Abstract
We aimed to investigate the role of the amount of visceral fat and liver fat in the association between adult weight change and insulin resistance at middle age. In the Netherlands Epidemiology of Obesity study, adult weight change was calculated with recalled body weight at age 20 years and measured body weight at middle age. Measures of insulin resistance were calculated using both fasting and postprandial glucose and insulin concentrations. Visceral fat was assessed by magnetic resonance (MR) imaging and liver fat by proton-MR spectroscopy (N = 1758). We examined the association between adult weight change and insulin resistance with linear regression, adjusted for confounding factors. To investigate mediation, we additionally adjusted for total body fat, visceral fat, and liver fat. In participants who gained ≥50% of body weight during adulthood, homeostatic model assessment for insulin resistance (HOMA-IR) was 3.22 (95% CI 2.76; 3.77) times higher than in weight maintainers. In a joint model, total body fat mediated this association for 8.1% (95% CI −9.2; 25.4), visceral fat for 32.0% (18.6; 45.4%) and liver fat for 22.5% (15.0; 30.1). The association between adult weight gain and insulin resistance at middle age is largely mediated by both visceral fat and liver fat.
Highlights
Adult weight gain and obesity are well-established causal risk factors for the development of type 2 diabetes mellitus, cardiovascular disease and obesity-related cancers [1,2,3]
The proportion of women was higher in participants who gained more than 25% of body weight between age 20 and middle age than in participants who gained less than 25% during adulthood
Participants who gained more than 25% of body weight were less likely to be highly educated, and waist circumference, total body fat, visceral fat and liver fat at middle age were higher than in participants who gained less than 25% of body weight, in both men and women
Summary
Adult weight gain and obesity are well-established causal risk factors for the development of type 2 diabetes mellitus, cardiovascular disease and obesity-related cancers [1,2,3] In line with these findings, adult weight gain was strongly associated with increased insulin resistance in multiple studies [4,5,6,7,8,9]. We observed that larger gain in body weight during adulthood was associated with more visceral fat and liver fat at middle age, compared with weight maintenance [16] This finding is in agreement with the ‘lipid overflow’ hypothesis, which postulates that lipids are stored in the visceral area and in and around organs (ectopic fat) when the subcutaneous adipose tissue has reached its limited storage capacity [17,18]. In addition to visceral adipose tissue, excess liver fat has been associated with insulin resistance [19], as well as with a higher risk of type 2 diabetes mellitus, cardiovascular disease and mortality [20]
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