Circulating and Adipose Levels of Adipokines Associated With Insulin Sensitivity in Nonobese Subjects With Type 2 Diabetes

J Clin Endocrinol Metab. 2016 Oct;101(10):3765-3771. doi: 10.1210/jc.2016-1883. Epub 2016 Aug 8.

Abstract

Context: The adipokines chemerin, dipeptidyl peptidase 4, and adiponectin influence insulin sensitivity. Whether their circulating levels and adipose secretion are altered in nonobese individuals with type 2 diabetes mellitus (T2DM) is unknown.

Objective: The objective of this study was to investigate SC adipose secretion and serum levels of the three adipokines in relation to T2DM features.

Design: Fourteen nonobese T2DM and 13 healthy men were investigated. Insulin sensitivity and glucose control were assessed by hyperinsulinemic euglycemic clamp, homeostasis model assessment, and glycated hemoglobin.

Main outcome measure: Association of circulating and adipose-secreted adipokines with fat cell volume and insulin sensitivity was measured.

Participants: Volunteers in an outpatient academic clinic participated.

Results: Although adipose secretion was similar between the groups, serum chemerin was higher (70 ± 10 vs 50 ± 1 ng/ml; P = .005), adiponectin lower (4.7 ± 1.3 vs 6.8 ± 2.2 μg/ml; P = .005), and dipeptidyl peptidase 4 unaltered in T2DM. Serum adiponectin (r = 0.53; P = .005) and chemerin (r = -0.42; P = .03) correlated with adipose secreted levels. Secreted and circulating chemerin correlated positively with adipocyte volume (r > 0.40; P < .05), whereas serum adiponectin correlated negatively with this measure (r = -0.61; P = .001). Adiponectin serum half-life was decreased in T2DM (168 ± 24 vs 186 ± 18 minutes; P = .029) and correlated negatively with glycated hemoglobin (r = -0.45; P = .03) and adipocyte volume (r = -0.56; P < .003). Serum adiponectin (r = 0.57; P = .017) and chemerin (r = -0.52; P = .03) associated with clamp measures independently of T2DM diagnosis.

Conclusions: In nonobese men, circulating adiponectin and chemerin levels are altered in T2DM without changes in adipose secretion. Adipocyte volume is important for variations in serum chemerin and adiponectin and for serum clearance of adiponectin. In T2DM, poor glucose control also plays a role for adiponectin clearance.

MeSH terms

  • Abdominal Fat / metabolism*
  • Adipocytes
  • Adiponectin / blood
  • Adiponectin / metabolism*
  • Adult
  • Aged
  • Chemokines / blood
  • Chemokines / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Dipeptidyl Peptidase 4 / blood
  • Dipeptidyl Peptidase 4 / metabolism*
  • Humans
  • Insulin Resistance*
  • Intercellular Signaling Peptides and Proteins / blood
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Middle Aged

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Chemokines
  • Intercellular Signaling Peptides and Proteins
  • RARRES2 protein, human
  • Dipeptidyl Peptidase 4