Insulin resistance persists despite a metabolically healthy obesity phenotype.

OBJECTIVE: Metabolically healthy obesity (MHO) is often defined as the absence of metabolic syndrome in the presence of obesity. However, phenotypic features of MHO are unclear. Insulin sensitivity in MHO was cross-sectionally compared with metabolically unhealthy obesity (MUO) and a reference group of young healthy participants without obesity. METHODS: Sedentary adults (n = 96) undergoing anthropometric, blood chemistries, maximal aerobic capacity, and euglycemic-hyperinsulinemic clamp measurements were classified by BMI (<25 and ≥30 kg/m2 ). MUO was defined as having obesity with metabolic syndrome (≥2 additional risk factors). Data were analyzed using a linear mixed models approach. RESULTS: Body weight was similar between MHO and MUO. Body fat (percentage) and high-density lipoprotein cholesterol were higher (p < 0.001), and systolic blood pressure, triglycerides, glucose, and insulin were lower in MHO versus MUO (p < 0.03, all). The MHO group also had lower high-density lipoprotein cholesterol and higher low-density lipoprotein cholesterol, diastolic blood pressure, and insulin compared with the reference. Both the MHO and MUO groups displayed impaired insulin sensitivity compared with the reference control (p < 0.001). CONCLUSIONS: Participants with MHO had distinct clinical measures related to hypertension, lipid metabolism, and glycemic control compared with a healthy reference group. Peripheral insulin resistance in obesity independent of metabolic status portends increased risk for type 2 diabetes in the MHO patient population.

Exertional Rhabdomyolysis After CrossFit Exercise.

Multiple studies have reported the metabolic benefits of high-intensity exercise programs like CrossFit. If these high-intensity exercises are not done in a proper structured pattern, adverse outcomes like rhabdomyolysis can occur. Here we discuss a case of a patient who undertook one session of CrossFit exercise and developed exertional rhabdomyolysis. A 22-year-old Caucasian male presented to the emergency department with complaints of generalized body ache and passage of dark-colored urine. His symptoms began after two days of an exhaustive session of CrossFit exercise. Blood test in the emergency showed elevated creatine kinase (CK) of 132,540 units per liter (U/L), normal renal function (creatinine and blood urea nitrogen), and normal serum electrolytes. His clinical symptoms and lab findings were consistent with exertional rhabdomyolysis. He was treated with aggressive intravenous fluids and oral hydration therapy. He did not develop any complication and he was discharged on the sixth day. This case report demonstrates a possible preventable rhabdomyolysis that developed secondary to undue participation in CrossFit exercise.

Lipids and ketones dominate metabolism at the expense of glucose control in pulmonary arterial hypertension: a hyperglycaemic clamp and metabolomics study.

Individuals with idiopathic pulmonary arterial hypertension (PAH) display reduced oral glucose tolerance. This may involve defects in pancreatic function or insulin sensitivity but this hypothesis has not been tested; moreover, fasting nutrient metabolism remains poorly described in PAH. Thus, we aimed to characterise fasting nutrient metabolism and investigated the metabolic response to hyperglycaemia in PAH.12 participants (six PAH, six controls) were administered a hyperglycaemic clamp, while 52 (21 PAH, 31 controls) underwent plasma metabolomic analysis. Glucose, insulin, C-peptide, free fatty acids and acylcarnitines were assessed from the clamp. Plasma metabolomics was conducted on fasting plasma samples.The clamp verified a reduced insulin response to hyperglycaemia in PAH (-53% versus control), but with similar pancreatic insulin secretion. Skeletal muscle insulin sensitivity was unexpectedly greater in PAH. Hepatic insulin extraction was elevated in PAH (+11% versus control). Plasma metabolomics identified 862 metabolites: 213 elevated, 145 reduced in PAH (p<0.05). In both clamp and metabolomic cohorts, lipid oxidation and ketones were elevated in PAH. Insulin sensitivity, fatty acids, acylcarnitines and ketones correlated with PAH severity, while hepatic extraction and fatty acid:ketone ratio correlated with longer six-min walk distance.Poor glucose control in PAH could not be explained by pancreatic ß-cell function or skeletal muscle insulin sensitivity. Instead, elevated hepatic insulin extraction emerged as an underlying factor. In agreement, nutrient metabolism in PAH favours lipid and ketone metabolism at the expense of glucose control. Future research should investigate the therapeutic potential of reinforcing lipid and ketone metabolism on clinical outcomes in PAH.

Exercise Training Rapidly Increases Hepatic Insulin Extraction in NAFLD.

PURPOSE: We aimed to determine the immediacy of exercise intervention on liver-specific metabolic processes in nonalcoholic fatty liver disease. METHODS: We undertook a short-term (7-d) exercise training study (60 min·d treadmill walking at 80%-85% of maximal heart rate) in obese adults (N = 13, 58 ± 3 yr, 34.3 ± 1.1 kg·m, >5% hepatic lipid by H-magnetic resonance spectroscopy). Insulin sensitivity index was estimated by oral glucose tolerance test using the Soonthorpun model. Hepatic insulin extraction (HIE) was calculated as the molar difference in area under the curve (AUC) for insulin and C-peptide (HIE = 1 - (AUCInsulin/AUCC-Pep)). RESULTS: The increases in HIE, V˙O2max, and insulin sensitivity index after the intervention were 9.8%, 9.8%, and 34%, respectively (all, P < 0.05). Basal fat oxidation increased (pre: 47 ± 6 mg·min vs post: 65 ± 6 mg·min, P < 0.05) and carbohydrate oxidation decreased (pre: 160 ± 20 mg·min vs post: 112 ± 15 mg·min, P < 0.05) with exercise training. After the intervention, HIE correlated positively with adiponectin (r = 0.56, P < 0.05) and negatively with TNF-α (r = -0.78, P < 0.001). CONCLUSIONS: By increasing HIE along with peripheral insulin sensitivity, aerobic exercise training rapidly reverses some of the underlying physiological mechanisms associated with nonalcoholic fatty liver disease, in a weight loss-independent manner. This reversal could potentially act through adipokine-related pathways.

Exercise-induced improvements in glucose effectiveness are blunted by a high glycemic diet in adults with prediabetes.

AIMS: Glucose effectiveness (GE) refers to the ability of glucose to influence its own metabolism through insulin-independent mechanisms. Diminished GE is a predictor of progression to type 2 diabetes. Exercise training improves GE, however, little is known about how dietary interventions, such as manipulating the glycemic index of diets, interact with exercise-induced improvements in GE in at-risk populations. METHODS: We enrolled 33 adults with obesity and pre-diabetes (17 males, 65.7 ± 4.3 years, 34.9 ± 4.2 kg m-2) into a 12-week exercise training program (1 h day-1 and 5 day week-1 at ~ 85% of maximum heart rate) while being randomized to concurrently receive either a low (EX-LOG: 40 ± 0.3 au) or high (EX-HIG: 80 ± 0.6 au) glycemic index diet. A 75-g oral-glucose-tolerance test (OGTT) was performed before and after the intervention and GE was calculated using the Nagasaka equation. Insulin resistance was estimated using a hyperinsulinemic-euglycemic clamp and cardiorespiratory fitness using a VO2max test. RESULTS: Both EX-LOG and EX-HIG groups had similar improvements in weight (8.6 ± 5.1 kg, P < 0.001), VO2max (6 ± 3.5 mL kg-1 min-1, P < 0.001) and clamp-measured peripheral insulin resistance (1.7 ± 0.9 mg kg-1 min-1, P < 0.001), relative to baseline data. GE in EX-LOG and EX-HIG was similar at baseline (1.9 ± 0.38 vs. 1.85 ± 0.3 mg dL-1 min-1, respectively; P > 0.05) and increased by ~ 20% post-intervention in the EX-LOG arm (∆GE: 0.07-0.57 mg dL-1 min-1, P < 0.05). Plasma free fatty acid (FFA) concentrations also decreased only in the EX-LOG arm (∆FFA: 0.13 ± 0.23 mmol L-1, P < 0.05). CONCLUSIONS: Our data suggest that a high glycemic index diet may suppress exercise-induced enhancement of GE, and this may be mediated through plasma FFAs.

VT ablation: New Developments and Approaches.

OPINION STATEMENT: Over the past decade, catheter ablation has emerged as an important therapeutic option for ventricular tachycardia (VT) in both patients with and without structural heart disease. In patients without structural heart disease, catheter ablation serves as sole therapy for the treatment of VT. For those with structural heart disease, VT ablation has generally been reserved for patients who experience ICD therapies, and particularly those who fail antiarrhythmic agents. With the growing number of patients with implantable devices as well as improvements in heart failure therapy resulting in improved survival among ICD patients, the overall number of patients needing therapy for VT continues to increase. The past years have witnessed significant advances in our understanding of the arrhythmic substrate in various cardiomyopathies, resulting in substrate-based approaches for targeted VT ablation. Further, the growth in better technologies and techniques for VT ablation, such as the use of percutaneous epicardial ablation, the innovation of multielectrode catheters for rapid mapping, the use of intracardiac echocardiography (ICE) for mapping unusual sites, and activation and entrainment mapping of previously unmappable VTs assisted by mechanical circulatory support devices, has overcome the limitations and greatly improved the success rates of catheter ablation. This review summarizes recent advances and novel approaches in both technology and techniques for catheter ablation of ventricular tachycardia.