Dataset Information

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

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 (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.

SUBMITTER: Tang A

PROVIDER: S-EPMC6572215 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Tang Alice A Coster Adelle C F ACF Tonks Katherine T KT Heilbronn Leonie K LK Pocock Nicholas N Purtell Louise L Govendir Matthew M Blythe Jackson J Zhang Jialiang J Xu Aimin A Chisholm Donald J DJ Johnson Nathan A NA Greenfield Jerry R JR Samocha-Bonet Dorit D

Journal of clinical medicine 20190508 5

<h4>Background</h4>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.<h4>Methods</h4>Individuals studied using the hyperinsulinaemic-euglycaemic clamp at the Garvan Institute of Medical Research from 2008 to 2010 (<i>n</i> = 99) were retrospectively grouped into Lean (body mass index (BMI) < ...[more]

PMID: 31071971

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Project description:AimWeight loss reduces risk factors associated with obesity. However, long-term metabolic improvement remains a challenge. We investigated quantitative gene expression of subcutaneous adipose tissue in obese individuals and its relationship with low calorie diet and long term weight maintenance induced changes in insulin resistance.Research designThree hundred eleven overweight and obese individuals followed a dietary protocol consisting of an 8-week low calorie diet followed by a 6-month ad libitum weight-maintenance diet. Individuals were clustered according to insulin resistance trajectories assessed using homeostasis model assessment of insulin resistance (HOMA-IR) index. Adipose tissue mRNA levels of 267 genes selected for regulation according to obesity, metabolic status and response to dieting was assessed using high throughput RT-qPCR. A combination of discriminant analyses was used to identify genes with regulation according to insulin resistance trajectories. Partial correlation was used to control for change in body mass index.ResultsThree different HOMA-IR profile groups were determined. HOMA-IR improved during low calorie diet in the 3 groups. At the end of the 6-month follow-up, groups A and B had reduced HOMA-IR by 50%. In group C, HOMA-IR had returned to baseline values. Genes were differentially expressed in the adipose tissue of individuals according to groups but a single gene, CIDEA, was common to all phases of the dietary intervention. Changes in adipose tissue CIDEA mRNA levels paralleled variations in insulin sensitivity independently of change in body mass index. Overall, CIDEA was up-regulated in adipose tissue of individuals with successful long term insulin resistance relapse and not in adipose tissue of unsuccessful individuals.ConclusionThe concomitant change in adipose tissue CIDEA mRNA levels and insulin sensitivity suggests a beneficial role of adipose tissue CIDEA in long term glucose homeostasis, independently of weight variation.Trial registrationClinicalTrials.gov NCT00390637.

Dataset Information

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

Publications

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

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