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

Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney 2010, Australia
St. Vincent’s Clinical School, UNSW Sydney, Sydney 2010, Australia
School of Mathematics and Statistics, UNSW Sydney, Sydney 2052, Australia
Department of Endocrinology and Diabetes Center, St. Vincent’s Hospital, Sydney 2010, Australia
Adelaide Medical School, University of Adelaide, Adelaide 5005, Australia
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
Faculty of Health Sciences, The University of Sydney, Camperdown 2006, Australia
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2019, 8(5), 623;
Received: 11 April 2019 / Revised: 29 April 2019 / Accepted: 30 April 2019 / Published: 8 May 2019
(This article belongs to the Section Endocrinology & Metabolism)
PDF [1962 KB, uploaded 14 May 2019]


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 (ObSen) or insulin-resistant (ObRes), 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 ObSen compared with ObRes (p = 0.02), and was not different between ObSen and Lean (p = 0.41). While BMI did not change over time (p = 0.24), android and visceral fat increased significantly in this cohort (ptime ≤ 0.0013), driven by ObRes (p = 0.0087 and p = 0.0001, respectively). Similarly, systolic blood pressure increased significantly over time (ptime = 0.0003) driven by ObRes (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 ObSen and the Lean groups at baseline persisted over time. Insulin resistance in overweight and obese individuals predisposed to further metabolic deterioration over time. View Full-Text
Keywords: insulin resistance; obesity; fat-free mass; hyperinsulinaemic-euglycaemic clamp; liver fat insulin resistance; obesity; fat-free mass; hyperinsulinaemic-euglycaemic clamp; liver fat

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Tang, A.; Coster, A.C.F.; Tonks, K.T.; Heilbronn, L.K.; Pocock, N.; Purtell, L.; Govendir, M.; Blythe, J.; Zhang, J.; Xu, A.; Chisholm, D.J.; Johnson, N.A.; Greenfield, J.R.; Samocha-Bonet, D. Longitudinal Changes in Insulin Resistance in Normal Weight, Overweight and Obese Individuals. J. Clin. Med. 2019, 8, 623.

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