compared to 0-5 years, whereas there was marginal increase for 11-15 years of age. A 11.5% increase was observed for 16-18 years compared to 11-15 years age group. The cross-sectional phantom dimensions were calculated from ED measurements obtained from three regions of the thorax. Conclusions: This study has provided age- and gender-specific reference scan lengths, AP and transverse dimensions and ED for radiological examinations of the thorax. This information is useful to develop age- and gender-specific preset protocols and fabricate phantoms of the thorax for the pediatric and adult Indian population.

Significance of single and multi-voxel 1H magnetic resonance spectroscopy in the quantification of myocellular lipid in young non-obese Asian Indian males.

To prospectively assess intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) using single voxel spectroscopy (SVS) and multi voxel magnetic resonance spectroscopy (MVS) in soleus muscle and correlate results with metabolic variables in non-obese (BMI < 23 kg/m2) Asian Indian males. Thirty one patients with diabetes (cases) and twelve normoglycaemic subjects (controls) underwent point resolved spectroscopy sequence (PRESS) of soleus muscle using SVS and MVS in a 3 T MRI scanner. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured from MRI images and body composition was measured from dual-energy x-ray absorptiometry (DXA). The mean IMCL from SVS and MVS were 1.6% and 2.6% in cases and 2.3% and 3.4% in controls respectively. The mean EMCL from SVS and MVS were 1.8% and 3% in cases and 1.5% and 3% respectively in controls. A significant correlation between IMCL and total fat mass (rho = 0.42, p < 0.01) and total body fat (rho = 0.46; p < 0.01) were observed in cases while using the SVS technique and no correlations were found in the MVS technique. The SVS showed significant correlations between total myocellular lipids with VAT and SAT in cases alone. Total myocellular lipids acquired using both techniques showed a significant correlation with BMI, waist circumference, total fat mass, total body fat and truncal fat in cases alone. Quantification of IMCL of soleus muscle using the SVS technique is useful in studying the relationship with metabolic markers in non-obese Asian Indians with diabetes.

Radiation dose reference card for interventional radiology procedures: Experience in a tertiary referral centre.

BACKGROUND: Fluoroscopy-guided interventions can potentially increase radiation risk to patients, if awareness on angiographic imaging technique and radiation dose is neglected. AIM: To develop patient radiation dose reference card from standardized imaging techniques for various radiology interventions performed using flat detector based angiography system. MATERIALS AND METHODS: Real-time monitoring of angiographic exposure parameters and radiation dose were performed for 16 types of radiological interventions. Effective dose (ED) was estimated from dose area product (DAP) using PCXMC Monte Carlo simulation software. Radiation risk levels were estimated based on Biological Effects of Ionising radiation (BEIR) report VII predictive models for an Asian population. RESULTS: Pulse rates of 7.5 pps and 0.6 mm Copper filtration during fluoroscopy and 4 frames per second (fps) and 0.1-0.3 mm Cu filtration during image acquisitions were found to reduce radiation dose. Owing to increased number of image acquisitions, DAP was highest during diagnostic spinal angiography 186.7 Gycm2 (44.0-377.5). This resulted in highest ED of 59.4 mSv with moderate risk levels (1 in 1000 to 1 in 500). Most of the radiological interventions had low radiation risk levels (1 in 10,000 to 1 in 1000). CONCLUSION: The patient radiation dose reference card is valuable to the medical community and can aid in patient counselling on radiation induced risk from radiological interventions.

A Study on the Use of Radiation-Protective Apron among Interventionists in Radiology.

OBJECTIVE: Radiation-protective aprons are commonly used by interventionists to protect against the harmful effects of ionizing radiation. Choice of appropriate aprons with respect to lead equivalence and weight is necessary for effective protection and reduced physical strain. This study evaluates the knowledge and practice of using radiation-protective aprons by interventionists. MATERIALS AND METHODS: Ninety-one interventional radiologists who attended an annual interventional conference were provided with a questionnaire which included age, years of experience, area of expertise, type and weight of apron used, and physical strain caused due to the use of apron. RESULTS: About 14.3% of the interventionists practiced in an angiographic suite for less than an hour a day, 45% for 2-4 h, 21% for 4-6 h, 10% for 6-10 h, and the rest above 10 h/day. About 68% of the interventionists wore 0.5 mm lead-equivalent (Pbeq) aprons; 15.4% with 0.25 mm Pbeq; about 5.5% with 0.35 mm Pbeq aprons, and the remaining were not aware of the lead equivalence. About 47% reported that they had body aches due to wearing single-sided aprons. Interventionists working more than 10 h/day wearing single-sided lead apron predominantly complained of shoulder pain and back pain. CONCLUSION: A large fraction of interventionists reported that they had physical strain. It is suggestive for interventionists to wear correct fit and light-weight aprons with appropriate lead equivalence.

A simple quality control tool for assessing integrity of lead equivalent aprons.

BACKGROUND: Protective lead or lead-equivalent (Pbeq) aprons play a key role in providing necessary shielding from secondary radiation to occupational workers. Knowledge on the integrity of these shielding apparels during purchase is necessary to maintain adequate radiation safety. AIM: The aim of the study was to evaluate the lead equivalence in aprons based on simple quality assessment tool. MATERIALS AND METHODS: 0.25 mm and 0.5 mm lead and lead-free aprons from 6 manufacturers were assessed using a calibrated digital X-ray unit. The percentage attenuation values of the aprons were determined at 100 kVp using an ionization chamber and the pixel intensities were analyzed using digital radiographic images of lead apron, copper step wedge tool, and 2 mm thick lead. RESULTS: Mean radiation attenuation of 90% and 97% was achieved in 0.25 mm and 0.5 mm lead or lead-free aprons respectively. The pixel intensities from 0.25 mm Pbeq apron correspond to 0.8-1.2 mm thickness of Cu while 0.5 mm Pbeq aprons correspond to 2.0-2.8 mm of Cu. CONCLUSION: Pixel intensity increased with increase in the thickness of copper step wedge indicating a corresponding increase in lead equivalence in aprons. It is suggestive that aprons should be screened for its integrity from the time of purchase using computed tomography (CT), fluoroscopy, or radiography. It is recommended that this simple test tool could be used for checking lead equivalence if any variation in contrast is seen in the image during screening.

Radiation dose from percutaneous transluminal coronary angioplasty procedure performed using a flat detector for different clinical angiographic projections.

The radiation dose from complex cardiac procedures is of concern due to the lengthy fluoroscopic screening time and vessel complexities. This study intends to assess radiation dose based on angiographic projection and vessel complexities for clinical protocols used in the performance of percutaneous transluminal coronary angioplasty (PTCA). Dose-area product (DAP), reference air kerma (K a,r) and real-time monitoring of tube potentials and tube current for each angiographic projection and dose setting were evaluated for 66 patients who underwent PTCA using a flat detector system. The mean DAP and cumulative K a,r were 32.71 Gy cm2 (0.57 Gy), 51.24 Gy cm2 (0.9 Gy) and 102.03 Gy cm2 (1.77 Gy) for single-, double- and triple-vessel PTCA, respectively. Among commonly used angiographic projections, left anterior oblique 45°-caudal 35° reached 2 Gy in 55 min using a low-dose fluoroscopy setting and 21 min for a medium-dose setting. Use of a low-dose setting for fluoroscopic screening showed a radiation dose reduction of 39% compared with a medium-dose setting.

Circulating triacylglycerols but not pancreatic fat associate with insulin secretion in healthy humans.

BACKGROUND: Loss of adequate insulin secretion for the prevailing insulin resistance is critical for the development of type 2 diabetes and has been suggested to result from circulating lipids (triacylglycerols [TG] or free fatty acids) and/or adipocytokines or from ectopic lipid storage in the pancreas. This study aimed to address whether circulating lipids, adipocytokines or pancreatic fat primarily associates with lower insulin secretion. SUBJECTS/METHODS: Nondiabetic persons (n=73), recruited from the general population, underwent clinical examinations, fasting blood drawing to measure TG and adipocytokines and oral glucose tolerance testing (OGTT) to assess basal and dynamic insulin secretion and sensitivity indices. Magnetic resonance imaging and 1H-magnetic resonance spectroscopy were used to measure body fat distribution and ectopic fat content in liver and pancreas. RESULTS: In age-, sex- and BMI-adjusted analyses, total and high-molecular-weight adiponectin were the strongest negative predictors of fasting beta-cell function (BCF; ß=-0.403, p=0.0003 and ß=-0.237, p=0.01, respectively) and adaptation index (AI; ß=-0.210, p=0.006 and ß=-0.133, p=0.02, respectively). Circulating TG, but not pancreatic fat content, related positively to BCF (ß=0.375, p<0.0001) and AI (ß=0.192, p=0.003). Similar results were obtained for the disposition index (DI). CONCLUSIONS: The association of serum lipids and adiponectin with beta-cell function may represent a compensatory response to adapt for lower insulin sensitivity in nondiabetic humans.

Radiation dose and risk in children undergoing cardiac interventions performed using flat detector angiography systems.

The purpose of the study was to measure radiation doses and estimate risk from various beam projections in children undergoing cardiac interventions. The dose area product (DAP) was measured for eleven patent ductus arteriosus device closures (PDA), four atrial septal defect device closures (ASD), and three balloon pulmonary valvuloplasty (BPV) interventions performed using a flat detector system. The total mean DAPs for PDA, ASD and BPV were 1.9 Gycm2, 9.8 Gycm2 and 6.2 Gycm2 respectively. The fluoroscopic kerma dose rates increased by 10%, 33% and 92% when changing the projection from posterior-anterior to lateral projection for PDA interventions among infants, <5 yrs and >5 yrs respectively. The effective dose (ED) and organ doses were estimated from DAP using Monte Carlo software. Lungs received the highest organ dose of 7.4 mGy (PDA), 20.7 mGy (ASD) and 17.3 mGy (BPV) compared to other organs. The mean EDs from PDA, ASD and BPV were 2.5 mSv, 6.1 mSv and 4.9 mSv respectively. PDA intervention performed in infants had a radiation risk 66% higher than children aged between 3-10 years. Their lifetime attributable risk as per BEIR VII for cancer incidence was 1 in 907 males and 1 in 1047 females.

Can Pixel Value Ratio be Used in the Assessment of Ceramic Bone Substitute Incorporation? Observations from a Pilot Study.

BACKGROUND: Assessment of bone graft substitute incorporation is critical in the clinical decision making process and requires special investigations. We examined if the pixel value ratio (PVR) obtained in routine follow-up digital radiographs could be used for such assessment. MATERIAL/METHODS: Radiographic images were acquired using either computed radiography or flat panel digital radiography systems. The PVR from radiographs of thirty children with ceramic bone substitute grafting were analyzed using the software from the picture archival and communication system (PACS) workstation. Graft incorporation was also assessed using the van Hemert scale. Three independent observers (A, B, C) measured PVRs at two different time points during the first and the last follow-up visits. PVR was compared with the van Hemert scale scores and analyzed using Spearman's rank correlation. RESULTS: The mean intra-observer reliability was 0.8996, and inter-observer reliabilities were 0.69 (A vs. C), 0.78 (A vs. B), and 0.85 (B vs. C) for the first follow-up visit and 0.74 (A vs. C), 0.82 (A vs. B), and 0.70 (B vs. C) for the last follow-up measurements. Spearman's correlation showed a strong negative association between PVR values and van Hemert scale scores, as the healing process advanced on serial measurements at each follow-up (r=-0.94, n=60, z=-7.24, p≤0.0001). The reliability of the PVR measurements was assessed using an aluminum step wedge and ceramic graft. CONCLUSIONS: PVR is potentially a reliable indicator of bone graft incorporation and can aid in clinical decision making provided standard radiographic techniques are used.

Radiation doses and estimated risk from angiographic projections during coronary angiography performed using novel flat detector.

Coronary angiography (CA) procedure uses various angiographic projections to elicit detailed information of the coronary arteries with some steep projections involving high radiation dose to patients. This study intends to evaluate radiation doses and estimated risk from angiographic projections during CA procedure performed using novel flat detector (FD) system with improved image processing and noise reduction techniques. Real-time monitoring of radiation doses using kerma-area product (KAP) meter was performed for 140 patients using Philips Clarity FD system. The CA procedure involved seven standard projections, of which five were extensively selected by interventionalists. Mean fluoroscopic time (FT), KAP, and reference air kerma (Ka,r) for CA procedure were 3.24 min (0.5-10.51), 13.99Gycm2 (4.02-37.6), and 231.43 mGy (73.8-622.15), respectively. Effective dose calculated using Monte Carlo-based PCXMC software was found to be 4.9mSv. Left anterior oblique (LAO) 45° projection contributed the highest radiation dose (28%) of the overall KAP. Radiation-induced risk was found to be higher in females compared to males with increased risk of lung cancer. An increase of 10%-15% in radiation dose was observed when one or more additional projections were adopted along with the seven standard projections. A 14% reduction of radiation dose was achieved from novel FD system when low-dose protocol during fluoroscopy and medium-dose protocol during cine acquisitions were adopted, compared to medium-dose protocol.

Time course of postprandial hepatic phosphorus metabolites in lean, obese, and type 2 diabetes patients.

BACKGROUND: Impaired energy metabolism is a possible mechanism that contributes to insulin resistance and ectopic fat storage. OBJECTIVE: We examined whether meal ingestion differently affects hepatic phosphorus metabolites in insulin-sensitive and insulin-resistant humans. DESIGN: Young, lean, insulin-sensitive humans (CONs) [mean ± SD body mass index (BMI; in kg/m(2)): 23.2 ± 1.5]; insulin-resistant, glucose-tolerant, obese humans (OBEs) (BMI: 34.3 ± 1.7); and type 2 diabetes patients (T2Ds) (BMI: 32.0 ± 2.4) were studied (n = 10/group). T2Ds (61 ± 7 y old) were older (P < 0.001) than were OBEs (31 ± 7 y old) and CONs (28 ± 3 y old). We quantified hepatic γATP, inorganic phosphate (Pi), and the fat content [hepatocellular lipids (HCLs)] with the use of (31)P/(1)H magnetic resonance spectroscopy before and at 160 and 240 min after a high-caloric mixed meal. In a subset of volunteers, we measured the skeletal muscle oxidative capacity with the use of high-resolution respirometry. Whole-body insulin sensitivity (M value) was assessed with the use of hyperinsulinemic-euglycemic clamps. RESULTS: OBEs and T2Ds were similarly insulin resistant (M value: 3.5 ± 1.4 and 1.9 ± 2.5 mg · kg(-1) · min(-1), respectively; P = 0.9) and had 12-fold (P = 0.01) and 17-fold (P = 0.002) higher HCLs, respectively, than those of lean persons. Despite comparable fasting hepatic γATP concentrations, the maximum postprandial increase of γATP was 6-fold higher in OBEs (0.7 ± 0.2 mmol/L; P = 0.03) but only tended to be higher in T2Ds (0.6 ± 0.2 mmol/L; P = 0.09) than in CONs (0.1 ± 0.1 mmol/L). However, in the fasted state, muscle complex I activity was 53% lower (P = 0.01) in T2Ds but not in OBEs (P = 0.15) than in CONs. CONCLUSIONS: Young, obese, nondiabetic humans exhibit augmented postprandial hepatic energy metabolism, whereas elderly T2Ds have impaired fasting muscle energy metabolism. These findings support the concept of a differential and tissue-specific regulation of energy metabolism, which can occur independently of insulin resistance. This trial was registered at clinicaltrials.gov as NCT01229059.

Transition from image intensifier to flat panel detector in interventional cardiology: Impact of radiation dose.

Flat panel detector (FPD) technology in interventional cardiology is on the increase due to its varied advantages compared to the conventional image intensifier (II) systems. It is not clear whether FPD imparts lower radiation doses compared to II systems though a few studies support this finding. This study intends to compare radiation doses from II and FPD systems for coronaryangiography (CAG) and Percutaneous Transluminal Coronary Angioplasty (PTCA) performed in a tertiary referral center. Radiation doses were measured using dose area product (DAP) meter from patients who underwent CAG (n = 222) and PTCA (n = 75) performed using FPD angiography system. The DAP values from FPD were compared with earlier reported data using II systems from the same referral center where the study was conducted. The mean DAP values from FPD system for CAG and PTCA were 24.35 and 63.64 Gycm(2) and those from II system were 27.71 and 65.44 Gycm(2). Transition from II to FPD system requires stringent dose optimization strategies right from the initial period of installation.

Evidence for a direct effect of the NAD+ precursor acipimox on muscle mitochondrial function in humans.

Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD(+)) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that the nicotinic acid derivative acipimox, an NAD(+) precursor, would directly affect mitochondrial function independent of reductions in nonesterified fatty acid (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI 33.4 ± 0.8 kg/m(2)) received either placebo or acipimox 250 mg three times daily dosage for 2 weeks. Acipimox treatment increased plasma NEFA levels (759 ± 44 vs. 1,135 ± 97 µmol/L for placebo vs. acipimox, P < 0.01) owing to a previously described rebound effect. As a result, skeletal muscle lipid content increased and insulin sensitivity decreased. Despite the elevated plasma NEFA levels, ex vivo mitochondrial respiration in skeletal muscle increased. Subsequently, we showed that acipimox treatment resulted in a robust elevation in expression of nuclear-encoded mitochondrial gene sets and a mitonuclear protein imbalance, which may indicate activation of the mitochondrial unfolded protein response. Further studies in C2C12 myotubes confirmed a direct effect of acipimox on NAD(+) levels, mitonuclear protein imbalance, and mitochondrial oxidative capacity. To the best of our knowledge, this study is the first to demonstrate that NAD(+) boosters can also directly affect skeletal muscle mitochondrial function in humans.

Comparison of liver fat indices for the diagnosis of hepatic steatosis and insulin resistance.

CONTEXT: Hepatic steatosis, defined as increased hepatocellular lipid content (HCL), associates with visceral obesity and glucose intolerance. As exact HCL quantification by 1H-magnetic resonance spectroscopy (1H-MRS) is not generally available, various clinical indices are increasingly used to predict steatosis. OBJECTIVE: The purpose of this study was to test the accuracy of NAFLD liver fat score (NAFLD-LFS), hepatic steatosis index (HSI) and fatty liver index (FLI) against 1H-MRS and their relationships with insulin sensitivity and secretion. DESIGN, SETTING AND PARTICIPANTS: Ninety-two non-diabetic, predominantly non-obese humans underwent clinical examination, 1H-MRS and an oral glucose tolerance test (OGTT) to calculate insulin sensitivity and ß-cell function. Accuracy of indices was assessed from the area under the receiver operating characteristic curve (AROC). RESULTS: Median HCL was 2.49% (0.62;4.23) and correlated with parameters of glycemia across all subjects. NAFLD-LFS, FLI and HSI yielded AROCs of 0.70, 0.72, and 0.79, respectively, and related positively to HCL, insulin resistance, fasting and post-load ß-cell function normalized for insulin resistance. Upon adjustment for age, sex and HCL, regression analysis revealed that NAFLD-LFS, FLI and HSI still independently associated with both insulin sensitivity and ß-cell function. CONCLUSION: The tested indices offer modest efficacy to detect steatosis and cannot substitute for fat quantification by 1H-MRS. However, all indices might serve as surrogate parameters for liver fat content and also as rough clinical estimates of abnormal insulin sensitivity and secretion. Further validation in larger collectives such as epidemiological studies is needed.

Initial clinical application of modified Dixon with flexible echo times: hepatic and pancreatic fat assessments in comparison with (1)H MRS.

OBJECTS: Hepatic and pancreatic fat content become increasingly important for phenotyping of individuals with metabolic diseases. This study aimed to (1) evaluate hepatic fat fractions (HFF) and pancreatic fat fractions (PFF) using (1)H magnetic resonance spectroscopy (MRS) and the recently introduced fast mDixon method, and to examine body fat effects on HFF and PFF, (2) investigate regional differences in HFF and PFF by mDixon. MATERIALS AND METHODS: HFF and PFF were quantified by mDixon with two flexible echo times and by single voxel (1)H MRS in 24 healthy subjects. The regional differences of PFF within the pancreas were assessed with mDixon. Abdominal visceral and subcutaneous fat was assessed by T1-weighted MRI at 3T. RESULTS: Both methods correlated well for quantification of HFF (r = 0.98, p < 0.0001) and PFF (r = 0.80, p < 0.0001). However, mDixon showed a higher low limit in HFF and PFF. PFF showed no regional differences using mDixon. In addition, both visceral and subcutaneous fat correlated with pancreatic fat, while only visceral fat correlated with liver fat, employing both (1)H MRS and mDixon. CONCLUSION: The novel and fast two-point mDixon exhibits a good correlation with the gold-standard (1)H MRS for assessment of HFF and PFF, with limited sensitivity for assessing lower fat content.