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

Alice Tang; Adelle C F Coster; Katherine T Tonks; Leonie K Heilbronn; Nicholas Pocock; Louise Purtell; Matthew Govendir; Jackson Blythe; Jialiang Zhang; Aimin Xu; Donald J Chisholm; Nathan A Johnson; Jerry R Greenfield; Dorit Samocha-Bonet

doi:10.3390/jcm8050623

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

J Clin Med. 2019 May 8;8(5):623. doi: 10.3390/jcm8050623.

Authors

Alice Tang^{1

2}, Adelle C F Coster³, Katherine T Tonks^{4

5

6}, Leonie K Heilbronn⁷, Nicholas Pocock⁸, Louise Purtell⁹, Matthew Govendir¹⁰, Jackson Blythe^{11

12}, Jialiang Zhang¹³, Aimin Xu¹⁴, Donald J Chisholm^{15

16}, Nathan A Johnson¹⁷, Jerry R Greenfield^{18

19

20}, Dorit Samocha-Bonet^{21

22}

Affiliations

¹ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. a.tang@unswalumni.com.
² St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. a.tang@unswalumni.com.
³ School of Mathematics and Statistics, UNSW Sydney, Sydney 2052, Australia. A.Coster@unsw.edu.au.
⁴ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. k.tonks@garvan.org.au.
⁵ St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. k.tonks@garvan.org.au.
⁶ Department of Endocrinology and Diabetes Center, St. Vincent's Hospital, Sydney 2010, Australia. k.tonks@garvan.org.au.
⁷ Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia. leonie.heilbronn@adelaide.edu.au.
⁸ St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. n.pocock@unsw.edu.au.
⁹ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. louise.purtell@qut.edu.au.
¹⁰ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. m.govendir@unsw.edu.au.
¹¹ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. jackson.blythe@outlook.com.
¹² St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. jackson.blythe@outlook.com.
¹³ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China. hjzhang@hku.hk.
¹⁴ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China. amxu@hku.hk.
¹⁵ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. d.chisholm@garvan.org.au.
¹⁶ St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. d.chisholm@garvan.org.au.
¹⁷ Faculty of Health Sciences, The University of Sydney, Camperdown 2006, Australia. nathan.johnson@sydney.edu.au.
¹⁸ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. j.greenfield@garvan.org.au.
¹⁹ St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. j.greenfield@garvan.org.au.
²⁰ Department of Endocrinology and Diabetes Center, St. Vincent's Hospital, Sydney 2010, Australia. j.greenfield@garvan.org.au.
²¹ Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia. d.samochabonet@garvan.org.au.
²² St. Vincent's Clinical School, UNSW Sydney, Sydney 2010, Australia. d.samochabonet@garvan.org.au.

Abstract

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/m²) or overweight/obese (BMI ≥ 25 kg/m²), 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.

Keywords: fat-free mass; hyperinsulinaemic-euglycaemic clamp; insulin resistance; liver fat; obesity.

Grants and funding

N/A/Diabetes Australia Research Trust