Adipose tissue-derived adipsin marks human aging in non-type 2 diabetes population.

Introduction: Adipsin or complement factor D is an adipokine that augments insulin secretion, is altered in various degrees of obesity, and is involved in alternative complement pathway. However, whether adipsin has any independent association with risk factors and biomarkers in patients with type 2 diabetes (T2D) remains elusive.

Research design and methods: We performed an oral glucose tolerance test on a subset of 43 patients with T2D from the community health cohort to access the role of adipsin in insulin secretion. We further cross-sectionally examined the role of adipsin in plasma, adipose tissue (AT), and secretion in a community cohort of 353 subjects and a hospital cohort of 52 subjects.

Results: We found that plasma adipsin has no significant correlation with insulin secretion in people with diabetes. Among the risk factors of T2D, adipsin levels were independently associated only with age, and a positive correlation between plasma adipsin and age among subjects without T2D was lost in patients with T2D. Plasma adipsin levels, AT adipsin expression, and secretion were upregulated both in T2D and aging, with a corresponding drop in Homeostatic Model Assessment for assessing β-cell function. Adipsin expression was positively associated with other aging biomarkers, such as β-galactosidase, p21, and p16. These results also corroborated with existing plasma proteomic signatures of aging, including growth, and differentiation factor-15, which strongly correlated with adipsin.

Conclusions: Our results demonstrate an increase in circulating adipsin in T2D and aging, and it scores as a candidate plasma marker for aging specifically in non-T2D population.