Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals.

Background: Large cohort longitudinal studies have almost unanimously concluded that metabolic health in obesity is a transient phenomenon, diminishing in older age. We aimed to assess the fate of insulin sensitivity per se over time in overweight and obese individuals.
Methods: Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 ( n = 99) were retrospectively grouped into Lean (body mass index (BMI) < 25 kg/m ² ) or overweight/obese (BMI ≥ 25 kg/m ² ), with the latter further divided into insulin-sensitive (Ob _Sen ) or insulin-resistant (Ob _Res ), based on median clamp M-value (M/I, separate cut-offs for men and women). Fifty-seven individuals participated in a follow-up study after 5.4 ± 0.1 years. Hyperinsulinaemic-euglycaemic clamp, dual-energy X-ray absorptiometry and circulating cardiovascular markers were measured again at follow-up, using the same protocols used at baseline. Liver fat was measured using computed tomography at baseline and proton magnetic resonance spectroscopy at follow-up with established cut-offs applied for defining fatty liver.
Results: In the whole cohort, M/I did not change over time ( p = 0.40); it remained significantly higher at follow-up in Ob _Sen compared with Ob _Res ( p = 0.02), and was not different between Ob _Sen and Lean ( p = 0.41). While BMI did not change over time ( p = 0.24), android and visceral fat increased significantly in this cohort ( p _time ≤ 0.0013), driven by Ob _Res ( p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (p _time = 0.0003) driven by Ob _Res ( p = 0.0039). The best correlate of follow-up M/I was baseline M/I (Spearman's r = 0.76, p = 1.1 × 10 ^-7 ).
Conclusions: The similarity in insulin sensitivity between the Ob _Sen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time.