David William McMillan

Study Design: Prospective case series with body mass index (BMI)-matched case-controls. Objectives: To compare resting and postprandial inflammasome biomarkers and metabolic measurements in people with and without chronic spinal cord injury (SCI). Setting: A tertiary academic rehabilitation center in an urban, metropolitan setting in the southeastern United States. Methods: Blood samples were collected from 5 individuals with chronic SCI and 5 BMI-matched controls without chronic SCI at baseline and at 80 and 400 min following the consumption of a 600-kcal liquid meal comprised of 35% fat, 50% carbohydrate, and 15% protein. Inflammasome biomarkers included apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin-18 (IL-18), caspase-1 (CASP-1), and triggering receptor expressed on myeloid cells-2 (TREM-2). Metabolic biomarkers included glucose, insulin, triglyceride (TG), non-esterified fatty acid (NEFA), and glycerol. Results: Individuals with chronic SCI showed higher mean baseline concentrations of all inflammatory markers. There were greater mean postprandial decreases of ASC and CASP-1, with values remaining below baseline at 400 min. IL-18 remained near baseline. TREM-2 declined modestly in both groups. There were relative differences in glycemic and lipemic postprandial responses between groups at 80 min. Conclusions: In this case series, individuals with chronic SCI exhibited higher mean baseline inflammasome biomarker levels and different postprandial trajectories compared to controls. These preliminary hypothesis-generating observations warrant adequately powered studies to clarify the role of inflammasome-related mechanisms in inflammatory and metabolic dysregulation of chronic SCI.

Objectives: This systematic review with meta-analysis compared cardiometabolic syndrome (CMS) in adults with chronic (≥1 year) spinal cord injury (SCI) to non-SCI individuals (controls) and athletes, analyzing the effect of specific injury characteristics and exploring temporal and geographical trends. Methods: Ovid Medline, Embase, Cochrane, CINAHL, Scopus, and Web of Science were searched from inception to September 2024. Adults with chronic SCI were included based on observational and baseline data derived from experimental studies. Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields assessed quality. Weighted means with 95% bootstrapped confidence intervals (CI) were computed for risk stratification. Group differences were assessed using random effects meta-analysis, calculating weighted mean differences with 95% bootstrapped CI. Temporal and geographical trends were evaluated with linear regression based on sample-size-weighted distributions and relevant covariates. Results: Of 31,163 identified records, 471 studies were included (n ≤ 31,782 SCI participants). CMS was present in men with SCI, paraplegia, tetraplegia, and injuries above T6; men with complete SCI (AIS A); and men and women with motor-complete SCI (AIS A–B). Compared to controls, adults with SCI had a lower body mass index (BMI), higher total and visceral fat, and worse lipid and carbohydrate profiles, including increased insulin resistance (IR). Tetraplegia was associated with greater visceral fat, poorer glycemic control, and lower BMI, insulin sensitivity, high-density lipoprotein-cholesterol (HDL-C), and triglycerides than paraplegia. Motor-complete SCI had lower BMI, HDL-C, and fasting glucose than motor-incomplete injuries. Injuries above T6 had lower blood pressure and higher fasting insulin levels than those below T6. Athletes with SCI had a lower BMI, fat mass, and fasting glucose, and higher systolic blood pressure than non-athletes with SCI, but frequently presented with obesity and carbohydrate dysfunction. Temporal analysis revealed increasing obesity trends and improved systolic blood pressure, while other CMS risk factors remained unchanged. We also identified global variations in obesity, lipids, blood pressure, and carbohydrate patterns. Conclusions: With a large sample, we revealed a widespread cardiometabolic burden in chronic SCI, even among athletes. Specifically, obesity, IR, and hypoalphalipoproteinemia worsened with increasing injury severity, alongside rising obesity trends and geographic disparities in risk profiles. These patterns highlight the evolution of what was deemed an epidemic into a global cardiometabolic pandemic.

Background: A spinal cord injury (SCI) from trauma or disease impairs sensorimotor pathways in somatic and autonomic divisions of the nervous system, affecting multiple body systems. Improved medical practices have increased survivability and life expectancy after SCI, allowing for the development of extensive metabolic comorbidities and profound changes in body composition that culminate in prevalent obesity. Summary: Obesity is the most common cardiometabolic component risk in people living with SCI, with a diagnostic body mass index cutoff of 22 kg/m2 to account for a phenotype of high adiposity and low lean mass. The metameric organization of specific divisions of the nervous system results in level-dependent pathology, with resulting sympathetic decentralization altering physiological functions such as lipolysis, hepatic lipoprotein metabolism, dietary fat absorption, and neuroendocrine signaling. In this manner, SCI provides a unique opportunity to study in vivo the “neurogenic” components of certain pathologies that otherwise are not readily observable in other populations. We discuss the unique physiology of neurogenic obesity after SCI, including the altered functions mentioned above as well as structural changes such as reduced skeletal muscle and bone mass and increased lipid deposition in the adipose tissue, skeletal muscle, bone marrow, and liver. Key Message: The study of neurogenic obesity after SCI gives us a unique neurological perspective on the physiology of obesity. The lessons learned from this field can guide future research and advancements to inform the study of obesity in persons with and without SCI.

Individuals with spinal cord injuries (SCI) commonly present with component risk factors for cardiometabolic risk and combined risk factors for cardiometabolic syndrome (CMS). These primary risk factors include obesity, dyslipidemia, dysglycemia/insulin resistance, and hypertension. Commonly referred to as “silent killers”, cardiometabolic risk and CMS increase the threat of cardiovascular disease, a leading cause of death after SCI. This narrative review will examine current data and the etiopathogenesis of cardiometabolic risk, CMS, and cardiovascular disease associated with SCI, focusing on pivotal research on cardiometabolic sequelae from the last five years. The review will also provide current diagnosis and surveillance criteria for cardiometabolic disorders after SCI, a novel obesity classification system based on percent total body fat, and lifestyle management strategies to improve cardiometabolic health.

The Cambridge Handbook of Community Psychology - December 2021

Purpose: The purpose of this study was to assess the acute effects of exercise mode and intensity on postprandial macronutrient metabolism. Methods: Ten healthy men age 39 ± 10 yr with chronic paraplegia (13.2 ± 8.8 yr, ASIA A–C) completed three isocaloric bouts of upper-body exercise and a resting control. After an overnight fast, participants completed circuit resistance exercise (CRE) first and the following conditions in a randomized order, separated by >48 h: i) control (CON), ~45-min seated rest; ii) moderate-intensity continuous exercise (MICE), ~40-min arm cranking at a resistance equivalent to ~30% peak power output (PPO); and iii) high-intensity interval exercise (HIIE), ~30 min arm cranking with resistance alternating every 2 min between 10% PPO and 70% PPO. After each condition, participants completed a mixed-meal tolerance test consisting of a 2510-kJ liquid meal (35% fat, 50% carbohydrate, 15% protein). Blood and expired gas samples were collected at baseline and regular intervals for 150 min after a meal. Results: An interaction (P < 0.001) was observed, with rates of lipid oxidation elevated above CON in HIIE until 60 min after a meal and in CRE at all postprandial time points up to 150 min after a meal. Postprandial blood glycerol was greater in MICE (P = 0.020) and CRE (P = 0.001) compared with CON. Furthermore, nonesterified fatty acid area under the curve had a moderate-to-strong effect in CRE versus MICE and HIIE (Cohen’s d = −0.76 and −0.50, respectively). Conclusions: In persons with paraplegia, high-intensity exercise increased postprandial energy expenditure independent of the energy cost of exercise. Furthermore, exercise combining resistance and endurance modes (CRE) showed the greater effect on postprandial lipid oxidation.

Introduction Whole body energy expenditure and lipid oxidation (Lox) are upregulated during and after exercise. Persons with spinal cord injury (SCI) generally have a blunted ability to utilize fat during exercise, but it is unknown if their substrate partitioning is affected during recovery from exercise. Purpose To determine the effect of a single session of upper body circuit resistance exercise (CRE) on energy expenditure and Lox during exercise recovery in persons with and without SCI. Methods Twenty four persons (3 groups; 7 male and 1 female per group) without paralysis (neurologically intact; N) or with chronic (≥ 1 yr) paraplegia (P) or tetraplegia (T) participated. Energy expenditure and substrate partitioning were assessed via indirect calorimetry before, during, and three times after (up to 120 min after) a single session of CRE, or time-matched seated control (CON). Results During CRE, all groups experienced a similar relative increase in oxygen consumption (49 ± 13, 55 ± 11, and 48 ± 15% VO_2peak for N, P, and T, respectively). The Post_0-120 energy expenditure was greater following CRE vs. CON (P < 0.01) and independent of injury characteristics (10.6, 22.6, and 14.3% higher than CON for N, P, and T; P = 0.21). The absolute increase in Lox above CON during recovery was similar for N, P, and T (5.74 ± 2.81, 6.62 ± 3.10, and 4.50 ± 3.91 g, respectively; P = 0.45). Conclusions Energy expenditure and lipid utilization was increased similarly following circuit exercise in persons without and with spinal cord injury in a manner independent of level of injury.

Spinal cord injury (SCI) results in disordered fat metabolism. Autonomic decentralization might contribute to dyslipidemia in SCI, in part by influencing the uptake of dietary fats through the gut-lymph complex. However, the neurogenic contributions to dietary fat metabolism are unknown in this population. We present a subset of results from an ongoing registered clinical trial (NCT03691532) related to dietary fat absorption. We fed a standardized (20 kcal⋅kgFFM^–1) liquid meal tolerance test (50% carb, 35% fat, and 15% protein) that contained stable isotope lipid tracer (5 mg⋅kgFFM^–1 [U-¹³C]palmitate) to persons with and without motor complete thoracic SCI. Blood samples were collected at six postprandial time points over 400 min. Changes in dietary fatty acid incorporated into the triacylglycerol (TAG) pool (“exogenous TAG”) were used as a marker of dietary fat absorption. This biomarker showed that those with paraplegia had a lower amplitude than non-injured participants at Post₂₄₀ (52.4 ± 11.0 vs. 77.5 ± 16.0 μM), although this failed to reach statistical significance (p = 0.328). However, group differences in the time course of absorption were notable. The injury level was also strongly correlated with time-to-peak exogenous TAG concentration (r = −0.806, p = 0.012), with higher injuries resulting in a slower rise in exogenous TAG. This time course documenting exogenous TAG change is the first to show a potential neurogenic alteration in SCI dietary fat absorption.

Spinal cord injury (SCI) results in an array of cardiometabolic complications, with obesity being the most common component risk of cardiometabolic disease (CMD) in this population. Recent Consortium for Spinal Cord Medicine Clinical Practice Guidelines for CMD in SCI recommend physical exercise as a primary treatment strategy for the management of CMD in SCI. However, the high prevalence of obesity in SCI and the pleiotropic nature of this body habitus warrant strategies for tailoring exercise to specifically target obesity. In general, exercise for obesity management should aim primarily to induce a negative energy balance and secondarily to increase the use of fat as a fuel source. In persons with SCI, reductions in the muscle mass that can be recruited during activity limit the capacity for exercise to induce a calorie deficit. Furthermore, the available musculature exhibits a decreased oxidative capacity, limiting the utilization of fat during exercise. These constraints must be considered when designing exercise interventions for obesity management in SCI. Certain forms of exercise have a greater therapeutic potential in this population partly due to impacts on metabolism during recovery from exercise and at rest. In this article, we propose that exercise for obesity in SCI should target large muscle groups and aim to induce hypertrophy to increase total energy expenditure response to training. Furthermore, although carbohydrate reliance will be high during activity, certain forms of exercise might induce meaningful postexercise shifts in the use of fat as a fuel. General activity in this population is important for many components of health, but low energy cost of daily activities and limitations in upper body volitional exercise mean that exercise interventions targeting utilization and hypertrophy of large muscle groups will likely be required for obesity management.

Spinal cord injury (SCI) results in dramatic changes in body composition, with lean mass decreasing and fat mass increasing in specific regions that have important cardiometabolic implications. Accordingly, the recent Consortium for Spinal Cord Medicine (CSCM) released clinical practice guidelines for cardiometabolic disease (CMD) in SCI recommending the use of compartmental modeling of body composition to determine obesity in adults with SCI. This recommendation is guided by the fact that fat depots impact metabolic health differently, and in SCI adiposity increases around the viscera, skeletal muscle, and bone marrow. The contribution of skeletal muscle atrophy to decreased lean mass is self-evident, but the profound loss of bone is often less appreciated due to methodological considerations. General-population protocols for dual-energy x-ray absorptiometry (DXA) disregard assessment of the sites of greatest bone loss in SCI, but the International Society for Clinical Densitometry (ISCD) recently released an official position on the use of DXA to diagnose skeletal pathology in SCI. In this review, we discuss the recent guidelines regarding the evaluation and monitoring of obesity and bone loss in SCI. Then we consider the possible interactions of obesity and bone, including emerging evidence suggesting the possible influence of metabolic, autonomic, and endocrine function on bone health in SCI.