Costa, Damla N.

Background: Whether there are sex and obesity differences in fat oxidation and free fatty acid (FFA) mobilization during low-intensity exercise is unclear. Methods: We studied 21 (nine females) participants without and 24 (16 females) with obesity during 5 h of treadmill walking (~2 mph). We measured energy expenditure (EE) and substrate oxidation (indirect calorimetry) and FFA-palmitate kinetics and oxidation with isotopic palmitate infusions ([U- 13 C]palmitate and [1- 14 C]palmitate or [9,10- 3 H]palmitate). Skeletal muscle samples were collected at 1.5 and 5 h of exercise and 24 h after exercise. We calculated fatty acid (FA) oxidation, palmitate rate of disappearance (Rd), and intramyocellular triglyceride-derived palmitate fractions during exercise. Results: At rest, EE was 1.24 ± 0.23 kcal/min, with FA oxidation contributing 49 ± 13% of total EE. During exercise, FA oxidation accounted for 73 ± 8% of EE, and was not different between males and females ( P = 0.34). Plasma FFA-palmitate concentrations were greater in females than males ( P = 0.003), mean palmitate Rd and plasma palmitate clearance were not different ( P = 0.32 and 0.14, respectively). Plasma FFA-palmitate Rd was correlated with EE ( r = 0.49, P = 0.001), with a proportionally greater Rd response in females ( P < 0.001). Although absolute plasma FFA-palmitate oxidation rates were comparable between sexes, the percent contribution of FFA-palmitate oxidation to EE was greater in females ( P = 0.001). During exercise, intramyocellular triglyceride-palmitate fraction amounts remained stable. Conclusions: Lipid oxidation during low-intensity exercise is similar in males and females, independent of obesity, although next-day values were greater in participants with normal weight. EE correlates with plasma palmitate disappearance rates, but is proportionally greater in females. The contribution of plasma palmitate oxidation is greater in females than in males during low-intensity exercise.

Adult males and females have markedly different body composition, and energy expenditure and have different degrees of risk for metabolic diseases. A major aspect of metabolic regulation involves the appropriate storage and disposal of glucose and fatty acids. The use of sophisticated calorimetry, tracer, and imaging techniques has provided insight into the complex metabolism of these substrates showing that the regulation of these processes varies tremendously throughout the day, from the overnight fasting condition to meal ingestion, to the effects of physical activity. The sexual dimorphism in substrate metabolism is most readily observed in how fatty acids are stored and mobilized. The objective of this review is to provide a comprehensive and critical summary of the reported sex differences in the mobilization, oxidation, and storage of fat and carbohydrate in adipose tissue and skeletal muscle. We will describe how adipose tissue lipolysis differs between sexes and how this varies between fed, fasted, and exercise conditions. We will also review what is known about endogenous and exogenous fatty acid storage in adipose tissue and muscle, as well as how oxidation compares between men and women in response to exercise. What has been learned about the cellular level regulation of these processes will be described. Although glucose metabolism exhibits fewer differences between men and women, we will also review the existing knowledge on this topic.

Background: Serum C-peptide concentration is often utilized for diagnostic, prognostic, or therapeutic assessment in diabetes mellitus. However, there are limited clinical data regarding diagnostic and predictive value of C-peptide measured during hospitalizations for hyperglycemia. Materials and Methods: Adults admitted to Mayo Clinic inpatient facilities due to an acute hyperglycemic emergency between January 2017 and November 2022 were included in our study. Predictive capacity of C-peptide for discontinuation of therapeutic insulin was examined in the entire cohort and the subgroup of non-autoimmune non-pancreatitis diabetes (NANP-DM). Results: We included 187 patients (63 women) in our study. During hospitalization, patients with type 1 diabetes antibodies displayed diminished serum C-peptide concentration ( P = 0.014), correlating inversely with subsequent hemoglobin A1c% [ r = (−0.22), P = 0.005]. Initial C-peptide concentrations did not differ between patients requiring insulin therapy during follow-up and those who did not ( P = 0.16). C-peptide concentrations showed limited predictive capacity for achieving glycemic control. Subgroup analyses in NANP-DM exhibited similar limited capacity for anticipating therapeutic insulin needs and achieving glycemic controls. Discussion: C-peptide concentration did not exhibit a robust predictive capability for future need of insulin therapy and achieving glycemic control, limiting its utility in clinical practice within inpatient settings.

Abstract Context The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated. Objective We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity. Methods Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations. One study involved a 2-step insulin clamp and the other study was a single step insulin clamp. For both studies the goal was to achieve plasma glucose concentrations of 95 mg/dL during the clamp irrespective of fasting glucose concentrations. The percent change in ISR from fasting to the end of the insulin clamp interval was the main outcome. Linear regression and analysis of covariance were used to test for the effects of insulin on ISR and to test for group differences. Results ISR was greater in obese volunteers (P &lt; .001) under fasting and hyperinsulinemic clamp conditions. The change in plasma glucose from baseline to the end of the insulin clamp interval was highly correlated with the change in ISR (r = 0.61, P &lt; .001). From baseline to the end of the clamp we observed a 27% (SD 20) suppression of ISR. The participants who underwent a 2-step insulin clamp had greater suppression of ISR during the second step than the first step (P &lt; .001). The proportional suppression of ISR during euglycemic hyperinsulinemia was not different between nonobese and obese groups (P = .19). Conclusion Hyperinsulinemia suppresses endogenous insulin secretion and the relative change in insulin secretion produced by exogenous insulin did not differ between nonobese and obese people.