The following is a summary of “Body Fat Distribution, Fasting Insulin Levels, and Insulin Secretion: A Bidirectional Mendelian Randomization Study,” published in the June 2023 issue of Endocrinology & Metabolism by Gagnon, et al.
The relationship between hyperinsulinemia and adiposity has yet to be fully understood, and the directionality of this association still needs to be explored. For a study, researchers sought to investigate the causal direction of the effects between fasting insulin (FI) levels and body fat accumulation/distribution using a two-sample bidirectional Mendelian randomization (MR) approach.
Summary statistics from large-scale genome-wide association studies were utilized for various factors, including body mass index (BMI, n = 806,834), waist-to-hip ratio adjusted for BMI (WHRadjBMI, n = 694,649), abdominal subcutaneous, visceral, and gluteofemoral adipose tissue, FI levels (n=98,210), pancreatic islets gene expression (n=420), and hypothalamus gene expression (n=155). Robust MR methods were employed, incorporating both statistically and biologically driven genetic instruments.
The study found a positive association between BMI, WHRadjBMI, and FI levels. The relationship remained consistent across all robust MR methods and even when considering genetic variants related to hypothalamus gene expression associated with food behavior. When waist circumference and BMI were controlled for one another in multivariable MR analyses, it was discovered that the direct effect of waist circumference on FI was 2.43 times greater than the effect of BMI on FI. FI levels were not significantly associated with adiposity. However, when genetic instruments related to insulin secretion in pancreatic islets were considered, insulin showed a positive association with BMI and abdominal subcutaneous and gluteofemoral adipose tissue but not visceral adipose tissue.
While further experimental investigations were required to confirm the findings, the results of the MR study suggested that abdominal adiposity may play a crucial role in determining circulating insulin levels. Alternatively, insulin secretion may promote the accumulation of peripheral adipose tissue.