Photo Credit: Love Employee
The following is a summary of “At any Level of Adiposity, Relatively Elevated Leptin Concentrations Are Associated With Decreased Insulin Sensitivity,” published in the February 2024 issue of Endocrinology by Chiriacò, et al.
In glucose homeostasis and its association with obesity, the considerable variability in interindividual responses has prompted investigations into potential explanatory factors, such as variations in adipokine concentrations. Leptin, a key regulator of energy balance and metabolism, has been of particular interest due to its role in modulating glucose metabolism despite its known correlation with adiposity. For a study, researchers sought to assess whether differences in glucose homeostasis exist among individuals with comparable levels of adiposity but varying leptin concentrations. To achieve this, a cohort of 1,290 healthy adults aged 30-60 years, comprising 577 males and 713 females with a mean body mass index (BMI) of 25 ± 3 kg/m2, was analyzed. The participants underwent comprehensive body composition and metabolic assessments, including a 75-g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp, evaluation of β-cell function, and lipidomics profiling.
Results revealed that individuals were categorized into relatively high and low leptin groups (RHL and RLL) based on their deviation from the sex-specific leptin-fat mass (%) regression line. Despite similar glucose tolerance levels, those in the RHL group exhibited significantly elevated fasting and oral glucose tolerance test insulin concentrations (+30% and +29%, respectively; P < .0001), along with increased insulin secretion (+17% and +11%, respectively; P < .0001). Furthermore, irrespective of BMI, individuals in the RHL group demonstrated diminished whole-body (−17-23%, P < .0001) and adipose tissue insulin sensitivity (−24%, P < .0001) compared to those in the RLL group. Notably, even lean individuals in the RHL group displayed comparable insulin sensitivity and β-cell function to overweight or obese individuals in the RLL group.
In conclusion, individuals with disproportionately elevated leptin levels relative to their fat mass exhibit characteristics of whole-body and adipose tissue insulin resistance, as well as hyperinsulinemia, regardless of their BMI status. The findings underscored the importance of considering leptin levels in understanding variations in glucose homeostasis among individuals with similar levels of adiposity.
Reference: academic.oup.com/jcem/article-abstract/109/2/461/7256797