Impact of the adipokine adiponectin and the hepatokine fetuin-A on the development of type 2 diabetes: prospective cohort- and cross-sectional phenotyping studies.

Abstract

BACKGROUND:

Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity.

OBJECTIVE:

To determine to what extent circulating adiponectin and fetuin-A are independently associated with incident type 2 diabetes in humans, and the major mechanisms involved.

METHODS:

Relationships with incident diabetes were tested in two cohort studies: within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (628 cases) and the Nurses' Health Study (NHS; 470 cases). Relationships with body fat compartments, insulin sensitivity and insulin secretion were studied in the Tübingen Lifestyle Intervention Program (TULIP; N = 358).

RESULTS:

Circulating adiponectin and fetuin-A, independently of several confounders and of each other, associated with risk of diabetes in EPIC-Potsdam (RR for 1 SD: adiponectin: 0.45 [95% CI 0.37-0.54], fetuin-A: 1.18 [1.05-1.32]) and the NHS (0.51 [0.42-0.62], 1.35 [1.16-1.58]). Obesity measures considerably attenuated the association of adiponectin, but not of fetuin-A. Subjects with low adiponectin and concomitantly high fetuin-A had the highest risk. Whereas both proteins were independently (both p<1.8×10(-7)) associated with insulin sensitivity, circulating fetuin-A (r = -0.37, p = 0.0004), but not adiponectin, associated with insulin secretion in subjects with impaired glucose tolerance.

CONCLUSIONS:

We provide novel information that adiponectin and fetuin-A independently of each other associate with the diabetes risk. Furthermore, we suggest that they are involved in the development of type 2 diabetes via different mechanisms, possibly by mediating effects of their source tissues, expanded adipose tissue and nonalcoholic fatty liver.

• Authors: Norbert Stefan, Qi Sun, Andreas Fritsche, Jürgen Machann, Fritz Schick, Felicia Gerst, Charlotte Jeppesen, Hans-Georg Joost, Frank B Hu, Heiner Boeing, Susanne Ullrich, Hans-Ulrich Häring, Matthias B Schulze
• Journal: PloS one (PLoS One) Vol. 9 Issue 3 Pg. e92238 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24643166 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ADIPOQ protein, human
• Adiponectin
• Biomarkers
• alpha-2-HS-Glycoprotein

Topics

• Adiponectin (blood)
• Adult
• Aged
• Biomarkers (blood)
• Body Mass Index
• Cross-Sectional Studies
• Diabetes Mellitus, Type 2 (blood)
• Female
• Glucose Intolerance (blood)
• Humans
• Insulin Resistance
• Male
• Middle Aged
• Multivariate Analysis
• Phenotype
• Prospective Studies
• Risk
• Waist Circumference
• alpha-2-HS-Glycoprotein (metabolism)