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Computer vision is a subcategory of artificial intelligence focused on extraction of information from images and video. It provides a compelling new means for objective orthopaedic gait assessment in horses using accessible hardware, such as a smartphone, for markerless motion analysis. This study aimed to explore the lameness assessment capacity of a smartphone single camera (SC) markerless computer vision application by comparing measurements of the vertical motion of the head and pelvis to an optical motion capture multi-camera (MC) system using skin attached reflective markers. Twenty-five horses were recorded with a smartphone (60 Hz) and a 13 camera MC-system (200 Hz) while trotting two times back and forth on a 30 m runway. The smartphone video was processed using artificial neural networks detecting the horse's direction, action and motion of body segments. After filtering, the vertical displacement curves from the head and pelvis were synchronised between systems using cross-correlation. This rendered 655 and 404 matching stride segmented curves for the head and pelvis respectively. From the stride segmented vertical displacement signals, differences between the two minima (MinDiff) and the two maxima (MaxDiff) respectively per stride were compared between the systems. Trial mean difference between systems was 2.2 mm (range 0.0-8.7 mm) for head and 2.2 mm (range 0.0-6.5 mm) for pelvis. Within-trial standard deviations ranged between 3.1-28.1 mm for MC and between 3.6-26.2 mm for SC. The ease of use and good agreement with MC indicate that the SC application is a promising tool for detecting clinically relevant levels of asymmetry in horses, enabling frequent and convenient gait monitoring over time.

Differences in peak vertical ground reaction forces (dFz peak ) between contralateral forelimbs and hindlimbs are considered the gold standard for quantifying weight-bearing lameness. However, measuring kinematics for the same purpose is more common and practical. Vertical movement asymmetries (VMA) of the horse's upper body have previously been correlated to fore- and hindlimb lameness. But the combined response of head, withers and pelvis VMA to fore- and hindlimb dFz peak has not yet been thoroughly investigated. Deriving the kinetic responses from kinematics would help the interpretation and understanding of quantified weight-bearing lameness. In this retrospective study, 103 horses with a wide range of fore- and hindlimb dFz peak had been trotted on a force-measuring treadmill synchronized with an optical motion capture system. VMA of the head, withers and pelvis as well as dFz peak were extracted. Multiple linear mixed models and linear regressions of kinematic variables were used to model the dFz peak . It was hypothesised that all included VMA would have a significant influence on the dFz peak outcome variables. The results showed a complex relationship between VMA and dFz peak where both amplitude and timing of the VMA were of importance. On average, the contribution percentage of VMA to fore/hind dFz peak were 66/34% for head, 76/24% for withers and 33/67% for pelvis. The linear regressions for the fore/hindlimb models achieved mean measurement root mean squared errors of 0.83%/0.82% dFz peak . These results might help determine the clinical relevance of upper body VMA and distinguish between primary fore, hind, ipsilateral and diagonal weight-bearing lameness., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The study investigated between-rider differences in pelvic roll and pitch motion during horseback riding as the horse walked around circles without rein contact (walk on long reins), with rein contact, and with moderate collection. Ten horses were ridden by five riders on left and right 10 m circles, in a partly crossed design, yielding 14 trials. Each trial included each of the three walk variations in both directions. Riders wore an inertial measurement unit (IMU), logging at 100 Hz, dorsally on the pelvis. Pelvic roll and pitch data were split into strides based on data from IMU-sensors on the horse's hind cannons. Data were analyzed using signal decomposition into the fundamental frequency (the stride frequency) and its first two harmonics. Mixed models accounting for the type of walk were used to analyze how riders differed in roll and pitch pelvic motion in two ways: comparing amplitudes of the frequency components and comparing whole stride mean data. Graphically pelvic pitch showed substantial timing and amplitude differences between riders, and this was confirmed statistically. Pelvic roll timing was similar, but amplitude varied between the riders, both graphically and statistically. Individual rider patterns tended to persist across different horses and all exercises. These results suggest that exercises at walk can be ridden with different pelvis pitch timing, a fact that has so far not been discussed in the equestrian literature. Whether pelvic pitch timing affects the horse's performance remains to be investigated., (Copyright © 2021. Published by Elsevier Inc.)

Objectively assessing horse movement symmetry as an adjunctive to the routine lameness evaluation is on the rise with several commercially available systems on the market. Prerequisites for quantifying such symmetries include knowledge of the gait and gait events, such as hoof to ground contact patterns over consecutive strides. Extracting this information in a robust and reliable way is essential to accurately calculate many kinematic variables commonly used in the field. In this study, optical motion capture was used to measure 222 horses of various breeds, performing a total of 82 664 steps in walk and trot under different conditions, including soft, hard and treadmill surfaces as well as moving on a straight line and in circles. Features were extracted from the pelvis and withers vertical movement and from pelvic rotations. The features were then used in a quadratic discriminant analysis to classify gait and to detect if the left/right hind limb was in contact with the ground on a step by step basis. The predictive model achieved 99.98% accuracy on the test data of 120 horses and 21 845 steps, all measured under clinical conditions. One of the benefits of the proposed method is that it does not require the use of limb kinematics making it especially suited for clinical applications where ease of use and minimal error intervention are a priority. Future research could investigate the extension of this functionality to classify other gaits and validating the use of the algorithm for inertial measurement units., Competing Interests: Declaration of Competing Interest The salary of Christoffer Roepstorff was partially funded by Qualisys AB. However, Qualisys AB had no influence on the outcome of this study. No other authors declare any conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lameness is a symptom indicative of pain or injury of the locomotor apparatus. Lame horses generally should not be ridden. However, owners' ability to assess lameness has been questioned. This study's aim was to use subjective lameness assessments and objective gait analysis to generate a descriptive overview of movement and weight-bearing asymmetries of owner-sound riding horses. 235 horses were subjectively assessed in a field study, and the owner's perception of their horse's orthopedic health was recorded through an online survey. 69 horses were re-evaluated by gait analysis at an equine hospital. During trot on an instrumented treadmill, the gait was scored by a veterinarian using lameness grades from 0/5 (sound) to 3/5 (moderate lameness visible at trot). Movement asymmetry of the head (HDmin) and pelvis (PDmin) and weight-bearing asymmetry were quantified simultaneously. The prevalence of subjectively scored lameness grade ≥2/5 in one or more limbs was 55% during study part 1 and 74% during study part 2. Movement asymmetry of the head and/or pelvis exceeding HDmin ≥12 mm and/or PDmin ≥6 mm was found in 57% of the horses. 58% showed weight-bearing asymmetries between contralateral front and/or hind limbs of ≥3% body mass. Gait analysis showed considerable variability of movement and weight-bearing asymmetry values, sometimes independent of the clinical lameness grade, especially in the forehand. Several horses with lameness grade ≤1/5 had asymmetry values greater than mentioned thresholds. The analysis of movement and weight-bearing asymmetry revealed that these objective variables did not necessarily act uniformly and therefore should be interpreted with caution., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Asymmetric forces exerted on the horse's back during riding are assumed to have a negative effect on rider-horse interaction, athletic performance, and health of the horse. Visualized on a saddle pressure mat, they are initially blamed on a nonfitting saddle. The contribution of horse and rider to an asymmetric loading pattern, however, is not well understood. The aim of this study was to investigate the effects of horse and rider asymmetries during stance and in sitting trot on the force distribution on the horse's back using a saddle pressure mat and motion capture analysis simultaneously. Data of 80 horse-rider pairs (HRP) were collected and analyzed using linear (mixed) models to determine the influence of rider and horse variables on asymmetric force distribution. Results showed high variation between HRP. Both rider and horse variables revealed significant relationships to asymmetric saddle force distribution (P < .001). During sitting trot, the collapse of the rider in one hip increased the force on the contralateral side, and the tilt of the rider's upper body to one side led to more force on the same side of the pressure mat. Analyzing different subsets of data revealed that rider posture as well as horse movements and conformation can cause an asymmetric force distribution. Because neither horse nor rider movement can be assessed independently during riding, the interpretation of an asymmetric force distribution on the saddle pressure mat remains challenging, and all contributing factors (horse, rider, saddle) need to be considered., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim of the present study was to determine time to steady state of insulin degludec (IDeg), a basal insulin analog with an ultralong duration of action, after once-daily subcutaneous administration in subjects of varying age, diabetes type, and ethnicity., Methods: Time to steady state was analyzed in 195 subjects across five Phase I randomized single-center double-blind studies: three in subjects with type 1 diabetes (T1DM), including one in elderly subjects, and two in subjects with type 2 diabetes (T2DM), including one with African American and Hispanic/Latino subpopulations. Subjects received once-daily IDeg (100 U/mL, s.c.) at doses of 0.4-0.8 U/kg for 6-12 days. Time to clinical steady state was measured from first dose until the serum IDeg trough concentration exceeded 90% of the final plateau level. The IDeg concentrations were log-transformed and analyzed using a mixed-effects model with time from first dose and dose level (where applicable) as fixed effects, and subject as a random effect., Results: Steady state serum IDeg concentrations were reached after 2-3 days in all subjects. In trials with multiple dose levels, time to steady state was independent of dose level in T1DM (P = 0.51) and T2DM (P = 0.75)., Conclusions: Serum IDeg concentrations reached steady state within 2-3 days of once-daily subcutaneous administration in all subjects with T1DM or T2DM, including elderly and African American and Hispanic/Latino subjects. At steady state, serum IDeg concentrations were unchanged from day to day., (© 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Background and Objectives: Patients with diabetes mellitus inject insulin in different regions of the body. This study investigated the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a new-generation once-daily basal insulin with an ultra-long duration of action, after subcutaneous (SC) administration in different injection regions., Methods: In this study, 20 healthy subjects received single SC doses of IDeg (0.4 U/kg; separated by 13-21 days) in the thigh, abdomen and deltoid in a randomised, open-label, single-centre, single-dose, complete crossover trial. Each dose was followed by a 24-h euglycaemic clamp and 120-h pharmacokinetic blood sampling. The obtained pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by simulation using a pharmacokinetic/pharmacodynamic model., Results: Total IDeg exposure [area under the IDeg serum concentration-time curve 0-120 h after a single dose (AUCIDeg,0-120h,SD)] and maximum serum concentration [maximum IDeg serum concentration after a single dose (C max,IDeg,SD)] were higher (6-7 and 23-27 %, respectively) following a single SC dose in the deltoid or abdomen, compared with the thigh, as also observed with other insulin preparations. No statistical difference was observed in these measures between deltoid and abdominal administration. No pronounced differences were observed in the glucose-lowering effect of IDeg [area under the glucose infusion rate (GIR) curve 0-24 h after a single dose (AUCGIR,0-24h,SD) and maximum GIR after a single dose (GIRmax,SD)] when injected in the thigh, abdomen or deltoid (AUCGIR,0-24h,SD 2,572, 2,833 and 2,960 mg/kg, respectively). Simulated mean steady-state pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg exposure and effect regardless of injection region, with comparable total glucose-lowering effects [area under the GIR curve at steady state (AUCGIR,τ,SS)] between the thigh, abdomen and deltoid., Conclusions: These findings support administering IDeg SC in the thigh, upper arm or abdominal wall without affecting IDeg absorption or effect at steady state.

Introduction/aim: Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of long-acting and short-acting insulin analogs. The primary objective of this study was to investigate the pharmacodynamic response of once-daily IDegAsp dosing in patients with type 1 diabetes. Pharmacokinetic response, as well as safety and tolerability, were assessed as secondary objectives., Methodology: This was a single-center, open-label, single-arm study. Twenty-two subjects received once-daily insulin degludec (IDeg) (0.42 U/kg) for five consecutive days [with separate bolus insulin aspart (IAsp) as needed for safety and glycemic control], to achieve clinical steady state of the basal component. On Day 6, they received a single injection of IDegAsp (0.6 U/kg, comprising 0.42 U/kg IDeg and 0.18 U/kg IAsp). Pharmacodynamic response was assessed using a 30-h euglycemic glucose clamp, with blood glucose stabilized at a target of 5.5 mmol/L., Results: The glucose infusion rate profile showed a rapid onset of action and a distinct peak due to IAsp, followed by a separate, flat and stable basal glucose-lowering effect due to the IDeg component. Modeling data suggested that the pharmacodynamic profile of IDegAsp was retained with twice-daily dosing (allowing for coverage of two main meals daily). IDegAsp was well tolerated and no safety issues were identified in this trial., Conclusions: In conclusion, the IAsp component of IDegAsp has a fast onset of appearance and a peak covering the prandial phase, while the IDeg component has a flat and an evenly distributed pharmacokinetic profile over 24 h. IDegAsp is the first co-formulation of a basal insulin analog with an ultra-long duration of action and a mealtime insulin analog in a single soluble injection. These properties translate into clinically relevant benefits, including improved glycemic control and reduction in hypoglycemia.

Background: Pharmacokinetic and pharmacodynamic profiles of exogenous insulin may be affected by intrinsic factors, such as age, ethnicity/race, and hepatic and renal function. Insulin degludec (IDeg) is a basal insulin with an ultralong duration of action and a flat and stable glucose-lowering effect profile., Objective: The purpose of this study was to investigate whether the pharmacokinetic and pharmacodynamic responses to IDeg at steady state vary according to patient race/ethnicity., Methods: This randomized, single-center, double-blind, 2-period crossover trial investigated responses to IDeg in 59 patients with type 2 diabetes mellitus from 3 groups: African American, Hispanic/Latino, and white. Patients were allocated randomly to a sequence of 2 treatment periods, separated by a 7- to 21-day washout period, with once-daily IDeg or insulin detemir dosing for 6 days at a predefined fixed dose level (0.6 U/kg). Differences in pharmacokinetic and pharmacodynamic variables among groups were analyzed using an ANOVA with treatment period, an interaction between race/ethnicity, and treatment as fixed factors, subject as a random effect, and residual variance, depending on treatment., Results: Total exposure to IDeg during one dosing interval at steady state (AUCIDeg,τ,SS) was similar among the racial/ethnic groups (ratio [95% CI]: African American vs white, 1.10 [0.91-1.31]; African American vs Hispanic/Latino, 1.13 [0.95-1.34]; and Hispanic/Latino vs white, 0.97 [0.82-1.16]). The total glucose-lowering effect of IDeg (AUCGIR,τ,SS) was also similar among the groups, with no statistically significant difference in pairwise comparisons (1940, 1735, and 2286 mg/kg in African American, white, and Hispanic/Latino patients, respectively). Steady state was reached in all groups after 2 to 3 days of dosing. In all groups, both exposure and glucose-lowering effect for IDeg were evenly distributed between the first and second 12 hours of the 24-hour dosing interval at steady state (mean AUCIDeg,0-12h,SS/AUCIDeg,τ,SS = 53%-54%; AUCGIR,0--12h,SS/AUCGIR,τ,SS = 47%-52%)., Conclusion: The similar pharmacokinetic and pharmacodynamic responses to IDeg in 3 racial/ethnic groups of patients with type 2 diabetes mellitus suggest that the flat, stable, and ultralong pharmacokinetic and pharmacodynamic profiles of IDeg are preserved irrespective of race/ethnicity. Although insulin doses must be adjusted on an individual basis, similar pharmacokinetic and pharmacodynamic responses to IDeg are observed in patients with differing race/ethnicity., (Copyright © 2014 The Authors. Published by EM Inc USA.. All rights reserved.)

Background and Objective: Insulin degludec is a basal insulin with a slow and distinct absorption mechanism resulting in an ultra-long, flat, and stable pharmacokinetic profile in patients with diabetes mellitus. The aim of this study was to examine the effect of hepatic impairment on the single-dose pharmacokinetics of insulin degludec., Methods: Twenty-four subjects, allocated to one of four groups (n=6 per group) based on level of hepatic impairment (normal hepatic function, Child-Pugh grade A, B, or C), were administered a single subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post-dose and fractionated urine samples were collected to measure pharmacokinetic parameters., Results: No difference was observed in pharmacokinetic parameters [area under the 120-h serum insulin degludec concentration-time curve (AUC120 h), maximum insulin degludec concentration (C max), and apparent clearance (CL/F)] for subjects with impaired versus normal hepatic function after a single dose of insulin degludec. The geometric mean [coefficient of variation (CV) %] AUC120 h values were 89,092 (16), 83,327 (15), 88,944 (23), and 79,846 (19) pmol·h/L for normal hepatic function and mild, moderate, and severe hepatic impairment, respectively. Simulated steady-state insulin degludec pharmacokinetic profiles showed an even distribution of exposure across a 24-h dosing interval regardless of hepatic function status., Conclusions: The ultra-long pharmacokinetic properties of insulin degludec were preserved in subjects with hepatic impairment and there were no statistically significant differences in absorption or clearance compared with subjects with normal hepatic function.

Background: Insulin degludec is a new-generation basal insulin with an ultra-long duration of action. We evaluated the pharmacokinetic properties of insulin degludec in subjects with normal renal function; mild, moderate or severe renal impairment; or end-stage renal disease (ESRD) undergoing hemodialysis., Methods: Thirty subjects (n = 6 per group) received a single subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post-dose and fractionated urine samples were collected., Results: The ultra-long pharmacokinetic properties of insulin degludec were preserved in subjects with renal impairment, with no statistically significant differences in absorption or clearance, compared with subjects with normal renal function. In subjects with ESRD, pharmacokinetic parameters were similar whether the insulin degludec pharmacokinetic assessment period included hemodialysis or not, and total exposure was comparable to subjects with normal renal function. Simulated mean steady-state pharmacokinetic profiles were comparable between groups., Conclusion: This study indicated dose adjustments due to impaired renal function should not be required for insulin degludec.

Aims/hypothesis: Insulin degludec (Des(B30)LysB29(γ-Glu Nε-hexadecandioyl) human insulin; IDeg) is a new basal insulin with an ultra-long flat action profile. The acute physiological responses to hypoglycaemia with IDeg and insulin glargine (A21Gly,B31Arg,B32Arg human insulin; IGlar) were compared., Methods: Twenty-eight adult type 1 diabetic patients with normal hypoglycaemia awareness (age = 41 ± 12 years, HbA1c = 7.8 ± 0.6% [62.8 ± 7 mmol/mol]) were randomised to once-daily IDeg or IGlar for 5 days in a two-period crossover design. Participants and research staff were blinded to group assignment. Patients were assigned the lowest available randomisation number from a set of blinded randomisation codes provided by the trial sponsor. Hypoglycaemia was induced by administering three times the usual daily insulin dose at midnight on day 5. Plasma glucose (PG) was stabilised by glucose clamp (5.5 mmol/l) for 7-9 h post dosing. Next morning, PG was allowed to decrease stepwise from 5.5 to 3.5 mmol/l (maintained for 30 min) to 2.5 mmol/l (for 15 min). PG was then increased to 3.9 mmol/l (for 120 min), before being returned to baseline. Hypoglycaemic symptom score (HSS), hypoglycaemic awareness, cognitive function, counter-regulatory hormones and vital signs were assessed during each glucose plateau. The primary analysis was to compare IDeg vs IGlar with respect to HSS at nadir PG concentration (2.5 mmol/l)., Results: The full analysis set for treatment comparisons comprised data from all 28 exposed patients. Rates of PG decline and PG at nadir were similar for IDeg and IGlar. No treatment differences in HSS (estimated difference: 0.17 [95% CI -1.71, 2.05]; p > 0.05), cognitive function or awareness were observed at any time. Growth hormone and cortisol responses during hypoglycaemia were greater with IDeg than IGlar (AUC treatment ratio [IDeg/IGlar]: 2.44 [1.30, 4.60], p < 0.01; and 1.23 [1.01, 1.50]; p < 0.05), and adrenaline (epinephrine) responses trended higher (1.40 [0.96, 2.04], p = 0.07). The rates of recovery from hypoglycaemia were similar., Conclusions/interpretation: IDeg and IGlar elicit comparable symptomatic and cognitive responses to induced hypoglycaemia. IDeg may elicit a moderately greater endocrine response, but times to PG recovery were similar for the two insulins., Trial Registration: ClinicalTrials.gov NCT01002768., Funding: Novo Nordisk.

Women have been shown to have higher muscle triacylglycerol (IMTG) levels than men and could therefore be expected to have lower insulin sensitivity than men, since previous studies have linked high IMTG to decreased insulin sensitivity. Therefore, insulin sensitivity of whole body and leg glucose uptake was studied in 9 women in the follicular phase and 8 men on a controlled diet and matched for maximal oxygen uptake per kilogram of lean body mass and habitual activity level. A 47% higher (P < 0.05) IMTG level was found in women than in men, and, at the same time, women also displayed 22% higher whole body insulin sensitivity (P < 0.05) and 29% higher insulin-stimulated leg glucose uptake (P = 0.05) during an euglycemic-hyperinsulinemic (approximately 70 microU/ml) clamp compared with matched male subjects. The higher insulin sensitivity in women could not be explained by higher expression of muscle glucose transporter GLUT4, insulin receptor, or Akt expression or by the ability of insulin to stimulate Akt Thr(308) or Akt Ser(473) phosphorylation. However, a 30% higher (P < 0.05) capillary density and 31% more type 1 muscle fiber expressed per area in the vastus lateralis muscle were noted in women than in matched men. It is concluded that despite 47% higher IMTG levels in women in the follicular phase, whole body as well as leg insulin sensitivity are higher than in matched men. This was not explained by sex differences in proximal insulin signaling in women. In women, it seems that a high capillary density and type 1 muscle fiber expression may be important for insulin action.

This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action compared with a high-carbohydrate diet [65 energy-% (CHO)]. After 4 days of isocaloric diet on two occasions (Fat/CHO), 12 male subjects performed 1 h of one-legged knee extensor exercise (approximately 80% peak workload). Four hours after exercise, insulin-stimulated glucose uptake was determined in both legs during a euglycemic-hyperinsulinemic clamp. Muscle biopsies were obtained in both legs before and after the clamp. Four hours after exercise, insulin-stimulated glucose uptake was improved (approximately 70%, P<0.001) independent of diet composition and despite normal insulin-stimulated regulation of insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, Akt, GSK-3, and glycogen synthase. Interestingly, exercise resulted in a sustained reduction (approximately 20%, P<0.05) in MCoA content 4 h after exercise that correlated (r=0.65, P<0.001) with improved insulin-stimulated glucose uptake. Four days of Fat diet resulted in an increased content of intramyocellular triacylglycerol (P<0.01) but did not influence muscle MCoA content or whole body insulin-stimulated glucose uptake. However, at the muscular level proximal insulin signaling and insulin-stimulated glucose uptake appeared to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle.

Objective: Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin-resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity., Research Design and Methods: Forearm skeletal muscle lipolysis was investigated in 13 lean and 10 obese men using [(2)H(5)]glycerol combined with the measurement of arteriovenous differences before and during beta-adrenergic stimulation using the nonselective beta-agonist isoprenaline (ISO). Muscle biopsies were taken from the vastus lateralis muscle before and during ISO to investigate hormone-sensitive lipase (HSL) protein expression and serine phosphorylation., Results: Baseline total glycerol release across the forearm was significantly blunted in obese compared with lean subjects (P = 0.045). This was accompanied by lower HSL protein expression (P = 0.004), HSL phosphorylation on PKA sites Ser(563) (P = 0.041) and Ser(659) (P = 0.09), and HSL phosphorylation on the AMPK site Ser(565) (P = 0.007), suggesting a blunted skeletal muscle lipolysis in obesity. Total forearm glycerol uptake during baseline did not differ significantly between groups, whereas higher net fatty acid uptake across the forearm was observed in the obese (P = 0.064). ISO induced an increase in total glycerol release from skeletal muscle, which was not significantly different between groups. Interestingly, this was accompanied by an increase in HSL Ser(659) phosphorylation in obese subjects during ISO compared with baseline (P = 0.008)., Conclusions: Obesity is accompanied by impaired fasting glycerol release, lower HSL protein expression, and serine phosphorylation. It remains to be determined whether this is a primary factor or an adaptation to the obese insulin-resistant state.