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 β-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.

Background: Glucose effectiveness (GE) refers to the ability of glucose to influence its own metabolism through insulin-independent mechanisms. 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. Objective: To determine the effect of glycemic index of the diet on exercise-induced enhancement of GE in people with obesity and insulin resistance. Design: A randomized, controlled, parallel-group, repeated-measures study. Participants: 33 adults with obesity and pre-diabetes (17 males, 65.7±4.3 yrs, 34.9±4.2 kg/m 2) Interventions: Participants were recruited into a 12-week exercise training program (1 hr/d, 5 d/wk 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 diet. A 75-g oral-glucosetolerance test (OGTT) was performed before and after the intervention and GE was calculated using the Nagasaka equation. Results: Both EX-LOG and EX-HIG groups had similar improvements in weight (8.6±5.1 Kg, P<0.001), VO 2max (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

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.

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.