Adipose Tissue Insulin Resistance in Children and Adolescents: Linking Glucose and Free Fatty Acid Metabolism to Hepatic Injury Markers.

Abstract

Obesity is one of the leading causes of the development of insulin resistance, diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. With the progression of insulin resistance, both glucose and free fatty acid (FFA) plasma levels are elevated, leading to cardiometabolic complications such as impaired glucose tolerance (IGT), type 2 diabetes and liver fat accumulation. Oral minimal models were used to estimate insulin sensitivity indexes (SI and SI_FFA) in 375 adolescents with obesity. Differences between NGT and IGT were assessed by using Mann-Whitney test, while the relationship between insulin sensitivities and plasma alanine transaminase (ALT) by using Spearman correlation and linear regression model of the log transformed variables. Also, 48 youth repeated the OGTT and the measurement of liver function test after ~1.3 years of follow-up. Insulin sensitivity indexes resulted to be statistically different in NGT compared to IGT (P<10^-6) and correlated to each other (ρ=0.7, P<10^-6). Lipolysis was completely suppressed after 30min in NGT, compared to 120min in IGT. SI and SI_FFA were both statistically correlated with ALT ρ= -0.19 (P<10^-3). Also, the percentages of variation of SI_FFA and ALT between the first and second visit correlated significantly (ρ= -0.47, P=0.002). FFA minimal model can be used to estimate adipose tissue lipolysis in youth with obesity. The relationship of SI and SI_FFA and with ALT, along with the progression of the impairment of adipose tissue insulin sensitivity, showed a systemic insulin resistance state, underlying the interrelationship of glucose and FFA metabolism and with hepatic damage.