Adipose cellularity and long-term development of impaired glucose metabolism: Swedish cohort study from 1988 through 2016.

Abstract

Adipocyte volume and number form adipose tissue cellularity, and adipocyte volume relates to impaired glucose metabolism (IGM). We studied how the cellularity relates to future long-term IGM development. We investigated 1014 participants living in Stockholm, Sweden 1986-2016 for abdominal subcutaneous adipocyte volume and number and IGM (impaired fasting glucose (≥6.1 mmol/l) and/or type 2 diabetes). A re-examination was conducted 2018-2022 on 241 participants (after on average 15 years); 127 remained without IGM, 47 had developed IGM and 43 remained as IGM. We compared baseline adipocyte volume and number for the three groups by analysis of variance and studied the odds ratio for future IGM as compared with always being healthy by logistic regression, correcting for relevant co-factors. Subcutaneous adipocytes were 20% larger in those having IGM from start or developed it later compared with those without IGM throughout (p = 0.005-0.03). Subcutaneous adipocyte number was similar in all three groups (p = 0.26). By comparing upper and lower tertiles for adipocyte volume/number the odds ratio for developing IGM was 2.8 (95% confidence interval CI; 1.2-6.5) for large adipocytes and 0.8 (0.4-2.0) for many adipocytes. Large adipocytes as a risk factor for future IGM was independent of sex, age, observation time, waist-to-hip ratio, body fat, physical activity or undergoing bariatric surgery, but not of insulin resistance measure, which strongly associated with adipocyte volume (r = 0.65). Adipocyte volume, but not number, associates with risk of long-term development of IGM. Large adipocytes confer this increased risk, maybe through insulin resistance. The Stockholm County Council (963296, 994175, 986118), the Centre for Innovative Medicine at Karolinska Institutet (986109), and the Swedish Society of Medicine (1001156). The Novo Nordisk Foundation supports the Novo Nordisk Foundation Center for Basic Metabolic Research (grants NNF18CC0034900 and NNF23SA0084103). None of the funding sources had any involvement in the study.